Nagahisa Yoshimura

Masanori Hangai

OCT Atlas
With 374 Figures

123
Nagahisa Yoshimura, MD, PhD
Department of Ophthalmology and Visual Sciences
Kyoto University Graduate School of Medicine,
Kyoto 6060-8507, Japan

Masanori Hangai, MD, PhD

Department of Ophthalmology
Saitama Medical University
Saitama 350-0495, Japan

ISBN-13 978-3-642-38624-4 ISBN 978-3-642-38625-1 (eBook)

DOI 10.1007/978-3-642-38625-1

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 V

Preface

At the time of its first clinical application, optical describing the functionality of OCT are very impor-
coherence tomography (OCT) imaging was limited tant in the education of young ophthalmologists and
particularly by the clarity of images. However, OCT eye care personnel. In this book, with Professor
provided a great advantage over other diagnostic Hangai, we chose high quality OCT images of rather
modalities, as it could noninvasively provide tomo- common diseases as well as images of several rare
graphic images of the retina of a living eye. As a result, diseases. We also tried to make the explanation of
a number of new findings in retinal diseases were these OCT images as simple as possible.
made using the time-domain OCT. Later, in 2002, the
second generation OCT devices (Stratus 3000 OCT©) Unfortunately, because the original version was pub-
were released and the quality of OCT images im- lished in the Japanese language and this English ver-
proved dramatically. Prior to the release of the first sion is published two years after the Japanese version,
commercially available spectral-domain (SD) OCT in there may be some obsolete descriptions and new
2006, we had an opportunity to use this SD-OCT. references could be added. Even with such drawbacks,
I was so excited with the quality of these images, and I believe this OCT Atlas will be helpful in further
I felt as if we were observing in vivo histopathology understanding retinal diseases.
of retinal lesions. Furthermore, with the release of
the Heidelberg Spectralis© with noise reduction tech- Nagahisa Yoshimura, MD, PhD
nology, this further enhanced the quality of images. April 2014
Kyoto with cherry blossom
OCT has now become an essential medical equipment
in ophthalmic care, and I believe quality textbooks

Second Preface

Biological information such as color, light absorption/ than the optical images that consist of the intensity of
back-reflection, cross-sectional images, polarization, back-reflections from each depth point within the
motion and function is provided by the reflection fundus. Therefore, we need to continue to cultivate
of light from the fundus. Our progress in clinically our ability to interpret the OCT B-scan images.
diagnosing and treating retinal diseases depends on
the advancement of technology by which this bio- Interpretation of the OCT B-scan images requires
logical information is extracted from the reflected both a basic knowledge of the factors affecting
light from the fundus. the acquisition of OCT B-scans and the pattern of
features seen on OCT B-scans characteristic to each
Originally, the clinical basics of retinal diseases were retinal disease. We believe that the presentation of
established based on direct observation of the fundus selected cases with typical OCT images is one of the
by biomicroscopy alone. However, biomicroscopic most powerful methods to efficiently learn how to
observation was limited by the observer’s inability to interpret OCT B-scan images. Particularly, cases of
provide sufficient systematic, 3-dimensional informa- common diseases we daily see would be useful
tion. Optical coherence tomography (OCT) now to strengthen our ability to interpret and diagnose
enables clinicians the ability to obtain high-resolution retinal diseases. We hope that this »OCT Atlas« pro-
cross-sectional images. The reduction in speckle- vides a useful source of information in the interpreta-
noise has improved the visualization of each retinal tion of OCT images to our readers.
layer and also provides imaging of pathological retinal
diseases with definition similar to that of histo- Masanori Hangai, MD, PhD
pathology. However, in vivo OCT images are not April 2014
identical to light microscopic sections, but no more Saitama with cherry blossom
 VII

Table of Contents

1 The basis of OCT interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 B-scan interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Normal retina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Normal choroidal imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.4 Displaying B-scans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.5 Depth resolution misinterpretations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.6 Artifacts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

2 Vitreoretinal interface pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

2.1 Idiopathic macular holes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Case 1 Physiological PVD: Flattening of foveal depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Case 2 Idiopathic macular holes: Progression from stage 1 (cystoid space type) to stage 2 . . . . . . . . . . . . . 30
Case 3 Idiopathic macular hole: Stage 1 foveal cystoid space formation type . . . . . . . . . . . . . . . . . . . . . . 31
Case 4 Idiopathic macular hole: Stage 1 foveal detachment type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Case 5 Idiopathic macular hole: Stage 1 photoreceptor dehiscence type . . . . . . . . . . . . . . . . . . . . . . . . 33
Case 6 Idiopathic macular hole: Stage 1 small foveal detachment type . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Case 7 Idiopathic macular hole: A case just before progression from stage 1 to stage 2 . . . . . . . . . . . . . . . 35
Case 8 Idiopathic macular hole: Typical example of stage 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Case 9 Idiopathic macular hole: Postoperative course for macular hole closure under gas tamponade . . . . . 38
Case 9 DONFL appearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Case 10 Idiopathic macular hole: Postoperative course for macular hole closure . . . . . . . . . . . . . . . . . . . . 40
Case 11 Idiopathic macular hole: Typical example of stage 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
After surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Case 12 Idiopathic macular hole: Typical example of stage 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Case 13 Idiopathic macular hole: Old case of stage 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Stage 4 after surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Case 14 Idiopathic macular holes: Progression from lamellar to full-thickness macular holes . . . . . . . . . . . . 46
Case 15 Stage 1 macular hole: Spontaneous separation of perifoveal PVD . . . . . . . . . . . . . . . . . . . . . . . . . 47
Case 16 Stage 1 macular hole: Macular microhole formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Case 17 Stage 2 macular hole: Spontaneous closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Case 18 Stage 3 macular hole: Spontaneous closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Case 19 Stage 4 macular hole: Spontaneous closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Case 20 Traumatic macular hole: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Case 21 Lamellar macular hole: a typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Case 22 Lamellar macular hole: Differentiation from a MPH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Macular microholes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Case 23 Macular microhole: with macular PVD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Case 24 Macular microhole: with complete PVD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Case 25 Macular microhole: Case without PVD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

2.2 Idiopathic epiretinal membrane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Case 26 Idiopathic epiretinal membrane: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Case 27 Idiopathic epiretinal membrane: Exposure of the fibrocellular membrane . . . . . . . . . . . . . . . . . . . 64
Case 28 Idiopathic epiretinal membrane: Membrane with significant whitening . . . . . . . . . . . . . . . . . . . . 65
Case 29 Idiopathic epiretinal membrane: Significant columnar structure formation . . . . . . . . . . . . . . . . . . 66
Case 30 Idiopathic epiretinal membrane: Case ① where macular PVD has not been complete . . . . . . . . . . . 67
Case 31 Idiopathic epiretinal membrane: Case ② where macular PVD has been complete . . . . . . . . . . . . . . 68
Case 32 Epiretinal membrane secondary to retinal hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Case 33 Macular pseudohole: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Case 34 Macular pseudohole: Case where macular PVD has not been complete . . . . . . . . . . . . . . . . . . . . . 71

2.3 Vitreomacular traction syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Case 35 Vitreomacular traction syndrome: Case showing disease development . . . . . . . . . . . . . . . . . . . . . 73
Case 35 Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
VIII Table of Contents

Case 36 Vitreomacular traction syndrome: Case with macular detachment . . . . . . . . . . . . . . . . . . . . . . . . 75

Case 37 Vitreomacular traction syndrome: A highly myopic eye with foveoschisis . . . . . . . . . . . . . . . . . . . 76

3 Diabetic retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.1 Diabetic retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

3.2 Diabetic macular edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

Case 38 Diabetic macular edema: Early-stage case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Case 39 Cystoid macular edema: Case with CME limited to layers anterior to the ELM . . . . . . . . . . . . . . . . . 87
Case 40 Cystoid macular edema: Case with CME extending to the outer retina . . . . . . . . . . . . . . . . . . . . . . 88
Case 41 Cystoid macular edema: Exacerbation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Case 42 Cystoid macular edema: Foveal detachment with recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Case 43 Cystoid macular edema: Subfoveal accumulation of hard exudates and the development
of ischemic maculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Case 44 Cystoid macular edema: Subretinal leakage from a parafoveal cystoid space . . . . . . . . . . . . . . . . . 92
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Case 45 Cystoid macular edema: Subfoveal leakage from a foveal cystoid space . . . . . . . . . . . . . . . . . . . . 94
Case 46 Cystoid macular edema: Photoreceptor damage from outer plexiform layer edema . . . . . . . . . . . . . 95
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Case 47 Cystoid macular edema: Microaneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Case 48 Ischemic maculopathy: Cystoid macular degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Case 49 Ischemic maculopathy: Thinned macula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Case 50 Vitreomacular traction syndrome: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Case 51 Proliferative diabetic retinopathy: Progressive proliferation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Case 52 Proliferative diabetic retinopathy: Preretinal hemorrhages and vitreomacular traction syndrome . . . 102

4 Retinal vascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

4.1 Retinal vein occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Case 53 Central retinal vein occlusion: Progression from non-ischemic to ischemic ① . . . . . . . . . . . . . . . . . 108
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Case 54 Central retinal vein occlusion: Progression from non-ischemic to ischemic ② . . . . . . . . . . . . . . . . . 110
Case 55 Central retinal vein occlusion: Ischemic type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Case 56 Hemi-central retinal vein occlusion: Non-ischemic type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Case 57 Branch retinal vein occlusion: Significant inner retinal layer ischemia . . . . . . . . . . . . . . . . . . . . . . 114

4.2 Retinal artery occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115

Case 58 Central retinal artery occlusion: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Case 59 Central retinal artery occlusion: Cilioretinal artery not occluded . . . . . . . . . . . . . . . . . . . . . . . . . 117
Case 60 Central retinal artery occlusion: Incomplete occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Case 61 Branch retinal artery occlusion: Case of good visual acuity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Case 62 Branch retinal artery occlusion: Incomplete occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

4.3 Idiopathic juxtafoveal macular telangiectasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

Case 63 Macular telangiectasia: Yannuzzi classification Type 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Case 64 Macular telangiectasia: Yannuzzi classification Type 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Case 65 Macular telangiectasia: Yannuzzi classification Type 2 Stage 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Case 66 Macular telangiectasia: Yannuzzi classification Type 2 Stage 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Case 67 Macular telangiectasia: Yannuzzi classification Type 2 Stage 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Case 68 Coats’ disease: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

4.4 Retinal arterial macroaneurysm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Case 69 Retinal arterial macroaneurysm: Subretinal hemorrhages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Case 70 Retinal arterial macroaneurysm: Foveal detachment from an inferior arterial macroaneurysms . . . . . 132

5 Central serous chorioretinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

5.1 Central serous chorioretinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Case 71 Acute central serous chorioretinopathy: Smoke-stack pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Case 72 Acute central serous chorioretinopathy: A slowly leaking ink-blot pattern . . . . . . . . . . . . . . . . . . . 140
Case 73 Acute central serous chorioretinopathy: Intense leakage with ink-blot pattern . . . . . . . . . . . . . . . . 141
Case 74 Chronic central serous chorioretinopathy: Choroidal thickening . . . . . . . . . . . . . . . . . . . . . . . . . 142
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Case 75 Chronic central serous chorioretinopathy: A case of recurrence . . . . . . . . . . . . . . . . . . . . . . . . . 143

Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Case 76 Chronic central serous chorioretinopathy: Changes in the photoreceptor outer segment . . . . . . . . 145
Case 77 Chronic central serous chorioretinopathy: Example of poor visual acuity . . . . . . . . . . . . . . . . . . . 146
Case 78 Acute bullous retinal detachment: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

6 Age-related macular degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

6.1 Drusen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

6.2 Pigment epithelial detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Case 79 Soft drusen: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Case 80 Soft drusen: Confluent drusen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Case 81 Cuticular drusen: Case with vitelliform detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Case 82 Cuticular drusen: Fellow eye of case 81 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Case 83 Reticular pseudodrusen: Fellow eye of RAP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Case 84 Reticular pseudodrusen: Case with atrophic age-related macular degeneration (atrophic AMD) . . . . 162
Case 85 Reticular pseudodrusen and soft drusen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Case 86 Serous pigment epithelial detachment: Case without CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
Case 87 Pigment epithelial detachment: Reactive proliferation of retinal pigment epithelial cells . . . . . . . . 165
Case 88 Drusenoid PED: Case where CNV is suspected . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
17 months later . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Case 89 Large pigment epithelial detachment: Case where CNV is suspected . . . . . . . . . . . . . . . . . . . . . . 168
Case 90 Pigment epithelial detachment: Case with type 1 CNV ① . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Case 91 Pigment epithelial detachment: Case with type 1 CNV ② . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
Case 92 Large pigment epithelial detachment: Case where CNV is present . . . . . . . . . . . . . . . . . . . . . . . 171
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

6.3 Atrophic age-related macular degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

Case 93 Atrophic age-related macular degeneration: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . 176
Case 94 Atrophic age-related macular degeneration: Atrophic lesions of various sizes . . . . . . . . . . . . . . . . 177
Case 95 Atrophic age-related macular degeneration: Fellow eye of PCV . . . . . . . . . . . . . . . . . . . . . . . . . 178

6.4 Choroidal neovascularization and exudative age-related macular degeneration . . . . . . . . . . . . . . 179

Case 96 Exudative age-related macular degeneration: Type 1 CNV with a SRD . . . . . . . . . . . . . . . . . . . . . 181
Case 97 Exudative age-related macular degeneration: Type 1 CNV with low activity . . . . . . . . . . . . . . . . . 182
Case 98 Exudative age-related macular degeneration: Type 1 CNV with relatively strong exudative changes . . 183
Six months later . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
Case 99 Exudative age-related macular degeneration: Case with extensive Type 1 and 2 CNV exudative
changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Six months after treatment with anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
Case 100 Exudative age-related macular degeneration: Type 1 and 2 CNV with extensive serous
retinal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
Case 101 Exudative age-related macular degeneration: Type 1 and 2 CNV with cystic changes . . . . . . . . . . . 188
Case 102 Exudative age-related macular degeneration: Type 2 CNV localized in the fovea centralis . . . . . . . . 189
Case 103 Exudative age-related macular degeneration: Type 2 CNV with strong exudative changes . . . . . . . 190

6.5 Polypoidal choroidal vasculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

Case 104 Polypoidal choroidal vasculopathy: Small lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
Case 105 Polypoidal choroidal vasculopathy: Case confused with central serous chorioretinopathy . . . . . . . 195
After treatment with anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
Case 106 Polypoidal choroidal vasculopathy: Fibrin deposits ① . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Case 107 Polypoidal choroidal vasculopathy: Fibrin deposits ② . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
Case 108 Polypoidal choroidal vasculopathy: A large branching vascular network . . . . . . . . . . . . . . . . . . . 199
Case 109 Polypoidal choroidal vasculopathy: Large foveal cystoid space . . . . . . . . . . . . . . . . . . . . . . . . . 200
Enlargement of hemorrhagic pigment epithelial detachment . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Enlargement of the abnormal vascular network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
Case 110 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment epithelial detachment ① . . . . . . 203
Case 111 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment epithelial detachment ② . . . . . . 204
Spontaneous remission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
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Case 112 Polypoidal choroidal vasculopathy: Optic disc type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206

Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Case 113 Polypoidal choroidal vasculopathy: Polypoidal lesions and pigment epithelial detachment . . . . . . 208
Case 114 Polypoidal choroidal vasculopathy: Tomographic notch sign . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Case 115 Polypoidal choroidal vasculopathy: Case where the branching vascular network
has detached . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Case 116 Polypoidal choroidal vasculopathy: A massive lesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

6.6 Retinal angiomatous proliferation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212

Case 117 Retinal angiomatous proliferation: Stage 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
Case 118 Retinal angiomatous proliferation: Stage 2A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Case 119 Retinal angiomatous proliferation: Stage 2B ① . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Case 120 Retinal angiomatous proliferation: Stage 2B ② . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Case 121 Retinal angiomatous proliferation: Stage 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
After treatment with anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

6.7 Malattia leventinese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

Case 122 Malattia leventinese: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
6.8 Idiopathic choroidal neovascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Case 123 Idiopathic choroidal neovascularization: A fresh case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Case 124 Idiopathic choroidal neovascularization: Envelopment by RPE cells . . . . . . . . . . . . . . . . . . . . . . 225
After treatment with anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Case 125 Idiopathic choroidal neovascularization: The scarring process . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Course without treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228

7 Retinal degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

7.1 Multiple evanescent white dot syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
Case 126 Multiple evanescent white dot syndrome: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

7.2 Acute zonal occult outer retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

Case 127 Acute zonal occult outer retinopathy: Eye with a history of MEWDS . . . . . . . . . . . . . . . . . . . . . . 236

7.3 Punctate inner choroidopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238

Case 128 Punctate inner choroidopathy: Atrophic pigmented scars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Case 129 Punctate inner choroidopathy: Case complicated by CNV (fellow eye of case 128) . . . . . . . . . . . . . 240
Case 130 Punctate inner choroidopathy: Yellowish-white spots and CNV . . . . . . . . . . . . . . . . . . . . . . . . . 241

7.4 X-linked juvenile retinoschisis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242

Case 131 X-linked juvenile retinoschisis: Retinoschisis over a wide area . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
Case 132 X-Linked juvenile retinoschisis: Retinoschisis confined to the macula . . . . . . . . . . . . . . . . . . . . . 245

7.5 Stargardt disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

Case 133 Stargardt disease: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

7.6 Vitelliform macular dystrophy and adult-onset foveomacular vitelliform dystrophy . . . . . . . . . . . . 249
Case 134 Adult-onset foveomacular vitelliform dystrophy: Vitelliform stage . . . . . . . . . . . . . . . . . . . . . . . 251
Case 135 Adult-onset foveomacular vitelliform dystrophy: Pseudohypopyon stage . . . . . . . . . . . . . . . . . . 252
Case 136 Adult-onset foveomacular vitelliform dystrophy: The course . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

7.7 Pseudoxanthoma elasticum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

Case 137 Pseudoxanthoma elasticum: A case of Type 1 CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Case 138 Pseudoxanthoma elasticum: A case of Type 2 CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Case 139 Pseudoxanthoma elasticum: A case of polypoidal lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Case 140 Pseudoxanthoma elasticum: Outer retinal tubulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258

7.8 Cancer-associated retinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Case 141 Cancer-associated retinopathy: Damage to the outer retinal layers . . . . . . . . . . . . . . . . . . . . . . . 260
Case 142 Cancer-associated retinopathy: Retinal vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
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7.9 Bietti crystalline dystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262

Case 143 Bietti crystalline dystrophy: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Case 144 Bietti crystalline dystrophy: Outer retinal tubulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264

7.10 Retinitis pigmentosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265

Case 145 Retinitis pigmentosa: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Case 146 Retinitis pigmentosa: Cystoid macular edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Case 147 Retinitis pigmentosa: Vitreomacular traction syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270

7.11 Fundus albipunctatus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

Case 148 Fundus albipunctatus: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272

7.12 Oguchi disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274

Case 149 Oguchi disease: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Case 150 Oguchi disease: Cystoid space formation and golden sheen fundus reflex (fellow eye of case 149) . . 276

8 Uveitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
8.1 Behçet disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
Case 151 Behçet disease: Cystoid edema and foveal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Case 152 Behçet disease: Retinal atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Case 153 Behçet disease: Acute attack . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281

8.2 Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282

Case 154 Sarcoidosis: Cystoid macular edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Case 155 Sarcoidosis: Foveal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284

8.3 Vogt-Koyanagi-Harada disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

Case 156 Vogt-Koyanagi-Harada disease: Large foveal cystoid space . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Case 157 Vogt-Koyanagi-Harada disease: Prominent choroidal thickening . . . . . . . . . . . . . . . . . . . . . . . . 289
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Case 158 Vogt-Koyanagi-Harada disease: Reattachment process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Case 159 Vogt-Koyanagi-Harada disease: Choroidal folds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294

8.4 Sympathetic ophthalmia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295

Case 160 Sympathetic ophthalmia: After vitreous surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296

8.5 Toxocariasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

Case 161 Toxocariasis: Proliferative membrane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298

8.6 Acute retinal necrosis (Kirisawa-type uveitis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299

Case 162 Acute retinal necrosis (Kirisawa-type uveitis): A typical example . . . . . . . . . . . . . . . . . . . . . . . . . 300

9 Pathologic myopia and related diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303

9.1 Myopia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Case 163 Intrachoroidal cavitation: A Typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
Case 164 Intrachoroidal cavitation: Connection with the vitreous cavity . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Case 165 Lacquer cracks: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
Case 166 Lacquer cracks: A mild case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Case 167 ILM detachment: Case without foveoschisis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312
Case 168 Myopic foveoschisis: Case without foveal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Case 169 Myopic foveoschisis: Case with foveal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
One year after surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Case 170 Myopic foveoschisis: Case with macular retinal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Two and a half years after surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Case 171 Myopic foveoschisis: Traction from the thickened posterior vitreous cortex . . . . . . . . . . . . . . . . . 318
Case 172 Myopic foveoschisis: Macular hole formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Case 173 Myopic foveoschisis: MHRD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
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Case 174 Myopic foveoschisis: Before and after surgery for MHRD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Case 175 Myopic subretinal hemorrhages: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
Four months later . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Case 176 Myopic choroidal neovascularization: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
Case 177 Myopic choroidal neovascularization: Small CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
After anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
Case 178 Myopic choroidal neovascularization: Large CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Case 179 Myopic choroidal neovascularization: A young example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
One year after anti-VEGF treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Case 180 Myopic choroidal neovascularization: Foveoschisis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330

9.2 Dome-shaped macula and inferior staphyloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331

Case 181 Dome-shaped macula: A typical example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
Case 182 Inferior staphyloma: Serous retinal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Continuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334

10 Retinal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335

10.1 Rhegmatogenous retinal detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
Case 183 Rhegmatogenous retinal detachment: A case where retinal detachment has stopped
at the fovea centralis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Case 184 Rhegmatogenous retinal detachment: Macular detachment . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
Case 185 Rhegmatogenous retinal detachment: Foveal inner segment defects . . . . . . . . . . . . . . . . . . . . . 339
Case 186 Optic disc pit maculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340

11 Lesion morphology index based on OCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341

Service Part . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
Case Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
 XIII

List of Abbreviations

AI indocyanine green angiography IS/OS photoreceptor inner segment/outer segment

AMD age-related macular degeneration junction
BRAO branch retinal artery occlusion MA microaneurysm
CME cystoid macular edema MHRD macular hole retinal detachment
CNS central nervous system MP-1 microperimeter
CNV choroidal neovascularization MPPE multifocal posterior pigment epitheliopathy
COST cone outer segment tip OCT Optical Coherence Tomography
CRAO central retinal artery occlusion ONL outer nuclear layer
CRV central retinal vein OPL outer plexiform layer
CRVO central retinal vein occlusion PCV polypoidal choroidal vasculopat
(non-ischemic/ischemic) hemi-CRVO (HCRVO) PDT photodynamic therapy
from major branch RVO (BRVO) PED pigment epithelial detachment
CSC central serous chorioretinopathy PVD posterior vitreous detachment
EDI enhanced depth imaging RAO retinal artery occlusion
EDI-OCT enhanced depth imaging optical coherence RAP retinal angiomatous proliferation
tomography RNFL retinal nerve fiber layer
ELM external limiting membrane RPE retinal pigment epithelium
ERM epiretinal membrane RRD rhegmatogenous retinal detachment
FA fluorescein angiography RVO retinal vein occlusion
FAF fundus autofluorescence SD-OCT spectral-domain optical coherence tomography
GCL ganglion cell layer IPL = inner plexiform layer SRD serous retinal detachment
ICC intrachoroidal cavitation SRN subretinal neovascularization
IJRT idiopathic juxtafoveolar retinal telangiectasia VKH Vogt-Koyanagi-Harada disease
IMT idiopathic macular telangiectasia, VMD Vitelliform macular dystrophy
INL inner nuclear layer
 1 1

The basis of OCT interpretation

1.1 B-scan interpretation –2
1.1.1 Factors that determine resolving power – 2
1.1.2 Removing speckle noise by multiple B-scan averaging –3

1.2 Normal retina –4

1.3 Normal choroidal imaging –9

1.4 Displaying B-scans – 10

1.5 Depth resolution misinterpretations – 11

1.6 Artifacts – 13
1.6.1 The effect of involuntary eye movement – 13
1.6.2 Phenomena caused by the optical properties of tissue – 14
1.6.3 Aspects relating to measurement principles – 16
1.6.4 Sensitivity attenuation – 16

References – 19
 2 Chapter 1 · The basis of OCT interpretation

1.1 B-scan interpretation Most current spectral-domain OCT (SD-OCT) products

1 use spectral ranges of 30–50 nm and centre wavelengths of
1.1.1 Factors that determine resolving power 840–870 nm using superluminescent diode (SLD) light sources.
This results in depth resolutions of 5–7 µm (. Fig. 1-1). One
OCT depth resolution exception includes the SPOCT-HR manufactured by OPTOPOL.
OCT depth resolution is determined by the wavelength band This product uses 2 types of SLD light sources with an 85 nm
of the light source (centre wavelength and wavelength range), spectral range in sum resulting in a high depth resolution of
and is unrelated to OCT detection technologies, such as time- 3 µm (term ultrahigh resolution).
domain and spectral-domain (SD). Namely, OCT depth
resolution (∆Z) can be shown with the following mathematical Speckle noise
formula: In addition to depth resolution, speckle noise has an effect on the
resolving power of B-scans(1). As shown in . Fig. 1-2, when B-scan
∆Z = 0.44 × λ2/∆λ images are enlarged, a low-reflective speckle pattern can be seen,
(where λ is centre wavelength and ∆λ is wavelength range) known as speckle noise(2). Speckle noise occurs when an object
is scanned with coherent light, and is the most common cause of
According to this formula, the use of an 840 nm centre wave- blurring to retinal layer boundaries on OCT B-scan images(1, 3, 4).
length and a 40 nm wavelength range will produce depth resolu- High speed image acquisition of SD-OCT allows effective reduc-
tion of 7.76 µm. tion of speckle noise, which generates high resolution B-scan
images.

. Fig. 1-1 Depth resolution and light source wavelength range

The light source wavelength range and corresponding depth resolution of commercially available OCT

. Fig. 1-2 Speckle noise

Scanning with coherent light in OCT imaging produces weakly reflective speckle pattern known as speckle noise. Speckle noise becomes apparently visible
when the B-scan is enlarged.
1.1 · B-scan interpretation
3 1
1.1.2 Removing speckle noise by multiple speckle noise pattern changes with every B-scan The accuracy of
B-scan averaging multiple B-scan averaging depends on the ability to take multiple
scans of the exactly identical location of interest without blurring.
Multiple B-scan averaging To perform multiple B-scan averaging with high accuracy, it is
Multiple B-scan averaging means performing multiple scans of important to have high-speed scanning capabilities and eye
the identical retinal location of interest, aligning and adding the tracking. By successfully averaging an adequate number of scans,
image signals, and finally dividing by the number of scans (. Fig. speckle noise can be sufficiently removed and retinal layer
1-3). Whereas the actual image is stationary, speckle noise is boundaries become distinct (. Fig. 1-4).
diluted by the reciprocal of the total number of scans since

. Fig. 1-3 The principle of multiple B-scan averaging

. Fig. 1-4 Results of multiple B-scan averaging.

A: After 1 B-scan, B: after averaging 10 B-scans, C: after averaging 100 B-scans.
The retinal layer structures becomes more distinct with increasing number of averaged B-scans.
 4 Chapter 1 · The basis of OCT interpretation

1.2 Normal retina a significant angle to the fibers’ orientation. Thus, HFL becomes
1 weakly reflective and becomes indistinguishable from the simi-
OCT creates an image of the intensity of light reflection and scat- larly weakly reflective outer nuclear layer (. Fig. 1-7). However,
tering in chorioretinal tissue. The »fiber layers« and »layer when OCT measurement beam enters the pupil from an eccen-
boundaries«, which strongly reflect light, are highly reflective, tric position, the beam obliquely reaches the retinal surface, and
and the »cellular layers«, which weakly reflects light, are weakly consequently passes the retina perpendicular to the HFL on one
reflective (. Fig 1-5). In sum, there are 3 principles to retinal side (. Fig. 1-6). This increases the reflectivity of HFL causing it
OCT imaging: to be a highly reflective layer.(6, 7) (. Fig. 1-7). This is similar to
4 Cellular layer = weakly reflective, when the retinal layer tilts as a result of retinal detachment or
4 Fibrous layer = highly reflective, drusen (. Fig. 1-8).
4 Boundaries = highly reflective. The axonal endings of the synapse phase of the outer plexi-
form layer combine with tight junctions to form a sheet-like
Cellular layer structure acting as the boundary surface with high reflectivity.
The ganglion cell layer, inner nuclear layer and outer nuclear
layer that are mainly comprised of neuronal cell bodies are weak- Boundary surface
ly reflective. The actual outer nuclear layer is thinner than it ap- Since photoreceptor cells orderly align themselves parallel to
pears, since Henle fiber layer (HFL), histologically fiber layer of OCT probe light, the external limiting membrane (ELM), the
the outer plexiform layer, is included in the low-reflectivity phase photoreceptor inner segment/outer segment junction, and cone
typically thought to be the outer nuclear layer. outer segment tip (COST) form the boundary surface, and can
be seen as 3 highly reflective lines. Since the retinal pigment epi-
Fiber layer thelium (RPE) is also an aligned unicellular layer, its apex and
The nerve fibers of the retinal nerve fiber layer and the inner base each form a boundary and are visible as 2 highly reflective
plexiform layer run parallel to the retinal surface. The OCT mea- lines on ultrahigh resolution OCT.
surement beam enters almost perpendicular to this path, result-
ing in intense reflectivity and scattering to make it a highly reflec- Why is the RPE highly reflective even though
tive layer. The outer plexiform layer, however, is an exception. it is made up of cells?
Since the nerve fibers of HFL tilt forward and towards the periph- The reflectivity of the RPE is thought to be due to melanin pig-
ery of the macula(5) (. Fig. 1-6), the measurement beam enters at ment. However, the RPE can be seen as 2 distinct lines in 3 µm

. Fig. 1-5 Normal retina (speckle noise free)

1.2 · Normal retina
5 1

. Fig. 1-6 The path of HFL

A: Light microscopic image of normal retina, B: diagram of the relationship between HFL and measurement beam (orange arrows).
Reflectivity is enhanced when the retina is tilted and the measurement beam enters the HFL perpendicularly.
(A was modified according to Fine B, Yanoff M. Ocular Histology, 2nd ed. Harper&Row, 1979, p 57)

. Fig. 1-7 The appearance of HFL in the normal retina

A, B: When the OCT measurement beam passes through the centre of the pupil, the HFL is obscured since there is no tilt in the retinal image. C–F: When
the OCT measurement beam passes through the temporal side (C, D) and nasal side (E, F) of the pupil, the nasal retina and temporal retina each tilt back-
ward respectively, and exhibit increased reflectivity in the HFL.

. Fig. 1-8 The appearance of HFL in eyes with macular diseases

A: Serous retinal detachment (SRD) in central serous chorioretinopathy (CSCR). B: Drusen in retinal angiomatous proliferation (RAP). There are areas where
HFL becomes highly reflective and thereby visible due to retinal tilt against the OCT measurement beam as a result of lesions.
 6 Chapter 1 · The basis of OCT interpretation

. Fig. 1-9 A comparison of light microscopic and tomographic views of the retinal pigment epithelium (RPE). The RPE is seen as 2 highly reflective lines on
3 µm SD-OCT. The highly reflective RPE line is comprised of 2 highly reflective lines representing apical and basal (including Bruch‘s membrane) membranes
and hyporeflective line between these 2 lines representing cytoplasm. These 2 lines can be distinguished in 3 µm SD-OCT, but not on standard resolution
(5~7 µm) SD-OCT.
(Modified according to Fine B, Yanoff M. Ocular Histology, 2nd ed. Harper&Row, 1979, p67)

. Fig. 1-10 RPE line, resolution, and speckle noise

The aggregation of RPE high reflectivity – low reflectivity – high reflectivity can be observed in 3 µm single scan SD-OCT image. However, in 7 µm OCT, only
one bold highly reflective line can be seen even when speckle noise is removed.

ultrahigh resolution OCT (manufactured by Canon) (. Fig. 1-9) What is the natural shape of the third line?
(1). Using 5–7 µm depth resolution, only 1 aggregate line is seen During SD-OCT examination, one further highly reflective line
even when speckle noise is removed (. Fig. 1-10). The 2 highly can be seen between the so-called photoreceptor inner segment/
reflective lines that can be seen in OCT with a depth resolution outer segment junction (IS/OS) lines and the RPE. This is the
of 3 µm correspond to the 2 boundary surfaces that are the apex third line following the ELM lines and IS/OS line, so it is referred
and base of the RPE, which become 2 distinct, highly reflective to as the third line. It is debated as to what this line corresponds
lines due to the low reflectivity of the cells between them. Nor- to, but when observed in ultrahigh resolution (3 µm) SD-OCT,
mally, the base is consistent with the lines of Bruch’s membrane. it is thought to be the cone outer segment tip (COST) in the
However, when an RPE detachment occurs, Bruch’s membrane macular area (. Fig. 1-11)(1, 8). Outside the macular area, yet
can be distinguished at an SD-OCT depth resolution of just another highly reflective line has been observed, thought to be the
5–7 µm. rod outer segment tip (ROST), between the IS/OS and the RPE.
The COST line disappears due to milder photoreceptor cell ab-
normalities than the IS/OS and ELM lines.
1.2 · Normal retina
7 1

. Fig. 1-11 COST and ROST in SD-OCT with a depth resolution of 3 µm

A: Horizontal B-scan. COST is observed from the fovea centralis to the outside of the macula ( ), whereas ROST is observed from the periphery of the
macula to the outside of the macula ( ). B: The enlarged image of A representing fovea centralis. The fovea centralis OS is long and the IS/OS looks moun-
tain-shaped, but the COST always appears to run parallel to the vicinity of the RPE, suggesting this is the cone sheath, which is enveloped by the apical
processes of the retinal pigment epithelium. C: Periphery of the macula – outside of the macula enlarged image of A. Another line ( ) was observed
between the COST line ( ) and the RPE apical line. This is the ROST.

The mystery of photoreceptor cell inner pendently, Spaide et al. reviewed the literature of retinal histology
and outer segment junction line starting from 1990 and created a scale model of photoreceptor
The anatomical structure of the highly reflective lines that cor- cells. When compared with B-scan images from Spectralis HRA
respond to the photoreceptor inner and outer segment junction + OCT the IS/OS line correspond to the ellipsoid portion of
is the subject of debate. the IS and the COST line corresponds to the termination of the
In recent years, Drexler et al. have been able to observe indi- OS enveloped by RPE apical processes (cone sheath or contact
vidual photoreceptor cells through adaptive-optics (AO) ultra- cylinder)(10).
high-resolution (UHR) SD-OCT(9) (. Fig. 1-12). This AO-OCT
system allows correction of chromatic and monochromatic Symmetry of the normal retinal layer structure
ocular aberrations, and has enhanced lateral as well as depth Within the neural retinal layer structure, the retinal nerve fiber
resolution to micron levels (2–3 µm). Since photoreceptor cells layer (RNFL) is symmetrical between upper and lower hemi-
can be distinguished in the AO UHR SD-OCT imaging, the ELM sphere. However, there is no symmetry of the RNFL nasally and
and IS/OS become dotted lines. In this imaging, ellipsoids where temporally to the fovea centralis. In contrast, the other layers
the mitochondria accumulates have a high reflectivity, and are outside the RNFL (ganglion cell layer, inner plexiform layer, in-
thought to constitute the IS/OS line. In this OCT, we see highly ner nuclear layer, outer plexiform layer, and outer nuclear layer)
reflective bands in 2 locations, immediately in front of the fovea are symmetrical nasally and temporally to the fovea centralis in
centralis and the RPE (. Fig. 1-12). Anatomically, the OS of cone addition to having upper and lower symmetry, that is, 2-dimen-
photoreceptor cells terminate before reaching the RPE and are sionally symmetry centered at the fovea centralis.(11, 12) (. Fig.
enveloped by the RPE apical processes. The outer line of these 1-13, 1-14).
2 high reflectivity bands is thought to be due to the COST. Inde-
 8 Chapter 1 · The basis of OCT interpretation

. Fig. 1-12 Photoreceptor cell images on adaptive-optics ultrahigh-resolution SD-OCT

Photoreceptor cells run parallel to the optical axis and are arranged like rice plant. The highly reflective planes of the photoreceptor cells form the IS/OS
lines and COST line. In AO UHR-SD-OCT, these lines appear as dotted lines, but in standard resolution SD-OCT, they appear as contiguous lines.
(Modified according to Fernández EJ, et al. Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human
retina. Opt Express. 2008; 16: 11083-11094)

. Fig. 1-13 B-scans in a normal eye

A: OCT horizontal scan. The RNFL gets thicker nasally and thinner temporally. Apart from the RNFL, all other layers are symmetrical. B: OCT vertical scan. All
layers have vertical symmetry. The RNFL is thicker at the periphery, the outer nuclear layer is thicker at the fovea centralis, and the ganglion cell layer forms
a peak outside the fovea.

inner segment
outer segment
retinal nerve fiber layer
1.3 · Normal eye choroidal imaging
9 1

. Fig. 1-14 Retinal layer thickness colour map

A: Retinal nerve fiber layer, B: ganglion cell layer, C: inner plexiform layer, D: inner nuclear layer, E: outer plexiform layer + outer nuclear layer, F: photo-
receptor inner segment, G: photoreceptor outer segment. Each retinal layer has high symmetry, but the ganglion cell layer and inner nuclear layer are
slightly thinner temporally.
(Modified according to Ooto S, et al. Effects of age, gender, and axial length on the three-dimensional profile of normal macular layer structures. Invest
Ophthalmol Vis Sci. 2011; 52: 8769-8779)

1.3 Normal choroidal imaging an inverted mirror image as shown in . Fig. 1-15. Usually, to
avoid signal attenuation in the depth direction and to increase the
EDI-OCT visualization signal of the retina, the reference surface is set to
SD-OCT has a coherence gate (depth at which the interference the vitreous side; however, the reference surface of the inverted
image can be obtained) of about 2 mm. An interference signal mirror image surface is on the choroidal side. This mirror image
can be obtained when the retinal tissue examined enters this co- appears in the imaging frame when the OCT objective lens gets
herence gate, but the signal intensity attenuates in the depth di- closer to the patient’s eye during scanning. Retinal signal inten-
rection (see . Fig. 1-35 7 page 18). Consequently, to obtain high- sity is not high in this mirror image, but choroidal signal inten-
quality images in SD-OCT, it is important to bring the retinal sity increases. When averaging 100 scans of this mirror image,
tissue to the upper imaging range. In contrast, EDI-OCT creates the speckle noise is removed and visualization of the choroid and

. Fig. 1-15 An explanatory diagram of EDI-OCT

A: Mirror image, B: normal image.
 10 Chapter 1 · The basis of OCT interpretation

. Fig. 1-16 SS-OCT B-scan image and choroidal thickness map

A: Horizontal B-scan, B: choroidal thickness map. From the left: hypermetropia, emmetropia, myopia.
(Modified according to Hirata M, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography.
Invest Ophthalmol Vis Sci. 2011; 52: 4971-4978)

lamina cribrosa is markedly improved. This imaging method is Choroidal thickness

reported by Spaide et al., and is known as enhanced depth imag- Choroidal thickness of normal eyes decreases with older age and
ing (EDI)(13). longer axial length(15, 16). In addition, the choroidal thickness in
the macular area is thinner nasally and thicker temporally re-
SS-OCT gardless of ocular axial length(15, 17).
Many commercially available SD-OCT use SLD light sources with
centre wavelengths of 840–870 nm. Recently, 1,050 nm swept
source OCT (SS-OCT) prototypes have been developed, which 1.4 Displaying B-scans
are known to excel in choroidal visualization (. Fig. 1-16A). Since
1,050 nm light is better at permeating the RPE than 800–900 nm Displaying reflection intensity
light it is possible to use more light in choroidal image acquisition. When the reflection intensity of light is displayed in black, the
In addition, there is little signal intensity attenuation in the depth background image is white. Conversely, when it is displayed in
direction as seen in SD-OCT, resulting in clear images of not white, the background image is black (. Fig. 1-17).
only the choroid but also of the vitreous body. With SS-OCT,
averaging B-scans for choroidal thickness measurements is not Displaying false colours
required and dense raster scan can be performed to create 3-di- False colour displays are often used to indicate the reflection dis-
mensional choroidal thickness maps. Currently, there are already tribution (. Fig. 1-18). Colours are applied to the reflection in-
reports on choroidal thickness of normal eyes measured using tensity of light, such as warm colours for strong reflectivity and
SS-OCT(14, 15) (. Fig. 1-16B). cool colours for weak reflectivity. The colours, however, do not

. Fig. 1-17 B-scan with white background and black background

1.5 · Depth resolution misinterpretations
11 1

. Fig. 1-18 B-scan with false colour display

have a specific meaning. In high-definition B-scans with speckle

noise removed, subtle changes in reflection intensity attributed
to layer boundaries or small lesions can be recognized on mono-
chromatic displays. However, with false colour displays, subtle
changes in reflective light intensity are harder to discern.

1.5 Depth resolution misinterpretations

Speckle noise removal has more impact than

depth resolution on layer structure visualization
The thickness of each retinal layer in the macula exceeds 30 µm
in thickness (. Fig. 1-19)(11). Thus, theoretically, if time-domain
OCT with a depth resolution of 10 µm such as OCT 2000 or
Stratus OCT is used, the retinal layer structure of the macula
should be clearly visualized. When speckle noise is removed from
Stratus OCT imaging, each retinal layer is indeed clearly visual- . Fig. 1-19 Average macular retinal thickness
ized (. Fig. 1-20)(3). In contrast, the layer structure does not be- (Modified according to Ooto S, et al. Effects of age, gender, and axial length
on the three-dimensional profile of normal macular layer structures. Invest
come distinct even when the depth resolution is increased to
Ophthalmol Vis Sci. 2011; 52: 8769-8779)
3 µm(1).
Therefore, the removal of speckle noise is highly important
in improving the resolving power of each retinal layer through
OCT (. Fig. 1-21, 1-22).

ELM and IS/OS boundaries can be visible with

removal of speckle noise
The external limiting membrane and photoreceptor inner and
outer segment junction are histologically merely boundaries,
and thus have almost no thickness to them. However, if the outer
nuclear layer (over 30 µm) and the IS (about 23 µm) anterior and
posterior to the ELM, respectively, could be resolved, the ELM
could theoretically be visualized. Similar to the previous section,
analysis of these layers is indeed possible even with the OCT 2000
and Stratus OCT after speckle-noise reduction (. Fig. 1-23)(3).
This indicates that the speckle noise, but not the depth resolu-
tion, is mainly responsible for the unclear visibility of the ELM
and IS/OS in time-domain OCT.

. Fig. 1-20 Speckle noise removal in OCT 3000

A: B-scan. B, C: Image based on the averaging of 13 scans.
(Modified according to Sander B, et al. Enhanced optical coherence tomogra-
phy imaging by multiple scan averaging. Br J Ophthalmol. 2005; 89: 207–212)
 12 Chapter 1 · The basis of OCT interpretation

1 A B

. Fig. 1-21 3 µm single scan SD-OCT image without speckle noise reduction (A) vs. 7 µm SD-OCT . Fig. 1-22 3 µm single scan SD-OCT image with-
image with speckle-noise removed (B) out speckle noise reduction (A) vs. 7 µm SD-OCT
Ganglion cell layer (GCL, red double arrows) boundaries are obscured even at a depth resolution of image with speckle-noise removed (B)
3µm. GCL boundaries appear distinct after speckle noise removal even at a depth resolution of 7 µm. Cases of cystoid macular edema. Layers where
lesions exist can be clearly seen after speckle noise
removal.
(Modified according to Hangai M, et al. Ultrahigh-
resolution versus speckle noise-reduction in
spectral-domain optical coherence tomography.
Opt Express. 2009; 17: 4221-4235)

. Fig. 1-23 Speckle noise removal in OCT 2000

Even with a depth resolution of 20 µm (OCT 2000), the ELM and IS/OS are visualized after an average of 9 scans is performed and speckle noise is reduced.
(According to Sander B, et al. Enhanced optical coherence tomography imaging by multiple scan averaging. Br J Ophthalmol. 2005; 89: 207-212)
1.6 · Artifacts
13 1
1.6 Artifacts flicks, and drifts (. Fig. 1-24). In time-domain OCT, distortion
occurs on each B-scan image as a result of involuntary eye move-
1.6.1 The effect of involuntary eye ment due to the slow imaging speed (. Fig. 1-25). Thus, it is dif-
movement ficult to capture the same image and to remove speckle noise.
High speed image acquisition in SD-OCT allows 3-dimensional
Involuntary eye movement raster scanning and precise averaging of B-scans to remove
Involuntary eye movement is high-frequency micro-movement speckle noise. However, involuntary eye movement can cause
of the eyeball that occurs when the eyeball gazes steadily at a fixed jagged pattern in the 3-dimensional imaging and averaging
target. These movements are composed of 3 elements: tremors, errors in speckle-noise removal (. Fig. 1-27).

tremor :movement
tremor : Extremely small, high-frequency Extremely small, high-frequency movement
tremor : Extremely small, high-frequency movement

drift : Small, smooth movements drift : Small, smooth movements

drift : Small, smooth movements

flick : A little, jerk-like movements flick : A little, jerk-like movements (microsaccades)

(microsaccades)
flick : A little, jerk-like movements (microsaccades)

. Fig. 1-24 The 3 elements of involuntary eye movement (schematic diagram)

. Fig. 1-26 3-dimensional image

obtained with spectral-domain OCT
. Fig. 1-25 Image distortion in time-domain OCT Involuntary eye movement can be seen
The distortion is different in each scan. as jagged patterns known as ridges.

B B
B
Failure Failure
Failure

A
A

Success Success
Success

. Fig. 1-27 Errors in B-scan averaging

A: An averaging error occurred due to involuntary eye movement thought to be a flick. B: The B-scan image appears blurred due to an averaging error
thought to be the effect of a tremor.
 14 Chapter 1 · The basis of OCT interpretation

1.6.2 Phenomena caused by the optical absorbed by intact retina and RPE reaches the posterior choroid
1 properties of tissue and sclera. While usually difficult to visualize, the visualization
of these tissues become enhanced (. Fig. 1-30).
Shadows caused by measurement beam blockage
OCT measurement beams can be blocked by 1) blood flow (. Fig. Low-reflectivity due to tilting
1-28) and 2) opaque lesions (. Fig. 1-29), resulting in more poste- When a measurement beam is perpendicular to the nerve fibers
rior tissue not being visualized. Blood flow causes loss of the in- and boundaries, the reflectivity of these structures reaches its
terference signal known as fringe washout. Signals lost posterior maximum, resulting in visualization. However, when the retinal
to retinal blood vessels exhibit findings known as shadows. angle tilts in relation to the measurement beam due to retinal
The effect of the blockage is stronger with more opaque detachment or retinal pigment epithelial detachment, reflectivity
lesions. Heavy hemorrhage and dense hard exudates can cause of these layers becomes diminished (. Fig. 1-31). Conversely,
complete measurement beam blockage resulting in no visibility HFL, which originally runs diagonally to the outer plexiform
of posterior tissues.. layer, becomes highly reflective when perpendicular to the
measurement beam (. Fig. 1-31, Fig. 1-6 7 page 5).
High-reflectivity caused by excessive measurement
beam penetration
Conversely, in lesions where retinal degeneration or atrophy
is apparent, the light that is normally reflected and scattered or

. Fig. 1-28 Measurement beam blockage caused by retinal blood vessels (IR + OCT vertical scans)
Arrows (→) indicate shadows caused by retinal blood vessels

. Fig. 1-29 Measurement beam blockage caused by opaque lesions (color fundus photography + OCT B-scans)
A: Due to retinal hemorrahge, B: due to dense hard exudates.

artifacts
1.6 · Artifacts
15 1

. Fig. 1-30 Cone dystrophy (IR + OCT macula horizontal scan)

Choroidal sensitivity is remarkably high beneath the thinned and degenerated macula.

. Fig. 1-31 Decrease in reflection intensity caused by retinal tilt (OCT B-scan)
A: Retinal pigment epithelial detachment. The IS/OS lines in the uninvolved retina perpendicular to the optical axis are highly reflective, whereas the reflec-
tivity of the IS/OS lines in the retinal pigment epithelial detachment area is comparatively low. B: Central serous chorioretinopathy. Within the detached
retina, the perpendicularly oriented portion continues to have high reflectivity while the tilted portion has comparatively low reflectivity. C: Dome-shaped
macula. Reflectivity of each layer and IS/OS lines on the more tilted side is comparatively low.

artifacts
 16 Chapter 1 · The basis of OCT interpretation

1.6.3 Aspects relating to measurement principles 3. Image not in optimal imaging depth range
1 4. Insufficient eyelid opening
Reflection of virtual images
SD-OCT has inverted virtual images (termed mirror images) Listed below are issues caused by the subject.
outside the imaging frame (. Fig. 1-32). As a result, the virtual 1. Media opacity (corneal opacity, cataract, vitreous opacity)
images of tissue and lesions sometimes enter the imaging frame. 2. Ocular surface problems (dry eye, examination immediately
When this occurs, both real and virtual images are visualized in after contact lens wear for slit lamp examination)
the imaging frame at the same time (. Fig. 1-33). 3. Poor fixation
Involuntary eye movements cause the vitreous body to
change its position against the eye ball. Thus, opacities within the Decreases in image sensitivity reduces measurement results of
posterior vitreous cavity and posterior vitreous membrane are retinal and retinal nerve fiber layer thickness. Since sensitivity
sometimes seen as multiple overlapping layers in B-scan images attenuation caused by the subject are difficult to improve, effort
with speckle noise removed because these tissues change their must be made to resolve imaging-related sensitivity attenuation.
position during multiple scanning for averaging (. Fig. 1-33).
Defocusing
In OCT focusing, various mechanisms are used depending on
1.6.4 Sensitivity attenuation the OCT model such as adjusting the focus in SLO imaging, and
devices with automatic optimization features. Defocusing is the
Causes of sensitivity attenuation main cause of decreased image sensitivity (. Fig. 1-34).
Decreases in image sensitivity can occur from various causes.
Listed below are issues caused by imaging.
1. Being out of focus
2. The measurement beam enters the pupil eccentrically and
does not intersect the retina perpendicularly

. Fig. 1-32 Real images and virtual images

Usually, a virtual image is an upside down real image, and the contralateral side (lower section) is highly sensitive.

artifacts
1.6 · Artifacts
17 1

. Fig. 1-33 Virtual images overlapping the real images

A: Asteroid hyalosis, B: Stage 3 macular hole, C: Vitreomacular traction syndrome.
When images are averaged, involuntary eye movement causes flickering of the posterior vitreous cortex resulting in characteristic overlap and reflection.

. Fig. 1-34 Decreased sensitivity due to defocusing

A: Image with well-adjusted focus (Quality index 46 dB), B: Image with poorly adjusted focus (Quality index 29 dB).

Artifacts
 18 Chapter 1 · The basis of OCT interpretation

Sensitivity attenuation along depth direction

1 In principle, the SD-OCT has a narrow imaging depth range for and retinal detachment are problematic (. Fig. 1-37, 1-38). In the
obtaining highly sensitive images. The sensitivity decreases with next generation swept source OCT (SS-OCT), longer imaging
Imaging range (coherence gate) (. Fig. 1-35, 1-36). Tissue and depth can be achieved without significant decrease in sensitivity
lesions with axially elongated structure such as severe myopia (. Fig. 1-37).

. Fig. 1-35 Relationship between imaging range depth and OCT signal
intensity

. Fig. 1-36 Relationship between imaging range depth and SD-OCT signal
intensity
Sensitivity attenuation increases with depth. A: 46 dB, B: 40 dB, C: 31 dB.

. Fig. 1-37 Image of SD-OCT sensitivity attenuation compared with SS-OCT . Fig. 1-38 SD-OCT sensitivity attenuation in a peripapillary circle scan
in a dome shaped macula Image of retinal nerve fiber layer on a circle scan centered at the optic disc.
A: SD-OCT. Downward image sensitivity is low. B: EDI-OCT. Downward Due to tilting of the sclera around the optic disc, severe myopia results
image sensitivity is similarly low. C: SS-OCT (Topcon Corporation proto- in an image elongated along depth direction and a decreasing downward
type). There are no areas of apparently decreased sensitivity. sensitivity.
References
19 1
References

1) Hangai M, Yamamoto M, Sakamoto A, et al. Ultrahigh-resolution versus

speckle noise-reduction in spectral-domain optical coherence tomogra-
phy. Opt Express. 2009; 17:4221–4235.
2) Schmitt JM, Xiang SH, Yung KM. Speckle in optical coherence tomogra-
phy. J Biomed Optics. 1999; 4:95–105.
3) Sander B, Larsen M, Thrane L, et al. Enhanced optical coherence tomogra-
phy imaging by multiple scan averaging. Br J Ophthalmol. 2005; 89:207–
212.
4) Sakamoto A, Hangai M, Yoshimura N. Spectral-domain optical coherence
tomography with multiple B-scan averaging for enhanced imaging of
retinal diseases. Ophthalmology. 2008; 115:1071–1078.
5) Fine B and Yanoff M. Ocular Histology 2nd ed. Harper & Row, 1979, p57.
6) Otani T, Yamaguchi Y, Kishi S. Improved visualization of Henle fiber layer
by changing the measurement beam angle on optical coherence tomog-
raphy. Retina. 2011; 31:497–501.
7) Lujan BJ, Roorda A, Knighton RW, et al. Revealing Henle’s fiber layer using
spectral domain optical coherence tomography. Invest Ophthalmol Vis
Sci. 2011; 52:1486–1492.
8) Srinivasan VJ, Monson BK, Wojtkowski M, et al. Characterization of outer
retinal morphology with high-speed, ultrahigh-resolution optical coher-
ence tomography. Invest Ophthalmol Vis Sci. 2008; 49:1571–1579.
9) Fernández EJ, Hermann B, Povazay B, et al. Ultrahigh resolution optical
coherence tomography and pancorrection for cellular imaging of the liv-
ing human retina. Opt Express. 2008; 16:11083–11094.
10) Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer
retina by optical coherence tomography: literature review and model.
Retina. 2011; 31:1609–1619.
11) Ooto S, Hangai M, Tomidokoro A, et al. Effects of age, gender, and axial
length on the three-dimensional profile of normal macular layer struc-
tures. Invest Ophthalmol Vis Sci. 2011; 52:8769–8779.
12) Curcio CA, Messinger JD, Sloan KR, et al. Human chorioretinal layer thick-
nesses measured in macula-wide, high-resolution histologic sections. In-
vest Ophthalmol Vis Sci. 2011; 52:3943–3954.
13) Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-do-
main optical coherence tomography. Am J Ophthalmol. 2008; 146:496–
500.
14) Ikuno Y, Maruko I, Yasuno Y, et al. Reproducibility of retinal and choroidal
thickness measurements in enhanced depth imaging and high-penetra-
tion optical coherence tomography. Invest Ophthalmol Vis Sci. 2011;
52:5536–5540
15) Hirata M, Tsujikawa A, Matsumoto A, et al. Macular choroidal thickness
and volume in normal subjects measured by swept-source optical coher-
ence tomography. Invest Ophthalmol Vis Sci. 2011; 52:4971–4978.
16) Manjunath V, Taha M, Fujimoto JG, et al. Choroidal thickness in normal
eyes measured using Cirrus HD optical coherence tomography. Am J Oph-
thalmol. 2010; 150:325–329.
17) Ikuno Y, Tano Y. Retinal and choroidal biometry in highly myopic eyes with
spectral-domain optical coherence tomography. Invest Ophthalmol Vis
Sci. 2009; 50:3876–3880.
 21 2

Vitreoretinal interface pathology

2.1 Idiopathic macular holes – 23
References – 28

Case 1 Physiological PVD: Flattening of foveal depressions – 29

Case 2 Idiopathic macular hole: Progression from Stage 1 (cystoid
space type) to Stage 2 – 30
Case 3 Idiopathic macular hole: Stage 1 foveal cystoid space
formation type – 31

Case 4 Idiopathic macular hole: Stage 1 foveal detachment type – 32

Case 5 Idiopathic macular hole: Stage 1 photoreceptor dehiscence
type – 33
Case 6 Idiopathic macular hole: Stage 1 small foveal detachment
type – 34
Case 7 Idiopathic macular hole: Case just before progression
from stage 1 to stage 2 – 35

Case 8 Idiopathic macular holes: Typical example of stage 2 – 36

Case 9 Idiopathic macular hole: Postoperative course for macular hole
closure under gas tamponade – 38

Case 9 DONFL appearance – 39

Case 10 Idiopathic macular hole: Postoperative course for macular hole
closure – 40

Case 11 Idiopathic macular hole: Typical example of stage 3 – 41

Case 11 After surgery – 42

Case 12 Idiopathic macular hole: Typical example of stage 4 – 43

Case 13 Idiopathic macular hole: Old case of stage 4 – 44

Case 13 Stage 4 after surgery – 45

Case 14 Idiopathic macular hole: Progression from lamellar to full-thickness
macular holes – 46
Case 15 Stage 1 macular hole: Spontaneous separation
of perifoveal PVD – 47

Case 16 Stage 1 macular hole: Macular microhole formation – 48

Case 17 Stage 2 macular hole: Spontaneous closure – 49

Case 18 Stage 3 macular hole: Spontaneous closure – 50

Case 19 Stage 4 macular hole: Spontaneous closure – 51

Case 20 Traumatic macular hole: A typical example – 52

Case 21 Lamellar macular hole: A typical example – 54

Case 22 Lamellar macular hole: Differentiation from a MPH – 55

Macular microholes – 56
References – 56

Case 23 Macular microhole: with macular PVD – 57

Case 24 Macular microhole: with complete PVD – 58

Case 25 Macular microhole: Case without PVD – 59

2.2 Idiopathic epiretinal membrane – 60

References – 62

Case 26 Idiopathic epiretinal membrane: A typical example – 63

Case 27 Idiopathic epiretinal membrane: Exposure of the fibrocellular
membrane – 64
Case 28 Idiopathic epiretinal membrane: Membrane with significant
whitening – 65
Case 29 Idiopathic epiretinal membrane: Significant columnar structure
formation – 66
Case 30 Idiopathic epiretinal membrane: Case ① where macular PVD
has not been complete – 67
Case 31 Idiopathic epiretinal membrane: Case ② where macular PVD
has not been complete – 68

Case 32 Epiretinal membrane secondary to retinal hemangioma – 69

Case 33 Macular pseudohole: A typical example – 70

Case 34 Macular pseudohole: Case where macular PVD has not been
complete – 71

2.3 Vitreomacular traction syndrome – 72

References – 72

Case 35 Vitreomacular traction syndrome: Case showing disease

development – 73

Case 35 Continuation – 74
Case 36 Vitreomacular traction syndrome: Cases with macular
detachment – 75
Case 37 Vitreomacular traction syndrome: A highly myopic eye with
foveoschisis – 76
2.1 · Idiopathic macular holes
23 2
2.1 Idiopathic macular holes optic disc, thereby completing the course of PVD (. Fig. 2-1E). In
idiopathic macular holes, the perifoveal PVD generates an ante-
Background rior traction force towards the fovea centralis, which causes the
Idiopathic macular holes occur frequently in middle-aged to el- structure of the fovea to collapse, forming full-thickness macular
derly individuals (between 50 and 70 years of age) with emme- holes. Kishi et al. state that, PVD occurs when the thin elastic
tropia. The female to male ratio is more than 3:1(1). Onset is seen posterior wall of the premacular liquefied pocket contracts with
bilaterally in over 10%. In 1988, Gass categorized the progression age (. Fig. 2-3)(12). In the final stage of this process, the following
to hole formation into 4 stages based on biomicroscopic find- 3 patterns emerge:
ings(2) and suggested that treatment by vitreous surgery was po- 4 full-thickness macular hole formation
tentially effective. In 1991, Kelly and Wendel reported that full- 4 PVD is completed without progressing to full-thickness
thickness macular holes could be closed by vitreous surgery and macular hole with foveal structural abnormalities remaining
gas tamponade(3), after which vitreous surgery became standard 4 PVD is completed without evident abnormalities in foveal
treatment. Currently, most macular holes can be closed in com- shape
bination with internal limiting membrane peeling. Gass reflected
on the findings of macular hole surgery and revised the catego- It is not clear why the physiological PVD leads to these 3 patterns,
ries himself in 1995(4). Afterwards, the concept of foveal trac- but abnormal adhesion of the posterior vitreous cortex and
tion occurring during the process of posterior vitreous detach- fovea (13) as well as thin foveal thickness are thought to be in-
ment (PVD) was proposed with the introduction of OCT in volved.
1997, establishing the basis for understanding macular hole
pathology (5–10).

Pathogenesis
The progression of physiological PVD can be elucidated by
OCT(11) (. Fig. 2-1, 2-2). In the course of physiological PVD,
posterior vitreous cortex detachment progresses from outside of
the macula, via the periphery of the macula to the fovea (. Fig.
2-2A). This leads to perifoveal detachment of the posterior vitre-
ous cortex with its persistent attachment to the fovea (termed
perifoveal PVD, . Fig. 2-1C, 2-2C). The remaining attachment to
the fovea is resolved leading to macular PVD (. Fig. 2-1D, 2-2D).
Finally, a glial ring (Weiss ring) is found on the fundus image
once there is separation of the posterior vitreous cortex from the

. Fig. 2-2 The process of physiological PVD and OCT imaging

. Fig. 2-1 The process of physiological PVD . Fig. 2-3 Physiological PVD and the premacular liquefied pocket
(Modified according to Uchino E, et al. Initial stages of posterior vitreous Contraction of the posterior wall of the precortical vitreous pocket is be-
detachment in healthy eyes of older persons evaluated by optical co- lieved to cause perifoveal PVD
herence tomography. Arch Ophthalmol. 2001; 119: 1475–1479)
 24 Chapter 2 · Vitreoretinal interface pathology

Stage classification dehiscence at the umbo. Thus, dividing Stage 1 up based on the
Observations with OCT have complemented macular hole stage presence or absence of photoreceptor dehiscence is essential.
classifications(2, 4) based on ophthalmoscopic observations made In this book, Stage 1A represents no photoreceptor de-
2 by Gass(5–10). However, it is difficult for Gass’s Stage 1A and Stage hiscence at the foveola, and Stage 1B represents dehiscence. If
1B to fully support OCT findings. The essence of idiopathic defined in this way, the classification is decided based on the
macular hole onset is the disruption or removal of the Müller stage of PVD and the foveal shape (. Fig. 2-4).
cell cone (illustrated below) resulting in foveal photoreceptor

Understanding macular hole stage classification better

Stage 1 is a stage where the fovea shape is variably deformed wards the fovea centralis is lost is Stage 3, and the stage where
due to perifoveal PVD, but have not developed a full thickness PVD is completed and macular hole an operculum can no longer
macular hole. There are cases where foveal cystoid spaces are be seen with OCT (the Weiss ring is seen on an biomicroscopy) is
initially formed, cases where foveal detachment develops first, Stage 4. The Stage 1 roof, Stage 2 flap and Stage 3 operculum are
or cases where both occur (. Fig. 2-4). Changes strongly related thought to be the same tissue. When the macular holes reach full
to visual impairment are foveal photoreceptor dehiscence, and thickness, the centrifugal elevation of the edge of the macular
as mentioned previously, In this book, Stage 1A is before dehis- hole progresses and visual impairment increases.
cence and Stage 1B is after dehiscence. A full-thickness macular In view of the relationship with posterior vitreous detachment,
hole forms when a cleft develops in the anterior walls of the cys- in Stage 1 and Stage 2 the posterior vitreous cortex and the
toid space and foveal detachment or foveal photoreceptor de- fovea are connected. In Stage 3 the posterior vitreous cortex is
hiscence occurs. The stage where the posterior vitreous cortex detached from the fovea, but is still connected to the optic disc.
and fovea are connected by a flap is Stage 2, the stage where In Stage 4 posterior vitreous detachment is complete and the
the flap is disconnected from the fovea centralis to become an posterior vitreous cortex is not visualized since it is outside the
operculum and traction from the posterior vitreous cortex to- OCT imaging range (. Fig. 2-5).

. Fig. 2-4 Foveal deformation and stage classifications . Fig. 2-5 Posterior vitreous cortex and stage classifications
2.1 · Idiopathic macular holes
25 2
Spontaneous separation of perifoveal PVD when the perifoveal PVD is spontaneously separated, regardless
and foveal deformation, in particular lamellar of the development of a Stage 1 macular hole, abnormal contour
macular holes of the foveal depression, such as flat and v-shaped foveal surface,
In Stage 1 macular holes, defined as, the fovael deformation remains (. Fig. 2-6, 2-7). These foveal contour abnormalities are
secondary to perifoveal PVD, the perifoveal PVD frequently frequently seen with OCT in the fellow eye of patients with uni-
separates into a completed macular PVD without progression to lateral macular holes (13).
full thickness macular holes. This process results in various
foveal deformation. When the spontaneous separation occurs The state of fellow eyes
in Stage 1 macular holes that have cystoid spaces with clefts in As mentioned above, a high rate of foveal contour abnormalities
the Henle fiber layer (HFL), lamellar macular holes develop, are seen in the fellow eyes of eyes with unilateral macular holes.
which are characterized by the clefts remaining in the HFL and In cases where perifoveal PVD is seen, some patients have re-
diminished fovea or parafovea (. Fig. 2-6, 2-11)(8, 14). On the sidual foveal deformation (9%) whereas in others the normal
other hand, when spontaneous separation of perifoveal PVD contour is maintained (7%) (. Fig. 2-6)(13). When perifoveal PVD
occurs in Stage 1 macular holes with foveal detachment or foveal is seen in the fellow eye, macular hole incidence increases by six-
photoreceptor dehiscence, the disruption of the inner and outer fold(16). In cases of complete PVD some patients have residual
segments of photoreceptors in the fovea are left, which accounts foveal deformation (17%) while others maintain a normal foveal
for the pathogenesis of a part of macular microholes (. Fig. 2-6, contour (36%).
2-7, macular microhole paragraph 7 see page 58)(15). In addition,

. Fig. 2-6 Spontaneous separation of perifoveal PVD and residual deformation of the fovea (diagram)
 26 Chapter 2 · Vitreoretinal interface pathology

Spontaneous closure collected macular hole opercula(29). Moreover, when observed by

While rare, spontaneous closure can occur in all stages from OCT, there are cases where the elevated photoreceptor layer of
Stage 1 to Stage 4(17–21). In addition, reopening can occur after the macular hole edges is observed without a defect of IS/OS, and
2 spontaneous closure(22). After spontaneous macular hole closure, other cases where a (large) part of IS/OS is defective. These find-
the foveal depression shows abnormal contour similar to that ings may reflect photoreceptor inner and outer segments lost
seen after spontaneous separation of perifoveal PVD. during or after macular hole formation.

Postoperative visual prognosis Postoperative OCT findings

The macular hole closure rate has improved with internal limit- Even if macular hole closure is confirmed with biomicroscopy
ing membrane peeling. In the literature, macular hole closure shortly after macular hole surgery (1 month after), various foveal
rates are reported to be between 76.4 and 100%. However, out- contour abnormalities such as defects of foveal inner and outer
comes in postoperative visual acuity can vary greatly even when segments, foveal detachment, loss of IS/OS and ELM reflectivity,
macular hole closure is achieved. Despite cases of postoperative thinning of the fovea centralis and the IS/OS and ELM lines
visual acuity improving to over 1.0, there are also cases of visual depressed onto the retinal pigment epithelium (RPE) line can be
acuity not changing much at all: such cases of poor visual prog- seen with OCT. These findings are associated with visual impair-
nosis are a remaining problem(23–28). Although the reason why ment(30–35). Among these findings, defects of foveal inner and
postoperative visual prognosis varies so greatly from case to case outer segments and foveal detachment gradually decrease and
has not become apparent, the preoperative state of foveal photo- disappear, and there are also cases where IS/OS and ELM reflec-
receptor cells is presumed to have an effect on prognosis. Old age, tivity recovers(35).
poor preoperative vision, a large macular hole diameter, a long Tadayoni et al. have reported the occurrence of various find-
period after onset and advanced stages are mentioned as risk ings of retinal nerve fiber layer defects in the posterior pole after
factors resulting in poor visual prognosis. However, in previous macular hole surgeries with internal limiting membrane peel-
reports on long-term results, only ageing, poor preoperative ing(36). This feature has been thought to be dissociated retinal
visual acuity and advanced stages are identified as significant risk nerve fiber layer, because these findings are confined to the reti-
factors(23, 28). In addition, there are many reports that could not nal nerve fiber layer when observed by vertical OCT B-scans
identify any particular significant factor. Indeed, there are cases through the fovea and retinal sensitivity abnormalities are not
of poor visual acuity recovery even when the period after onset detected on visual field or microperimetry testing (37–39). How-
has been short, the cause of which is presumed to be foveal pho- ever, when observed by serial OCT B-scans with speckle
toreceptor cells being torn and lost during macular hole forma- noise removed, damage is observed from the ganglion cell
tion. This is also backed up by reports on cases where the inner layer to the inner plexiform layer particularly temporal to the
segments of photoreceptor cells are included in the surgically macula(41, 42).

. Fig. 2-7 Foveal deformation with and without spontaneous separation of perifoveal PVD in the fellow eyes of patients with a macular hole. (OCT)

Understanding perifoveal PVD and the Müller cell cone

Yamada et al. reported that the fovea centralis has a cone- leading to macular hole formation (. Fig. 2-9, 2-10)(40). Hangai et
shaped structure with lightfew cell nuclei that is comprised of al. and Takahashi et al. observed OCT images indicating the pho-
Muller cells, referred to as the Müller cell cone (. Fig. 2-8)(39). toreceptor layer dehiscence at the foveola associated with peri-
Based on these histological findings, Gass hypothesized that foveal PVD and isolated Muller cell cone as if perifoveal PVD
the Müller cell cone function as a plug to bind together the pulled out the Muller cell cone, resulting in the dehiscence.(9, 10).
photoreceptor cells in the foveola, and when these disconnect, Thus, the function of the Müller cell cone is thought to be struc-
there is photoreceptor dehiscence of the foveola at the umbo, tural support of the fovea centralis.
2.1 · Idiopathic macular holes
27 2

. Fig. 2-8 The structure known as the fovea centralis Müller cell cone (surrounded by orange dotted line, optical light microscopic image and OCT image)
(The left figure has been modified according to Yamada E. Some structural features of the fovea centralis in the human retina.
Arch Ophthalmol. 1969:82; 151–159)

. Fig. 2-9 Diagram indicating the foveal photoreceptor layer disruption . Fig. 2-10 3D-OCT imaging indicating the foveal photoreceptor layer
This diagram shows the involvement of the Müller cell cone in macular hole disruption
formation following the forward traction vector force generated by peri- The Müller cell cone with dehiscence of the foveal photoreceptor cell layer;
foveal PVD the surface of the fovea centralis is being pulled forward as a result of peri-
foveal PVD and the Muller cell cones appears over the disrupted photo-
receptor layer at the umbo. (Modified according to Hangai M, et al. Three-
dimensional imaging of macular holes with high-speed optical coherence
tomography. Ophthalmology. 2007; 114: 763–773)
 28 Chapter 2 · Vitreoretinal interface pathology

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Case 1 · Physiological PVD: Flattening of foveal depressions
29 2
Case 1 Physiological PVD: Flattening of foveal depression

A 68-year-old male, OS, BCVA 0.5

A: OCT horizontal scan of the left eye: at initial diagnosis. PVD ( ) has not yet extended to the macular area. B: OCT horizontal scan of the same area of the
left eye: 4 months after initial diagnosis. Progression of macular PVD is evident in the temporal macula. C: OCT horizontal scan of the same area of the left
eye: 7 months after initial diagnosis. Macular PVD is complete and an operculum appears (7) have formed. Foveal depressions have flattened ( )

Image interpretation points

Over the course of physiological PVD, foveal contour abnor- macular hole. Foveal depression have flattened. Left eye best-
malities may remain or appears once the posterior vitreous corrected visual acuity remains unchanged at 1.2. Abnormalities
cortex and fovea have separated and macular PVD is complete. may also remain inside the fovea.
This case involves the fellow eye of a right eye with Stage 3
 30 Chapter 2 · Vitreoretinal interface pathology

Case 2 Idiopathic macular holes: Progression from stage 1 (cystoid space type) to stage 2

A 53-year-old female, OS, BCVA 1.2 at the initial diagnosis, and 0.3 six months later
2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A yellow ring can be seen in the fovea centralis.
C: IR + OCT horizontal scan of the left eye: at initial diagnosis. Perifoveal PVD developed, the posterior vitreous cortex ( ) has pulled the fovea centralis
forward and foveal depressions have been flattened. D: IR + OCT horizontal scan of the left eye: 4 months after initial diagnosis. Foveal cystoid space ( ) is
formed. Best-corrected visual acuity is unchanged. E: IR + OCT horizontal scan of the left eye: 6 months after initial diagnosis. Progression to Stage 2 macu-
lar hole. Best-corrected visual acuity to 0.3

Image interpretation points

This is the fellow eye of a patient with a Stage 3 macular hole. wall of the cystoid space separated and the foveal photorecep-
Progression from a Stage 1 to Stage 2 macular hole was ob- tor layer dehisced into a full-thickness macular hole. Visual
served. At initial diagnosis, perifoveal PVD had developed, acuity did not decrease with the formation of cystoid space or
foveal depression had been flattened and small foveal detach- small foveal detachment, but did decline with foveal dehis-
ments were observed. A cystoid space formed 4 months after cence. The incidence of a macular hole in macular hole fellow
initial diagnosis; 6 months after initial diagnosis the anterior eyes is 13–22%.
Case 3 · Idiopathic macular hole: Stage 1 foveal cystoid space formation type
31 2
Case 3 Idiopathic macular hole: Stage 1 foveal cystoid space formation type

A 64-year-old female, OS, BCVA 1.2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: yellow ring can be seen in the fovea centralis, C: IR + OCT horizontal
scan of the left eye + enlarged version [red dashed box]: Perifoveal PVD has been formed. The posterior vitreous cortex ( ) has pulled the fovea forward,
forming the cystoid space and clefts in the HFL ( ). The anterior wall of the cystoid space has been lifted high up. Small foveal detachments can be seen.
*
A columnar structure ( ) thought to be Müller cells is seen in the clefts of HFL. Centrifugal forward traction towards the fovea centralis is transmitted via
the columnar structure to the foveal photoreceptor layer. D: IR + OCT vertical scan of the left eye: same findings as in C

Image interpretation points

This is a stage 1 macular hole where a foveal cystoid space acuity remained good for 6 months after initial diagnosis, if
and HFL clefts are formed. Perifoveal PVD causes the elevation the anterior wall separation occurs together with the foveal
of the anterior wall of the cystoid space. A small foveal de- photoreceptor dehiscence, this eye will progress to a full-thick-
tachment is observed as a small protrusion of the COST line. ness macular hole.
No visual acuity decline was seen at initial diagnosis and visual
 32 Chapter 2 · Vitreoretinal interface pathology

Case 4 Idiopathic macular hole: Stage 1 foveal detachment type

A 62-year-old female, OS, BCVA 0.5

2

A: Color fundus photograph in the left eye: at initial diagnosis, B: Enlarged version of A [red dashed box]: Foveal abnormalities are obscured. C: IR + OCT
horizontal scan of the left eye + enlarged version [red dashed box]: at initial diagnosis. Perifoveal PVD has developed, the posterior vitreous cortex ( ) has
pulled the fovea forward and foveal detachment can be seen. No photoreceptor dehiscence visible, but enhanced reflectivity can be seen in the area corre-
sponding to the Müller cell cone (blue dashed circle). D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: 1 month after initial
diagnosis. Photoreceptor dehiscence has occurred (red dashed circle). Best-corrected visual acuity declined to 0.3

Image interpretation points

A stage 1 macular hole where foveal photoreceptor dehiscence tion. It is interesting that the area corresponding to the Müller
was preceded by foveal detachment. There are also cases cell cone becomes highly reflective before the development of
where photoreceptor layer dehiscence progresses directly photoreceptor dehiscence.
from foveal detachment without foveal cystoid space forma-
Case 5 · Idiopathic macular hole: Stage 1 photoreceptor dehiscence type
33 2
Case 5 Idiopathic macular hole: Stage 1 photoreceptor dehiscence type

A 60-year-old female, OS, BCVA 0.5

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A yellow ring is visible. C: Color fundus photo-
graph in the left eye, D: Enlarged version of C [red dashed box]: 1 month after initial diagnosis. E: IR + OCT horizontal scan of the left eye + enlarged version
[red dashed box]: at initial diagnosis. Photoreceptor dehiscence has occurred and the Müller cell cone can be seen. The posterior vitreous cortex ( ) in
perifoveal PVD is pulling the fovea forward. F: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: 1 month after initial diagnosis.
The Müller cell cone is still visible; this could almost be a scan of the same area as E, but with expansion of the macular hole. Best-corrected visual acuity
is unchanged

Image interpretation points

This is a case of stage 1 macular holes where photoreceptor ing. This is also supported by the observation that the macular
dehiscence has occurred without forming a foveal cystoid hole appears to expand scans of the same area as soon as
space or foveal detachment. Contraction of the Müller cell 1 month after initial diagnosis.
cone is mild, which could indicate that dehiscence is just end-
 34 Chapter 2 · Vitreoretinal interface pathology

Case 6 Idiopathic macular hole: Stage 1 small foveal detachment type

A 64-year-old female, OD, BCVA 0.8

2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A yellow ring can be seen in the fovea centralis.
C: IR + OCT horizontal scan of the right eye: Perifoveal PVD has occurred, the posterior vitreous cortex ( ) has pulled the fovea centralis forward and
foveal depression has flattened. Small foveal detachment, i.e., uplift of the foveal COST line and highly reflective foveal photoreceptor outer segment are
seen. D: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: same findings as C

Image interpretation points

This is the case of a fellow eye of a patient with a stage 2 mac- is mild. Visual acuity starts to decline once foveal dehiscence oc-
ular hole. The small protrusion in the COST line indicates the currs. These changes could be found because this is the fellow
presence of small foveal detachment. Visual acuity impairment eye of a patient with a full-thickness macular hole.
Case 7 · Idiopathic macular hole: A case just before progression from stage 1 to stage 2
35 2
Case 7 Idiopathic macular hole: A case just before progression from stage 1 to stage 2

A 61-year-old male, OS, BCVA 0.2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. An irregular-shaped yellow ring is visible. C: IR +
OCT horizontal scan of the left eye + enlarged version [red dashed box]: Photoreceptor dehiscence has occurred and a flap-like elevation can be seen that
is similar to the flap seen in a stage 2 macular hole, however, this macular hole is bridged by a moderately reflective thin membranous tissue connecting to
the external limiting membrane. Tissue thought to be the Müller cell cone ( ) can be seen in the center of the flap-like structure. Note the elongation of
the photoreceptor outer segment in the elevated edge of the macular hole. D: IR + OCT vertical scan of the left eye: it is only evident that foveal detach-
ment and a foveal cystoid space are present

Image interpretation points

This is a case of a stage 1 macular hole progressing to stage 2. dehiscence and poor visual acuity. Usually, visual acuity impair-
Probably, the anterior wall of the cystoid space have separated ment increases when photoreceptor dehiscence occurs.
and are changing into a flap. This has caused photoreceptor
 36 Chapter 2 · Vitreoretinal interface pathology

Case 8 Idiopathic macular hole: Typical example of stage 2

A 62-year-old female, OS, BCVA 0.08

2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A macular hole is with one-third the size of the
optic disc diameter is seen. C: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box], D: IR + OCT vertical scan + enlarged version [red
dashed box]: A flaccid posterior vitreous cortex ( ) attached to the flap can be seen. The photoreceptor layer on the elevated edge of the macular hole
(posterior medial to the ELM line) is preserved with few defects. E: Color fundus photograph in the left eye, F: Enlarged version of E [red dashed box]:
3 weeks after macular hole surgery. Macular hole closure can be seen. G: Color fundus photograph of the same eye, H: Enlarged version of G [red dashed
box]: 6 months after surgery. Best-corrected visual acuity improved to 0.7. Dissociated optic nerve fiber layer (DONFL) appearance that was not evident
3 weeks after surgery have appeared
I: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box], J: IR + OCT vertical scan of the left eye + enlarged version [red dashed box]:
3 weeks after surgery. Best-corrected visual acuity was 0.1. Disruption of the IS/OS at the fovea centralis and thinning of the outer nuclear layer can be
seen. As the ELM approaches the RPE, indicating the significantly thin photoreceptor inner and outer segments. Defective damages to the inner retinal
layers in the temporal macula are visible, although this area was not in contact with any instruments during surgery. No evident abnormalities are visible
in the upper and lower retinal nerve fiber layer. K: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box], L: IR + OCT vertical scan of
the left eye + enlarged version [red dashed box]: 6 months after surgery. There is visible restoration of IS/OS line and COST line, and the thickness of the
photoreceptor inner and outer segments has been re-instated. Nevertheless, the outer nuclear layer of the fovea centralis is still slightly thin. In addition
to localized thinning of the macular upper and lower retinal nerve fiber layer consistent with DONFL appearance, there is also thinning throughout the
macula compared with postoperative week 3. Particularly, temporal retinal thinning has progressed. Retinal nerve fiber layer reflectivity has disappeared
and thinning is noticeable up to the ganglion cell layer.
Case 8 · Idiopathic macular hole: Typical example of stage 2
37 2

Image interpretation points

This is a typical stage 2 macular hole in which the flap is pulled can be seen. However, 6 months after surgery these abnormal
forward by the posterior vitreous cortex. Cystoid spaces are findings have disappeared and each line has been restored.
formed in the HFL; the photoreceptor layer on the edge of the Nevertheless the foveal outer nuclear layer remains thinned.
macular hole have been detached and elevated from the RPE. These 3 lines are useful in knowing the extent of the foveal
The degree of the photoreceptor damages can be estimated photoreceptor cell damages, but it should be kept in mind that
by the status of the photoreceptor inner and outer segments restoration may occur. DONFL appearance not seen immediately
beneath the ELM line of the elevated area. In this case, there after surgery are visible in postoperative month 1–6; note the
are few defects in photoreceptor inner and outer segments diffuse thinning in the retinal nerve fiber layer in the upper and
and the good visual acuity prognosis is expected. lower parts of the macula, particularly at the DONFL sites.
Immediately after surgery, features indicating foveal photo- There is significant thinning of the temporal macula up to the
receptor cell damages such as disruption of the IS/OS and ganglion cell layer. This defect is thought to be due to internal
COST lines as well as the approach of the ELM line to the RPE limiting membrane peeling.
 38 Chapter 2 · Vitreoretinal interface pathology

Case 9 Idiopathic macular hole: Postoperative course for macular hole closure under gas tamponade

A 65-year-old female, OD, BCVA 0.2

2

A: Color fundus photograph in the right eye: 1 week after surgery. Macular hole closure has been achieved. SF6 gas remains. B: Color fundus photograph in
the right eye: 1 month after surgery. Best-corrected visual acuity has improved to 0.4. Numerous arcuate striae with slightly darker color, so-called DONFL
appearance, can be seen. C: Color fundus photograph in the right eye, D: Enlarged version of C [red dashed box]: 6 months after surgery. Best-corrected
visual acuity is 0.4. DONFL appearance remains. E: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: 1 week after surgery. The
macular hole have closed, but a foveal cystoid space and photoreceptor inner and outer segment defects can be seen along the closure junction line.
F: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: The cystoid space have disappeared, and high reflectivity can be seen at the
junction line in the foveal outer nuclear layer. Photoreceptor inner and outer segment defects remain. Retinal nerve fiber layer defects consistent with the
arcuate striae in DONFL appearance can be seen. G: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: 6 months after surgery.
Foveal photoreceptor inner and outer segment defects appear to have been reduced.

Image interpretation points

The macular holes are thought to have closed in 1 day after tamponade treatment period was shortened. It takes time for
surgery. Despite closure, there are cystoid spaces, photo- photoreceptor inner and outer segment defects to disappear.
receptor IS/OS defects in the junction line, and incomplete Interpretation of the OCT features corresponding to DONFL
restoration of the foveal contour. This may account for the appearance is addressed in the next page..
risk of macular hole reopening that increases when the gas
Case 9 · DONFL appearance
39 2
Case 9 DONFL appearance

H: Color fundus photograph in the right eye: 5 months after surgery. DONFL appearance can be seen over the macular area where internal limiting membrane
peeling was performed. I: Microperimetry-1 in the right eye: 5 months after surgery. Several points where visual sensitivity has declined to 13 dB or less are
detected even outside the fovea. J: IR + OCT horizontal scan of right eye + enlarged version [red dashed box]: Note that the defects of the inner retinal layers
in the temporal macula corresponding to the arcuate striae extend deeper than the retinal nerve fiber layer. K: IR + OCT vertical scan of the right eye + en-
larged version [red dashed box]: Thinning of the retinal nerve fiber layer can be seen in both the superior and inferior areas of DONFL appearance.

Image interpretation points

This page shows the OCT images of DONFL appearance. gery, these abnormal findings are thought to be due to inner
While most areas of DONFL appearance show only retinal limiting membrane peeling. In this particular case, the micro-
nerve fiber layer defects or thinning on a vertical scan through perimety test points were set as dense as possible and a decline
the fovea, the temporal areas of DONFL appearance show de- in retinal sensitivity was identified on several points. However,
fects from the retinal nerve fiber layer to the ganglion cell layer the sites with deep retinal defects are too small compared to the
and sometimes the inner plexiform layer. Since the temporal test point distribution in standard visual field and microperime-
macula was not in contact with any instruments during sur- try testing to be detected by the testing.

macular hole
 40 Chapter 2 · Vitreoretinal interface pathology

Case 10 Idiopathic macular hole: Postoperative course for macular hole closure

Left eye of a 58-year-old female with vision corrected to 0.3

2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A macular hole surrounded by a fluid cuff. C: Color
fundus photograph in the left eye, D: Enlarged version of C [red dashed box]: 2 months after surgery. Best-corrected visual acuity has improved to 0.7. The
macular hole has closed and a white opacity remains in the fovea centralis. E: IR + OCT horizontal scan of left eye: before surgery. A stage 2 macular hole.
F: IR + OCT horizontal scan of the left eye: 9 days after surgery. The macular hole has closed, but foveal detachment remains. A part of SF6 gas remains. High
reflectivity can be seen at the junction line. G: IR + OCT horizontal scan of the left eye: 2 months after surgery. Foveal detachment still remains. H: IR + OCT
horizontal scan of the left eye + enlarged version [red dashed box]: 5 months after surgery. Best-corrected visual acuity has improved to 0.7. Foveal detach-
ment has disappeared. High reflectivity remains at the junction line. Thin membranous structure is seen on the surface of the closed macular hole. The
photoreceptor outer segment is still thin.

Image interpretation points

A macular hole is thought to have closed 1 day after surgery; findings 5 months after surgery revealed that thin membranous
however, foveal detachment sometimes remains over 3 months structure had formed in front of the foveal retinal nerve fiber
after closure was achieved. Photoreceptor layer restitution also layer. This suggests that glial cell migration results in the forma-
takes several months. Scarring formed by the migration of glial tion of a cellular fibrous membrane, which may be involved in
cells is thought to be involved in macular hole closure. Foveal macular hole closure.
Case 11 · Idiopathic macular hole: Typical example of stage 3
41 2
Case 11 Idiopathic macular hole: Typical example of stage 3

A 65-year-old female, OS, BCVA 0.07

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A small macular hole with approximately one-
quarter the size of the optic disc diameter is seen. C: IR + OCT horizontal scan of the left eye, D: IR + OCT vertical scan of the left eye: An operculum can be
seen in the posterior vitreous cortex ( ). E, F: Enlarged version of C and D [red dashed box]: The photoreceptor layers beneath the ELM on the elevated
edges of the macular hole are preserved with few defects.

Image interpretation points

This is a typical stage 3 macular hole, in which the posterior have become detached and elevated from the RPE. The degree
vitreous cortex including an operculum. No glial ring was seen of the photoreceptor cell disorder can be estimated by the sta-
with an biomicroscopic examination, the posterior vitreous tus of the photoreceptor inner and outer segments beneath the
cortex is attached to the optic disc, and the posterior vitreous ELM. In this example, there are few photoreceptor inner and
cortex in the front of the macula is usually visible in the imag- outer segment defects and the good visual acuity prognosis can
ing range in OCT images. Cystoid spaces are formed in the HFL be expected.
and the photoreceptor layers on the edge of the macular hole
 42 Chapter 2 · Vitreoretinal interface pathology

Case 11 After surgery

A 65-year-old female, OS, BCVA 0.8

2

G: Color fundus photograph in the left eye, H: Enlarged version of A [red dashed box]: 3 weeks after macular hole surgery. Macular hole closure can be seen.
I: IR + OCT horizontal scan of the left eye: 3 weeks after surgery. Vision corrected to 0.8. Reflectivity of foveal IS/OS line is already being restored, although it is
still weak. The thickness of the photoreceptor inner and outer segments and outer nuclear layer is almost normal. Damages of the temporal inner retina can
be seen. J: IR + OCT oblique scan of the left eye: 3 weeks after surgery. Foveal photoreceptor IS/OS defects can be seen on this scan. K: IR + OCT oblique scan
of the left eye: 2 months after surgery. Best-corrected visual acuity has improved to 1.0. No photoreceptor IS/OS defects could be identified.

Image interpretation points

This is the fellow eye of a patient with a stage 4 macular hole. ment defect is a minor finding that cannot be identified unless
While a small inner and outer segment defect remains imme- dense serial scans are performed. Before surgery, there were few
diately after surgery, the IS/OS is being restored 2 months after defects found in the inner and outer segments of the elevated
surgery. No thinning can be seen in the outer nuclear layer edges of the macular hole, suggesting damages to foveal photo-
or photoreceptor inner and outer segments at the fovea. The receptor cells were not severe. The thinning of the temporal
foveal contour appears to have been restored close to its inner retinal layers is attributable to internal limiting membrane
normal form. The small photoreceptor inner and outer seg- peeling.
Case 12 · Idiopathic macular hole: Typical example of stage 4
43 2
Case 12 Idiopathic macular hole: Typical example of stage 4

A 69-year-old female, OD, BCVA 0.07

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial consultation. A fairly large macular hole is visible measur-
ing approximately one-half the optic disc diameter in size. C: IR + OCT horizontal scan of the right eye.
D: IR + OCT vertical scan of the right eye: Posterior vitreous cortex is not seen in the imaging frame. E, F: Enlarged version of C and D [red dashed box]:
The inner and outer segments beneath the ELM on the elevated edges of the macular hole are preserved with few defects.

Image interpretation points

This is a stage 4 macular hole where a glial ring can be ob- macular hole is useful in knowing damages to foveal photore-
served with a biomicroscopy and the posterior vitreous cortex ceptor cells. In this example, there are few defects in these layers
is outside the OCT imaging frame. The status of the inner and and good visual acuity prognosis is expected.
outer segments beneath the ELM on the elevated edges of the
 44 Chapter 2 · Vitreoretinal interface pathology

Case 13 Idiopathic macular hole: Old case of stage 4

A 73-year-old female, OD, BCVA 0.1

2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A comparatively large macular hole approxi-
mately 1/2 the optic disc diameter can be seen. C: IR + OCT horizontal scan of the right eye.
D: IR + OCT vertical scan of the right eye: Cystoid spaces are significant not only in the HFL but also in the inner nuclear layer. The posterior vitreous cortex
is not in the OCT imaging range.
Enlarged version of E, F, C and D [red dashed box]: Defects of the photoreceptor inner and outer segments beneath the ELM on the elevated edges of the
macular hole are significant

Image interpretation points

This is the case of a stage 4 macular hole where a glial ring is point as can be seen on the upper temporal portion of the
seen with an biomicroscopy and the posterior vitreous cortex macular hole. In addition to the large macular hole size, the
is outside the imaging frame. In this example, the fellow eye severe defects of the inner and outer segments beneath the
also has a stage 4 macular hole. Given the chronic nature of this ELM on the elevated area illustrates serious photoreceptor
macular hole, there is significant displacement of the fixation damages.
Case 13 · Stage 4 after surgery
45 2
Case 13 Stage 4 after surgery

G: Color fundus photograph in the right eye, H: Enlarged version of G [red dashed box]: 1 week after first surgery. Macular hole closure has not been
achieved. I: IR + OCT vertical scan of the right eye: 1 week after first surgery. The edge of the macular hole has become flattened, but the macular hole is
not closed. SF6 gas remains. J: IR + OCT horizontal scan of the right eye, K: IR + OCT vertical scan of the right eye: 1 month after the second surgery. Best-cor-
rected visual acuity was 0.15. Macular hole closure has been achieved, but foveal thinning is pronounced.

Image interpretation points

This is the fellow eye of a patient with a stage 4 macular hole. appears to be minimal nerve tissue remaining in the fovea
In this case the macular hole was large and was only closed centralis. The macular hole may have been closed by filling in
after a second surgery was performed. Unfortunately, there with interstitial tissue such as glial tissue.
 46 Chapter 2 · Vitreoretinal interface pathology

Case 14 Idiopathic macular holes: Progression from lamellar to full-thickness macular holes

A 65-year-old male, OS, BCVA 1.2

2

A: Color fundus photograph, B: Enlarged version of A [red dashed box]: at initial diagnosis. Lamellar macular hole findings are evident. C: Same area as B:
5 months after initial diagnosis. A full-thickness macular hole have developed. D: IR + OCT vertical scan of the left eye + enlarged version [red dashed box]:
Features characteristic to lamellar macular hole, such as clefts in the HLF and diminished foveal outer nuclear layer, are evident. E: IR + OCT vertical scan of
the left eye: 3 months after initial diagnosis. Best-corrected visual acuity has declined to 0.9. The lamellar macular hole has progressed to a full-thickness
macular hole. Little elevation in the edges of the macular hole is seen. F: IR + OCT vertical scan of the left eye: 5 months after initial diagnosis. Best-correct-
ed visual acuity has further declined to 0.7. Elevation in the edges of the macular hole is noted.

Image interpretation points

A lamellar macular hole develops when a perifoveal PVD hole after becoming lamellar. Foveal outer nuclear layer thinning
spontaneously separates from the fovea in eyes with a stage 1 is significant in a lamellar macular hole, sometimes causing
macular hole or when a macular hole closes spontaneously. foveal photoreceptor dehiscence.
However, this case progressed into a full-thickness macular
Case 15 · Stage 1 macular hole: Spontaneous separation of perifoveal PVD
47 2
Case 15 Stage 1 macular hole: Spontaneous separation of perifoveal PVD

A 46-year-old female, OD, BCVA 1.2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: 6 months after initial diagnosis. A double yellow ring is visible. C: IR
+ OCT horizontal scan of the right eye + enlarged version [red dashed box]: 6 months after initial diagnosis. Perifoveal PVD is evident with elevation of the
foveal surface and a tiny foveal detachment (7) resulting from centrifugal forward traction of the fovea centralis. indicates the posterior vitreous cortex.
D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 9 months after initial diagnosis. Best-corrected visual acuity is 1.2. Perifo-
veal PVD has separated spontaneously, elevation of the foveal surface has disappeared and the foveal detachment has receded (7). E: IR + OCT horizontal
scan of the right eye + enlarged version [red dashed box]: 12 months after initial diagnosis. Best-corrected visual acuity is 1.2. The small foveal detachment
has disappeared.

Image interpretation points

A perifoveal PVD was observed at initial diagnosis, but without lar PVD was complete. Elevation of the foveal surface disappeared
evidence of foveal deformation. Six months after initial diagno- and slight abnormal reflectivity of the photoreceptor inner and
sis, the foveal surface was elevated and a small foveal detach- outer segments in the fovea centralis remained. 12 months after
ment had developed; 9 months after initial diagnosis the macu- initial diagnosis, the fovea centralis was restored to normal.
 48 Chapter 2 · Vitreoretinal interface pathology

Case 16 Stage 1 macular hole: Macular microhole formation

A 58-year-old female, OD, BCVA 0.8

2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A yellow ring is visible with a yellow dot in the
center. C: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: at initial diagnosis. Perifoveal PVD evident with elevation of the
foveal surface and a small foveal detachment ( ) resulting from centrifugal forward traction of the fovea centralis. shows the posterior vitreous cortex.
D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 2 months after initial diagnosis. Best-corrected visual acuity is 0.9. Spon-
taneous separation of perifoveal PVD is in progress. E: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 3 months after initial
diagnosis. Best-corrected visual acuity has improved to 1.2. Perifoveal PVD has separated and a flaccid posterior vitreous cortex can be seen. Photoreceptor
inner and outer segment defects (macular microholes) remain.

Image interpretation points

Upon initial diagnosis, there was a perifoveal PVD causing and the perifoveal PVD separated spontaneously. Three months
elevation of the foveal surface where the posterior vitreous after initial diagnosis, elevation of the foveal surface had reced-
cortex adheres. Also seen was a small foveal detachment ed and findings known as »a macular microhole« could be seen
which was more likely a disruption of the foveal IS/OS and in the photoreceptor inner and outer segments. Best-corrected
COST. In this case, however, foveal deformation did not worsen visual acuity was relatively good.
Case 17 · Stage 2 macular hole: Spontaneous closure
49 2
Case 17 Stage 2 macular hole: Spontaneous closure

A 72-year-old male, OD, BCVA 0.6

A: IR + OCT vertical scan of the right eye: at initial diagnosis. A stage 2 macular hole is seen. B: IR + OCT vertical scan of the right eye: 1 month after initial
diagnosis. Best-corrected visual acuity has improved to 1.0. Spontaneous closure can be seen but perifoveal PVD has not separated. indicates the pos-
terior vitreous cortex. This image appears to indicate stage 1 macular hole with foveal detachment. C: IR + OCT vertical scan of the right eye: 6 months after
initial diagnosis. Best-corrected visual acuity is 1.2. Centrifugal forward traction resulting from perifoveal PVD continues; a flap-like foveal anterior wall is
beginning to separate (7). D: IR + OCT horizontal scan of the right eye: 12 months after initial diagnosis. Best-corrected visual acuity is 1.2. Macular PVD is
complete and an operculum (7) is attached to the posterior vitreous cortex. Foveal detachment continues to recede. E: IR + OCT vertical scan of the right
eye: 12 months after initial diagnosis. Similar findings to D noted. A mirror image of the operculum outside the imaging range is reflected

Image interpretation points

This is an unusual case where the macular hole temporarily was previously stage 2. There are instances where visual acuity
progressed into a stage 2 full-thickness macular hole, but is not completely improved despite spontaneous closure,
spontaneously closed and returned to stage 1 regardless of however, this patient’s corrected vision improved to over 1.0
the presence of perifoveal PVD. If the initial visit had been with closure.
1 month later, it would not have been evident that the hole
 50 Chapter 2 · Vitreoretinal interface pathology

Case 18 Stage 3 macular hole: Spontaneous closure

A 68-year-old male, OD, BCVA 0.3

2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. Stage 3 macular hole is seen. C: Same area as B:
8 months after initial diagnosis. The macular hole has closed spontaneously. D: IR + OCT vertical scan of the right eye: at initial diagnosis. An operculum (7)
and a macular hole are seen. Cystoid spaces in the HFL and elevation of the photoreceptor layers at the edges of the macular hole are also seen. indi-
cates the posterior vitreous cortex. E: IR + OCT vertical scan of the right eye: 1 month after initial diagnosis. Visual acuity has improved to 0.5. The macular
hole has closed spontaneously and the foveal detachment remains. F: IR + OCT vertical scan of the right eye: 8 months after initial diagnosis. Best-corrected
visual acuity has improved to 0.9. Foveal detachment remains. The operculum (7) and posterior vitreous cortex are further from the retina. The foveal
depression has recovered.

Image interpretation points

This is an example of spontaneous closure of a stage 3 macular closed by surgery, foveal detachment can remain for around
hole. The edges of the macular hole have been centrifugal half a year. While the spontaneous closure of macular holes is
elevated. Foveal detachment remained until long after spon- unusual, they can occur at any stage.
taneous closure. Even in cases where macular holes have been
Case 19 · Stage 4 macular hole: Spontaneous closure
51 2
Case 19 Stage 4 macular hole: Spontaneous closure

A 68-year-old male, OD, BCVA 0.3

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A stage 4 macular hole is seen. C: Same area
as B: 1 month after initial diagnosis. Best-corrected visual acuity has improved to 0.7. A lamellar macular hole findings is seen. D: IR + OCT horizontal scan
of the right eye: at initial diagnosis. A full-thickness macular hole is seen. There is slight elevation in the edges of the macular hole. E: IR + OCT horizontal
scan of the right eye 1 month after initial diagnosis. The macular hole has closed spontaneously. Features characteristic to lamellar macular holes, such as
clefts in the HFL and diminished foveal outer nuclear layer, are evident. F: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]:
8 months after initial diagnosis. Foveal detachment and lamellar macular hole features remain. Best-corrected visual acuity has improved to 1.2. Note the
remaining clefts in the HFL and thin foveal outer nuclear layer, indicating lamellar macular hole.

Image interpretation points

This is an example of spontaneous closure of a stage 4 macular Although unusual, the spontaneous closure of macular holes
hole. Features characteristic to lamellar macular holes, such as is thought to be one of the pathogenic mechanisms of lamellar
clefts in the HFL and diminished foveal outer nuclear layer, are macular hole formation.
demonstrated after spontaneous closure of the macular hole.
 52 Chapter 2 · Vitreoretinal interface pathology

Case 20 Traumatic macular hole: A typical example

An 11-year-old male, OS, BCVA 0.3

2

A: Color fundus photograph in the left eye: at initial diagnosis. A macular hole about half the optic disc diameter can be seen. The edges of the macular
hole are irregular. The upper posterior pole of the retina appears significantly whitened as a result of commotio retinae with mottled pigmentation visible
within. B: 10 minutes after simultaneous FA/IA angiography of the left eye: Tissue staining and mottled blockades of fluorescence is evident in the upper
posterior pole of the retina. C: IR + OCT vertical scan of the left eye: The upper retina, particularly the outer retinal layers, are significantly atrophic. There
is reactive proliferation of the RPE cells from the base of the macular hole to the area of retinal atrophy. D: IR + OCT vertical scan of the left eye: 3 months
after surgery. Best-corrected visual acuity has improved to 0.5. The macular hole has closed, but atrophy of the fovea is significant.

Image interpretation points

This is a case of traumatic macular hole secondary to com- in this case after spontaneous closure was not observed
motio retinae of the left eye caused by a football. While spon- 6 months after diagnosis. Retinal atrophy of the fovea and the
taneous closure is common, closure was achieved surgically area of the upper macula were significant.
Case 20 · Traumatic macular hole: A typical example
53 2
Understanding the difference between lamellar macular holes and macular pseudoholes
The ophthalmoscopic findings of lamellar macular holes and curred. The posterior vitreous cortex can remain during peri-
macular pseudoholes (MPH) are similar, whereas the patho- foveal PVD onset even in lamellar macular hole formation. Such
genesis and OCT findings differ. Lamellar macular holes can be cases with lamellar macular hole can be accompanied by ERM
seen when the anterior wall of stage 1 macular holes comes off formation, leading to retinal thickening and folds. Importantly,
or when macular holes close spontaneously. They are thought if significant thinning is seen in the outer nuclear layer of or near
to be a pathological condition on the same spectrum as idio- the fovea centralis, it can be classified as a lamellar macular hole.
pathic macular holes. On the other hand, MPH are similar to This is because thinning of or near the fovea centralis occurs
epiretinal membranes (ERM) except the fovea centralis is with centrifugal traction generated by perifoveal PVD. On the
spared from thickening due to a hole opening in the posterior other hand, such lesions rarely occur with centripetal traction by
vitreous cortex at the fovea centralis. These two diseases can ERM shrinkage, which is mainly associated with the pathological
usually be differentiated by proper interpretation of OCT condition of MPH. Thinning of the outer nuclear layer in or near
images, however a definitive diagnosis is sometimes difficult the fovea centralis in lamellar macular holes are sometimes pro-
without observing the process by which macular PVD oc- gressive and can develop into full-thickness macular holes.

. Fig. 2-11 Lamellar macular holes and MPHs

 54 Chapter 2 · Vitreoretinal interface pathology

Case 21 Lamellar macular hole: a typical example

A 53-year-old female, OS, BCVA 0.3

2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: No ERM or retinal folds are visible. C: Retinal thickness color map of
the left eye, D: IR + OCT horizontal scan of the left eye: ω (omega)-shaped foveal deformation is evident. Clefts in the HFL and thin ERM (↔) are evident but
little macular retinal thickening or retinal folds can be seen. E: IR + OCT vertical scan of the left eye + enlarged version [red dashed box]: Significant thin-
ning of the outer nuclear layer near the fovea centralis noted. Reflectivity of the IS/OS and COST is attenuated or disappearing. F: IR + OCT horizontal scan
of the left eye + enlarged version [red dashed box]: same findings as D

Image interpretation points

This is the case of a typical lamellar macular hole showing In this case, clefts in the HFL and ERM are visible only on OCT,
ω-shaped foveal deformation. A lamellar macular hole is but without typical retinal thickening or folds seen with MPH. In
thought to be a subtype of an idiopathic macular hole where contrast, there are areas of outer nuclear layer thinning as seen
the perifoveal PVD has separated spontaneously from a in E, which can develop into a full-thickness macular hole.
stage 1 hole or when a macular hole has closed spontaneously.
Case 22 · Lamellar macular hole: Differentiation from a MPH
55 2
Case 22 Lamellar macular hole: Differentiation from a MPH

A 55-year-old female, OS, BCVA 0.3

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: Retinal folds are visible, while membrane whitening is mild. C: Retinal
thickness color map of the left eye. D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: ERM (↔) can be seen although retinal
thickening and retinal folds are mild. The pumpkin-shaped foveal deformation is seen, which is probably formed as a result of cleft formation in the HFL ( )
*
and inner layer protrusions due to the centripetal contraction of the ERM. The outer nuclear layer of the fovea centralis has thinned significantly. E: IR +
OCT vertical scan of the left eye: same findings as D

Image interpretation points

This case appears to have involved both centrifugal traction mation. Importantly, the foveal outer nuclear layer is diminished
by perifoveal PVD and centripetal traction by ERM as causes of to approximately a half of the inner and outer segment thickness.
foveal deformation. Here, the pumpkin-shaped foveal cavity is This occurs due to a centrifugal tractional force generated by peri-
laterally wide. This is because this shape was formed a result of foveal PVD in macular hole formation, but never occurs as a result
cleft formation in the HFL. In contrast, MPH foveal depressions of a centripetal tractional force by ERM in MPH.
tend to be laterally narrow. In summary, the cleft in the HFL and diminished outer nuclear
In addition to the cleft formation, the parafoveal inner retinal lay- layer is formed by the centrifugal traction by perifoveal PVD, and
er centrally protruded as a result of centripetal shrinkage of the the protrusion of the parafovea inner retinal layer by the centrip-
ERM may be responsible for the pumpkin-shaped foveal defor- etal traction by ERM contraction.

macular pseudohole
 56 Chapter 2 · Vitreoretinal interface pathology

Macular microholes

Background
2 A macular microhole is a disease state without a well-established
definition. Currently, it is loosely defined as a class of disease with
a reduction in reflectivity or defect within the IS/OS line on OCT
B-scan images. On funduscopic exam, 50–150 µm sharply de-
marcated reflections known as »red spots« are seen, while on
fluorescein angiography there are no RPE changes seen. On OCT,
foveal IS/OD disruption or outer retinal defects are found in or
near the fovea centralis. Although there are cases without subjec-
tive complaints, symptoms are usually associated with acute on-
set of central scotoma, mild decrease in visual acuity and meta-
morphopsia. Epidemiologically, macular microholes occur in
wide variety of patients ranging in age from their 20s to the el-
derly with no gender predilection. They are usually unilateral
with 80% of cases with vision over 0.5. Typically, the vision does
not worsen further and can improve as the IS/OS defects recov-
er(4, 5).

Pathogenesis and OCT findings

It is clear that macular microholes can be caused by the PVD
formation process as a result of centrifugal forward traction from
the posterior vitreous cortex on the fovea centralis. In these cases,
the perifoveal PVD spontaneously separates in a stage 1A macu-
lar hole. In 1/3 of the cases there is a macular PVD where the
posterior vitreous cortex and operculum can be observed on
OCT. When the PVD is complete, however, these are not seen in
the OCT imaging range and only a Weiss’ ring is seen with an
biomicroscopy. While PVD formation can explain macular mi-
croholes occuring in older patients, the etiology of macular mi-
croholes is unknown in young patients without a macular PVD.
Such cases need to be differentiated from trauma, solar retinopa-
thy, or central serous chorioretinopathy. Solar retinopathy,
caused by looking directly at the sun for example in observation
of solar eclipse, may be diagnosed based on history, RPE abnor-
malities, or moderate reflectivity of all retinal layers on OCT.
Central serous chorioretinopathy, on the other hand, can be dif-
ferentiated based on RPE and choroidal abnormalities.

References

1) Cairns JD, McCombe MF. Microholes of the fovea centralis. Aust N Z J Oph-
thalmol. 1988; 16:75–79.
2) Reddy CV, Folk JC, Feist RM. Microholes of the macula. Arch Ophthalmol.
1996; 114:413–416.
3) Zambarakji HJ, Schlottmann P, Tanner V, et al. Macular microholes: patho-
genesis and natural history. Br J Ophthalmol. 2005; 89:189–193.
4) Emerson GG, Spencer GR, Klein ML. Macular microholes. Retina. 2007;
27:595–600.
5) Takahashi A, Nagaoka T, Yoshida A. Stage 1-A macular hole: a prospective
spectral-domain optical coherence tomography study. Retina. 2011;
31:127–147.
Case 23 · Macular microhole: with macular PVD
57 2
Case 23 Macular microhole: with macular PVD

A 72-year-old female, OS, BCVA 0.6

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. Abnormal reflection known as a red spot can
be seen in the fovea centralis. C: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: Macular PVD has occurred, and an operculum
(7) attached to the posterior vitreous cortex ( ) is noted. Disruption of the photoreceptor IS/OS and outer segment can be observed. This is essentially
the same as a small foveal detachment in a stage 1 macular hole. Abnormal high reflectivity can be seen in the foveal outer nuclear layer. This is thought to
be a remnant of the foveal deformation caused by perifoveal PVD traction that was likely present prior to initial diagnosis or of spontaneous macular hole
closure. The foveal depression is flattening (V-shaped). D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: 2 months after initial
diagnosis. The microhole hasdisappeared and the IS/OS, ELM and COST line group has been almost restored. The V-shaped foveal depression remains.

Image interpretation points

The pathological condition known as macular microholes PVD spontaneously separates and only a foveal photoreceptor
appears to be generated by, at least 2 different causes. A com- IS/OS defect remains. In this case as seen with initial reports, the
mon finding of the disease group is a small foveal photorecep- posterior vitreous cortex including an operculum is seen in front
tor IS/OS defect or a defect of foveal inner and outer segments. of the macula on OCT. In both this case and case 16, the poste-
A primary cause of this disease group is spontaneous separa- rior vitreous cortex including an operculum and foveal deforma-
tion of perifoveal PVD during the formation of a macular hole. tion including disruptions of the OS/OS and/or inner and outer
As seen in case 16 with a stage 1A macular hole, the perifoveal segmentsare important diagnostic points.
 58 Chapter 2 · Vitreoretinal interface pathology

Case 24 Macular microhole: with complete PVD

A 59-year-old female, OD, BCVA 0.8

2

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. An abnormal reflection known as »red spots«
can be seen in the fovea centralis. C: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: The posterior vitreous cortex cannot be
seen. Note the inner and outer segment defect at the fovea centralis. This is essentially the same as a small foveal detachment in a Stage 1 macular hole.
Abnormal high-reflectivity can also be seen in the foveal outer nuclear layer, which could be traces of deformation resulting from perifoveal PVD or of
spontaneous macular hole closure. The foveal depression is flattening. D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]:
3 months after initial diagnosis. The microhole has disappeared and the IS/OS, ELM and COST line group has been restored. The irregular foveal deforma-
tion and flattering of the foveal depression remains.

Image interpretation points

In this case, a macular microhole wes only seen in the right PVD is complete. In this case, evidence for macular microholes
eye. Here, macular microhole formation is thought to be the caused by spontaneous perifoveal PVD separation is supported
result of spontaneous perifoveal PVD separation; however, by the irregular deformation and flattening of the foveal depres-
unlike case 23, the posterior vitreous cortex cannot be seen sion, abnormal reflectivity of the foveal outer nuclear layer, and
on OCT making interpretation slightly difficult. Since a glial the spontaneous disappearance of the macular microhole.
ring were observed by biomicroscopy, we can determine that
Case 25 · Macular microhole: Case without PVD
59 2
Case 25 Macular microhole: Case without PVD

A 43-year-old female, OD, BCVA 1.0

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. A abnormal reflection known as »red spots« can
be seen in the fovea centralis. C: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: ( ) shows the posterior vitreous cortex
detached outside and at the periphery of the macula. D: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: The IS/OS and COST
lines centralis are defective selectively at the fovea centralis.

Image interpretation points

This patient noticed decreased vision during a routine vision to tractional forces by the posterior vitreous cortex. After 3 years,
testing for contact lenses. Macular microholes were seen in the visual acuity and OCT findings remained unchanged. The
both eyes. Since the PVD only occurred to the periphery of the pathogenesis of a macular microhole without macular PVD is
macula, the foveal disruption does not appear to be secondary still unknown.
 60 Chapter 2 · Vitreoretinal interface pathology

2.2 Idiopathic epiretinal membrane PVD. It is suggested that after the onset of PVD, cell proliferation
and migration occur, with the posterior vitreous cortex remain-
Background ing on the retinal surface as scaffolding. An extracellular matrix
2 ERM is a disease that a membrane visible with an ophthalmo- containing collagen is produced by these cells, which leads to
scope is formed on the retinal surface of the macula, which causes membrane thickening. ERM is a disease that a membrane visible
retinal folds and thickening resulting in visual impairment and with an ophthalmoscope is formed on the retinal surface of the
metamorphopsia. ERM occurs typically after PVD is complete. macula, which causes retinal folds and thickening resulting in
Cases in which there is no primary pathology known to cause visual impairment and metamorphopsia. ERM occurs typically
ERMs are termed as idiopathic ERM. This is often seen unilater- after PVD is complete. Contraction of the fibrocellular mem-
ally in the elderly and there is no gender predilection. In about brane causes the retinal folds(4). Most idiopathic ERMs are
10% of idiopathic ERM cases macular PVD is not complete(1). thought to occur as a result of this mechanism. The types of cells
The membrane may appear clear, translucent, or white. The reti- involved include glial cells differentiated into myofibroblast-like
nal folds vary from mild radial folds to severe folds accompanied cells, vitreous cells, retinal pigment epithelium (RPE) cells, and
by dislocation of the fovea. In severe cases, there is leakage fibrous astrocytes(5–12).
from retinal vessels and formation of cystoid spaces. Premacular
membranes resulting in eyes with retinal breaks, after retinal Migratory cell membrane formation theory (. Fig. 2-13)
detachment surgeries (known as macular pucker in this case) or This theory postulates that when PVD stops around the fovea
uveitis are known as secondary ERMs. Therefore, a detailed ex- and optic disc or along the retinal blood vessels where the pos-
amination of the peripheral fundus is required. terior vitreous cortex is attenuated and strongly adheres cell mi-
gration occurs through cracks in the internal limiting membrane
Pathogenesis (ILM) formed at this time due to vitreous separation as well as
Two hypotheses have been proposed for vitreoretinal interface preexisting ILM dehiscences of the retina ans optic disc. This
membrane formation based on surgically collected tissue and process forms a fibrocellular membrane through cell-cell junc-
histopathological findings of autopsied eyes. While different, tions and extracellular matrix production(4). ERM without PVD
they are not necessarily conflicting hypotheses. and vitreomacular traction syndrome are thought to fall into this
category. Vitreomacular traction syndrome is often secondary to
Residual posterior vitreous membrane scaffolding other retinal diseases such as diabetic maculopathy where there
theory (. Fig. 2-12) may be factors that strengthen vitreous traction. There are some
Kishi et al. demonstrated that there are elliptical defects in the cases in which the membrane appears to have multiple layers;
posterior vitreous cortex after PVD is complete and the(2) vitre- this fibrocellular membrane may be the posterior vitreous cortex
ous cortex remains on the macular surface(3). Thus, the posterior separated into two layers, or a complex of the ILM and posterior
vitreous cortex can remain on the macular surface as a result of vitreous cortex.

. Fig. 2-12 Residual posterior vitreous membrane scaffolding theory . Fig. 2-13 Migratory cell membrane formation theory
2.2 · Idiopathic epiretinal membrane
61 2
OCT findings retinal fold formation and retinal thickening. Consequently,
On OCT, an ERM is seen as a highly reflective thick membrane. ERM is characterized by a mountain-shaped retinal thickening,
Folds are seen in the inner retinal layer beneath the membrane, forming a peak in the fovea centralis (. Figs. 2-12, 2-14)(16). The
but no in the membrane itself. There are cases where a gap be- centripetal traction vector in the retinal tangential direction
tween ERM and retinal surface is weakly reflective; there are also causes radial folds in the inner retina that can be seen with an
cases where the gap are filled with moderate reflectivity. The fi- ophthalmoscope. In the fovea centralis, the forward traction vec-
brous membrane that had been formed in a gap between ERM tor mainly acts to thicken the outer nuclear layer, causing eleva-
and macular surface, is sometimes exposed and lifted towards the tion of the IS/OS and a small foveal detachment. As a result, IS/
vitreous cavity due to progressive contraction of the ERM. When OS defects occur in 24~77% of cases(17–21). When observed with
seen on a 9 mm scan, ERM is most often present in isolation on an adaptive optics scanning laser ophthalmoscope (SLO), micro-
the macular surface with no continuity from the posterior vitre- folds occur on the photoreceptor cell level, which is correlated
ous cortex (. Fig. 2-12); however, in about 10% of cases, the PVD with metamorphopsia(22). On the other hand, thickening of the
is incomplete and a thick highly reflective ERM continuing from parafovea occurs mainly in the inner retina, which has also been
the posterior vitreous cortex can be seen (. Fig. 2-13). In addi- claimed to correlate with metamorphopsia.(23).
tion, in cases of incomplete PVD a retinal surface ERM can
sometimes be seen beneath the detached posterior vitreous cor- Macular pseudoholes
tex. In cases where the posterior vitreous cortex has been re- A macular pseudohole is a subtype of ERM, and hence forward
moved during surgery, a ERM remains on the macular surface in traction by the ERM does not work toward the fovea centralis.
30% of cases despite no defects in the posterior vitreous cortex. This results in thickening of the macula with the fovea centralis
(13) To explain this phenomenon, the migratory cell membrane remaining unthickened (. Fig. 2-14). In contrast, in vitreomacular
formation theory postulates that an ERM forms in the gaps of the traction syndrome, centrifugal forward traction occurs resulting
posterior vitreous cortex and retina, and then the posterior vitre- in a distinctive trapezoidal-shaped retinal thickening (. Fig. 2-13).
ous cortex becomes detached from the ERM, resulting in the
formation of 2 distinct membranes. Another theory postulates Prognosis
that the posterior vitreous cortex separates into two layers allow- There are cases that do not necessarily lead to loss of visual acuity
ing the ERM to form with the posterior layer providing a scaffold even when an ERM is noted. In addition, cases where there is
after the anterior layer has detached.(14, 15). progressive visual acuity loss during follow-up examinations
As a result of contraction, ERMs transmit centripetal forward accounts for less than 10% of the total cases. ERM contraction is
traction toward the fovea centralis in the macular surface causing thought to rapidly progress and then stop.

. Fig. 2-14 Comparison between epiretinal membrane (A) and macular pseudoholes (B)
 62 Chapter 2 · Vitreoretinal interface pathology

References 13) Yamashita T, UemuraA, Sakamoto T. Intraoperative characteristics of the

posterior vitreous cortex in patients with epiretinal membrane. Graefes
Arch Clin Exp Ophthalmol. 2008; 246:333–337.
1) Sidd RJ, Fine SL, Owens SL, et al. Idiopathic preretinal gliosis. Am J Oph-
14) Kakehashi A, Schepens CL, de Sousa-Neto A, et al. Biomicroscopic findings
2 thalmol. 1982; 94:44–48.
2) Kishi S, Shimizu K. Oval defect in detached posterior hyaloid membrane in
of posterior vitreoschisis. Ophthalmic Surg. 1993; 24:846–850.
15) Heilskov TW, Massicotte SJ, Folk JC. Epiretinal macular membranes in eyes
idiopathic preretinal macular fibrosis. Am J Ophthalmol. 1994; 118:451–
with attached posterior cortical vitreous. Retina. 1996; 16:279–284.
456.
16) Arichika S, Hangai M, Yoshimura N. Correlation between thickening of the
3) Kishi S, Demaria C, Shimizu K. Vitreous cortex remnants at the fovea after
inner and outer retina and visual acuity in patients with epiretinal mem-
spontaneous vitreous detachment. Int Ophthalmol. 1986; 9:253–260.
brane. Retina. 2010; 30:503–508.
4) Gass JDM. Macular dysfunction caused by epiretinal membrane contrac-
17) Mitamura Y, Hirano K, Baba T, et al. Correlation of visual recovery with
tion. Stereoscopic atlas of macular diseases. Diagnosis and treatment 4th
presence of photoreceptor inner/outer segment junction in optical co-
ed., CV Mosby, St. Louis, 1997. pp176–180.
herence images after epiretinal membrane surgery. Br J Ophthalmol.
5) Clarkson JG, Green WR, Massof D. A histopathologic review of 168 cases of
2009; 93:171–175.
preretinal membrane. Am J Ophthalmol. 1977; 84:1–17.
18) Suh MH, Seo JM, Park KH, et al. Associations between macular findings by
6) Kampik A, Green WR, Michels RG, et al. Ultrastructural features of progres-
optical coherence tomography and visual outcomes after epiretinal
sive idiopathic epiretinal membrane removed by vitreous surgery. Am J
membrane removal. Am J Ophthalmol. 2009; 147:473-480.e3.
Ophthalmol. 1980; 90:797–809.
19) Falkner-Radler CI, Glittenberg C, Hagen S, et al. Spectral-domain optical
7) Hui YN, Goodnight R, Zhang XJ, et al. Glial epiretinal membranes and con-
coherence tomography for monitoring epiretinal membrane surgery.
traction. Immunohistochemical and morphological studies. Arch Oph-
Ophthalmology. 2010; 117:798–805.
thalmol. 1988; 106:1280–1285.
20) Inoue M, Morita S, Watanabe Y, et al. Inner segment/outer segment junc-
8) Smiddy WE, Maguire AM, Green WR, et al. Idiopathic epiretinal mem-
tion assessed by spectral-domain optical coherence tomography in pa-
branes. Ultrastructural characteristics and clinicopathologic correlation.
tients with idiopathic epiretinal membrane. Am J Ophthalmol. 2010;
Ophthalmology. 1989; 96:811–820.
150:834–839.
9) Morino I, Hiscott P, McKechnie N, et al. Variation in epiretinal membrane
21) Oster SF, Mojana F, Brar M, et al. Disruption of the photoreceptor inner
components with clinical duration of the proliferative tissue. Br J Ophthal-
segment/outer segment layer on spectral domain-optical coherence to-
mol. 1990; 74:393–399.
mography is a predictor of poor visual acuity in patients with epiretinal
10) Okada M, Ogino N, Matsumura M, et al. Histological and immunohisto-
membranes. Retina. 2010; 30:713–718.
chemical study of idiopathic epiretinal membrane. Ophthalmic Res. 1995;
22) Ooto S, Hangai M, Takayama K, et al. High-resolution imaging of the pho-
27:118–128.
toreceptor layer in epiretinal membrane using adaptive optics scanning
11) Kampik A, Kenyon KR, Michels RG, et al. Epiretinal and vitreous membranes:
laser ophthalmoscopy. Ophthalmology. 2011; 118:873–881.
comparative study of 56 cases. Retina. 2005; 25:1445–1454.
23) Watanabe A, Arimoto S, Nishi O. Correlation between metamorphopsia
12) Bringmann A, Wiedemann P. Involvement of Müller glial cells in epiretinal
and epiretinal membrane optical coherence tomography findings. Oph-
membrane formation. Graefes Arch Clin Exp Ophthalmol. 2009; 247:865–
thalmology. 2009; 116:1788–1793.
883.
Case 26 · Idiopathic epiretinal membrane: A typical example
63 2
Case 26 Idiopathic epiretinal membrane: A typical example

A 76-year-old male, OD, BCVA 0.6

A: Color fundus photograph in the right eye: Retinal wrinkling, mild membrane whitening and tortuosity of the retinal blood vessels are noted. B: Enlarged
version of A [red dashed box]: Same findings as A can be observed. C: Retinal thickness color map of the right eye, D: IR + OCT horizontal scan of the right
eye: ERM (↔) and a small foveal detachment ( ) can be seen. E: IR + OCT vertical scan of the right eye: Retinal folds are noticeable in the horizontal direc-
tion. A gap between ERM (↔) and ILM appears to be vacant adherent only to the peaks of the folds. F: IR + OCT horizontal scan of right eye: 2 months after
surgery. Retinal thickening is reduced, but the foveal depression has not been restored. Best-corrected visual acuity has improved to 0.9

Image interpretation points

ERMs are thought to occur as a result of fibrocellular membrane curs as a result of concentric contraction of the residual posterior
formation that develops when cells migrate to a gap in the re- vitreous cortex. Retinal folds are noticeable on vertical scans that
sidual posterior vitreous cortex and ILM in eyes with macular intersect the retinal blood vessels because ERMs strongly adhere
PVD. The area in which an ERM is formed is narrower than the to the blood vessels. The gap between ERM and ILM is fulfilled
9 mm OCT scan area in most cases and ERM stumps can be seen with moderately reflective fibrocellular membraneous tissue in
in the images. Retinal thickening and retinal fold formation oc- some eyes while it appears to be vacant as seen in this case.
 64 Chapter 2 · Vitreoretinal interface pathology

Case 27 Idiopathic epiretinal membrane: Exposure of the fibrocellular membrane

A 58-year-old female, OS, BCVA 0.8

2

A: Left eye fundus photograph, B: Enlarged version of A [red dashed box]: Retinal folds, whitening and tortuosity of the retinal blood vessels can be viewed.
C: Retinal thickness color map of the left eye. D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: Exposure of flaccid swollen
fibrous tissue from ERM (↔) stumps can be seen. This extends from the moderately reflective fibrous membrane that exists between the ERM and the ILM.
The IS/OS and COST lines of the fovea centralis are normal. E: IR + OCT oblique scan of the left eye: Same findings as D can be seen. Retinal folds are not
clearly seen. This is because the gap between the ERM and ILM is fulfilled with moderately reflective fibrocellular tissue, which is also responsible for the
whitening of the ERM on a color fundus photograph. ↔ shows ERM. F: IR + OCT horizontal scan of the left eye: Flaccid coil-shaped fibrous structures repre-
senting exposed fibrocellular membrane are clearly visible. Columnar structure running obliquely to the retina in parallel represents Muller cells in the ILM
detachment. These 2 structures can be differentiated based on the characteristic pattern.

Image interpretation points

Findings of fibrous, flaccid tissue rising towards the vitreous and ILM is fulfilled with the fibrous membrane that exhibits
cavity from ERM stumps is often seen. These findings are moderate reflectivity. These features suggest extensive fibro-
consistent with thickened white areas when viewed with an plasia and cell migration towards the ERM and ILM gap leading
ophthalmoscope. In cases such as these, retinal folds exist to substantial ERM contraction.
but become indistinct on OCT since the gap between the ERM
Case 28 · Idiopathic epiretinal membrane: Membrane with significant whitening
65 2
Case 28 Idiopathic epiretinal membrane: Membrane with significant whitening

A 74-year-old female, OS, BCVA 0.4

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: at initial diagnosis. Significant macular whitening accompanies radial
retinal folds. C: Retinal thickness color map of the left eye: Significant thickening can be seen. D: IR + OCT horizontal scan of the left eye: The rippling folds
extending to the outer nuclear layer indicate strong centripetal forward tractional force. The fovea centralis shows thickening of the outer nuclear layer,
while the parafoveal retina shows thickening of the inner retinal layers. ↔ shows ERM. E: IR + OCT vertical scan of the left eye: Retinal folds that can be
readily seen in the fundus photograph are indistinct. Fibrocellular membrane tissue filling the ERM and ILM gap may be responsible for the unclear visibili-
ty of retinal folds, and also for the membrane whitening. ↔ shows ERM. F: IR + OCT vertical scan of the left eye: ILM detachment or splitting of the retinal
nerve fiber layer can be seen. A columnar structure thought to be Müller cells can be seen in the separation gap.

Image interpretation points

This is a case where retinal whitening and contraction are strength of the traction. Ripples and the columnar structure cor-
significant. The gap between the highly reflective ERM and ILM responding to Müller cells in the retinal nerve fiber layer separa-
has been completely filled with moderately reflective fibro- tion gaps show the centripetal forward traction. The end of
cellular membrane tissue, which is thought to be why mem- the ERM is visible and the fibrous membrane exposed outside
brane whitening is exhibited on a color fundus photograph. can sometimes be seen. This can be interpreted as findings
Significant thickening, ripples in the outer plexiform layer, and which demonstrate that concentric contraction has progressed.
separation of the retinal nerve fiber layer demonstrate the
 66 Chapter 2 · Vitreoretinal interface pathology

Case 29 Idiopathic epiretinal membrane: Significant columnar structure formation

A 58-year-old female, OS, BCVA 0.3

2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: Substantial macular whitening accompanies radial retinal folds.
C: Retinal thickness color map of the left eye. D: IR + OCT horizontal scan of the left eye: The ERM (↔) contracts and the fibrocellular membrane ( )
formed in the ERM and ILM gap, is exposed and becomes flaccid. The retinal nerve fiber layer is splitting and a columnar structure corresponding to Muller
cells is seen in the gap. E: IR + OCT vertical scan of left eye: Exposure of the fibrocellular membrane ( ) can be seen. A columnar structure (red dashed cir-
cle) corresponding to Müller cells in the separation gap of the ILM detachment can be seen. The orientation of the columnar structure appears to show the
direction of the traction. ↔ shows ERM. F: IR + OCT vertical scan of the left eye: A fibrocellular membrane tissue that formed between the ERM and the ILM
has detached from the macular surface and has become flaccid

Image interpretation points

This is a case where whitening and contraction of ERM are detached ILM shows centripetal traction. The end of the ERM is
substantial. Significant thickening, ripples in the inner layers, visible and the fibrocellular membrane exposed can sometimes be
and separation of the retinal nerve fiber layer demonstrate the seen. This can be interpreted as findings that also demonstrate
strength of the traction. The orientation of the columnar struc- that concentric contraction has progressed.
ture in the retinal nerve fiber layer splitting gap and beneath the
Case 30 · Idiopathic epiretinal membrane: Case ① where macular PVD has not been complete
67 2
Case 30 Idiopathic epiretinal membrane: Case ① where macular PVD has not been complete

A 66-year-old female, OD, BCVA 0.7

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Membrane whitening and radial retinal folds can be seen. C: Retinal
thickness color map of the right eye: Thickening is not very significant. D: IR + OCT horizontal scan of the right eye: The macular PVD stops at the periphery
of the macula and the posterior vitreous cortex adherent to the macula has developed into the ERM ↔. Compared to the detached posterior vitreous cor-
tex ( ), the ERM is highly reflective and linear. Contraction of ERM leads to formation of retinal folds and a small foveal detachment (7). E: IR + OCT verti-
cal scan of the right eye: PVD appears to have stopped in the retinal blood vessel area ( ). indicates the posterior vitreous cortex

Image interpretation points

This is a case where macular PVD is incomplete and has macular traction syndrome in the disease processes include
stopped at the retinal blood vessel of the macula. Cell migra- both centripetal and centrifugal traction, but the morphological
tion occurred from cracks in the ILM along the retinal blood changes that occur in the retina are a little different. Vitreo-
vessels. A fibrovascular membrane has formed in the gap be- macular traction syndrome is trapezoidal-shaped thickening
tween the attached posterior vitreous cortex and ILM, which due to strong centrifugal forward traction, whereas in this case
is thought to develop into an ERM. Contraction occurs in the foveal thickening and retinal folds due to centripetal forward
ERM development process, generating centripetal forward traction is primary. However, both diseases conditions may be
traction. This is similar to the pathogenic mechanism of vitreo- on the same spectrum.
 68 Chapter 2 · Vitreoretinal interface pathology

Case 31 Idiopathic epiretinal membrane: Case ② where macular PVD has been complete

Left eye of a 74-year-old female with vision corrected to 0.8

2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: Whitening and tortuosity of the retinal blood vessels can be seen.
C: Retinal thickness color map of the left eye. D: IR + OCT horizontal scan of the left eye: Macular PVD is stopping at the foveal border ( ). This state is
known as perifoveal PVD. ERM (↔) is formed even in the area where PVD has progressed. E: IR + OCT vertical scan of the left eye: Retinal folds are noticeable
in the horizontal direction. ↔ shows ERM. F: IR + OCT horizontal scan of left eye: 2 months after surgery. Retinal thickening has decreased. Thinning of the
temporal retina that occurs when the ILM has detached cannot be seen. Thus, it is very likely that the retinal surface membrane is not the ILM, but the ERM.

Image interpretation points

In this case, the posterior vitreous cortex and ERM can be seen posterior vitreous cortex and ILM. In this case, the posterior vitreous
at the same time part way through the PVD process. An ERM is cortex in the macula separated into two layers and PVD only of the
thought to be formed as a result of fibrocellular membrane for- inner layer progressed and then stopped at the parafovea. ERM
mation that occurs when cells migrate to a gap in the residual appears to be formed with the posterior layer acting as a scaffold.
Case 32 · Epiretinal membrane secondary to retinal hemangioma
69 2
Case 32 Epiretinal membrane secondary to retinal hemangioma

A 53-year-old female, OS, BCVA 0.6

A: Color fundus photograph in the left eye: Thick, yellowish-white ERM is noticeable over a wide area of posterior pole. B: Left eye panoramic fundus photo-
graph in the left eye: Hemangioma of the retina can be seen infero temporally. C: Panoramic fluorescein angiography (FA) in the left eye: Significant leakage
from hemangioma of the retina and an avascular region in the periphery can be observed. D: IR + OCT horizontal scan of the left eye: Seemingly thick »rigid«
ERM can be seen. Retinal thickening is mild. Retinal schisis (red dashed circle) secondary to the traction toward the retinal blood vessel can be observed su-
periorly. Proliferative membrane tissue rising towards the vitreous cavity is noted ( ). E: IR + OCT vertical scan of the left eye: Irregular retinal folds ( ) can
be seen above the macula. F: IR + OCT horizontal scan of the left eye: Proliferative membrane tissue rising towards the vitreous cavity is noticeable ( ). Reti-
nal schisis (red dashed circle) can be observed temporally.

Image interpretation points

This is a case of an ERM thought to be secondary to retinal hem- an idiopathic ERM, the thickness of the membrane to be more
angioma. ERM occurs frequently secondary to fundus diseases significant, and increased retinal traction. Significant membrane
such as retinal tears, retinal vascular diseases and uveitis. In this thickening, irregularities in the retinal folds and retinoschisis for-
type of ERM, there is a tendency for the area to be wider than mation in the outer plexiform layer are also noticeable in this case.
 70 Chapter 2 · Vitreoretinal interface pathology

Case 33 Macular pseudohole: A typical example

A 73-year-old female, OD, BCVA 0.7

2

A: Color fundus photograph in the right, B: Enlarged version of A [red dashed box]: Significant whitening can be seen in the inferior macula. C: Retinal
thickness color map of the right eye. D: IR + OCT horizontal scan of the right eye, E: IR + OCT vertical scan of the right eye: ERM (↔) cannot be seen in the
fovea centralis, and a V-shaped foveal depression can be seen. Excluding the foveal shape, this is no different than a typical ERM OCT image. F: Enlarged
version of E [red dashed box]: ERM stumps can be clearly seen ( )

Image interpretation points

An ERM develops as a membrane characterized by concentric tex. In other words, the foveal thickening characteristic to ERM is
contraction. The posterior vitreous cortex that remains on the missing. In addition, macular pseudohoes can be distinguished
macular surface after PVD onset becomes scaffolding along from lamellar macular holes by retinal findings, i.e. retinal folds,
which cell migration and fibrous membrane formation occur. and retinal thickening outside the fovea centralis as a result of
Macular pseudoholes (MPH) occur as a result of the same concentric contraction of ERM. Nevertheless, ERM can also form
pathogenic mechanism as ERM; however, with MPH, a hole is after lamellar circular hole formation sometimes making it diffi-
formed at the foveal area of the residual posterior vitreous cor- cult to differentiate the two entities.
Case 34 · Macular pseudohole: Case where macular PVD has not been complete
71 2
Case 34 Macular pseudohole: Case where macular PVD has not been complete

A 56-year-old male, OD, BCVA 1.5

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Whitening and radial retinal folds can be seen. C: Retinal thickness
color map of the right eye. D: IR + OCT horizontal scan of the right eye: Thick ERM ↔ is noted. ERM cannot be seen over the fovea centralis. ERM is formed
along the posterior vitreous cortex ( ). The foveal depression is V-shaped. E: IR + OCT horizontal scan of the right eye: ERM scan. ERM (↔), continuing
from the posterior vitreous cortex ( ), can be observed. A posterior vitreous cortex defect are visible on the supero nasal ERM

Image interpretation points

This is a case of macular pseudohole where ERM is formed forward traction is primary in vitreomacular traction syndrome,
when the PVD has stopped in the periphery of the macula. causing macular trapezoidal-shaped thicknening, in this case,
PVD often stops along the retinal blood vessels to which the centripetal forward traction is primary, leading to mountain-
posterior vitreous cortex is firmly adherent , and thereby the shaped retinal thickening and fold formation in the macula. The
dehiscence of the ILM occurs duo the traction of the detached fovea centralis exhibits a V-shaped or U-shaped depression.
posterior vitreous cortex toward the ILM. Cell migration often Despite the macular PVD being incomplete, the reason for the
occurs through the ILM dehiscence into the gap between the defect formation foveal posterior vitreous cortex defects over
posterior vitreous cortex and ILM and produces fibrocellular the fovea centralis is not known. Posterior vitreous cortex de-
membrane, thus forming the ERM. fects may occur as a result of ERM contraction, or may develop
ILM dehiscence along the retinal blood vessels contraction with extensive separation of the posterior vitreous cortex into
occurs in this formation process resulting in centripetal for- two layers. In the latter hypothesis, the posterior layer is clipped
ward traction similar to the pathogenic mechanism of vitreo- out over the fovea centralis and taken away adherent to the
macular traction syndrome. However, whereas centrifugal detached anterior layer.
 72 Chapter 2 · Vitreoretinal interface pathology

2.3 Vitreomacular traction syndrome and myofibroblasts, which were reportedly found in eyes with
ERM and an extracellular matrix primarily made of collagen
Background were found to be present in fibrocellular membrane in eyes with
2 Vitreomacular traction syndrome is like a stage 1 macular hole vitreomacular traction syndrome, supporting the speculation
or an epiretinal membrane with incomplete macular PVD in that these 2 diseases have common pathogenic conditions.(6–9).
that it occurs in conditions where the perifoveal detachment of
the posterior vitreous cortex with persistent adherence of the
vitreous to the fovea or retinal surface of the macula. However, References
the attachment to the retinal surface in this disease state is often
more broad or occurs in multiple areas. Strong centrifugal for- 1) Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syn-
drome. Am J Ophthalmol. 1995; 119:55–61.
ward traction is applied to the macula so that the macular area is
2) Kishi S, Demaria C, Shimizu K. Vitreous cortex remnants at the fovea after
raised into a tent shape (trapezoid) and the retina thickens. Cys- spontaneous vitreous detachment.Int Ophthalmol. 1986; 9:253–260.
toid space formation and fovea or macular detachment often ac- 3) Spaide RF, Wong D, Fisher Y, et al. Correlation of vitreous attachment and
company this disease. In 11% of cases, PVD occurs during fol- foveal deformation in early macular hole states. Am J Ophthalmol. 2002;
low-up and cystoid spaces decrease(1). There is both a focal- and 133:226–229.
4) Koizumi H, Spaide RF, Fisher YL, et al. Three-dimensional evaluation of
wide- adhesion type vitreomacular traction syndrome where the
vitreomacular traction and epiretinal membrane using spectral-domain
focal type has a vitreomacular adhesion within a central macula optical coherence tomography. Am J Ophthalmol. 2008; 145:509–517.
region with physiological strong attachment between posterior 5) Gass JDM. Macular dysfunction caused by epiretinal membrane contrac-
vitreous body and macular surface that was reprorted by Kishi et tion. Stereoscopic atlas of macular diseases. Diagnosis and treatment 4th
al. and Spaide et al. as a cause of vitreofoveal traction in the de- ed., CV Mosby, St. Louis, 1997. pp176–180.
6) Smiddy WE, Green WR, Michels RG, et al. Ultrastructural studies of vitreo-
velopment of a macular hole(2, 3) while the broad type over a
macular traction syndrome. Am J Ophthalmol. 1989 15; 107:177–185.
wider area(4). Vitreomacular traction syndrome often accompa- 7) Shinoda K, Hirakata A, Hida T, et al. Ultrastructural and immunohisto-
nies other eye diseases such as diabetic maculopathy, severe chemical findings in five patients with vitreomacular traction syndrome.
myopia, and uveitis. Abnormal vitreoretinal interface adhesion Retina. 2000; 20:289–293.
and degeneration of vitreous gel due to inflammation may be 8) Gandorfer A, Rohleder M, Kampik A, et al. Epiretinal pathology of vitreo-
involved in the pathogenic processes of this disease. ERM cases macular traction syndrome. Br J Ophthalmol. 2002; 86:902–909.
9) Chang LK, Fine HF, Spaide RF, et al. Ultrastructural correlation of spectral-
without a PVD sometimes progress to vitreomacular traction
domain optical coherence tomographic findings in vitreomacular trac-
syndrome. The pathogenesis of vitreomacular traction syndrome tion syndrome. Am J Ophthalmol. 2008; 146:121–127.
can be explained by the migratory cell membrane formation
theory described for ERM pathogenesis earlier in this chapter.
Based on this theory, the PVD stops at the strongly adhesive
retinal blood vessels, fovea and optic disc with cells then migrat-
ing from cracks in the ILM and to gaps in the posterior vitreous
cortex and ILM. As a result of extracellular matrix production,
these migrating cells form a fibrocellular membrane which ad-
heres to the posterior vitreous cortex and macular surface.(5) (see
page 60, . Fig. 2-13).
Thus, vitreomacular traction syndrome and ERM without
complete macular PVD appear to have pathogenic mechanisms
on the same spectrum with some different conditions. ERM may
be a condition where fibrocellular membrane formation occurs
primarily beneath the posterior vitreous cortex attached to the
macular surface, thus leading to macular thickening and fold
formation through centropetal forward traction generated by
membrane contraction(4). In contrast, vitreomacular traction
syndrome may be a condition where fibrocellular membrane
formation occurs beneath both attached and detached posterior
vitreous cortex, thus leading to a tent-shaped elevation of the
macula through centrifugal forward traction generated by the
detached posterior vitreous cortex(4).
Vitreomacular traction syndrome often accompanies ERM.
In these cases, the posterior vitreous cortex is presumed to sepa-
rate in eyes with vitreomacular traction syndromeinto two layers
where the anterior layer detaches from the retina and the poste-
rior layer remains on the retina and becomes the origin of the
ERM (4). In histopathological observations of surgical samples
and autopsied eyes, cells mainly comprising fibrous astrocytes
Case 35 · Vitreomacular traction syndrome: Case showing disease development
73 2
Case 35 Vitreomacular traction syndrome: Case showing disease development

Right eye of a 74-year-old male with vision corrected to 0.8

A: IR + OCT horizontal scan of the right eye, B: IR + OCT horizontal scan of the right eye: at initial diagnosis. Macular PVD is in progress. Adhesion of the
posterior vitreous cortex ( ) remains in the optic disc, fovea centralis and the temporal macula. C: IR + OCT horizontal scan of the right eye + enlarged
version [red dashed box]: 1 year after initial diagnosis. Best corrected visual acuity is 0.7. Macular PVD is not progressing; however, there is separation of
the posterior vitreous cortex, an increase in the tension of the detached anterior layer of the posterior vitreous cortex ( ) and contraction of the posterior
vitreous cortex adhered to the macular surface seen. Mild retinal thickening, retinal folds and foveal detachment are all seen. It is unknown whether the
membrane of the posterior part is the ILM or the result of the separation of the posterior vitreous cortex into two layers, but the third membrane beneath
these 2 membranes that appears afterwards suggests that these membranes are anterior and posterior layers separated posterior vitreous cortex. The
anterior layer of the posterior vitreous cortex is causing centrifugal forward traction.
(Continues on the following page)

vitreomacular traction syndrome

 74 Chapter 2 · Vitreoretinal interface pathology

Case 35 Continuation

D: Color fundus photograph in the right eye: 2 years after initial diagnosis. Visual acuity reduced to 0.3. E: IR + OCT horizontal scan of the right eye, F: IR + OCT
vertical scan of the right eye, G: IR + OCT horizontal scan of the right eye: Traction of the posterior vitreous cortex that has separated into two layers is increas-
ing and macular area thickening is worsening. The posterior vitreous cortex ( ) is strongly adherent to the retinal blood vessels and fovea centralis and its
anterior layer is applying strong centrifugal forward traction. Cystoid spaces are formed in the macula. G shows the optically virtual image of the thickened
anterior layer of the posterior vitreous cortex reflected in multiple layers as an averaging artifact, which indicates that the membrane is intensely shook by eye
movement. Another membrane is seen below the posterior vitreous membrane that has separated into two layers is noticeable on the retinal surface.

Image interpretation points

Cell migration and fibrocellular membrane formation resulting of the ERM, thus causing the macula to thicken into a tent-
in strong adhesion occur on the posterior vitreous cortex and shaped (trapezoid). With eye movements, the posterior vitreous
in the gap between the posterior vitreous cortex and ILM gaps cortex demonstrates significant trembling, which could enhance
while macular PVD in stopped around the fovea and along the cell migration. In vitreomacular traction syndrome, multiple
strongly adherent retinal blood vessels. In this disease, centri- membranes are seen on OCT. In this case, it is likely that there
fugal forward traction due to the detached posterior vitreous is initially separation of the posterior vitreous membrane into
cortex with persistent adhesion to the fovea and blood vessels two layers followed by ILM detachment as the traction worsens.
is superior to centripetal forward traction by the contraction
Case 36 · Vitreomacular traction syndrome: Case with macular detachment
75 2
Case 36 Vitreomacular traction syndrome: Case with macular detachment

A 75-year-old female, OD, BCVA 0.3

A: Color fundus photograph in the right eye: Whitening in the macula is apparent. B: IR + OCT horizontal scan of the right eye: The posterior vitreous
cortex ( ) is thick and linear, adherent to a wide area of the macula. The retina in the macula is highly elevated to form macular detachment. The optically
virtual image of the thickened posterior vitreous cortex is reflected in multiple layers as an averaging artifact and the membrane can be seen trembling
significantly with eye movements. In addition, retinoschisis and a columnar structure thought to be Müller cells can be seen in the outer plexiform layer,
inner nuclear layer and retinal nerve fiber layer.

Image interpretation points

This individual became aware of blurred vision one month prior fibrocellular membrane formation appears to have made the
to presentation. The posterior vitreous cortex has thickened posterior vitreous cortex thickened and hard. The presence of
and adhered to the wide area of the macula. Progression of macular detachment is suggestive of strong forward traction.
 76 Chapter 2 · Vitreoretinal interface pathology

Case 37 Vitreomacular traction syndrome: A highly myopic eye with foveoschisis

A 71-year-old female, OS, BCVA 0.5

2

A: Color fundus photograph in the left eye: A tessellated fundus is seen. B: Retinal thickness color map of the left eye, C: IR + OCT horizontal scan of the
left eye: The posterior vitreous cortex ( ) is adhered to the surface of the fovea. The fovea is highly elevated by the centrifugal forward traction, and large
foveal cystoid space and retinoschisis in the outer plexiform layer are seen. The optically virtual image of the thickened posterior vitreous cortex is re-
flected in multiple layers as an averaging artifact, and the membrane can be seen trembling significantly with eye movements. Highly myopic eyes are
susceptible to retinoschisis formation when such forward traction works on the fovea.. D: IR + OCT vertical scan of the left eye: A slight detachment of a
thin membrane on the retinal surface in the inferior macula is visible ( ).

Image interpretation points

Vitreomacular traction syndrome tends to occur in severely are characteristics of vitreomacular traction syndrome. Vitreo-
myopic eyes. Adhesion of the posterior vitreous cortex to the macular traction is one of the causes for developing myopic
surface of the fovea and tent-shaped thickening of the retina foveoschisis.
 77 3

Diabetic retinopathy
3.1 Diabetic retinopathy – 78
3.1.1 Background – 78

3.2 Diabetic macular edema – 79

3.2.1 Background – 79
3.2.2 SD-OCT findings – 80
References – 85

Case 38 Diabetic macular edema: Early-stage case – 86

Case 39 Cystoid macular edema: Case with CME limited to layers anterior
to the ELM – 87

Case 40 Cystoid macular edema: Case with CME extending

to the outer retina – 88

Case 41 Cystoid macular edema: Exacerbation – 89

Case 42 Cystoid macular edema: Foveal detachment with recurrence – 90

Case 43 Cystoid macular edema: Subfoveal accumulation of hard

exudates and the development of ischemic maculopathy – 91

Case 44 Cystoid macular edema: Subretinal leakage from a parafoveal

cystoid spaces – 92

Case 44 Continuation – 93

Case 45 Cystoid macular edema: Subfoveal leakage from a foveal cystoid

spaces – 94

Case 46 Cystoid macular edema: Photoreceptor damage from outer

plexiform layer edema – 95

Case 46 Continuation – 96

Case 47 Cystoid macular edema: Microaneurysms – 97

Case 48 Ischemic maculopathy: Cystoid macular degeneration – 98

Case 49 Ischemic maculopathy: Thinned macula – 99

Case 50 Vitreomacular traction syndrome: A typical example – 100

Case 51 Proliferative diabetic retinopathy: Progressive proliferation – 101

Case 52 Proliferative diabetic retinopathy: Preretinal hemorrhages

and vitreomacular traction syndrome – 102
 78 Chapter 3 · Diabetic retinopathy

3.1 Diabetic retinopathy aggregation, and thickening of the capillary basement membrane
have been reported(4, 5). Retinal MAs are the earliest changes that
3.1.1 Background can be observed by ophthalmoscopy. More MAs indicate more
severe retinopathy/maculopathy(6), and an increase in the num-
Pathological conditions that cause visual ber of MAs(7) suggest worsening of retinopathy/maculopathy(7).
impairment Hyperpermeability occurs as a result of lesions in these capil-
3 Clinically significant pathological conditions that cause visual laries, causing macular edema and hard exudate formation.
impairment are ① diabetic macular edema, and ② proliferative
diabetic retinopathy. Although not as frequent, ③ ischemic mac- Retinal capillary lesions in the advanced
ulopathy is also a significant cause of severe visual impairment. nonproliferative stage
An exacerbation of hyperpermeability and capillary nonperfusion
Retinal capillary bed occur as retinopathy progresses. Arterioles become occluded and
The retinal capillary perifoveal capillary bed forms 4 layers be- accumulated MAs and tortuous capillaries, which are known as
tween the retinal nerve fiber layer and inner nuclear layer. It is intraretinal microvascular abnormalities (IRMAs) is seen in the
located at specific retinal layer boundaries, such as the external vicinity. When capillary occlusion sites dilate, venous beading,
margin of the inner nuclear layer, the external margin of the gan- venous tortuosity, flame-shaped hemorrhages (surface hemor-
glion cell layer, the inner margin of the inner nuclear layer, and rhages), and dot and blot hemorrhages (deep hemorrhages) in-
the ganglion cell layer to the retinal nerve fiber layer (listed from crease. The IRMAs indicates initiation of the proliferative phase
the major network)(1–3). The dilated capillaries in eyes with (preproliferative diabetic retinopathy).
diabetic retinopathy can be easily seen as highly reflective spots
on OCT, therefore easily recognizing the depth of the capillary Diabetic macular edema
bed (. Fig. 3-1). The perifoveal capillary bed only exists as one Described in detail in the next page.
layer on the external margin of the ganglion cell layer(1). There
are no retinal blood vessels in the central part of the fovea, Soft exudate (cotton-wool spots)
0.5 mm wide in diameter, and it is known as the foveal avascular Soft exudates is a common finding that can be seen not only in
zone (FAZ). diabetic retinopathy but also in retinal vein occlusions, hyperten-
sive retinopathy and HIV retinopathy; with the presence of mul-
Retinal capillary lesions in the early tiple soft exudates suggesting the presence of an acute nonperfu-
nonproliferative stage sion area formation or a wide area of nonperfusion. On OCT they
Early changes in diabetic retinopathy occur in the retinal capil- can be seen as highly reflective localized thickening in the retinal
laries. Loss of capillary pericytes, microaneurysm (MA) forma- nerve fiber layer (. Fig. 3-2). Highly reflectivity remains due to
tion and loss of endothelial cells, inversely endothelial cell gliosis after the disappearance of the soft exudates(8).

. Fig. 3-1 The retinal capillary network in an OCT B-scan (case of early diabetic retinopathy)
Capillary vessels are depicted as highly reflective dots

. Fig. 3-2 OCT B-scan image of soft exudates

It can be seen as highly reflective localized thickening (→) of the retinal nerve fiber layer
3.2 · Diabetic macular edema
79 3
3.2 Diabetic macular edema MAs and dilated capillaries and is often surrounded by circinate
exudates. Diffuse edema occurs as a result of hyperpermeability
3.2.1 Background of retinal capillaries in the macula.

Classification of retinal edema Macular edema patterns and retinal thickness

Retinal edema is divided into macular edema and retinal nerve Otani et al. classified diabetic macular edema patterns that can
fiber layer (RNFL) edema. The former is extracellular tissue be seen with OCT-2000 into sponge-like retinal swelling, cystoid
swelling due to leakage from capillaries and microaneurysms macular edema, and serous retinal detachment (. Fig. 3-3); and
(MAs). The latter is thickening due to an increase in intracellular stated that visual acuity was most correlated with macular retinal
volume caused by a shortage in arterial blood supply, which typ- thickness regardless of the type of pattern(9).
ically occurs in soft exudate formation.
Macular exudative changes
Leakage mechanism In 15–26% of the cases that develop cystoid macular edema,
Diabetic macular edema occurs regardless of the presence of repeated foveal detachment occurs due to the leakage into
proliferative diabetic retinopathy and is a pathological condition the subretinal space(9–11). Lipid accumulation mainly occurs
that destroys the foveal photoreceptors leading to permanent vi- from the outer plexiform layer to subretinal space, and leads
sual impairment. It is further divided into both focal edema and to formation of intraretinal and subretinal hard exudates(12).
diffuse edema, based on differences in the leakage mechanism. Serum lipid levels are a risk factor in hard exudate forma-
Focal edema occurs as a result of leakage from accumulated tion.(13–15)

. Fig. 3-3 Patterns of diabetic macular edema seen with a time-domain OCT image
A: Sponge-like retinal swelling, B: Cystoid macular edema, C: Serous retinal detachment.
(Modified according to Otani T, et al. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999; 127: 688–693)
 80 Chapter 3 · Diabetic retinopathy

3.2.2 SD-OCT findings times complicated, lesions of diabetic macular edema are formed
depending on leakage sites, leakage pressure, and properties of
Typical locations for cystoid spaces leaking serous fluid.
Individual cystoid spaces can be seen with spectral-domain OCT
(SD-OCT). Cystoid spaces are frequently found in the fovea cen- Cystoid spaces and intracavity reflectivity
tralis, parafovea, outer plexiform layer, and inner nuclear layer, SD-OCT has led to the understanding that the reflectivity inten-
3 and each have their own shape(16–18) (. Fig. 3-4). Diabetic macu- sity of cystoid spaces varies from weakly reflective to moderately
lar edema are sometimes accompanied by foveal detachment reflective (. Fig. 3-5). This is thought to reflect the different
(. Fig. 3-4). Among cystoid spaces, cystoid spaces in the outer properties of accumulating exudates in the cystoid spaces. Some-
plexiform layer, the fovea and parafovea, and foveal detachment times hemorrhages accumulate in the cystoid spaces, which then
are most influential in macular thickening. A variety of, some- becomes highly reflective and shows niveau formation.

. Fig. 3-4 Typical locations for cystoid spaces

A: Schema that shows the typical locations for cystoid spaces in diabetic macular edema, B: Light microscopic view of diabetic macular edema,
C, D: SD-OCT images of diabetic macular edema.
(B is modified according to Gass JD, et al. Cystoid macular edema and papilledema following cataract extraction. A fluorescein fundoscopic and angio-
graphic study. Arch Ophthalmol. 1966; 76: 646–661)

. Fig. 3-5 The reflectivity intensity and accumulated fluid properties in cystoid spaces
A: »Serous exudate within thin-wall cystoid spaces« that can be seen in a tissue samples, B: The appearance of cystoid spaces that differs with intracavity
reflectivity in OCT
(A is modified according to Tso MO. Pathological study of cystoid macular edema. Trans Ophthalmol Soc UK. 1980; 100: 408–413)
3.2 · Diabetic macular edema
81 3
The appearance of cystoid spaces in the outer it difficult to see cystoid spaces clearly (. Fig. 3-5–3-7). Thicken-
plexiform layer ing of the retinal nerve fiber layer can often block the OCT mea-
When observed with SD-OCT, we can see that outer plexiform surement beam, making it difficult to observe the structures in-
layer edema is basically comprised of cystoid spaces. When the cluding cystoid spaces below the retinal nerve fiber layer. We can
intracavity reflections of cystoid spaces are moderate they cannot figure out if it is cystoid edema through comparisons with later-
be distinguished from the septum of the cystoid spaces, making phase FA.

. Fig. 3-6 Case of outer plexiform layer edema

The outer plexiform layer edema appears diffuse at first glance, but hyperreflective foci, accumulating in the internal walls of cystoid spaces, highlight the
outline of the cystoid spaces. Cystoid macular edema is clear in FA.

. Fig. 3-7 Case of outer plexiform layer edema

The borders of the cystoid spaces are blurring when the lumen is moderately reflective, but the hemorrhages filled in some of the cystoid spaces highlight
the outline of the cystoid spaces.
 82 Chapter 3 · Diabetic retinopathy

Hyperreflective foci to be leaked lipoproteins and a precursor to hard exudates(19).

Bolz et al. reported that it is possible to see multiple highly reflec- When macular edema is ameliorated by grid photocoagulation,
tive spots, which they termed as hyperreflective foci, through the hyperreflective foci gather and coalesce, and become a hard
SD-OCT with speckle noise removed(19). Hyperreflective foci exudate that can be seen with an ophthalmoscope(20). There is no
cannot be seen with an ophthalmoscope fundus photography, or anatomical barrier to fluid movement within the retina, but the
infrared imaging and are findings that cannot be clearly depicted external limiting membrane (ELM) is comprised of the zonula
3 by single-scan SD-OCT. They are smaller than the hard exudates adherens between Müller cells and photoreceptors at the base of
that can be seen in fundus photography. There are distinguishing the outer segments, and thus had very narrow gaps, which limit
characteristics in the favorite accumulation locations and distri- particularly the movement of large molecules.(21). Hyperreflec-
bution patterns of hyperreflective foci, which most significantly tive foci cannot pass through the gaps in the ELM since they are
occur in areas of outer plexiform layer edema. The foci arrange large molecules and thereby are filtered by the ELM to align
themselves in a line along cystoid space cavity walls, MA walls, along the ELM(22). When vascular leakage is excessive and the
the anterior border of the external limiting membrane (ELM), internal pressure of the cystoid spaces increases, the structure of
the posterior border of the photoreceptor inner segment in the the ELM likely rupture to permit hyperreflective foci to leak
foveal detachment area, and the anterior border of the retinal below the retina. The hyperreflective foci that are leaked below
pigment epithelium (RPE) (. Fig. 3-8).(19) Since the retinal capil- the retina either become trapped along the posterior margin of
laries can also be seen as moderately reflective dots, differentia- the inner segment or accumulate on the surface of the RPE.
tion between hyperreflective foci and retinal capillaries is neces- When foveal detachment disappears as a result of vitreous sur-
sary. It is particularly misleading if there is dilation of capillaries. gery, grid photocoagulation, or a natural process, it can accumu-
However, retinal capillaries are present only in the inner nuclear late to become thick hard exudate beneath the fovea, causing
layer or layers interior to it, and show weaker reflectivity than visual acuity loss(12, 22).
hyperreflective foci. (. Fig. 3-1). Hyperreflective foci are thought

A
B

. Fig. 3-8 Typical localization of hyperreflective foci

Hyperreflective foci are typically found in and around outer plexiform layer edema. They are present arranged in lines along the walls of cystoid spaces, the
walls of MAs, the anterior border of the ELM, the posterior margin of the photoreceptor inner segment, and the surface of the RPE
3.2 · Diabetic macular edema
83 3
Retinal microaneurysms spaces includes isolated MAs (. Fig. 3-9A–E), MAs in contact
Retinal microaneurysm (MA) can be seen from an early stage with or adjacent to cystoid spaces (. Fig. 3-9F), and MAs that can
of diabetic retinopathy and are closely related to the disease be seen inside cystoid spaces (. Fig. 3-9C). The wall types of MAs
progress(4–7). The sizes of MAs in humans are quite variable, with include those where highly reflective rings can be seen around
15–55 µm (vascular casting method)(23) and 14–136 µm (whole- the entire circumference (. Fig. 3-9E), those where highly reflec-
mount immunostaining method)(24) MAs in diameter being re- tive rings can be partially seen (. Fig. 3-9F), and those where
ported. In histological observations, various types of MAs can be highly reflective rings cannot be seen (. Fig. 3-9G). The MAs
seen including those filled with multiple leukocytes or erythro- without the ring-shaped high reflectivity were more frequently
cytes; those with various endothelium conditions, such as con- associated with cystoid spaces than those with circumferential
tinuous, hypercellular, multi-layered, and defective cells; those high reflectivity(26).
with a thin wall or varyingly thickened and sclerotic due to hya-
line degeneration, fibrosis and degenerative lipid deposits(4, 5, 25). Nonperfusion area and OCT findings
The majority of MAs occur from the deeper capillary bed of the The nonperfusion area demonstrates significant thinning of the
inner nuclear layer(24, 25), and some can be observed extending to inner retina(26, 27). However, when macular edema is significant,
the outer nuclear layer(24). MAs that extend to this depth may be the thinning of the inner retinal layers is difficult to identify.
involved in the edema formation in the outer plexiform layer.
Utilizing SD-OCT with speckle noise removed, the depth and Visual prognosis and OCT findings
properties of MAs can be observed(26). When observed with this It is now possible to see and measure foveal structures indicating
method, MAs are circular or elliptical with a mean diameter of with the health of photoreceptor cells such as the ELM, IS/OS,
118.3/111.6 µm (horizontal diameter/vertical diameter), ranging and OS thickness with SD-OCT, and these indicators correlate
from 49.0 to 233.7 µm.(26) The spatial relationship with cystoid with visual acuity in diabetic macular edema(28–31).

. Fig. 3-9 Retinal microaneurysms seen on SD-OCT with speckle noise removed
A: Present in the retinal nerve fiber layer, B: Present in the ganglion cell layer and inner plexiform layer, C: Present in the outer plexiform layer, D: Present
in the inner nuclear layer, E: Present in the outer plexiform layer, F: In contact with cystoid spaces, G: Present in the cystic cavity. Retinal MAs can be seen in
various layers of the retina.
(Modified according to Horii T, et al. Optical coherence tomographic characteristics of microaneurysms in diabetic retinopathy. Am J Ophthalmol. 2010;
150: 840–848)
 84 Chapter 3 · Diabetic retinopathy

Mechanisms by which macular edema injure sure, enhancing the leakage to the photoreceptor layer and sub-
photoreceptor layer retinal space(9).
Permanent visual impairment as a result of macular edema is
caused by the destruction of the foveal photoreceptor layer. How- Ischemic maculopathy
ever, edema does not directly cause photoreceptor layer damage. Capillary nonperfusion in diabetic retinopathy typically occurs
The mechanism for photoreceptor cell destruction is complex. in the equator, and eventually expands to the macula as well
3 With SD-OCT, we are now able to observe leakages from cystoid as to the periphery. The capillary nonperfusion involving the
spaces into subretinal space, and this phenomenon appears to be macular, particularly the fovea, causes severe visual acuity loss.
involved in the destruction of the foveal photoreceptor layer. In addition, the enlargement of foveal avascular zone (FAZ) also
When internal pressure of cystoid spaces increase, they expand occurs in diabetic retinopathy, leading to visual acuity loss. These
to become in contact with the ELM, and thereby strong pressure disease conditions are termed ischemic maculopathy. The FAZ
is applied to the ELM. As a result, the structures of ELM as an of 1,000 µm or less in diameter does not cause visual acuity
anatomical barrier to the large molecules broken down, permit- decrease, whereas when the FAZ that expanded more than
ting leakage of fluid and large molecules to the photoreceptor 1,000 µm causes visual acuity loss(32). Sometimes the breakdown
layer and subretinal layer (. Fig. 3-10). This leakage repeats its of the capillary bed on the temporal macula extends to the fovea
stop-and-resume cycle. Photoreceptor damages appear to be due leading to severe visual impairment. These disease conditions are
to the mechanical obstruction by the leakage and due to the ac- termed ischemic maculopathy.
cumulation of hard exudate and hemorrhages beneath the foveal Ischemic maculopathy can sometimes be seen in type 1 dia-
photoreceptor layer. As described previously, the macular thick- betes. When observed with OCT, the fovea centralis displays
ness is associated to visual acuity loss.One possible mechanism cystoid macular degeneration or macular thinning. This is an
to account for this association is that when macular thickness important factor that impedes visual improvement even after
become greater cystoid spaces increase in size and internal pres- diabetic macular edema is resolved after treatment(33).

. Fig. 3-10 Diagram showing the leakage mechanism into the macular subretinal space
When the internal pressure of the cystoid spaces increases, contents break through the ELM and leak into the subretinal space
3.2 · Diabetic macular edema
85 3
References 23) Fryczkowski AW, Chambers RB, Craig EJ, et al. Scanning electron micro-
scopic study of microaneurysms in the diabetic retina. Ann Ophthalmol.
1) »Pattern and location of retinal vessels,« In The Retinal Circulation, Ed. by 1991; 23:130–136.
Wise GN, Dollery CT, Henkind P, Harper & Row. 1971, pp 20–31. 24) Moore J, Bagley S, Ireland G, et al. Three dimensional analysis of microa-
2) Iwasaki M, Inomata H. Relation between superficial capillaries and foveal neurysms in the human diabetic retina. J Anat. 1999; 194:89–100.
structures in the human retina. Invest Ophthalmol Vis Sci. 1986; 27:1698– 25) Stitt AW, Gardiner TA, Archer DB. Histological and ultrastructural investi-
1705. gation of retinal microaneurysm development in diabetic patients. Br J
3) Snodderly DM, Weinhaus RS. Retinal vasculature of the fovea of the Ophthalmol. 1995; 79:362–367.
squirrel monkey, Saimiri sciureus: three-dimensional architecture, visual 26) Horii T, Murakami T, Nishijima K, et al. Optical coherence tomographic
screening, and relationships to the neuronal layers. J Comp Neurol. 1990; characteristics of microaneurysms in diabetic retinopathy. Am J Ophthal-
297:145–163. mol. 2010; 150:840–848.
4) Cogan DG, Toussaint D, Kuwabara T. Retinal vascular patterns. IV. Diabetic 27) Unoki N, Nishijima K, Sakamoto A, et al. Retinal sensitivity loss and struc-
retinopathy. Arch Ophthalmol. 1961; 66:366–378. tural disturbance in areas of capillary nonperfusion of eyes with diabetic
5) De Venecia G, Davis M, Engerman R. Clinicopathologic correlations in retinopathy. Am J Ophthalmol. 2007; 144:755–760.
diabetic retinopathy. I. Histology and fluorescein angiography of micro- 28) Otani T, Yamaguchi Y, Kishi S. Correlation between visual acuity and foveal
aneurysms. Arch Ophthalmol. 1976; 94:1766–1773. microstructural changes in diabetic macular edema. Retina. 2010; 30:774–
6) Klein R, Meuer SM, Moss SE, et al. The relationship of retinal micro- 780.
aneurysm counts to the 4-year progression of diabetic retinopathy. Arch 29) Forooghian F, Stetson PF, Meyer SA, et al. Relationship between photo-
Ophthalmol. 1989; 107:1780–1785. receptor outer segment length and visual acuity in diabetic macular
7) Klein R, Meuer SM, Moss SE, et al. Retinal microaneurysm counts and edema. Retina. 2010; 30:63–70.
10-year progression of diabetic retinopathy. Arch Ophthalmol. 1995; 30) Maheshwary AS, Oster SF, Yuson RM, et al. The association between per-
113:1386–1391. cent disruption of the photoreceptor inner segment-outer segment junc-
8) Kozak I, Bartsch DU, Cheng L, et al. Hyperreflective sign in resolved cotton tion and visual acuity in diabetic macular edema. Am J Ophthalmol. 2010;
wool spots using high-resolution optical coherence tomography and 150:63–67.
optical coherence tomography ophthalmoscopy. Ophthalmology. 2007; 31) Murakami T, Nishijima K, Sakamoto A, et al. Association of pathomorphol-
114:537–543. ogy, photoreceptor status, and retinal thickness with visual acuity in dia-
9) Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with betic retinopathy. Am J Ophthalmol. 2011; 151:310–317.
optical coherence tomography. Am J Ophthalmol. 1999; 127:688–693. 32) Byeon SH, Chu YK, Lee H, et al. Foveal ganglion cell layer damage in
10) Catier A, Tadayoni R, Paques M, et al. Characterization of macular edema ischemic diabetic maculopathy: correlation of optical coherence tomo-
from various etiologies by optical coherence tomography. Am J Ophthal- graphic and anatomic changes. Ophthalmology. 2009; 116:1949–1959.
mol. 2005; 140:200–206. 33) Jonas JB, Martus P, Degenring RF, et al. Predictive factors for visual acuity
11) Gaucher D, Sebah C, Erginay A, et al. Optical coherence tomography fea- after intravitreal triamcinolone treatment for diabetic macular edema.
tures during the evolution of serous retinal detachment in patients with Arch Ophthalmol. 2005; 123:1338–1343.
diabetic macular edema. Am J Ophthalmol. 2008; 145:289–296.
12) Otani T, Kishi S. Tomographic findings of foveal hard exudates in diabetic
macular edema. Am J Ophthalmol. 2001; 131:50–54.
13) Klein BE, Moss SE, Klein R, et al. The Wisconsin Epidemiologic Study of
Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retino-
pathy and hard exudate. Ophthalmology. 1991; 98:1261–1265.
14) Chew EY, Klein ML, Ferris FL 3rd, et al. Association of elevated serum lipid
levels with retinal hard exudate in diabetic retinopathy. Early Treatment
Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol. 1996;
114:1079–1084.
15) Miljanovic B, Glynn RJ, Nathan DM, et al. A prospective study of serum
lipids and risk of diabetic macular edema in type 1 diabetes. Diabetes.
2004; 53:2883–2892.
16) Gass JD, Norton EW. Cystoid macular edema and papilledema following
cataract extraction. A fluorescein fundoscopic and angiographic study.
Arch Ophthalmol. 1966; 76:646–661.
17) Tso MO. Pathological study of cystoid macular edema. Trans Ophthalmol
Soc U K. 1980; 100:408–413.
18) Wolter JR. The histopathology of cystoid macular edema. Albrecht Von
Graefes Arch Klin Exp Ophthalmol. 1981; 216:85–101.
19) Bolz M, Schmidt-Erfurth U, Deak G, et al; Diabetic Retinopathy Research
Group Vienna. Optical coherence tomographic hyperreflective foci:a mor-
phologic sign of lipid extravasation in diabetic macular edema. Ophthal-
mology. 2009; 116:914–920.
20) Deák GG, Bolz M, Kriechbaum K, et al; Diabetic Retinopathy Research
Group Vienna. Effect of retinal photocoagulation on intraretinal lipid
exudates in diabetic macular edema documented by optical coherence
tomography. Ophthalmology. 2010; 117:773–779.
21) Marmor MF. Mechanisms of fluid accumulation in retinal edema. Doc
Ophthalmol. 1999; 97:239–249.
22) Ota M, Nishijima K, Sakamoto A, et al. Optical coherence tomographic
evaluation of foveal hard exudates in patients with diabetic maculopathy
accompanying macular detachment. Ophthalmology. 2010; 117:1996–
2002.
 86 Chapter 3 · Diabetic retinopathy

Case 38 Diabetic macular edema: Early-stage case

A 58-year-old male,OS, BCVA 1.2

A: Left eye fundus photograph: A hard exudate and MAs can be seen in the parafovea. B: FA in the left eye (2 min), C: Enlarged version of B [white dashed
box]: MAs are detected in the perifoveal capillary bed and in its vicinity. Weak fluorescent leakage can be seen. D: IR + OCT horizontal scan of the left eye +
enlarged version [red dashed box]: The foveal depression is maintained and there is very little retinal thickening, but capillaries in the macular area are
dilating and 4 rows of highly reflective spots can be observed. These rows of highly reflective spots indicate 4-layer capillary network in the external and
internal margins of the inner nuclear layer, the external margin of the ganglion cell layer and the ganglion cell layer itself to the retinal nerve fiber layer.
E: IR + OCT tilted scan of the left eye + enlarged version [red dashed box]: MAs are visible in the parafovea and a small foveal cystoid space can be noted

Image interpretation points

This is a case of early phase diabetic macular edema with mini- and Henle‹s fibrous layer (HFL). The foveal depression is main-
mal macular retinal thickening. MA formation and weak fluo- tained and no clear retinal thickening is visible. Capillaries in the
rescent leakage can be seen in the perifoveal capillary bed and macular area are dilating, and the 4-layer capillary network can
very small localized cystoid spaces are visible in the parafovea be seen more clearly than usual.
Case 39 · Cystoid macular edema: Case with CME limited to layers anterior to the ELM
87 3
Case 39 Cystoid macular edema: Case with CME limited to layers anterior to the ELM

An 80-year-old female, OD BCVA 0.8

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Dot and blot hemorrhages and cystoid macular edema (CME) can
be seen in the macula. Hard exudates can be seen above the macula. C: FA in the right eye (75 sec): Multiple MAs and CME can be seen in the macula.
D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Cystoid spaces can be seen in the fovea, parafovea, and the inner nuclear
layer, but no edema can be seen in the outer plexiform layer. Foveal cystoid spaces are confined anterior to the ELM line and IS/OS lines, and each line is
being maintained. E: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: Same findings as in D can be seen

Image interpretation points

The cystoid spaces is confined to the retinal layers anterior to to the leakage from the perifoveal capillary bed. The ELM and
the ELM within the fovea, parafovea and inner nuclear layer in IS/OS lines are maintained and visual acuity remains good.
the vicinity of the fovea. These cystoid spaces appear to be due
 88 Chapter 3 · Diabetic retinopathy

Case 40 Cystoid macular edema: Case with CME extending to the outer retina

Left eye of an 80-year-old female with vision corrected to 0.2

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: Dot and blot hemorrhages are seen over the entire macula and hard
exudates can be seen in the fovea. C: FA in the left eye (28 sec): Multiple MAs are noted over the entire macula. D: FA in the left eye (5 min): CME is evident
in the fovea and macular edema can be seen outside the fovea. The nonperfusion area is not visible. E: IR + OCT horizontal scan of the left eye: This macular
edema is comprised of foveal cystoid space (*), parafoveal cystoid spaces and and inner nuclear layer cystoid spaces. A highly reflective lesion is visible
beneath the fovea corresponding to accumulation of hard exudates. F: Enlarged version of E [red dashed box]: The ELM, IS/OS and COST lines in the fovea
have disappeared

Image interpretation points

Accumulation of hard exudates beneath the fovea is one When this accumulated fluid in the cystoid spaces passes
cause of severe visual impairment in diabetic macular edema. through the ELM, a passage into the subretinal space formed.
Cystoid spaces in diabetic macular edema are common in the In the case of diabetic macular edema, as leakage into the
fovea centralis, parafovea, outer plexiform layer and inner subretinal space continues, hard exudates are deposited be-
nuclear layer. As the internal pressure rises within these cystoid neath the fovea leading to severe visual acuity loss.
spaces, subretinal leakage occurs causing foveal detachment.

Microaneurysm
Case 41 · Cystoid macular edema: Exacerbation
89 3
Case 41 Cystoid macular edema: Exacerbation

A 64-year-old female, OS, BCVA 1.0

A: FA in the left eye (11 min), B: enlarged version of A [white dashed box]: At initial diagnosis. Typical CME in a petaloid pattern can be seen in the fovea.
Leakage outside the fovea is mild. C: FA in the left eye (3 min), D: Enlarged version of C [white dashed box]: 17 months after initial diagnosis. The petaloid
pattern of CME has fused and become, and a multilayered petaloid pattern can be seen outside of it. Leakage over the macula is increased. E: IR + OCT hori-
zontal scan of the left eye: At initial diagnosis. Foveal and parafoveal cystoid spaces (*) in contact with the ELM line and a slight foveal detachment ( )
can be seen. F IR + OCT horizontal scan of the left eye: 7 months after initial diagnosis. Best-corrected visual acuity has reduced to 0.7. The edema has ex-
tended to the nasal side. Foveal detachment ( ) can be seen. G: IR + OCT horizontal scan of the left eye: 17 months after initial diagnosis. Best-corrected
visual acuity has further decreased to 0.3. Cystoid spaces in the outer plexiform layer and inner nuclear layer over the entire macula is increased. This cor-
responds to the parafoveal, multilayered petaloid pattern in FA

Image interpretation points

This case show the exacerbation of diabetic macular edema. The the edema in each retinal layer, as well as retinal thickening can
macular edema was initially found mainly in the foveal and para- be quantitatively understood with OCT. OCT also allows observa-
foveal regions, and then has progressed to the outer plexiform tion of photoreceptor damages. However, in this case, the status
layer and inner nuclear layer of the entire macula. The lateral ex- of ELM, IS/OS and COST lines are indistinct due to blockade of OCT
pansion of macular edema is observed with FA, but the extent of measurement beams by the multiple cystoid spaces.
 90 Chapter 3 · Diabetic retinopathy

Case 42 Cystoid macular edema: Foveal detachment with recurrence

A 61-year-old male, OS, BCVA 0.8

A: Color fundus photograph in the left eye: At initial diagnosis. B: Color fundus photograph in the left eye: 3 months after initial diagnosis. Best-corrected
visual acuity has reduced to 0.4. C: FA in the left eye (5 min): At initial diagnosis. CME can be seen in the fovea and parafovea. D: IR + OCT horizontal scan
of left eye + enlarged version [red dashed box]: At initial diagnosis. A foveal cystoid space (*) in contact with the ELM and foveal detachment ( ) can
be seen. The inside of the cystoid spaces is moderately reflective, which is thought to be due to high viscosity fluid. The photoreceptor inner and outer
segments of the fovea are diminished. E: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: 3 months after initial diagnosis.
The foveal detachment has subsided ( ), but foveal cystoid spaces remain. The foveal photoreceptor inner and outer segments are thinned. F: IR + OCT
horizontal scan of the left eye + enlarged version [red dashed box]: 4 months after initial diagnosis. Best-corrected visual acuity is 0.4. Foveal detachment
( ) has reoccurred. The foveal photoreceptor inner and outer segments are lost at their entire depth.

Image interpretation points

This is a case where foveal detachment due to a foveal cystoid but it only exists in very narrow gaps. As the cystoid spaces
space repeatedly occurred,and the photoreceptor inner and expand and come into contact with the ELM, they apply strong
outer segments in the fovea were damaged. Leakage is due to pressure to this structure leading to its disintegration and
the microaneurysms of perifoveal capillary bed. The foveal cys- leakage below the retina. The photoreceptor inner and outer
toid space has extended to the outer retina and is connected segments become defective as this fluid pass through them, and
with the subretinal space via the ELM structure. The ELM is the repeated foveal detachments exacerbate the damage done to
area where the adhesion complex between the photoreceptor the foveal photoreceptor inner and outer segments.
inner segment and outer edges of the Müller cells is aligned,
Casw 43 · Cystoid macular edema: Subfoveal accumulation of hard exudates and the development of ischemic maculopathy
91 3
Case 43 Cystoid macular edema: Subfoveal accumulation of hard exudates and the development
of ischemic maculopathy
Right eye of a 59-year-old female with vision corrected to 0.7

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: 1 month after initial diagnosis. Flame-shaped hemorrhages can
be seen in the posterior pole, soft exudate is exhibited near the upper arcade vessels, and hard exudate is visible on the nasal macula. Fine yellowish-white
granules are observed in the fovea. C: FA in the right eye (2 min): A focal nonperfusion area can be seen near the upper arcade vessels. D: Color fundus
photograph in the right eye, E: Enlarged version of D [red dashed box]: 12 months after initial diagnosis. Accumulation of hard exudates beneath the
foveas is noticeable. F: FA in the right eye (3 min): 12 months after initial diagnosis. A nonperfusion area can be seen from the fovea centralis to the upper ar-
cade vessels. G: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 10 months after initial diagnosis. Best-corrected visual acuity
is 0.7. Foveal detachment is noted and hyperreflective foci are aligned on the anterior border of the ELM and posterior margin of the photoreceptor inner
segment. H: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Same area as G, 12 months after initial diagnosis. Best-corrected
visual acuity has reduced to 0.2. Foveal detachment has disappeared, and hard exudates have accumulated on the RPE beneath the fovea centralis. The
ELM and IS/OS lines have disappeared in the foveal area with hard exudate accumulation and significant thinning of the foveal photoreceptor layer can be
seen. (A, D, and H were modified according to Ota M, et al. Optical coherence tomographic evaluation of foveal hard exudates in patients with diabetic
maculopathy accompanying macular detachment. Ophthalmology. 2010; 117: 1196–2002)

Image interpretation points

This is a case where accumulation of hard exudates progressed posterior margin of photoreceptor inner segment. Since hyper-
beneath the fovea centralis and visual acuity loss became worse reflective foci are large molecules, they cannot pass through
during 1 year of observation. Subfoveal accumulation of hard gaps in the ELM and appear to be filtered through the ELM and
exudates is one of causes for visual acuity loss associated with align. The structure of the ELM eventually ruptures and the
foveal detachment. At the initial diagnosis, fine yellowish-white hyperreflective foci appear to become trapped in the posterior
granules were observed in the fovea, which probably corresponds margin of the inner segment. Images showing the process of
to a part of hyperreflective foci on OCT images. Foveal detach- subfoveal hard exudate accumulation are not available, but it is
ment was present, and hyperreflective foci were seen aligned in certain that alignment of the hyperreflective foci can be ob-
an orderly manner along the anterior border of the ELM and the served before the subfoveal accumulation of hard exudates.
 92 Chapter 3 · Diabetic retinopathy

Case 44 Cystoid macular edema: Subretinal leakage from a parafoveal cystoid space

A 64-year-old male, OD, BCVA 0.4

A: Color fundus photograph in the right eye: at initial diagnosis. Retinal hemorrhages and hard exudates can be seen in the macula, and soft exudates can
be seen near the upper arcade vessels. B: FA in the right eye (1 min), C: FA in the right eye (13 min): At initial diagnosis. Multiple MAs are observed in the
macula. Focal nonperfusion areas are seen in the peripheral macula and outside the macula. D: IR + OCT vertical scan of the right eye + enlarged version
[red dashed box]: 6 months after initial diagnosis. Best-corrected visual acuity has reduced to 0.1. A parafoveal cystoid space (*) are opening below the
retina. A density boundary is forming near the opening suggesting leakage. E: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]:
8 months after initial diagnosis. Best-corrected visual acuity is 0.2. The parafoveal cystoid space and its opening have disappeared and an increase in reflec-
tivity can be seen in the same area (red dashed circle). The photoreceptor inner and outer segments in the area of leakage are lost ( ).
(D is modified according to and H according to Ota M, et al. Optical coherence tomographic evaluation of foveal hard exudates in patients with diabetic
maculopathy accompanying macular detachment. Ophthalmology. 2010; 117: 1196–2002) (Continued on the next page)

Image interpretation points

Foveal photoreceptor layer degeneration due to foveal detach- highly reflective lesions remain within the retina where the
ment causes visual impairment in diabetic macular edema. cystoid space with an opening was present. This, it appears that
It is now possible to observe the process of subretinal leakage mechanical damages due to subretinal fluid efflux is one of
from cystoid spaces with SD-OCT. The photoreceptor inner the causes of visual acuity loss associated with repeated foveal
and outer segments disappear in the area of leakage, and detachment.
Case 44 · Cystoid macular edema: Subretinal leakage from a parafoveal cystoid space
93 3
Case 44 Continuation

F: Color fundus photograph in the right eye: 11 months after initial diagnosis. Best-corrected visual acuity is 0.2. Hard exudates in the macula has decreased
and a soft exudate has appeared above the fovea. G: FA in the right eye (1 min), H: FA in the right eye (13 min): 11 months after initial diagnosis. Multiple
MAs can be seen in the macula. The nonperfusion area of the macula has expanded. I: Color fundus photograph in the right eye: 16 months after initial
diagnosis. Visual acuity has further reduced to 0.05. Accumulation of hard exudates beneath the fovea is seen. J: IR + OCT horizontal scan of the right eye +
enlarged version [red dashed box]: 12 months after initial diagnosis. Best-corrected visual acuity is 0.1. Hyperreflective foci can be seen in the detached
outer layer of the retina, and are falling and accumulating on the RPE ( ). The photoreceptor inner and outer segments have disappeared over a wide area
of the macula. K: IR + OCT horizontal scan of the right eye: 13 months after initial diagnosis. BCVA further decreased to 0.07. One month after J, subfoveal
accumulation of hard exudate is evident ( ) and significant thinning in the fovea is noted.

Image interpretation points

In this case, the foveal photoreceptor layer had once undergone retinal layers along the foveal detachment and some foci can be
severe damages due to the mechanical injuries by the subretinal seen falling on the RPE. Accumulation of hard exudates beneath
fluid efflux, and then subfoveal accumulation of hard exudates the fovea occurs with the disappearance of foveal detachment, and
further enhanced the foveal damages. Multiple hyperreflective hyperreflective foci in the outer layer of the retina appears to be in-
foci, which are leaked lipoproteins, accumulate along the outer volved in this accumulation. Visual prognosis is poor in such cases.
 94 Chapter 3 · Diabetic retinopathy

Case 45 Cystoid macular edema: Subfoveal leakage from a foveal cystoid space

A 56-year-old male, OD, BCVA 0.5

A B

A: FA in the right eye (1 min), B: enlarged version of A [white dashed box]: At initial diagnosis. Scattered MAs and mild CME can be seen in the posterior
pole. C: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: At initial diagnosis. A leakage path ( ) is formed from the shrinked
foveal cystoid space to subretinal space. Diffuse moderate reflectivity is observed in the opening. * shows the foveal detachment. D: IR + OCT horizontal
scan of the right eye + enlarged version [red dashed box]: 5 months after initial diagnosis. Multiple leakage openings from the outer plexiform layer cystoid
spaces to subretinal space (red dashed square) are seen. Highly reflective lumps can be seen on the RPE beneath the openings.

Image interpretation points

Repeated foveal detachment involved in visual impairment space appears to be shrinked a result of connections between
due to diabetic macular edema appears to occur due to the foveal cystoid space and subretinal space. Five months after
leakage from a foveal cystoid space, parafoveal cystoid spaces, initial diagnosis, multiple leakage paths could be seen from
and outer plexiform layer cystoid spaces into the subretinal the cystoid spaces in the outer plexiform layer. The source of
space. In this case, leakage appeared to be mainly from a leakage can sometimes change over time leading to persistence
foveal cystoid spaces at initial diagnosis. The foveal cystoid of the foveal detachment.
Case 46 · Cystoid macular edema: Photoreceptor damage from outer plexiform layer edema
95 3
Case 46 Cystoid macular edema: Photoreceptor damage from outer plexiform layer edema

A 69-year-old female, OD, BCVA 0.4

A: Color fundus photograph in the right eye: At initial diagnosis. A few of hard exudates are seen in the macula. B: Color fundus photograph in the right
eye: 6 months after initial diagnosis. Hard exudates are increasing on the temporal macula. C: FA in the right eye (24 sec): 6 months after initial diagnosis.
Multiple MAs are visible in the macula, but no capillary nonperfusion can be seen. D: FA in the right eye (8 min): Significant cystic fluorescein accumulations
are noted in the entire posterior pole. E: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: At initial diagnosis. Foveal detach-
ment is visible (*). The hyperreflective foci accumulating along the internal walls of cystoid spaces highlight the outline of the cystoid spaces in the outer
nuclear layer of the temporal macula.
(Continued on the next page)

Image interpretation points

This is a case representative of outer plexiform layer edema the septum of each cystoid space is blurry due to moderate
in the temporal macula, with minimal edema observed in the reflectivity within the cystoid space. The hyperreflective foci
fovea centralis and inner nuclear layer. The changes in the being aligned along the internal wall of each cystoid space help
outer plexiform layer appear to be diffuse at first glance, but us identify the outline of the cystoid space..
 96 Chapter 3 · Diabetic retinopathy

Case 46 Continuation

F: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: 5 months after initial diagnosis. Best-corrected visual acuity is 0.3. Grid photo-
coagulation was performed 1 month after diagnosis. The cystoid edema in the outer plexiform layer in the temporal macula has subsided, and hard exudate
formation is evident inside the retina. Hyperreflective foci are aligned along anterior border of the ELM and posterior margin of the photoreceptor inner
segment of the detached retina (*). G: IR + OCT horizontal scan of the right eye: 6 months after initial diagnosis. Best-corrected visual acuity is 0.3. The outer
plexiform layer edema in the temporal macula that underwent grid photocoagulation has disappeared and an accumulation of hard exudate can be seen
beneath the fovea centralis ( ).

Image interpretation points

The cystoid edema of the outer plexiform layer in the temporal the fovea centralis, hyperreflective foci were seen aligned on
macula has disappeared after grid photocoagulation, but hard the anterior border of the ELM and on the posterior margin of
exudate is accumulating beneath the fovea centralis, causing the photoreceptor inner segment in the area of the foveal
atrophy of the foveal photoreceptor layer. Hard exudates are detachment. Accumulation of hard exudates cannot be seen
also formed within the retina where the cystoid spaces are on the RPE at this stage.
disappearing. Just before hard exudates accumulate beneath
Case 47 · Cystoid macular edema: Microaneurysms
97 3
Case 47 Cystoid macular edema: Microaneurysms

A 67-year-old female, OD, BCVA 0.3

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Dot and blot hemorrhages can be seen. The MAs and dot hemor-
rhages, which are present together in the macula, looks too similar to be distinguished on color fundus photography. C: FA in the right eye (1 min),
D: Enlarged version of C [white dashed box]: Multiple MAs are visible in the perifoveal capillary bed. Destruction of the perifoveal capillary bed can also
be observed. E: IR + OCT horizontal scan of the right eye, F: Same image as D: This has been redisplayed to show the alignment between the OCT B-scan
images E and G and the FA image. The red and blue dashed circles showing MAs on the FA image correspond to the red and blue dashed circles in the OCT
images E and G respectively. G: IR + OCT vertical scan of the right eye: MAs in contact with foveal cystoid spaces (*) (red dashed circle) and MAs in the
vicinity of the foveal cystoid space (blue dashed circle) can be seen. Both exist at the inner nuclear layer level.

Image interpretation points

MAs are depicted on OCT B-scan images as circular/elliptical inner nuclear layer, and roughly 50% are adjacent to, in contact
capsular structures with highly reflective walls. It is easy to dis- with or inside the cystoid spaces. MAs are enveloped by highly re-
cern the layer where MAs exist and their positional relationship flective walls of various extents, and the MAs with poor wall reflec-
with cystoid spaces on OCT. About 80% of MAs can be seen in the tivity are thought to be associated with cystoid space formation.
 98 Chapter 3 · Diabetic retinopathy

Case 48 Ischemic maculopathy: Cystoid macular degeneration

A 38-year-old female, OS, BCVA 0.01

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box], C: Enlarged version of A [blue dashed box]: At initial diagnosis.
Venous beading and intraretinal microvascular abnormalities (IRMAs, white dashed circle) can be seen, D: Color fundus photograph in the left eye,
E: Enlarged version of D [red dashed box]: 2 months after initial diagnosis. Best-corrected visual acuity is 0.01. Preretinal hemorrhages can be seen in
the lower arcade vessels. Ghost perifoveal capillary bed (no capillary blood flow) is visible. F: FA in the left eye (1 min): 2 months after initial diagnosis.
Nonperfused area is seen in the perifoveal capillary bed and the temporal half of the macula. G: IR + OCT horizontal scan of the left eye: At initial diagnosis.
Appearance of the cystoid edema can be seen in the macula. H: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: Same
area as G, 2 months after initial diagnosis. Cystoid edema has subsided, but the fovea centralis exhibits significant atrophy with cystoid spaces. There is
significant thinning of the inner retinal layers on the temporal side.

Image interpretation points

This is a case that appears to be cystoid macular edema at Cystic degeneration of the macula was clearly detected on
first glance, but is actually cystoid degeneration (also termed OCT, and there is also significant thinning of the temporal inner
cystic degeneration) due to macular ischemia. Remission of the layers of the retina. Currently, there are no methods of predict-
macular edema is due to blood supply to the macula being cut ing the onset or established treatments for diabetic ischemic
off as a result of retinal vascular nonperfusion in the macula. maculopathy.
Case 49 · Ischemic maculopathy: Thinned macula
99 3
Case 49 Ischemic maculopathy: Thinned macula

A 38-year-old female, OD, BCVA 0.01

A: Color fundus photograph in the right eye: At initial diagnosis. Retinal hemorrhages, venous beading, IRMAs, and hard exudate can be seen in the posterior
pole. B: FA in the right eye (1 min), C: FA in the right eye (10 min): At initial diagnosis. Nonperfusion area can be seen mainly in the equatorial area, but non-
perfusion of the perifoveal capillary bed and temporal macula is also observed. Leakage from superior retinal neovascular vessels can be seen. D: Color fun-
dus photograph in the right eye: 5 months after initial diagnosis. Best-corrected visual acuity is 0.01. Preretinal hemorrhages have occurred. Niveau forma-
tion of subhyaloid hemorrhages can be seen. Photocoagulation scars produced by PASCAL (PAttern SCAnning Laser) Photocoagulator (OptiMedica Corpora-
tion, Santa Clara, CA) can be seen. E: FA in the right eye (90 sec), F: FA in the right eye (13 min): 5 months after initial diagnosis. Blocking of fluorescence due
to preretinal hemorrhages, but nonperfusion is evident over a wide macular area. G: IR + OCT horizontal scan of the right eye: At initial diagnosis. Foveal
and parafoveal cystoid spaces (*) are noted. H: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Same area as G, 2 months after
initial diagnosis, 3 months before the preretinal hemorrhages. Best-corrected visual acuity is 0.02. The CME has completely subsided, but the fovea centralis
exhibits significant thinning. The ELM line is visible, but the IS/OS lines are not. Thinning of the inner retinal layer of the macula is significant, and the foveal
depression appears flattened and enlarged.

Image interpretation points

In this case, before the vitreous hemorrhages occurred, capil- a result of retinal vascular nonperfusion in the macula. Thinning
lary nonperfusion in the macula progressed rapidly resulting of the fovea centralis and inner retinal layers of the macula can
in foveal atrophy and leading to severe visual impairment. be seen with OCT. Panretinal photocoagulation was performed
Such acute development of perifoveal capillary bed nonper- but could not prevent the progression of diabetic ischemic
fusion is common in type 1 diabetes. Remission of the macular maculopathy. Currently, there are no established treatments for
edema is due to blood supply to the macula being cut off as diabetic ischemic maculopathy.
 100 Chapter 3 · Diabetic retinopathy

Case 50 Vitreomacular traction syndrome: A typical example

A 71-year-old female, OD, BCVA 0.07

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Significant macular whitening and capillary tortuosity due to the
ERM is seen. C: FA in the right eye (3 min): FA from 6 months before initial diagnosis. Leakage in the macular area can be seen. D: IR + OCT horizontal scan
of the right eye: Adhesion of the posterior vitreous cortex to the entire macula is exhibited in the horizontal scan passing through the fixation point.
E: IR + OCT vertical scan of the right eye: Adhesion of the posterior vitreous cortex to the macula can be observed over a wide area, and the macula is
being elevated into a tent-shape. The posterior vitreous cortex was separated into 2 layers.

Image interpretation points

Vitreomacular traction syndrome is common with diabetic normal adhesion occurring over a wider area of the vitreo-
macular edema, but the adhesion of the posterior vitreous cor- retinal interface in diabetic macular edema. There are many
tex is often wider than vitreomacular traction syndrome asso- cases where the entire macula is lifted into a tent-shape.
ciated with other retinal diseases. This appears be due to ab-
Case 51 · Proliferative diabetic retinopathy: Progressive proliferation
101 3
Case 51 Proliferative diabetic retinopathy: Progressive proliferation

A 29-year-old male, OS, BCVA 0.4

A: Color fundus photograph in the left eye: At initial diagnosis. Mild fibrovascular membrane is seen from the optic disc along the upper and lower arcades,
and focal preretinal hemorrhages above the optic disc. B: FA montage of the left eye (10 min): Significant fluorescein leakage can be seen from neovascu-
larization of the disc (NVD) and elsewhere on the retina (NVE) . Panretinal photocoagulation is performed to a certain extent. C: Color fundus photograph
in the left eye: 3 months after initial diagnosis. Best-corrected visual acuity in this left eye is now finger counting directly in front of the eye. Tractional reti-
nal detachment has occurred due to rapid proliferation of the fibrovascular membrane. D: IR + OCT horizontal scan of the left eye: At initial diagnosis. No
retinal detachment is visible. E: IR + OCT horizontal scan of the left eye: 3 months after initial diagnosis. Best-corrected vision is finger counting directly in
front of the left eye. The macula is detached as if being pulled by the optic disc due to contraction of the proliferative fibrovascular membrane. The RPE is
poorly depicted on OCT due to the elongation of the eye in the longitudinal direction.

Image interpretation points

This case represents the exacerbation process of proliferative damage to the macula. During follow-up after the addition of
diabetic retinopathy. At initial diagnosis, neovasculaization of retinal photocoagulation, there was rapid progress of proliferative
the disc (NVD) and elsewhere on the retina (NVE) are present, changes resulting in a macular tractional retinal detachment.
but visual acuity remained good since there was minimal Earlier surgical intervention would have been preferable.
 102 Chapter 3 · Diabetic retinopathy

Case 52 Proliferative diabetic retinopathy: Preretinal hemorrhages and vitreomacular traction

syndrome
A 37-year-old female, OS, BCVA 0.3

A: Left eye fundus photograph: At initial diagnosis. Neovascularization of the disc (NVE) and fibrovascular membrane from the optic disc along the arcade
vessels can be seen, and preretinal hemorrhages are seen in the posterior pole with niveau along the inferior arcade. B: Color fundus photograph: 2 weeks
after initial diagnosis. Preretinal hemorrhages have remarkably increased. There is only few hemorrhages in the fovea. C: FA in the left eye (10 min), pano-
rama: Fibrovascular membrane is formed over the posterior pole including the optic disc, and significant fluorescein leakage is seen. D: IR + OCT horizontal
scan of the left eye: At initial diagnosis. Vitreomacular traction syndrome can be observed. Hemorrhages can be seen between the posterior vitreous cortex
and the retina l surface ( ). E: Color fundus photograph + SS-OCT horizontal scan of the left eye: 2 weeks after initial diagnosis. Gaps between the posterior
vitreous cortex and the retina l surface are filled with hemorrhages (*). It is obvious that vitreomacular traction is present.

Image interpretation points

Preretinal hemorrhages can accumulate between the filling the gaps between the posterior vitreous cortex and
posterior vitreous cortex and retina l surface in cases where the retina l surface. Even though retinal lesions cannot be
PVD has not occurred. In this case vitreomacular traction visualized by SD-OCT, SS-OCT can provide images that allow
syndrome preceded massive preretinal hemorrhages. Large interpretation of retinal pathology hiding beneath the
amounts of preretinal hemorrhages are accumulating and massive preretinal hemorrhages.
 103 4

Retinal vascular diseases

4.1 Retinal vein occlusion – 104
References – 106

Case 53 Central retinal vein occlusion: Progression from non-ischemic

to ischemic ① – 108

Case 53 Continuation – 109

Case 54 Central retinal vein occlusion: Progression from non-ischemic

to ischemic ② – 110

Case 55 Central retinal vein occlusion: Ischemic type – 112

Case 56 Branch retinal vein occlusion: Non-ischemic type – 113

Case 57 Branch retinal vein occlusion: Significant inner layer ischemia – 114

4.2 Retinal artery occlusion – 115

References – 115

Case 58 Central retinal artery occlusion: A typical example – 116

Case 59 Central retinal artery occlusion: Cilioretinal artery not occluded – 117

Case 60 Central retinal artery occlusion: Incomplete occlusion – 118

Case 61 Hemi central retinal artery occlusion: Case of good visual acuity – 119

Case 62 Branch retinal artery occlusion: Incomplete occlusion – 120

4.3 Idiopathic juxtafoveal macular telangiectasia – 121

References – 122

Case 63 Macular telangiectasia: Yannuzzi classification Type 1 – 123

Case 64 Macular telangiectasia: Yannuzzi classification Type 1 – 124

Case 65 Macular telangiectasia: Yannuzzi classification Type 2 Stage 2 – 125

Case 66 Macular telangiectasia: Yannuzzi classification Type 2 Stage 3 – 126

Case 67 Macular telangiectasia: Yannuzzi classification Type 2 Stage 4 – 127

Case 68 Coats’ disease: A typical example – 128

4.4 Retinal arterial macroaneurysm – 129

References – 129

Case 69 Retinal arterial macroaneurysm: Subretinal hemorrhages – 130

Case 70 Retinal arterial macroaneurysm: Foveal detachment from

an inferior arterial macroaneurysms – 132
 104 Chapter 4 · Retinal vascular diseases

4.1 Retinal vein occlusion such severe visual impairment. The extent of retinal capillary
nonperfusion is responsible for both the visual prognosis and
Background the risks of developing neovascular glaucoma. It is common to
When the central retinal vein or its branches are occluded, the define an ischemic CRVO as having a nonperfusion area with
upstream vein dilates and becomes tortuous; flame-shaped or a diameter of 10-fold disc diameter or more,(16) but when
spotted retinal hemorrhages can occur depending on the depth dense retinal hemorrhages are present immediately after onset,
of bleeding. The main cause of visual impairment is macular it is not easy to determine the nonperfusion area fluorescein
edema. When significant retinal ischemia causes retinal neovas- angiography because of blocking of fluorescence light by the
4 cularization and iris rubeosis, this can lead to visual impairment hemorrhages. In such cases, poor visual acuity and visual field
due to vitreous hemorrhages and neovascular glaucoma. results, relative afferent pupillary defect , poor visual function
tests such as an electroretinogram, multiple soft exudates, ex-
Central retinal vein occlusion tension of the intraretinal circulation  time,(17) and significant
Central retinal vein occlusion (CRVO) occurs due to a central fluorescein leakage on FA suggest ischemic CRVO.
retinal venous obstruction mainly caused by thrombosis forming
at the lamina cribrosa level in the optic disc.(1) The central retinal OCT findings
vein sometimes divides into two branches when it exits the It has now become possible to quantitatively assess the extent
optic nerve; if one side is occluded, this results in a hemi-CRVO. of macular edema in CRVO with OCT. OCT is becoming an
The incidence of CRVO is 0.1–0.5%.(1–3) In the elderly, CRVO essential test for evaluating the effects of medical therapies that
often accompanies systemic disorders such as hypertension, use anti-vascular endothelial growth factor drugs and/or steroid
diabetes, ischemic (arteriosclerotic) heart disease(4–10), and drugs, evaluating recurrence, and determining the effects of grid
glaucoma.(4–7, 10) Aspirin and/or warfarin have also been reported photocoagulation and vitreous surgery. In addition, OCT can
as risk factors.(9) In contrast, vasculitis is typically associated with detect structures of macular edema such as cystoid spaces and
the onset of CRVO in young patients. However, the cause of serous retinal detachment (SRD, also termed foveal detachment)
CRVO in young patients is often unclear, and in such cases con- that other tests, including FA, cannot.18–21) It was previously be-
genital abnormalities of the central retinal vein at the level of the lieved that SRD accompanied severe CRVO, but we have now
lamina cribosa is suspected.(11) Bilateral involvement is seen in observed that SRD accompanies a higher percentage (about 80%)
about 10–15% of elderly patients, but in the majority of younger than previously thought thanks to OCT.(18, 21) Most SRDs (about
patients, the onset is in just one eye.(11, 12) CRVO is classified into 70%) can be seen as cone-shaped, small foveal detachments, and
non-ischemic and ischemic based on the extent of the capillary are thought to progress to dome-shaped SRDs based on the
bed nonperfusion, which corresponds to Hayreh’s classifications mechanism shown in Fig. 4-1.(21) The highest percentage of
of venous stasis retinopathy and hemorrhagic retinopathy.(13) cystoid spaces can be seen in the fovea centralis, inner nuclear
The incidence of non-ischemic CRVO is approximately twice layer, and outer plexiform layer (all >80%). It was shown that a
that of ischemic, but when followed long-term for one and a half foveal cystoid space reaching the external limiting membrane
years, 18.6–34% of non-ischemic CRVO progress to ischemic (ELM) result in poor visual acuity.(19) Macular edema in CRVO
CRVOs.(14, 15) Non-ischemic CRVO includes cases with a rela- exhibits maximum thickness in the fovea centralis, but the cor-
tively good prognosis where visual acuity and the ocular fundus relation between the thickness and visual acuity is not high.(22)
almost normalize naturally, although the prognosis is poor when This appears to be because, although macular ischemia is
macular edema is more advanced. most strongly associated with visual impairment, the macular
In addition to advanced macular edema, the development of thickening due to macular edema does not necessarily reflect the
macular ischemia and subsequent neovascular glaucoma are severity of macular ischemia. In practice, the state of the IS/OS
further causes of poor prognosis in ischemic CRVO. Neo- line, which is the index for the photoreceptor integrity, correlates
vascular glaucoma typically occurs within 3–4 months after with visual acuity more than foveal retinal thickness.(23) Such
CRVO onset. Visual prognosis is good in cases where visual observations of a foveal cystoid space and the IS/OS line are
acuity at the time of diagnosis is 0.5 or above, whereas visual useful, but when retinal hemorrhages and cystoid edema are
improvement is not achieved in the majority of cases under extensive, the photoreceptor IS/OS line cannot be clearly seen
0.1.(15) Ischemic maculopathy as a result of capillary nonperfu- due to blocking of OCT measurement beams.
sion including perifoveal capillary bed also appears to underlie

Hemi-retinal vein occlusion

subretinal detachment
4.1 · Retinal vein occlusion
105 4

. Fig. 4-1 Schematic diagram of serous retinal detachment development in retinal vein occlusion
A: The structure of the fovea centralis is drawn. The Müller cell cone in the foveola is highlighted in light green, and the Müller cells in the Muller cell cone
and parafovea are highlighted in deep green lines and the nerve fibers are highlighted in blue lines. B: When cystoid spaces form in the fovea centralis and
parafovea, the Müller cells are stretched as a result of the spatial expansion, consequently pulling the photoreceptor layer and leading to a cone-shaped
small foveal detachment ( ). C: Holes develop in the ELM and photoreceptor inner and outer segments, and fluids and sometimes hemorrhages leak from
within the cystoid spaces into the subretinal space causing serous retinal detachment. GCL=ganglion cell layer, INL=inner nuclear layer, OPL=outer plexi-
form layer, RPE=retinal pigment epithelium, ONL=outer nuclear layer. (Modified according to Tsujikawa A, et al. Serous retinal detachment associated with
retinal vein occlusion. Am J Ophthalmol. 2010; 149: 291–301)
 106 Chapter 4 · Retinal vascular diseases

Branch retinal vein occlusion References

Branch retinal vein occlusion (BRVO) occurs due to thrombus
forming at an arteriovenous crossing.(24) The retinal artery and 1) Green WR, Chan CC, Hutchins GM, et al. Central retinal vein occlusion:
a prospective histopathologic study of 29 eyes in 28 cases. Trans Am
vein at the crossing share common wall, and the vein is sus-
Ophthalmol Soc. 1981; 79:371–422.
ceptible to pressure from the artery. BRVO is associated with 2) Klein R, Klein BE, Moss SE, et al. The epidemiology of retinal vein occlu-
hypertension in about 3/4 of cases.(4, 7, 8) Venous occlusion areas sion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2000; 98:
are most common in the superotemporal arteriovenous crossing 133–141.
of the retina. BRVO develops in both eyes in 5–6% of cases upon 3) Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein
4 initial diagnosis and develops in the fellow during follow-up in occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol.
1996; 114: 1243–1247.
another 10% of cases. The causes of reduced visual acuity are
4) Appiah AP, Greenidge KC. Factors associated with retinal-vein occlusion
macular edema and retinal hemorrhages (particularly hemor- in Hispanics. Ann Ophthalmol. 1987; 19:307–309, 312.
rhages extending to the foveal and parafoveal cystoid spaces), in 5) Rath EZ, Frank RN, Shin DH, et al. Risk factors for retinal vein occlusions.
the early stage and prolonged macular edema, pigmentation of A case-control study. Ophthalmology. 1992; 99:509-514.
the fovea centralis, epiretinal membrane, vitreous hemorrhages, 6) The Eye Disease Case-Control Study Group. Risk factors for central reti-
nal vein occlusion. Arch Ophthalmol. 1996; 114:545–554.
and rhegmatogenous retinal detachment in the late to end stages.
7) Sperduto RD, Hiller R, Chew E, et al. Risk factors for hemiretinal vein
Visual acuity is good when there is no macular edema, but vision occlusion: comparison with risk factors for central and branch retinal
declines below 0.5 when macular edema occurs. A baseline mean vein occlusion: the eye disease case-control study. Ophthalmology.
visual acuity is reportedly 0.15-0.2, which is worse than thought. 1998; 105: 765–771.
With a natural course, vision rarely improves so much after 8) Hayreh SS, Zimmerman B, McCarthy MJ, et al. Systemic diseases asso-
ciated with various types of retinal vein occlusion. Am J Ophthalmol.
6 months, but will improve significantly within 2 years (by an
2001; 131:61–77.
average of 28 letters in ETDRS). Macular edema reportedly re- 9) Koizumi H, Ferrara DC, Bruè C, et al. Central retinal vein occlusion case-
gressed in 18% of cases 4.5 months after the patients had become control study. Am J Ophthalmol. 2007; 144:858–863.
aware of reduced visual acuity, while patients developed macular 10) Klein R, Moss SE, Meuer SM, et al. The 15-year cumulative incidence of
edema in 41% of the cases within 7.5 months.(25) Collateral cir- retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol.
culation spanning the nonperfusion area and temporal horizon- 2008; 126:513–518.
11) Walters RF, Spalton DJ. Central retinal vein occlusion in people aged
tal raphe often form when retinal hemorrhages are absorbed.
40 years or less: a review of 17 patients. Br J Ophthalmol. 1990; 74:
30–35.
OCT findings 12) Pollack A, Dottan S, Oliver M. The fellow eye in retinal vein occlusive
Macular retinal thickness measurements using OCT have be- disease. Ophthalmology. 1989; 96:842–845.
come indispensable in the follow-up of BRVO macular edema 13) Hayreh SS. Classification of central retinal vein occlusion. Ophthalmolo-
gy. 1983; 90:458-474.
and assessing therapeutic effects. OCT has a higher detection
14) Hayreh SS, Zimmerman MB, Podhajsky P. Incidence of various types of
rate for CME than FA, and is able to detect the SRD that FA can- retinal vein occlusion and their recurrence and demographic character-
not find. We have come to understand that SRD accompanying istics. Am J Ophthalmol. 1994; 117:429–441.
BRVO is not unusual when observed using OCT.(26) Macular 15) The Central Vein Occlusion Study Group. Natural history and clinical
edema in BRVO differs from that in CRVO in that significant management of central retinal vein occlusion. Arch Ophthalmol. 1997;
115:486–491
macular thickening occurs only on the nonperfused side and in
16) The Central Vein Occlusion Study Group. Baseline and early natural his-
the fovea, and therefore observation with vertical B scans is use- tory report. Arch Ophthalmol. 1993; 111:1087–1095.
ful. Foveal cystoid spaces, parafoveal cysts, and SRD even extend 17) Sinclair SH, Gragoudas ES. Prognosis for rubeosis iridis following central
to the perfused side. The nonperfusion in the distal area that does retinal vein occlusion. Br J Ophthalmol. 1979; 63:735–743
not involve the macula can cause a macular SRD.(27) BRVO does 18) Ozdemir H, Karacorlu M, Karacorlu S. Serous macular detachment in
share several characteristics in macular edema with that of central retinal vein occlusion. Retina. 2005; 25:561–563.
19) Yamaike N, Tsujikawa A, Ota M, et al. Three-dimensional imaging of cys-
CRVO. Specifically, these include: ① the SRD appears as a
toid macular edema in retinal vein occlusion. Ophthalmology. 2008;
cone-shaped small foveal detachment, and progresses to a dome- 115:355–362.
shaped SRD,(21) ② the cystoid spaces are most frequently seen 20) Jittpoonkuson T, Garcia PM, Rosen RB. Correlation between fluorescein
in the fovea centralis, inner nuclear layer, and outer plexiform angiography and spectral-domain optical coherence tomography in the
layer, eventually resulting in poor vision when the foveal cystoid diagnosis of cystoid macular edema. Br J Ophthalmol. 2010; 94:1197–
1200.
space reach the ELM,(19) and ③ the IS/OS line, which is an
21) Tsujikawa A, Sakamoto A, Ota M, et al. Serous retinal detachment
index for the photoreceptor integrity, are correlated with visual associated with retinal vein occlusion. Am J Ophthalmol. 2010; 149:
acuity.(28–30) In the acute phase, the occluded side of the fovea 291–301.
centralis cannot be clearly seen when there is significant retinal 22) Scott IU, Van Veldhuisen PC, Oden NL, et al; SCORE Study Investigator
hemorrhages and cystoid macular edema. Cases where visual Group. SCORE Study report 1: baseline associations between central
retinal thickness and visual acuity in patients with retinal vein occlusion.
acuity remains poor despite resolved macular edema often are
Ophthalmology. 2009; 116:504–512.
due to accompanying macular area pigmentation and thinning
of the macular area photoreceptor inner and outer segments and
outer nuclear layer. Several etiologies including SRD and sub-
retinal efflux of retinal hemorrhages may explain the damage to
the outer layer of the retina.
subretinal detachment
4.1 · Retinal vein occlusion
107 4
23) Ota M, Tsujikawa A, Kita M, et al. Integrity of foveal photoreceptor layer
in central retinal vein occlusion. Retina. 2008; 28:1502–1508.
24) Frangieh GT, Green WR, Barraquer-Somers E, et al. Histopathologic study
of nine branch retinal vein occlusions. Arch Ophthalmol. 1982; 100:
1132–1140.
25) Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein
occlusion: an evidence-based systematic review. Ophthalmology. 2010;
117:1094–1101.
26) Spaide RF, Lee JK, Klancnik JK Jr, et al. Optical coherence tomography of
branch retinal vein occlusion. Retina. 2003; 23:343–347.
27) Otani T, Yamaguchi Y, Kishi S. Serous macular detachment secondary to
distant retinal vascular disorders. Retina. 2004; 24:758–762.
28) Murakami T, Tsujikawa A, Ohta M, et al. Photoreceptor status after re-
solved macular edema in branch retinal vein occlusion treated with tis-
sue plasminogen activator. Am J Ophthalmol. 2007; 143:171–173.
29) Ota M, Tsujikawa A, Murakami T, et al. Association between integrity of
foveal photoreceptor layer and visual acuity in branch retinal vein occlu-
sion. Br J Ophthalmol. 2007; 91:1644–1649.
30) Ota M, Tsujikawa A, Murakami T, et al. Foveal photoreceptor layer in eyes
with persistent cystoid macular edema associated with branch retinal
vein occlusion. Am J Ophthalmol. 2008; 145:273–280.
 108 Chapter 4 · Retinal vascular diseases

Case 53 Central retinal vein occlusion: Progression from non-ischemic to ischemic ①

A 54-year-old male, OD, BCVA 0.3

A: Color fundus photograph in the right eye: At initial diagnosis. Flame-shaped and blot retinal hemorrhages, dilation and mild tortuosity of retinal
veins, optic disc edema as well as retinal whitening surrounded by soft exudates can be seen. B: FA in the right eye (36 sec), C: FA in the right eye (10 min),
D: enlarged version of C [white dashed box]: At initial diagnosis. This is a non-ischemic CRVO where capillary nonperfusion is hardly visible. CME is present.
E: IR + OCT horizontal scan of the right eye: At initial diagnosis. Significant CME and cone-shaped small foveal detachments ( ) are noted. Significant
edema ( ) in the retinal nerve fiber layer corresponding to a soft exudate is seen.
 Case 53 · Central retinal vein occlusion: Progression from non-ischemic to ischemic ①
109 4
Case 53 Continuation

F: Color fundus photograph in the right eye: 2 months after initial diagnosis and after panretinal photocoagulation. Best-corrected visual acuity remains
to be 0.3. G: FA in the right eye (1 min), H: FA in the right eye (10 min), I: enlarged version of H [white dashed box]: 2 months after initial diagnosis. A wide,
nonperfusion area excluding the area from the macula to the optic disc is formed and thus has progressed to ischemic CRVO. The area of CME has slightly
expanded. J: IR + OCT horizontal scan of the right eye: Same scan as E 2 months after initial diagnosis. Hemorrhages are noticeable in foveal and outer
plexiform layer cystoid spaces. Hemorrhages in the foveal cystoid space are thick and cause measurement beam blocking ( ). SRD is expanding in a
dome-shape fashion (*). Hyperreflective foci as described in the section on diabetic retinopathy can be seen. K: IR + OCT horizontal scan of the right eye:
Same scan as E 6 months after initial diagnosis. Best-corrected visual acuity is 0.2. The CME and SRD have disappeared 3 months after vitreous surgery
combined with ILM peeling, but there is significant thinning of the retinal inner layers and the photoreceptor layer from the fovea centralis to the temporal
macula. Loss of the outer nuclear layer and IS/OS reflectivity is present throughout the macula. Note the hard exudates on the temporal macula.

Image interpretation points

This is a case of CRVO combined with diabetic retinopathy appeared 6 months later and significant retinal thinning is pre-
which progressed from non-ischemic to ischemic 2 months sent in the temporal macula. Thinning of the inner layers is due
after initial diagnosis. Meanwhile, the CME remained and the to the formation of a nonperfusion area, and although the cause
SRD has changed from a cone-shaped small foveal detach- of outer layer thinning and the loss of IS/OS reflectivity remains
ment to dome-shaped SRD. Hemorrhages are accumulating unclear, CME and SRD are suspected to be involved.
in foveal cystoid space. The macular edema and SRD dis-

Central retinal vein subretinal detachment

occlusion
 110 Chapter 4 · Retinal vascular diseases

Case 54 Central retinal vein occlusion: Progression from non-ischemic to ischemic ②

A 65-year-old male, OS, BCVA 0.2

A: Color fundus photograph in the left eye: At initial diagnosis. Flame-shaped and blot retinal hemorrhages are visible. B: 1-minute left eye FA, C: FA in the
left eye (5 min): At initial diagnosis. CME is exhibited. Nonperfusion is not found. D: Macular thickness map of the left eye: Significant thickening is ob-
served over the entire macula. E: Color fundus photograph in the left eye: 20 months after initial diagnosis. Best-corrected visual acuity is 0.1. The flame-
shaped retinal hemorrhages have disappeared and spotted retinal hemorrhages can be seen in the fovea centralis and outside the macula. Exudative
changes are significant. F: FA in the left eye (1 min), G: FA in the left eye (10 min): 20 months after initial diagnosis. CME remains. A area of nonperfusion is
observed outside the macula. H: Macula thickness map of the left eye: 20 months after initial diagnosis. Thickening in the centre of the macula has subsided,
whereas thickening remains on the nasal side and inferotemporal side. I: FA montage of the left eye (75 sec): 20 months after initial diagnosis. A wide area
of nonperfusion has formed outside the arcade vessels

J: Color fundus photograph in the left eye + enlarged version + OCT horizontal scan: At initial diagnosis. Typical acute phase CME images can be seen.
Foveal cystoid spaces (*), inner nuclear layer small cystoid spaces, outer plexiform layer cystoid spaces, and cone-shaped foveal detachments are present.
K: Color fundus photograph in the left eye + enlarged version + OCT horizontal scan: Same scan 7 months after initial diagnosis, and 3 months after vitre-
ous surgery combined with ILM peeling. Best-corrected visual acuity further decreased to 0.05. Macular CME has subsided on the temporal side, but re-
mains on the nasal side. Macular retinal hemorrhages are visible in the outer plexiform layer and beneath the fovea centralis. The IS/OS on the temporal side
are disrupted. L: Color fundus photograph in the left eye + enlarged version + OCT horizontal scan: Same scan 20 months after initial diagnosis. The CME in
the nasal macula has become less severe. Retinal hemorrhages remain beneath the fovea centralis, and foveal IS/OS reflectivity has been lost.
Case 54 · Central retinal vein occlusion: Progression from non-ischemic to ischemic ②
111 4

Image interpretation points

This is a case where reduced visual acuity is noted as a result arcade vessels, subsequently requiring panretinal photocoagu-
of non-ischemic CME/Vitreous surgery combined with ILM lation. Persistent retinal hemorrhages can be seen beneath the
peeling was performed. Flame-shaped retinal hemorrhages, fovea centralis. Finally, visual prognosis was poor due to the
which is hemorrhages in the retinal nerve fiber layer, have dis- breakdown of the foveal structure such as the disappearance of
appeared over time, while the deeper blot hemorrhages have foveal IS/OS reflectivity, which is thought to be caused by the
worsened. Afterwards, exudative changes have progressed, retinal hemorrhages beneath the fovea centralis.
and a nonperfusion area has been formed mainly outside the

central retinal vein occlusion

 112 Chapter 4 · Retinal vascular diseases

Case 55 Central retinal vein occlusion: Ischemic type

A 72-year-old male, OS, BCVA 0.08

A: Color fundus photograph in the left eye: Excluding the lower area, flame-shaped and blot retinal hemorrhages and multiple soft exudates are exhibited.
B: FA in the left eye (1 min): Including the macula, a nonperfusion area is formed circumferentially in roughly the upper 240-degree retinal area around the
optic disc. C: Microperimetry-1 of the left eye: Excluding the lower temporal side, no retinal sensitivity can be detected in the macula. D: Macular thickness
map of the left eye: Excluding the temporal side, the retina is thickened in the macular area. E: IR + OCT horizontal scan of the left eye, F: IR + OCT vertical
scan of the left eye: There are CME and SRD ( ) is extending to the lower arcade. Increased reflectivity ( ) of the synapse phase of the outer plexiform
layer can be seen.

Image interpretation points

At initial diagnosis, a wide area of nonperfusion spanning the start of laminar flow was delayed by 7 seconds (at 30 seconds)
roughly the upper 240 degrees of the retina including the in the upper vein. In general, hemi-CRVO is caused by occlusion
macula was seen on FA and diagnosed as ischemic CRVO. of just one branch of the central retinal vein in cases where the
Visual acuity is poor. High reflectivity of the synapse phase central retinal vein divides into two branches as it exits the optic
of the outer plexiform layer suggests deepest capillary oc- nerve. This case is an example of both branches being occluded
clusion. Both the upper and lower first branch of the central near the branching therefore exhibiting the same findings as a
retinal vein are dilated, and on FA, laminar flow started at CRVO, but the extent of occlusion differs and the perfusion in the
approximately 23 seconds in the lower vein in FA, whereas lower portion of the retina is relatively preserved.
Case 56 · Hemi-central retinal vein occlusion: Non-ischemic type
113 4
Case 56 Hemi-central retinal vein occlusion: Non-ischemic type

Right eye of a 68-year-old male with vision corrected to 0.7

A: Color fundus photograph in the right eye: Flame-shaped and blot retinal hemorrhages and multiple soft exudates are visible in the upper half of the
retina. Retinal hemorrhages can also be seen in the fovea centralis. B: FA in the right eye (30 sec), C: FA montage of the right eye (2 min), D: 8-minute right
eye macular area FA: Dilation, tortuosity, and leakage of the retinal veins are observed. There is no areas of retinal nonperfusion. CME can be seen in the
upper half of the fovea centralis. E: IR + OCT horizontal scan of the right eye: CME and small cone-shaped foveal detachments ( ) are noted. F: IR + OCT
vertical scan of the right eye: CME is noted. A small number of hemorrhages are noticeable in the foveal cystoid spaces. Weakly reflective spaces are visible
in the retinal nerve fiber layer.

Image interpretation points

Soft exudates can be seen, suggesting that ischemia of the CRVO. OCT vertical scans are useful in the diagnosis of hemi-
retinal surface layer is significant. However, an area of nonper- CRVO and understanding its pathology.
fusion cannot be seen with FA, therefore this is a non-ischemic
 114 Chapter 4 · Retinal vascular diseases

Case 57 Branch retinal vein occlusion: Significant inner retinal layer ischemia

Right eye of a 56-year-old female with vision corrected to 0.06

A: Color fundus photograph in the right eye: Dilation of the upper first branch of the central retinal vein and significant flame-shaped retinal hemorrhages
in the circumference of the perfusion area of this branch including the fovea centralis can be seen. Retinal hemorrhages are relatively scarce and multiple
soft exudates are observed in the central part of the perfusion area of the branch. B: FA in the right eye (1 min): Almost all arterioles, venules and capillaries
are not perfused. C: IR + OCT horizontal scan of the right eye: Hemorrhages are visible in the foveal cystoid space (*). D: IR + OCT vertical scan of the right
eye: The dilated venous lumen is weakly reflective and no blocking of the imaging beam resulting from blood flow are noted, suggesting a significant
decrease in perfusion. The retinal nerve fiber layer edema consistent with soft exudates is is thickened in a non-cystic manner. The posterior portion of the
inner layer of the retina is not only poorly defined due to the effect of blocked imaging beams resulting from the retinal hemorrhages and the increased
reflectivity of the inner retinal layer.

Image interpretation points

This is a case where retinal arterioles and venules as well as dilated and occluded vein lumen can be seen in this case,
retinal capillaries were acutely occluded, leading to the signi- suggesting that the perfusion of the veins are significantly de-
ficant retinal ischemia. As ischemia acutely progresses, the creased. The significant edema would be present in the inner
axonal flow of ganglion cells is impaired and soft exudates nuclear layer and outer plexiform layer, but are not depicted due
form. This appears as non-cystic, localized thickening of to blocking of the imaging beams by the increased reflectivity
the retinal nerve fiber layer on OCT. Weak reflectivity of the of the inner retina.
4.2 · Retinal artery occlusion
115 4
4.2 Retinal artery occlusion onset, but foveal thickness remains unchanged leading to loss of
the foveal depression.(3, 4, 7, 8) The structure of the inner layers is
Background preserved in the area where perfusion remained intact.
Retinal artery occlusion (RAO) is a disease in which the central
retinal artery or one of its major branches is occluded. Causes of
this are considered to be embolus, thrombus, narrowing of blood References
vessels, vasospasm or decreased arterial blood flow, of which
embolus is the most common cause. Many cases are due to 1) Ozdemir H, Karacorlu S, Karacorlu M. Optical coherence tomography find-
ings in central retinal artery occlusion. Retina. 2006; 26:110–112
thrombus from arteriosclerotic plaques in the carotid artery or
2) Karacorlu M, Ozdemir H, Arf Karacorlu S. Optical coherence tomography
cardiac valves. Bacteria (bacterial endocarditis), lipids, tumor findings in branch retinal artery occlusion. Eur J Ophthalmol. 2006; 16:
(cardiac mucosal tumor) and air bubbles may also cause this 352–353.
disease. In young people, RAO can be associated with antiphos- 3) Ikeda F, Kishi S. Inner neural retina loss in central retinal artery occlusion.
pholipid syndrome. Patients become aware of sudden impair- Jpn J Ophthalmol. 2010; 54:423–429.
ment to their vision and visual field. Sometimes, a sudden loss of 4) Ritter M, Sacu S, Deák GG, et al. In vivo identification of alteration of inner
neurosensory layers in branch retinal artery occlusion. Br J Ophthalmol.
vision (amaurosis fugax) lasting 1–2 minutes precedes RAO. This
2012 ; 96 : 201–207.
occurs frequently in those around 60 years of age, especially in 5) Kroll AJ. Experimental central retinal artery occlusion. Arch Ophthalmol.
men, and 3/4 of the patients over 40 years of age have abnor- 1968; 79:453–469
malities in carotid artery. 6) Hayreh SS, Kolder HE, Weingeist TA. Central retinal artery occlusion and
In Central retinal artery occlusion (CRAO) exhibits wide- retinal tolerance time. Ophthalmology. 1980; 87:75–78.
7) Leung CK, Tham CC, Mohammed S, et al. In vivo measurements of macular
spread whitening of the fundus except in the foveola, which are
and nerve fibre layer thickness in retinal arterial occlusion. Eye (Lond).
not supplied by retinal blood vessels. This fundus appearance is 2007; 21:1464–1468.
known as a cherry-red spot. Uniform retinal whitening is evident 8) Takahashi H, Iijima H. Sectoral thinning of the retina after branch retinal
when occlusion is complete, and in cases of incomplete occlu- artery occlusion. Jpn J Ophthalmol. 2009; 53:494–500.
sion, mottled whitening is found to various extents. When the
cilioretinal artery is spared, the retina escapes whitening in a
limited area between the optic disc and fovea therefore pre-
serving vision to a certain extent.
If occlusion is formed more distal to the branching of the
central retinal artery or in the arteriolar level, acute ischemic
retinopathy is localized. This presents as BRVO and vision is
relatively preserved. In BRAO either the upper or lower temporal
retina demonstrates retinal whitening.

OCT findings
Increased reflectivity of the inner retinal layers and mild to
moderate retinal thickening consistent with retinal whitening
can be seen in the acute stage.(1–4) This is due to intracellular
swelling and cytolysis.(5) The retina may recover if the ischemia
due to arterial occlusion resolves within 100 minutes, but if time
exceeds this limit, cells undergo necrosis and lead to irreversible
damage.(6)
When an acute RAO is observed with OCT, the increased
reflectivity resulting from retinal arterial occlusion can be seen
from the retinal nerve fiber layer to the outer plexiform layer.
Reflectivity from the outer nuclear layer to the photoreceptor
inner and outer segments declines due to blocking of measure-
ment beams by the highly reflective inner layers. However, little
damages to these outer layers occur in RVO. If retinal artery ob-
struction is incomplete, an increase in reflectivity occurs in the
limited retinal layers, such as retinal nerve fiber layer-ganglion
cell layer and inner nuclear layer-outer plexiform layer, or is
limited to columnar regions of the ganglion cell layer or inner
nuclear layer. In BRAO and CRAO with the cilioretinal artery
spared, no high reflectivity is found outside the area of nonperfu-
sion. In 3–4 weeks, selective thinning of the inner retinal layers
occurs diffusely and progresses further over the course of several
months. Retinal thickness becomes roughly 60% of that prior to
 116 Chapter 4 · Retinal vascular diseases

Case 58 Central retinal artery occlusion: A typical example

A 69-year-old male, OS, BCVA hand motion

A: Color fundus photograph in the left eye: At initial diagnosis. Retinal whitening of the entire posterior pole with a cherry-red spot is seen. B: Macular
thickness map of the left eye: Significant thickening exceeding 500 µm can be seen particularly on the nasal macula. C: Color fundus photograph in the
left eye: 2 months after initial diagnosis. Best-corrected visual acuity is hand motion. Retinal whitening has disappeared and sheathing of the retinal
arteries is observed. The optic disc is atrophic and pale.
D: Goldmann visual field of the left eye: 2 months after initial diagnosis. A small island of visual field remains in the temporal periphery. E: IR + OCT vertical
scan of the left eye: At initial diagnosis. There is markedly increased reflectivity and thickening seen from the retinal nerve fiber layer to the inner plexiform
layer of the entire posterior pole, and layer boundaries are blurring. There is decreased reflectivity of the photoreceptor IS/OS and RPE except in the fovea
centralisdue to blocking of OCT measurement beam. F: IR + OCT vertical scan of the left eye: 2 months after initial diagnosis. The inner retinal layers of the
posterior pole are diffusely diminished, and the foveal depression has mostly disappeared. In comparison, the thickness of the outer nuclear layer and
photoreceptor inner and outer segments remain unchanged, and the IS/OS and ELM lines are preserved.

Image interpretation points

This is a typical example of CRAO where retinal whitening significant thinning of the inner retinal layer. Even 4 months
with a cherry-red spot can be seen. There is significant increase after initial diagnosis, visual acuity is not improved with hand
in reflectivity from the retinal nerve fiber layer to the inner motion and the visual field is lost except for a small island of
plexiform layer, and the inner nuclear layer remains relatively remaining in the temporal periphery.
hyporeflective. Two months after initial diagnosis, there is

inner retinal atrophy

Case 59 · Central retinal artery occlusion: Cilioretinal artery not occluded
117 4
Case 59 Central retinal artery occlusion: Cilioretinal artery not occluded

A 73-year-old femaleOD, BCVA 0.6

A: Color fundus photograph in the left eye: During initial diagnosis. Retinal whitening can be seen except in the area perfused by the cilioretinal artery.
B: Color fundus photograph in the right eye: 3 weeks after initial diagnosis. Best-corrected visual acuity has decreased to 0.2. Retinal whitening has subsided.
C: FA in the right eye (26 sec): The filling of the fluorescein dye is only visible in the area perfused by the cilioretinal artery with retrograde filling of proximal
veins and arteries via the optic disc collateral circulation. D: IR + OCT horizontal scan of the right eye, E: IR + OCT vertical scan of the right eye [red dashed
box]: At initial diagnosis. Hyperreflectivity and thickening of the inner retinal layers are observed except in the nasal macula, and layer boundaries are
blurring. Only the layers in the fovea centralis where there is less increase in reflectivity can be clearly distinguished. F: IR + OCT vertical scan of the right
eye + enlarged version [red dashed box]: 3 weeks after initial diagnosis. Best-corrected visual acuity has reduced to 0.2. The inner layers of the retina are
diminished, but remains highly reflective. The inner layers of the fovea centralis is also thinned, but can be clearly distinguished because there is little
increase in reflectivity. G: Retinal thickness map of the right eye: Significant decrease in the macular thickness is noted.

Image interpretation points

When the cilioretinal artery remains perfused, the retina have rapidly atrophied in 3 weeks, but the hyperreflectivity
avoids whitening in a very limited area sandwiched between persists. The structure of the retinal layers is clearly visible in the
the optic disc and macula. On OCT, excluding the nasal side fovea centralis. Whitening with sparing of the fovea centralis
and fovea centralis, retinal inner layer hyperreflectivity and can be seen in approximately 2/3 of cases and as in this case,
thickening is observed in the macula. The retinal inner layers final visual acuity recovered to 0.2.
 118 Chapter 4 · Retinal vascular diseases

Case 60 Central retinal artery occlusion: Incomplete occlusion

A 63-year-old male, OS, BAVA finger count

A: Color fundus photograph in the left eye + enlarged version [red dashed box]: Retinal whitening and a cherry-red spot are visible over the entire posterior
pole. Soft exudates-like lesions are formed along the arcade vessels, and the whitening in the macular area is irregular with less whitening around the
arterioles. B: FA in the left eye (21 sec): Retinal arterial filling is delayed by several seconds. The filling of choroidal circulation is already beginning. C: FA in the
left eye (29 sec): Venous laminar flow extends close to the optic disc. D: FA in the left eye (66 sec) + enlarged version [white dashed box]: Note the retinal cap-
illary filling in the macular area. Nonperfusion and narrowing of the arterioles around the arcade vessels can be seen. E: IR + OCT vertical scan of the left eye
+ enlarged version [red dashed box]: Significant increase in reflectivity of the ganglion cell layer, inner nuclear layer and inner and outer plexiform layer is ob-
served. In particular, hyperreflectivity can be seen in a columnar pattern within the ganglion cell layer. The outer plexiform layer demonstrates undulations.

Image interpretation points

In normal eyes, central retinal artery begins to fluoresce approx- remains perfused and has avoided retinal whitening in the area
imately in 10 to 15 second after dye injection (1 to 3 seconds around the arterioles. Soft exudate-like lesions are present along
after choroidal flush). This case was delayed to 21 seconds in the arcade vessels, and nonperfusion and narrowing of the arteri-
retinal artery filling. Eight seconds later, the laminar flow reached oles are noted. On OCT images, increased reflectivity in a columnar
the vein near the optic disc, and thus the retinal circulation time pattern is evident in the ganglion cell layer. Irregularities of the
(normally ranging 6.3–13 seconds) was normal. Based on these hyperreflectivity indicating inner retinal ischemia suggest regional
findings, this case likely demonstrates incomplete occlusion of differences in the amount of ischemia corresponding to irregulari-
the central retinal artery. Retinal whitening and a cherry-red ties in retinal whitening. In this case, best-corrected visual acuity
spots can be seen over the entire posterior pole, but the macula has improved to 0.04 6 months after initial diagnosis.
Case 61 · Branch retinal artery occlusion: Case of good visual acuity
119 4
Case 61 Branch retinal artery occlusion: Case of good visual acuity

A 58-year-old female, OD, BCVA 1.5

A B C

A: Color fundus photograph in the right eye: At initial diagnosis. Whitening can be seen in the upper half of the retina. Dilation and tortuosity of the upper
and lower veins are seen along with accompanying retinal hemorrhages in the upper retina. B: FA in the right eye (28 sec): There was no difference in the
arterial filling time between the upper and lower retina, but filling of the upper vein is delayed; there is no filling in the upper veins whereas the laminar flow
is seen in the lower veins. C: FA in the right eye (5 min): The artery in the upper retina is narrowed. D: IR + OCT vertical scan of the right eye + enlarged ver-
sion [red dashed box]: As is clear when comparing the upper and lower retina, significantly increased reflectivity can be observed in the inner plexiform
layer, inner nuclear layer and outer plexiform layer, but not in the ganglion cell layer. There is little retinal thickening. E: IR + OCT vertical scan of the right
eye + enlarged version [red dashed box]: 2 years after initial diagnosis. Best-corrected visual acuity remains to be 1.5. The inner layers of the area of occlu-
sion are severely diminished, but the considerable amount of the retinal nerve fiber layer and ganglion cell layer remains. The foveal structure and outer
layers in the area of occlusion appear almost preserved.

Image interpretation points

This is a BRVO case where one major branch of the central reti- ner plexiform layer, inner nuclear layer and outer plexiform layer
nal artery was occluded immediately distal to the branching. is significantly enhanced. This hyperreflectivity on OCT and reti-
Along with the whitening of the retina, this case demonstrates nal whitening reflect the same pathological condition. Visual
dilation and tortuosity of the upper and lower retinal veins as prognosis is much better central retinal artery occlusion. This is
well as retinal hemorrhages. Thus, impending CRVO appears to because the fovea and lower retina are almost intact.
have concurred with BRAO. On OCT, the reflectivity of the in-
 120 Chapter 4 · Retinal vascular diseases

Case 62 Branch retinal artery occlusion: Incomplete occlusion

A 59-year-old male, OD, BCVA 1.5

A: Color fundus photograph in the right eye: At initial diagnosis. Retinal whitening can be seen in the lower posterior pole. B: Macular thickness map of the
right eye: Moderate thickening is noted in the inferior macula. C: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box], D: IR + OCT
vertical scan of the right eye + enlarged version [red dashed box]: Enhanced reflectivity is mainly seen from the inner plexiform layer to the outer plexiform
layer in a columnar pattern. Outer half part of the inner nuclear layer is exhibiting high reflectivity. In addition, the reflectivity in each layer is increased in a
columnar pattern. The IS/OS and RPE reflectivity in the posterior portion of the highly reflective area is decreased due to blocking of OCT measurement
beam.

Image interpretation points

This is a lower BRAO. The increase in reflectivity was limited to it is possible that ischemia as a result of the disruption of blood
partial both along the depth and lateral direction, indicating flow in the capillary network of the inner nuclear layer in the
incomplete occlusion along the depth and lateral direction. outer margin is significant, whereas ischemia in the capillary
The increase in the reflectivity of the inner nuclear layer was network region of the inner nuclear layer is not as significant.
limited its deeper half portion, suggesting that the occlusion Highly reflective cylindrical areas can be seen in each layer, and
took place primarily in the retinal capillary bed along the exter- significant »speckled« areas of ischemia may exist.
nal margin of the inner nuclear layer. Based on these findings,
4.3 · Idiopathic juxtafoveal macular telangiectasia
121 4
4.3 Idiopathic juxtafoveal macular similar to diabetic macular edema, so differentiation is necessary.
telangiectasia Type 1 develops in adults and is thought to be a congenital capil-
lary abnormality confined to the parafoveal area, and in a sense,
Classification it is considered a subtype of Coats’ disease.
Idiopathic juxtafoveal macular telangiectasia (MacTel), which Yannuzzi classification Type 2 has no gender difference and is
was originally described by Gass as idiopathic juxtafoveolar reti- bilateral. MacTel Type 2 has few exudative lesions, and telangiec-
nal telangiectasia (IJRT), is a syndrome characterized by the tasis and fluorescent leakage without retinal thickening. No exu-
non-diabetic dilation of parafoveal capillaries and subsequent dative lesions such as MAs, CME, or hard exudates are visible. In
development of macular lesions that cause a slow decline in Type 2, singular findings are observed on the temporal side of the
visual acuity.(1) According to Gass and Blodi,(2) IJRT can be parafovea from an early stage. A decrease in retinal transparency,
divided into 3 groups based on fundus photograph and FA telangiectasis and fluorescein leakage on FA, enhancement of
findings (Group 1–3), and each group can be further subdivided. macular autofluorescence, enhanced confocal blue reflectance on
Their initial classification encompassed specific disease types, red-free imaging, and a decrease in macular pigment can also be
but Yannuzzi et al.(3) excluded these specific disease types and seen. The area of enhanced confocal blue reflectance and de-
created a more practical system by simplifying the classification. creased macular pigment are almost identical in area; and wider
In the Yannuzzi classification, after the extremely rare Group 3 than the area of fluorescein leakage and enhanced autofluores-
(occlusive telangiectasia) is excluded, the disease is classified into cence.(4) Green et al. showed small, extracellular fluid pooling
Type 1 (aneurysmal telangiectasia) and Type 2 (perifoveolar tel- localized in the inner layer of the retina on light microscopic
angiectasia) as shown in . Table 4-1. Type 2, which was previ- images of one eye diagnosed as Type 2.(5)  Yannuzzi et al. also
ously divided into 5 stages, is subclassified into just nonprolifera- observed thickening of the macular retina on OCT.(3) However
tive and proliferative. Currently, the Yannuzzi classification is in practice, retinal thickening is not evident in the majority of
commonly used, and Gass and Blodi’s stage classification is used Type 2 cases on OCT.(6–10)  Instead, a foveal defect covered by the
for the subclassification of Type 2. ILM on the anterior border described by Yannuzzi et al. as an
inner lamella cyst is a characteristic feature.(3) Type 2 differs from
Pathology Type 1 in that the main form of the disease is degeneration
Yannuzzi classification Type 1 and Type 2 can be considered dif- and atrophy of the fovea centralis. Gass thought the telangiectasis
ferent diseases. Type 1 is common in men and is unilateral. and resulting decline of metabolic function in Group 2A make the
Exudative lesions due to telangiectasis of the temporal side of cells in the inner retinal layers, in particular Müller cells, be ex-
the parafovea are a characteristic. Telangiectasis, capillary aneu- posed to chronic nutritional deprivation leading to the degenera-
rysms, cystoid macular edema (CME) and circinate hard exudate tion of these cells and the connecting photoreceptor cells.(11) It
are found, and on FA fluorescent leakage can be seen mainly on was recently demonstrated that 3 types of Müller cell markers
the temporal macula. When observed with OCT in the majority were negative in the foveal site where macular pigment was not
of cases, the macula is thickened due to CME, which is some- detected in immunohistochemistry of a Type 2 autopsied eye,
times accompanied by foveal detachment. These findings are which supports Gass’ hypothesis.(12)

. Table 4-1 The Gass classification and the Yannuzzi classification

IJRT (Gass-Blodi) IMT (Yannuzzi)

Group 1A: visible and exudative IJRT Type 1 (aneurysmal telangiectasia)

Group 1B: visible, exudative and focal IJRT

Group 2A Type 2 (perifoveal telangiectasia)

Stage 1: occult telangiectatic vessels

Stage 2: loss of transparency without clinically evident telangiectatic vessels

Stage 3: prominent dilated right-angle retinal venules

Stage 4: retinal pigment hyperplasia into the retina

Stage 5: SRN from proliferation of intraretinal capillaries

Group 2B: juvenile occult familial IJRT

Group 3A: occlusive IJRT

Group 3B: occlusive IJRT with CNS vasculopathy

CNS = central nervous system, IJRT = idiopathic juxtafoveolar retinal telangiectasia, IMT = idiopathic macular telangiectasia,
SRN = subretinal neovascularization
(Created with reference to Yannuzzi LA, et al. Idiopathic macular telangiectasia. Arch Ophthalmol. 2006; 124: 450−460)
 122 Chapter 4 · Retinal vascular diseases

OCT findings 10) Cohen SM, Cohen ML, El-Jabali F, et al. Optical coherence tomography
The characteristic OCT findings in Type 1 is CME mainly findings in nonproliferative group 2a idiopathic juxtafoveal retinal telan-
around the temporal side of the parafovea. Cystoid spaces can be giectasis. Retina. 2007; 27:59–66.
11) Gass JDM. Retinal capillary diseases. In: Stereoscopic Atlas of Macular Dis-
typically seen in the fovea centralis, parafovea, inner nuclear eases: Diagnosis and Treatment. 4th ed. Vol 1 CV. Mosby, St. Louis, 1997.
layer, and outer plexiform layer, and the retina is significantly pp 506–511.
thickened. Sometimes a foveal detachment may occur. Foveal 12) Powner MB, Gillies MC, Tretiach M, et al. Perifoveal Müller cell depletion in
cystoid spaces fuse with surrounding cystoid spaces to become a case of macular telangiectasia type 2. Ophthalmology. 2010; 117:2407–
larger as the disease progresses. In addition, dilated capillaries are 2416.
4 seen as highly reflective dots located in lines between the retinal
nerve fiber layer and external margin of the inner nuclear layer.
Capillary microaneurysms are also visible.
Characteristic Type 2 OCT findings include a lack of signifi-
cant retinal thickening, and defective changes like cystoid cystic
degeneration, known as an inner lamellar cyst, seen in the fovea
centralis or the temporal side of the parafovea.(3) The defective
changes appears to start in the inner retina because an early inner
lamellar cyst is bordered anteriorly by the internal limiting mem-
brane.(3) Cystoid spaces extend to the outer layers of the retina
and cause photoreceptor layer defects as the disease progresses.
However, IS/OS line irregularities can be observed from an early
stage. Dilated capillaries are not so evident as in Type 2.
Cystoid spaces are formed in both Type 1 and Type 2, but
their pathologies are completely different. The cystoid space for-
mation in Type 1 is basically identical with the CME in diebetic
macular edema and RVO, which is caused by retinal vascular
leakage and results in evident macular thickening. In Type 2, the
cystoid spaces are associated with minimal exudative changes,
such as weak fluorescein leakage and slight retinal thickening if
any, which can be interpreted as cystoid degeneration as a result
of the loss of the retinal cells.(6–10)

References

1) Gass JD. A fluorescein angiographic study of macular dysfunction second-

ary to retinal vascular disease. V. Retinal telangiectasis. Arch Ophthalmol.
1968; 80:592–605
2) Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update
of classification and follow-up study. Ophthalmology. 1993; 100:1536–
1546.
3) Yannuzzi LA, Bardal AM, Freund KB, et al. Idiopathic macular telangiecta-
sia. Arch Ophthalmol. 2006; 124:450–460.
4) Charbel Issa P, Berendschot TT, Staurenghi G, et al. Confocal blue reflec-
tance imaging in type 2 idiopathic macular telangiectasia. Invest Ophthal-
mol Vis Sci. 2008; 49:1172–1177.
5) Green WR, Quigley HA, De la Cruz Z, et al. Parafoveal retinal telangiectasis.
Light and electron microscopy studies. Trans Ophthalmol Soc U K. 1980;
100:162–170.
6) Gaudric A, Ducos de Lahitte G, Cohen SY, et al. Optical coherence tomog-
raphy in group 2A idiopathic juxtafoveolar retinal telangiectasis. Arch
Ophthalmol. 2006; 124:1410–1419.
7) Albini TA, Benz MS, Coffee RE, et al. Optical coherence tomography of
idiopathic juxtafoveolar telangiectasia. Ophthalmic Surg Lasers Imaging.
2006; 37:120–128.
8) Surguch V, Gamulescu MA, Gabel VP. Optical coherence tomography
findings in idiopathic juxtafoveal retinal telangiectasis. Graefes Arch Clin
Exp Ophthalmol. 2007; 245:783–788
9) Paunescu LA, Ko TH, Duker JS, et al. Idiopathic juxtafoveal retinal telangi-
ectasis: new findings by ultrahigh-resolution optical coherence tomogra-
phy. Ophthalmology. 2006 ; 113:48–57.
Case 63 · Macular telangiectasia: Yannuzzi classification Type 1
123 4
Case 63 Macular telangiectasia: Yannuzzi classification Type 1

A 54-year-old male, OS, BCVA 0.9

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: Circinate retinopathy can be seen centered at the temporal side of
the parafovea. CME is present in the fovea centralis. C: FA in the left eye (54 sec): Telangiectasis and capillary MAs are visible in the area surrounded by the
circinate retinopathy. D: FA in the left eye (5 min): Fluorescein leakage and fluorescein pooling into the cystoid spaces are exhibited. E: IR + OCT horizontal
scan of the left eye + enlarged version [red dashed box]: A foveal cystoid space (*), outer plexiform layer cystoid spaces ( ), and inner nuclear layer cys-
toid spaces are noted. Dilated capillaries are seen as 3 lines of highly reflective dots located along the boundary between the retinal nerve fiber layer and
ganglion cell layer, external margin of the ganglion cell layer, and the inner nuclear layer. F: IR + OCT vertical scan of the left eye + enlarged version [red
dashed box]: Note the capillary aneurysms in the margins of the foveal cystoid spaces (*).

Image interpretation points

Yannuzzi classification Type 1 is common in men, unilateral, and fluorescein leakage was seen on the temporal side of the
and characterized by telangiectasis and retinal thickening on fovea centralis by FA. Impressively, 3 layers of telangiectasia in
the temporal side of the parafovea accompanied by exudative the retinal capillary network can be observed by OCT. It is worth
lesions. In this case, telangiectasia, capillary aneurysms, CME noting the capillary aneurysms in the margins of the cystoid
and hard exudate were observed with an ophthalmoscope, spaces.

Temporal cystoid macular edema

 124 Chapter 4 · Retinal vascular diseases

Case 64 Macular telangiectasia: Yannuzzi classification Type 1

A 57-year-old male, OD, BCVA 1.0

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: Circinate retinopathy can be seen centered on the temporal side of
the parafovea. CME is visible in the fovea centralis. C: FA in the right eye (1 minute): Telangiectasia and capillary aneurysms are observed on the temporal
side of the parafovea. D: 4-minute right eye FA: Fluorescein leakage from the capillary aneurysms is noted. E: IR + OCT horizontal scan of the right eye +
enlarged version [red dashed box]: Foveal cystoid space (*), and cystoid spaces in the outer plexiform layer and inner nuclear layer can be observed.
Adjacent parafoveal cystoid space are connected to a foveal detachment. F: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]:
18 months after initial diagnosis. Best corrected visual acuity declined to 0.5. The foveal detachment has disappeared, while the foveal cystoid spaces and
parafoveal cystoid spaces have fused and expanded. The photoreceptor IS/OS beneath the cystoid space demonstrates significant atrophy. Note the
dilated capillary aneurysm in the inner nuclear layer near the border of the parafoveal cystoid space.

Image interpretation points

In this case, fluid is leaking from the parafoveal cystoid spaces and parafoveal cystoid spaces is atrophic, consistent with a
to below the retina, causing a foveal detachment. Eighteen decline in visual acuity. The exudative lesions of Yannuzzi classi-
months after initial diagnosis, the foveal detachment has dis- fication Type 1 can exacerbate slowly, but when fluid accumula-
appeared, but the photoreceptor IS/OS beneath the expanded tion into the subretinal space occurs, the progression of the
cystoid space created from the fusion and expansion of foveal decline in visual acuity is relatively quick.
Case 65 · Macular telangiectasia: Yannuzzi classification Type 2 Stage 2
125 4
Case 65 Macular telangiectasia: Yannuzzi classification Type 2 Stage 2

A 75-year-old female, OS, BCVA 1.0

A: Color fundus photograph in the left eye, B: Enlarged version of A [red dashed box]: A slight decline in retinal transparency and crystalline deposits (⇒)
are visible on the temporal side of the parafovea. C: FA in the left eye (5 minutes): Although subtle and diffuse hyperfluorescence can be seen on the tempo-
ral side of the parafovea, neither telangiectasia nor microaneurysms are observed. D: Fundus autofluorescence (FAF) in the left eye, E: Red-free imaging in
the left eye: Enhancement of FAF and blue light enhancement reflectivity is observed in a semi-circular area on the temporal side of the parafovea. It is
slightly wider than the area of hyperfluorescence on FA. F: IR + OCT horizontal scan of the left eye: The foveal depression has flattened due to atrophy of
the temporal side of the parafovea and IS/OS line irregularities are noted. G: IR + OCT oblique scan of the left eye + enlarged version [red dashed box]:
There is lamellar cystic degeneration ( ) on the temporal side of the parafovea and no retinal thickening.

Image interpretation points

Yannuzzi classification Type 2 has no gender difference, bilater- light hyperreflectivity in red-free imaging can be observed.
al, and characterized by telangiectasia and hyperfluorescence Instead of CME or retinal thickening, OCT imaging typically
without retinal thickening on the temporal side of the parafo- demonstrates retinal thinning. Cystic degeneration, known as
vea. This case corresponds to Gass-Blodi classification Stage 2: an inner lamellar cyst, also occurs in the temporal parafoveal
on the temporal side of the parafovea, a slight decrease in area of the macula. IS/OS line irregularities can be seen, suggest-
retinal transparency, crystalline deposits, weak and diffuse ing that damage to the photoreceptor cells is also present.
hyperfluorescence on FA, enhanced autofluorescence, and blue
 126 Chapter 4 · Retinal vascular diseases

Case 66 Macular telangiectasia: Yannuzzi classification Type 2 Stage 3

A 75-year-old female, OD, BCVA 0.8

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: A slight decline in retinal transparency and crystalline deposits (⇒)
are noted on the temporal side of the parafovea. C: FA in the right eye (50 seconds): D: Enlarged version of C [white dashed box]: Dilated and right-angled
retinal venule (⇒) are observed on the temporal side of the parafovea. E: FAF in the right eye, F: Red-free imaging in the right eye: Enhanced autofluores-
cence and blue light hyperreflectivity are visible in a semi-circular area on the temporal side of the parafovea and is larger than the hyperfluorescence area
on FA. G: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box], H: IR + OCT vertical scan of the right eye + enlarged version [red
dashed box]: Lamellar cystic degeneration (*) can be seen in the fovea centralis. The margins of the cystoid spaces are irregular. No retinal thickening is
visible. Note the irregularities in the IS/OS and COST lines.

Image interpretation points

This case shows the right-angle retinal venule, consistent with noticeable, but cystic degeneration, known as an inner lamellar
Gass-Blodi classification Stage 3. On the temporal side of the cyst is present in the temporal parafoveal area of the macula. The
parafovea, slight decrease in retinal transparency, crystalline term, »inner«, is derived from the fact that the anterior border of
deposits, weak and diffuse hyperfluorescence on FA, enhanced the cystoid space is the ILM. Irregularities in the IS/OS and COST
autofluorescence, and blue light hyperreflectivity in red-free lines are clearly visible, and there is thinning of the OS in the tem-
imaging are observed. By OCT, no CME or retinal thickening is poral portion of the parafovea.
Case 67 · Macular telangiectasia: Yannuzzi classification Type 2 Stage 4
127 4
Case 67 Macular telangiectasia: Yannuzzi classification Type 2 Stage 4

A 58-year-old male, OS, BCVA 0.7

A: Color fundus photograph in the left eye: RPE hyperplasia can be seen on the nasal side of the parafovea (⇒). B: FA + IA in the left eye (5 minutes):
Fluorescein hyperfluorescence is exhibited in the fovea and parafovea. Hypofluorescence due to light blocking by RPE are also observed on FA (⇒). C: Micro-
perimetry -1 of the left eye: A scotoma is visible on the temporal side of the parafovea. D: FAF in the left eye: There is increased autofluorescence in the fovea
centralis. E: Red-free imaging of the left eye: Annular blue light hyperreflectivitiy can be observed. It is wider than the area of hyperfluorescence on FA.
F: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: Defects are found in the outer layers of the retina on the temporal side of
the parafovea. Lamellar cystic degeneration (*) of the inner layers can be seen. The margins of the cystoid spaces are irregular. No retinal thickening is
visible. Areas of RPE hyperplasia ( ) are also present.

Image interpretation points

This case corresponds to Gass-Blodi classification Stage 4, as maintained at 0.7 due to the preservation of the outer layers on
RPE hyperplasia can be seen. Cystic degeneration, known as the nasal side of the fovea centralis. Outside of the foveal cen-
an inner lamellar cyst, has developed into photoreceptor layer tralis where the damage is more significant, the annular region
defects in the corresponding area of strong fluorescein hyper- of blue light hyperreflectivity on red-free imaging is seen. Blue
fluorescence seen on FA. The outer layer defect area causes the light hyperreflectivity is thought to correspond to the loss of
scotoma on microperimetry -1. Best corrected visual acuity macular pigment (lutein and zeaxanthine).
 128 Chapter 4 · Retinal vascular diseases

Case 68 Coats’ disease: A typical example

A 4-year-old girl, OD, BCVA 0.06

A: Color fundus photograph in the right eye: At initial diagnosis. A large amount of hard exudates and a wide area of SRD can be seen from the posterior
pole to the upper retina. B: Color fundus photograph of the periphery in the right eye: At initial diagnosis. Irregular dilation and aneurysms are visible
in the retinal blood vessels and capillaries in the upper temporal periphery. C: FA in the right eye (3 minutes, 30 seconds), D: FA in the left eye (4 minutes,
30 seconds): At initial diagnosis. Fluorescein leakage is observed from aneurysms in the peripheral retina and capillaries in the wide area inferior to the
aneurysms. E: Color fundus photograph in the right eye: Five months after cryopexy. Visual acuity has improved to 0.6. SRD above the posterior pole has
disappeared and a decrease in hard exudate is noted. F: IR + OCT vertical scan of the right eye: At initial diagnosis. SRD is exhibited over the entire posterior
pole. G: IR + OCT vertical scan of the right eye: 5 months after cryopexy. Retinal detachment is subsiding, and hard exudates ( ) remains below the retina
and in the outer plexiform layer.

Image interpretation points

Coats’ disease is non-familial, usually with unilateral onset, and ing irregular dilation and aneurysms in the retinal blood vessels,
common in men. It develops during infancy and childhood. and causing a large amount of hard exudates and SRD over a
When Coats’ disease develops in adults and is confined to the wide area. Sometimes, neovascular glaucoma may subsequently
parafovea, it is considered a disease similar to Yannuzzi Type 1. develop. Laser photocoagulation or cryopexy of the abnormal
It starts with abnormalities in the peripheral capillaries, form- blood vessels is effective.
4.4 · Retinal arterial macroaneurysm
129 4
4.4 Retinal arterial macroaneurysm References

Retinal arterial macroaneurysm is a disease that is common in 1) Rabb MF, Gagliano DA, Teske MP. Retinal arterial macroaneurysms. Surv
Ophthalmol. 1988; 33:73–96.
women aged 60–70 years.(1, 2) It occurs readily in elderly persons
2) Gass JDM. Macular dysfunction caused by retinal vascular diseases. In:
with hypertension and arteriosclerosis. Unilateral onset is most Stereoscopic atlas of macular diseases 4th ed, Vol 1. CV Mosby, St. Louis,
common, but bilateral onset is seen in 10%. It is usually sporadic 1997. pp 437–599.
in the first to 3rd of the 4 arterial branches, but can occur in 3) Lavin MJ, Marsh RJ, Peart S, et al. Retinal arterial macroaneurysms: a retro-
multiple sites. Although rare, it can occur in the cilioretinal spective study of 40 patients. Br J Ophthalmol. 1987; 71:817–825.
artery and optic disc. It sometimes coincides with retinal vein 4) Tonotsuka T, Imai M, Saito K, et al. Visual prognosis for symptomatic retinal
arterial macroaneurysm. Jpn J Ophthalmol. 2003; 47:498–502.
occlusion. The macroaneurysms sometimes show pulsation, but
5) Tsujiawa A, Sakamoto A, Ota M, et al. Retinal structural changes associat-
it is unknown whether or not this finding is a risk factor for hem- ed with retinal arterial macroaneurysm examined with optical coherence
orrhages. The main causes of reduced visual acuity are hemor- tomography. Retina. 2009; 29:782–792.
rhages below the retina and the ILM as a result of a rupture of 6) Tezel TH, Günalp I, Tezel G. Morphometric analysis of exudative retinal ar-
retinal arterial macroaneurysm, and macular edema and foveal terial macroaneurysms: a geometrical approach to exudate curves. Oph-
thalmic Res. 1994; 26:332–339.
detachment as a result of leakage from it.(3) It can also be the
7) Takahashi K, Kishi S. Serous macular detachment associated with retinal
cause of vitreous hemorrhage. The visual prognosis is relatively arterial macroaneurysm. Jpn J Ophthalmol. 2006; 50:460–464.
good in most cases with macular edema or vitreous hemorrhage
alone, but a large number of hemorrhages below the fovea cen-
tralis can lead to poor visual prognosis.(4) Visual prognosis is also
poor when macular edema is prolonged and circinate retinopa-
thy is formed.(5, 6) Retinal arterial macroaneurysm can usually be
seen with an ophthalmoscope, but where there is significant sub-
ILM or vitreous hemorrhages obscuring the retinal arterial mac-
roaneurysm, it is necessary to detect it by FA or IA for diagnosis.
One finding that is interesting is that despite the retinal
arterial macroaneurysm being present in the arcade arteries,
fluid can leak through the outer plexiform layer causing a foveal
detachment and lead to visual impairment.(5, 7) Retinal arterial
macroaneurysm is thought to form a linear cleft in the arterial
wall, in which smooth muscle cell abnormalities and fibrosis of
the retinal arterial wall has progressed. The macroaneurysm is
covered by a laminated membrane formed by fibrin and plate-
lets,(2) and thus the cleft may close spontaneously.
 130 Chapter 4 · Retinal vascular diseases

Case 69 Retinal arterial macroaneurysm: Subretinal hemorrhages

An 82-year-old female, OD, BCVA 0.05

A: Color fundus photograph in the right eye: Hemorrhages below the ILM (*) are evident in the inferior macula, and subretinal hemorrhages (☆☆) cover
the entire macula. The choroid of the fovea centralis cannot be visualized. B: FA + IA in the right eye (1 minute): A retinal arterial macroaneurysm is visible
(⇒). C: IR + OCT horizontal scan of the right eye: Hemorrhages below the ILM and hemorrhagic macular detachment are noted. D: IR + OCT vertical scan of
the right eye: Same findings as C

Image interpretation points

Rupture of a retinal arterial macroaneurysm is often the cause the cause of poor visual prognosis. However, as in this case
of bleeding into below the ILM and retina, resulting in visual where a large amount of subretinal hemorrhages below the
impairment. Hemorrhages block measurement beams so the fovea centralis prevent the choroid from being visualized, the
posterior tissue is not visualized. Hemorrhages below the ILM visual prognosis is poor. Gas tamponade was performed for
can be removed with vitreous surgery and are infrequently this case, but visual improvement was limited to 0.15.
Case 69 · Retinal arterial macroaneurysm: Subretinal hemorrhages
131 4

E: Color fundus photograph in the right eye: One week after gas tamponade. The subretinal hemorrhages have moved to outside the macula and choroidal
visibility near the fovea centralis has improved. F: Color fundus photograph in the right eye: Two months after gas tamponade. Best corrected visual acuity
is 0.08. Hemorrhages below the ILM are organized. Subretinal hemorrhages have been considerably absorbed. G: Color fundus photograph in the right
eye: Nine months after surgery. Best corrected visual acuity has improved to 0.15. Hemorrhages below the ILM and subretinal hemorrhages have mostly
disappeared. H: IR + OCT vertical scan of the right eye: One week after gas tamponade. Hemorrhages remain in the fovea centralis, but it is noticeable that
the ones in the superior macula have been largely absorbed. The subretinal hemorrhage in the inferior macula is unclear due to the blocking effect as a
result of hemorrhages below the ILM. I: IR + OCT vertical scan of the right eye: Subfoveal hemorrhages have disappeared. Note the disappearance, and
irregularities of the IS/OS line and abnormal reflectivity of the foveal photoreceptor layer.

Retinal arterial macroaneurysm

 132 Chapter 4 · Retinal vascular diseases

Case 70 Retinal arterial macroaneurysm: Foveal detachment from an inferior arterial macroaneurysms

A 73-year-old male, OS, BCVA 0.2

A: Color fundus photograph in the left eye: An arterial macroaneurysm and retinal hemorrhages are visible along the inferior retinal arcade. Hard exudates
can be seen in the fovea centralis. B: FA in the left eye (2 minutes): The arterial macroaneurysm is seen in the inferior retinal arcade. C: IR + OCT oblique
scan of the left eye: Outer plexiform layer edema is noted over a wide area from the arterial macroaneurysm to the inferonasal side of the macula. Foveal
cystoid spaces and foveal detachment ( ) can also be observed. D: IR + OCT horizontal scan of the left eye: The parafoveal cystoid space in the outer plexi-
form layer is opening into the subretinal space ( ).
(A, B are modified according to Tsujikawa A, et al. Retinal structural changes associated with retinal arterial macroaneurysm examined with optical coherence
tomography. Retina. 2009; 29: 782–792)

Image interpretation points

A leakage from retinal arterial macroaneurysm in the inferior centralis, it is thought that fluid leaking from the retinal arterial
arcade often spreads out into the fovea centralis leading to macroaneurysm flows through the outer plexiform layer like
foveal cystoid edema and detachment, resulting in visual im- an underground stream and pools in the fovea centralis. Outer
pairment. As in this case, outer plexiform layer edema is con- plexiform layer cystoid spaces near the fovea centralis are
tiguous with the retinal arterial macroaneurysm. However, thought to coalesce with the subretinal space and cause foveal
in cases where SRD is confined to the vicinity of the fovea detachment.
 133 5

Central serous chorioretinopathy

5.1 Central serous chorioretinopathy – 134
References – 138

Case 71 Acute central serous chorioretinopathy:

Smoke-stack pattern – 139

Case 72 Acute central serous chorioretinopathy:

A slowly leaking ink-blot pattern – 140

Case 73 Acute central serous chorioretinopathy:

Intense leakage with ink-blot pattern – 141

Case 74 Chronic central serous chorioretinopathy:

Choroidal thickening – 142

Case 75 Chronic central serous chorioretinopathy:

A case of recurrence – 143

Case 75 Continuation – 144

Case 76 Chronic central serous chorioretinopathy:

Changes in the photoreceptor outer segment – 145

Case 77 Chronic central serous chorioretinopathy:

Example of poor visual prognosis – 146

Case 78 Acute bullous retinal detachment:

A typical example – 147
 134 Chapter 5 · Central serous chorioretinopathy

5.1 Central serous chorioretinopathy using EDI-OCT. The results of such studies allowed us to con-
sider the pathogenic mechanism involved in SRD formation:
Background »increased choroidal permeability → choroidal stromal hyperten-
Central serous chorioretinopathy (CSC) is a disease that causes a sion → breakdown of the outer blood-retinal barrier at the RPE.
flat serous retinal detachment (SRD) in the macular area without
any known other causes. Patients become aware of metamor- Disease type and fluorescein fundus angiography
phopsia, scotoma, and micropsia. In its acute form, the decrease Typical (acute) CSC
in visual acuity is mild, and the visual prognosis is typically good
if the condition does not become chronic. CSC is common in jFA
middle-aged men (male: female=10:1), stress can be a catalyst for The early stage starts with punctate hyperfluorescence; and
5 onset, and a connection with type A personalities has been ob- during the late stages, severe leakage patterns known as ink-blots
served. The use of steroids is also involved in the onset and exac- and smoke-stacks may appear.
erbation of this disease.
The ink-blot pattern quickly leaks within the dome-shaped
Pathology pigment epithelial detachment (PED) and produces a stained
Breakdown of the outer blood-retinal barrier formed by the reti- appearance of the exudate beneath the RPE. There is a type
nal pigment epithelium (RPE) was thought to be linked to the that diffusely leaks from within the PED to below the retina
onset of CSC. In recent years, choroidal hyperpermeability has (. Fig. 5-1), and a type that quickly leaks below the retina
been suggested based on observation of abnormal choroidal (. Fig. 5-2). The latter is very similar to the smoke-stack pattern
tissue stains by indocyanine green angiography (IA).(1) Further- and leaks heavily from a pinhole break of the RPE, but since
more, increased choroidal thickness has also been observed rapid diffusion below the retina is prevented by fibrin clots

. Fig. 5-1 Ink-blot pattern: Type that diffusely leaks below the retina
A: FA + OCT horizontal scan + enlarged version. The pooling of the dye (ink-blot pattern) can be seen on FA. PED ( ) is visualized at this site
by OCT. In the enlarged image, fibrin is not detected below the retina; instead it is located within the PED.
B: Diagram. Significant leakage from the choroid is being blocked by fibrin within the PED and causes slow spreading of dye into the retina. The characteri-
stic of PED in this type is a dome-shaped swelling
5.1 · Central serous chorioretinopathy
135 5
surrounding the leakage, an ink-blot pattern with irregular Chronic CSC
configuration appears. Extensive RPE dysfunction can be seen, and is characterized by
The smoke-stack pattern represents heavy leakage from the the prolongation and recurrence of SRD. When the SRD is con-
pinhole RPE break at the border or in the center of the PED that fined to around the disc, the periphery of the macula, and outside
streams superiorly. The PED flattens as if it has collapsed and the macula during initial onset, there are no subjective symp-
leakage fluid does not accumulate within the PED; so it does not toms; so examinations will sometimes expose cases that are
accompany an ink-blot pattern that reflects the form of the PED already recurring or protracted at the initial visit. SRD is similar
(. Fig. 5-3). with acute CSC but shows a relatively smaller detachment. In
addition, subretinal deposits, yellowish-white deposits, RPE at-
jIA rophy, and pigmentation are often observed. Concentrated sub-
Choroidal filling delay, dilation of the choroidal veins, and mid- to retinal fluid spreads downward with gravity; and when this is
late-stage abnormal choroidal tissue staining indicating choroidal prolonged, extensive RPE atrophy occurs in the inferior retina
vessel hyperpermeability can be seen. These abnormal features resulting in RPE atrophic tracts expressed by tear drops and
are frequently noticeable even where there are any particular flasks.
findings on FA and often remains even after SRD has resolved.

. Fig. 5-2 Ink-blot pattern: Type that quickly leaks underneath the retina
In some cases with the ink-blot pattern, fibrin accumulates surrounding the leaking point of the RPE, and a circular space is formed where leakage fluid
pools. The leakage fluid slowly spreads through the fibrin capsule into the subretinal space. The PED stops swelling and relaxes. In such cases, the IS/OS line
is sometimes visible around the defect area, suggesting another possibility that the leakage generates a cystoid space in the outer retinal layers similar to
Harada‘s disease. A: FA + OCT oblique scan + enlarged version. Rapid leakage can be seen on FA. Small defects ( ) are observed in the RPE by OCT, and
the PED is becoming flaccid. Fibrin is accumulating to envelop the RPE defect area, and the inside is weakly reflective. B: Diagram. Leakage fluid is rapidly
flowing through the small defect in the RPE to underneath the retina. Fibrin is surrounding the leaking point of the RPE.
 136 Chapter 5 · Central serous chorioretinopathy

jFA Acute CSC

Diffuse, weak leakage is more frequent than clear pin-point jDetached sensory retina
leakage. There are many cases without distinct leakage points. Roughly 1–2 months after onset, the photoreceptor outer seg-
RPE dysfunction can be seen as window defects. ments (OS) maintain homogeneous reflectivity and thickness,
but after 2 months, OS irregularities form including OS thickness
jIA heterogeneity, elongation of the foveal OS, and OS high reflectiv-
Choroidal abnormal findings are observed over a wide area as in ity.(14, 15) As the period after initial onset becomes more pro-
the typical example. longed, highly reflective spots corresponding to ophthalmoscop-
ically-identified subretinal deposits become more significant,
Acute bullous retinal detachment foveal OS elongation becomes more noticeable, part of the elon-
5 Numerous SRDs and PEDs in the posterior pole and equatorial gated OS starts shedding, and these shed OS can be seen above
area occasionally occurs secondary to CSC. The SRDs some- the RPE. The shed OS appears highly reflective on infrared
times become confluent and lead to bullous retinal detachments imaging.
that extend into the inferior fundus. This is thought to be the
fulminant form of CSC. In practice, many patients have a present jSubretinal findings and the RPE
or past history of CSC. Cases without systemic diseases are com- RPE defects thought to be leakage points can be seen in or
mon in middle-aged men. Renal transplant patients and patients at the edge of the PED. There may be a fibrin clot that covers
with systemic diseases receiving systemic steroids as treatment the RPE defect and weakly reflective zone within the fibrin
are also affected. Gender is not relevant in such cases. Yellowish- clot believed to form due to fresh leakage fluid.(16, 17) There
white fibrin deposits beneath the retina can be seen with a rela- are cases where tense, dome-shaped PED can be seen and
tively large PED. those with relaxed, concave PED. Location of fibrin clot for-
mation and PED shapes are closely related to leakage patterns
jFA (. Fig. 5-1–5-3).
In the early phase, there are multiple punctiform leakage spots,
which exhibits significant fluorescein leakage in later phases. Chronic CSC
jDetached sensory retina
Prognosis The SRD is flat and can sometimes only be seen with OCT.(12)
There are many cases of spontaneous remission, and in a large The above-mentioned photoreceptor OS irregularities (OS thick-
portion, visual acuity improves substantially without treatment. ness heterogeneity, OS thickening, OS high reflectivity, and OS
However, even if visual acuity is restored to 1.0 and above, shedding) and sub- and intra- retinal deposits are significant due
numerous disorders such as a decrease in color sensitivity, a to chronicity. If CSC is further prolonged or recurrence occurs,
decrease in contrast sensitivity, relative scotoma, micropsia, and this can cause significant foveal thinning.
metamorphopsia may persist. Visual acuity remains below 0.7
in roughly 5% of cases. Patients with prolonged or recurrent jSubretinal findings and the RPE
SRD sometimes show visual impairments of below 0.1. The vi- The PED often can be relaxed, flat, and exist over a wide area.
sual prognosis of cases where the SRD is large is worse compared These PEDs cannot be determined on an biomicroscopy. The
to those where it is small. When the SRD is in remission, there presence of PED can be easily determined on OCT because the
are cases where the ocular fundus is almost restored to normal, linear Bruch’s membrane is visible beneath PED.
but the majority exhibit irregular depigmentation of the RPE or
extensive RPE atrophy. 20–30% of cases undergo at least one Reattached sensory
recurrence. RPE abnormalities are also seen in the fellow eye in In patients with good visual acuity, there are often no abnor-
1/3 of cases, but less than 20% result in SRD. malities in the foveal ELM, IS/OS and COST lines, and foveal
thickness tends to be normal.
OCT findings As the decrease in visual acuity progresses, foveal retinal
In acute CSC, the following findings have been reported thanks thickness thins and the ELM, IS/OS, and COST lines become
to time-domain OCT: SRD, thickening, high reflectivity and ir- irregular or disappear over a wide area.(12, 14, 18) Lack of re-
regularities (granulation) of the detached foveal retina, RPE ab- flectivity of the IS/OS and COST lines and thinning of the
normalities, sub- and intraretinal deposits, fibrin,(1–10) thinning foveal portion of the retina are findings correlated with the
of the fovea as in cases of poor visual recovery after reattach- number of foveal cone photoreceptor cells.(19) The reflectivity
ment,  as well as attenuation or disappearance of the foveal lines most easily affected from the early stage are ① COST, ②
ELM and IS/OS reflectivity, and cystic degeneration.(4, 11, 12) The IS/OS, and ③ ELM, in that order. Even in eyes with good visual
usefulness of OCT in the diagnosis and pathological understand- acuity, IS/OS and COST line irregularities confined to outside
ing of CSC has been well known. In practice, even shallow SRDs the fovea centralis are commonly encountered. A decrease in
which cannot be clearly determined with an biomicroscopy or retinal sensitivity consistent with these sites can also be ob-
fluorescein fundus angiography can be detected by OCT.(13) An served.(20)
even more accurate pathological understanding is possible with
SD-OCT.
5.1 · Central serous chorioretinopathy
137 5
The choroid eye where CSC has not developed.(22) Photodynamic therapy
It was previously known that choroidal vessel hyperpermeability (PDT) and laser photocoagulation are both effective in treating
existed in CSC.(1) Improved visualization of the choroid using SRD in CSC; however PDT improves choroidal thickening,
EDI-OCT has demonstrated that the choroid indeed thickens in whereas it persists even after laser photocoagulation was suc-
CSC.(21) Choroidal thickening accompanying choroidal vessel cessfully done.(23)
hyperpermeability is sometimes even detected in the fellow

. Fig. 5-3 Smoke-stack pattern

A: FA + OCT horizontal scan. A smoke-stack pattern of fluorescein leakage is visible on FA. Concave-shaped flat PED can be seen on OCT and the leakage
point is also visualized. Outer retinal defect ( ) due to jet stream can be seen. B: Diagram. Leakage fluid is not accumulating beneath the pigment epi-
thelium, but instead, is strongly flowing into the subretinal space. Fibrin is not accumulating beneath the RPE or the retina. Leakage spots are consistent
with small or concave-shaped PED.

central serous chorioretinopathy

 138 Chapter 5 · Central serous chorioretinopathy

References 22) Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness in fellow
eyes of patients with central serous chorioretinopathy. Retina. 2011;
1) Iida T, Kishi S, Hagimura N, et al. Persistent and bilateral choroidal vascular 1603–1608.
abnormalities in central serous chorioretinopathy. Retina. 1999; 19:508– 23) Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treat-
512. ment of central serous chorioretinopathy. Ophthalmology. 2010; 117:
2) Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of cen- 1792–1799.
tral serous chorioretinopathy. Am J Ophthalmol. 1995; 120:65–74.
3) Iida T, Hagimura N, Sato T, et al. Evaluation of central serous chorioretin-
opathy with optical coherence tomography. Am J Ophthalmol. 2000;
129:16–20.
4) Wang MS, Sander B, Larsen M. Retinal atrophy in idiopathic central serous
chorioretinopathy. Am J Ophthalmol. 2002; 133:787–793.
5 5) Piccolino FC, de la Longrais RR, Ravera G, et al. The foveal photoreceptor
layer and visual acuity loss in central serous chorioretinopathy. Am J Oph-
thalmol. 2005; 139:87–99.
6) Montero JA, Ruiz-Moreno JM. Optical coherence tomography characteri-
sation of idiopathic central serous chorioretinopathy. Br J Ophthalmol.
2005; 89:562–564.
7) Saito M, Iida T, Kishi S. Ring-shaped subretinal fibrinous exudate in central
serous chorioretinopathy. Jpn J Ophthalmol. 2005; 49:516–519.
8) Hussain N, Baskar A, Ram LM, et al. Optical coherence tomographic pat-
tern of fluorescein angiographic leakage site in acute central serous cho-
rioretinopathy. Clin Experiment Ophthalmol. 2006; 34:137–140.
9) Mitarai K, Gomi F, Tano Y. Three-dimensional optical coherence tomo-
graphic findings in central serous chorioretinopathy. Graefes Arch Clin
Exp Ophthalmol. 2006; 244:1415–1420.
10) Kon Y, Iida T, Maruko I, Saito M. The optical coherence tomography-oph-
thalmoscope for examination of central serous chorioretinopathy with
precipitates. Retina. 2008; 28:864–869.
11) Iida T, Yannuzzi LA, Spaide RF, et al. Cystoid macular degeneration in
chronic central serous chorioretinopathy. Retina. 2003; 23:1–7.
12) Eandi CM, Chung JE, Cardillo-Piccolino F, et al. Optical coherence tomog-
raphy in unilateral resolved central serous chorioretinopathy. Retina.
2005; 25:417–421.
13) Wang M, Sander B, Lund-Andersen H, et al. Detection of shallow detach-
ments in central serous chorioretinopathy. Acta Ophthalmol Scand. 1999;
77:402–405.
14) Ojima Y, Hangai M, Sasahara M, et al. Three-dimensional imaging of the
foveal photoreceptor layer in central serous chorioretinopathy using
high-speed optical coherence tomography. Ophthalmology. 2007; 114:
2197–2207.
15) Matsumoto H, Kishi S, Otani T, et al. Elongation of photoreceptor outer
segment in central serous chorioretinopathy. Am J Ophthalmol. 2008;
145:162–168.
16) Fujimoto H, Gomi F, Wakabayashi T, et al. Morphologic changes in acute
central serous chorioretinopathy evaluated by Fourier-domain optical
coherence tomography. Ophthalmology. 2008; 115:1494–1500.
17) Shinojima A, Hirose T, Mori R, et al. Morphologic findings in acute central
serous chorioretinopathy using spectral domain-optical coherence to-
mography with simultaneous angiography. Retina. 2010; 30:193–202.
18) Matsumoto H, Sato T, Kishi S. Outer nuclear layer thickness at the fovea
determines visual outcomes in resolved central serous chorioretinopathy.
Am J Ophthalmol. 2009; 148:105–110.
19) Ooto S, Hangai M, Sakamoto A, et al. High-resolution imaging of resolved
central serous chorioretinopathy using adaptive optics scanning laser
ophthalmoscopy. Ophthalmology. 2010; 117:1800–1809.
20) Ojima Y, Tsujikawa A, Hangai M, et al. Retinal sensitivity measured with the
micro perimeter 1 after resolution of central serous chorioretinopathy.
Am J Ophthalmol. 2008; 146:77–84.
21) Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical
coherence tomography of the choroid in central serous chorioretinopa-
thy. Retina. 2009; 29:1469–1473.
Case 71 · Acute central serous chorioretinopathy: Smoke-stack pattern
139 5
Case 71 Acute central serous chorioretinopathy: Smoke-stack pattern

A 48-year-old male, OD, BCVA 1.0

A: Color fundus photograph in the right eye: At initial visit. One week after onset. SRD two times the diameter of the optic disc is noted in the macula.
B: FA in the right eye (45 seconds): A leakage point can be seen on the inferior temporal side of the parafovea. C: FA in the right eye (2 minute): Extensive
leakage in a smoke-stack pattern is visible. D: FA + IA in the right eye (12 minutes): Filling of the dye in the subretinal space shows fungiform pattern. On
IA stains abnormally in the superior macula due to choroidal hyperpermeability. E: IR + OCT horizontal scan of the right eye + enlarged version [red dashed
box]: During initial diagnosis. The photoreceptor outer segments exhibit relatively homogeneous reflectivity, and the thickness is also uniform. Elongation
is noted only in a small part of the OS. F: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: A flat PED ( ) is seen over the flac-
cid PED including the leakage point. (7) indicates Bruch’s membrane

Image interpretation points

It is common to see relatively homogeneous reflectivity and patient clinic. The patient had a history of CSC that had sponta-
thickness of the OS in CSC within 1–2 months of acute onset. neously resolved roughly 6 years earlier. This is a recurrence, but
In this case, the patient became aware of metamorphopsia and the abnormal OS findings were mild. A flaccid, flat PED could be
visual impairment one week before being referred to the out- seen in the area of the smoke-stack pattern leakage point.
 140 Chapter 5 · Central serous chorioretinopathy

Case 72 Acute central serous chorioretinopathy: A slowly leaking ink-blot pattern

A 43-year-old male, OS, BCVA 1.5

A: Color fundus photograph in the left eye: During initial diagnosis. Eight days after onset. SRD two times the diameter of the optic disc is noted in the
macula. B: FA in the left eye (80 seconds): During initial diagnosis. A leakage point can be seen on the nasal side of the macula. C: FA + IA in the left eye
(10 minutes): Fluorescein filling with typical ink-blot pattern is exhibited. ICG stains abnormally due to choroidal hyperpermeability, which is evident on
the temporal side of the macula. D: IR + OCT horizontal scan of left eye + enlarged version [red dashed box]: During initial diagnosis. The photoreceptor
OS is uniform in thickness but highly reflective ( ). E: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: During initial diagnosis.
A dome-shaped PED consistent with a round pooling of fluorescein can be seen. A part of the outer retinal layer is pulled down to attach on the RPE by the
adhesive force of fibrin and exhibits a dripping pattern. (7) indicates Bruch’s membrane. F: IR + OCT horizontal scan of left eye + enlarged version [red
dashed box]: Spontaneous remission of SRD 8 months after initial diagnosis. Corrected visual acuity has improved to 1.2. No foveal abnormalities are visi-
ble, but COST line irregularities can be seen on the nasal side of the parafovea. IS/OS and ELM irregularities are indistinct. (7) indicates Bruch’s membrane.

Image interpretation points

This is a case of spontaneous resolution of acute CSC 8 months The sub-RPE fluorescein pooling exhibits an ink-blot pattern.
after onset. In this case, fluid from the choroid leaked heavily There is likely less heavy leakage below the retina due to
within the PED resulting in the dome-shaped appearance and the fibrin restricting the flow of fluid. The photoreceptor OS
is also slowly leaking to underneath the retina causing a SRD. generally becomes highly reflective as time progresses.
Case 73 · Acute central serous chorioretinopathy: Intense leakage with ink-blot pattern
141 5
Case 73 Acute central serous chorioretinopathy: Intense leakage with ink-blot pattern

A 38-year-old male, OS, BCVA 0.7

A: Color fundus photograph in the left eye: During initial diagnosis. Four months after onset. Round (with a clear zone in the center) fibrin is noted in the
fovea. B: FA in the left eye (1 minute): During initial diagnosis. A leakage point can be seen on the superior nasal side of the fovea. A resolved leakage spot
is observed on the superior temporal side of the parafovea. C: FA + IA in the left eye (10 minutes): Fluorescein filling with an ink-blot pattern is visible. ICG
stains abnormally due to choroidal hyperpermeability, which can be observed in the macula. D: IR + OCT oblique scan of the left eye + enlarged version
[red dashed box]: During initial diagnosis. Scan passes through the enlarged, round area of dye filling. RPE defect ( ) can be seen at the border of the PED,
and a weakly reflective round area ( ), consistent with the clear on fundus photographs, is seen on the RPE defect surrounded by the moderately reflective
*
fibrin, indicating significant leakage from the defect. The PED has lost its tension. (7) indicates Bruch’s membrane. E: IR + OCT horizontal scan of the left
eye + enlarged version [red dashed box]: During initial diagnosis. Scan passes through the resolved leakage spots. Dome-shaped PED and fibrin clots ( )
in contact with the PED on the nasal side are noticeable. (7) indicates Bruch’s membrane. F: IR + OCT horizontal scan of the left eye + enlarged version [red
dashed box]: Two years after initial diagnosis. The SRD has disappeared and best-corrected visual acuity has improved to 1.5. No foveal abnormalities are
visible, but disappearance of the COST line on the temporal macula can be seen. No IS/OS or ELM irregularities are noted.

Image interpretation points

This is a case of a patient referred 4 months after onset of out pooling, the PED becomes flaccid. Fibrin clots have formed
symptoms. Laser photocoagulation was performed 1.5 months below the retina, and the leakage fluid forms weakly reflective
after the initial diagnosis and the SRD regressed the next day. cavities within the fibrin clots, which correspond to an ink-blot
Highly active leakage spots, as in this case, have significant pattern on FA. Dome-shaped PED is seen in the resolved leakage
leakage to below the retina via the defect point at the border spot, and subretinal leakage decreases due to fibrin plugs (just
of the PED. Since the leakage fluid flows through the PED with- before cessation).
 142 Chapter 5 · Central serous chorioretinopathy

Case 74 Chronic central serous chorioretinopathy: Choroidal thickening

A 42-year old male, OS, BCVA 0.4

A: Color fundus photograph in the left eye: Six months after onset. A shallow SRD and subretinal deposits can be seen in the macula. B: FA + IA in the left
eye (15 minutes): Diffuse hyperfluorescence (FA) and choroidal hyperpermeability (IA) are noted in and inferior to the fovea centralis. An atrophic tract is
observed in the inferior posterior pole. C: FA + OCT horizontal scan of the left eye, D: IR + EDI-OCT horizontal scan of the left eye: Thinning of the fovea and
a flat large PED are visible. There is choroidal thickening throughout the entire posterior pole. In the sites where choroidal thickening is most significant,
the anterior scleral border cannot be seen. E: 1 µm SS-OCT of the left eye: Choroidal thickening and a weakly reflective cavity ( ) between the sclera and
choroid are clearly visible over the entire macular area.

Image interpretation points

This is a case of chronic CSC with recurrence in both eyes for A weakly reflective cavity exists between the anterior scleral bor-
5 years. In this current presentation, the initial diagnosis was der and posterior choroid, and choroidal thickening in that area is
6 months after onset of symptoms. The extent of the choroidal significant. The RPE appears to be pushed forward by the choroidal
thickening could be clearly visualized using 1 µm SS-OCT thickening. Three months after initial diagnosis, the SRD has spon-
(swept source OCT). taneously regressed but the choroidal thickening remains.
Case 75 · Chronic central serous chorioretinopathy: A case of recurrence
143 5
Case 75 Chronic central serous chorioretinopathy: A case of recurrence

A 52-year-old female, OD, BCVA 0.9

A: Color fundus photograph in the right eye: During initial diagnosis. One week after onset. SRD 1.5 times the diameter of the optic disc can be seen.
B: FA + IA in the right eye (1 minute): During initial diagnosis. A leakage point visible on the inferior nasal side of the fovea centralis. C: FA + IA in the right
eye (11 minutes): Mild smoke-stack pattern leakage can be seen. D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: During
initial diagnosis. Uneven thickness and irregular posterior surface of the photoreceptor OS are already noticeable in the detached retina, and punctate highly
reflective dots exist in the internal margin of the ELM and in the photoreceptor OS. A flat PED can be seen over the entire fovea centralis. (7) indicates
Bruch’s membrane (Continued on the next page)
 144 Chapter 5 · Central serous chorioretinopathy

Case 75 Continuation

E: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Three months after initial diagnosis. Best-corrected visual acuity is 1.0. There
is no remission of the SRD, and elongation of the foveal OS is significant. F: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Ten
months after initial diagnosis. Best-corrected visual acuity is 1.5. The SRD that initially showed no remission for 7 months after initial diagnosis has started to
recede. The elongated foveal photoreceptor OS has shed and deposited on the RPE. The reattached IS/OS is distinct, but the COST line remains lost. G: IR + OCT
horizontal scan of the right eye: 12 months after initial diagnosis. Best-corrected visual acuity is 1.2. Recurrent exacerbation of the SRD. Hyperreflectivity of the
photoreceptor outer segment is noted. H: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 14 months after initial diagnosis.
Best-corrected visual acuity is 1.2. The SRD has almost disappeared, and the foveal IS/OS and COST lines have been restored, but they are still irregular.

Image interpretation points

This was a case of prolonged SRD over approximately 14 months, Long-term abnormalities were seen in the foveal photoreceptor
where there was repeated episodes of remission and exacer- OS, but the IS/OS and COST lines were quickly restored after
bation. The patient became aware of metamorphopsia one reattachment 14 months after initial diagnosis, therefore main-
week prior to being referred, but the irregular form of the taining good visual acuity. There are cases where visual acuity is
photoreceptor OS suggested the SRD was not a recent event. good despite a long detachment period as in this case. It appears
Elongation of the foveal photoreceptor OS, and OS tip that simply the length of the detachment period is not the only
shedding and deposition on the RPE were also observed. cause of poor visual prognosis.

chronic central serous chorioretinopathy

recurrence
Case 76 · Chronic central serous chorioretinopathy: Changes in the photoreceptor outer segment
145 5
Case 76 Chronic central serous chorioretinopathy: Changes in the photoreceptor outer segment

Right eye of a 41-year-old male with vision corrected to 0.8

A: Color fundus photograph in the right eye: During initial diagnosis. Four months after onset. A SRD two times the diameter of the optic disc is noted.
B: Enlarged version of A [red dashed box]: Subretinal deposits are visible in the fovea centralis. C: FA + IA in the right eye (11 minutes): During initial diagno-
sis. Weak leakage can be observed in the superior fovea centralis. ICG stains abnormally due to choroidal hyperpermeability in the fovea centralis. D: IR + OCT
horizontal scan of the right eye + enlarged version [red dashed box]: During initial diagnosis. SRD is seen. Highly reflective OS and dots corresponding to
foveal OS elongation and subretinal deposits on fundus photographs, respectively, are seen. A flat PED can be seen. (7) indicates Bruch’s membrane.
E: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Seven months after initial diagnosis. Best-corrected visual acuity is 0.9. There
is exacerbation of the amount of foveal OS elongation and sub- and intraretinal deposits. Shedding of the OS has started. F: IR + OCT horizontal scan of the
right eye + enlarged version [red dashed box]: Two years and 6 months after initial diagnosis. The IS/OS line has been restored, but thinning is evident in the
fovea centralis, and the COST line has not recovered over a wide macular area. (7) indicates Bruch’s membrane. Best-corrected visual acuity is 1.0.

Image interpretation points

This was a case of chronic CSC where 4 months had passed diagnosis, the SRD recurred, but disappeared again at 13 months,
since initial diagnosis, and significant changes could be seen in with no subsequent recurrences. Foveal thinning was observed
the foveal photoreceptor OS, although relatively good visual and although the COST had not been restored, the IS/OS line had
acuity was maintained. The area of leakage was within the clearly been restored despite being irregular. Resolution of good
fovea centralis, and upon follow-up 8 months after initial visual acuity occurred as well.
diagnosis, the SRD disappeared. Eleven months after initial
 146 Chapter 5 · Central serous chorioretinopathy

Case 77 Chronic central serous chorioretinopathy: Example of poor visual acuity

A 70-year-old male, OS, BCVA 0.1

A: Color fundus photograph in the left eye: During initial diagnosis. Four years after onset. SRD with the diameter of one optic disc and foveal subretinal
deposits are visible. B: Enlarged version of A [red dashed box]: A decrease in RPE pigment of the fovea centralis is observed. C: FA + IA in the left eye
(14 minutes): During initial diagnosis. Diffuse, weak fluorescein leakage is seen in the fovea centralis. ICG stains abnormally due to choroidal hyperperme-
ability over a wide area of the posterior pole. D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: During initial diagnosis.
A flat SRD can be seen. E: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box]: Two months after initial diagnosis. The SRD has dis-
appeared. Best-corrected visual acuity has improved to 0.6. The fovea centralis is thin and the IS/OS and COST lines within the (↔) area of the macula have
been lost. Reactive hyperplasia ( ) of the RPE can be seen. (7) indicates Bruch’s membrane. F: IR + OCT horizontal scan of the left eye + enlarged version
[red dashed box]: Six months after initial diagnosis. Thinning of the fovea centralis has progressed further; IS defects are noted, and best-corrected visual
acuity has once again decreased to 0.1. Almost no restoration of the IS/OS and COST lines can be seen within the (↔) area. (7) indicates Bruch’s membrane

Image interpretation points

This is a case of chronic CSC that has caused severe foveal de- the RPE. One month after initial diagnosis, reattachment was
struction. The patient became aware of metamorphopsia and achieved after performing PDT. With time, extensive foveal
visual impairment approximately 4 years prior to diagnosis. thinning as well as IS/OS and COST line disappearance became
During initial diagnosis, choroidal hyperpermeability was seen apparent. It is notable that foveal thinning and visual acuity loss
over a wide area, and significant abnormalities were visible in progressed even after reattachment.
Case 78 · Acute bullous retinal detachment: A typical example
147 5
Case 78 Acute bullous retinal detachment: A typical example

A 56-year-old male, OU, BCVA 1.5 OD and 0.9 OS

A: Color fundus photograph in the left eye, B: Color fundus photograph in the left eye: Multiple PEDs are seen in both eyes. Yellowish-white fibrin deposits
are visible on the superior arcade of the left eye. C: FA + IA in the right eye (8 minutes), D: FA + IA in the left eye (15 minutes): Multiple PEDs are evident in
both eyes. Significant fluorescein leakage from the PED is noted above the optic disc of the left eye. E: IR + OCT vertical scan of the left eye: A large SRD ( )
*
can be seen within the macula extending inferiorly. F: FA + OCT horizontal scan of the left eye: Note a large dome-shaped PED in the site of significant
fluorescein accumulation. (7) indicates Bruch’s membrane

Image interpretation points

Bullous retinal detachment differs from CSC in that there are initial diagnosis. Twenty days after initial diagnosis, PDT was
many (frequently more than 3) PEDs. The patient became performed on the left eye and the SRD disappeared and visual
aware of reduced visual acuity in the left eye 17 days before acuity improved to 1.5. There was no recurrence after 2 years.

pigment epithelial detachments; subretinal detachment

 149 6

Age-related macular degeneration

6.1 Drusen – 153

6.2 Pigment epithelial detachment – 155

6.2.1 References – 156

Case 79 Soft drusen: A typical example – 157

Case 80 Soft drusen: Fused drusen – 158

Case 81 Cuticular drusen combination vitelliform detachment – 159

Case 82 Cuticular drusen: Fellow eye of case 81 – 160

Case 83 Reticular pseudodrusen: Fellow eye of RAP – 161

Case 84 Reticular pseudodrusen: Case with atrophic age-related macular

degeneration (atrophic AMD) – 162

Case 85 Reticular pseudodrusen and soft drusen – 163

Case 86 Serous pigment epithelial detachment: Case without CNV – 164

Case 87 Pigment epithelial detachment: Reactive proliferation of retinal

pigment epithelial cells – 165

Case 88 Drusenoid PED: Case where CNV is suspected – 166

Case 88 17 months later – 167

Case 89 Large pigment epithelial detachment: Case where CNV

is suspected – 168

Case 90 Pigment epithelial detachment: Case with type 1 CNV ① – 169

Case 91 Pigment epithelial detachment: Case with type 1 CNV ② – 170

Case 92 Large pigment epithelial detachment: Case where CNV

is present – 171

Case 92 Continuation – 172

6.3 Atrophic age-related macular degeneration – 173

6.3.1 References – 175
Case 93 Atrophic age-related macular degeneration:
A typical example – 176

Case 94 Atrophic age-related macular degeneration: Atrophic lesions

of various sizes – 177

Case 95 Atrophic age-related macular degeneration:

Fellow eye of PCV – 178

6.4 Choroidal neovascularization and exudative age-related macular

degeneration – 179
6.4.1 References – 180

Case 96 Exudative age-related macular degeneration:

Type 1 CNV with a SRD – 181

Case 97 Exudative age-related macular degeneration:

Type 1 CNV with low activity – 182

Case 98 Exudative age-related macular degeneration:

Type 1 CNV with relatively strong exudative changes – 183

Case 98 Six months later – 184

Case 99 Exudative age-related macular degeneration: Case with extensive

Type 1 and 2 CNV exudative changes – 185

Case 99 Six months after treatment with anti-VEGF treatment – 186

Case 100 Exudative age-related macular degeneration: Type 1 and 2 CNV

with extensive serous retinal detachment – 187

Case 101 Exudative age-related macular degeneration: Type 1 and 2 CNV

with cystic changes – 188

Case 102 Exudative age-related macular degeneration:

Type 2 CNV localized in the fovea centralis – 189

Case 103 Exudative age-related macular degeneration:

Type 2 CNV with strong exudative changes – 190

6.5 Polypoidal choroidal vasculopathy – 191

6.5.1 References – 193

Case 104 Polypoidal choroidal vasculopathy: Small lesions – 194

 151

Case 105 Polypoidal choroidal vasculopathy: Case confused with central

serous chorioretinopathy – 195

Case 105 After treatment with anti-VEGF formulation – 196

Case 106 Polypoidal choroidal vasculopathy: Fibrin deposits ① – 197

Case 107 Polypoidal choroidal vasculopathy: Fibrin deposits ② – 198

Case 108 Polypoidal choroidal vasculopathy:

A large branching vascular network – 199

Case 109 Polypoidal choroidal vasculopathy:

Large foveal cystoid space – 200

Case 109 Enlargement of hemorrhagic pigment epithelial

detachment – 201

Case 109 Enlargement of the branching vascular network – 202

Case 110 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment

epithelial detachment ① – 203

Case 111 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment

epithelial detachment ② – 204

Case 111 Spontaneous remission – 205

Case 112 Polypoidal choroidal vasculopathy: Optic disc type – 206

Case 112 Continuation – 207

Case 113 Polypoidal choroidal vasculopathy: Polypoidal lesions

and pigment epithelial detachment – 208

Case 114 Polypoidal choroidal vasculopathy: Tomographic notch sign – 209

Case 115 Polypoidal choroidal vasculopathy: Case where the branching

vascular network has detached – 210

Case 116 Polypoidal choroidal vasculopathy: A massive lesion – 211

6.6 Retinal angiomatous proliferation – 212

6.6.1 References – 213

Case 117 Retinal angiomatous proliferation: Stage 1 – 214

Case 118 Retinal angiomatous proliferation: Stage 2A – 215

Case 119 Retinal angiomatous proliferation: Stage 2B ① – 216

Case 120 Retinal angiomatous proliferation: Stage 2B ② – 217

Case 121 Retinal angiomatous proliferation: Stage 3 – 218

Case 121 After treatment with anti-VEGF treatment – 219

6.7 Malattia leventinese – 220

6.7.1 References – 220

Case 122 Malattia leventinese: A typical example – 221

6.8 Idiopathic choroidal neovascularization – 223

6.8.1 References – 223

Case 123 Idiopathic choroidal neovascularization: A fresh case – 224

Case 124 Idiopathic choroidal neovascularization:

Envelopment by RPE cells – 225

Case 124 After treatment with anti-VEGF formulation – 226

Case 125 Idiopathic choroidal neovascularization:

The scarring process – 227

Case 125 Course without treatment – 228

6.1 · Drusen
153 6
6.1 Drusen accompanied by choroidal neovascularization (CNV). It should
be noted that, in cases of drusenoid PED, serous retinal detach-
Background ment (SRD) can be seen below the sensory retina between large
Drusen are the general term for small, round, yellowish-white drusen. These findings do not indicate the presence of CNV,
slightly elevated lesions that can be seen in the ocular fundus as but are instead due to the retina being lifted up by the drusen(6).
a result of age-related changes. Drusen are generally classified into According to the International Classification of AMD, eyes with
soft drusen and hard drusen where soft drusen are a significant multiple soft drusen are diagnosed as having early ARM (early
risk factor of age-related macular degeneration (AMD) along with age-related maculopathy) and can easily develop exudative or
hyperpigmentation of the retinal pigment epithelium (RPE)(1–3). atrophic AMD.
There are peculiar forms of drusen, such as cuticular drusen
(formerly known as basal laminar drusen) and reticular pseudo- Cuticular drusen
drusen. Cuticular drusen (also basal laminar drusen) are another spe-
cific kind of drusen. These drusen are relatively rare in Japan but
Soft drusen and hard drusen can be seen in cases of familial drusen (malattia leventinese).
Various classifications are used for drusen, among which the Countless hyperfluorescent dots are distinctive findings that can
classification based on drusen size (soft drusen v.s. hard drusen) be seen on FA imaging (milky-way or stars-in-the-sky). The loca-
has been most commonly used. If the diameter of the drusen is tion of these drusen is beneath the RPE, which is the same as
63 µm or above (with the diameter of the vein entering the typical drusen. The cause of these small hyperfluorescent dots on
optic disc margin at 125 µm as a reference), they are soft drusen. FA is likely damages to the RPE cells as a result of steep protru-
Below this size they are classified as hard drusen(4). As they are sion of drusen into the RPE. These damaged sites exhibit hyper-
differentiated by size alone, there is no actual difference between fluorescence due to window defects. Since Japanese people some-
soft and hard drusen. times have a high melanin content in their RPE cells, stars-in-
the-sky findings are not seen so often.
OCT findings In typical cases, small, steep protrusions in the RPE known
As shown in . Fig. 6-1, soft drusen appear as protrusions of the as »sawtooth figure« are visible on OCT. The case shown in . Fig.
RPE into the retina and as a straight thin line posterior to the 6-2 is of familial drusen where countless small, hyperfluorescent
elevated RPE (▶) on OCT. This thin line is thought to be Bruch’s dots are scattered around the foveal lesions. When observed with
membrane(5). In general, when the RPE is elevated from Bruch’s OCT, these protruding lesions can be seen spreading not only to
membrane [pigment epithelial detachment (PED) or drusen], the outer nuclear and outer plexiform layer but also to the inner
the straight line of Bruch’s membrane becomes clearly visible. nuclear layer.(7, 8). Cuticular drusen can cause vitelliform detach-
In contrast, when there is no RPE elevation (the normal state), ment (yolk-like retinal detachment)(9, 10).
the line of Bruch’s membrane is not delineated. Detecting
Bruch’s membrane line in this way can be considered an ab- Reticular pseudodrusen
normal finding. In recent years, reticular pseudodrusen (or reticular drusen) have
The space between the elevated RPE and Bruch’s membrane become a topic of interest. According to a report on a Beaver
corresponds to the contents of the drusen. As shown in . Fig. 6-1, Dam study, the prevalence at baseline of these drusen was 0.7%
the contents are sometimes moderately reflective and sometimes of the total population, more common in women than in men,
barely reflective at all. and the cumulative incidence over 15 years was 3%(11). The pres-
ence or absence of reticular drusen was determined with only
Drusenoid PED fundus photographs in this study, however, the frequency of
Large soft drusen cannot be distinguished from PED on bio- identification may have been even higher if fundus autofluores-
microscopic or OCT observation. Confluent large soft drusen cence or OCT had been used. The importance of this type of
are known as drusenoid PED. Drusenoid PED is frequently drusen has been growing with the increase in elderly individuals.

. Fig. 6-1 OCT image of typical drusen

A: Drusen is seen as protrusions of the RPE. (▶) indicates Bruch’s membrane. B: Enlarged version of A. Part of the photoreceptor inner and outer segment
junction on the drusen is becoming indistinct ( ) and the outer retinal layers on the drusen are atrophic.
 154 Chapter 6 · Age-related macular degeneration

. Fig. 6-2 Malattia leventinese

A: 1-minute, 38-second FA. Countless small, hyperfluorescent dots can be seen around the macula. B: OCT vertical
scan, cuticular drusen are seen as tall protrusions from Bruch’s membrane of the RPE.

6 Reticular pseudodrusen have been documented for a long ticular pseudodrusen into three stages based on these OCT
time, but their properties have become clearer with characteriza- findings (. Fig. 6-4)(12). Reticular pseudodrusen are considered
tion based on OCT findings(8). In OCT images, deposits on the closely associated with the onset of exudative and atrophic AMD.
apical side of RPE can be seen as triangular shapes, which differ Reticular drusen can occur in combination with normal
from typical drusen (. Fig. 6-3). Zweifel et al. have divided re- pseudodrusen.

. Fig. 6-3 Reticular pseudodrusen

Highly reflective deposits are seen between the RPE and sensory retina. Stage 1 reticular pseudodrusen can be seen in the fovea centralis and two Stage 3
reticular pseudodrusen can be seen to the right of the fovea. This image was acquired with a 1,050 nm wavelength prototype swept-source OCT.

. Fig. 6-4 Stage classification of reticular pseudodrusen

A is the photoreceptor inner and outer segment junction (IS/OS) line, B is the COST line, and C indicates the RPE. In Stage 1, deposits do not push up the
line of the IS/OS line. In Stage 2 the IS/OS line is pushed up into the retina. In Stage 3 the deposits pass through this line.
(Modified according to Zweifel SA, et al. Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology. 2010; 117: 303-312)
6.2 · Pigment epithelial detachment
155 6
6.2 Pigment epithelial detachment proliferation (RAP). According to this report, visual prognosis
varies greatly based on the type of PED. All cases of PED accom-
Pigment epithelial detachment (PED) is the state in which the panied by vascular PED, hemorrhagic PED, and RAP eventually
RPE detach from Bruch’s membrane between the RPE basal become scar lesions. On the other hand, the prognosis for pseu-
lamina and inner collagen fiber layer of Bruch’s membrane. The do-vitelliform PED and confluent drusen is relatively good,
origin of the fluid accumulated between the detached RPE whereas serous PED falls into an intermediate category of prog-
and Bruch’s membrane is thought to be the choroid according nosis (. Table 6-1).
to Gass’s theory(2), and the sensory retina according to Bird and PED accompanied by polypoidal choroidal vasculopathy
Marshall’s theory(13). When CNV is present, CNV itself and (PCV) is also significant in Japan. About half the cases of PCV
exudations derived from CNV are depicted in OCT images as an are known to have PED during initial diagnosis(15). . Fig. 6-5
origin of the fluid. is PED seen in PCV. Two successive PEDs can be seen, but the
The report by Hartnett et al. is well known as a traditional reflectivity inside the two PEDs differs greatly. The PED on the
classification for PED(14). In this classification, PED is divided left is weakly reflective and the adjacent one on the right is
into pseudo-vitelliform PED, confluent drusen, serous PED, vas- moderately reflective. In general, the content of a PED exhibiting
cular PED, hemorrhagic PED and retinal vascular abnormality; low reflectivity on OCT is not fibrovascular, whereas the content
here vascular PED and hemorrhagic PED can be considered the of a PED exhibiting moderate or high reflectivity is considered
same. PED accompanied by retinal vascular abnormality is cur- fibrovascular. Given its high reflectivity, the PED on the right side
rently described as PED accompanied by retinal angiomatous of this image is thought to have CNV (. Fig. 6-5).

. Table 6-1 Classification and natural course of pigment epithelial detachment

Type of PED Outcome Follow-up period

Unchanged Atrophic lesions Scar lesions

Pseudo-vitelliform PED 40% 60% 0% 21 months

Confluent drusen 22% 65% 9% 41 months

Serous PED 28% 38% 34% 30 months

Vascular PED 0% 0% 100% 36 months

Hemorrhagic PED 0% 0% 100% 14 months

Retinal vascular abnormality 0% 0% 100% Immediate laser treatment

(Modified according to Hartnett ME, et al. Classification of retinal pigment epithelial detachments associated with drusen. Graefes Arch Clin Exp
Ophthalmol. 1992; 230: 11-19)

. Fig. 6-5 PED and the reflectivity intensity of its contents

The contents of PEDs have various reflectivity intensities. In general, if it is weakly reflective, then no CNV is thought to exist, whereas in cases where mode-
rate or high reflectivity is exhibited, CNV is thought to be present. In this figure, the right fibrovascular PED includes CNV. (▶) indicates Bruch’s membrane.
 156 Chapter 6 · Age-related macular degeneration

6.2.1 References

1) Gass JDM. Pathogenesis of disciform detachment of the neuroepithelium.

III. Senile disciform macular degeneration. Am J Ophthalmol. 1967; 63:617–
644.
2) Gass JD. Drusen and disciform macular detachment and degeneration.
Arch Ophthalmol. 1973; 90:206–217.
3) The International ARM Epidemiology Study Group. An international clas-
sification and grading system for age-related maculopathy and age-relat-
ed macular degeneration. Surv Ophthalmol. 1995; 39:367–374.
4) Klein R, Davis MD, Magli YL, et al. The Wisconsin age-related maculopathy
grading system. Ophthalmology. 1991; 98:1128–1134.
5) Pircher M, Goetzinger E, Findl O, et al. Human macula investigated in vivo
with polarization-sensitive optical coherence tomography. Invest Ophthal-
mol Vis Sci. 2006; 47:5487–5494.
6 6) Sikorski BL, Bukowska D, Kaluzny JJ, et al. Drusen with accompanying fluid
underneath the sensory retina. Ophthalmology. 2011; 118:82–92.
7) Spaide RF, Curcio C. Drusen characterization with multimodal imaging.
Retina. 2010; 30:1441–1454.
8) Souied EH, Leveziel N, Letien V, et al. Optical coherent tomography fea-
tures of malattia leventinese. Am J Ophthalmol. 2006; 141:404–407.
9) Gass JD, Jallow S, Davis B. Adult vitelliform macular detachment occurring
in patients with basal laminar drusen. Am J Ophthalmol. 1985; 99:445–459.
10) Freund KB, Laud K, Lima LH, et al. Acquired vitelliform lesions. correlation
of clinical findings and multiple modality analyses. Retina. 2011; 31:13–25.
11) Klein R, Meuer SM, Knudtson MD, The epidemiology of retinal reticular
drusen. Am J Ophthalmol. 2008; 145:317–326
12) Zweifel SA, Spaide RF, Curcio CA, et al. Reticular pseudodrusen are sub-
retinal drusenoid deposits. Ophthalmology. 2010; 117:303–312.
13) Bird AC, Marshall J. Retinal pigment epithelial detachments in the elderly.
Trans Ophthalmol Sco U K. 1986; 105:674–682.
14) Hartnett ME, Weiter JJ, Garsd A, et al. Classification of retinal pigment
epithelial detachments associated with drusen. Graefes Arch Clin Exp
Ophthalmol. 1992; 230:11–19.
15) Tsujikawa A, Sasahara M, Otani A, et al. Pigment epithelial detachment in
polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007; 143:102–111.
Case 79 · Soft drusen: A typical example
157 6
Case 79 Soft drusen: A typical example

A 63-year-old female, OD, BCVA 0.8

A: Color fundus photograph in the right eye, B: Enlarged version of A: Small drusen () can be seen. The diameter is larger than the diameter of the retinal
vein that enters the optic disc, so they are soft drusen. C: IR + OCT horizontal scan of the right eye: The drusen can be seen as protrusions of the RPE.
D: Enlarged version of C [red dashed box]: The RPE protrusions are clearly visible ( ). E: Even larger version of D: RPE proliferation ( ) in the apex of the
drusen is visible. The RPE proliferation is in contact with the photoreceptor inner and outer segment junction (IS/OS). A part of the COST line is disrupting
immediately nasal to the junction (▶). The ELM is normal despite an anterior projection being visible. A reflectivity thought to be Bruch’s membrane
is only slightly visible at the base of the drusen (immediately above (▶)).

Image interpretation points

This is a case of typical, small soft drusen. Drusen are frequent In addition, near the apex of the drusen, the gap between the
findings in aged patients. In this case a detailed observation IS/OS line and RPE is shortened. In this case, the inside of the
with OCT allowed visualization of the disruption of COST line. drusen appear moderately reflective.
 158 Chapter 6 · Age-related macular degeneration

Case 80 Soft drusen: Confluent drusen

A 75-year-old male, OD, BCVA 0.8

A: Color fundus photograph in the right eye: Large drusen are numerous (). B: IA in the right eye (5 minutes): The drusen appear hypofluorescent on IA.
CNV is not detected. C: FA + OCT horizontal scan of the right eye: The content of the drusen appears moderately reflective. The posterior vitreous cortex is
visible ( ) D: Enlarged version of C [red dashed box]: A straight line representing Bruch’s membrane is seen at the base of the drusen (▶). Parts of the ELM,
IS/OS and COST lines are disrupting in the apex of the drusen or the PED ( ). The outer retinal layer structure of the fovea centralis is being preserved as
normal (red dashed circle).

Image interpretation points

Large drusen are pathologically the same as PED. In this case, retinal layer structure in the fovea centralis is relatively healthy.
damage to the outer retinal layers in contact with the apex of While the content of the drusen is exhibiting fairly homogeneous
the temporal largest druse is noticeable even though visual moderate reflectivity, the presence of CNV is unlikely. This is con-
acuity is somewhat preserved at 0.8. As shown in the red sistent with CNV not being seen on IA.
dashed circle in D, the may be due to the fact that the outer
Case 81 · Cuticular drusen: Case with vitelliform detachment
159 6
Case 81 Cuticular drusen: Case with vitelliform detachment

A left eye of a 79-year-old female, OS, BCVA 1.2

A: Color fundus photograph in the left eye: A accumulation of large soft drusen can be seen temporal to the optic disc. Yellow spots about 1/2 the diameter
of the optic disc are present in the fovea centralis. Small soft drusen are scattered temporal to the fovea centralis. B: FAF in the left eye: Relatively strong
hyperfluorescence is visible temporal to the fovea centralis. The fovea centralis is exhibiting round hypofluorescence, and small hypofluorescent foci are
scattered around it. C: FA in the left eye (10 minutes, 18 seconds): Relatively strong hyperfluorescence can be seen nasal to the fovea centralis. Countless
small hyperfluorescent dots are visible in the temporal macula, exhibiting a »stars-in-the-sky« image. D: IA in the left eye (10 minutes, 18 seconds): Hypo-
fluorescence is observed in the inferior fovea, which looks like a niveau. Relatively large hypofluorescent foci and small hyperfluorescent foci are mixed
together and scattered around the fovea centralis. E: IR + OCT horizontal scan of the left eye: Anterior centrifugal traction towards the fovea centralis as a
result of the posterior vitreous cortex ( ) is appreciated (perifoveal PVD is occurring). The foveal retina has detached (vitelliform detachment) and a deposit,
the result of shedding of the photoreceptor outer segment, can be seen (*). Typical cuticular drusen images could not be appreciated with this scan.

Image interpretation points

Cuticular drusen were also referred to as basal laminar drusen. in composition. Therefore, it is now common to use the term
At one time, cuticular drusen were thought to occur due to cuticular drusen. On fluorescein angiography (FA), cuticular
nodular thickening of the RPE basal lamina, and their location drusen exhibit a distinctive pattern known as »stars-in-the-sky«.
was thought to differ from typical soft drusen. Later, it was In addition, they can be combined with acquired vitelliform
revealed that both existed between the RPE basal lamina lesions, as seen in this case.
and Bruch’s membrane, and that there were no differences
 160 Chapter 6 · Age-related macular degeneration

Case 82 Cuticular drusen: Fellow eye of case 81

A 79-year-old female, OD, BCVA 1.2

A: Color fundus photograph in the right eye: Right eye of case 81. Large soft drusen and cuticular drusen can be seen similar to the left eye. B: FA in the
right eye (6 minutes, 8 seconds): The cuticular drusen are exhibiting a »stars-in-the-sky« pattern. Hyperfluorescence and hypofluorescence are mixed in the
fovea centralis due to acquired vitelliform lesions. C: IA in the right eye (6 minutes, 8 seconds): The fovea centralis is exhibiting hypofluorescence. Small
hypofluorescent foci are scattered over the posterior pole. D: OCT horizontal scan of the right eye: Perifoveal PVD is observed, similar to the left eye. There
is a vitelliform detachment in the fovea centralis. E: Enlarged version of D [white dashed box]: A »saw-tooth pattern« is seen in the blue dashed circle area.

Image interpretation points

Cuticular drusen have been known to be combined with a result of the posterior vitreous detachment can be seen in
acquired vitelliform lesions, as seen in case 81. In this case, both eyes. Hence, the possibility that this traction is causing the
anterior centrifugal traction towards the fovea centralis as acquired vitelliform lesions cannot be denied.
Case 83 · Reticular pseudodrusen: Fellow eye of RAP
161 6
Case 83 Reticular pseudodrusen: Fellow eye of RAP

A 78-year-old female, OS, BCVA 1.2

A: Color fundus photograph: Numerous drusen are visible. A reticular pattern is seen in the deep retinal layers within the white dashed circles. B: FAF in
the left eye: Some drusen are exhibiting hyperfluorescence while others are exhibiting hypofluorescence. Reticular autofluorescence abnormalities can
be observed within the white dashed circle in the superotemporal area. C: Enlarged version of B [red dashed box]: Hypofluorescence corresponding to
reticular pseudodrusen is shown. D: FA + OCT horizontal scan of the left eye: Small PED and reactive proliferation of RPE cells is noticeable in the inferior
macula ( ). Temporal to these lesions, highly reflective features are seen on the RPE to penetrate the ELM line. These are reticular pseudodrusen.
E: Enlarged version of D [red dashed box]: Stage 2 and 3 reticular pseudodrusen are seen ( ).

Image interpretation points

In soft drusen, the RPE protrudes into the retina and deposits important for diagnosis, it is important to capture a wide area
can be seen underneath the RPE; by contrast, in reticular of posterior pole particularly including the fovea and supero-
pseudodrusen, deposits are characteristically seen on the RPE. temporal region. Reticular pseudodrusen can also sometimes
Reticular pseudodrusen is a pathological condition that has be seen nasally as well. In this case, RAP was seen in the fellow
recently received a lot of attention. While OCT is extremely eye.
 162 Chapter 6 · Age-related macular degeneration

Case 84 Reticular pseudodrusen: Case with atrophic age-related macular degeneration

(atrophic AMD)
An 84-year-old female, OD, BCVA 0.3

A: Color fundus photograph in the right eye: Large geographic atrophic lesions can be seen in the macula where choroidal macrovessels are fairly translu-
cent. Reticular lesions are exhibited in the white dashed circle. B: Red-free imaging in the right eye: A reticular structure is visible in the white dashed circle.
White spots are seen around the fovea centralis. C: IR + OCT horizontal scan of the right eye: Reticular pseudodrusen can be seen within the blue dashed
box. No RPE reflectivity can be seen within the red dashed box. D: Enlarged version of C [blue dashed box]: Stage 2 and 3 reticular pseudodrusen are seen
(▶). E: Enlarged version of C [red dashed box]: No significant RPE reflectivity can be seen ( ). In addition, the outer retinal layers are seen to be preserved
only on the left margin of the image and the photoreceptor cells have almost entirely disappeared. This is atrophic AMD.

Image interpretation points

This is a case of reticular pseudodrusen accompanying atrophic ly rare to see them in combination with PCV. Choroidal signal
AMD. When examining the image more closely, reticular pseudo- enhancement occurs due to RPE atrophy in the geographic
drusen can be found at an unexpectedly high frequency. They atrophic lesion area where the choroid is seen more clearly.
often accompany atrophic AMD and RAP, however, it is relative-
Case 85 · Reticular pseudodrusen and soft drusen
163 6
Case 85 Reticular pseudodrusen and soft drusen

A 74-year-old male, OD, BCVA 1.2

A: Color fundus photograph in the right eye: Soft drusen can be seen in the macular area around the fovea centralis. Drusen up to 250 µm in size are
present along with other slightly smaller ones. Relatively small, uniform size of yellowish-white spots are visible superotemporally. These are reticular
pseudodrusen. B: IA + OCT oblique scan of the right eye: In the late stage IA image, the soft drusen are exhibiting hypofluorescence. The reticular pseudo-
drusen are also hypofluorescent. In the OCT image, it is clear that the reticular pseudodrusen and soft drusen are coexisting. The coexistence of both
drusen is actually common, and not unusual. C: Enlarged version of B [red dashed box]: The difference between reticular pseudodrusen ( ) and soft
drusen (▶) is clear. The two can be distinguished more easily using OCT than with an ophthalmoscope.

Image interpretation points

The OCT findings of reticular pseudodrusen and soft drusen posterior to the RPE. In this case, the content of the soft drusen
are completely different. The reticular pseudodrusen appear as appears moderately reflective, and findings demonstrating CNV
deposits anterior to the RPE, while soft drusen are deposits cannot be found in this case.
 164 Chapter 6 · Age-related macular degeneration

Case 86 Serous pigment epithelial detachment: Case without CNV

A 49-year-old female, OS, BCVA 0.7

A: Color fundus photograph in the left eye: A PED about 3/4 the diameter of the optic disc is visible. B: FA in the left eye (1 minute, 6 seconds): A part of
the PED appears hyperfluorescent. C: IA in the left eye (1 minute, 6 seconds): CNV cannot be detected. D: FA + OCT horizontal scan of the left eye: The con-
tent of the PED is weakly reflective and no CNV reflectivity is appreciated. (▶) indicates Bruch’s membrane. Highly reflective dots, thought to originate
from the migrated RPE cells, can be seen in the outer nuclear layer. E: FA + OCT vertical scan of the left eye: The posterior vitreous cortex slightly detached
from the ILM can be seen ( ). F: Enlarged version of E [red dashed box]: Bruch’s membrane (▶) and a highly reflective feature, likely RPE cell proliferation,
( ) beneath the RPE can be seen.

Image interpretation points

Bruch’s membrane is clearly seen at the base of the PED (▶). be proliferated RPE ( ). The ELM and IS/OS lines above the PED
The high reflectivity that can be seen posterior to the PED may are well preserved.
Case 87 · Pigment epithelial detachment: Reactive proliferation of retinal pigment epithelial cells
165 6
Case 87 Pigment epithelial detachment: Reactive proliferation of retinal pigment epithelial cells

A 78-year-old female, OD, BCVA 0.9

A: A fundus photograph in the right eye: A PED about 1.5 the diameter of the optic disc can be seen (). B: in the right eye (1 minute, 4 seconds) FA:
A part of the PED appears hyperfluorescent. CNV is not detected on FA. C: IR + OCT vertical scan of the right eye: A flat PED can be seen. D: Enlarged
version of C [red dashed box]: A straight line representing Bruch’s membrane can be seen on the posterior aspect of the PED (▶). The content of the PED
is homogeneous and moderately reflective. Findings showing proliferation of the RPE can be seen in the center of the PED ( ). This kinds of findings
are frequently seen in relatively old PED. Small drusen exist adjacent to the PED (▶).

Image interpretation points

The »straight highly reflective line« thought to originate from figure D, but the IS/OS is not always clearly defined in the area
Bruch’s membrane cannot be detected unless the RPE detaches where RPE reactive proliferation has occurred ( ). As a result, we
from Bruch’s membrane. In figure D of this case, this line can can infer that the sensory retina on the PED undergoes partial
only be seen in the area of small drusen (▶), and under the damage.
large PED. The ELM can be traced almost from end-to-end in
 166 Chapter 6 · Age-related macular degeneration

Case 88 Drusenoid PED: Case where CNV is suspected

An 84-year-old male, OS, BCVA 0.9

A: Color fundus photograph in the left eye: Soft drusen of various sizes and PED are visible. B: IR + OCT horizontal scan of the left eye: The line indicating
Bruch’s membrane is seen over a wide area from the area near the optic disc to the area temporal to the fovea centralis. The content of the PED and drusen
varies from weakly reflective to moderately reflective. C: Enlarged version of B [red dashed box]: Flat RPE protrusions with irregular undulation are seen nasal
to the large PED (▶). This suggests the presence of CNV. High reflectivity due to RPE proliferation anterior to the large PED is exhibited ( ). The reflectivity of
the content of the PED is not homogeneous; it is relatively weakly reflective near the fovea centralis. A SRD (*) can be seen in the nasal side of the fovea cen-
tralis. The content of the drusen temporally is moderately reflective. These are also findings that suggest the presence of CNV. (Continued on the next page)

Image interpretation points

This is a case where it is difficult to determine if CNV is occur- RPE and Bruch’s membrane strongly suggest the presence of
ring. Here, exudative changes primarily cannot be seen with CNV. An extremely careful follow-up is necessary in cases like
an ophthalmoscope. The undulating RPE protrusions near the this.
optic disc and the relatively strong reflectivity between the
Case 88 · Drusenoid PED: Case where CNV is suspected
167 6
Case 88 17 months later

An 84-year-old male, OS, BCVA 0.4

D: Color fundus photograph in the left eye: faint retinal hemorrhage can be seen ( ). E: IA in the left eye: Polypoidal lesions are observed inferotemporal
to the optic disc ( ). In addition, an abnormal vascular network exists superiorly to this (▶). This is a typical image of PCV. F: IA + OCT horizontal scan of
the left eye: Flat, undulating RPE protrusions are visible in the area corresponding to the abnormal vascular network near the optic disc. This feature is also
known as the »double layer sign«, but this term dates back to the era of time-domain OCT. G: IA + OCT oblique scan of the left eye: This is a scan passing
through polypoidal lesions. Drusen are seen further above temporal to the large PED (▶). H: Enlarged version of G [red dashed box]: The polypoidal lesions
are visible as steep RPE protrusions ( ). The reflectivity of its content differs from the reflectivity of the drusen located superotemporally. We can see that
the content of the large PED is not homogeneous.

Image interpretation points

PCV developed 17 months after initial diagnosis. It would be temporally, and to correlate these features with the CNV area
useful to compare the moderate reflectivity of the polypoidal detected on IA.
lesions with the weak reflectivity within the large PED supero-

drusenoid pigment epithelial detachment

 168 Chapter 6 · Age-related macular degeneration

Case 89 Large pigment epithelial detachment: Case where CNV is suspected

A 76-year-old male, OS, BCVA 0.8

A: Left eye fundus photograph: Large soft drusen are scattered over the entire posterior pole. A large PED is visible in the macular area including the
fovea centralis. There is RPE pigmentation in the center of the PED. B: IR + OCT horizontal scan of the left eye: A large PED is seen. C: Enlarged version of B
[red dashed box]: The reactive RPE proliferations are exhibiting high reflectivity in the sensory retina ( ). They are located both anteriorly and posteriorly
to the ELM. The structures below these features are not well defined due to high reflectivity. While the RPE appears to be disrupting, this is likely due to
shadows caused by RPE proliferations. Although it is a relatively tall PED, but Bruch’s membrane can be visualized over almost the entire length. Part of
the PED content appears to have a reflective structure suggesting the presence of CNV, but it cannot be confirmed only based on OCT imaging.

Image interpretation points

Highly reflective structures such as blood vessels, hard exudates, and pigmentation, can cause shadows which obscure
visualization of other objects below.
Case 90 · Pigment epithelial detachment: Case with type 1 CNV
169 6
Case 90 Pigment epithelial detachment: Case with type 1 CNV ①

A 73-year-old male, OS, BCVA 0.4

A: FA in the left eye (1 minute, 21 seconds): Annular hyperfluorescent foci along the circumference of the PED about 1.5 times the diameter of the optic
disc is observed in and around the fovea centralis. Within this area, there is also hyperfluorescence due to CNV roughly the diameter of the disc. B: IA in the
left eye (1 minute, 21 seconds): The PED is exhibiting hypofluorescence. Reticular hyperfluorescence representing CNV is clearly seen in the PED. C: IR +
OCT horizontal scan of the left eye: The PED is clearly visible. The choroid is poorly visible due to a decrease in penetration of OCT probe light in the PED
area ( ). D: Enlarged version of C [red dashed box]: The CNV is moderately reflective ( ). The IS/OS is not well visualized in the PED area.

Image interpretation points

This is the case of a Caucasian male patient. There are not convex as seen in this case, it is difficult to determine if the
many cases of Japanese people where CNV is clearly visible IS/OS is actually or if it is obscure just because of the decrease
within a PED. Even in PCV, Type 1 CNV typically grows along in light reflection/backscattering due to the oblique position
the posterior surface of the RPE as in this case. of the retina against the OCT probe light.
It is useful to correlate disruption of foveal outer retinal struc-
ture with visual acuity loss. However, when the retina becomes
 170 Chapter 6 · Age-related macular degeneration

Case 91 Pigment epithelial detachment: Case with type 1 CNV ②

A 64-year-old female, OD, BCVA 0.7

A: Color fundus photograph in the right eye: A PED roughly the diameter of the optic disc is observed in the fovea centralis ( ). Multiple soft drusen can
be seen superior to the PED. Exudative changes in the sensory retina are mild. B: FA in the right eye (5 minutes, 30 seconds): Fluorescein has accumulated
in the PED, which exhibits hyperfluorescence ( ). In the superior parafovea, faint hyperfluorescence and a stronger, granular hyperfluorescence is visible.
C: IA in the right eye (5 minutes, 30 seconds): The PED is hypofluorescent. Branching CNV is seen in the area exhibiting faint hyperfluorescence on FA ( ).
D: IA + OCT vertical scan of the right eye: Undulations of the RPE are noticeable at the edge of and superior to the PED. The space between the undulating
RPE and Bruch’s membrane is moderately reflective. E: Enlarged version of D [red dashed box]: Bruch’s membrane is clearly visible on the posterior aspect
of the abnormal RPE (▶). Extension of CNV inside the PED is not clear on this scan ( ).

Image interpretation points

In this case, the IS/OS cannot be seen in the sensory retina simply a finding due to optical properties. This image undeniably
above the PED. It is not clear if this represents damage to the shows that CNV may be present over entire posterior aspect of
outer retinal layers due to pressure from the PED or if this is the detached RPE.
Case 92 · Large pigment epithelial detachment: Case where CNV is present
171 6
Case 92 Large pigment epithelial detachment: Case where CNV is present

A 76-year-old male, OS, BCVA 0.6

A: Color fundus photograph in the left eye: A large PED about 4 times the diameter of the optic disc is exhibited in the macula. A notch is seen at the
superotemporal edge of the PED ( ). This kind of large PED usually have CNV. B: FAF in the left eye: The PED is exhibiting hyperfluorescence. A hypo-
fluorescent ring exists around the PED. The notched area is exhibiting even stronger hyperfluorescence ( ). C: FA in the left eye (31 seconds): The PED
is exhibiting hypofluorescence. The notched area is exhibiting granular hyperfluorescence ( ). D: IA in the left eye (31 seconds): The PED is also hypo-
fluorescent on IA, and the notched area is exhibiting hyperfluorescence due to CNV ( ). E: FA + OCT horizontal scan on the left eye: In this late stage FA
image, the PED is hyperfluorescent due to fluoroscein pooling. CNV is detected on OCT in the location corresponding to the hyporeflective notch. ( ).
(Continued on the next page)
 172 Chapter 6 · Age-related macular degeneration

Case 92 Continuation

F: IR + OCT horizontal scan of the left eye: 17 months after initial diagnosis. The PED is temporarily flattened as a result of anti-VEGF treatment and sub-
Tenon’s steroid injection. No abnormal findings can be seen in the OCT image passing through the fovea centralis. G: IR + OCT vertical scan of the left eye:
The PED and CNV inside the PED (▶) is detected on the OCT image passing through the notching in the superotemporal area. H: Color fundus photograph
in the left eye: Exudative changes are occurring in the sensory retina. The white arrow represents the OCT scan line for figure I. I: OCT horizontal scan of the
left eye: Two years after initial diagnosis. CNV is present over an extensive area beneath the RPE temporal to the fovea centralis. The gap of the RPE shown
in ( ) is an RPE tear. J: FA in the left eye (30 seconds): The long vertical hyperfluorescent area represents the RPE tear ( ). K: IA in the left eye (3 seconds):
A large CNV originating at the temporal edge of the macula ( ) is seen.

Image interpretation points

The PED was temporarily flattened as a result of anti-VEGF treat- diagnosis). Cases with a large PED have CNV almost without
ment and sub-Tenon’s steroid injection (17 months after initial exception. It is important to detect CNV using FA, IA and OCT.

pigment epithelial detachment

6.3 · Atrophic age-related macular degeneration
173 6
6.3 Atrophic age-related macular degeneration and are seen as highly reflective dots. This feature is also a
characteristic.(3) Cystic changes sometimes occur in the sensory
Background retina, and should not be mistaken for exudative changes.(4)
Atrophic AMD or dry AMD is a type of age-related macular There are detailed reports on OCT findings for atrophic
degeneration (AMD) often seen in Caucasians. The frequency AMD. According to Fleckenstein et al., various changes can be
of atrophic AMD used to be very low in Asians, including the seen around atrophic lesions, as shown in . Fig. 6-7.(5) All these
Japanese, but this type of AMD has been on the rise in recent changes occur on the RPE and Bruch’s membrane level.
years. The most significant factors correlated with the onset of The RPE disappears in the atrophic lesion, and the edge of
atrophic AMD and exudative AMD are age-related changes in the atrophic change demonstrate several patterns, as shown in
the RPE and Bruch’s membrane. Fundus findings such as drusen . Fig. 6-8, indicating the diversity of pathogenesis of atrophic
and RPE pigmentation changes (pigmentation and depigmenta- AMD.
tion) represent these age-related changes. Thus, atrophic AMD The ELM, IS/OS, RPE and outer nuclear layer usually dis-
and exudative AMD are not separate diseases; rather exudative appear inside the atrophic lesion. In many cases, a relatively thin
changes can occur during atrophic AMD, and exudative AMD line thought to be Bruch’s membrane remains with debris origi-
can become atrophic during its course. nating from the outer retinal layers left anteriorly (. Fig. 6-9).
Recently, the concept of viewing atrophic AMD as one spec- While OCT is extremely crucial in the diagnosis of atrophic
trum of reticular pseudodrusen in reticular macular diseases has AMD (. Fig. 6-10), useful information can also be obtained from
been proposed (reticular pseudodrusen and exudative AMD are fundus autofluorescence (FAF) imaging. Holz et al. have demon-
not unrelated and are, in fact, closely related).(1) strated through a large scale of prospective studies that they can
predict the rate of progression of atrophic AMD based on FAF
OCT findings image patterns.(6)
OCT images of atrophic AMD show distinctive findings such There is debate as to whether degeneration of the sensory retina
as atrophy and thinning of the sensory retina, atrophy and loss or degeneration of the RPE occurs first in the onset of this disease.
of the RPE, and choroidal signal enhancement (. Fig. 6-6).(2, 3) While no conclusion has been reached regarding this issue, recent
In addition, RPE cells are migrating within the sensory retina studies suggest that RPE degeneration occurs first.(7, 8)

. Fig. 6-6 OCT B-scan image for atrophic AMD

The foveal retina is significantly thinned. The RPE is atrophic and lost. In addition, choroidal signal enhancement is seen beneath the atrophied RPE (bet-
ween ▶). See the red dashed box area in . Fig. 6-10.

. Fig. 6-7 Findings visible around the atrophic lesion of atrophic AMD
Changes in the RPE and Bruch’s membrane and subsequent findings can be seen.
RNFL= retinal nerve fiber layer, GCL= ganglion cell layer, IPL= inner plexiform layer, INL= inner nuclear layer, IPRL=interface of inner and outer photo-
receptor segment layer, OPL= outer plexiform layer, ONL= outer nuclear layer.
(Modified according to Fleckenstein M, et al. High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular
degeneration. Invest Ophthalmol Vis Sci. 2008; 49: 4137-4144)
 174 Chapter 6 · Age-related macular degeneration

. Fig. 6-8 Findings visible at the edge of the atrophic lesion of atrophic AMD
The pattern of RPE loss is not uniform and exhibits varied findings. IPRL = interface of inner and outer photoreceptor segment layer.
(Modified according to Fleckenstein M, et al. High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular
6 degeneration. Invest Ophthalmol Vis Sci. 2008; 49: 4137-4144)

. Fig. 6-9 Findings visible in the atrophic lesion of atrophic AMD

The RPE has disappeared and the debris exists on the remaining Bruch’s membrane.
(Modified according to Fleckenstein M, et al. High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular
degeneration. Invest Ophthalmol Vis Sci. 2008; 49: 4137-4144)

. Fig. 6-10 Atrophic lesions on OCT

Enlarged version of . Fig. 6-6 [red dashed box]. On the right side, there is an area where the RPE and outer retinal layers are almost normal. In the area
indicated by ( ), the RPE, IS/OS and ELM are almost normal but on the foveal side the ELM has disappeared and IS/OS reflectivity is irregular. In the
area indicated by ( ) the RPE has partially lost, and the corresponding retinal tissue external to the ELM is disrupted. Moving towards the fovea, the
RPE has almost disappeared. In addition, the outer nuclear layer is thinned. In the red dashed circle near the fovea centralis, a structure exhibiting high
reflectivity can be seen within the sensory retina. This likely represents migrated RPE cells.
6.3 · Atrophic age-related macular degeneration
175 6
6.3.1 References

1) Smith RT, Sohrab MA, Busuioc M, et al. Reticular macular disease. Am J

Ophthalmol. 2009; 148:733-743.
2) Ho J, Witkin AJ, Liu J, et al. Duker JS. Documentation of intraretinal retinal
pigment epithelium migration via high-speed ultrahigh-resolution opti-
cal coherence tomography. Ophthalmology. 2011; 118:687-693.
3) Lujian BL, Rosenfeld PJ, Gregori G, et al. Spectral domain optical coherence
tomographic imaging of geographic atrophy. Ophthalmic Surg Lasers Im-
aging. 2009; 40:96-101.
4) Cohen SY, Dubois L, Nghiem-Buffet S, et al. Retinal pseudocysts in age-
related geographic atrophy. Am J Ophthalmol. 2010; 150:211-217.
5) Fleckenstein M, Charbel Issa P, Helb HM, et al. High-resolution spectral
domain-OCT imaging in geographic atrophy associated with age-related
macular degeneration. Invest Ophthalmol Vis Sci. 2008; 49:4137-4144.
6) Holz FG, Bindewald-Wittch A, Fleckenstein M, et al. FAM-Study Group.
Progression of geographic atrophy and impact of fundus autofluores-
cence patterns in age-related macular degeneration. Am J Ophthalmol.
2007; 143:463-472.
7) Sayegh RG, Simader C, Scheschy U, et al. A systematic comparison of spec-
tral-domain optical coherence tomography and fundus autofluorescence
in patients with geographic atrophy. Ophthalmology. 2011; 118:1844-1851.
8) Fleckenstein M, Schmitz-Valckenberg S, Martens C, et al. Fundus autofluo-
rescence and spectral-domain optical coherence tomography character-
istics in a rapidly progressing form of geographic atrophy. Invest Ophthal-
mol Vis Sci. 2011; 52:3761-3766.
 176 Chapter 6 · Age-related macular degeneration

Case 93 Atrophic age-related macular degeneration: A typical example

A 65-year-old male, OS, BCVA 0.04

A: Color fundus photograph: A geographic atrophic lesion of about 1.5 disc diameter is visible in the macula. The large blood vessels of the choroid are
visible around the atrophic lesion. Relatively small drusen and reticular pseudodrusen are observed. B: FA in the left eye (42 seconds): The round atrophic
lesion is exhibiting hyperfluorescence due to window defects. Blocked fluorescence is seen in one part of the lesion due to reactive proliferation of the
RPE. Multiple drusen can be seen around the atrophic lesion. C: IA in the left eye (42 seconds): The large blood vessels of the choroid are clearly visible. The
drusen are essentially exhibiting hypofluorescence. D: IR + OCT horizontal scan of the left eye: Retinal atrophy is exhibited in the geographic lesion area
( ). E: Enlarged version of D [red dashed box]: The ELM and IS/OS are not visible between the two (▶). The RPE is also lost. As a result, choroidal signal
enhancement can be seen. The outer retinal layers are partially visible in a small area. In addition, highly reflective patterns ( ) can be seen within the
retina. Reticular pseudodrusen can also be seen.

Image interpretation points

This is atrophic AMD with a typical geographic atrophic lesion. macular dystrophies. Whether or not various pathological con-
While previously rare in Japanese people, the frequency of ditions can be differentiated with OCT findings alone is the sub-
these lesions has increased in recent years. The RPE is lost over ject of future investigation.
a wide area, though similar findings are also seen in cone and
Case 94 · Atrophic age-related macular degeneration: Atrophic lesions of various sizes
177 6
Case 94 Atrophic age-related macular degeneration: Atrophic lesions of various sizes

A 65-year-old male, OS, BCVA 0.4

A: Color fundus photograph: Drusen of various sizes and RPE pigmentation changes can be seen over a wide area of the macula. The atrophic lesions pres-
ent as punctiform patterns. B: FAF in the left eye: Relatively large hypofluorescent foci and small hyperfluorescent foci are mixed together. The hypofluores-
cent foci are bordered by hyperfluorescence. The atrophic lesions are hypofluorescent. C: IR + OCT horizontal scan of the left eye: The foveal retina is
thinned. D: Enlarged version of C [red dashed box]: Loss of the outer retinal layers and RPE is mild and localized. Visual acuity is relatively good. Reticular
pseudodrusen can also be seen.

Image interpretation points

This is a case of relatively mild atrophic AMD. Multiple drusen Cases where drusen are numerous can develop exudative AMD,
are present but the fundus appearance differs from geographic or progress to atrophic AMD, as seen in this case. The risk factor
atrophic lesions. There is a mild visual decline (best-corrected for the pattern of progression is an important area of study but
visual acuity 0.4) and the lesions can be diagnosed as atrophic there is currently no consensus.
AMD.
 178 Chapter 6 · Age-related macular degeneration

Case 95 Atrophic age-related macular degeneration: Fellow eye of PCV

An 84-year-old male, OD and OS, BCVA 0.4 and 0.6 respectively

A: Color fundus photograph in the right eye: An atrophic lesion of about 1 disc diameter is observed in the fovea centralis. Multiple large drusen are
scattered around the lesion (▶). The atrophic foveal lesion may have developed from a serous PED. B: Color fundus photograph in the left eye: A polypoidal
lesion is visible inferonasal to the fovea centralis ( ). It is accompanied by a large PED. C: IA in the left eye (40 seconds): A typical polypoidal lesion and an
abnormal vascular network ( ) can be seen. The PED is exhibiting hypofluorescence (*). CNV appears to exist within the PED. D: IR + OCT horizontal scan
of the right eye: The fovea is significantly thinned. E: Enlarged version of D [red dashed box]: The ELM, IS/OS and RPE are not seen in the area indicated by
(▶). Migrating RPE cells are seen within the sensory retina ( ). Thinning of the fovea is evident.

Image interpretation points

This case is the same as case 88. During initial diagnosis, the Cases that progress from serous PED to a geographic atrophic
right eye exhibited atrophic AMD, and the left eye exhibited lesion such as in this case appear to be common in Japanese
drusenoid PED. PCV subsequently occurred in the left eye. This people. In addition, there are cases where prolonged courses
case illustrates the fact that both atrophic and exudative AMD of central serous chorioretinopathy progress to geographic
progress from drusen and that PCV falls into the category of atrophy.
exudative AMD.
6.4 · Choroidal neovascularization and exudative age-related macular degeneration
179 6
6.4 Choroidal neovascularization RPE and extends to the subretinal space. Unfortunately, the
and exudative age-related macular clinical setting is limited to biomicroscopy, confocal laser
degeneration ophthalmoscopy, FA, IA, and OCT. Given its ability to obtain
tomographic image of lesions, the OCT is an practical option for
Background discriminating Type 1 and Type 2 CNV.
Choroidal neovascularization (CNV) is the state in which new While Type 1 CNV is seen in most cases of exudative AMD,
vessel growth originating from the choroid penetrates Bruch’s Type 2 CNV is not as common as previously understood.(3) Most
membrane to beneath the RPE or the sensory retina. Terms such cases thought to be Type 2 CNV. During the era of time-domain
as classic or occult CNV are often used to classify CNV (. Fig. OCT where resolution was poor were the so-called »mixed type«
6-11). To be strict, these terms, are used to describe findings on (a mixture of Type 1 and Type 2 components). Therefore, pure
FA.(1) FA does not provide detailed information about depth. As Type 2 CNV is rare in AMD patients. When such cases were seen,
a result, this classification system cannot be used to describe the secondary causes of CNV had to be considered. Abnormal vas-
retinal layer structures in which a lesion exists. For example, a cular network of PCV is Type 1 CNV.(4, 5)
label of classic or occult CNV will not discriminate CNV localized Idiopathic CNV and CNV associated with severe myopia are
beneath the RPE or CNV extending through the RPE. almost without exception Type 2 CNV and they do not have any
On the other hand, Gass’s classification of Type 1 CNV and components of Type 1 CNV.(6) Type 2 CNV often occurs in angi-
Type 2 CNV are also often used(2) (. Fig. 6-12). These terms oid streaks, as well, where Type 1 CNV is sometimes seen.(7, 8)
are based on histopathological descriptions where Type 1 CNV Even using the latest spectral-domain OCT, the beam does
is confined to sub-RPE space and Type 2 CNV penetrates the not sufficiently penetrate the RPE in cases where strong exuda-

. Fig. 6-11 FA of classic CNV and occult CNV

A: Predominantly classic CNV. Strong fluoroscein leakage can be seen from CNV inferonasal to the fovea centralis. B: Occult with no classic CNV. The fluoros-
cein is confined to the sub-RPE space and leakage is weak..

. Fig. 6-12 Type 1 CNV and Type 2 CNV

A: Schematic diagram of Type 1 CNV, B: Schematic diagram of Type 2 CNV.
Type 1 CNV spreads beneath the RPE, whereas Type 2 CNV breaks through the RPE and extends to beneath the sensory retina. In general, exudative
changes in the sensory retina are stronger in Type 2 CNV.
RPE= retinal pigment epithelium, ICL= inner collagenous layer, EL= elastic layer, OCL= outer collagenous layer, CC= choriocapillaris
 180 Chapter 6 · Age-related macular degeneration

. Fig. 6-13 CNV OCT findings

A: Scanning in normal mode. The state of the RPE is difficult to determine due to strong retinal exudative changes and CNV. B: Scanning in EDI-OCT. We can
clearly see that there is no breakdown in the RPE line. C: 1,050 nm SS-OCT image. The state of the RPE is clearly seen as a result of a long-wavelength light
source. All the scans are taken from approximately the same site in the same eye.

tive changes are found in the sensory retina. As a result, the type 6.4.1 References
of CNV cannot be reliably determined (. Fig. 6-13A). In such
cases EDI-OCT images(9) can be useful (. Fig. 6-13B). In addi- 1) Macular Photocoagulation Study Group. Subfoveal neovascular lesions in
age-related macular degeneration. Guidelines for evaluation and treat-
tion, changes beneath the RPE may be easier to detect using high-
ment in the macular photocoagulation study. Arch Ophthalmol. 1991;
penetration OCT (also termed SS-OCT), which is highly likely 109:1242–1257.
to spread in the near future (widelly used SD-OCT uses an OCT 2) Gass JM. Biomicroscopic and histopathologic considerations regarding
light source with a central wavelength of about 840 nm, whereas the feasibility of surgical excision of subfoveal neovascular membranes.
this new SS-OCT uses a scanning light source of 1, 050 nm) Am J Ophthalmol. 1994; 118:285–298.
(. Fig. 6-13C). 3) Coscas F, Coscas G, Souied E, et al. Optical coherence tomography identi-
fication of occult choroidal neovascularization in age-related macular de-
generation. Am J Ophthalmol. 2007; 144:592–599.
4) Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for
choroidal neovascularization in age-related macular degeneration? Retina.
2010; 30:1333–1349.
5) Imamura Y, Engelbert M, Iida T, et al. Polypoidal choroidal vasculopathy:
a review. Surv Ophthalmol. 2010; 55:501–515.
6) Gass JDM. Stereoscopic atlas of Macular Diseases. Diagnosis and Treat-
ment. 4th Ed. Mosby, St. Louis, 1997.
7) Sawa M, Gomi F, Tsujikawa M, et al. Long-term results of intravitreal beva-
cizumab injection for choroidal neovascularization secondary to angioid
streaks. Am J Ophthalmol. 2009; 148:584–590.
8) Costa RA, Calucci D, Cardillo JA, et al. Selective occlusion of subfoveal
choroidal neovascularization in angioid streaks by using a new technique
of ingrowth site treatment. Ophthalmology. 2003; 110:1192–1203.
9) Spaide RF. Enhanced depth imaging optical coherence tomography of
retinal pigment epithelial detachment in age-related macular degenera-
tion. Am J Ophthalmol. 2009; 147:644–652.

choroidal neovascularization
Case 96 · Exudative age-related macular degeneration: Type 1 CNV with a SRD
181 6
Case 96 Exudative age-related macular degeneration: Type 1 CNV with a SRD

Right eye of 58 year male with vision corrected to 0.1

A: Color fundus photograph in the right eye: A SRD of about 1.5 disc diameters is seen in the fovea centralis. Drusen are scattered. No exudative changes
such as retinal hemorrhages or hard exudates are visible. B: FA in the right eye (3 minutes, 36 seconds): Granular hyperfluorescence is observed in the SRD
area. Fluoroscein leakage is mild. C: IA in the right eye (3 minutes, 36 seconds): A abnormal vascular network appears to exist on IA. A Hyperfluorescent fo-
cus suggestive of polypoidal lesions is seen ( ). D: IR + OCT horizontal scan of the right eye: A flat RPE protrusion and a SRD can be seen on OCT. The area
between the RPE and Bruch’s membrane is exhibiting moderate reflectivity. E: Enlarged version of D [red dashed box]: CNV exhibiting moderate reflectivity
is confined to sub-RPE space ( ). Bruch’s membrane is depicted as a straight, highly reflective line indicated by (▶). The location of Type 1 CNV is always
between the RPE and Bruch’s membrane. The foveal photoreceptor outer segment is not seen and the fovea centralis is thinned.

Image interpretation points

This is a case where PCV should be considered based on the IA findings, it may be reasonable to consider this a Type 1 CNV.
findings. Nevertheless, only a flat protruding fibrovascular PED Also note, Bruch’s membrane is easily visible.
is seen rather than a steep RPE protrusion. Based on these OCT

choroidal neovascularization
serous retinal detachment
 182 Chapter 6 · Age-related macular degeneration

Case 97 Exudative age-related macular degeneration: Type 1 CNV with low activity

A 57-year-old male, OS, BCVA 0.4

A: Color fundus photograph in the right eye: Annular RPE depigmentation about 1.5 disc diameters is observed in the fovea centralis. B: FAF in the left
eye: The area of abnormal RPE pigment is exhibiting hyperfluorescence. The surrounding area is slightly hypofluorescent. C: FA in the left eye (1 minute,
12 seconds): Faint hyperfluorescence can be seen in the fovea centralis. D: FA + OCT horizontal scan of the left eye: A flat RPE protrusion can be seen on
OCT. The content of the PED is exhibiting moderate reflectivity. E: Enlarged version of D [red dashed box]: The highly reflective line of the PED appears to
be breaking down in the site encircled by the red dashed line (red dashed circle). The subfoveal IS/OS is poorly visible.

Image interpretation points

It may be difficult to determine if CNV is present in this case. acuity of 0.4. Mild edema can be seen in the retina, and it is
Even if CNV exists, its activity is low. The structure of the foveal highly likely that CNV is penetrating slightly below the retina in
IS/OS is abnormal, consistent with the best-corrected visual the area of the red dashed line seen in E.

choroidal neovascularization
Case 98 · Exudative age-related macular degeneration: Type 1 CNV with relatively strong exudative changes
183 6
Case 98 Exudative age-related macular degeneration: Type 1 CNV with relatively strong
exudative changes
A 57-year-old male, OD, BCVA 1.2

A: Color fundus photograph: Mottled depigmentation can be seen in the RPE in the fovea centralis. A flat SRD is also present. B: FA in the right eye
(27 seconds): Hyperfluorescence consistent with the site exhibiting the RPE depigmentation is visible. These are findings characteristic to occult CNV.
C: IA in the right eye (27 seconds): The choroidal vessels can be observed more clearly in the region exhibiting hyperfluorescence on FA. D: IR + OCT hori-
zontal scan of the right eye: A SRD is observed in the fovea centralis. Cystic changes can be seen in the sensory retina. E: Enlarged version of D [red dashed
box]: The flat RPE protrusion is due to CNV (*). The line of Bruch’s membrane (▶) is clearly visible beneath the RPE. Cystic changes ( ) are exhibited in the
sensory retina. The photoreceptor outer segment of the detached retina is slightly elongated. Highly reflective spots are scattered in the outer retinal layers
(red dashed circle). These may be penetrated macrophages. (Continued on the next page)

Image interpretation points

This is a case of Type 1 CNV with a few findings indicating PCV is relatively strong as evidenced by the exudative changes found
on angiography and OCT images. The activity of CNV in this case in the sensory retina.

choroidal neovascularization
 184 Chapter 6 · Age-related macular degeneration

Case 98 Six months later

F: Color fundus photograph in the right eye: There is almost no change compared to the fundus photograph from 6 months earlier. G: IR + OCT horizontal
scan of the right eye: There is almost no change observed in the RPE protrusion and SRD compared with the IR and OCT from 6 months earlier. H: Enlarged
version of G [red dashed box]: Type 1 CNV is clearly visible. Cystic changes ( ) remain in the sensory retina. Photoreceptor outer segment changes (▶) are
insignificant. The detached posterior vitreous cortex ( ) is seen outside the fovea centralis. The line on the outer edge of the choroid can be traced (▶) as
a result of averaging multiple B-scans at the identical location of interest. Choroidal thickness in this case appears to be normal.

Image interpretation points

This is a case where there was almost no progress in 6 months but PEDs larger and taller than this case are not seen in central
based on just a follow-up. Differentiation from central serous serous chorioretinopathy.
chorioretinopathy is difficult with biomicroscopic findings,
Case 99 · Exudative age-related macular degeneration: Case with strong Type 1 and 2 CNV exudative changes
185 6
Case 99 Exudative age-related macular degeneration: Case with extensive Type 1 and 2 CNV
exudative changes
A 59-year-old male, OS, BCVA 0.15

A: Color fundus photograph in the left eye: CNV with retinal hemorrhages is seen in the fovea centralis. Fibrin is seen deposited over the CNV. B: FA in the
left eye (40 seconds): Intense hyperfluorescence can be seen. CME is also visible. C: Enlarged image of IA in the left eye (1 minute, 17 seconds): Reticular
pattern of CNV is seen, which is similar to the abnormal vascular network that can be seen in PCV. The CNV appears to originate inferonasally to the fovea
centralis ( ). D: IR + OCT vertical scan of left eye: Cystoid spaces are is observed. Although the RPE line is incomplete, it is mostly visible and relatively flat.
There are highly reflective clumps above the RPE due to hemorrhages, fibrin and Type 2 CNV. E: IR + OCT horizontal scan of left eye: Similar findings as D
are noted. In the red dashed circle outside the fovea centralis, there is a flat RPE protrusion corresponding to Type 1 CNV. In the other area, the RPE is flat
and visible over the entire length of the scan. (Continued on the next page)

Image interpretation points

Fibrin deposits can be seen on the fundus photograph. A clas- OCT; however, since the RPE protrusion is not significant, it may
sic CNV pattern is exhibited on FA, and a reticular, branched be Type 2 CNV combined with fibrin. Type 1 CNV also exists be-
CNV is seen on IA. Type 2 CNV is not clearly appreciated on neath the RPE in the red dashed circle in E.

choroidal neovascularization
 186 Chapter 6 · Age-related macular degeneration

Case 99 Six months after treatment with anti-VEGF treatment

F: Color fundus photograph in the left eye: The exudative changes seen in the fovea centralis has disappeared. Scar formation can be seen. G: IR + OCT
horizontal scan of the left eye: The CNV has scarred and there is a large RPE protrusion. No exudative changes can be seen in the retina. H: Enlarged version
of G [red dashed box]: CNV enveloped by the RPE is clearly visible (▶). The highly reflective ( ) Bruch’s membrane can be traced beneath the scarred CNV
(▶). Temporally, there is a flat RPE protrusion with Type 1 CNV within the red dashed circle. I: IR + OCT vertical scan of the left eye: The internal reflectivity of
the scar lesions is relatively high.

Image interpretation points

These are images taken 6 months after intravitreal injection of tinues to be 0.15 with no improvement after treatment. There is
bevacizumab (Avastin). We can see that the RPE is enveloping a flat RPE protrusion (the red dashed circle in C), which indicates
the CNV with resultant scarring. No exudative changes are ob- that Type 1 CNV remains. Scarred Type 2 CNV also remains beneath
served in the sensory retina. Best-corrected visual acuity con- the significant RPE protrusion nasal to the fovea centralis.

choroidal neovascularization
Case 100 · Exudative age-related macular degeneration: Type 1 and 2 CNV extensive serous retinal detachment
187 6
Case 100 Exudative age-related macular degeneration: Type 1 and 2 CNV with extensive serous
retinal detachment
An 87-year-old male, OS, BCVA 0.6

A: Color fundus photograph in the left eye: Large CNV is seen in the fovea centralis and a subretinal hemorrhage exists around it. There are also fibrin deposits.
B: FAF in the left eye: The CNV and surrounding hemorrhages are exhibiting hypofluorescence. The weak hyperfluorescence around it appears annular. C: FA in
the left eye (1 minute, 8 seconds): Hyperfluorescence can be seen as a result of fluorescein accumulation in the CNV and cystoid spaces. D: IA in the left eye
(1 minute, 8 seconds): CNV is easily appreciated on IA. E: IR + OCT horizontal scan of the left eye: The RPE is not well defined due to strong exudative changes
in the sensory retina. We can see a SRD (*). F: IR + OCT vertical scan of left eye: The RPE protrusion can be seen ( ). This protrusion indicates Type 1 CNV. The
subfoveal lesion is comprised of CNV and fibrin (*).

Image interpretation points

This is a case with large CNV. Significant exudative changes can is protruding slightly ( ) and Type 1 CNV appears to exist in this
be seen in the sensory retina. Blocking of OCT probe light by area. OCT allows detection of a wider SRD than a biomicroscopy
the CNV causes the poor OCT image below it. (*). The RPE line does.

choroidal neovascularization
 188 Chapter 6 · Age-related macular degeneration

Case 101 Exudative age-related macular degeneration: Type 1 and 2 CNV with cystic changes

A 67-year-old male, OD, BCVA 0.05

A: Color fundus photograph in the right eye: A flat PED is seen in the fovea centralis. Subfoveal CNV appears to exist. B: FA in the right eye (3 minutes):
A significant hyperfluorescent focus is visible in the late-stage FA image. C: IA in the right eye (52 seconds): The branched CNV is easily seen on IA.
D: Enlarged version of C [red dashed box]: The CNV root appear to be branching out in a fan shape. E: IR + OCT vertical scan of the right eye: A large
cystoid space is seen (*). The large RPE protrusion is clearly visible. F: Enlarged version of E [red dashed box]: The cystoid spaces and RPE protrusion (▶)
are clearly visible. In the area of the irregular RPE line at the superior fovea centralis, Type 2 CNV can be seen extending beneath the sensory retina (red
dashed circle).

Image interpretation points

A classic CNV pattern is seen on FA. On OCT, a large RPE pro- CNV can be seen penetrating the RPE. The Type 2 CNV seen on
trusion caused by Type 1 CNV can seen. Superior to this, type 2 OCT corresponds to classic CNV on FA.

choroidal neovascularization
Case 102 · Exudative age-related macular degeneration: Type 2 CNV localized in the fovea centralis
189 6
Case 102 Exudative age-related macular degeneration: Type 2 CNV localized in the fovea centralis

A 71-year-old female, OD, BCVA 0.05

A: Color fundus photograph in the right eye: Well-defined CNV can be seen in the fovea centralis. The tigroid fundus as seen in myopic eyes is observed,
but the axial length is 22.63 nm. B: FA in the right eye (40 seconds): Typical classic CNV is observed. C: IA in the right eye (40 seconds): Reticular CNV is seen.
D: IR + OCT horizontal scan of the right eye: CNV with high reflectivity is visible beneath the fovea centralis. The high reflectivity in contact with the retina
is due to fibrin. Little protrusion can be seen in the RPE ( ). No elements of Type 1 CNV can be seen. The choroid is thinned.

Image interpretation points

AMD is accompanied by Type 1 CNV in most cases; in fact, it is consider secondary CNV if only Type 2 CNV was found. The choroid
rare to see CNV consisting of only Type 2 CNV. It is necessary to is thinned, which may be due to age-related choroidal atrophy.

choroidal neovascularization
 190 Chapter 6 · Age-related macular degeneration

Case 103 Exudative age-related macular degeneration: Type 2 CNV with strong exudative changes

Right eye of a 71-year-old male with vision corrected to 0.1

A: Color fundus photograph in the right eye: Retinal whitening is seen in the macula. Hard exudates are seen inferotemporal to the fovea centralis. B: FA in
the right eye (7 minutes, 26 seconds): Intense hyperfluorescence indicating CME is exhibited. The fluorescence pattern is classic CNV. C: IA in the right eye
(7 minutes, 26 seconds): CNV shows faint hyperfluorescence. D: IR + OCT horizontal scan of the right eye: CME accompanied by a large foveal cystoid space
(*) exists over the entire macular area. The RPE line is seen over almost the entire length and appears flat on this scan. There are highly reflective clumps
above the RPE, which are due to CNV and fibrin. E: IR + EDI-OCT horizontal scan of the right eye: The RPE can be seen more clearly when scanned with
EDI-OCT.

Image interpretation points

This is a case where strong exudative changes are observed. face. In this case, the EDI-OCT confirms that there are no RPE
The whitened retina reduces the penetration of the OCT beam; protrusions indicative of Type 1 CNV. The highly reflective
as a result, the RPE is not well characterized. Using EDI-OCT, clumps seen below the sensory retina in the SD-OCT imaging
the RPE is more clearly depicted compared to the retinal sur- are a complex ofType 2 CNV and the resulting exudates.

choroidal neovascularization
6.5 · Polypoidal choroidal vasculopathy
191 6
6.5 Polypoidal choroidal vasculopathy membrane.(10) In addition, it has also become apparent that
polypoidal lesions are frequently attached posteriorly to the RPE
Background and detached from Bruch’s membrane.(10, 11) . Fig. 6-15 shows a
Polypoidal choroidal vasculopathy (PCV) is a disease first re- schematic diagram of the development of PCV and the cor-
ported in 1982 by Yannuzzi et al. It was at first thought to be responding OCT image.
a peculiar disease in black women(1–4) (. Fig. 6-14), but sub- A »double layer sign« is a distinctive OCT finding of PCV.
sequent research found it to be one of the phenotypes of AMD Because of the low axial resolution of time-domain OCT, it can-
that can be seen at a high frequency in Asians including the Jap- not resolve the abnormal vascular network, Bruch’s membrane
anese.(5, 6) In Japan, about half the cases of exudative AMD are and choriocapillaris, which are depicted as a bold single line.
PCV.(7) It is common in men with a history of smoking and is A »double layer sign« describes the parallel appearance of
often seen with hypertension. There was heated debate in Japan the detached RPE line and this bold line derived from the com-
as to whether PCV is essentially CNV or a choroidal vascular plex.(12) With SD-OCT, however, this term is no longer suitable
abnormality, but histopathological investigations are not enough given the improved resolution. As previously mentioned, PED is
to draw a conclusion at present. However, in the Western macular a finding frequently seen in this disease. A notch often exists in
society, PCV is thought to be CNV.(8) While IA is an extremely the periphery of a PED secondary to CNV. CNV is frequently
important tool in the diagnosis of PCV, macular specialists in the found in this notched edge of the PED. Gass called this
West does not perform IA as routinely as those in Japan; as a re- phenomenon »notch sign«.(13) On OCT, a notch can be seen in
sult, it is highly likely that the disease frequency of PCV is under- the RPE line consistent with the notch sign on FA. These findings
estimated in the West. PCV is composed of two main elements. are called »tomographic notch sign«.(14) These signs are often
The first is branching vascular network vessels in Japan. The seen in PCV. In recent years, we have been able to depict the
second element is a vasodilative lesion known as a polypoidal choroid more clearly using EDI-OCT.(15) As a result, the relation-
structure.(9) ship between choroidal thickness and various fundus diseases
has been gathering attention. For example, we know that choroi-
OCT findings dal thickness significantly increases in central serous chorio-
Studies up until now using OCT have found that the location of retinopathy.(16) It is also reported that the choroid is thicker in
the abnormal vascular network is between the RPE and Bruch’s PCV than in typical AMD.(17)

. Fig. 6-14 Schematic diagram of PCV

In this figure, the optic disc is depicted as the origin of the abnormal vascular network, but the origin also exists in the macula in the macular type PCV
common in Japanese people. Bulging of the tips of the abnormal vascular network forms polypoidal lesions. PEDs are a frequently observed finding.
(Modified according to Yannuzzi LA, et al. Indocyanine green angiography. 1997, Mosby-Year Book, p331)
 192 Chapter 6 · Age-related macular degeneration

. Fig. 6-15 Schematic diagram of the development of PCV

A: The abnormal vascular network exists within Bruch’s membrane. B: As exudative changes from the polypoidal lesion get stronger, exudate fluid accumu-
lates in the sub-RPE space and a PED develops. C: When the exudative changes get even stronger, the polypoidal lesion detaches from Bruch’s membrane
with their attachment to the posterior aspect of the RPE. D: OCT findings. The polypoidal lesion is attached to the posterior aspect of the RPE and is deta-
ching from Bruch’s membrane ( ). (Modified according to Tsujikawa A, Sasahara M, Otani A, et al. Pigment epithelial detachment in polypoidal choroidal
vasculopathy. Am J Ophthalmol. 2007; 143: 102-111)
6.5 · Polypoidal choroidal vasculopathy
193 6
6.5.1 References

1) Stern RM, Zakov N, Zegarra H, et al. Multiple recurrent serosanguineous

retinal pigment epithelial detachments in black women. Am J Ophthal-
mol. 1985; 100:560–569.
2) Yannuzzi LA, Sorenson J, Spaide RF, et al. Idiopathic polypoidal choroidal
vasculopathy. Retina. 1990; 10:1–8.
3) Kleiner RC, Brucker AJ, Johnston RL. The posterior uveal bleeding syn-
drome. Retina. 1990; 10:9–17.
4) Perkovich BT, Zakov ZN, Berlin LA, et al. An update on multiple recurrent
serosanguineous retinal pigment epithelial detachments in black women.
Retina. 1990; 10:18–26.
5) Uyama M, Wada M, Nagai Y, et al. Polypoidal choroidal vasculopathy:
natural history. Am J Ophthalmol. 2002; 133:639–648.
6) Sho K, Takahashi K, Yamada H, et al. Polypoidal choroidal vasculopathy:
incidence, demographic features, and clinical characteristics. Arch
Ophthalmol. 2003; 121:1392–1396.
7) Maruko I, Iida T, Saito M, et al. Clinical characteristics of exudative age-
related macular degeneration in Japanese patients. Am J Ophthalmol.
2007; 144:15–22.
8) Rosa RH Jr, Davis JL, Eifrig CW. Clinicopathologic reports, case reports, and
small case series: clinicopathologic correlation of idiopathic polypoidal
choroidal vasculopathy. Arch Ophthalmol. 2002; 120:502–508.
9) Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiog-
raphy of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;
15:100–110.
10) Tsujikawa A, Sasahara M, Otani A, et al. Pigment epithelial detachment in
polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007; 143:102–111.
11) Ojima Y, Hangai M, Sakamoto A, et al. Improved visualization of polypoi-
dal choroidal vasculopathy lesions using spectral-domain optical coher-
ence tomography. Retina. 2009; 29:52–59.
12) Sato T, Kishi S, Watanabe G, et al. Tomographic features of branching
vascular networks in polypoidal choroidal vasculopathy. Retina. 2007;
27:589–594.
13) Gass JM. Serous retinal pigment epithelial detachment with a notch.
A sign of occult choroidal neovascularization. Retina. 1984; 4:205–220.
14) Sato T, Iida T, Hagimura N, et al. Correlation of optical coherence tomogra-
phy with angiography in retinal pigment epithelial detachment associat-
ed with age-related macular degeneration. Retina. 2004; 24:910–914.
15) Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-
domain optical coherence tomography. Am J Ophthalmol. 2008; 146:496–
500.
16) Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical
coherence tomography of the choroid in central serous chorioretinopathy.
Retina. 2009; 29:1469–1473.
17) Chung SE, Kang SW, Lee JH, et al. Choroidal thickness in polypoidal
choroidal vasculopathy and exudative age-related macular degeneration.
Ophthalmology. 2011; 118:840–845.
 194 Chapter 6 · Age-related macular degeneration

Case 104 Polypoidal choroidal vasculopathy: Small lesions

A 65-year-old male, OS, BCVA 0.1

A: Color fundus photograph in the left eye: A small, elevated orange-red lesion is visible superonasal to the fovea centralis, but they are easily overlooked
if not observed in detail. A SRD exists in the macula. Drusen are not seen. B: FA in the left eye (5 minutes, 10 seconds): The elevated orange-red lesions
superonasal to the fovea centralis are exhibiting granular hyperfluorescence. C: IA in the left eye (5 minutes, 10 seconds): Small polypoidal lesions are clear-
ly visible on IA ( ). An abnormal vascular network is observed superior to the polypoidal lesion. D: IR + OCT horizontal scan of the left eye: A SRD is seen.
A small RPE protrusion can be seen ( ). Bruch’s membrane is seen beneath the elevated RPE. E: IR + OCT diagonal scan of the left eye: A flat RPE elevation
is visible in the area corresponding to the abnormal vascular network (▶). The relatively tall protrusion area corresponds to the polypoidal lesions detected
on IA ( ).

Image interpretation points

This is a case of PCV with extensive SRD and a small polypoidal While differentiation with central serous chorioretinopathy
lesion. is difficult with ophthalmoscopic findings, but the protruding
lesions seen on OCT are typical of PCV.
Case 105 · Polypoidal choroidal vasculopathy: Case confused with central serous chorioretinopathy
195 6
Case 105 Polypoidal choroidal vasculopathy: Case confused with central serous chorioretinopathy

A 63-year-old female, OS, BCVA 0.4

A: Color fundus photograph in the left eye: A SRD about 1.5 disc diameters can be seen in the macula. A white spot is evident in the fovea centralis. This
may be fibrin deposits. Drusen are barely visible in the posterior pole. B: FA in the left eye (28 seconds): A small, granular hyperfluorescent focus can be
seen in the fovea centralis. C: IA in the left eye (28 seconds): A small polypoidal lesion is seen on IA. D: IR + OCT horizontal scan of the left eye: A SRD can be
seen (*). There is an steep RPE protrusion. E: Enlarged version of C [red dashed box]: We can see that two polypoidal lesions ( ) and an abnormal vascular
network exist superonasally (white dashed circle). F: Enlarged version of D [red dashed box]: There is moderate reflectivity seen inside the RPE protrusion.
This suggests that the content is solid (including fibrovascular components) ( ). A highly reflective structure suggestive of a polypoidal lesion appears to
be penetrating the foveal sensory retina, but this may be a fibrin clot. A flat RPE protrusion can be seen nasally adjacent to the steep protrusion. Bruch’s
membrane is seen (▶). We can clearly see that the posterior vitreous cortex is attached to the retinal surface (▶). (Continued in the next page)

Image interpretation points

This is a case that can be confused with central serous chorio- this case is the highly reflective particulates (probably infiltrat-
retinopathy. In addition to the importance of IA, the steep, ing cells) within the protruding lesion.
protruding lesion on OCT is typical of PCV. A characteristic of
 196 Chapter 6 · Age-related macular degeneration

Case 105 After treatment with anti-VEGF treatment

An 63-year-old female, OS, BCVA 0.6

G: Color fundus photograph in the left eye: The SRD in the macula has disappeared, but white spots can still be seen in the center. H: IR + OCT horizontal
scan of the left eye: The disappearance of the SRD can be confirmed with OCT. The fovea is significantly thinned. The area where the retina had been de-
tached can be seen on the left IR image. I: Enlarged version of H [red dashed box]: The protruding lesion that existed before treatment has decreased in
size, but remains visible ( ). Moderate internal reflectivity is still visible in the protruding lesion. Bruch’s membrane is seen (▶). There is a disruption in the
structure of the outer retinal layers in the area of the RPE protrusion: the ELM is relatively preserved, but the IS/OS and COST lines cannot be clearly seen.

Image interpretation points

This is a case where the therapeutic value of anti-VEGF treatment is clear. While the SRD has significantly decreased, the CNV
remains with partial scarring.

polypoidal choroidal vasculopathy

Case 106 · Polypoidal choroidal vasculopathy: Fibrin deposits
197 6
Case 106 Polypoidal choroidal vasculopathy: Fibrin deposits ①

A 77-year-old female, OD, BCVA 0.05

A: Color fundus photograph in the right: Retinal whitening due to fibrin deposits about 2 disc diameters in size are visible in the macular area. Drusen are
unremarkable. There are subretinal hemorrhages inferior to the fovea centralis. B: FA in the right eye (14 minutes, 55 seconds): The fovea centralis is hypo-
fluorescent, but hyperfluorescence can be seen around it. This is tissue staining due to fibrin. C: IA in the right eye (1 minute, 36 seconds): While indistinct
on FA, a polypoidal lesion and a abnormal vascular network including relatively thick vesselsare easily seen on IA. D: Enlarged version of C [red dashed box]:
Polypoidal lesions and an abnormal vascular network resembling a »coil« are clearly visible. E: OCT horizontal scan of the right eye: The high reflectivity in
the outer retinal layers is due to fibrin (*). The structure of the inner retinal layers is relatively preserved. F: Enlarged version of E [red dashed box]: Fibrin,
depicted as highly reflective, appears to be penetrating the outer retinal layers (*). This may be correlated with the poor visual acuity. While the RPE line is
indistinct there appears to be a RPE protrusion ( ). Multiple inflammatory cells can be seen infiltrating the retina (▶).

Image interpretation points

On FA, lesions behind fibrin deposits are indistinct due to Although both use near-infrared light sources, each modality
blocking of OCT beam. In this case, insufficient information has different visualization power. It is important to properly use
can be obtained with OCT, while IA clearly depicts the choroid. both angiography and OCT in the diagnosis.
 198 Chapter 6 · Age-related macular degeneration

Case 107 Polypoidal choroidal vasculopathy: Fibrin deposits ②

A 63-year-old male, OD, BCVA 0.09

A: Color fundus photograph in the right eye: A elevated orange-red lesion is noticeable below in fovea centralis of the right eye ( ). A SRD is visible over
a wide area from the fovea centralis to the inferior fundus. B: FA in the right eye (6 minute, 23 seconds): Intense hyperfluorescent foci can be seen in the
fovea centralis and immediately nasally ( ). C: IA in the right eye (6 minutes, 37 seconds): The lesions with hyperfluorescent foci on FA are exhibiting strong
hyperfluorescence even on IA. These are polypoidal lesions ( ). An abnormal vascular network is also seen (white dashed circle). D: IR + OCT vertical scan
of the right eye: A SRD and a steep RPE protrusion are seen. E: Enlarged version of D [red dashed box]: The retina is protruding into the vitreous body due to
a protrusion that exists below the fovea centralis. Fibrin deposits in the outer retinal layers are exhibiting moderate to relatively high reflectivity (*). There
appears to be a RPE tear between the two (▶). The RPE protrusion indicated by (▶) is exhibiting moderate reflectivity and likely includes vascular components.

Image interpretation points

Fibrin deposits are sometimes apparent in PCV. In such case, of fibrin deposits. PCV exhibiting a classic CNV pattern due to
the pattern of classic CNV can be shown on FA due to staining fibrin deposits often responds well to treatment.
Case 108 · Polypoidal choroidal vasculopathy: A large abnormal vascular network
199 6
Case 108 Polypoidal choroidal vasculopathy: A large branching vascular network

A 78-year-old female, OS, BCVA 0.6

A: Color fundus photograph in the left eye: Circinate hard exudates are observed superotemporal to the fovea centralis of the left eye. No retinal hemor-
rhages are seen. There are drusen in the temporal macula. B: FA in the left eye (1 minute, 10 seconds): Hyperfluorescent foci can be seen temporal to the
optic disc and superotemporal to the fovea centralis ( ). The hard exudates are exhibiting hypofluorescence. C: IA in the left eye (1 minute, 10 seconds):
The hyperfluorescent lesions on FA are exhibiting hyperfluorescence on IA ( ). Both are polypoidal lesions. An branching vascular network is visible
immediately above the polypoidal lesions temporal to the optic disc. D: FA + OCT horizontal scan of the left eye: A SRD can be seen over a wide area. The
hard exudates exhibit strong reflectivity ( ). Flat elevation of the RPE is seen representing the branching vascular network (▶) in the spot corresponding
to the polypoidal lesion. Moderate reflectivity indicating choroidal neovascularization is noticeable between the RPE and Bruch’s membrane. E: FA + OCT
diagonal scan of the left eye: This is a scan passing through polypoidal lesions temporal to the fovea centralis. The polypoidal lesions exhibit a steep rise
and are composed of contents of both moderately and weakly reflective contents ( ). Cystoid spaces are seen in the sensory retina (*).

Image interpretation points

We can clearly see that hard exudates exhibit strong re- cular network is seen, which is seen as a flat RPE elevation on
flectivity on OCT images. In this case, a large branching vas- OCT.
 200 Chapter 6 · Age-related macular degeneration

Case 109 Polypoidal choroidal vasculopathy: Large foveal cystoid space

A 69-year-old female, OD, BCVA 0.06

A: Color fundus photograph in the right eye: A subretinal hemorrhage about 1.5 disc diameters in size is visible temporal in the temporal macula of the
right eye. The RPE of the fovea centralis appears to be atrophic. Multiple large drusen are seen superior to the optic disc. B: FA in the right eye (11 minutes,
30 seconds): Significant CME can be seen ( ). C: IA in the right eye (11 minutes, 30 seconds): A branching vascular network ( ) not visible on FA has
been detected. A polypoidal lesion is seen at the end of this branching vascular network (▶). Drusen can be seen as hyperfluorescent dots. D: FA + OCT
horizonta l scan of the right eye: A large cystoid space (*) is seen in the fovea centralis. High reflectivity due to a subretinal hemorrhage is seen temporally
( ). The temporal retina is detaching. A flat RPE elevation is visible immediately temporal to the fovea centralis (▶). E: FA + OCT vertical scan of the right
eye: A large fibrovascular PED with moderately reflective content can be seen ( ). The RPE line below the fovea centralis cannot be accurately traced
(between the two ▶). This corresponds to RPE atrophy that can be viewed with an ophthalmoscope.
(Continued on the next page)

Image interpretation points

This is a case where a large foveal cystoid space can be seen. and the existence of CNV may be associated with the develop-
RPE atrophy below the cystoid space may be attributed to the ment of CME in this case.
existence of the branching vascular network. Both RPE atrophy
 Case 109 · Enlargement of hemorrhagic pigment epithelial detachment
201 6
Case 109 Enlargement of hemorrhagic pigment epithelial detachment

F: Color fundus photograph in the right eye: Subretinal hemorrhage is increasing in size with partial organization. G: IR + OCT vertical scan of the right eye:
A RPE protrusion and hemorrhages anteriorly can be seen in the scan passing through the polypoidal lesion. H: Enlarged version of G [red dashed box]:
A tall PED is expanding (*). ( ) indicates high reflectivity due to the hemorrhage. I: IR + OCT vertical scan of the right eye: A vertical scan even further
temporally. A RPE protrusion with a steep rise is visible. While moderate reflectivity ( ) is observed immediately below the RPE it is unclear if this is CNV.
(continued on the next page)

Image interpretation points

Two months after initial diagnosis, a large hemorrhagic PED there does not appear to be an interruption in the line. In this
has developed. The highly reflective line of the RPE is partially area, there may be CNV confined to the RPE.
obscured by blockage of OCT beamdue to hemorrhages, but

polypoidal choroidal vasculopathy

 202 Chapter 6 · Age-related macular degeneration

Case 109 Enlargement of the abnormal vascular network

J: FA in the right eye: Fluoroscein accumulation is seen within the cystoid space ( ). K: IA in the right eye (10 minute, 15 seconds): The CNV is expanding
and its activity is increasing. Thick neovascular root is visible ( ). L: IR + OCT horizontal scan of the right eye: A tall PED can be seen temporally (*).
M: Enlarged version of L [red dashed box]: The cystoid spaces are clearly seen. The straight, thin, highly reflective line is Bruch’s membrane (▶). The RPE
is irregular and indistinct within the red dashed circle. Moderate reflectivity is seen immediately above Bruch’s membrane. This is Type 2 CNV.

Image interpretation points

After 1.5 months, CNV has passed through the RPE to form from the time of the initial diagnosis. Also, note that Bruch’s
Type 2 and is expanding in the area indicated by the red membrane is clearly defined.
dashed circle in M. It is highly likely that Type 2 CNV existed

polypoidal choroidal vasculopathy

Case 110 · Polypoidal choroidal vasculopathy: A large hemorrhagic pigment epithelial detachment
203 6
Case 110 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment epithelial detachment ①

A 64-year-old male, OD, BCVA 0.15

A: Color fundus photograph in the right eye: A large hemorrhagic PED is seen. There is little subretinal hemorrhage in the inferotemporal macula because a
tall polypoidal lesion is present in this area. B: FA in the right eye (1minute): Fluorescence is blocked due to subretinal hemorrhages, but a hyperfluorescent
lesion can be seen temporal to the fovea centralis ( ). C: IA in the right eye (1 minute): The subretinal characteristics are difficult to discern on IA due to
thick subretinal hemorrhages. D: FA + OCT horizontal scan of the right eye: We can see that CNV is expanding along the posterior surface of the RPE ( ).
E: Enlarged version of D [red dashed box]: A steep protrusion is seen in the RPE whose content is moderately reflective. A hyporeflective cavity appears to
exist within the protrusion ( ). There is a flat RPE protrusion in the (*) area indicated by ( ) and Bruch’s membrane is seen below this protrusion.
This corresponds to the area of an branching vascular network. The RPE line is slightly indistinct in the red dashed circle area.

Image interpretation points

This is a typical example of a large hemorrhagic PED associated with PCV. In this case, the thick subretinal hemorrhages obscure the
lesions on IA. The OCT findings are, however, suggestive of PCV.
 204 Chapter 6 · Age-related macular degeneration

Case 111 Polypoidal choroidal vasculopathy: A large hemorrhagic pigment epithelial detachment ②

A 56-year-old female, OS, BCVA 1.0

A: Color fundus photograph in the left eye: Subretinal hemorrhages and a hemorrhagic PED can be seen over a wide area from the fovea centralis to above
the vascular arcades. A large, elevated, orange-red lesion about 1.5 disc diameters is present superior to the fovea centralis ( ). B: IA montage of the left
eye (7 minutes, 3 seconds) in the left eye: Fluorescence is blocked due to thick subretinal hemorrhages and choroidal characteristics cannot be seen in detail.
The orange-red lesion superior to the fovea centralis is partially hyperfluorescent. The extent of subretinal hemorrhage and hemorrhagic PED is clearly
visible. C: FA + OCT horizontal scan of the left eye: The nasal RPE is relatively flat. There is a steep RPE protrusion adjacent to a gently sloping protrusion
outside of the fovea centralis. D: Enlarged version of C [red dashed box]: The RPE line (▶) is becoming partially indistinct temporal to the fovea centralis
(red dashed circle). Multiple small highly reflective dots are present in the outer retinal layers ( ). These may represent infiltrating macrophages.
(Continued on the next page)

Image interpretation points

This is also a case of hemorrhagic PED associated with PCV. reflective dots seen in the outer retinal layers are probably
Visual acuity is well preserved considering the significant fundus infiltrating macrophages.
findings. This is due to the preservation of the fovea. The highly
Case 111 · Spontaneous remission
205 6
Case 111 Spontaneous remission

E: Color fundus photograph in the left eye: Six weeks after initial diagnosis. Subretinal and choroidal hemorrhages have organized and are becoming yellow.
F: Color fundus photograph in the left eye: 22 months after initial diagnosis. The hemorrhages have been absorbed. The previous areas of hemorrhages
now exhibit a greyish white appearance. G: IR + OCT horizontal scan of the left eye: Image from the same day as F. The retinal contour is close to normal.
A mild, flat elevation is seen in the RPE. H: Enlarged version of G [red dashed box]: Defects are seen in the outer retinal layers at the fovea centralis. The
IS/OS and COST lines are no longer visible ( ). The high reflectivity seen in the foveal outer nuclear layer is reactive RPE migration or macrophages that
have phagocytized erythrocytes ( ). Bruch’s membrane (▶) is clearly visible below the RPE elevation immediately outside the fovea centralis.

Image interpretation points

This case illustrates that there can be significant improvement fovea centralis after the disappearance of hemorrhages regard-
without treatment despite large hemorrhages in the setting of less of no involvement of the fovea in the hemorrhagic lesions.
PCV. Damage can occur to the photoreceptor outer layer in the The mechanism of this is unknown.

polypoidal choroidal vasculopathy

pigment epithelial detachment
 206 Chapter 6 · Age-related macular degeneration

Case 112 Polypoidal choroidal vasculopathy: Optic disc type

A 70-year-old male, OD, BCVA 1.2

A: Color fundus photograph in the right eye: Elevated orange-red lesions are visible both superior and inferior to the fovea centralis and superiorly outside
the vascular arcade. The orange-red lesion superiorly outside the vascular arcade is associated with a hemorrhagic PED. B: FA in the right eye (1 minute,
15 seconds): Hyperfluorescent lesions can be seen over a wide area from the fovea centralis to the vascular arcade. The origin of the branching vascular
network is adjacent to the optic disc with one part exhibiting intense hyperfluorescence. C: IA in the right eye (1 minute, 15 seconds): The hyperfluorescent
lesions seen on FA are the a wide area of branching vascular network and polypoidal lesions. D: FA + OCT horizontal scan of the right eye: A undulating
RPE elevation with moderately reflective contents is seen suggestive of a fibrovascular PED. Bruch’s membrane is also seen. The RPE elevation is seen to
begin immediately adjacent to the optic disc indicating that the branching vascular network is CNV. E: Enlarged version of D [red dashed box]: There is no
interruption in the RPE line. The moderate reflectivity below the RPE is due to fibrovascular components (*). Bruch’s membrane (▶) is clearly visible. The
structure of the sensory retina is relatively preserved. F: FA + OCT vertical scan of the right eye: It is clear that CNV exists over a wide area.
(Continued on the next page)
Case 112 · Polypoidal choroidal vasculopathy: Optic disc type
207 6
Case 112 Continuation

G: Color fundus photograph in the right eye: Eight months after initial diagnosis. Suprachoroidal hemorrhages have. Best-corrected visual acuity is 0.1.
H: FA + OCT horizontal scan of the right eye: This is a B-scan through the active lesion superior to the optic disc. I: Enlarged version of H [red dashed box]:
The RPE appears to be disrupted at the sites indicated by ( ), however, these are in fact artifacts resulting from signal blocking due to blood vessels in
the sensory retina.

Image interpretation points

In this case, there are large subretinal and suprachoroidal hemorrhages associated with PCV, clearly indicating that PCV lesions are
only present in the sub-RPE space.

polypoidal choroidal vasculopathy

 208 Chapter 6 · Age-related macular degeneration

Case 113 Polypoidal choroidal vasculopathy: Polypoidal lesions and pigment epithelial detachment

A 56-year-old male, OD, BCVA 0.5

A: Color fundus photograph in the right eye: At initial diagnosis. A relatively new PED is seen seemingly with notches nasally and temporally at the edge of
the PED. Best-corrected visual acuity is 0.5. B: FA in the right eye (43 seconds): At initial diagnosis. Hyperfluorescent lesions consistent with the notched
sites are noticeable. C: IA in the right eye (43 seconds): During initial diagnosis. There appears to be polypoidal lesions consistent with the notched sites on
IA. D: Color fundus photograph in the right eye: Six months after initial diagnosis. The PED has slightly flattened and hard exudates are deposited along its
upper margin. The color of the RPE is abnormal on the temporal notch. Best-corrected visual acuity is 0.9. E: FA in the right eye (1 minute, 17 seconds):
Six months after initial diagnosis. The inside of the PED is hyperfluorescent. F: IA in the right eye (1 minute, 17 seconds): Six months after initial diagnosis.
The temporal notches exhibit intense fluorescence suggestive of a polypoidal lesion. I also appears to exist nasally. G: IA + OCT horizontal scan of the right
eye: 1 year, 6 months after initial diagnosis. There are 2 PEDs seen adjacent to the each other in the superotemporal to the fovea centralis. The temporal
PED is weakly reflective inside while the nasal PED is moderately reflective. (*). H: Enlarged version of G [red dashed box]: Bruch’s membrane is clearly seen
(▶). Type 2 CNV appears to be growing beneath the sensory retina from the RPE defect (red dashed circle).

Image interpretation points

The reflectivity of the two adjacent RPE protrusions differs significantly indicating different contents. The moderate reflectivity of
the nasal PED is due to CNV.
Case 114 · Polypoidal choroidal vasculopathy: Tomographic notch sign
209 6
Case 114 Polypoidal choroidal vasculopathy: Tomographic notch sign

An 84-year-old female, OD, BCVA 0.5

A: Color fundus photograph in the right eye: A serous PED about 1.5 disc diameters is seen temporally and includes the fovea centralis. No retinal hemor-
rhages or hard exudates are visible. B: FA in the right eye (3 minute, 43 seconds): Stronger hyperfluorescence can be seen in the temporal part of the PED.
There are notches at the superior and nasal (corresponding to the fovea centralis) margins of the PED. C: IA in the right eye (3 minutes, 43 seconds): Slight
hyperfluorescence is seen at the sites corresponding to the notches; however, a definitive diagnosis of PCV cannot be made. D: IR + OCT horizontal scan of
the right eye: A serous PED (*) is observed. A so-called »tomographic notch sign« is seen nasally with moderately reflective contents ( ). This indicates the
existence of vascular components. E: IR + OCT horizontal scan of the right eye: A serous PED (*) and a »tomographic notch sign« can be seen ( ).

Image interpretation points

This is a case where a serous PED is observed, a notch sign can cannot be confirmed with angiography and it is typical to classify
be seen on angiography, and a »tomographic notch sign« is this case as AMD.
visible on OCT. While PCV is suspected, the diagnosis of PCV
 210 Chapter 6 · Age-related macular degeneration

Case 115 Polypoidal choroidal vasculopathy: Case where the branching vascular network
has detached
An 81-year-old male, OD, BCVA 0.04

A: FA in the right eye (4 minute, 10 seconds): Irregular hyperfluorescent lesions about 2 disc diameters in size can be seen in the fovea centralis. B: IA in the
right eye (4 minutes, 10 seconds): An branching vascular network and polypoidal lesions are seen. C: Enlarged version of B [white dashed box]: Polypoidal
lesions are accumulating in grape-like structures. D: IR + OCT horizontal scan of the right eye: The polypoidal lesion is exhibiting steep RPE protrusion.
There is moderate reflectivity within the foveal PED. The branching vascular network is detaching from Bruch’s membrane ( ). E: Enlarged version of D
[red dashed box]: It is clear that the branching vascular network is detaching from Bruch’s membrane ( ). The polypoidal lesion and branching vascular
network have almost the same reflectivity and are also connected. The foveal sensory retina is significantly thinned, consistent with the patient's poor visu-
al acuity.

Image interpretation points

In this case, the branching vascular network is detaching from detachment is much less frequent than the detachment of
Bruch’s membrane. Normally, the branching vascular network polypoidal lesions. As a result, this kind of case is extremely
stably exists between Bruch’s membrane and RPE and its unusual.
Case 116 · Polypoidal choroidal vasculopathy: A massive lesion
211 6
Case 116 Polypoidal choroidal vasculopathy: A massive lesion

A 70-year-old male, OD, BCVA 0.1

A: Color fundus photograph in the right eye: A large lesion is occupying the posterior pole and the fovea is atrophic. There are also atrophic lesions superior
and inferior to the fovea centralis and hard exudates are visible temporal and inferior to the fovea. A large polypoidal lesion, which is still active, is observed
immediately inferior to the optic disc. B: FA in the right eye (52 seconds): The entire posterior pole of the retina is exhibiting strong hyperfluorescence.
C: IA in the right eye (52 seconds): A large branching vascular network is seen in the macula. D: IA + OCT horizontal scan of the right eye: The branching
vascular network can be seen as moderate reflectivity beneath the RPE ( ). There is a RPE disruption below the fovea centralis and Type 2 CNV is growing
into subretinal space (red dashed circle). E: IA + OCT vertical scan of the right eye: This is a scan passing through a large, elevated, orange-red lesion inferior
to the optic disc. A large polypoidal lesion is seen. There is moderate reflectivity ( ) beneath the RPE at the apex of the polypoidal lesion, suggestive of
fibrovascular contents.

Image interpretation points

This is a case of PCV with a large lesion. While the fovea is exists in the periphery of the large branching vascular network,
already atrophic, a highly active, elevated, orange-red lesion indicating that exudative changes is still ongoing.
 212 Chapter 6 · Age-related macular degeneration

6.6 Retinal angiomatous proliferation OCT findings

OCT images of RAP differ according to the stage.(5) In Stage 1,
Background mild intraretinal edema can be seen in the outer plexiform layer.
Retinal angiomatous proliferation is a pathological condition As the disease stage progresses, clear, highly reflective lesion be-
that was described by Yannuzzi et al. in 2006(1) (. Fig. 6-16). The comes visible in the retina. The highly reflective lesion is thought
condition where neovascularization originating from retinal to represent intraretinal neovascularization. Defects in the RPE
blood vessels occurs has been known for a long time based on corresponding to the intraretinal neovascularization can always
ophthalmoscopic findings, so rather than discovering the pathol- be seen, but it is sometimes difficult to ascertain if the disease
ogy, it is more appropriate to say this pathology was established stage is an early stage. The low frequency at which SRDs are seen
based on Yannuzzi’s systematic description. Gass proposed the in OCT images is a characteristic of RAP cases.
concept of occult chorioretinal anastomosis, which appears con- There are few histopathological reports on RAP. In a recent
tradictory to the disease concept of neovascularization derived paper by Klein and Wilson, neovascularization derived from
from retinal blood vessels.(2) Nevertheless, the concept of RAP retinal blood vessels reportedly passes through the small RPE
6 being neovascularization derived from retinal blood vessels is defect in the PED and appears to spread immediately beneath
more convincing. the RPE.(6) However, there do not yet appear to be any reports
Freund et al. contrasted this neovascularization with Type 1 demonstrating the correspondence between OCT and histologi-
CNV and Type 2 CNV classified by Gass and proposed that it cal images. . Fig. 6-17 contrasts the histological image in the re-
be called Type 3 CNV.(3) The clinical and genetic backgrounds port by Klein and Wilson with the OCT image from our similar
of patients with RAP differ slightly from the narrowly defined case. We can see that the histological image on the left and OCT
AMD and PCV, consistent with the difference in pathological image on the right correspond very well.
conditions of RAP and the other AMD types.(4)

. Fig. 6-16 Schematic diagram of RAP

A: Stage 1; Proliferation of the retinal blood vessels occurs. There are no changes beneath the RPE at this point. B: Stage 2A; The proliferative neovascular-
ization derived from the retinal blood vessels is growing to all layers of the retina, but no PED is developing. C: Stage 2B; A PED develops. D: Stage 3;
Anastomosis of retinal and choroidal neovascularization is complete. (These images are cited from Yannuzzi LA, Negr .A Nco S, Iida T, Carvalho C,
Rodriguez-Coleman H, Slakter J, Freund KB, Sorenson J, Orlock D, Borodoker N. Retinal angiomatous proliferation in age-related macular degeneration.
Retina. 2001;21:416–434.)
6.6 · Retinal angiomatous proliferation
213 6

. Fig. 6-17 Contrast of a histological image with an OCT image in similar RAP cases
In the histological image on the left, neovascularization is confined to the sensory retina ( ). The PED and neovascularization exist in contact with each
other. A partial RPE defect can be seen in the PED (▶). In the OCT image on the right, there is spreading of retinal neovascularization, indicated by ,
toward the RPE defect, indicated by ▶. (The histological image on the left is modified according to, Klein ML, Wilson DJ. Clinicopathologic correlation of
choroidal and retinal neovascular lesions in age-related macular degeneration. Am J Ophthalmol. 2011; 151: 161–169)

6.6.1 References

1) Yannuzzi LA, Negrao S, Iida T, et al. Retinal angiomatous proliferation in

age-related macular degeneration. Retina. 2001; 21:416–434.
2) Gass JDM, Agarwal A, Lavina AM, et al. Focal inner retinal hemorrhages in
patients with drusen: an early sign of occult choroidal neovascularization
and chorioretinal anastomosis. Retina. 2003; 23:741–751.
3) Freund KB, Ho IV, Barbazetto IA, et al. Type 3 neovascularization:
the expanded spectrum of retinal angiomatous proliferation. Retina.
2008; 28:201–211.
4) Matsumoto H, Sato T, Kishi S. Tomographic features of intraretinal neovas-
cularization in retinal angiomatous proliferation. Retina. 2010; 30:425–430.
5) Hayashi H, Yamashiro K, Gotoh N, et al. CFH and ARMS2 variations in age-
related macular degeneration, polypoidal choroidal vasculopathy, and
retinal angiomatous proliferation. Invest Ophthalmol Vis Sci. 2010; 51:5914–
5919.
6) Klein ML, Wilson DJ. Clinicopathologic correlation of choroidal and retinal
neovascular lesions in age-related macular degeneration. Am J Ophthal-
mol. 2011; 151:161–169.

retinal angiomatous proliferation

 214 Chapter 6 · Age-related macular degeneration

Case 117 Retinal angiomatous proliferation: Stage 1

An 85-year-old male, OS, BCVA 1.2

A: Color fundus photograph in the left eye: Multiple soft drusen exist in the macular area. A part of them are drusenoid PED rather than drusen. B: FAF in
the left eye: The drusenoid PED is exhibiting hyperfluorescence. The punctate hyperfluorescent foci that appear to be surrounding the macula are reticular
pseudodrusen. C: FA in the left eye (52 seconds): Two lesions exhibiting strong hyperfluorescence are visible. These are due to intraretinal neovasculariza-
tion (IRN). The drusen are hyperfluorescent even on FA. D: IA in the left eye (1 minute, 52 seconds): Different from FA, the drusen are exhibiting hypofluo-
rescence. IRN is seen. E: FA + OCT horizontal scan of the left eye: RPE protrusions as a result of drusen can be seen. The content of the drusen is exhibiting
moderate reflectivity. F: Enlarged version of E [red dashed box]: Moderate reflectivity extending in a longitudinal direction can be seen within the retina
( ). This appears to be IRN when pieced together with other findings. Small defects in the RPE can be seen immediately below the IRN (▶).

Image interpretation points

This is Stage 1 RAP. The intraretinal neovascularization (IRN) Notably, Bruch’s membrane is depicted as a thin, straight, highly
is clearly visible. There appear to be small defects in the reflective line at the base of the drusen. The content of the
RPE corresponding to IRN. RAP is often binocular and Stage 1 drusen exhibits moderate reflectivity, and the ELM and IS/OS of
cases are often discovered in the fellow eye of advanced the sensory retina immediately above the drusen is not depicted.
RAP.
Case 118 · Retinal angiomatous proliferation: Stage 2A
215 6
Case 118 Retinal angiomatous proliferation: Stage 2A

An 81-year-old male, OD, BCVA 0.15

A: Color fundus photograph: Macular edema can be seen temporal to the fovea centralis, but the changes that can be seen with an biomicroscopy are rela-
tively mild. Drusen are scattered. B: FA in the right eye (12 minutes, 26 seconds): Strong hyperfluorescent lesion can be seen temporal to the fovea centralis
( ). C: IA in the right eye (12 minutes, 26 seconds): Hyperfluorescence due to IRN can be seen ( ). D: IR + OCT vertical scan of the right eye: Cystoid spaces
(▶) can be seen superior and inferior to the fovea centralis E: Enlarged version of D [red dashed box]: Moderate reflectivity extending longitudinally across
retinal layers can be seen ( ). This is IRN. The RPE line is continuous and no clear defect can be seen. Particulates exhibiting high reflectivity are seen in the
outer nuclear layer (▶).

Image interpretation points

This is Stage 2A RAP. IRN is seen. The RPE line is flat and is Some researchers believe the highly reflective dots visible in the
not accompanied by a PED. It should be noted that the RAP outer nuclear layer are macrophages. The existence of these
stage classification does not necessarily represent disease punctiform highly reflective dots is generally thought to reflect
development. Rather, it would be best to consider the system a highly active clinical picture.
as a useful method of categorization.
 216 Chapter 6 · Age-related macular degeneration

Case 119 Retinal angiomatous proliferation: Stage 2B ①

A 71-year-old female, OS, BCVA 1.0

A: Color fundus photograph in the left eye: Multiple soft drusen can be seen in the macula. Preretinal hemorrhages and a few fibrin deposits are visible
slightly temporal to the fovea centralis. Good visual acuity is achieved since foveal changes are mild. B: FA in the left eye (46 seconds): Hyperfluorescent
lesions are seen superotemporal to the fovea centralis ( ). C: IAin the left eye (1 minute, 55 seconds): The hyperfluorescent lesions seen on FA can be con-
firmed as chorioretinal anastomosis ( ). D: IA + OCT horizontal scan of the left eye: A B-scan image passing through the fovea centralis. A subfoveal SRD is
seen (*). Cystoid spaces are seen in the sensory retina temporal to the fovea centralis. A PED exists temporally (▶). E: IA + OCT vertical scan of the left eye:
This is a B-scan passing through the area of chorioretinal anastomosis. Multiple infiltrating cells can be seen in the sensory retina ( ). The intraretinal neo-
vascularization appears to be growing down within the PED through the RPE break (red dashed circle). Bruch’s membrane is seen at the base of the PED (▶).

Image interpretation points

This is Stage 2B or Stage 3 RAP. Due to difficulty in determining tomosis of the choroidal and retinal blood vessels (chorioretinal
the internal state of PEDs on OCT, it is difficult to confirm anas- anastomosis) on OCT.
Case 120 · Retinal angiomatous proliferation: Stage 2B
217 6
Case 120 Retinal angiomatous proliferation: Stage 2B ②

An 84-year-old male, OD, BCVA 0.4

A: Color fundus photograph in the right eye: Retinal hemorrhages as well as fibrin deposits are visible in the fovea centralis. Multiple drusen are seen in
the macular area. B: FA in the right eye (1 minute, 24 seconds): Two strong hyperfluorescent foci are visible ( ). The drusen are also exhibiting strong
hyperfluorescence. C: IA in the right eye (1 minute, 24 seconds): Chorioretinal anastomosis is clearly seen ( ). The PED is hypofluorescent on IA ((▶ ) area).
D: IA + OCT horizontal scan of the right eye: A large PED can be seen. A break is noticeable in the RPE (▶). Such findings are sometimes referred to as
»bump sign«. Moderate reflectivity due to fibrin deposits and IRN is visible anterior to the RPE break ( ). Exudative changes can be seen in the retina.
E: IA + OCT vertical scan of the right eye: A large PED is visible. The high reflectivity (▶) observed on the posterior surface of the RPE may be neovascular-
ization that has grown into the PED, but it could also be exudate. Cystoid spaces can be seen in the sensory retina.

Image interpretation points

In this case, a large PED is seen suggesting RAP Stage 2B. Since this wavelength does not allow the OCT beam to suffi-
Neovascularization can be seen growing into the PED through ciently reach below the RPE, it is difficult to determine the con-
the RPE break represented by the partial disruption in the tents of the PED. Even with the development of OCT using 1 µm
RPE line. band light sources, it is not easy to determine the contents of
Most spectral-domain OCT devices currently on the market the PED.
use a light source with a center wavelength of about 840 nm.
 218 Chapter 6 · Age-related macular degeneration

Case 121 Retinal angiomatous proliferation: Stage 3

A 72-year-old female, OS, BCVA 0.2

A: Color fundus photograph in the left eye: Multiple drusen can be seen mainly in the temporal macula. A portion of them are reticular pseudodrusen.
A large PED is seen at the fovea centralis. Tiny retinal hemorrhages are also visible. B: FA in the left eye (3 minutes, 18 seconds): A CME is appreciated.
C: IA in the left eye (3 minutes, 18 seconds) : The PED is exhibiting hypofluorescence. CNV is seen ( ). D: IA + OCT horizontal scan of the left eye: A large
PED can be seen. The RPE line is disrupted. Cystoid spaces are observed in the sensory retina and a SRD is visible between the fovea centralis and optic
disc. Traction as exerted by the posterior vitreous cortex is also present (▶). E: Enlarged version of D [red dashed box]: Moderate reflectivity is seen within
the PED (*). This is a fibrovascular PED. The RPE line is disrupted ( ). The neovascularization from the retina appears to be growing posterior to the RPE
through the RPE break temporal to the fovea centralis. The reflectivity intensity of the lesions anterior and inferior to the RPE break appears constant,
suggesting this is continuous tissue. Multiple cystoid spaces (*) are seen within the sensory retina. The RPE nasal to the PED is gently elevated (red dashed
circle). CNV appears to exist in this area.
(Continued on the next page)

Image interpretation points

This is a case of typical Stage 3 RAP. The retinal neovasculariza- ing with CNV. The RPE nasal to the lesions is gently sloping and
tion can be seen passing through the RPE tear and anastomos- CNV appears to exist below this.
Case 121 · After treatment with anti-VEGF treatment
219 6
Case 121 After treatment with anti-VEGF treatment

A 72-year-old female, OS, BCVA 0.1

F: Color fundus photograph in the left eye: Exudative changes in the macular area are receding. Retinal hemorrhages are no longer seen. G: IR + OCT hori-
zontal scan of the left eye: The cystoid spaces have also almost disappeared on OCT. The internal reflectivity of the PED is actually increasing, indicating the
existence of a fibrovascular PED. H: Enlarged version of G [red dashed box]: Moderate reflectivity is observed within the PED ( ). Bruch’s membrane is
clearly seen at the base of the PED (▶). The CNV below the RPE that was seen before treatment remains (red dashed circle).

Image interpretation points

It is clear that exudative changes in the retina are receding as a When there is an RPE protrusion as in this case, neovasculariza-
result of treatment with anti-VEGF treatment. tion may be present on the choroidal side of the RPE. Thus, it is
important to closely observe the features in the choroidal side of
the RPE line.

retinal angiomatous proliferation

 220 Chapter 6 · Age-related macular degeneration

6.7 Malattia leventinese 6.7.1 References

Background 1) Stone EM, Lotery AJ, Munier FL, et al. A single EFEMP1 mutation associat-
ed with both Malattia Leventinese and Doyne honeycomb retinal dystro-
Malattia leventinese is a rare disease with a dominant form of
phy. Nat Genet. 1999; 22:199–202.
hereditary characterized by juvenile binocular onset and radially 2) Souied EH, Leveziel N, Letien V, et al. Optical coherent tomography fea-
arranged drusen. Drusen in the vicinity of the fovea centralis are tures of malattia leventinese. Am J Ophthalmol. 2006; 141:404–407.
large, have a strong tendency to become confluent, and those in 3) Gerth C, Zawadzki RJ, Werner JS, et al. Retinal microstructure in patients
the periphery often exhibit a typical radial array. This disease is with EFEMP1 retinal dystrophy evaluated by Fourier domain OCT. Eye
sometimes referred to by the disease names of familial drusen or (Lond). 2009; 23:480–483.

Doyne’s honeycomb retinal dystrophy. It is known that genetic

abnormalities in Fibulin-3 (EFEMP1) are associated with this
disease.(1)

6 OCT findings
Patients with malattia leventinese characteristically maintain
good visual acuity despite the prominent abnormalities in the
fundus. Since previous reports on histopathological findings for
malattia leventinese have not been enough, the reason for this is
not entirely understood. However, based on a small number of
reports on OCT findings, visual acuity may be maintained due to
relatively mild changes in the sensory retina. One report using
time-domain OCT stated that while the RPE and Bruch’s mem-
brane appeared thick, the sensory retina was relatively well pre-
served.(2) However, according to a report using spectral-domain
OCT, damage to the IS/OS can be seen.(3)
Case 122 · Malattia leventinese: A typical example
221 6
Case 122 Malattia leventinese: A typical example

A 39-year-old male, OD and OS, BCVA 1.5 and 1.5 respectively

A: Color fundus photograph in the left eye: There is a large number of drusen over a wide area of the macula. Drusen can also be seen near the optic disc.
B: Enlarged version of A [white dashed box]: Drusen surrounding the optic disc are clearly visible. Most of the drusen near the fovea centralis are confluent.
C: Color fundus photograph: The same findings as the left eye are seen. RPE pigment changes are also present. D: FA in the right eye (1 minute, 42 seconds):
The RPE pigment changes near the fovea centralis are exhibiting hypofluorescence. Multiple drusen forming a radial pattern can be seen temporal to the fovea
centralis. E: Enlarged version of D [white dashed box]: Drusen forming a radial pattern are clearly visible. F: IA in the right eye (1 minute, 42 seconds): The small
drusen are also exhibiting hyperfluorescence on IA. No CNV can be seen. G: IR + OCT horizontal scan of the right eye: The subfoveal RPE is gently elevated. The
retinal structure is largely preserved. H: Enlarged version of G [red dashed box]: The ELM can be traced in the area indicated by ( ). The photoreceptor
inner segment is disrupted on the nasal and temporal side of the area indicated by ( ). A relatively tall PED is seen nasally ( ). In the red dashed circle
area, an outer retinal tubulation is seen. Reflectivity of Bruch’s membrane appears to be increasing (▶).
 222 Chapter 6 · Age-related macular degeneration

I: IR + OCT vertical scan of the right eye: The retinal structure is well preserved. J: Enlarged version of I [red dashed box]: The RPE is slightly elevated from
Bruch’s membrane, and deposits with moderate reflectivity are seen between the RPE and Bruch’s membrane. Reflectivity of Bruch’s membrane appears
stronger than normal on this scan as well. The ELM line can be traced. There is a RPE break in the red dashed circle area.

Image interpretation points

Malattia leventinese is a relatively rare disease. As with typical protein deposits. While older reports state that there is histo-
drusen, the drusen are located beneath the RPE. Mutated pro- logical thickening of Bruch’s membrane, further studies will
teins (EFEMP1) are known to be deposited in sub-RPE space be necessary to determine if Bruch’s membrane does indeed
in this disease. The moderate reflectivity between the RPE and have increased reflectivity indicating the thickened Bruch’s
Bruch’s membrane is thought to be due to these mutated membrane.
6.8 · Idiopathic choroidal neovascularization
223 6
6.8 Idiopathic choroidal neovascularization 6.8.1 References

Background 1) Cleasby GW. Idiopathic focal subretinal neovascularization. Am J Ophthal-

mol. 1976; 81:590–599.
Idiopathic choroidal neovascularization (idiopathic CNV) is a
2) Machida S, Hasegawa Y, Kondo M, et al. High prevalence of myopia in
disease often seen in relatively young women, mostly occuring in Japanese patients with idiopathic focal subretinal neovascularization.
moderately myopic eyes.(1) The diagnosis of idiopathic CNV can Retina. 2006; 26:170–175.
only be applied once all other factors that cause CNV have been 3) Iida T, Hagimura N, Sato T, et al. Optical coherence tomographic features
excluded. Presumed ocular histoplasmosis is one disease that of idiopathic submacular choroidal neovascularization. Am J Ophthalmol.
requires differentiation, although it is believed that this disease 2000; 130:763–768.

does not exist in Japan. The biggest challenge in clinical settings,

however, is differentiation from myopic CNV.(2) Whereas idio-
pathic CNV primarily occurs in patients under 50, myopic CNV
rarely occurs in patients under 50.
Punctate inner choroidopathy (PIC) is also cited as a disease
requiring differentiation. Please refer to »Chapter 7 Retinal de-
generation« for PIC (7 p. 238–241).

OCT findings
CNV seen in this disease is Type 2 CNV. Tall, cone-shaped CNV
is seen in the active stage, but as the disease progresses, CNV is
enveloped by the RPE, making the borders of the RPE and CNV
indistinct. As a result, this disease often looks like Type 1 CNV
on OCT.(3)
 224 Chapter 6 · Age-related macular degeneration

Case 123 Idiopathic choroidal neovascularization: A fresh case

A 33-year-old female, OS, BCVA 0.6, refraction –4.75D, axial length 25.96 mm

A: Color fundus photograph in the left eye: This is a tigroid fundus. Annular CNV can be seen at the fovea centralis. Thin subretinal hemorrhages are present
around the CNV. B: FA in the left eye (1 minute, 31 seconds): Annular hyperfluorescence due to fluorescein leakage from CNV is visible. Hyperfluorescent
lesions due to window defects are seen inferotemporal to the CNV. C: IA in the left eye (1 minute, 31 seconds): Annular hypofluorescent lesion is exhibited
on the CNV at the fovea centralis on IA. D: IR + OCT horizontal scan of the left eye: CNV at the fovea centralis is seen. There is also a very thin SRD. The RPE
line is disrupted as a result of CNV. E: Enlarged version of D [red dashed box]: While the ELM line is seen over almost the entire length of the scan, the IS/OS
line is disrupted near the CNV.

Image interpretation points

This is Type 2 CNV that has occurred in a relatively young female RPE line is disrupted as a result of CNV and envelopment of CNV
with moderate myopia. As these images were taken soon after by the RPE has not yet been completed.
disease onset, the characteristics of Type 2 CNV are evident. The
Case 124 · Idiopathic choroidal neovascularization: Envelopment by RPE cells
225 6
Case 124 Idiopathic choroidal neovascularization: Envelopment by RPE cells

A 36-year-old male, OD, BCVA 0.4, refraction –7.0D, axial length 27.12 mm

A: Color fundus photograph in the right eye: This is a tigroid fundus. Annular CNV can be seen beneath the fovea centralis. Thin subretinal hemorrhages are
present around the CNV. B: FA in the right eye (23 seconds): Annular hyperfluorescence due to fluorescein leakage from CNV is seen. Around this, there is
hypofluorescence due to subretinal hemorrhages. C: IA in the right eye (23 seconds): The hypofluorescent area is smaller on IA than on FA. This finding indi-
cates that the hypofluorescence on FA is not only due to retinal hemorrhages, but also due to a combination of two elements. The infrared light in IA can
pass through the hemorrhages. The hypofluorescence surrounding the CNV on IA is due to the RPE cells enveloping the CNV. D: FA + OCT horizontal scan of
the right eye: Type 2 CNV is enveloped by the RPE. A thin SRD (*) is present around the CNV. E: Enlarged version of D [red dashed box]: Subretinal hemor-
rhages ( ), CNV with moderate reflectivity anteriorly (red dashed circle), as well as cells infiltrating into the sensory retina can be seen ( ). (Continued on
the next page)

Image interpretation points

While idiopathic CNV generally occurs in women with moderate infiltrating cells can be seen immediately anterior to the CNV,
myopia, this is Type 2 CNV that has occurred in a relatviely young and the border region between the outer plexiform layer and
male with high myopia. While the possibility cannot be ex- the outer nuclear layer. While it is natural to assume these repre-
cluded that this is a case of myopic CNV, this disease entity rarely sent reactive proliferations of RPE cells and macrophages that
occurs in the 4th decade of life. This case may have been typical have phagocytized erythrocytes, there is not enough evidence
Type 2 CNV, but the scarring mechanism had already started to support this claim.
at initial diagnosis. Moderate reflectivity thought to be due to
 226 Chapter 6 · Age-related macular degeneration

Case 124 After treatment with anti-VEGF treatment

A 36-year-old male, OD, BCVA 0.8

F: Color fundus photograph in the right eye: There is a scar forming beneath the fovea centralis. The hemorrhages has disappeared. G: IR + OCT horizontal
scan of the right eye: A RPE protrusion is seen beneath the fovea centralis. No SRD can be seen. H: IR + OCT vertical scan of the right eye: Cystoid spaces
are seen at the superior part of the fovea. I: Enlarged version of H [red dashed box]: A cystoid space ( ) is present in the Henle’s fibrous layer of the outer
plexiform layer. The ELM is seen almost entirely uninterrupted (red dashed circle). The IS/OS is difficult to distinguish. However, if closely observed, the
irregular ELM and IS/OS lines can just barely be seen (red dashed circle). Infiltrating cells are scattered in the retina.

Image interpretation points

Vitreous injection of bevacizumab (Avastin) was successful. acuity has improved. The CNV has scarred enveloped by the RPE.
The retinal structure is relatively well preserved and visual The SRD has disappeared.

idiopathic choroidal neovascularization

Case 125 · Idiopathic choroidal neovascularization: The scarring process
227 6
Case 125 Idiopathic choroidal neovascularization: The scarring process

A 38-year-old female, OD, BCVA 0.8, refraction –12.5D, axial length 27.65 mm

A: Color fundus photograph in the right eye: The optic disc is tilted. There is an atrophic lesion between the optic disc and fovea centralis. CNV probably
occurred at this location in the past and spontaneously receded. Still active CNV can be seen beneath the fovea centralis. B: FA in the right eye (3 minutes,
2 seconds): Hyperfluorescence due to fluorescien leakage from CNV is seen with relatively indistinct border. The atrophic lesion is also exhibiting hyper-
fluorescence with distinct border. C: IA in the right eye (3 minutes, 2 seconds): A hypofluorescent ring is seen around the CNV. This may be due to the pro-
liferative reaction of the RPE cells as seen in case 124. D: FA + OCT horizontal scan of the right eye: Type 2 CNV can be seen. Retinal changes are not pro-
nounced. The SRD is essentially not seen. E: Enlarged version of D [red dashed box]: CNV growing past the RPE is seen. The line thought to be the IS/OS is
somewhat traceable, but is partially indistinct (▶). High reflectivity due to infiltrating cells can be seen in the retina ( ). (Continued on the next page)

Image interpretation points

There is a scar lesion superonasally outside the fovea centralis. accompanied by punctate inner choroidopathy. Although the
It should be taken into consideration that this case might be CNV is still active, the RPE has already begun to envelope it.
 228 Chapter 6 · Age-related macular degeneration

Case 125 Course without treatment

A 38-year-old female, OD, BCVA 1.2, refraction –12.5D, axial length 27.65 mm

F: Color fundus photograph in the right eye: A small scar lesion is seen beneath the fovea centralis. G: IR + OCT horizontal scan of the right eye: A gently
sloping RPE protrusion due to envelopment by RPE cells is seen beneath the fovea centralis. In the area of peripapillary atrophy ( ), the reflectivity of
the underlying sclera is enhanced by the excessive measurement beam penetration due to the RPE defects and choroidal atrophy. H: Enlarged version of G
[red dashed box]: The proliferated RPE cells and scar tissue beneath the fovea centralis has similar reflectivity, making the RPE line indistinct. The structure
of the outer retinal layers is preserved and the ELM line has been almost completely restored. The IS/OS line can also be mostly traced. I: Time-course of
OCT horizontal scan images of the right eye: From the left, images of relatively fresh CNV, scarring in progress (at initial diagnosis), and scarring upon com-
pletion (1 year after initial diagnosis, enlarged version of H) are shown side-by-side.

Image interpretation points

Since the patient declined treatment, a follow up was per- The scarring process of Type 2 CNV was observed and the
formed without treatment for one year after intial diagnosis. natural progression of the disease can be appreciated.

idiopathic choroidal neovascularization

 229
7

Retinal degeneration
7.1 Multiple evanescent white dot syndrome – 232
References – 232

Case 126 Multiple evanescent white dot syndrome:

A typical example – 233, 234

7.2 Acute zonal occult outer retinopathy – 235

References – 235

Case 127 Acute zonal occult outer retinopathy: Eye with a history
of MEWDS – 236

7.3 Punctate inner choroidopathy – 238

References – 238

Case 128 Punctate inner choroidopathy: Atrophic pigmented scars – 239

Case 129 Punctate inner choroidopathy: Case complicated by CNV

(fellow eye of case 128) – 240

Case 130 Punctate inner choroidopathy: Yellowish-white spots

and CNV – 241

7.4 X-linked juvenile retinoschisis – 242

References – 242

Case 131 X-linked juvenile retinoschisis: Retinoschisis over

a wide area – 243, 244

Case 132 X-Linked juvenile retinoschisis: Retinoschisis confined

to the macula – 245

7.5 Stargardt disease – 246

References – 246

Case 133 Stargardt disease: A typical example – 247, 248

7.6 Vitelliform macular dystrophy and adult-onset foveomacular

vitelliform dystrophy – 249
References – 250
Case 134 Adult-onset foveomacular vitelliform dystrophy:
Vitelliform stage – 251

Case 135 Adult-onset foveomacular vitelliform dystrophy:

Pseudohypopyon stage – 252

Case 136 Adult-onset foveomacular vitelliform dystrophy:

The course – 253

7.7 Pseudoxanthoma elasticum – 254

References – 254

Case 137 Pseudoxanthoma elasticum: A case of Type 1 CNV – 255

Case 138 Pseudoxanthoma elasticum: A case of Type 2 CNV – 256

Case 139 Pseudoxanthoma elasticum: A case of polypoidal lesions – 257

Case 140 Pseudoxanthoma elasticum: Outer retinal tubulation – 258

7.8 Cancer-associated retinopathy – 259

References – 259

Case 141 Cancer-associated retinopathy: Damage to the outer retinal

layers – 260

Case 142 Cancer-associated retinopathy: Retinal vasculitis – 261

7.9 Bietti crystalline dystrophy – 262

References – 262

Case 143 Bietti crystalline dystrophy: A typical example – 263

Case 144 Bietti crystalline dystrophy: Outer retinal tubulation – 264

7.10 Retinitis pigmentosa – 265

References – 266

Case 145 Retinitis pigmentosa: A typical example – 267, 268

Case 146 Retinitis pigmentosa: Cystoid macular edema – 269

Case 147 Retinitis pigmentosa: Vitreomacular traction syndrome – 270

7.11 Fundus albipunctatus – 271

References – 271
 231

Case 148 Fundus albipunctatus: A typical example – 272

7.12 Oguchi disease – 274

References – 274

Case 149 Oguchi disease: A typical example – 275

Case 150 Oguchi disease: Cystoid space formation and golden sheen
fundus reflex (fellow eye of case 149) – 276
 232 Chapter 7 · Retinal degeneration

7.1 Multiple evanescent white dot syndrome References

Background 1) Jampol LM, Sieving PA, Pugh D, et al. Multiple evanescent white dot syn-
drome. I. Clinical findings. Arch Ophthalmol. 1984; 102:671–674.
Multiple evanescent white dot syndrome (MEWDS) was first re-
2) Sieving PA, Fishman GA, Jampol LM, et al. Multiple evanescent white dot
ported by Jampol in 1984.(1, 2) It typically affects young women, syndrome. II. Electrophysiology of the photoreceptors during retinal pig-
is unilateral, causes rapid visual decline, and sometimes results ment epithelial disease. Arch Ophthalmol. 1984; 102:675–679.
in complaints of visual field defects and photopsia. The patho- 3) Ikeda N, Ikeda T, Nagata M, et al. Location of lesions in multiple evanes-
genesis is unclear, but precursory flu-like symptoms suggest a cent white dot syndrome and the cause of the hypofluorescent spots ob-
viral infection. Various grey-white to yellowish-white patches served by indocyanine green angiography. Graefes Arch Clin Exp Ophthal-
mol. 2001; 239:242–247.
ranging from 100 to 200 µm in size frequently occur between the
4) Ie D, Glaser BM, Murphy RP, Gordon LW, et al. Indocyanine green angiog-
deep layers of the retina and RPE mainly in the posterior pole. raphy in multiple evanescent white-dot syndrome. Am J Ophthalmol.
In particular, yellow to orange granularity is visible in the fovea 1994; 117:7–12.
centralis. The fundus findings disappear in the early stage of the 5) Obana A, Kusumi M, Miki T. Indocyanine green angiographic aspects of
disease and are sometimes not visible during initial diagnosis. multiple evanescent white dot syndrome. Retina. 1996; 16:97–104.
6) Barile GR, Reppucci VS, Schiff WM, et al. Circumpapillary chorioretino-
Hyperfluorescent dots that are described as »wreathlike« can
7 be seen during the early phase on FA. Most of these hyper-
pathy in multiple evanescent white-dot syndrome. Retina. 1997; 17:75–
77.
fluorescent dots are consistent with yellowish-white spots 7) Gross NE, Yannuzzi LA, Freund KB, et al. Multiple evanescent white dot
although they are not entirely identical. Fluorescein staining of syndrome. Arch Ophthalmol. 2006; 124:493–500.
these lesions can be seen in the late phase FA.(3–7) Distinctive 8) Spaide RF, Koizumi H, Freund KB. Photoreceptor outer segment abnor-
malities as a cause of blind spot enlargement in acute zonal occult outer
hypofluorescent spots can be seen in the late phase on IA. These
retinopathy-complex diseases. Am J Ophthalmol. 2008; 146:111–120.
hypofluorescent spots can be observed with a biomicroscopy 9) Bryan RG, Freund KB, Yannuzzi LA, et al. Multiple evanescent white dot
even when the white spots are indistinct.(3–7) syndrome in patients with multifocal choroiditis. Retina. 2002; 22:317–
The symptoms of MEWDS and fundus findings spontane- 322.
ously recede within approximately 1 to 3 months, and it is con- 10) Fine HF, Spaide RF, Ryan EH Jr, et al. Acute zonal occult outer retinopathy
sidered a disease with good visual prognosis. However, there are in patients with multiple evanescent white dot syndrome. Arch Ophthal-
mol. 2009; 127:66–70.
cases where visual acuity only recovers to 0.6–0.7 or recurs.
11) Nguyen MH, Witkin AJ, Reichel E, et al. Microstructural abnormalities in
These cases are thought to be an intermediate type of MEWDS MEWDS demonstrated by ultrahigh resolution optical coherence tomog-
and acute zonal occult outer retinopathy (AZOOR), which has a raphy. Retina. 2007; 27:414–418.
relatively poor prognosis. MEWDS is considered part of a wide 12) Sikorski BL, Wojtkowski M, Kaluzny JJ, et al. Correlation of spectral optical
disease concept known as AZOOR complex syndrome.(8–10) coherence tomography with fluorescein and indocyanine green angiog-
raphy in multiple evanescent white dot syndrome. Br J Ophthalmol. 2008;
92:1552–1557.
OCT findings
13) Li D, Kishi S. Restored photoreceptor outer segment damage in multiple
The IS/OS line focally disappears in the acute phase and is known evanescent white dot syndrome. Ophthalmology. 2009; 116:762–770.
to recover in the recovery phase.(11–14) This IS/OS defect area is 14) Hangai M, Fujimoto M, Yoshimura N. Features and function of multiple
reportedly consistent with white dots or hypofluorescent spots evanescent white dot syndrome. Arch Ophthalmol. 2009; 127:1307–1313.
on IA,(11) but this consistency is only during the acute phase.(14)
In the acute phase, moderately reflective lesions extending from
the RPE to the outer nuclear layer via the disrupted IS/OS level,
consistent with the disrupted part of the IS/OS, can be observed
(the IS/OS line defects and hypofluorescent spots on IA are
consistent during this phase).(13, 14) These moderately reflective
lesions take on an impressive columnar or patchy form particu-
larly in the fovea centralis. The IS/OS line eventually disappears
over a wide area, and the moderately reflective lesions becomes
smaller and concurrently increases in number. These moder-
ately reflective lesions at the later phase are still consistent with
hypofluorescent spots on IA.(14) The moderately reflective lesions
eventually disappear, and the IS/OS line is restored to almost
normal over the course of 1 to 3 months, but irregularities
occasionally remain.
Case 126 · Multiple evanescent white dot syndrome: A typical example
233 7
Case 126 Multiple evanescent white dot syndrome: A typical example

A 35-year-old female, OS, BCVA 1.5

A: Color fundus photograph in the left eye: At initial diagnosis. Multiple grey-white or yellowish-white spots of various sizes are visible around the optic
disc. The large spots are annular and hollow in the middle. B: Static automated perimetry in the left eye: At initial diagnosis. Enlargement of Mariotte’s blind
spot is significant. C: FA montage of the left eye (7 minutes): At initial diagnosis. The white spots exhibit hyperfluorescence. D: IA montage of the left eye
(15 minutes): At initial diagnosis. The white spots become distinct hypofluorescent spots in the IA late stage. Weak hypofluorescence is evident around the
optic disc and arcade vessels. E: IA + OCT horizontal scan of the left eye + enlarged version [red and blue dashed box]: At initial diagnosis. Moderately reflec-
tive lesions ( ) consistent with hypofluorescent spots on IA are seen to extend from the RPE to the outer nuclear layer. F: IA + OCT vertical scan of the left
eye + enlarged version [red and blue dashed box]: Two weeks after initial diagnosis. Best-corrected visual acuity declined to 0.7. The hyporeflective spots on
IA has decreased in size and increased in number. ( ). Small moderately reflective lesions on OCT corresponds with these hyporeflective spots on IA, and
has decreased in height and width. The IS/OS line in the the area with these findings is missing.
(Continued on the next page)
 234 Chapter 7 · Retinal degeneration

Case 126 Continuation

G: Microperimetry-1 (MP-1) of the left eye: Temporal changes are shown. From the left, the number of days from initial visit (best-corrected visual acuity)
is: initial visit (1.5), 4 days (0.5), 13 days (0.5), 20 days (0.7), and 34 days (1.2). Scotomas appear to be shifting from the nasal side to the temporal side.
H: Enlarged version of the OCT horizontal scan of the fovea centralis in the left eye: Figures are arranged corresponding to the MP-1 results in the time after
initial visit. The IS/OS of the fovea centralis disappeared, and the columnar moderate reflectivity extending from the RPE to the outer nuclear layer at the
foveola has appeared and then disappeared, after which the IS/OS has restored. Retinal sensitivity decrease on MP-1 seems to correspond to these OCT
findings. I: Enlarged version of the OCT vertical scan of the extrafoveal region in the left eye: Images ① at initial diagnosis, ② 4 days later, and ③ 34 days
later. The moderately reflective lesions in the inferior macula became smaller, and eventually disappeared. The IS/OS line is almost completely restored.
(Modified according to Hangai M, et al. Features and functions of multiple evanescent white dot syndrome Arch Ophthalmol. 2009; 127: 1307–1313)

Image interpretation points

This is a typical case of MEWDS. The patient consulted us optic disc on the MP-1, but this gradually shifted to the temporal
4 days after becoming aware of visual field defects in her right side and had almost resolved about one month later. On OCT,
eye. Enlargement of Mariotte’s blind spot was observed at moderately reflective lesions spreading from the RPE to the outer
initial diagnosis, but there was no visual acuity impairment. nuclear layer and disruption of the surrounding IS/OS line, could
After 4 days, best-corrected visual acuity had declined to 0.5, be seen in the region corresponding to that of the decreased
but it spontaneously improved to 1.2 after 34 days. Irregularity retinal sensitivity. During the disease course, a decrease in size of
and disruption of the foveal IS/OS line corresponding to the moderately reflective findings and enlargement of the disrupted
visual acuity decline were noted, followed by the development IS/OS line were observed. Eventually, the IS/OS line was restored
of a columnar, moderately reflective lesions spreading from the associated with improvement of retinal sensitivity. The moder-
RPE to all foveal layers. These abnormal findings disappeared ately reflective lesions at the photoreceptor level were consistent
together with visual acuity improvement about one month with hypofluorescent spots on IA and were considered distinctive
after initial diagnosis. During initial diagnosis, a severe decline MEWDS findings.
in retinal sensitivity was mainly observed in the vicinity of the
7.2 · Acute zonal occult outer retinopathy
235 7
7.2 Acute zonal occult outer retinopathy References

Background 1) Gass JD. Acute zonal occult outer retinopathy. Donders Lecture: The
Netherlands Ophthalmological Society, Maastricht, Holland, June 19,
Acute zonal occult outer retinopathy (AZOOR) is a disease first
1992. J Clin Neuroophthalmol. 1993; 13:79–97.
reported by Gass in 1994.(1) It typically affects one or both eyes of 2) Gass JD, Agarwal A, Scott IU. Acute zonal occult outer retinopathy: a long-
young women with moderate to high myopia, no clear abnor- term follow-up study. Am J Ophthalmol. 2002; 134:329–339.
malities are exhibited on ophthalmoscopy or fluorescein fundus 3) Gass JD. Are acute zonal occult outer retinopathy and the white spot syn-
angiography, and patients become aware of rapid visual acuity dromes (AZOOR complex) specific autoimmune diseases? Am J Ophthal-
decline, visual field defects, and photopsia. Visual acuity is pre- mol. 2003; 135:380–381.
4) Spaide RF, Koizumi H, Freund KB. Photoreceptor outer segment abnor-
served at 0.5 or above in roughly 70% of cases, but AZOOR can
malities as a cause of blind spot enlargement in acute zonal occult outer
cause severer visual impairment in rare cases.(2) Central scoto- retinopathy-complex diseases. Am J Ophthalmol. 2008; 146:111–120.
mas are common visual field defects. 5) Fine HF, Spaide RF, Ryan EH Jr, Matsumoto Y, Yannuzzi LA. Acute zonal
Differences from MEWDS include no clear abnormalities on occult outer retinopathy in patients with multiple evanescent white dot
biomicroscopy or fluorescein fundus angiography, visual impair- syndrome. Arch Ophthalmol. 2009; 127:66–70.
6) Li D, Kishi S. Loss of photoreceptor outer segment in acute zonal occult
ment recovering only about 1/4, and visual field defects being
outer retinopathy. Arch Ophthalmol. 2007; 125:1194–1200.
hard to cure. Narrowing of retinitis pigmentosa-like retinal blood 7) Zibrandtsen N, Munch IC, Klemp K, Jørgensen TM, Sander B, Larsen M.
vessels and RPE depigmentation spots can be seen in some cases. Photoreceptor atrophy in acute zonal occult outer retinopathy. Acta Oph-
Diseases where the clinical symptoms overlap include AZOOR, thalmol. 2008; 86:913–916.
MEWDS, acute idiopathic blind spot enlargement, punctate 8) Takai Y, Ishiko S, Kagokawa H, Fukui K, Takahashi A, Yoshida A. Morpho-
logical study of acute zonal occult outer retinopathy (AZOOR) by multi-
inner choroidopathy (PIC), and multifocal choroiditis and
planar optical coherence tomography. Acta Ophthalmol. 2009; 87:408–
panuveitis. These diseases are thought to belong in the same 418.
broader category and are known as the »AZOOR complex 9) Fujiwara T, Imamura Y, Giovinazzo VJ, Spaide RF. Fundus autofluorescence
diseases«.(3, 4) In addition, AZOOR can occur in eyes affected by and optical coherence tomographic findings in acute zonal occult outer
MEWDS.(5) Photoreceptor abnormalities can be identified on retinopathy. Retina. 2010; 30:1206–1216.
multifocal ERG and OCT tests even in cases where there are no
biomicroscopic abnormalities in the fundus, and the diagnostic
value of conducted comparisons of abnormalities in these tests is
high. There is also diagnostic value to the lateral difference in
ERG.

OCT findings
The characteristics of AZOOR are IS/OS line defects or indis-
tinctiveness on OCT despite normal appearance with a bio-
microscopy.(4, 6–9) The areas of IS/OS line abnormalities have
distinct margins and are comparable with visual field defect areas
and decreased response areas of multifocal ERG. Moderately
reflective spots seen in MEWDS or other abnormal features
suggestive of inflammatory responses are not evident in AZOOR.
As the disease progresses, the outer segment is damaged, the
outer nuclear layer thins, and the retinal layer structure becomes
irregular. IS/OS abnormalities heal to a certain extent, but do not
completely heal as in MEWDS, so it is common for irreversible
damage such as outer nuclear layer thinning to remain.
 236 Chapter 7 · Retinal degeneration

Case 127 Acute zonal occult outer retinopathy: Eye with a history of MEWDS

A 45-year-old female, OD, BCVA 0.08, refraction -11.5 D, axial length 27.43 mm

A: Color fundus photograph in the right eye: At initial diagnosis. Relatively large, uniform white spots can be seen. B: Static automated perimetry in the
right eye: At initial diagnosis. A central scotoma and enlargement of Mariotte’s blind spot is evident. C: Static automated perimetry in the right eye: After
5 months. Best-corrected visual acuity has improved to 0.6. A central scotoma and enlargement of Mariotte’s blind spot has improved. D: FA + OCT horizon-
tal scan of right eye: Two weeks after initial diagnosis. Best-corrected visual acuity is 0.3. Decreased, defective or irregular IS/OS line is seen over the entire
posterior pole. Moderately reflective lesions can be seen from the RPE to the outer nuclear layer ( ). E: IA + OCT horizontal scan of the right eye: Five
months after initial diagnosis. The IS/OS line has almost been restored to normal. The COST line remains partially defective.
(Continued on the next page)
Case 127 · Acute zonal occult outer retinopathy: Eye with a history of MEWDS
237 7

F: Color fundus photograph: Nine months after initial diagnosis. Depigmentation of the RPE is visible in the macula and around the optic disc. G: Static
automated perimetry in the right eye: Nine months after initial diagnosis. Best-corrected visual acuity has decreased to 0.4. Enlargement of Mariotte’s blind
spot can once again be seen, but central scotomas are not apparent. H: Static automated perimetry in the right eye: 20 months after initial diagnosis. Best-
corrected visual acuity has improved to 0.7. Enlargement of Mariotte’s blind spot has improved. I: FA + IA in the right eye (13 minutes): Nine months after
initial diagnosis. Multiple IA hypofluorescent spots containing FA hyperfluorescence consistent with RPE depigmentation spots are depicted. J: FA + OCT
horizontal scan of the right eye: Nine months after initial diagnosis. IS/OS line irregularity can be seen from the optic disc to the parafovea and at the fovea
centralis. K: FA + OCT horizontal scan of the right eye: 20 months after initial diagnosis. The IS/OS line has almost recovered.

Image interpretation points

This patient became aware of visual field defects one week decline occurred once again. RPE depigmentation spots as seen
prior to their initial consultation. The patient was diagnosed with in punctate inner choroidopathy (PIC) were seen, and abnormal
MEWDS after visual field and visual acuity spontaneously im- reflectivity of the IS/OS line around the optic disc corresponding
proved approximately 2 months later based on fundus findings, to the visual field abnormality was detected. The patient was
visual field testing, and OCT findings. Nine months after initial diagnosed with AZOOR. This is a case where the pathologies of
diagnosis, enlargement of Mariotte’s blind spot and visual acuity MEWDS, AZOOR and possibly PIC are considered to overlap.
 238 Chapter 7 · Retinal degeneration

7.3 Punctate inner choroidopathy References

Background 1) Watzke RC, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J
Ophthalmol. 1984; 98:572–584.
Punctate inner choroidopathy (PIC) typically affects both eyes of
2) Amer R, Lois N. Punctate inner choroidopathy. Surv Ophthalmol. 2011;
women with moderate myopia. Patients become aware of blurred 56:36–53.
vision, photopsia, and scotomas. A the early phase, multiple 3) Patel KH, Birnbaum AD, Tessler HH, et al. Presentation and outcome of pa-
yellowish-white lesions are observed in the posterior pole. As tients with punctate inner choroidopathy at a tertiary referral center. Ret-
the condition regresses, these lesions change to characteristic ina. 2011; 31:1387–1391.
atrophic pigmented scars .(1–4) Those with similar lesions in a 4) Essex RW, Wong J, Fraser-Bell S, et al. Punctate inner choroidopathy: clini-
cal features and outcomes. Arch Ophthalmol. 2010; 128:982–987.
wider area than posterior pole accompanied by uveitis are known
5) Archer DB, Maguire CJ. Multifocal choroiditis. Trans Ophthalmol Soc U K.
as multifocal choroiditis and panuveitis (MCP) and is believed to 1975; 95:184–191.
be part of the same disease spectrum.(5, 6) Atrophic pigmented 6) Watzke RC, Claussen RW. The long-term course of multifocal choroiditis
scars are similar to the lesions of ocular toxoplasmosis (POHS). (presumed ocular histoplasmosis) . Am J Ophthalmol. 1981; 91:750–760.
Viral infection and autoimmunity are suspected to be involved 7) Amer R, Lois N. Punctate inner choroidopathy. Surv Ophthalmol. 2011;
56:36–53.
in the onset although the details are unclear. Inflammation at
7 the photoreceptor cell, RPE, and choroidal levels appears to be
involved in the disease process.
On FA, the yellowish-white lesions are hyperfluorescent and
become hypofluorescent after pigmented scarring, but hyper-
fluorescence or faint leakage can be seen in the hypofluorescent
margins. On IA, the both yellowish-white lesions and atrophic
pigmented scars exhibit hypofluorescence. This is thought to be
due to a blockage by inflamed lesions or filling defects on the
choroidal level. Normal visual acuity is maintained in half of the
cases. CNV develops subsequently in 40% of cases, which is the
primary cause of poor visual prognosis.(7)

OCT findings
RPE atrophy and increased choroidal reflectivity due to excessive
measurement beam penetration, undulating irregularities of the
IS/OS line, and thinning of the outer nuclear layer are observed
consistent with early stage, yellowish-white lesions. Consistent
with atrophic pigmented scars, RPE defects or irregularities and
even severer thinning of the outer retinal layers can be seen; and
the atrophic lesions of the outer retinal layers exhibit character-
istic features, as if the outer retina is being drawn into the RPE
defect. The disruption of Bruch‹s membrane is sometimes de-
tected, and severe retraction of the retina into the disrupted site
is noticeable. This is probably due to severe localized and rapid
atrophy in the outer retinal layers. Increased choroidal reflectivity
and posterior bending of Bruch’s membrane can sometimes be
seen. CNV secondary to PIC is essentially Type 2, but multiple
CNV lesions can sometimes be observed.
Case 128 · Punctate inner choroidopathy: Atrophic pigmented scars
239 7
Case 128 Punctate inner choroidopathy: Atrophic pigmented scars

A 31-year-old female, OS, BCVA 1.5, refraction -5.0 D

A: Color fundus photograph in the left eye: Yellowish-white spots and adjacent atrophic pigmented scars are depicted in 4 locations in the peripheral
macula. B: FA + IA in the left eye (9 minutes): The yellowish-white spots are hyperfluorescent, and atrophic pigmented scars hypofluorescent on FA. Both are
hypofluorescent on IA. C: FA + OCT vertical scan of the left eye + enlarged version [red dashed box]: RPE and IS/OS irregularities consistent with yellowish-
white spots and atrophic pigmented scars are visible. D: IR + OCT oblique scan of the left eye + enlarged version [red dashed box]: A disruption in Bruch’s
membrane is consistent with the atrophic pigmented scar, and significant atrophy of the outer retinal layers that is being retracted into that disruption can
be seen. Increased reflectivity is noted in the inner layers of the choroid in the vicinity of the RPE and Bruch’s membrane disruption. This is different from the
increased reflectivity as a result of excessive measurement beam penetration due to RPE atrophy because the high reflectivity is limited to a certain axial
level. There are no foveal abnormalities.

Image interpretation points

The patient became aware of metamorphopsia in her right eye Both lesions exhibits hyperfluorescence and hypofluorescence,
two weeks before visiting their local doctor. She was diagnosed respectively, on FA, whereas both are hypofluorescent on IA.
with ocular toxoplasmosis and administered acetylspiramycin, The latter was thought to be due to a blockage of as a result of
but her condition did not improve so they were referred to us. inflamed lesions or a filling defect on the choroidal level. A break-
Hemorrhages due to CNV and a serous retinal detachment were down of the outer retinal layers could be seen involving the
observed in the yellowish-white spot area of the right eye (case choroid and RPE, consistent with the yellowish-white spots and
129). The yellowish-white spots as an early lesion and atrophic atrophic pigmented scars.
pigmented scars were both present in the left eye (this case).
 240 Chapter 7 · Retinal degeneration

Case 129 Punctate inner choroidopathy: Case complicated by CNV (fellow eye of case 128)

A 31-year-old female, OD, BCVA 0.4, refraction -6.0 D

A: Color fundus photograph in the right eye: A greyish-white fibrin over the CNV lesion and accompanying retinal hemorrhages are exhibited slightly superior
to the fovea centralis. A small fresh lesion is visible inferior to the fovea centralis. B: FA + IA in the right eye (1 minute, 20 seconds): Significant leakage can be
seen from the CNV on FA, indicating classic CNV. C: FA + OCT horizontal scan on the right eye + enlarged version [red dashed box]: Bruch’s membrane consis-
tent with the yellowish-white spot is indistinct and prominent retraction of the retina is noted (red dashed circle). The RPE line protrusion is barely visible,
indicating Type 2 CNV ( ). D: FA + OCT vertical scan of the right eye + enlarged version [red dashed box]: Type 2 CNV is depicted in the parafovea, and RPE
elevation and retinal retraction is noticeable in the area consistent with the yellowish-white spots immediately superior to the parafovea.

Image interpretation points

This case is considered early PIC without atrophic pigmented scarred 3 months after initial diagnosis. The presence of hyper-
scar lesions. Type 2 CNV is occurring in the parafovea, which is fluorescent, yellowish-white spots on FA, which are hypofluores-
the cause of visual acuity decline. Retinal retraction (rapid and cent on IA, in both eyes and atrophic pigmented scars in the
localized atrophy of the outer retinal layers) can be seen in fellow eye suggest a diagnosis of PIC. The distinctive retinal
the yellowish-white spots on OCT. Highly reflective intraretinal retraction on OCT is also helpful.
deposits can also be seen. The yellowish-white spots have
Case 130 · Punctate inner choroidopathy: Yellowish-white spots and CNV
241 7
Case 130 Punctate inner choroidopathy: Yellowish-white spots and CNV

A 26-year-old female, OD and OS, BCVA 1.5 and 0.9, respectively, right refraction -0.25 D and left
refraction -1.25 D

A: Right eye fundus photograph: Multiple small, yellowish-white spots can be seen in the macula and the retina nasal to the optic disc. B: FA + IA in the right
eye (11 minutes): The yellowish-white spots are hyperfluorescent on FA and hypofluorescent on IA. C: Color fundus photograph in the left eye: Several small,
yellowish-white spots are observed in the macula. D: FA + IA in the left eye ( 10 minutes): Fluorescein leakage is seen in the yellowish-white spots around
the fovea centralis. The yellowish-white spots exhibit hypofluorescence on IA, and hypofluorescence can also be seen in the areas without evident yellow-
ish-white spots. E: IR + OCT horizontal scan of left eye + enlarged version [red dashed box]: A disruption is visible in Bruch’s membrane. RPE irregularity,
unique IS/OS irregularities, and moderate reflectivity in front of the RPE are exhibited.

Image interpretation points

The patient had become aware of metamorphopsia in their unilateral, and CNV rarely occurs. Furthermore, disruption in
left eye 5 months earlier. Yellowish-white spots were observed Bruch’s membrane as seen in this case are considered specific
in both eyes and exhibited hyperfluorescence on FA and findings in PIC where significant inflammation occurs from
hypofluorescence on IA. This characteristic is similar to the the RPE to the inner layers of the choroid.
yellowish-white spots in MEWDS. However, MEWDS is mostly
 242 Chapter 7 · Retinal degeneration

7.4 X-linked juvenile retinoschisis References

Background 1) Haas J. über das Zusammenvorkommen von Veränderungen der Retina

und Choroidea. Arch Augenheilkd. 1898; 37:343–348.
X-linked juvenile retinoschisis is a disease that has been well
2) Sauer CG, Gehrig A, Warneke-Wittstock R. et al. Positional cloning of the
described.(1) Characteristic, radiating inner retinal cystoid spaces gene associated with X-linked juvenile retinoschisis. Nat Genet. 1997;
associated with retinoschisis can be seen in the fovea centralis of 17:164–170.
both eyes in almost all cases, and peripheral retinoschisis occurs 3) Molday LL, Wu WW, Molday RS. Retinoschisin(RS1) , the protein encoded
in about half of patients. by X-linked retinoschisis gene, is anchored to the surface of retinal photo-
This disease is known to occur due to the mutation of the RS1 receptor and bipolar cells through its interactions with a Na/K APTase-
SARM1 complex. J Biol Chem. 2007; 282:32792–32801.
gene located in the short arm of the X chromosome (Xp22).(2)
4) Hayashi T, Omoto S, Takeuchi T, et al. Four Japanese male patients with
This anomaly causes the mutation of amino acids in retinoschi- juvenile retinoschisis: only three have mutations in the RS1 gene. Am J
sin, which is a gene product of RS1. Retinoschisin is a protein Ophthalmol. 2004; 38:788–798.
expressed in photoreceptor cells (both cones and rods) and bipo- 5) Yanoff M, Kertesz Rahn E, Zimmerman LE. Histopathology of juvenile reti-
lar cells, and is a factor of cell adhesion.(3) This disease is thought noschisis. Arch Ophthalmol. 1968; 79:49–53.
6) Manschot W. Pathology of hereditary juvenile retinoschisis. Arch Ophthal-
to due to this protein mutation resulting in abnormal retinal cell
7 adhesion. However, not all X-linked retinoschisis patients carry 7)
mol. 1972; 88:131–138.
Gao H, Kusumi R, Yung, CW. Optical coherence tomographic findings in
the RS1 genetic mutation, and this disease reportedly has genetic X-linked juvenile retinoschisis. Arch Ophthalmol. 2005; 123:1006–1008.
diversity.(4) 8) Minami Y, Ishiko S, Takai Y, et al. Retinal changes in juvenile X linked reti-
noschisis using three dimensional optical coherence tomography. Br J
OCT findings Ophthalmol. 2005; 89:1663–1664.
9) Prenner JL, Capone A Jr, Ciaccia S, et al. Congenital X-linked retinoschisis
Classic reports on the histopathology of this disease describe classification system. Retina. 2006; 26:S61–S64.
the retinal nerve fiber layer schisis that can be seen in advanced 10) Gerth C, Zawadzki RJ, Werner JS, et al. Retinal morphological changes of
cases, but there are no mentions of foveal lesions.(5, 6) There have patients with X-linked retinoschisis evaluated by Fourier-domain optical
been many reports on what retinal layers the lesions of this dis- coherence tomography. Arch Ophthalmol. 2008; 126:807–811.
ease occur in based on time-domain OCT, but the depth resolu- 11) Gregori NZ, Berrocal AM, Gregori G, et al. Macular spectral-domain optical
coherence tomography in patients with X linked retinoschisis. Br J Oph-
tion this device is insufficient and does not always show satis-
thalmol. 2009; 93:373–378.
factory results.(7–9) In recent years, we have come to understand 12) Yu J, Ni Y, Keane PA, et al. Foveomacular schisis in juvenile X-linked reti-
that schisis occurs in the nerve fiber layer, inner nuclear layer, noschisis: an optical coherence tomography study. Am J Ophthalmol.
outer nuclear layer, and outer plexiform layer in the fovea based 2010; 149:973–978.
on spectral-domain OCT.(10–12) It was also demonstrated that 13) Apushkin MA, Fishman GA, Janowicz MJ. Correlation of optical coherence
tomography findings with visual acuity and macular lesions in patients
retinoschisis occurs in the inner nuclear layer in the intermediate
with X-linked retinoschisis. Ophthalmology. 2005; 112:495–501.
periphery. Schisis in this intermediate periphery was named
lamellar schisis by Prenner et al.(9)
X-linked juvenile retinoschisis is a disease, which has become
more apparent owing to advancements in OCT rather than the
histopathology that we had relied on up until now and did not
necessarily represent the actual state of the disease. However,
it has also been reported that retinal disorders depicted by
OCT and visual function are not necessarily correlated;(13) and
although OCT is no doubt useful in understanding the patho-
logy, OCT alone is not sufficient.
Case 131 · X-linked juvenile retinoschisis: Retinoschisis over a wide area
243 7
Case 131 X-linked juvenile retinoschisis: Retinoschisis over a wide area

A 19-year-old male, OD and OS, BCVA 0.3 and 0.6, respectively

A: Color fundus photograph in the right eye: Radiating inner retinal cystoid spaces associated with retinoschisis can be seen in the fovea centralis.
B: Enlarged version of A [white dashed box]: Radiating inner retinal cystoid spaces is apparent. C: IR + OCT horizontal scan of the left eye: A large retino-
schisis cavity is visible in the macula. Retinoschisis is exhibited in the throughout the posterior pole. The retinoschisis is divided by columnar structures.
D: Enlarged version of C [red dashed box]: Retinoschisis is located in the inner nuclear layer. E: Enlarged version of C [blue dashed box]: Retinoschisis is
depicted in the inner nuclear layer.
(Continued on the next page)
 244 Chapter 7 · Retinal degeneration

Case 131 Continuation

F: Color fundus photograph in the right eye: Radiating inner retinal cystoid spaces associated with retinoschisis can be seen in the fovea centralis. Yellow
spots that are visible on the inferior, temporal side of the macula are derived from exudative changes due to retinoschisis in the periphery. G: Enlarged version
of F [white dashed box]: Radiating inner retinal cystoid spaces is apparent. H: IR + macular OCT vertical scan of the left eye: A large retinoschisis cavity is
depicted ( ). Retinoschisis can be seen throughout the posterior pole ( ). I: Enlarged version of H [red dashed box]: The foveal schisis cavity appears to be
divided by thick columnar structures. The cystoid spaces are located in the inner nuclear layer. Cystic changes in the peripheral macula are also visible in the
inner nuclear layer. J: Color fundus photograph montage of the left eye: Holes ( ) in the inner retinal layers are visible in the inferior, temporal periphery.

Image interpretation points

Retinoschisis appears to mainly be present in the inner nuclear in the retinal nerve fiber layer, outer nuclear layer, and outer
layer in this case. Retinoschisis seems to mostly be located in plexiform layer. Schisis was seen in the intermediate periphery in
the inner nuclear layer, but it is reported that schisis also occurs 82% of cases in a report by Prenner et al.
Case 132 · X-Linked juvenile retinoschisis: Retinoschisis confined to the macula
245 7
Case 132 X-Linked juvenile retinoschisis: Retinoschisis confined to the macula

A 17-year-old male, OD, BCVA 0.15

A: Color fundus photograph in the right eye: Radiating inner retinal cystoid spaces associated with retinoschisis can be seen in the fovea centralis.
B: FA in the right eye (18 seconds): Faint hyperfluorescence is visible in the fovea centralis. There appears to be dye leakage from the retinal blood vessels.
C: IA in the right eye (18 seconds): There are few particular findings. D: IR + OCT horizontal scan of the right eye: A large cystoid space is seen in the fovea
centralis (*). The intermediate periphery is relatively normal. E: Enlarged version of D [red dashed box]: Retinoschisis is evident in the inner nuclear layer.
F: Enlarged version of D [blue dashed box]: The retinal structure in the intermediate area of the fovea centralis and optic disc is also relatively normal.

Image interpretation points

In this case, retinoschisis is confined to the vicinity of the fovea centralis and retinoschisis is located in the inner nuclear layer.
In this disease, retinoschisis tends to easily occur in this layer in retinoschisis.
 246 Chapter 7 · Retinal degeneration

7.5 Stargardt disease References

Background 1) Allikmets R, Singh N, Sun H, et al. A photoreceptor cell-specific ATP-bind-

ing transporter gene (ABCR) is mutated in recessive Stargardt macular
Stargardt disease, also known as fundus flavimaculatus, is a
dystrophy. Nature Genet. 1997; 15: 236–246.
bilateral, progressive hereditary form of macular dystrophy. In 2) Bernstein PS, Tammur J, Singh N, et al. Diverse macular dystrophy pheno-
the Western world, it is the most frequent macular dystrophy and type caused by a novel complex mutation in the ELOVL4 gene. Invest Oph-
develops in relatively young patients in their teens and 20s. The thal Vis Sci. 2001; 42: 3331–3336.
frequency of this disease in Japan is unknown, but it is consider- 3) Yang Z, Chen Y, Lillo C, et al. Mutant prominin 1 found in patients with
ably lower compared with the Western world. It is autosomal macular degeneration disrupts photoreceptor disk morphogenesis in
mice. J Clin Invest. 2008; 118: 2908–2916.
recessive. There are also reports of genealogies exhibiting a
4) Lim JI, Tan O, Fawzi AA, et al. A pilot study of Fourier-domain optical coher-
dominant mode of inheritance, but these should be differentiated ence tomography of retinal dystrophy patients. Am J Ophthalmol. 2008;
as Stargardt-like diseases. ABCA4 (ATP binding cassette trans- 146:417–426.
porter A4) is well known as the genetic abnormality.(1) According 5) Birnbach CD, Järveläinen M, Possin DE, et al. Histopathology and immu-
to reports from the Western world, this genetic abnormality is nocytochemistry of the neurosensory retina in fundus flavimaculatus.
Ophthalmology. 1994; 101:1211–1219.
present in close to 80% of Stargardt disease cases, although
7 ELOVL 4 (elongation of very long chain fatty acids protein 4)(2)
6) Voigt M, Querques G, Atmani K, et al. Analysis of retinal flecks in fundus
flavimaculatus using high-definition spectral-domain optical coherence
and PROM1 (prominin 1)(3) are also reported as causative genes. tomography. Am J Ophthalmol. 2010; 150:330–337.
However, these genetic abnormalities do not necessarily result 7) Genead MA, Fishman GA, Anastasakis A. Spectral-domain OCT peripapil-
in Stargardt disease, and abnormalities in ABCA4 are also asso- lary retinal nerve fiber layer thickness measurements in patients with
Stargardt disease. Br J Ophthalmol. 2011; 95:689–693.
ciated with the onset of cone-rod dystrophy and retinitis pig-
8) Chen Y, Ratnam K, Sundquist SM, et al. Cone photoreceptor abnormalities
mentosa. correlate with vision loss in patients with Stargardt disease. Invest Oph-
Fundus findings in Stargardt disease are extremely varied. thalmol Vis Sci. 2011; 52:3281–3292.
Fundus findings change as the disease stage progresses. A dark
choroid is a well-known clinical finding on FA. However, this
finding is not unique to Stargardt disease and is not seen in all
cases of the disease. The detection frequency varies according to
the disease stage, and when FA was performed with a confocal
laser ophthalmoscopy, the ability of this device to adjust fluores-
cence gains make it difficult to detect dark choroid.

OCT findings
There are several reports on OCT findings for Stargardt disease.
An earliest report showed that changes were greater in the outer
retinal layers than in the inner layers,(4) and a more detailed ex-
amination is currently being conducted. Yellow spots are thought
to be due to lipofuscin deposited on the RPE.(5) It is proposed that
the yellow spots can be divided into 5 stages based on their posi-
tional relationship with the RPE and IS/OS.(6) In addition, it has
been reported that retinal nerve fiber layer thickness around the
optic disc is thicker than normal eyes, similar to retinitis pigmen-
tosa.(7) The tomographic features of this disease include loss of
photoreceptor and RPE cells and subsequent choroidal signal
enhancement, which is similar to other degenerative diseases or
atrophic form of age-related macular degeneration. Further-
more, reactive proliferation of the RPE cells can be seen in con-
junction with these changes.
Currently, there are ongoing Phase I and Phase II clinical
trials on stem cell therapy. As a representative retinal degenera-
tive condition, detailed comparative studies between visual func-
tion and structure have been conducted in Stargardt disease. One
topic being addressed is the detailed study of the state of photo-
receptor cells using adaptive optics confocal scanning laser oph-
thalmoscopy.(8)
Case 133 · Stargardt disease: A typical example
247 7
Case 133 Stargardt disease: A typical example

A 43-year-old female, OD, BCVA 0.1

A: Color fundus photograph in the right eye: An atrophic lesion of about 2 disc diameters is seen in the fovea centralis. Yellow spots are visible over the
entire posterior pole. B: FAF in the right eye: There is significant hyopfluorescence within the atrophic lesion. Small hypofluorescent spots are scattered
around the atrophic lesion. The yellow spots are exhibiting hyperfluorescence. C: FA in the right eye (18 seconds): Background fluorescence is low, which
as a typical dark choroid. The atrophic lesion in the macula is exhibiting hyperfluorescence due to window defects. The pigmentation inside this area is
significantly hypofluorescence. D: IA in the right eye (18 seconds): The large choroidal vessels are seen through the translucent atrophic lesion even on IA.
Mottled hypofluorescence is exhibited around the atrophic lesion. E: Electroretinogram (ERG) in the right eye: Recorded according to International Society
for Clinical Electrophysiology of Vision (ISCEV) criteria. Both cone and rod responses are relatively well preserved. The state of the left eye is almost the
same as the right eye.
(Continued on the next page)
 248 Chapter 7 · Retinal degeneration

Case 133 Continuation

F: IR + OCT horizontal scan of the right eye: The retina in the macula is significantly thin. G: IR + OCT oblique scan of the right eye: The yellow spots scattered
around the atrophic lesion are visible as protrusions in the RPE. The choroidal signal enhancement ( ) is visible due to loss of the RPE within the atrophic
lesion. H: Enlarged version of G [red dashed box]: We can see that the loss of the RPE is more apparent the closer it gets to the center of the atrophic lesion
(blue dashed circle). The RPE is relatively well preserved around the atrophic lesion, but the photoreceptor inner and outer segment junction line is inter-
rupted, and the ELM line in the intermediate area (between the two) appears to be »bowing« downwards (red dashed circle). The yellow spots can mainly
be seen as highly reflective lesions between the ELM and RPE ( ).

Image interpretation points

In this case, c2798A>T and c4195G>A compound heterozygote This disease does not appear to have specific OCT findings,
mutations were detected in the ABCA4 gene. This is typical although it does exhibit findings very similar to cone dystrophy
Stargardt disease where the dark choroid can be seen on FA. and atrophic AMD.
7.6 · Vitelliform macular dystrophy and adult-onset foveomacular vitelliform dystrophy
249 7
7.6 Vitelliform macular dystrophy and adult- The clinical features of these two diseases are similar, and the
onset foveomacular vitelliform dystrophy differences are not well understood. Neither disease has been
recorded in recent years, and only fragmented histopathological
Background information is available. In addition, it has recently become a
Vitelliform macular dystrophy (VMD), or Best disease, was first topic that impaired RPE phagocytosis of the photoreceptor outer
reported over 100 years ago by Best in 1905.(1) This disease has segments as a result of various causes leads to development
an autosomal dominant form of inheritance and is caused by a of  vitelliform lesions. Gass et al. reported on vitelliform lesions
mutation of the VMD2 gene.(2) The VMD2 gene is located on associated with cuticular drusen in 1985,(8) but impaired photo-
11q13 of the long arm of chromosome 11 and its gene product is receptor outer segment phagocytosis and subsequent develop-
known as bestrophin. Bestrophin is a Ca2+ dependent chloride ment of vitelliform lesions actually occurs with chronic foveal
channel protein localized in the cell membrane at the base of RPE detachment. This occurs in diseases such as reticular drusen,(9)
cells.(3, 4) vitreoretinal traction syndrome, and central serous chorioretino-
Vitelliform macular dystrophy is essentially a bilateral disease pathy. Freund et al. referred to this state as »acquired vitelliform
(and unilateral in rare cases). This disease typically affects children lesions«.(10)
aged 6 to 12 years, often results in relatively mild visual dys- With characteristic fundus findings, the diagnosis of VMD is
function, is sometimes only discovered on fundus examinations, straightforward; however, diagnosis can be difficult in cases that
and maintains relatively good visual function until middle-age. have entered the atrophic stage. FA (corona sign), fundus auto-
A typical finding of VMD is a decrease in the length to diameter fluorescence (hyperfluorescence) and OCT findings are useful
ratio (L/D ratio) in electrooculography (EOG), although it is – for diagnosis, with a unique hyperreflective feature in fundus
difficult to conduct EOG tests during childhood. Fundus find- autofluorescence being particularly useful. In the most advanced
ings of this disease are known to change with age. Moehler and stage of the disease, however, the hyperfluorescence on auto-
Fine proposed dividing this disease into 5 stages from 0 to IV; fluorescence attenuates and the diagnostic value decreases.(11)
Stage 0, the subclinical stage; Stage I, the vitelliform stage; Stage
II, the pseudohypopyon stage; Stage III, the vitelliruptive stage; OCT findings
and Stage IV, the atrophic stage.(5) Known OCT findings for VMD and AOFVD are shown in
In contrast, adult-onset foveomacular vitelliform dystrophy . Table 7-1.(12–15) However, there are no reports comparing the
(AOFVD) was first described by Gass in 1974.(6) This disease is OCT findings between the two diseases; as a result, it is unknown
a type of pattern dystrophy and often develops in those in their if there are essential differences between the two. Additionally,
40s and 50s. Fundus findings are very similar to VMD, but lesions a very recent report on the genetic analysis of numerous cases
are often small compared with VMD. This disease includes uni- was published in France. According to this report, age of onset
lateral cases. EOG test results are generally normal but there are was the biggest factor in differentiating both diseases, whereas
also cases where the L/D ratio decreases. The hereditary form is the L/D ratio of EOG tests is apparently not a good index for
autosomal dominant with a low penetration rate. Peripherin/ differentiation.(16)
RDS mutations are reported in AOFVD, although there are also
cases in which VMD2 genetic mutations can be found.(7) Visual
dysfunction is also mild in this disease.

. Table 7-1 OCT findings in vitelliform macular dystrophy and adult-onset foveomacular vitelliform dystrophy.

Subclinical stage or vitelliform stage Partial disruption of the IS/OS line

The COST line is more clearly depicted than usual
Amorphous material deposits are visible between the sensory retina and RPE

Pseudohypopyon stage The optically empty zone in the superior fovea (area of low reflectivity)
Highly reflective deposits in the inferior fovea

Vitelliruptive stage Optical empty zone

Enhanced reflectivity of the RPE
Partial disruption of the IS/OS line

Atrophic stage Thinning of all retinal layers

Complete disappearance of the IS/OS line
Reactive proliferation of the RPE cells

The current consensus is that subfoveal deposits can be seen between the sensory retina and RPE in VMD. In the previous era of time-domain OCT,
deposits were seen to be located beneath the RPE due to low depth resolution, but it is clear that such previous interpretation was wrong after the
introduction of high resolution spectral-domain OCT.
 250 Chapter 7 · Retinal degeneration

References

1) Best F. Über eine hereditäre Maculaaffektion. Beiträg zur Vererbungslhere.

Z Augenheilkd. 1905; 13:199–212.
2) Petrunkhin K, Koisti MJ, Bakall B, et al. Identification of the gene responsi-
ble for Best macular dystrophy. Nat Genet. 1998; 19:241–247.
3) Marmorstein AD, Marmostein LY, Rayborn M, et al. Bestrophin, the prod-
uct of the Best vitelliform macular dystrophy gene (VMD2), localizes to
the basolateral plasma membrane of the retinal pigment epithelium. Proc
Natl Acad Sci USA. 2000; 97:12758–12763.
4) Sun H, Tsunenari T, Yau KW, et al. The vitelliform macular dystrophy protein
defines a new family of chloride channels. Proc Natl Acad Sci USA. 2002;
99:4008–4013.
5) Moehler CW, Fine SL. Long-term evaluation of patients with Best’s vitelli-
form dystrophy. Ophthalmology. 1981; 88:688–692.
6) Gass JDM. A clinicopathologic study of a peculiar foveomacular dystro-
phy. Trans Am Ophthalmol Soc. 1974; 72:139–156.

7 7) Seddon JM, Afshari MA, Sharma S, et al. Assessment of mutations in the

Best macular dystrophy (VMD2)gene in patients with adult-onset foveo-
macular vitelliform dystrophy, age-related maculopathy, and bull’s eye
maculopathy. Ophthalmology. 2001; 108:2060–2067.
8) Gass JDM, Jallow S, Davis B. Adult vitelliform macular detachment occur-
ring in patients with basal laminar drusen. Am J Ophthalmol. 1985;
99:445–459.
9) Zweifel SA, Spaide RF, Yannuzzi LA. Acquired vitelliform detachment in
patients with subretinal drusenoid deposits (reticular pseudodrusen).
Retina. 2011; 31:229–234.
10) Freund KB, Laud K, Lima LH, et al. Acquired vitelliform lesions. Correlation
of clinical findings and multiple imaging analyses. Retina. 2011; 31:13–25.
11) Spaide RF, Noble K, Morgan A, et al. Vitelliform macular dystrophy. Oph-
thalmology. 2006; 113:1392–1400.
12) Ferrara DC. Costa RA, Tsang S, et al. Multimodal fundus imaging in Best
vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;
248:1377–1386.
13) Puche N, Querques G, Benhamou N, et al. High-resolution spectral do-
main optical coherence tomography features in adult onset foveomacular
vitelliform dystrophy. Br J Ophthalmol. 2010; 94:1190–1196.
14) Querques G, Bux AV, Prato R, et al. Correlation of visual function impair-
ment and optical coherence tomography findings in patients with adult-
onset foveomacular vitelliform macular dystrophy. Am J Ophthalmol.
2008; 146:135–142.
15) Querques G, Regenbogen M, Quijano C, et al. High-definition optical co-
herence tomography features in vitelliform macular dystrophy. Am J Oph-
thalmol. 2008; 146:501–507.
16) Meunier I, Sénéchal A, Dhaenens CM, et al. Systemic screening of BEST1
and PRPH2 in juvenile and adult vitelliform macular dystrophies: a ration-
ale for molecular analysis. Ophthalmology. 2011; 118:1130–1136.
Case 134 · Adult-onset foveomacular vitelliform dystrophy: Vitelliform stage
251 7
Case 134 Adult-onset foveomacular vitelliform dystrophy: Vitelliform stage

Right and left eye of a 60-year-old male, OD and OS, BCVA 0.8 and 1.2, respectively

A: Color fundus photograph in the right eye: A yellowish-white spot is visible in the fovea centralis. A yellowish-white spots is also seen near the inferotem-
poral vascular arcade. B: FAF in the right eye: Intense hyperfluorescence is noted in the fovea centralis and its surroundings are slightly hypofluorescent.
C: FA in the right eye (4 minutes, 32 seconds): Very faint hyperfluorescence can be seen around the fovea centralis. The yellowish-white spot inferotempo-
rally also appears to be exhibiting hyperfluorescence. D: IA in the right eye (4minutes, 32 seconds): The fovea centralis is exhibiting hypofluorescence.
E: IR + OCT horizontal scan of the right eye: Moderately reflective deposits are seen beneath the fovea centralis. F: Enlarged version of E [red dashed box]:
The subfoveal deposits (*) are amorphous. Both the RPE line and ELM (7) are continuous and the COST line is as clearly seen as IS/OS line. This appears
to be typical of this disease. Reactive proliferation of the RPE cells can be seen ( ). The IS/OS line is intermittently visible.

Image interpretation points

Based on the patient’s medical history and fundus findings, sensory retina and RPE. The COST line is clearly seen outside
this is unmistakably AOFVD. Intense autofluorescence on FAF of the lesion site. Such an enhanced COST line also present in
is useful for diagnosis. Subfoveal deposits exist between the the fellow eye.
 252 Chapter 7 · Retinal degeneration

Case 135 Adult-onset foveomacular vitelliform dystrophy: Pseudohypopyon stage

A 59-year-old female, OS, BCVA 0.6

A: Color fundus photograph in the left eye: A lesion of about 1 disc diameter is visible in the fovea centralis and a yellowish-white spot exhibiting a niveau
pattern can be seen inferiorly. The yellow color is weak above this area. B: FAF in the left eye: Significant hyperfluorescence is seen in the inferior fovea.
C: FA in the left eye (29 seconds): The superior fovea is slightly hyperfluorescent. The inferior fovea with the yellowish-white lesion is hypofluorescent.
D: IA in the left eye (29 seconds): The superior fovea is hyperfluorescent, while the inferior fovea with the yellowish-white lesion is hypofluorescent.
E: IA + OCT vertical scan of the left eye: A so-called vitelliform detachment ( ) is visible below the fovea centralis. Moderate reflectivity from vitelliform
deposits is visible below the detached retina. F: Enlarged version of E [red dashed box]: The vitelliform deposits are clearly visible (*). The IS/OS is partially
indistinct in the detached area of the retina. In addition, the photoreceptor outer segment has merged with the vitelliform deposits and cannot be distin-
guished. The structure of the outer retinal layers is well preserved in the area without retinal detachment (blue dashed circle). The RPE is flat.

Image interpretation points

This is a case of pseudohypopyon stage AOFVD. It is clear that and RPE. The vitelliform detachment is also clearly visible.
the vitelliform deposits are located between the sensory retina
Case 136 · Adult-onset foveomacular vitelliform dystrophy: The course
253 7
Case 136 Adult-onset foveomacular vitelliform dystrophy: The course

Course of the right eye of a 59-year-old female (fellow eye of case 135)

A, B, C: Color fundus photographs in the right eye: At initial diagnosis A, 1 year and 2 months after initial diagnosis B, and 2 years and 8 months after initial
diagnosis C. The subfoveal yellowish-white lesion is becoming indistinct over time. Best-corrected visual acuity of the left eye is 0.8 in A, 0.6 in B and 0.4 in
C. D, E, F: OCT horizontal scans of the right eye: The same course is shown: At initial diagnosis D, 1 year and 2 months after initial diagnosis E, and 2 years
and 8 months after initial diagnosis F. Subfoveal vitelliform deposits get smaller and eventually disappear leaving behind a foveal detachment. G: Enlarged
version of D [red dashed box]: H: Enlarged version of F [blue dashed box]: The ELM and IS/OS (red dashed circle) are preserved in G where visual acuity is
relatively good. The IS/OS is becoming indistinct with the degeneration of the outer retinal layers in H ( ) and highly reflective patterns (blue dashed
circle) thought to be reactive proliferation of the RPE cells in the foveal retina are visible.

Image interpretation points

This is the fellow eye of case 135. Subretinal deposits can be atrophic degeneration of the outer retinal layers with remaining
seen on OCT when vitelliform lesions are clearly visibly with an foveal detachment.
ophthalmoscopy. The deposits disappear with time followed by
 254 Chapter 7 · Retinal degeneration

7.7 Pseudoxanthoma elasticum References

Background 1) Finger RP, Charbel Issa P, Ladewig MS, et al. Pseudoxanthoma elasticum:
genetics, clinical manifestations and therapeutic approaches. Surv Oph-
Pseudoxanthoma elasticum (PXE) is a relatively rare systemic
thalmol. 2009; 54:272–285.
disease. Lesions occur in the skin, gastrointestinal tract, cardio- 2) Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC
vascular system and the eyes.(1) A mutation of ABCC6 gene that transporter cause pseudoxanthoma elasticum. Nat Genet. 2000; 25:223–
exists in p13.1 of chromosome 16 is believed to cause tearing and 227.
degeneration of systemic elastic fibers.(2) Changes seen in the 3) Charbel Issa GP, Finger RP, Holz FG, et al. Multimodal imaging including
fundus include angioid streaks (AS), peau d’orange fundus, crys- spectral domain OCT and confocal near infrared reflectance for charac-
terization of outer retinal pathology in pseudoxanthoma elasticum. Invest
talline bodies, optic disc drusen, comet lesions and CNV.(1) AS
Ophthalmol Vis Sci. 2009; 50:5913–5918.
are radiating, jaggy, and tapering streaks (clefts) spreading from 4) Zweifel SA, Engelbert M, Laud K, et al. Outer retinal tubulation: a novel
the peripapillary region that are caused by tears in Bruch’s mem- optical coherence tomography finding. Arch Ophthalmol. 2009; 127:1596–
brane due to elastic fiber abnormalities. In addition to PXE, AS 1602.
can be seen in patients with Ehlers-Danlos syndrome, Paget’s 5) Dreyer R, Green WR. The pathology of angioid streaks:a study of twenty-
one cases. Trans Pa Acad Ophthalmol Otolaryngol. 1978; 31:158–167.
disease and Marfan syndrome.(1)
7 6) Zweifel SA, Imamura Y, Freund KB, et al. Multimodal fundus imaging of
pseudoxanthoma elasticum. Retina. 2011; 31:482–491.
OCT findings
OCT findings vary. Since abnormalities in the elastic fibers that
compose Bruch’s membrane are the basis of the disease, abnor-
mal features on OCT are found primarily in the outer retinal
layers. Disruption in Bruch’s membrane in the sites correspond-
ing to AS and decreased reflectivity of the RPE and Bruch’s mem-
brane corresponding to peau d’orange fundus are known to occur
prior to the onset of CNV.(3) As the disease progresses, undulat-
ing Bruch’s membrane appears and round, ovoid or tubular struc-
tures known as outer retinal tubulations are formed in the outer
nuclear layer.(3, 4) Pathologically, these structures are thought to
to be proliferated RPE,(5) the details of which are unclear. So-
called Type 2 CNV is often seen, although Type 1 CNV can also
develop.
Finally, vitelliform detachment and reticular pseudodrusen-
like changes have also been reported in AS.(6)
Case 137 · Pseudoxanthoma elasticum: A case of Type 1 CNV
255 7
Case 137 Pseudoxanthoma elasticum: A case of Type 1 CNV

A 63-year-old male, OD, BCVA 0.5

A: Color fundus photograph in the right eye: ASs are visible around the optic disc. B: FA in the right eye (7 minutes, 15 seconds): Relatively intense hyper-
fluorescence can be seen superior to the optic disc. Mild hyperfluorescence is visible temporal to the optic disc. The fovea centralis is hypofluorescent.
C: IA in the right eye (7 minutes, 15 seconds): CNV appears to be present over a wide area immediately temporal to the optic disc. D: IR + OCT horizontal
scan of the right eye: CNV is present over a wide area below the RPE from the optic disc to slightly temporal to the fovea centralis. The undulation of Bruch’s
membrane is clearly seen (7). E: Enlarged version of D [red dashed box]: The undulation of Bruch’s membrane (7) and the disruption in Bruch’s membrane
(red dashed circle) are clearly visible. Moderate reflectivity is visible between the RPE and Bruch’s membrane where Type 1 CNV (*) is present.

Image interpretation points

Type 1 CNV has occurred in this case. The undulation of Bruch’s membrane and the disruption in Bruch’s membrane are typical
findings of PXE.
 256 Chapter 7 · Retinal degeneration

Case 138 Pseudoxanthoma elasticum: A case of Type 2 CNV

A 58-year-old female, OD, BCVA 1.5

A: Color fundus photograph in the right eye: CNV with hemorrhages can be seen between the optic disc and the fovea centralis. indicates AS in the
temporal macula. ASs are also present nasal to the optic disc. B: FA + OCT horizontal scan of the right eye: This is a horizontal scan of the area inferior to the
CNV. The two red dashed circles both correspond to ASs, as seen in the left FA image. Bending of Bruch’s membrane is occurring in the AS area. A SRD is
visible. C: FA + OCT diagonal scan of the right eye: This is a scan passing through the CNV. We can see that Type 2 CNV is present ( ). Below the CNV,
Bruch’s membrane is flat without disruption (7). Cystoid spaces are visible in the outer plexiform layer. The granular, highly reflective dots inside the neural
retina are either lipid deposits or macrophages that have phagocytized erythrocytes and deposited lipids.

Image interpretation points

This is a case of typical PXE with thick AS. Bending of Bruch’s centralis in B. Type 2 CNV is visible in C. While it is typical for
membrane can be seen in the AS site. A PED exists nasal to the Type 2 CNV to occur in this disease, Type 1 CNV can also develop.
the bent Bruch’s membrane in the AS site close to the fovea
Case 139 · Pseudoxanthoma elasticum: A case of polypoidal lesions
257 7
Case 139 Pseudoxanthoma elasticum: A case of polypoidal lesions

A 71-year-old male, OD and OS, BCVA 1.5 and 0.7, respectively

A: Color fundus photograph in the right eye: ASs are visible around the optic disc. B: Color fundus photograph in the left eye: ASs are visible, similar to
the right eye. C: FA in the left eye (42 seconds): A round hyperfluorescent spot is seen superonasal to the fovea centralis. D: IA in the left eye (42 seconds):
On IA, this appears to be a polypoidal lesion ( ). An abnormal vascular network is also seen inferonasally. E: IR + OCT horizontal scan of the left eye: A RPE
protrusion exhibiting a steep elevation is visible. F: Enlarged version of E [red dashed box]: Mild reflective lesions are seen within the polypoidal lesion ( ).
The RPE on the immediately nasal to the polypoidal lesion is gently sloping away from Bruch’s membrane (red dashed circle). This corresponds with the
abnormal vascular network.

Image interpretation points

Although rare, PXE can be seen in combination with polypoidal choroidal vasculopathy (PCV). This combination questions the
basic pathogenesis of PCV.
 258 Chapter 7 · Retinal degeneration

Case 140 Pseudoxanthoma elasticum: Outer retinal tubulation

A 54-year-old male, OS, BCVA 0.15

A: Color fundus photograph in the left eye: ASs are visible around the optic disc. CNV with pigmentation can be seen in the fovea. B: FA in the left eye
(48 seconds): There is a thick rodlike structure exhibiting significant hyperfluorescence nasal to the fovea centralis. C: IR + OCT vertical scan of the left eye:
Scan of the thick rodlike structure area in B. Type 2 CNV is visible. D: Enlarged version of C [red dashed box]: A structure ( ) enveloped by a moderately
reflective ring known as an outer retinal tubulation is seen between the CNV and outer plexiform layer. Another tubulation cut longitudinally (red dashed
circle) is shown nasal to the CNV (white dashed circle). The outer retinal tubulation is often exhibiting a small highly reflective dot in its center. Cystoid
spaces ( ) are visible in the sensory retina of the CNV.

Image interpretation points

The biological explanation of outer retinal tubulation is un- those seen in retinoblastoma. Outer retinal tubulations have a
clear. It appears to be a reactive change originating from the tubular-shaped structure which exhibit a staining pattern on FA.
RPE or outer retinal layers in which the RPE and photoreceptor Refer to the page on crystalline retinopathy (7 pages 262–264).
cells undergo damage. It may resemble rosettes similar to
7.8 · Cancer-associated retinopathy
259 7
7.8 Cancer-associated retinopathy References

Background 1) Sawyer RA, Selhorst JB, Zimmerman LE, et al. Blindness caused by photo-
receptor degeneration as a remote effect of cancer. Am J Ophthalmol.
Cancer-associated retinopathy (CAR)1) is a relatively rare disease
1976; 81:606–613.
classified as an autoimmune retinopathy. In CAR, autoantibodies 2) Thirkill CE, Roth AM, Keltner JL. Cancer-associated retinopathy. Arch Oph-
to protein expressed in the retina form in the serum of cancer thalmol. 1987; 105:372–375.
patients and cause damage to the retinal photoreceptor cells.(2) 3) Saito W, Kase S, Ohguro H, et al. Slowly progressive cancer-associated
Small cell lung cancer is well known as an underlying disease, and retinopathy. Arch Ophthalmol. 2007; 125:1431–1433.
there are also reports citing endometrial cancer and thymoma. 4) Mohamed Q, Harper CA. Acute optical coherence tomographic findings in
cancer-associated retinopathy. Arch Ophthalmol. 2007; 125:1132–1133.
The antigen proteins recognized by the autoantibodies are
diverse. Since not all patients with CAR have autoantibodies to
recoverin, the lack of anti-recoverin antibodies does not exclude
the diagnosis of CAR.
Symptoms are progressive and often follow a relatively acute
or subacute course, although cases with gradual progression are
also encountered.(3) Diagnosis is not straightforward, as antireti-
nal autoantibodies and progressive retinal degeneration need to
be verified. As mentioned above, a negative anti-recoverin anti-
body test cannot rule out this disease; in these cases, more spe-
cific laboratory tests are required to determine the presence or
absence of autoantibodies for other retinal antigens. OCT is use-
ful for the verification of retinal degeneration. CAR is unlikely in
cases where damage to the outer retinal layers cannot be verified
with OCT. Supplementary tests other than OCT include visual
field tests (perimetry), attenuation of rod and cone response with
ERG, fundus autofluorescence and fluorescein fundus angiogra-
phy.

OCT findings
OCT findings for CAR vary depending on the stage of disease
progression. Thinning of the entire retina is evident in advanced
cases. In such cases, evaluation with a retinal thickness map is
useful for diagnosis.(4) Damage to the inner retinal layers in the
intermediate periphery has also been reported. CME can also be
seen, similar to retinitis pigmentosa. There are very few reporting
the findings of the inner retinal layers on OCT from early stages
of disease. These early cases primarily involve changes in the
outer retinal layers, starting with the disappearance of the IS/OS
line. The sample size is insufficient to examine the differences
with retinitis pigmentosa.
 260 Chapter 7 · Retinal degeneration

Case 141 Cancer-associated retinopathy: Damage to the outer retinal layers

A 77-year-old female, OD, BCVA 1.0

A: Color fundus photograph in the right eye: Narrowing of the retinal artery is evident. The retina around the vascular arcade is pale. B: FAF in the right eye:
The macular area is hypofluorescent and its surroundings are exhibiting hyperfluorescence. Islets of hypofluorescent foci are visible. C: FA in the right eye
(40 seconds): Mild fluoroscein leakage is seen from the retinal blood vessels. Choroidal background fluorescence is mottled and has a salt-and-pepper
appearance. D: IA in the right eye (40 seconds): There are scattered small hypofluorescent spots. E: IR + OCT horizontal scan of the right eye: The outer retinal
layers in the intermediate periphery are damaged. F: Enlarged version of E [red dashed box]: The IS/OS is disrupted and ELM is »bowing« in  . It is
unclear whether this is an inherent pattern for this condition or whether these are secondary changes.

Image interpretation points

In this case, the patient had significant bilateral concentric on the degeneration of the outer retinal layers evident on
visual field contraction. The diagnosis of CAR was made based OCT.
Case 142 · Cancer-associated retinopathy: Retinal vasculitis
261 7
Case 142 Cancer-associated retinopathy: Retinal vasculitis

A 54-year-old female, OD, BCVA 0.4

A: Color fundus photograph in the right eye: Retinal hemorrhages are seen immediately superior to the vascular arcade. The fundus is otherwise relatively
unremarkable. B: FAF in the right eye: Hyperfluorescence is seen along the vascular arcades. C: FA in the right eye (47 seconds): Significant fluoroscein
leakage from the retinal blood vessels is seen. The area of hyperfluorescence corresponds to the hyperfluorescent area on fundus autofluorescence. The
fovea centralis is hypofluorescent. D: IA in the right eye (47 seconds): A oblong hypofluorescence in the fovea centralis can be seen on IA. E: IR + OCT hori-
zontal scan of right eye: Damage to the outer retinal layers is visible. F: Enlarged version of E [red dashed box]: Loss or irregularity of the IS/OS line is seen.
The outer nuclear layer and photoreceptor IS/OS are lost nasal to the fovea centralis (red dashed circle).

Image interpretation points

This is a case of CAR in conjunction with retinal vasculitis in a In this case, testing for anti-recoverin antibodies was positive.
patient with small cell lung cancer.
 262 Chapter 7 · Retinal degeneration

7.9 Bietti crystalline dystrophy References

Background 1) Bietti G. Ueber familiares Vorkommen von Retinitis punctata albescence

(Verbunden mit»Dystrophia marginalis cristallinea cornea«) . Glitzen des
Bietti crystalline dystrophy is a hereditary retinal degenerative
Glaskopers und andeen degenerativen Augenveranderungen. Klin Mbl
disease with an autosomal recessive mode of inheritance dis- Augenhelik. 1937; 99:737–756.
covered by the Italian ophthalmologist Bietti in 1937.(1) Although 2) Kaiser-Kupfer MI, Chan CC, Markello TC, et al. Clinical biochemical and
it can be confused with typical retinitis pigmentosa, this disease pathologic correlations in Bietti’s crystalline dystrophy. Am J Ophthalmol.
is characterized by multiple yellowish-white deposits known as 1994; 118:569–582.
crystalline bodies. These deposits can sometimes be found in the 3) Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is
caused by mutations in the novel gene CYP4V2. Am J Hum Genet. 2004;
peripheral cornea. These findings allow for a clear diagnosis. In
74:817–826.
the majority of cases, night blindness and tunnel vision gradu- 4) Lin J, Nishiguchi KM, Nakamura M, et al. Recessive mutations in the
ally progress between the age of 20 and 50.(2) CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystal-
The frequency of crystalline dystrophy is known to have an line corneoretinal dystrophy. J Med Genet. 2005; 42:e38.
ethnic difference and is seen at a relatively high frequency in 5) Yeoh J, Rahman W, Chen F, et al. Choroidal imaging in inherited retinal
disease using the technique of enhanced depth imaging optical coher-
Japanese and Chinese people.(2) CYP4V2 is well known as a caus-
7 ative gene of this disease.(3, 4) This gene product belongs to the
ence tomography. Graefes Arch Clin Exp Ophthalmol. 2010; 248:1719–
1728.
cytochrome P450 superfamily and is also associated with lipid 6) Pennesi ME, Weleber RG. High-resolution optical coherence tomography
metabolism. shows new aspects of Bietti crystalline retinopathy. Retina. 2010; 30:531–
532.
OCT findings 7) Zweifel SA, Engelbert M, Laud K, et al. Outer retinal tubulation; a novel
optical coherence tomography finding. Arch Ophthalmol. 2009; 127:1596–
There are few reports on the retinal histopathological findings of 1602.
this disease and there are no established OCT findings. In studies 8) Kojima H, Otani A, Ogino K, et al. Outer retinal circular structures in pa-
using EDI-OCT, choroidal thickness is thinned significiantly.(5) tients with Bietti crystalline retinopathy. Br J Ophthalmol. 2012:in press.
In our studies, crystalline bodies were mainly seen on the RPE
or Bruch’s membrane after the RPE had been lost.(6) Typical
findings of this disease are round or funicular structures visible
in the retinal outer nuclear layer. These structures are thought to
be outer retinal layer structures(7) reported as outer retinal tubu-
lations. In our cases, outer retinal tubulation was seen in all cases
of crystalline dystrophy.(8)
Case 143 · Bietti crystalline dystrophy: A typical example
263 7
Case 143 Bietti crystalline dystrophy: A typical example

A 53-year-old female with, OS, BCVA 1.5

A: Color fundus photograph in the left eye: Extensive degeneration is visible in the posterior pole of the retina. There is no optic disc atrophy and narrowing
of the retinal artery is insignificant. B: Enlarged version of A [white dashed box]: Small yellowish-white deposits are visible ( ). The foveal retina is relatively
close to normal in color. C: FAF in the left eye: A wide area temporal to the fovea centralis is exhibiting hypofluorescence. There is an area of almost normal
autofluorescence that corresponds to the foveal area of relatively normal retinal color in the fundus photograph. Around the area of extensive hypo-
flurescence, there is an mixed appearance of hypofluorescence and normal fluorescence exhibiting in a granular mottled appearance. D: IR + OCT oblique
scan of the left eye: The ELM and IS/OS lines are partially seen in the fovea centralis (blue dashed circle). Three round or ovoid structures are seen in a line
inferonasal to the fovea centralis ( ). E: Enlarged version of D [red dashed box]: Crystalline bodies appear to be in contact with the anterior aspect of
Bruch’s membrane after the RPE has shed ( ). Round or ovoid structures (outer retinal tubulation) can be seen in the outer nuclear layer (blue dashed
circles). There is extensive atrophy and loss of the RPE.

Image interpretation points

There is no significant difference between the degeneration gated. Nevertheless, the structures in this case appeared round
of the outer retinal layers seen in this example and that seen or ovoid regardless of the OCT scan, perhaps because they are
in typical retinal degenerative diseases. Outer retinal tubula- almost spherical. The basic pathogenesis of these structures is
tion, however, is more commonly found in Bietti crystalline unknown, but they can be seen in various degenerative diseases
dystrophy. Depending on the direction of the OCT scans, with variable frequency.
structures in outer retinal tubulation are not round, but elon-
 264 Chapter 7 · Retinal degeneration

Case 144 Bietti crystalline dystrophy: Outer retinal tubulation

A 42-year-old female, OD, BCVA 0.8

A: Color fundus photograph in the right eye: Extensive degeneration is visible in the posterior pole of the retina. There is no optic disc atrophy and narrowing
of the retinal artery is insignificant. Crystalline bodies are unremarkable. B: IR + subfoveal OCT horizontal scan of the right eye: The RPE is lost extensively
and Bruch’s membrane is seen. The RPE is partially visible in the area of the red dashed circle. The ELM is also depicted with an irregular pattern in this area.
Cross-sections of outer retinal tubulation are lined up consecutively in the area indicated by the blue dashed circle. The reflectivity immediately beneath
the RPE representing choriocapillaris is not seen, indicating loss of choriocapillaris. C: Enlarged version of B [red dashed box]: Damages in the outer retinal
layers and loss of the RPE is evident. Outer retinal tubulation is present in the outer nuclear layer as well.

Image interpretation points

When examined closely, small, a highly reflective punctiform tion. While it is unclear what these represent, they may be simi-
structures can be seen in the center of the outer retinal tubula- lar to retinal rosette formations.
7.10 · Retinitis pigmentosa
265 7
7.10 Retinitis pigmentosa well preserved. In contrast in cone dystrophy, the retinal struc-
ture of the intermediate periphery is often well preserved since
Background degeneration starts near the fovea centralis. Thus, OCT images
Retinitis pigmentosa (RP) is a collective term for diseases that of both diseases show opposing findings. Hood et al. studied
cause hereditary and progressive degeneration of the photo- OCT findings for boundaries between areas of RP degeneration
receptor cells (rods are damaged first) and the RPE. One in every and relatively healthy areas, and noted that damage to the photo-
4,000 suffers from RP. Frequent symptoms include night blind- receptor outer segment occurs first, followed by thinning of the
ness, dark adaptation impairment and photophobia. As it pro- outer nuclear layer and outer plexiform layer. There is continued
gresses, tunnel vision typically advances from the intermediate loss of the photoreceptor outer segment, finally resulting in fur-
periphery to the periphery, eventually leading to loss of central ther thinning of the outer nuclear layer and outer plexiform layer.
vision. (11) As expected, foveal retinal thickness and visual acuity are

The mode of inheritance is typically divided into autosomal strongly correlated.(12)

dominant, autosomal recessive, sex-linked, digenic and sporadic. There are many reports on comparisons between photo-
In Japan, there are a few cases of RP exhibiting a dominant mode receptor damage as detected on OCT and visual function or
of inheritance, but autosomal recessive inheritance and sporadic other test findings such as with FAF testing. One report found
cases account for the majority. Cases that exhibit systemic symp- that OCT findings and visual function were strongly correlated
toms in addition to ocular fundus abnormalities have specific upon examining macular OCT features of RP patients divided
disease names (e.g. Usher syndrome). into normal, CME, vitreoretinal traction syndrome, and macular
It is well known that mutations in rhodopsin and peripherin atrophy groups.(13) The depiction of the IS/OS on OCT is also
induce RP. However, as mentioned above, there are few cases in strongly correlated with visual function.(14, 15) A comparison of
Japan that exhibit a dominant inheritance and less information is IS/OS findings, FAF and visual field tests suggested that there
available on RP mutations in the Japanese. were multiple patterns that could represent the progression of
visual dysfunction in RP.(16)
OCT findings
Reports on the retinal nerve fiber layer (RNFL) thickness in RP
vary considerably.(1–3) Originally, thinning of the RNFL was re-
ported; however, subsequent studies cite thickening of the RNFL
using SD-OCT. In comparison, there was no significant differ-
ence between the thickness of the retinal ganglion cell layer in
eyes with RP and normal eyes.(3) The cause of RNFL thickening
is unclear, although the proliferation of retinal glial cells is
thought to be a factor.(2)
CME is also frequently seen in RP. There are significant
differences in the rate of detection depending on the type of
OCT and imaging method used, with detection rates as low as
10%(4, 5) and as high as 40%.(6) One report states that there is
no significant correlation between the frequency of detection
of CME and mode of inheritance,(6) while another report of
high frequency of CME in cases of dominant inheritance is avail-
able.(7) Another report claims that examining whether or not the
IS/OS is depicted is better correlated with visual acuity than ex-
amining the spread of CME horizontally or vertically on OCT.(8)
There does not appear to be a strong correlation between the
presence or absence of CME and visual function in RP patients.
Epiretinal membranes (ERM) and vitreomacular traction
syndromes are seen at a high frequency in RP. Figures are diverse;
one report claims to have seen ERMs in 64.3% of cases(9) while
another claims it occurs in less than 1%.(3)
The basic pathology of RP is apoptosis of the photoreceptor
cells.(10) Retinal degeneration starts from the intermediate
periphery since apoptosis of the rods precedes apoptosis of
the cones. As a result, changes in the outer retinal layers in the
intermediate periphery occur first on OCT where the IS/OS line
can no longer be detected.
The RPE undergoes reactive changes and partial migration of
reactive RPE cells can be seen towards the inner sensory retina.
The retinal structure near the fovea centralis is often relatively
 266 Chapter 7 · Retinal degeneration

References

1) Walia S, Fishman GA, Edward DP, et al. Retinal nerve fiber layer defects in
RP patients. Invest Ophthalmol Vis Sci. 2007; 48:4748–4752.
2) Walia S, Fishman GA. Retinal nerve fiber layer analysis in RP patients using
Fourier-domain OCT. Invest Ophthalmol Vis Sci. 2008; 49:3525–3528.
3) Hood RC, Lin CE, Lazow MA, et al. Thickness of receptor and post-receptor
retinal layers in patients with retinitis pigmentosa measured with fre-
quency-domain optical coherence tomography. Invest Ophthalmol Vis Sci.
2009; 50:2328–2336.
4) Hagiwara A, Yamamoto S, Ogata K, et al. Macular abnormalities in patients
with retinitis pigmentosa: prevalence on OCT examination and outcomes
of vitreoretinal surgery. Acta Ophthalmol. 2011; 89:e122–125.
5) Hirakawa H, Iijima H, Gohdo T, et al. Optical coherence tomography of cys-
toid macular edema associated with retinitis pigmentosa. Am J Ophthal-
mol. 1999; 128:185–191.
6) Hajali M, Fishman GA, Anderson RJ. The prevalence of cystoid macular

7 oedema in retinitis pigmentosa patients determined by optical coher-

ence tomography. Br J Ophthalmol. 2008; 92:1065–1068.
7) Sandberg MA, Brockhurst RJ, Gaudio AR, et al. Visual acuity is related to
parafoveal retinal thickness in patients with retinitis pigmentosa and
macular cysts. Invest Ophthalmol Vis Sci. 2008; 49:4568–4572.
8) Oishi A, Otani A, Sasahara M, et al. Photoreceptor integrity and visual acu-
ity in cystoid macular oedema associated with retinitis pigmentosa. Eye
(Lond) . 2009; 23:1411–1416.
9) Grigoropoulos VG, Emfietzoglou J, Nikolaidis P, et al. Optical coherence
tomography findings in patients with retinitis pigmentosa and low visual
acuity. Ophthalmic Surg Lasers Imaging. 2010; 41:35–39.
10) Adler R. Mechanisms of photoreceptor death in retinal degenerations.
From the cell biology of the 1990s to the ophthalmology of the 21st cen-
tury? Arch Ophthalmol. 1996; 114:79–83. Review.
11) Hood DC, Lazow MA, Locke KG, et al. The transition zone between healthy
and diseased retina in patients with retinitis pigmentosa. Invest Ophthal-
mol Vis Sci. 2011; 52:101–108.
12) Sandberg MA, Brockhurst RJ, Gaudio AR, et al. The association between
visual acuity and central retinal thickness in retinitis pigmentosa. Invest
Ophthalmol Vis Sci. 2005; 46:3349–3354.
13) Aleman TS, Cideciyan AV, Sumaroka A, et al. Retinal laminar architecture in
human retinitis pigmentosa caused by Rhodopsin gene mutations. Invest
Ophthalmol Vis Sci. 2008; 49:1580–1590.
14) Aizawa S, Mitamura Y, Baba T, et al. Correlation between visual function
and photoreceptor inner/outer segment junction in patients with retinitis
pigmentosa. Eye (Lond) . 2009; 23:304–308.
15) Oishi A, Nakamura H, Tatsumi I, et al. Optical coherence tomographic pat-
tern and focal electroretinogram in patients with retinitis pigmentosa. Eye
(Lond) . 2009; 23:299–303.
16) Murakami T, Akimoto M, Ooto S, et al. Association between abnormal au-
tofluorescence and photoreceptor disorganization in retinitis pigmento-
sa. Am J Ophthalmol. 2008; 145:687–694.
Case 145 · Retinitis pigmentosa: A typical example
267 7
Case 145 Retinitis pigmentosa: A typical example

A 45-year-old male, OD, BCVA 1.0

A: Color fundus photograph: The optic disc normal in color. The retinal arteries are narrowed. Degeneration is apparent peripheral to the vascular arcade.
Bone spicule pigmentation is also present. B: FAF in the right eye: Annular hypofluorescence is visible around the fovea centralis. Autofluorescence is
increasing around the fovea centralis. C: FA in the right eye (2 minutes, 5 seconds): The fovea centralis is exhibiting significant hypofluorescence and there
is a slightly hypofluorescent area surrounding it. Multiple, relatively large, patchy hypofluorescent foci are visible peripheral to the vascular arcade.
D: IA in the right eye (2 minutes, 5 seconds): The large choroidal vessels are clearly seen in the area of retinal atrophy peripheral to the vascular arcade.
Choroidal background fluorescence appears almost normal where the retinal color is also normal. E: IR + OCT horizontal scan of the right eye: The structure
of the fovea is almost normal. F: Enlarged version of E [red dashed box]: Small cystoid spaces are visible near the fovea. The outer retinal layer structure is
relatively well preserved in the area indicated by  . The outer retinal layer structure peripheral to this area is damaged. Best-corrected visual acuity
is good at 1.0 since the foveal structure is maintained. 7 indicates mild ERM.
(Continued on the next page)
 268 Chapter 7 · Retinal degeneration

Case 145 Continuation

G: FAF and corresponding OCT horizontal scan in the right eye: Comparison of FAF and OCT images. On the FAF, the fovea centralis is exhibiting relatively
intense hypofluorescence. Around this, there is a region of weaker hypofluorescence. Mild hyperfluorescence surrounds this region which is itself surrounded
by another region of hypofluorescence forming a ring-shape. The area outside the annular hypofluorescence shows hyperfluorescence. On OCT, the RPE
and outer retinal layer structure is relatively well preserved in the hypofluorescent area near the fovea centralis. The RPE is also fairly well preserved in the
hyperfluorescent area around this, but neither the ELM nor the IS/OS are visible. Damage to the RPE appears severe (particularly temporally), looking as if it
is »fuzzy«, in the hypofluorescent ring area around this. In addition, only a small part of the outer nuclear layer appears to be remaining. The outer retinal
layer structure has completely disappeared even further peripherally. RPE reflectivity appears normal at first glance.

Image interpretation points

This is a typical case of RP. There is damage to the outer retinal RPE abnormalities between these areas. Good correspondence
layers in the periphery and the structure near the fovea centralis between FAF and OCT images provides important information.
is relatively well preserved. Interestingly, there are characteristic

Retinitis pigmentosa
Case 146 · Retinitis pigmentosa: Cystoid macular edema
269 7
Case 146 Retinitis pigmentosa: Cystoid macular edema

A 18-year-old male, OD, BCVA 0.6

A: Color fundus photograph in the right eye: A fundus reflex unique to young people is apparent. The color of the macula is relatively normal, but the the
area peripheral to the vascular arcades is degenerative and exhibiting a grey appearance. B: IR + OCT horizontal scan of the right eye: A large cystoid space
(*) is visible in the fovea centralis. C: IR + OCT vertical scan of the right eye: A large cystoid space (*) is also noticeable in the fovea centralis in this vertical
scan. Cystoid spaces are seen side by side in the inner nuclear layer and outer plexiform layer peripheral to the large cystoid space. D: Enlarged version of B
[red dashed box]: The ELM and IS/OS, although indistinct, are seen in the foveal outer retinal layers ( ). There is significant damage to the outer retinal
layers outside of this area, and the IS/OS line cannot be seen. The retinal nerve fiber layer is preserved.

Image interpretation points

This is a case of RP in a relatively young patient. A large cystoid is not seen. Since this is a young patient, an ERM is not visible.
space is seen in the fovea centralis. Damage to the outer retinal The RNFL is well preserved, although retinal nerve fiber layer
layers is more pronounced peripheral to the vascular arcades can reportedly be thicker than normal in RP.
and, although the outer plexiform layer is visible, the IS/OS line
 270 Chapter 7 · Retinal degeneration

Case 147 Retinitis pigmentosa: Vitreomacular traction syndrome

A 57-year-old female, OD, BCVA 0.3

A: Color fundus photograph in the right eye: The optic disc is pale and there is significant narrowing of the retinal arteries. The color of the macular retina
is relatively normal. Degeneration is apparent in the area peripheral to the vascular arcades. Bone spicule pigmentation is present inferior to the vascular
arcades. B: IR + OCT horizontal scan of the right eye: The fovea centralis is elevated as a result of the traction by the considerably thickened posterior vitreous
cortex (7). Cystoid spaces can be seen in the fovea centralis (*). C: Enlarged version of B [red dashed box]: The ELM and partially remaining IS/OS are visible
in the fovea centralis (red dashed circle). The outer retinal layer structure peripheral to the fovea centralis has almost disappeared. Small highly reflective dots
are visible in the outer nuclear layer, which may be derived from the RPE ( ). D: IR + OCT vertical scan of the right eye: Traction to the fovea is clearly visible.

Image interpretation points

This is a case of RP in conjunction with vitreomacular traction limited information available on the outcomes of vitreous
syndrome. A thickened posterior vitreous cortex is a typical surgery in these cases.
feature. These findings are common in older patients. There is
7.11 · Fundus albipunctatus
271 7
7.11 Fundus albipunctatus References

Background 1) Lauber H. Die sogenannter retinitis punctata albescens. Klin Monatsbl

Augenheilkd. 1910; 48:133–148.
Fundus albipunctatus is a disease that exhibits an autosomal re-
2) Niwa Y, Kondo M, Ueno S, et al. Cone and rod dysfunction in fundus
cessive mode of inheritance and was first reported by Lauber.(1) albipunctatus with RDH5 mutation: an electrophysiological study. Invest
Typical ophthalmoscopic findings include white dots visible Ophthalmol Vis Sci. 2005; 46:1480–1485.
from the posterior pole to the intermediate periphery of the 3) Yamamoto H, Simon A, Eriksson U, et al. Mutations in the gene encoding
fundus. This disease typically involves stationary night blindness 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus
with electrophysiological abnormalities in both rods and cones albipunctatus. Nat Genet. 1999; 22:188–191.
4) Schatz P, Preising M, Lorenz B, et al. Fundus albipunctatus associated with
in the setting of good visual acuity. This disease has been classi-
compound heterozygous mutations in RPE65. Ophthalmology. 2011;
fied as stationary night blindness; however, cases of progressive 118:888–894.
visual dysfunction have been reported in recent years.(2) 5) Querques G, Carrillo P, Querques L, et al. High-definition optical coher-
Mutations in retinol dehydrogenase (RDH5) are known to be ence tomographic visualization of photoreceptor layer and retinal flecks
a cause of fundus albipunctatus.(3) Currently, at least 25 muta- in fundus albipunctatus associated with cone dystrophy. Arch Ophthal-
mol. 2009; 127:703–706.
tions have been reported. The majority of these reports come
6) Schatz P, Preising M, Lorenz B, et al. Lack of autofluorescence in fundus
from Japan, where this disease is frequently seen in Japanese albipunctatus associated with mutations in RDH5. Retina. 2010; 30:1704–
people. RPE65 is also reported as a causative gene.(4) 1713.
7) Genead MA, Fishman GA, Lindeman M. Spectral-domain optical coher-
OCT findings ence tomography and fundus autofluorescence characteristics in patients
with fundus albipunctatus and retinitis punctata albescens. Ophthalmic
There are a number of miscellaneous reports on spectral-domain
Genet. 2010; 31:66–72.
OCT findings.(5–8) The white dots in the ocular fundus tend to 8) Sergouniotis PI, Sohn EH, Li Z, et al. Phenotypic variability in RDH5 retin-
become less noticeable as the disease stage progresses and OCT opathy (Fundus Albipunctatus) . Ophthalmology. 2011 ; 118 : 1661–1670.
findings may change in accordance with this. Nevertheless, there
are only a few reports that have conducted detailed follow-ups
of multiple cases. The white dots can be seen as protruding,
dome-shaped, highly reflective structures extending from Bruch’s
membrane to the ELM. They can sometimes be accompanied by
cone dystrophy and a decrease in foveal thickness. In addition,
highly reflective deposits are visible posterior to the ELM in
elderly patients as well as loss of the photoreceptor outer segment.
 272 Chapter 7 · Retinal degeneration

Case 148 Fundus albipunctatus: A typical example

An 18-year-old female, OD, BCVA 0.9

A: Color fundus photograph in the right eye: Although unremarkable in the macula, characteristic white dots are visible peripheral to the vascular arcades
and nasal to the optic disc. B: Enlarged version of A [white dashed box]: White dots are clearly visible. C: IR + OCT vertical scan of the right eye: This is a
scan passing through the fovea centralis. The IS/OS in the fovea centralis is disrupted. D: Enlarged version of C [red dashed box]: Disruption in the IS/OS of
the fovea centralis is clearly visible. Faint highly reflective images are present in the foveal ELM, which appears to be changes that have occurred as a
consequence of photoreceptor cell loss. The IS/OS line exhibits the same thickness as the RPE.
Case 148 · Fundus albipunctatus: A typical example
273 7

E: IR + OCT horizontal scan of the right eye: This is a horizontal scan superior to the fovea centralis. Highly reflective structures extending from the RPE to
the ELM are seen to partially penetrate the ELM. Small, highly reflective dots are visible in the outer nuclear layer immediately anterior to these structures.
F: Enlarged version of E [red dashed box]: The highly reflective structures appear to be extending to just inside the ELM (red dashed circle). G: IR + OCT
horizontal scan of the right eye: This is a scan passing through the area immediately above the fovea centralis. No IS/OS defects are evident in this image.
H: Enlarged version of G [red dashed box]: The IS/OS line temporal to the fovea centralis is depicted as a discontinuous line (red dashed circle)

Image interpretation points

This case presents OCT findings typical of fundus albipuncta- with the RPE. The poorly visible COST and IS/OS lines may be
tus. The white dots are described as dome-shaped, highly a characteristic of fundus albipunctatus, but further study of
reflective structures that appear to pass through the ELM from multiple cases is required to confirm this. A comparison study
the RPE level or Bruch’s membrane. However, upon closer with the RDH5 mutation is, of course, necessary.
observation these structures do not appear to be in contact
 274 Chapter 7 · Retinal degeneration

7.12 Oguchi disease References

Background 1) Oguchi C. Types of night blindness. Japanese Journal of Ophthalmology

1907; 11: 123–134.
Oguchi disease is a disease first reported by Chuta Oguchi in
2) Fuchs S, Nakazawa M, Maw M, et al. A homozygous 1-base pair deletion in
1907.(1) It exhibits a typical retinal color expressed as a »golden the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat
sheen«, which can be restored to its normal color through Genet. 1995; 10:360–362.
prolonged dark adaptation (Mizuo-Nakamura phenomenon). 3) Yamamoto S, Sippel KC, Berson E, et al. Defects in the rhodopsin kinase
Oguchi disease is a type of congenital stationary night blindness gene in the Oguchi form of stationary night blindness. Nat Genet. 1997;
that exhibits an autosomal recessive mode of inheritance where 15:175–178.
4) Dryja TP. Molecular genetics of Oguchi disease, Fundus albipunctatus, and
mutations of arrestin (SAG)(2) and rhodopsin kinase (GRK1)(3)
other forms of stationary night blindness: LVII Edward Jackson Memorial
are reportedly associated with the onset of this disease. Arrestin Lecture. Am J Ophthalmol. 2000; 130:547–563.
and rhodopsin kinase are proteins that act to render activated 5) Hayashi T, Gekka T, Takeuchi T, et al. A novel homozygous GRK1 mutation
rhodopsin inactive. In Oguchi disease, the activity of these (P391H) in 2 siblings with Oguchi disease with markedly reduced cone
proteins is decreased causing the rhodopsin present in the rod responses. Ophthalmology. 2007; 114:134–141.
6) Yamada K, Motomura Y, Matsumoto CS, et al. Optical coherence tomo-
outer segments to remain active. As a result, a prolonged time
7 course is required for dark adaptation of the rods.(4) Historically,
graphic evaluation of the outer retinal architecture in Oguchi disease. Jpn
J Ophthalmol. 2009; 53:449–451.
Oguchi disease has been classified as stationary night blindness; 7) Hashimoto H, Kishi S. Shortening of the rod outer segment in Oguchi dis-
however, there are cases where progressive tunnel vision and ease. Graefes Arch Clin Exp Ophthalmol. 2009; 247:1561–1563.
cone dysfunction is seen.(5) 8) Takada M, Otani A, Ogino K, et al. Spectral-domain optical coherence to-
mography findings in the Mizuo-Nakamura Phenomenon of Oguchi dis-
OCT findings ease. Retina. 2011; 31:626–628.

Very little information has been available on OCT findings for

Oguchi disease. There are three studies from Japan; however,
each only reports one case. According to these reports, the
parafoveal IS/OS line becomes clearly visible when the Mizuo-
Nakamura phenomenon occurs(6) and the photoreceptor outer
segment is shortened in the area where a golden sheen fundus
reflex is visible.(7) In this area, the IS/OS line, COST line, and
RPE line are depicted as a highly reflective thick line in bright
conditions and the fused 3 lines becomes separated into three
lines when the Mizuo-Nakamura phenomenon occurs.(8)
Case 149 · Oguchi disease: A typical example
275 7
Case 149 Oguchi disease: A typical example

A 51-year-old male, OD, BCVA 1.2

A: Color fundus photograph in the right eye: A golden sheen fundus reflex is visible in the inferior retina. B: Enlarged version of A [white dashed box]: We
can see the golden sheen appearance and normal retinal color around the blood vessels. C: IR + OCT horizontal scan of the right eye: Foveal retinal thick-
ness is preserved, but thinning is evident in the outer retinal layers both temporally and near the optic nerve. D: Enlarged version of C [red dashed box]:
The retinal structure near the fovea centralis appears normal. A thin ERM is visible (7). The ELM and IS/OS are indistinct in the peripheral areas indicated by
 . E: Enlarged version of D [red dashed box]: The outer retinal layer structure near the fovea centralis including the ELM, IS/OS and COST lines appears
almost normal (blue dashed circle). Temporally, the ELM is approaching to the RPE, the IS/OS line is disappearing, and the outer nuclear layer is thinning
and is almost completely lost at the most temporal area (red dashed circle).

Image interpretation points

There are only a few reports on SD-OCT findings in Oguchi periphery of the macula. Even further peripherally, RPE stratifi-
disease. While the macular structure is preserved in this case, cation and disappearance of the outer nuclear layer is observed.
there is thinning of the ELM, IS/OS, and COST lines in the
 276 Chapter 7 · Retinal degeneration

Case 150 Oguchi disease: Cystoid space formation and golden sheen fundus reflex
(fellow eye of case 149)
A 51-year-old male, OS, BCVA 1.0

A: Color fundus photograph in the left eye: A golden sheen fundus reflex is visible in the inferior retina similar to the right eye. B: IR + OCT vertical scan of
left eye: A foveal cystoid space is seen. The superior RPE is exhibiting high reflectivity. Damage to the outer retinal layers of the inferior macula is significant
when compared the the superior macula. C: Enlarged version of B [red dashed box]: Loss of the RPE and photoreceptor layer is evident in the area indicated
by the red dashed circle. Choroidal signal enhancement is visible consistent with this damaged area. The foveal outer retinal layer structure is relatively well
preserved, consistent with the patient’s good visual acuity (1.0). High RPE reflectivity is noted superior to the fovea centralis ( ). The outer nuclear layer is
severely thinned in this area too. D: IR + OCT horizontal scan of the left eye golden sheen fundus reflex area + enlarged version [red dashed box]: The red and
blue dashed circles indicate the corresponding retinal blood vessels. We can see that the IS/OS line is a thick line in the area exhibiting a golden sheen fundus
reflex. The ELM line is normal and there is no obvious thinning of the photoreceptor inner and outer segments. (D was modified according to Takada M, et al.
Spectral-domain optical coherence tomography findings in the Mizuo-Nakamura phenomenon of Oguchi disease. Retina. 2011; 31: 626–628)

Image interpretation points

In this case, the RPE and IS/OS lines are depicted separately reports, it is unclear whether these findings are characteristic of
as a result of prolonged dark adaptation. With limited case Oguchi disease.
 277 8

Uveitis
8.1 Behçet disease – 278
References – 278

Case 151 Behçet disease: Cystoid edema and foveal detachment – 279

Case 152 Behçet disease: Retinal atrophy – 280

Case 153 Behçet disease: Acute attack – 281

8.2 Sarcoidosis – 282

References – 282

Case 154 Sarcoidosis: Cystoid macular edema – 283

Case 155 Sarcoidosis: Foveal detachment – 284

8.3 Vogt-Koyanagi-Harada disease – 285

References – 286

Case 156 Vogt-Koyanagi-Harada disease: Large foveal cystoid space – 287

Case 156 Continuation – 288

Case 157 Vogt-Koyanagi-Harada disease: Prominent choroidal

thickening – 289

Case 157 Continuation – 290

Case 158 Vogt-Koyanagi-Harada disease: Reattachment process – 291

Case 158 Continuation – 292

Case 159 Vogt-Koyanagi-Harada disease: Choroidal folds – 293

Case 159 Continuation – 294

8.4 Sympathetic ophthalmia – 295

References – 295

Case 160 Sympathetic ophthalmia: After vitreous surgery – 296

8.5 Toxocariasis – 297

References – 297

Case 161 Toxocariasis: Proliferative membrane – 298

8.6 Acute retinal necrosis (Kirisawa-type uveitis) – 299

References – 299

Case 162 Acute retinal necrosis (Kirisawa-type uveitis):

A typical example – 300
 278 Chapter 8 · Uveitis

8.1 Behçet disease References

Background 1) Unoki N, Nishijima K, Kita M, et al. Structural changes of fovea during

remission of Behçet’s disease as imaged by spectral domain optical
Behçet disease is a disease characterized by four main symptoms:
coherence tomography. Eye (Lond). 2010; 24: 969–975.
recurrent aphthous ulcer of the oral mucosa, skin manifestations, 2) Takeuchi M, Iwasaki T, Kezuka T, et al. Functional and morphological
intraocular inflammation, and vulvar ulcer. The prevalence of changes in the eyes of Behçet’s patients with uveitis. Acta Ophthalmol.
HLA-B51 is high. Ninety % of eye symptoms are bilateral acute 2010; 88: 257–262.
uveitis that occurs repeatedly. This disease is nongranulomatous
uveitis, and hypopyon sometimes occurs. The sudden, violent
occurrence of inflammation is called an acute attack. Repeated
acute attacks accompanied by retinal perivasculitis with hemor-
rhages, patchy retinal whitening, macular edema, and optic
disc edema cause macular degeneration and optic nerve atrophy
resulting in a poor visual prognosis. Topical therapy with triam-
cinolone is reported to be effective for macular edema. The
use of colchicine and cyclosporine is effective as a systemic
therapy, but systemic administration of steroids is contraindi-
8 cated. Recently, intravenous treatment with the anti-human
TNF-α monoclonal antibody infliximab (Remicade) has been
confirmed as more effective than traditional therapies.

OCT findings
Behçet disease develops macular edema accompanied by foveal
detachment, which characterized by the intraretinal and sub-
retinal infiltration of leukocytes. Repeated acute attacks cause
the retina to thin and leads to poor visual acuity.(1, 2) Thinning of
the outer retinal layers in the macular area is directly linked to
visual acuity decline. Retinal vasculitis and retinal edema can
occur significantly in the extensive area where both the inner and
outer layers of the retina thin.
Case 151 · Behçet disease: Cystoid edema and foveal detachment
279 8
Case 151 Behçet disease: Cystoid edema and foveal detachment

A 30-year-old female, OD and OS, BCVA 0.02 and 0.2, respectively

A: Color fundus photograph in the right eye: There is clouding of the vitreous body. RPE atrophy is evident inferior and nasal to the optic disc, and retinal
hemorrhages and focal accumulations of yellow-white deep retinal exudates are visible. B: Color fundus photograph in the left eye: Retinal hemorrhages
and patchy retinal whitening noticeable. CME is also visible. C: Anterior segment photograph: A posterior synechia is seen. D: IR + OCT horizontal scan of
the right eye: A foveal detachment and a SRD in the vicinity of the optic disc can be seen. E: IR + OCT horizontal scan of the left eye: A typical image of CME
is visible.

Image interpretation points

The patient became aware of blurred vision and reduced in her right eye, and typical CME was seen in her left eye. This
visual acuity 6 months earlier and visited their local doctor. was an incomplete form of Behçet disease. In this case, infiltra-
Only topical steroid therapy was initiated since she was preg- tion of neutrophils into the retina or vitreous cavity was not
nant. At initial diagnosis, a foveal detachment was seen evident.
 280 Chapter 8 · Uveitis

Case 152 Behçet disease: Retinal atrophy

A 51-year-old male, OD, BCVA 0.7

A: Color fundus photograph in the right eye: At initial diagnosis. CME is visible. B: Color fundus photograph in the right eye: 3 years and 5 months after
initial diagnosis. Best-corrected visual acuity has declined to 0.05. The vitreous is cloudy. Narrowing of retinal blood vessels and optic nerve atrophy are
apparent. C: OCT horizontal scan of the right eye: At initial diagnosis. Time-domain OCT image. CME and a foveal detachment are noted. D: IR + OCT hori-
zontal scan of the right eye + enlarged version [red dashed box]: 3 years and 5 months after initial diagnosis. The entire retina is thin. The structure of layers
within the fovea centralis in particular is indistinct, and infiltration of leukocytes and RPE stratification is visible. E: IR + OCT vertical scan of the right eye:
3 years and 5 months after initial diagnosis. Foveal atrophy is significant and the infiltration of leukocytes, and RPE stratification is exhibited. ERM is seen.

Image interpretation points

The patient became aware of blurred vision in their right seen. After the third acute attack that occured 3 years and
eye 3 months earlier and was referred to our hospital. At initial 5 months after initial diagnosis, retinal atrophy had occurred
diagnosis, CME accompanied by a foveal detachment was over a wide area.

cystoid macular edema

Case 153 · Behçet disease: Acute attack
281 8
Case 153 Behçet disease: Acute attack

A 48-year-old female, OD and OS, 0.5 and 0.1, respectively

A: Color fundus photograph in the right eye: During an acute attack of the right eye. B: Color fundus photograph in the left eye: During an acute attack
of the left eye that occurred 14 months after A. Best-corrected visual acuity declined to 0.1 (1.2 at initial diagnosis). Patchy retinal whitening is evident in
the macular area of both eyes. C: FA in the left eye (8 minutes): Left eye during an acute attack. Leakage from retinal capillaries in the macular area is visible
beyond the vitreous opacity. D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: During an acute attack of the right eye.
Moderate reflectivity ( ) due to accumulating infiltrated leukocytes is apparent. Infiltrated leukocytes can also be seen in the vitreous cavity (red dashed
circle). The foveal IS/OS line has disappeared and the outer segment on the temporal side of the fovea centralis is thin. E: IR + OCT oblique scan of the left
eye + enlarged version [red dashed box]: During an acute attack of the left eye. Infiltrated leukocytes and thinning of the foveal outer segment is exhibited.

Image interpretation points

The first acute attack had occurred in the right eye 4 years area. No cystoid edema or SRDs could be seen. Irregularities
prior, and a follow-up was continued after symptoms receded and disappearance of the IS/OS line and thinning of the outer
with therapy using colchicine and cyclosporine. Patchy retinal segment were seen in both eyes, which were the cause of
whitening was visible in the macula in both eyes during acute visual impairment.
attacks, and leukocyte infiltration was seen on OCT in the same
 282 Chapter 8 · Uveitis

8.2 Sarcoidosis References

Background 1) Uyama M. Uveitis in sarcoidosis. Int Ophthalmol Clin. 2002; 42: 143–150.
2) Larsson J, Hvarfner C, Skarin A. Intravitreal triamcinolone in two patients
Sarcoidosis is a systemic, noncaseating granulomatous disease
with refractory macular oedema in sarcoid uveitis. Acta Ophthalmol
that affects multiple organs starting with the lungs, eyes, lymph Scand. 2005; 83: 618–619.
nodes, and skin. It is characterized by noncaseating, epithelioid 3) Wong M, Janowicz M, Tessler HH, et al. High-resolution optical coherence
granuloma (sarcoid nodules) and is accompanied by granuloma- tomography of presumed sarcoid retinal granulomas. Retina. 2009; 29:
tous angiitis and microangiopathy.(1) The incidence is twice 1545–1546.
higher in women than in men and is common in women in their
20s and 60s and men in their 20s. The frequency of ocular lesions
in Japan is high at 60–80%. Prognosis is relatively good, although
death as a result of cardiac lesions etc. has been reported in 10–
20% of the cases, so diagnosis is important.
Ocular lesions include granulomatous anterior uveitis, tra-
becular nodules, tent-like adhesion of the peripheral iris, vitreous
clouding (snowball-like, beaded, lump-like, and particle-like),
retinal perivasculitis (particularly periphlebitis), exudative cho-
8 rioretinal spots, and chorioretinal atrophic lesions. Periphlebitis,
perivenous tubercles, and sometimes, a nonperfusion area are
visible on FA.

OCT findings
CME is a typical finding in sarcoidosis.(2) Retinal granulomatous
lesions appear to occupy the inner retinal layers.(3) Although
Behçet disease is accompanied by the intraretinal and subretinal
infiltration of leukocytes this is not seen in sarcoidosis.

cystoid macular edema

Case 154 · Sarcoidosis: Cystoid macular edema
283 8
Case 154 Sarcoidosis: Cystoid macular edema

A 76-year-old female, OD and OS, BCVA 0.3 and 0.2, respectively

A: Color fundus photograph in the right eye, B: Color fundus photograph in the left eye. CME is visible. Patchy choroidal atrophy is evident around the
optic disc. C: FA in the right eye (6 minutes), D: FA in the left eye (4 minutes). CME can be seen in both eyes. Retinal periphlebitis and the formation of a
nonperfusion area are noted outside the arcade vessels. E: IA + OCT horizontal scan of the right eye, F: IA + OCT horizontal scan of the left eye: CME is
visible in both eyes.

Image interpretation points

The patient became aware of reduced visual acuity in both the patient was referred to us. CME was visible in both eyes on
eyes 15 months before visiting her local doctor who diagnosed FA and OCT, but no findings consistent with retinal periphlebitis
her with uveitis and gave her eye drops. CME exacerbated and outside the macula could be seen on OCT.
 284 Chapter 8 · Uveitis

Case 155 Sarcoidosis: Foveal detachment

A 60-year-old female, OS, BCVA 0.5

A: Color fundus photograph in the left eye: Edema is evident around the optic disc and in the macular area. B: FA + IA in the left eye (5 minutes): On FA,
CME is visible in the posterior pole, and retinal periphlebitis and exudative chorioretinal spots are noted around the arcade vessels. Small, hypofluorescent
lesions are scattered above the arcade vessels on IA. Macular choroidal vessels are not sufficiently depicted due to macular edema. C: FA + IA in the left
eye (6 minutes): Multiple patchy hyperfluorescent lesions corresponding to exudative chorioretinal spots are depicted in the equatorial area on FA. Hypo-
fluorescent spots are visible on IA, but they are not consistent with the multiple, patchy hyperfluorescent lesions on FA. D: IA + OCT horizontal scan of the
left eye: CME accompanied by a foveal detachment is visible.

Image interpretation points

After being diagnosed with uveitis, the patient continued ste- ERM not including the fovea centralis and a foveal detachment
roid eye drop instillation; nevertheless, vitreous clouding and are visible on OCT and progressing to a macular pseudohole.
CME developed one year later. CME is evident on FA and OCT.
8.3 · Vogt-Koyanagi-Harada disease
285 8
8.3 Vogt-Koyanagi-Harada disease folds develops, choroidal depigmentation progresses, and a typi-
cal sunset glow fundus is finally formed.
Background
Vogt-Koyanagi-Harada disease (VKH) is characterized by bilat- Vogt-Koyanagi type
eral serous retinal detachments (SRDs). Patients become aware Mainly characterized by inflammation of the anterior segment.
of rapid visual decline as a result. This disease is common in Granulomatous iridocyclitis occurs causing inflammatory cells
Asians and is considered a systemic autoimmune disease toward in the anterior chamber, iris nodules, and keratic precipitate. The
melanocytes. Typical eye symptoms, increased cerebrospinal anterior chamber becomes shallow as a result of swelling of the
fluid cell count, and typical extraocular symptoms are useful for ciliary body, and supraciliary effusions in eyes with severe in-
diagnosis. Five to seven days before eye symptoms occur, pre- flammation.
monitory signs such as flu-like symptoms, headache, nausea,
fatigue, hair hyperesthesia, tinnitus, and dizziness manifest in Fluorescein fundus angiography
roughly one-third of cases. During the recovery phase, choroidal jFA
depigmentation develops in the eyes and over the entire body. Multiple punctate leaking points are visible at the early phase,
The eyes exhibit a sunset glow fundus appearance and skin and multilobular fluorescent accumulation is visible during the
depigmentation spots; whitening of the hair, eyebrows, and eye- late phase. A weakly reflective border known as a dark rim can
lashes occurs over the entire body.(1) be seen around the foveal fluorescent accumulation.(2)

Disease types jIA

This disease can be divided into the following two types based on A choroidal filling delay is evident. Hypofluorescence is seen
the main lesion site. consistent with a SRD.

Harada type OCT findings

Mainly characterized by lesions in the posterior pole of the fun- jSensory retina
dus. A typical multilobular SRD occurs in the posterior pole. A Typical OCT findings include membranous structures (also
yellowish-white rim is often observed around the foveal SRD. called septa) that partition the subretinal space. Exactly what
Choroidal folds can also occur. There is also a papilledema type this membranous structure is has become the subject of debate.
consisting mainly of redness and swelling of the optic disc. About One theory states that this membranous structure is part of
2 months after onset, the SRD starts to disappear radial retinal the retina,(3, 4) and another states that it is fibrin membrane.(5)

. Fig. 8-1 Schematic diagram showing how the membranous structure characteristic of acute VKH disease form and, with high-dose steroid therapy, resolve.
A: Choroidal interstitial pressure is enhanced, and subretinal or intraretinal leakages occur from the failed junctions between RPE cells. B: Fluid exudates
accumulate subretinally, causing serous retinal detachment, and within the retina, forming a cystoid space between photoreceptor inner and outer segment.
The leakage fluid contains fibrin, and the intraretinal cystoid space is lined with a fibrin membrane. The fibrin also binds the detached outer segments to form
the membranous structure . C: Fibrin rapidly disappears with the administration of steroids, and consequently the outer segment loses its adhesive forces
to each other and resulting unbound pieces of the outer segment collapse on the RPE (Modified according to Ishihara K, et al. Acute Vogt-Koyanagi-Harada
disease in enhanced spectral-domain optical coherence tomography. Ophthalmology. 2009; 116: 1799–1807)
 286 Chapter 8 · Uveitis

However, when observed on images with speckle noise removed, References

① a IS/OS line in continuity with the IS/OS line in the attached
retina is visible in the membranous structure , ② and fluid space 1) Moorthy RS, Inomata H, Rao NA.Vogt-Koyanagi-Harada syndrome. Surv
Ophthalmol. 1995; 39: 265–292.
can sometimes be seen anterior to the IS/OS line. Furthermore,
2) Gass JDM. Harada’s disease. Stereoscopic atlas of macular diseases. Diag-
③ the width of the membranous structure is uniform in each nosis and treatment 4th ed., CV Mosby, St. Louis, 1997. pp176–180.
eye and similar between cases, and ④ the membranous struc- 3) Maruyama Y, Kishi S. Tomographic features of serous retinal detachment
ture  immediately disappears with steroid therapy and instead in Vogt-Koyanagi-Harada syndrome. Ophthalmic Surg Lasers Imaging.
granular structures accumulate on the RPE (clearly visible on 2004; 35: 239–242.
IR images). This can be interpreted as exudate containing a lot of 4) Tsujikawa A, Yamashiro K, Yamamoto K, et al. Retinal cystoid spaces in
acute Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 2005; 139:
fibrin accumulated in the space between the photoreceptor inner
670–677.
and outer segments forming a cystoid space. This cystoid space 5) Yamaguchi Y, Otani T, Kishi S. Tomographic features of serous retinal de-
is then lined with a fibrin membrane, and the outer segment, tachment with multilobular dye pooling in acute Vogt-Koyanagi-Harada
which originally has no adhesive force to each other, becomes disease. Am J Ophthalmol. 2007; 144: 260–265.
a membranous structure with the adhesive force of the fibrin 6) Ishihara K, Hangai M, Kita M, et al. Acute Vogt-Koyanagi-Harada disease in
enhanced spectral-domain optical coherence tomography. Ophthalmol-
(. Fig. 8-1).(6) In practice, reflectivity with amorphous structure
ogy. 2009; 116: 1799–1807.
that differs from the membranous structure is seen within the 7) Forster DJ, Cano MR, Green RL, et al. Echographic features of the Vogt-
cystoid space, which appears to be fibrin alone. The granular Koyanagi-Harada syndrome. Arch Ophthalmol. 1990; 108: 1421–1426.

8 structures seen after steroid therapy are thought to be unbound

pieces of the outer segments that has collapsed onto the RPE as a
8) Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treat-
ment of Vogt-Koyanagi-Harada disease. Retina. 2011; 31: 510–517.
9) Wu W, Wen F, Huang S, et al. Choroidal folds in Vogt-Koyanagi-Harada
result of dissolution of the fibrin that binded them.
disease. Am J Ophthalmol. 2007; 143: 900–901.
10) Gupta V, Gupta A, Gupta P, et al. Spectral-domain cirrus optical coherence
jThe choroid tomography of choroidal striations seen in the acute stage of Vogt-Koya-
Thickening of the choroid first became evident on ultrasonogra- nagi-Harada disease. Am J Ophthalmol. 2009; 147: 148–153.e2.
phy.(7) When observed with EDI-OCT and SS-OCT, prominent
choroidal thickening and obscuration of the choroidal striation
pattern are evident.(8) Sometimes, the choroid exhibits signifi-
cant undulations.(9, 10) On steroid therapy, choroidal thickening
recedes faster than the SRD disappears.(7, 8)
Case 156 · Vogt-Koyanagi-Harada disease: Large foveal cystoid space
287 8
Case 156 Vogt-Koyanagi-Harada disease: Large foveal cystoid space

A 24-year-old female, OD, BCVA 0.5

A: Color fundus photograph in the right eye, B: Enlarged version of A [red dashed box]: A multilobular SRD is visible. The foveal SRD is large, and partially
encompassed by a double yellow rims. Fibrin is visible on the temporal side ( ). C: IR + OCT horizontal scan of right eye: A scan along the lower arrow in B.
Membranous structure uniform in width on the RPE can be seen at the bottom of the cystoid space. Amorphous reflectivity (*) corresponding to fibrin is
observed inside. The outer retinal layers ( ) stretched out tongue-like and visible in the border of the foveal cystoid space correspond to the yellow rim.
Retinoschisis is evident in part of the posterior border of the outer plexiform layer. D: IR + OCT horizontal scan of the right eye + enlarged version [red
dashed box]: A scan along the upper arrow in B. The bottom of the cystoid space is formed anterior to the ELM, that is to say, it has formed within the outer
nuclear layer. E: IR + OCT vertical scan of the right eye: The cystoid space and SRD are partitioned by the outer retinal layers ( ) stretching out in a tongue-
like form and membranous structure continuing from it.
(Continued on the next page)
 288 Chapter 8 · Uveitis

Case 156 Continuation

F: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Third day after starting steroid therapy. Best-corrected visual acuity is 0.15.
The height of the cystoid space is decreasing, fibrin is decreasing, and the membranous structure is becoming irregular. G: IR + OCT horizontal scan of the
right eye + enlarged version [red dashed box]: Seventh day after starting steroid therapy. Best-corrected visual acuity is 0.4. The membranous structure on
the RPE is undergoing granular changes. Fibrin has disappeared. The newly formed outer segments becoming partially elongated, but they are highly re-
flective and irregular. H: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Tenth day after starting steroid therapy. The retina is
reattached, but the IS/OS is irregular, and the outer segment is thin. I: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: 32nd
day after starting steroid therapy. Best-corrected visual acuity has improved to 1.2. IS/OS and outer segment thickness has almost normalized.

Image interpretation points

We wish to understand the specific structures visible in the rapidly with steroid therapy and the membranous structure
color fundus photo in VKH syndrome through comparisons undergoes granular changes on the RPE during this process. This
between the ocular fundus and OCT. The area encompassed observation can be interpreted as the outer segment bound by
by the yellow rim is the cystoid space, which has a wall com- fibrin becoming scattered with the disappearance of the fibrin
posed of membranous structure. Fibrin precipitated in the and each of the scattered outer segments corresponding to the
cystoid space is lining the cystoid space. It is thought that granular structure. The IS/OS line is irregular, and the photo-
outer segments becomes bound by the fibrin, and acts as receptor outer segment is thin immediately after reattachment,
membranous structure. The cystoid space and fibrin recede but this usually normalizes in around 2 weeks.
Case 157 · Vogt-Koyanagi-Harada disease: Prominent choroidal thickening
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Case 157 Vogt-Koyanagi-Harada disease: Prominent choroidal thickening

A 42-year-old female, OS, BCVA 1.2

A: Color fundus photograph in the left eye: A SRD is seen. Retinal whitening can be seen around the optic disc and following the arcade vessels. B: Anterior
segment OCT image of the left eye: A supraciliary effusion and consequent shallow anterior chamber is seen. C: IR + OCT horizontal scan of the left eye:
A SRD (*) is noted. The RPE is protruding forward, and loss of the choroidal striation pattern is apparent. The shed outer segments are noticeable on the
RPE. D: IR + EDI-OCT horizontal scan of the left eye: Choroidal thickening is prominent, and the sclera is not depicted on EDI-OCT. The choroidal striation
pattern is blurred. E: IR + OCT vertical scan of left eye: A SRD (*) and RPE undulation is exhibited.
(Continued on the next page)
 290 Chapter 8 · Uveitis

Case 157 Continuation

F: IR + EDI-OCT horizontal scan of the left eye: At initial diagnosis. G: IR + EDI-OCT horizontal scan of the left eye: First day after starting steroid therapy.
The SRD and RPE protrusion are receding, but choroidal thickening is still significant, and the sclera is not visible. H: IR + EDI-OCT horizontal scan of the left
eye: Fifth day after starting steroid therapy. Choroidal thickening has receded significantly, and the sclera can be seen. The choroidal striation pattern is
being restored. I: IR + EDI-OCT horizontal scan of the left eye: 28th day after starting steroid therapy. The thickness and pattern of the choroid have almost
normalized. The sensory retina has almost normalized.

Image interpretation points

The patient became aware of reduced visual acuity in both prominent choroidal thickening and blurring of the choroidal
eyes 2 weeks earlier and visited our hospital. The patient was striation pattern was observed on EDI-OCT, and the scleral
aware of dizziness, hearing loss, and headache. Keratic pre- border could not be seen. Choroidal abnormalities and the SRD
cipitates and inflammation of the anterior chamber were ob- quickly resolved with steroid mass therapy and had almost
served. Supraciliary effusion was seen on anterior segment normalized about one month later. These findings suggest that
OCT, but the depth of the anterior chamber was normal. There severe inflammation of the choroid occurs in VKH syndrome.
was a SRD, but not any cystoid spaces. At initial diagnosis,
Case 158 · Vogt-Koyanagi-Harada disease: Reattachment process
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Case 158 Vogt-Koyanagi-Harada disease: Reattachment process

Right eye of a 26-year-old male with vision corrected to 0.6

A: Color fundus photograph in the right eye. B: FA in the right eye (3 minutes), During initial diagnosis. Multiple punctate leaking points are seen, particu-
larly around the optic disc. C: FA + IA in the right eye (10 minutes): Multilobular fluorescein accumulation is exhibited. The foveal lobule has a dark rim.
The area of the SRD is hypofluorescent on IA. D: Enlarged version of A [red dashed box]: The foveal cystoid space of one disc diameter is encompassed by a
yellow rim. Retinal folds are noted. E: Enlarged version of B [red dashed box]: Dye leakage can be seen into the foveal lobule. F: IR + OCT vertical scan of the
right eye: A high reflectivity thought to be due to a fibrin membrane lining is observed in the the inner wall of the foveal cystoid space, (*) and membranous
structure is visible at the bottom. Amorphous reflectivity corresponding to fibrin can be seen inside. The outer retinal layers ( ) are stretched out in a
tongue-like form in the border of the cystoid space corresponding to the yellow rim on the fundus photograph. A slight RPE elevation is depicted in the
leakage site on FA (red dashed circle)

G: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: Second day after starting steroid therapy. Membranous structure ( ) of
uniform thickness is noted extending from the outer segment. The structure posterior to the ELM is thinned in the area where membranous structure can
be seen. H: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: Third day after starting steroid therapy. I: IR + OCT vertical scan of
the right eye + enlarged version [red dashed box]: Fourth day after starting steroid therapy. J: IR + OCT vertical scan of the right eye + enlarged version
[red dashed box]: Fifth day after starting steroid therapy. I to K show the process where membranous structure dissolves and disappears, leaving behind
just granular high reflectivity. K: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]: One month after starting steroid therapy.
Best-corrected visual acuity has improved to 0.9. The outer segment is elongated and the IS/OS line is almost restored.
(Continued on the next page)

Image interpretation points

There is a yellow rim on fundus photo and a dark rim on FA membranous structure eventually disappears, leaving behind
along the SRD margin, which OCT reveals to be a cystoid just granular high reflectivity. This membranous structure is
space. The outer retinal layers is stretched out in a tongue-like thought to be the outer segment solidified with fibrin. The struc-
form along the border of the cystoid space, which corresponds ture posterior to the ELM is thin in the area where membranous
to this rim. Membranous structure can be seen at the bottom structure can be seen. This is because only the inner segment
of the cystoid space (on the RPE), but after starting steroid remains as a layer in this area with regenerating outer segments
therapy we can see that this membranous structure continues appearing as a highly reflective dots beneath the inner segment.
on from the outer segment and has a uniform thickness. After- One month after starting steroid therapy, the retina is reattached
wards, it gradually splits into a relatively weakly reflective and the outer segment is almost restored to its former state.
membranous structure and granular high reflectivity, and the
 292 Chapter 8 · Uveitis

Case 158 Continuation

G–K: IR + OCT vertical scan of the right eye + enlarged version [red dashed box]

thinning
membrane-like material
Case 159 · Vogt-Koyanagi-Harada disease: Choroidal folds
293 8
Case 159 Vogt-Koyanagi-Harada disease: Choroidal folds

A 68-year-old male, OD, BCVA 0.7

A: Color fundus photograph in the right eye: At initial diagnosis. Choroidal folds and papilledema are visible. B: FA + IA in the right eye (15 minutes):
At initial diagnosis. Significant fluorescein leakage is noted in the optic disc, and multiple lobular dye accumulations are observed around the optic disc.
C: Color fundus photo montage in the right eye: At initial diagnosis. Choroidal folds are seen over the entire fundus and choroidal detachments in the
periphery. D: FA + IA montages in the right eye (20 minutes): At initial diagnosis. Fluorescein leakage is also apparent around the temporal side. E: Anterior
segmentOCT image of the right eye: At initial diagnosis. A supraciliary effusion is visible.

F: IR + OCT vertical scan of the right eye: At initial diagnosis. Significant undulation is evident in the RPE, and SRDs (*) are visible in and superior to the
fovea centralis. G: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box]: Cystoid spaces existing in different layers are exhibited in
the lower macular area. The cystoid space nasal to the fovea can be seen within the Henle’s fibrous layer of the outer plexiform layer. H: IR + OCT vertical
scan of the right eye + enlarged version [red dashed box]: Two weeks after starting steroid therapy. Best-corrected visual acuity is 0.6. The significant undula-
tion in the RPE and the SRDs (*) appear to be worse with the gradual tapering of steroids. The outer segment undergoing shedding is depicted. I: IR + OCT
vertical scan of the right eye + enlarged version [red dashed box]: Three weeks after starting steroid therapy. Best-corrected visual acuity is 0.6. The RPE
undulation and SRDs are finally receding. The photoreceptor outer segment layer is mostly gone.
(Continued on the next page)
 294 Chapter 8 · Uveitis

Case 159 Continuation

F: IR + OCT vertical scan of the right eye, G: IR + OCT horizontal scan of the right eye + enlarged version [red dashed box], H, I: IR + OCT vertical scan of the
right eye + enlarged version [red dashed box]

Image interpretation points

The patient became aware of metamorphopsia and ocular 6 months for the RPE undulation and SRDs to recede. On OCT, in
pain in both eyes the day before being diagnosed. Choroidal addition to the commonly seen foveal cystoid spaces, significant
fold formation was significant, and a choroidal detachment RPE undulation and an unusual cystoid space formation in the
was visible in the periphery of the fundus. A supraciliary effu- outer plexiform layer were exhibited. Shedding of the outer seg-
sion was seen on an anterior segment OCT image. The patient ments was seen during the therapy.
was resistant to steroid therapy, and it took approximately
8.4 · Sympathetic ophthalmia
295 8
8.4 Sympathetic ophthalmia References

Background 1) Gupta V, Gupta A, Dogra MR, et al. Reversible retinal changes in the acute
stage of sympathetic ophthalmia seen on spectral domain optical coher-
Sympathetic ophthalmia is bilateral panuveitis that occurs be-
ence tomography. Int Ophthalmol. 2011; 31: 105–110.
tween 3 weeks and 6 months after a perforating ocular injury 2) Gallagher MJ, Yilmaz T, Cervantes-Castañeda RA, et al. The characteristic
accompanied by uveal damage orintraocular surgery. Excluding features of optical coherence tomography in posterior uveitis. Br J Oph-
a history of trauma or intraocular surgery, the onset mechanism thalmol. 2007; 91: 1680–1685.
is thought to be an autoimmune mechanism, similar to VKH
syndrome. Eye symptoms such as ocular pain, photophobia,
blurred vision, metamorphopsia, and reduced visual acuity can
be accompanied by extraocular symptoms such as headache,
fever, sensorineural hearing loss, and tinnitus. Similar to VKH
syndrome, HLA-DR4 and HLA-DR53 are found in most cases,
implying a genetic predisposition. Punctate or patchy leakages
can be seen from the RPE and multilobular fluorescein accumu-
lations are visible on FA. There are few reports on OCT, but
cystoid space-like SRDs can be exhibited and findings similar to
VKH syndrome are sometimes seen,(1) although this does not
apply to all cases.(2)
 296 Chapter 8 · Uveitis

Case 160 Sympathetic ophthalmia: After vitreous surgery

A 41-year-old female, OD and OS, BCVA 0.1 and 1.0, respectively

A: Color fundus photograph in the right eye: Eye with silicone oil tamponade after retinal detachment surgery. There is significant hyperemia of the optic
disc. B: Color fundus photograph in the left eye: Pigmentation, greyish-white lesions, and a flat foveal retinal detachment are visible in the macula and
around the optic disc. C: FA in the left eye (8 minutes): Fluorescein leakage can be seen from the optic disc and hypofluorescent lesions due to the occlusion
of the choriocapillaris are seen in the macula and around the optic disc. D: IR + OCT horizontal scan of the left eye + enlarged version [red dashed box],
E: IR + OCT vertical scan of the left eye + enlarged version [red dashed box]: Thickening of the RPE line consistent with pigmentation is depicted ( ).
The photoreceptor outer segment of the detached area is becoming highly reflective ( ) and is partially shedding as highly reflective granules. ( ).
F: IR + OCT horizontal scan of the left eye: Three months after starting steroid therapy. Best-corrected visual acuity is 1.2. The foveal IS/OS line is restored.
IS/OS line defects remain in the area temporal to the optic disc the optic disc ( )

Image interpretation points

The patient was hospitalized 4 months earlier to undergo eye. Sympathetic ophthalmia was diagnosed and the patient
vitreous surgery for a rhegmatogenous retinal detachment in the underwent pulse steroid therapy, but this was ineffective. The SRD
right eye, and 25 days later developed blurred vision in the left receded with combination therapy of cyclosporine and steroids.
8.5 · Toxocariasis
297 8
8.5 Toxocariasis References

Background 1) Suzuki T, Joko T, Akao N, et al. Following the migration of a Toxocara larva
in the retina by optical coherence tomography and fluorescein angiogra-
Toxocariasis occurs as a result of the ocular invasion by the larvae
phy. Jpn J Ophthalmol. 2005; 49: 159–161.
of Toxocara canis and Toxocara cati. It is common in ages 6 to 14 2) Higashide T, Akao N, Shirao E, et al. Optical coherence tomographic and
and differentiation from retinoblastoma is important since it ex- angiographic findings of a case with subretinal toxocara granuloma. Am J
hibits leukocoria. Recently, this condition has developed into Ophthalmol. 2003; 136: 188–190.
uveitis in adults due to the increase in number of pets and gour- 3) Shimizu Y, Imai M, Fukasawa A, et al. Premacular membrane peeling with-
met dining. Isolated, white elevated granulomatous lesions with out removal of subretinal granuloma in an eye with ocular toxocariasis.
Acta Ophthalmol Scand. 2005; 83: 395–396
blurred borders occur in the macular area and on the temporal
side of the optic disc, and the scar contraction of the lesions
causes retinal traction.

OCT findings
A mite body can be seen as a highly reflective lesion protruding
into the vitreous body from the RNFL.(1) There are localized
inflammatory findings in the early stages of activity including
highly reflective lesions in the inner retinal layers, retinal edema,
and highly reflective dots corresponding to inflammatory cells
in the vitreous body and retina. Furthermore, as this condition
progresses, a thick granulomatous membrane is formed in the
macular area and around the optic disc, and significant retinal
thickening and retinal folds can be seen.(2, 3)
 298 Chapter 8 · Uveitis

Case 161 Toxocariasis: Proliferative membrane

A 33-year-old female, OD, BCVA 0.1

A: Color fundus photograph in the right eye: An isolated, white elevated granulomatous lesion is visible from the optic disc to the macula. Retinal folds
can be observed as a result of scar contraction. B: FA in the right eye (2 minutes), C: FA in the right eye (16 minutes): Retinal capillary abnormalities and
leakages are seen as a result of traction. CME is also visible. Leakages are also noticeable from the adhesion site of the granulomatous lesions and retinal
blood vessels. D: IR + OCT horizontal scan of the right eye, E: IR + OCT vertical scan of the right eye: Thick proliferative membrane is exhibited on the
surface of the retina and appears elevated into the vitreous body. Folds in the retinal surface layer can be seen as a result of contractile traction. F: IR + OCT
horizontal scan of right eye: One month after vitreous surgery. Best-corrected visual acuity has improved to 0.3. The proliferative membrane has been
almost completely removed. Retinal thickening remains in the vicinity of the optic disc

Image interpretation points

The patient became aware of rapid visual decline in the of eating raw liver. Vitreous samples collected during surgery
right eye 3 months before visiting her local doctor. A white, were positive for Toxocara canis and Ascaris suum antibodies.
membrane-like structure had developed in the vitreous body Final best-corrected visual acuity was 0.6.
and the patient was referred to us. The patient had a history
8.6 · Acute retinal necrosis (Kirisawa-type uveitis)
299 8
8.6 Acute retinal necrosis References
(Kirisawa-type uveitis)
1) Usui Y, Goto H. Overview and diagnosis of acute retinal necrosis syn-
Background drome. Semin Ophthalmol. 2008; 23: 275–283.
2) Kawaguchi T, Spencer DB, Mochizuki M. Therapy for acute retinal necrosis.
Acute retinal necrosis is acute panuveitis that occurs in one or Semin Ophthalmol. 2008; 23: 285–290.
both eyes of healthy individuals of all ages as a result of a localized 3) Suzuki J, Goto H, Minoda H, et al. Analysis of retinal findings of acute reti-
infection of the eye with the varicella-zoster virus (VZV) or nal necrosis using optical coherence tomography. Ocul Immunol Inflamm.
herpes simplex virus (HSV). This disease progresses rapidly and 2006; 14: 165–170.
has a high risk of blindness due to phthisis bulbi, optic neuro- 4) Blair MP, Goldstein DA, Shapiro MJ. Optical coherence tomography of pro-
gressive outer retinal necrosis. Retina. 2007; 27: 1313–1314.
pathy and/or CRAO.(1, 2) Early detection is important, and if
acute iridocyclitis accompanied by mutton-fat keratic precipi-
tates and ocular hypertension is seen, it is important not to
overlook yellowish-white patches in the periphery of the retina,
retinal periarteritis, and hyperemia of the optic disc. The yellow-
ish-white patches indicate retinal necrotic lesions, and the
yellowish-white patchy lesions in the early phase become con-
fluent resulting in geographic lesions. Vasculitis also occurs in
the acute phase with perivascular hemorrhages, sheathing, and
terminal obliteration of arterioles. During the quiescent phase, in
approximately 90% of cases, a rhegmatogenous retinal detach-
ment occurs in the peripheral retinal necrotic area. An average
of two main branches of the retinal artery are occluded during the
quiescent phase. Hydatoid polymerase chain reaction (PCR) is
the most sensitive and specific for a definitive diagnosis.

OCT findings
During the acute phase, multiple highly reflective dots corre-
sponding to inflammatory cells can be seen mainly in the vitre-
ous body, and the inner retinal layers become highly reflective
consistent with yellowish-white patchy lesions. This is sometimes
accompanied by subretinal fluid and exudation. Irregular thin-
ning of the retina, cystoid space formation, and obscuration of
the retinal layer structure progresses as the retina gradually
breaks down.(3, 4) During the remission phase, significant retinal
thinning consistent with the sites of severe necrosis and retinal
detachment is visible.
 300 Chapter 8 · Uveitis

Case 162 Acute retinal necrosis (Kirisawa-type uveitis): A typical example

A 28-year-old female, OD, BCVA 0.4

A: Color fundus photograph in the right eye: At initial diagnosis. In the posterior pole, retinal detachment accompanied by retinal hemorrhages and effusive
retinal whitening, sheathed retinal artery, vitreous clouding, and a pale optic disc are seen. B: FA + IA in the right eye (14 minutes): The lower half of the
retinal blood vessels cannot be seen due to vitreous clouding. C: Color fundus photograph in the right eye: At initial diagnosis. Upper temporal periphery
of the fundus. Yellowish-white patchy lesions, retinal breaks, retinal hemorrhages, thinned retina, and sheathed retinal blood vessels are visible. D: IR + OCT
horizontal scan of the right eye: A retinal detachment accompanied by a foveal cystoid spaces is observed. Multiple infiltrating cells can be seen in the
vitreous cavity.
Case 162 · Acute retinal necrosis (Kirisawa-type uveitis): A typical example
301 8

E: Color fundus photograph in the right eye, F: Color photograph montage in the right eye: One month after surgery. Best-corrected visual acuity 0.2. The
retina is reattached under silicone oil tamponade. Three sheathed retinal blood vessels are visible. G: IR + OCT vertical scan of the right eye, H: IR + OCT
horizontal scan of the right eye: The retina is reattached, but the retina is significantly thin.

Image interpretation points

The patient was diagnosed with acute retinal necrosis in the retinal hemorrhages and clouding, sheathing of the retinal blood
right eye by her local doctor 20 days earlier and underwent vessels, and vitreous inflammation. The patient tested strongly
combination therapy with acyclovir, interferon, and steroids. positive for VZV. Once again, a combination therapy of acyclovir,
A bullous, retinal detachment had developed several days valacyclovir hydrochloride, and steroids was administered.
prior, and the patient was referred to us. The patient exhibited The retina was reattached by vitreous surgery and a silicone oil
rapid progression including peripheral retinal necrosis with tamponade, but breakdown of the retina was significant.
 303 9

Pathologic myopia and related

diseases
9.1 Myopia – 304
References – 307
Case 163 Intrachoroidal cavitation: A Typical example – 308
Case 164 Intrachoroidal cavitation: Connection with the vitreous cavity – 309
Case 165 Lacquer cracks: A typical example – 310
Case 166 Lacquer cracks: A mild case – 311
Case 167 ILM detachment: Case without foveoschisis – 312
Case 168 Myopic foveoschisis: Case without foveal detachment – 313
Case 169 Myopic foveoschisis: Case with foveal detachment – 314, 315
Case 170 Myopic foveoschisis: Case with macular retinal detachment – 316
Case 170 Two and a half years after surgery – 317
Case 171 Myopic foveoschisis: Traction from the thickened posterior vitreous
cortex – 318
Case 172 Myopic foveoschisis: Macular hole formation – 319
Case 173 Myopic foveoschisis: MHRD – 320
Case 174 Myopic foveoschisis: Before and after surgery for MHRD – 321
Case 175 Myopic subretinal hemorrhages: A typical example – 322, 323
Case 176 Myopic choroidal neovascularization: A typical example – 324
Case 177 Myopic choroidal neovascularization: Small CNV – 325
Case 177 After anti-VEGF treatment – 326
Case 178 Myopic choroidal neovascularization: Large CNV – 327
Case 179 Myopic choroidal neovascularization: A young example – 328, 329
Case 180 Myopic choroidal neovascularization: Foveoschisis – 330
9.2 Dome-shaped macula and inferior staphyloma – 331
References – 331
Case 181 Dome-shaped macula: A typical example – 332
Case 182 Inferior staphyloma: Serous retinal detachment – 333, 334
 304 Chapter 9 · Pathologic myopia and related diseases

9.1 Myopia is called a posterior staphyloma (. Fig. 9-1). In posterior staphy-

loma, the sclera (eyeball wall) protrudes posteriorly in various
Background areas of the posterior pole and can also exhibit complex forms.
Myopia is a disease seen at a high frequency in Asians. It is Curtin classified posterior staphyloma into 10 types ranging
more common in women than men and results in various fundus from I to X (1) (. Fig. 9-2). This classification is based on binocu-
changes from 30 years of age. Myopia that develops fundus lar indirect ophthalmoscopy findings and is not necessarily based
changes such as posterior staphyloma in the posterior pole or on precise evaluation of the ocular configuration. According to
chorioretinal atrophic lesions is known as pathologic myopia or Hsiang et al., Type II of the Curtin classification is the most
degenerative myopia. The basic element of degenerative myopia common posterior staphyloma seen in myopia of Japanese
is elongation of the axial length with the sclera stretching poste- people and accounts for over 50% throughout all ages. Type II
riorly. Ocular axial lengths of normally about 22 to 24 mm are decreases with age and Type IX, which features ridge-like ante-
sometimes seen to stretch beyond 30 mm. riorly protruding curvature of the sclera along vertical direction
Elongation of the sclera is not uniform and in particular, sig- of the fundus between the optic disc and fovea centralis, in-
nificant elongation occurs in the posterior pole. This condition creases. This kind of uneven deformation of the sclera is thought

. Fig. 9-1 Schematic diagram of posterior staphyloma

Compared with a normal eye (A), in a highly myopic eye the axial length is extended and the posterior pole of the fundus protrudes backwards (B)

. Fig. 9-2 Curtin classification and frequency of each type of posterior staphyloma in highly myopic eyes of Japanese people.
Type II decreases and Type IX increases with age.
(Modified according to Hsiang HW, et al. Clinical characteristics of posterior staphyloma in eyes with pathologic myopia. Am J Ophthalmol. 2008; 146: 102–110)
9.1 · Myopia
305 9

. Fig. 9-3 Chorioretinal and scleral changes visible in high myopia

Various chorioretinal and scleral changes occurs in conjunction with the posterior elongation of the ocular length in highly myopic eyes.
: Forward traction towards the inner retinal layers by retinal blood vessels resulting from posterior scleral elongation
: Forward traction towards the inner retinal layers by the ILM resulting from posterior scleral elongation
: Backward traction towards the outer retinal layers due to posterior scleral elongation

to play a large role in the onset of complications seen in degen- Lacquer cracks
erative myopia.(2) Breaks spontaneously occur in Bruch’s membrane with the elon-
An important element to understand pathogenesis of the gation of the axial length. These breaks are observed as linear
fundus lesions that occur in degenerative myopia is the presence lesions, often radially, in the fundus.(8) They are depicted as
of tissue that is easily stretched, and tissue that is difficult to abnormalities at the level of Bruch’s membrane and photo-
stretch that comprise the eyeball. When the sclera extends receptor inner and outer segment junction (IS/OS) on OCT.
posteriorly, traction to soft tissue is generated if there are dif-
ferences in the extensibility of the intraocular tissues. Specifi- Myopic foveoschisis or myopic macular retinoschisis
cally, the thickened posterior vitreous cortex, ILM, retinal This is a pathological condition resulting in retinoschisis as first
blood vessels, and Bruch’s membrane, which are relatively in- reported by Takano and Kishi in 1999.(9) It was identified as reti-
elastic cannot be so severely elongated posteriorly as the sclera, nal detachment during the era without OCT, but the true pathol-
thus causing various changes such as ILM detachment, retinal ogy has been revealed by OCT. In highly myopic eyes, retinal
nerve fiber layer separation, retinoschisis, and lacquer cracks detachment can occur without the formation of retinal breaks
(. Fig. 9-3). before the onset of macular hole retinal detachment (MHRD).
This condition is seen in 10–34% of highly myopic eyes.(9, 10)
Typical fundus findings seen in degenerative Various findings, such as IS/OS abnormalities, ERM formation,
myopia and their OCT images macular holes, retinal fold formation, and ILM detachment are
Intrachoroidal cavitation (ICC) seen on SD-OCT imaging at a high frequency.(11) Columnar
These are cavity-like findings in the choroid seen around the structures traversing the retina in the longitudinal direction
optic disc. This was formerly known as peripapillary detachment thought to be Müller cells are detected in the retinoschisis.(12)
in pathologic myopia (PDPM).(3) It was originally supposed to be Lower extensibility of the retinal blood vessels and ILM, than
a PED,(4) but this interpretation was found to be incorrect based other sensory retinal tissues play an important role in the onset
on examinations with high resolution OCT. The detection fre- of myopic foveoschisis.(13) That is to say, the sensory retina is
quency is 5–10% in myopic eyes of -8D or above.(5, 6) A large elongated posteriorly with posterior staphyloma formation, but
cavity in ICC develops in the choroid. Some believe that the con- the retinal blood vessels and ILM cannot follow the elongation of
tent of this cavity is vitreous humor.(7) ICC can exhibit visual field the sensory retina closely because of their poor extensibility, and
defects that are indistinguishable from glaucoma.(5, 6) consequently the superficial layer of the retina is pulled in the
longitudinal direction causing retinoschisis (. Fig. 9-3). MHRD
is thought to develop from myopic foveoschisis. Thus, myopic
foveaschisis is a progressive disease.(14) Visual acuity tend to
 306 Chapter 9 · Pathologic myopia and related diseases

. Fig. 9-4 An example of the formation process of a macular hole in high myopia
A: Stage 1, high reflectivity associated with the focal elevation of outer retinal layers can be seen ( ). B: Stage 2, outer lamellar hole formation ( ).
C: Inward expansion of the outer lamellar hole and progression of retinoschisis (*). D: The outer lamellar hole progresses forward and comes in contact
with the retinoschisis ( ).
(Modified according to Shimada N, et al. Progression from macular retinoschisis to retinal detachment in highly myopic eyes in associated with outer
lamellar hole formation. Br J Ophthalmol 2008; 92: 762–764.)

decrease in the cases that not only undergo intraretinal changes, et al. report that the progression from myopic foveoschisis to
but also vitreoretinal interface-related changes such as ERM foveal retinal detachment can be divided into 4 stages based on
formation, macular hole formation, and ILM detachment. OCT findings.
Cases with foveal detachment often develop macular holes.(15) Stage 1 involves the localized elevation of the foveal outer
Currently, vitreous surgery in combination with ILM peeling is a retinal layers and the increased reflectivity in these layers. In
standard treatment for cases of myopic foveoschisis with foveal Stage 2, a outer lamellar hole (a foveal detachment on OCT) de-
detachment.(15–17) velops in the fovea centralis and parafovea. Stage 3 comprises the
inward expansion of the lamellar hole into the retina. In Stage 4,
Myopic subretinal hemorrhages the inner border of the outer lamellar hole extends until it comes
Highly myopic eyes in which hemorrhages are seen at the fovea into contact with the innermost layer of the separated retina and
centralis require the differentiation of myopic subretinal hemor- retinal detachment has expanded(22) (. Fig. 9-4).
rhages from hemorrhages with choroidal neovascularization
(CNV). Myopic subretinal hemorrhages develop without the Paravascular retinal cysts
presence of CNV and are caused by breaks in Bruch’s membrane Paravascular retinal cysts were initially described as changes
and choroid that occurs with axial length elongation. The inci- in retinal thinning around retinal blood vessels,(23) but Shimada
dence is reportedly 3% in highly myopic eyes.(18) Lacquer cracks et al. paravascular retinal cysts to be intraretinal cavities around
are known to appear after myopic subretinal hemorrhages have the blood vessels on OCT images.(24) These changes are detected
subsided.(19) The visual prognosis for myopic subretinal hemor- in 49.5% of highly myopic eyes. Rupture of the inner walls of
rhages is generally good, but prognosis is poor in cases of poor paravascular retinal cysts can result in the development of para-
visual acuity at initial diagnosis, cases where the IS/OS is not vascular lamellar holes and can contribute to changes in the
depicted on OCT imaging at initial diagnosis, and cases where vitreoretinal interface (ILM detachment, ERM etc.) observed in
there is hypofluorescence on fundus autofluorescence.(20) eyes with degenerative myopia.(24)

Macular hole Vascular microfolds

Macular holes in highly myopic eyes result from a variety of Vascular microfolds are findings that are also seen frequently in
mechanisms including those similar to idiopathic macular holes, highly myopic eyes. Because the tissue extensibility of retinal
those which develop from myopic foveoschisis, and those which blood vessels is low compared with the sensory retina, the super-
develop from vitreomacular traction syndrome.(21, 22) Shimada ficial retinal layer is elevated by the blood vessels. These features
9.1 · Myopia
307 9
are termed vascular microfolds, and initially were reported as 12) Fujimoto M, Hangai M, Suda K, et al. Features associated with foveal reti-
findings seen after vitreous surgery in combination with ILM nal detachment in myopic macular retinoschisis. Am J Ophthalmol. 2010;
150: 863–870.
peeling,(25) but they are unrelated to surgery(26) and are evident
13) Shimada N, Ohno-Matsui K, Baba T, et al. Natural course of macular reti-
in 20–44.6% of highly myopic eyes.(25, 27) noschisis in highly myopic eyes without macular hole or retinal detach-
ment. Am J Ophthalmol. 2006; 142: 497–500.
ILM detachment 14) Gaucher D, Haouchine B, Tadayoni R, et al. Long-term follow-up of high
The ILM is seen to be separated from the retinal nerve fiber layer myopic foveoschisis : natural course and surgical outcome. Am J Ophthal-
in 2.4–6% of highly myopic eyes, which is termed ILM detach- mol. 2007; 143: 455–462.
15) Kobayashi H, Kishi S. Vitreous surgery for highly myopic eyes with foveal
ment.(27, 28) Based on the fact that myopic foveoschisis occurs in detachment and retinoschisis. Ophthalmology. 2003; 110: 1702–1707.
the majority of cases with ILM detachment, there is thought to 16) Ikuno Y, Sayanagi K, Ohji M, et al. Vitrectomy and internal limiting mem-
be a close relationship between ILM detachment and myopic brane peeling for myopic foveoschisis. Am J Ophthalmol. 2004; 137: 719–724.
foveoschisis.(2, 28) The onset mechanism of ILM detachment is 17) Scott IU, Moshfeghi AA, Flynn HW Jr. Surgical management of macular
not necessarily fully understood, but the posterior vitreous cor- retinoschisis associated with high myopia. Arch Ophthalmol. 2006; 124:
1197–1199.
tex that remains on the retinal surface is thought to play a role.
18) Tokoro T. Explanatory factors of chorioretinal atrophy. In : Tokoro T, ed.
This feature needs to be differentiated from RNFL detach- Atlas of Posterior Fundus Changes in Pathologic Myopia. Tokyo, Japan,
ment, which is caused by the inwards traction of the retinal blood Springer-Verlag, 1998. pp23–54.
vessels to the RNFL. 19) Ohno-Matsui K, Ito M, Tokoro T. Subretinal bleeding without choroidal
neovascularization in pathologic myopia. A sign of new lacquer crack for-
Myopic CNV mation. Retina. 1996; 16: 196–202.
20) Moriyama M, Ohno-Matsui K, Shimada N, et al. Correlation between visual
CNV is a complication seen in 4–11% of highly myopic eyes.(29–31) prognosis and fundus autofluorescence and optical coherence tomo-
Its natural course is extremely poor, and according to long-term graphic findings in highly myopic eyes with submacular hemorrhage and
follow-up reports, best-corrected visual acuity becomes less than without choroidal neovascularization. Retina. 2011; 31: 74–80.
0.1 in almost all cases.(32) The CNV is type 2 CNV, and patchy 21) Smiddy WE, Kim SS, Lujan BJ, et al. Myopic traction maculopathy : spectral
chorioretinal atrophy and lacquer cracks are important in the domain optical coherence tomographic imaging and a hypothesized
mechanism. Ophthalmic Surg Lasers Imaging. 2009; 40: 169–173.
onset of neovascularization.(33) CNV becomes an atrophic lesion 22) Shimada N, Ohno-Matsui K, Yoshida T, et al. Progression from macular
(Fuchs’ spot) over time, and macular holes frequently develop in retinoschisis to retinal detachment in highly myopic eyes is associated
cases where the chorioretinal atrophic lesion is larger than 1 disc with outer lamellar hole formation. Br J Ophthalmol. 2008; 92: 762–764.
diameter.(33) Photocoagulation and photodynamic therapy can be 23) Spencer LM, Foos RY. Paravascular vitreoretinal attachments. Role in reti-
used in the treatment of myopic CNV,(34, 35) but results in expan- nal tears. Arch Ophthalmol. 1970; 84: 557–564.
24) Shimada N, Ohno-Matsui K, Nishimuta A, et al. Detection of paravascular
sion of atrophic lesions. Therefore, anti-VEGF therapy is cur-
lamellar holes and other paravascular abnormalities by optical coherence
rently the first choice.(36) However, its long-term outcome still tomography in eyes with high myopia. Ophthalmology. 2008; 115: 708–717.
remains unclear. 25) Ikuno Y, Gomi F, Tano Y. Potent retinal arteriolar traction as a possible
cause of myopic foveoschisis. Am J Ophthalmol. 2005; 139: 462–467.
26) Sayanagi K, Ikuno Y, Gomi F, et al. Retinal vascular microfolds in highly
References myopic eyes. Am J Ophthalmol. 2005; 139: 658–663.
27) Forte R, Cennamo G, Pascotto F, et al. En face optical coherence tomogra-
1) Curtin BJ. The posterior staphyloma of pathologic myopia. Trans Am
phy of the posterior pole in high myopia. Am J Ophthalmol. 2008; 145:
Ophthal Soc. 1997; 75: 67–86.
281–288.
2) Hsiang HW, Ohno-Matsui K, Shimada N, et al. Clinical characteristics of
28) Sayanagi K, Ikuno Y, Tano Y. Tractional internal limiting membrane detach-
posterior staphyloma in eyes with pathologic myopia. Am J Ophthalmol.
ment in highly myopic eyes. Am J Ophthalmol. 2006; 142: 850–852.
2008; 146: 102–110.
29) Curtin BJ, Karlin BD. Axial length measurements and fundus changes of
3) Toranzo J, Cohen SY, Erginay A, et al. Peripapillary intrachoroidal cavita-
the myopic eyes. Am J Ophthalmol. 1971; 71: 42–50.
tion in myopia. Am J Ophthalmol. 2005; 140: 731–732.
30) Grossniklaus HE, Green WR. Pathologic findings in pathologic myopia.
4) Freund KB, Ciardella AP, Yannuzzi LA, et al. Peripapillary detachment in
Retina. 1992; 12: 127–133.
pathologic myopia. Arch Ophthalmol. 2003; 121: 197–204.
31) Hotchkiss ML, Fine SL. Pathologic myopia and choroidal neovasculariza-
5) Shimada N, Ohno-Matsui K, Nishimuta A, et al. Characteristics of peripapil-
tion. Am J Ophthalmol. 1981; 91: 177–183.
lary detachment in pathologic myopia. Arch Ophthalmol. 2006; 124: 46–52.
32) Yoshida T, Ohno-Matsui K, Yasuzumi K, et al. Myopic choroidal neovascu-
6) Shimada N, Ohno-Matsui K, Nishimuta A, et al. Peripapillary changes de-
larization : a 10-year follow-up. Ophthalmology. 2003; 110: 1297–1305.
tected by optical coherence tomography in eyes with high myopia. Oph-
33) Shimada N, Ohno-Matsui K, Yoshida T, et al. Development of macular hole
thalmology. 2007; 114: 2070–2076.
and macular retinoschisis in eyes with myopic choroidal neovasculariza-
7) Wei YH, Yang CM, Chen MS, et al. Peripapillary intrachoroidal cavitation in
tion. Am J Ophthalmol. 2008; 145: 155–161.
high myopia : reappraisal. Eye (Lond). 2009; 23: 141–144.
34) Chan WM, Ohji M, Lai TY, et al. Choroidal neovascularisation in pathologi-
8) Klein RM, Curtin BJ. Lacquer crack lesions in pathologic myopia. Am J Oph-
cal myopia : an update in management. Br J Ophthalmol. 2005; 89: 1522–
thalmol. 1975; 79: 386–392.
1528.
9) Takano M, Kishi S. Foveal retinoschisis and retinal detachment in severely
35) Hayashi K, Ohno-Matsui K, Shimada N, et al. Long-term results of photo-
myopic eyes with posterior staphyloma. Am J Ophthalmol. 1999; 128:
dynamic therapy for choroidal neovascularization in Japanese patients
472–476.
with pathologic myopia. Am J Ophthalmol. 2011; 151: 137–147.
10) Baba T, Ohno-Matsui K, Futagami S, et al. Prevalence and characteristics of
36) Gharbiya M, Giustolisi R, Allievi F, et al. Choroidal neovascularization in
foveal retinal detachment without macular hole in high myopia. Am J
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tomographic findings in myopic foveoschisis. Retina. 2010; 30: 623–628.
 308 Chapter 9 · Pathologic myopia and related diseases

Case 163 Intrachoroidal cavitation: A Typical example

A 40-year-old male, OS, BCVA 1.2, an axial length 29.46 mm

A: Color fundus photograph in the left eye: The optic disc cupping is large, suggesting glaucoma is present. Extensive peripapillary atrophy (PPA) is present.
Typical intrachoroidal cavitation is visible inferior to the optic disc ( ). B: IR + OCT circle scan of the left eye: A circle scan of the area around the optic disc.
Extensive intrachoroidal cavitation (*) is evident. Thin choroidal tissue appears to remain immediately beneath the retinal pigment epithelium. A septum is
present in the cavity ( ). C: Enlarged version of B [red dashed box]: We can see that intrachoroidal cavitation is a cavity inside the choroid and not a PED.
The cavity is clearly depicted in B, and on the enlarged image, the remaining thin choroidal tissue on the choroidal side of the highly reflective retinal
pigment epithelium is more apparent.

Image interpretation points

This is a case of extensive intrachoroidal cavitation. This was tion (ICC) better reflects the pathologic condition. There is in-
formerly reported under the name of peripapillary detach- sufficient research on the relationship between ICC and visual
ment in pathologic myopia (PDPM), but intrachoroidal cavita- dysfunction, which is the topic of future studies.
Case 164 · Intrachoroidal cavitation: Connection with the vitreous cavity
309 9
Case 164 Intrachoroidal cavitation: Connection with the vitreous cavity

A 59-year-old female, OS, BCVA 1.5, an axial length 27.90 mm

A: Color fundus photograph in the left eye: The ICC is not as clear as case 163 on photo. B: IR + OCT vertical scan of the left eye: Scan passing through the
optic disc. Small ICC (*) can be seen immediately inferior to the optic disc. A very thin septum exists between the ICC and vitreous cavity ( ). The sensory
retina is disrupted ( ). C: IR + OCT vertical scan of the left eye: Scan of the area immediately nasal to the scan in B. We can see that there is an intersection
between the ICC and vitreous body ( ). In such cases, the neural retina may become disrupted and the retinal nerve fibers rupture.

Image interpretation points

Some believe that the content of ICC is derived from the vitreous fluid. In this case, there is a clear connection between the ICC
and vitreous cavity.
 310 Chapter 9 · Pathologic myopia and related diseases

Case 165 Lacquer cracks: A typical example

A 67-year-old male, OS, BCVA 0.4, an axial length 28.22 mm

A: Color fundus photograph in the left eye: Multiple lacquer cracks can be clearly seen in the macular area. B: FA in the left eye (11 minutes, 10 seconds):
The lacquer cracks are depicted as hyperfluorescent lesions in late phase FA imaging. Small CNV is present in the inferior macula ( ). C: IA in the left eye
(11 minutes, 10 seconds): The lacquer cracks are exhibited as hypofluorescent lines in late phase IA imaging. D: IR + OCT oblique scan of the left eye:
Scan mostly passing through the fovea centralis. CNV is noted ( ). The RPE, IS/OS, and ELM are all defective in the lacquer cracks area (red dashed circle).
The choroid is thin. E: IR + OCT horizontal scan of the left eye: Scan passing through the lacquer crack area. Mild outward retraction of the inner retinal
layer structure and RPE defects as seen in atrophic AMD, degenerative disease, and PIC are visible. The sclera is significantly visible due to RPE defects (*).

Image interpretation points

Lacquer cracks are one of the initial changes seen in highly myopic eyes. This case is accompanied by myopic CNV. Lacquer cracks
are a risk factor in the onset of CNV.
Case 166 · Lacquer cracks: A mild case
311 9
Case 166 Lacquer cracks: A mild case

A 36-year-old male, OS, BCVA 0.9, an axial length 31.66 mm

A: Color fundus photograph in the left eye: In contrast to case 165, the lacquer cracks are not clear on an biomicroscopic examination. B: FA in the left
eye (15 minutes, 54 seconds): The lacquer cracks are depicted as hyperfluorescent lesions in late phase FA imaging. No CNV is present. C: IA in the left eye
(15 minutes, 54 seconds): There are hypofluorescent lesions both consistent and inconsistent with the hyperfluorescent lesions on FA on late phase IA
imaging. Not all of these hypofluorescent lesions are lacquer cracks. D: IR + OCT horizontal scan of the left eye: Vascular microfolds are apparent ( ).
Choroidal thinning is clearly exhibited. E: Enlarged version of D [red dashed box]: The ELM and IS/OS line are becoming indistinct in the hypofluorescent
area on IA (red dashed circle). This change is very mild consistent with the lack of clear lacquer cracks on biomicroscopy.

Image interpretation points

In contrast with case 165, only very mild structural changes IA imaging). To be strict, the lacquer cracks are detected liner
are evident in the outer retinal layers associated with lacquer lesions on biomicroscopy and hypofluorescent lesions on FA. The
cracks. There are few biomicroscopic findings. The mild change hypofluorescent lesions seen only on late phase IA imaging may
in reflectivity of ELM and IS/IS lines corresponds to the linear develop into lacquer cracks in the future, but it is inappropriate
lesions seen on angiographic imaging (particularly late phase to call the lesions themselves lacquer cracks.
 312 Chapter 9 · Pathologic myopia and related diseases

Case 167 ILM detachment: Case without foveoschisis

A 68-year-old male, OS, BCVA 1.2, an axial length 27.91 mm

A: Color fundus photograph in the left eye: A tilted optic disc with cyclotorsion and PPA are visible. A lacquer crack is evident superior to the fovea centralis.
B: FA in the left eye (1 minute, 52 seconds): Hyperfluorescence as a result of a lacquer crack is noted superior to the fovea centralis. C: IA in the left eye
(1 minute, 52 seconds): The lacquer crack is exhibiting hypofluorescence on IA. D: IR + OCT vertical scan of the left eye: Traction from the thickened posterior
vitreous cortex is evident below the macula in the inferior posterior pole ( ). E: Enlarged version of D [red dashed box]: The posterior vitreous cortex has
been detached inferiorly and in continuity with this the ILM and the thickened posterior vitreous cortex are detached from the retinal nerve fiber layer
together, with a columnar structure of Müller cells in the gap (blue dashed circle). Schisis ( ) can also be seen between the retinal nerve fiber layer and
ganglion cell layer. Compared with the inferior portion, the upper portion of the retinal nerve fiber layer is undulating, and the columnar structure is not
visible (red dashed circle). This is similar to findings seen in ERM.

Image interpretation points

This is a case of a highly myopic eye in which the posterior ERM). The thick and detached posterior vitreous cortex and
vitreous cortex and ILM are responsible for multiple lesions in bridging membrane in the upper macula are thought to be
the vitreoretinal interface. The state of the lesions is easy to generated by cell migration and extracellular matrix production
assess from findings in the gap between the posterior vitreous with the posterior vitreous cortex as scaffolding similar to the
cortex and retinal nerve fiber layer. It is also important to note pathogenesis of idiopathic ERM. The lesion in the inferior macula
the membrane formation as a result of cell migration and is known as ILM detachment.
extracellular matrix production (refer to page 60 for idiopathic
Case 168 · Myopic foveoschisis: Case without foveal detachment
313 9
Case 168 Myopic foveoschisis: Case without foveal detachment

A 66-year-old female, OD, BCVA 1.5, an axial length 30.31 mm

A: Color fundus photograph in the right eye: The optic disc is tilted and the anteriorly protruding scleral curvature is seen the immediate temporal margin
of the optic disc. The large blood vessels of the choroid are visible. ICC is present inferior to the optic disc. B: IR + OCT vertical scan of the right eye: ILM
detachment ( ) is observed in the left side of the OCT image. Retinoschisis is apparent over a wide area (*). Vascular microfolds that have developed as
a result of poor extensibility of the retinal blood vessels are evident in the superior macula ( ). The choroid is thinned. The extensibility of the retinal
blood vessels themselves is poor, which is thought to be the cause of traction on other retinal tissues. C: IR + OCT horizontal scan of the right eye: A vascular
microfold is depicted ( ). ILM detachment is present immediately temporal to the ILM detachment this ( ). RNFL schisis is also seen in association
with the vascular microfold and ILM detachment. Retinoschisis is also clearly depicted on this scan (*). The choroid is extremely thin.

Image interpretation points

A variety of changes occur simultaneously in highly myopic that occurs between tissue that stretches easily (sensory retina),
eyes. In this case, ILM detachment, vascular microfolds, and and tissue that is difficult to stretch (ILM, retinal blood vessels)
retinoschisis including RNFL schisis are occurring simultane- when posterior scleral elongation occurs. These pathologic myopic
ously. Complex changes occur at the same time due to traction changes are frequently seen.
 314 Chapter 9 · Pathologic myopia and related diseases

Case 169 Myopic foveoschisis: Case with foveal detachment

A 50-year-old female, OS, BCVA 0.4, an axial length 29.45 mm

A: Color fundus photograph in the left eye: The optic disc is tilted. Extensive PPA is visible. Foveal retinoschisis is not clear on the fundus photograph. How-
ever, the presence of retinoschisis in the vicinity of the lower arcade vessels is evident. B: IR + OCT horizontal scan of the left eye: Extensive retinoschisis is
evident in the macular area. Retinal detachment (*) is also seen in the fovea centralis. The posterior vitreous cortex is exhibited on the nasal side of the fo-
vea centralis ( ). C: Enlarged version of B [red dashed box]: Foveal detachment is clearly depicted. The vertical (longitudinal direction
of the eyeball) columnar structure in the area of retinoschisis is likely Müller cells.

Image interpretation points

This is an example of retinoschisis and foveal detachment that Other factors causing traction of the retina include inelastic
can be seen in highly myopic eyes. In this case, traction from retinal arterioles and the ILM. This patient complained of visual
the posterior vitreous cortex was observed, which may have decline and a foveal detachment was found; so vitreous surgery
partially contributed to the development of retinoschisis. in combination with ILM peeling was performed.

peripapillary atrophy
Case 169 · One year after surgery
315 9
Case 169 One year after surgery

A 50-year-old female, OS, BCVA 1.2, an axial length 29.45 mm

D: Color fundus photograph in the left eye: The results of surgery are not evident on the fundus photograph. Subfoveal atrophic lesions appear to be more
clearly depicted. Additionally, atrophic lesions appear to have progressed on the temporal side of the macula. E: IR + OCT horizontal scan of the left eye:
The detachment in the fovea centralis had disappeared and retinoschisis is also mostly resolved. F: IR + OCT vertical scan of the left eye: The fovea is thin.
The high reflectivity in the choroid and sclera below the fovea is due to foveal RPE atrophy. G: Enlarged version of F [red dashed box]: The area of ILM peel-
ing is clearly visible as an area with thinned RNFL ( ). Traction to the ILM and RNFL is evident in the site where the ILM has not been peeled. The RNFL
appears to be thin in the site of ILM peeling. Additionally, the IS/OS line is lost in the fovea with RPE atrophy, but is clearly exhibited in the other area.

Image interpretation points

The area where vitreous surgery in combination with ILM peel- where ILM peeling was performed compared with the site where
ing was performed is clearly visible. Significant changes were it was not performed. Foveal retinal thinning is well depicted.
observed in the structures of the inner retinal layers in the area
 316 Chapter 9 · Pathologic myopia and related diseases

Case 170 Myopic foveoschisis: Case with macular retinal detachment

A 70-year-old female, OD, BCVA 0.4, an axial length 28.20 mm

A: Color fundus photograph in the right eye: The optic disc is tilted horizontally. A large PPA is evident on the temporal side. Foveal retinoschisis is not
evident on the fundus photograph. B: IR + OCT horizontal scan of the right eye: Retinoschisis with macular retinal detachment is evident. The choroid is
extremely thin. C: Enlarged version of B [red dashed box]: Retinoschisis and retinal detachment (*) are clearly exhibited. Defects can be seen within the
photoreceptor layer (7). The ELM is partially depicted. The moderately reflective columnar structure running in the longitudinal direction of the retina is
likely composed of Müller cells.

Image interpretation points

These images clearly reveal the characteristics of myopic images. We can clearly see that the photoreceptor outer segment
foveoschisis with macular retinal detachment. No particular of the detached retina (the ELM is partially depicted) possess
tractional factors pulling the retina were found in these defects like nicks in a saw blade.
Case 170 · Two and a half years after surgery
317 9
Case 170 Two and a half years after surgery

A 70-year-old female, OD, BCVA 0.9, an axial length 28.20 mm

D: Color fundus photograph in the right eye: Fundus visibility is improved since cataract surgery was performed at the same time. E: IR + OCT horizontal scan
of the left eye: Retinoschisis has mostly disappeared. F: Enlarged version of E [red dashed box]: The area that underwent ILM peeling is indicated by ( ).
Thinning of the retinal nerve fiber layer is evident in this area. The foveal outer retinal layer structure (ELM and IS/OS lines) has almost returned to normal
(red dashed circle). This is consistent with good postoperative visual acuity.

Image interpretation points

This is a case where vitreous surgery combined with ILM in the retinal nerve fiber layer are not necessarily consistent with
peeling was effective. The retinal nerve fiber layer is thin in the good postoperative visual acuity.
area that underwent ILM peeling, but the significant changes
 318 Chapter 9 · Pathologic myopia and related diseases

Case 171 Myopic foveoschisis: Traction from the thickened posterior vitreous cortex

A 67-year-old female, OS, BCVA 0.6, an axial length 27.92 mm

A: Color fundus photograph in the left eye: Traction to the fovea centralis is unclear in this photograph. B: OCT horizontal scan of the left eye: We can clearly
see that the sensory retina is being pulled towards the vitreous cavity by the posterior vitreous cortex ( ). There is a site where the posterior vitreous
cortex is attached to the retinal surface on the nasal side of the fovea centralis (white dashed circle), and the retina appears to be projecting anteriorly as a
result of traction. The fovea centralis is thickened, and the internal state of the retina is unclear, but the IS/OS is depicted as almost normal. C: OCT vertical
scan of the left eye: Retinal traction due to the posterior vitreous cortex is clearly visible.
(A is modified according to Fujimoto M, et al. Features associated with foveal retinal detachment in myopic macular retinoschisis. Am J Ophthalmol. 2010;
150: 863–870)

Image interpretation points

Retinal traction due to the thickened posterior vitreous cortex cortex as well as cases without traction by posterior vitreous
is clearly depicted. Myopic foveoschisis includes cases such cortex such as case 170. This case may be on the same spectrum
as this one with retinal traction due to the posterior vitreous as vitreomacular traction syndrome.
Case 172 · Myopic foveoschisis: Macular hole formation
319 9
Case 172 Myopic foveoschisis: Macular hole formation

A 48-year-old male, OD, BCVA 0.7, an axial length 32.03 mm

A: Color fundus photograph in the right eye: This is a tigroid fundus with diffuse atrophy, a large PPA, and a ridge temporal to the optic disc in the posterior
pole. B: OCT horizontal scan of the right eye: Retinoschisis is evident ( ). The IS/OS line in the fovea centralis is not sufficiently depicted. In addition, small,
a highly reflective lesion is exhibited in the fovea centralis (red dashed circle). C: OCT horizontal scan of the right eye: State of the eye 4 months from B.
Retinoschisis is progressing. A slit shaped cleft is forming in the foveal photoreceptor inner and outer segment ( ). Best-corrected visual acuity at this time
is 0.7 and has not declined. D: IR + OCT horizontal scan of right eye: State of the eye after a further 13 months. A macular hole has formed, around which
retinal detachment is evident. Best-corrected visual acuity at this time is 0.3 and has declined.

Image interpretation points

These are images capturing the process of MHRD develop- the formation process of idiopathic macular holes. Macular hole
ment in high myopia. MHRD in this case has developed with- formation cannot be explained by a single mechanism alone,
out undergoing foveal detachment (outer layer lamellar hole). but instead, a variety of processes underlies the development of
The process leading from foveal photoreceptor cell dehiscence macular holes in high myopia.
to macular hole formation may have a similar mechanism to
 320 Chapter 9 · Pathologic myopia and related diseases

Case 173 Myopic foveoschisis: MHRD

A 74-year-old female, OD, BCVA 0.5, an axial length 28.72 mm

A: Color fundus photograph in the right eye: Diffuse choroidal atrophy is significant. A large temporal PPA and a ridge are evident. Retinal whitening due to
retinal detachment was biomicroscopically evident around the fovea centralis, which is unclear on this fundus photograph. B: OCT horizontal scan of the
right eye: The thickened posterior vitreous cortex ( ), retinoschisis (*), and macular detachment are visible. The macular hole is not depicted. C: OCT vertical
scan of the right eye: The macular hole is depicted. Retinal detachment (*) is evident in the posterior staphyloma.

Image interpretation points

The eye already exhibited MHRD at initial diagnosis.
Retinal traction due to the posterior vitreous cortex as well as retinoschisis and retinal detachment are clearly depicted.
Case 174 · Myopic foveoschisis: Before and after surgery for MHRD
321 9
Case 174 Myopic foveoschisis: Before and after surgery for MHRD

A 77-year-old female, OD, preoperative BCVA 0.2 and postoperative BCVA 0.2, an axial length 28.42 mm

A: Color fundus photograph in the right eye: An elliptical macular hole and surrounding retinal detachment are evident. B: Color fundus photograph in the
right eye: 7 months after surgery. The macular hole is indistinct. Retinal detachment is also unclear. C: Preoperative IR + OCT vertical scan of the right eye:
Retinoschisis and a retinal detachment (*) are visible. The macular hole is also depicted. Extensive ILM detachment ( ) is apparent. A columnar structure
is visible in the gap, which let us know that the lesion is ILM detachment. D: Postoperative IR + OCT vertical scan of the right eye: Vitreous surgery combined
with ILM peeling was performed in the area between the points indicated by (7). Retinoschisis has become less severe in the area that underwent ILM
peeling surgery. The ILM detachment remains inferior to the lower arcade vessels, and traction to the vessels (vascular microfolds) is still observed. The
macular hole remains. The superior margin of the macular hole is flattened, but the inferior portion remains elevated.

Image interpretation points

Macular hole closure sometimes cannot be achieved when surgery combined with ILM peeling. ILM peeling in the wider
the retinal detachment area is narrow even after vitreous area may have been required.
 322 Chapter 9 · Pathologic myopia and related diseases

Case 175 Myopic subretinal hemorrhages: A typical example

A 48-year-old male, OD, BCVA 0.4, an axial length 30.75 mm

A: Color fundus photograph in the right eye: A faint retinal hemorrhage is visible somewhat to the temporal side of the fovea centralis. This is a case with
a large circumferential PPA. B: FA in the right eye (26 seconds): A blockage due to the retinal hemorrhage is evident on FA imaging. C: IA in the right eye
(26 seconds): CNV is not detected even on IA imaging. D: IR + OCT horizontal scan of the right eye: A moderately reflective lesion is apparent in the sensory
retina (blue dashed circle). E: Enlarged version of D [red dashed box]: The moderately reflective lesion is seen as an elliptical shape and a liner one continuous
to it. The IS/OS line is disrupted. The RPE line is irregul ar. Subretinal hemorrhages exhibit weakly reflective lesions in the subretinal space.

Image interpretation points

This is a case of myopic subretinal hemorrhages that have case, often not as good as generally believed. The changes
developed without CNV in a highly myopic eye. When hemor- in the RPE may be secondary to hemorrhages, although it is
rhages spreads into the sensory retina, and consequently unclear exactly why they occur.
cause damages to the foveal outer retinal layer as seen in this
Case 175 · Four months later
323 9
Case 175 Four months later

A 48-year-old male, OD, BCVA 1.0, an axial length 30.75 mm

F: Color fundus photograph in the right eye: Retinal hemorrhages has disappeared and best-corrected visual acuity has improved to 1.0. G: IR + OCT horizontal
scan of the right eye: Irregular, highly reflective lesions are visible in the foveal outer retinal layers. H: Enlarged version of G [red dashed box]: RPE line
irregularities observed at initial diagnosis have mostly disappeared. The ELM and IS/OS lines have also been restored, although not completely. The irregular,
highly reflective lesions visible in the outer retinal layers are likely macrophages that have phagocytized erythrocytes.

Image interpretation points

Myopic subretinal hemorrhages generally have a good visual significant at initial diagnosis but resolved with time, and good
prognosis. In this case, changes in the outer retinal layers were visual acuity was eventually restored without treatment.
 324 Chapter 9 · Pathologic myopia and related diseases

Case 176 Myopic choroidal neovascularization: A typical example

A 61-year-old female, OD, BCVA 0.3, an axial length 29.43 mm

A: Color fundus photograph in the right eye: CNV of about half a disc diameter is visible in the upper temporal side of the fovea centralis. B: FA in the right
eye (46 seconds): Classic CNV is seen. C: IA in the right eye (1 minute, 46 seconds): CNV is hardly seen on IA. D: IR + OCT vertical scan of the right eye: Exten-
sive CNV is evident. E: Enlarged version of D [red dashed box]: The RPE line is mostly smooth. The retinal structure above the CNV is relatively well preserved
based on the observation that the ELM line is exhibited. A SRD is visible in the inferior macula and appears to be continuing from the fovea centralis.

Image interpretation points

This is typical type 2 CNV or otherwise known as classic CNV based on FA classification. A good visual prognosis is expected since
the foveal structure is relatively well preserved.
Case 177 · Myopic choroidal neovascularization: Small CNV
325 9
Case 177 Myopic choroidal neovascularization: Small CNV

A 76-year-old male, OD, BCVA 0.1, an axial length 30.14 mm

A: Color fundus photograph in the right eye: At initial diagnosis. An elliptical retinal hemorrhage exists in the nasal side of the fovea centralis, in the center
of which CNV is visible. Pigmentation in the temporal macula and atrophic lesions immediately to the pigmentation may be old CNV. The edge of posterior
staphyloma is evident near the lower arcade vessels. B: FA in the right eye (4 minutes, 48 seconds): A strongly hyperfluorescent lesion is noticeable on the
nasal side of the fovea centralis. C: IA in the right eye (4 minutes, 48 seconds): CNV is harder to detect on IA. D: IR + OCT vertical scan of the right eye:
Triangular CNV can be seen below the fovea centralis. E: Enlarged version of D [red dashed box]: No protrusions are visible in the RPE line. This is Type 2
CNV. A very flat SRD is apparent in the superior macula (*). We can see significant thinning of the choroid.
(Continued on the next page)

Image interpretation points

This is typical myopic CNV. The RPE is slightly undulating, but no protrusions are visible. This is type 2 CNV. The structure of the
foveal outer retinal layers is indistinct, but not thinned.
 326 Chapter 9 · Pathologic myopia and related diseases

Case 177 After anti-VEGF treatment

A 76-year-old male, OD, BCVA 0.9, an axial length 30.14 mm

F: Color fundus photograph in the right eye: CNV seen at initial diagnosis has disappeared. There is a faint retinal hemorrhage inferior to the fovea centralis.
G: FA in the right eye (4 minutes, 2 seconds): The hyperfluorescent lesion seen at initial diagnosis has disappeared. H: IA in the right eye (4 minutes, 2 seconds):
CNV is not detected on IA. I: IR + OCT vertical scan of the right eye: Subfoveal CNV cannot be detected. J: Enlarged version of I [red dashed box]: Scan of the
somewhat nasal side of the fovea centralis. The foveal shape is almost normal, but the IS/OS line in the superior macula macula where the SRD was present
is missing (red dashed circle).

Image interpretation points

This is a case where anti-VEGF treatment was remarkably Anti-VEGF treatment generally seems to have a high therapeutic
effective. Best-corrected visual acuity is also greatly improved. effect in cases with small CNV.
Case 178 · Myopic choroidal neovascularization: Large CNV
327 9
Case 178 Myopic choroidal neovascularization: Large CNV

A 52-year-old female, OS, BCVA 0.06, an axial length 29.04 mm

A: Color fundus photograph in the left eye: This is a case with a large temporal PPA. The CNV appears to be quite old. B: FA in the left eye (4 minutes,
6 seconds): Irregular hyper fluorescent lesions are evident, and thus CNV is noted as classic CNV. C: IA in the left eye (4 minutes, 6 seconds): CNV is depicted
although it is not so hyperfluorescent as in FA. D: FA + OCT horizontal scan of the left eye: Extensive subfoveal CNV can be seen. The temporal side CNV
exhibits a tall protrusion and spreads out flatly on the nasal side. This is Type 2 CNV. E: Enlarged version of D [red dashed box]: The temporal side CNV still
appears to be active based on the observation that multiple intraretinal highly reflective dots are visible (red dashed circle). The RPE is smooth and no
protrusions are apparent.

Image interpretation points

This is CNV observed in a relatively young patient. Elderly in this case, extensive CNV occurred despite the patient being
people generally tend to have more extensive CNV, although relatively young.
 328 Chapter 9 · Pathologic myopia and related diseases

Case 179 Myopic choroidal neovascularization: A young example

A 46-year-old female, OS, BCVA 0.6, an axial length 30.05 mm

A: Color fundus photograph in the left eye: CNV of about a third of a disc diameter is visible in the fovea centralis. Subretinal hemorrhages are present.
B: FA in the left eye (1 minute, 17 seconds): Classic CNV is depicted. C: IA in the left eye (1 minute, 17 seconds): CNV is only slightly noted on IA. D: OCT hori-
zontal scan of the left eye: Type 2 CNV is clearly exhibited. E: Enlarged version of D [red dashed box]: The RPE line is smooth. This is a typical finding of
type 2 CNV. A thin SRD is apparent in the temporal macula. The ELM line can somehow be traced above the CNV ( ).

Image interpretation points

This is CNV seen in a 46-year-old patient. Myopic CNV is usually idiopathic CNV (see pages 7 223–227) is difficult. This case may
rare in patients under 50 years of age. Differentiation from actually fall under idiopathic CNV.
Case 179 · One year after anti-VEGF treatment
329 9
Case 179 One year after anti-VEGF treatment

A 46-year-old female, OS, BCVA 1.5, an axial length 30.05 mm

F: Color fundus photograph in the left eye: The CNV is less extensive. G: OCT horizontal scan of the left eye: Scarred CNV in a trapezoidal shape is visible
in the nasal side of the fovea centralis. H: Enlarged version of G [white dashed box]: The RPE and IS/OS lines are mostly depicted. No SRD is visible in the
retina.

Image interpretation points

An intravitreal injection of anti-VEGF treatment was success- good visual acuity was achieved since there were few retinal
ful, and best-corrected visual acuity improved to 1.5 about changes.
a year later. Scarring of CNV remained after treatment, but
 330 Chapter 9 · Pathologic myopia and related diseases

Case 180 Myopic choroidal neovascularization: Foveoschisis

A 61-year-old female, OD, BCVA 0.3, an axial length 28.07 mm

A: Color fundus photograph in the right eye: CNV is visible in the lower macula ( ). Lacquer cracks are evident. B: IR + OCT horizontal scan of the right eye:
Scan passing through the CNV. Type 2 CNV exhibiting a sharp elevation is depicted. There is retinal detachment around the CNV, and retinoschisis is evident on
the temporal side. C: Enlarged version of B [red dashed box]: Type 2 CNV, retinal detachment (*) and retinoschisis ( ) are clearly visible. The CNV is being
enveloped by the RPE

Image interpretation points

It is unusual that myopic CNV is accompanied by a large retinal This case also includes foveoschisis, and it is unclear to what
detachment. extent CNV is involved in the onset of retinal detachment.
9.2 · Dome-shaped macula and inferior staphyloma
331 9
9.2 Dome-shaped macula and inferior
staphyloma
Background
Dome-shaped macula is a particular type of myopic posterior
staphyloma reported by Gaucher in 2008.(1) The Curtin classifica-
tion is well known as a classification for posterior staphyloma,(2)
but dome-shaped macula exhibits morphological abnormalities
that do not correspond to any of the Curtin classifications.
Posterior staphyloma exhibits a posterior projection of the sclera,
but dome-shaped macula is the anterior projection of the scleral
surface in the vicinity of the fovea centralis (. Fig. 9-5). Dome-
shaped macula causes macular lesions.
Various macular lesions also develop in the macular area . Fig. 9-5 Three-dimensional RPE reconstructed image of the macular
in cases of tilted disc syndrome where the inferior staphyloma area in a case of dome-shaped macula. We can see that the macular area is
projecting forward
margin overlaps in the macular area.(3) For example, chorioreti-
nal atrophy,(4) CNV,(5,6) localized SRD,(7) and PCV(8) are reported
to develop. In terms of the disease concept, dome-shaped macula
and tilted disc syndrome accompanied by inferior staphyloma References
are entirely different, but both diseases result in similar complica-
tions, and therefore may have similar onset mechanisms. 1) Gaucher D, Erginay A, Lecleire-Collet A, et al. Dome-shaped macula in
eyes with myopic posterior staphyloma. Am J Ophthalmol. 2008; 145:
There are also cases where differentiation between the two is
909–914.
not necessarily easy. The points of differentiation are basically in 2) Curtin BJ. The posterior staphyloma of pathologic myopia. Trans Am
the form of the posterior staphyloma. In dome-shaped macula, a Ophthalmol Soc. 1977; 75: 67–86.
anterior projecting area is visible in the posterior staphyloma, 3) Nakanishi H, Tsujikawa A, Gotoh N, et al. Macular complications on the
whereas only a posterior projection is visible in inferior staphy- border of an inferior staphyloma associated with tilted disc syndrome.
loma. However, cases diagnosed with dome-shaped macula do Retina. 2008; 28: 1493–1501.
4) Guiffre G. Chorioretinal degenerative changes in the tilted disc syn-
not always appear to exhibit a single anterior projection pattern.
drome. Int Ophthalmol. 1991; 15: 1–7.
Future studies on the classification of the patterns are needed. 5) Tsuboi S, Uchihori Y, Manabe R. Subretinal neovascularisation in eyes
with localised inferior posterior staphylomas. Br J Ophthalmol. 1984; 68:
OCT findings 869–872.
Dome-shaped macula is not rare. In particular, cases that ex- 6) Stur M. Congenital tilted disk syndrome associated with parafoveal sub-
retinal neovascularization. Am J Ophthalmol. 1988; 105: 98–99.
hibit a dome-shaped macula on OCT without lesions in the
7) Cohen SY, Quentel G. Guiberteau B, et al. Macular serous retinal detach-
macular area are frequent. When a SRD similar to central serous ment caused by subretinal leakage in tilted disc syndrome. Ophthalmol-
chorioretinopathy (CSC) is found, but dye leakages cannot be ogy. 1998; 105: 1831–1834.
found on FA in myopic eyes, a dome-shaped macula or tilted 8) Mauget-Faÿsse M, Cornut PL, Quaranta El-Maftouhi M, et al. Polypoidal
disc syndrome accompanied by inferior staphyloma need to be choroidal vasculopathy in tilted disk syndrome and high myopia with
staphyloma. Am J Ophthalmol. 2006; 142: 970–975.
suspected. In such cases, it is important to capture vertical scans
9) Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical
passing through the fovea centralis. coherence tomography of the choroid in central serous chorioretino-
There are many unclear points in the mechanism for the pathy. Retina. 2011; 151: 297–302.
formation of dome-shaped macula. Choroidal thickening was
initially considered, to which recent reports are contradictory.
Based on EDI-OCT imaging, Imamura et al. suggested that
in cases of dome-shaped macula localized thickening of the
subfoveal sclera leads to a chorioretinal anterior projection.(9)
However, the precise mechanisms remain unclear because
full-thickness sclera cannot be depicted in all eyes by EDI-OCT
imaging.
 332 Chapter 9 · Pathologic myopia and related diseases

Case 181 Dome-shaped macula: A typical example

A 39-year-old female, OD, BCVA 0.8, an axial length 29.25 mm

A: Color fundus photograph in the right eye: The optic disc is not tilted. Ring-shaped atrophy is evident around the optic disc ( ), suggesting the Curtin’s
type 3 staphyloma. B: IR + OCT vertical scan of the right eye: A SRD is visible in the fovea centralis. The RPE line is projecting anteriorly. The choroid is thin.
The choroid is thinnest at the apex of the dome-shaped macula. C: IR + EDI-OCT vertical scan of the right eye: Scleral thickness is relatively well preserved
at the apex of the dome-shaped macular, which was unclear using standard OCT imaging. D: SS-OCT vertical scan of the right eye: Image of a 12 mm-long
scan. We can clearly see that part of the backward projecting posterior staphyloma is projecting anteriorly forming a dome-shaped macula.

Image interpretation points

Dome-shaped macula and tilted disc syndrome with inferior is that part of the backward projecting posterior staphyloma
staphyloma are two different diseases. Differentiation of the projects anteriorly in dome-shaped macula, whereas no
two is not necessarily clear, but the fundamental difference anterior projection is evident in inferior staphyloma.
Case 182 · Inferior staphyloma: Serous retinal detachment
333 9
Case 182 Inferior staphyloma: Serous retinal detachment

A 45-year-old male, OS, BCVA 1.2, refraction -4.75 D

A: Color fundus photograph: A subfoveal SRD is visible. The optic disc exhibits no deformation. The choroidal vessels in the lower fundus are clearly in
this area. B: FAF in the left eye: The parafoveal and temporal peripapillary areas exhibit hyperfluorescence ( ). C: FA in the left eye (33 seconds): Hyper-
fluorescence is visible between the optic disc and fovea centralis. Fluorescein leakage spots are indistinct. D: IA in the left eye (33 seconds): The hyper-
fluorescent area on FA exhibits hypofluorescence on IA. E: IR + OCT horizontal scan of the left eye: A SRD is depicted in the macula. F: Enlarged version of
E [red dashed box]: This is very similar with OCT findings in CSC. Foveal thickness is well preserved. Elongation of the photoreceptor outer segment is
seen.
(Continued on the next page)
 334 Chapter 9 · Pathologic myopia and related diseases

Case 182 Continuation

G: IR + OCT vertical scan of the left eye: The RPE line consistent with the hyperfluorescent area on FA and hypofluorescent area on IA is steeply elevated.
Such elevation of the RPE is not evident on the horizontal scan shown in E. The white reflective spots on the IR image is the shed photoreceptor outer
segments. H: Enlarged version of G [red dashed box]: A small RPE protrusion is evident ( ). Intraretinal, granular, highly reflective findings are visible.
I: SS-OCT vertical scan: Image of a 12 mm-long scan (prototype SS-OCT). We can clearly see the presence of inferior staphyloma. The choroid is thin in the
area of staphyloma.

Image interpretation points

This is a case that was difficult to differentiate from CSC. Ab- However, choroidal thickening suggestive of CSC is not apparent.
normal shape of the eyeball may have resulted in damage to A small RPE protrusion is visible, but it is a common finding in
choroidal circulation leading to the development of SRD, but this disease. It is unclear if this has any pathological significance.
the combination of CSC and inferior staphyloma is undeniable.
 335 10

Retinal detachment
10.1 Rhegmatogenous retinal detachment – 336
References – 336

Case 183 Rhegmatogenous retinal detachment:

A case where retinal detachment has stopped
at the fovea centralis – 337

Case 184 Rhegmatogenous retinal detachment:

Macular detachment – 338

Case 185 Rhegmatogenous retinal detachment:

Foveal inner segment defects – 339

Case 186 Optic disc pit maculopathy – 340

 336 Chapter 10 · Retinal detachment

10.1 Rhegmatogenous retinal detachment OCT findings for reattached retinas

There are many cases where although the retina appears to be
Background biomicroscopy after surgery foveal detachment is found on OCT
Many cases of rhegmatogenous retinal detachment (RRD) in and subsides 6–12 months postoperatively.(3, 8–11) There are
young people are caused by atrophic retinal holes and progress reports that claim that the prolongation of foveal detachment
slowly. In contrast, RRD in middle-aged to elderly patients pro- after surgery is a cause of poor visual prognosis,(3) while there are
gress rapidly due to flap retinal tears and retinal breaks along the also reports claiming that it is unrelated.(9, 11) Lamellar macular
lattice degeneration caused by acute PVD. Preoperative risk fac- hole-like foveal abnormalities can remain postoperatively,(8, 9)
tors resulting in a poor visual prognosis include the presence and and cystoid macular edema can persist or develop halfway
extent of foveal detachment, time to foveal reattachment, area of through and be prolonged.(8, 10) There are also cases where ERM
retinal detachment, vitreous hemorrhages, ocular hypotension, or macular pucker occurs after surgery.(8) All these findings can
presence of choroidal detachment, unidentified retinal breaks, be the cause of poor visual acuity. The IS/OS and COST lines that
existence of giant tears, and onset of proliferative vitreoretino- become indistinct immediately after surgery are generally re-
pathy.(1) Postoperative development of foveal cystoid spaces, stored months later, but cases without recovery of these lines
ERM and macular pucker, which occur regardless of the presence have a poor visual prognosis.(6, 8–15) Foveal outer nuclear layer
of preoperative foveal detachment, can be the cause of poor thinning measured by SD-OCT is related to a poor postoperative
postoperative visual prognosis.(1) OCT allowed us to find that prognosis.(14, 15)
there are residual subretinal fluid and abnormal retinal findings
despite the retina appearing to be completely reattached on an
ophthalmoscope. References
1) Williams GA and Aaberg Jr TM. Techniques of scleral buckling. In: Ryan SJ,
OCT findings for detached retinas ed. Retina. 4th ed. Vol 3 Mosby Elsevier Inc, PA, 2006: 2035–2070.
10 Bullous retinal detachment with the fovea centralis detached is 2) Hagimura N, Suto K, Iida T, et al. Optical coherence tomography of the
not always sufficiently visible in cases of RRD where the retinal neurosensory retina in rhegmatogenous retinal detachment. Am J Oph-
detachment is so high that the detached retina is out of the thalmol. 2000; 129: 186–190.
3) Wolfensberger TJ, Gonvers M. Optical coherence tomography in the
OCT imaging frame. However, there are many cases where useful evaluation of incomplete visual acuity recovery after macula-off retinal
information can be obtained by successfully scanning the the detachments. Graefes Arch Clin Exp Ophthalmol. 2002; 240: 85–89.
fovea centralis. 4) Lecleire-Collet A, Muraine M, Menard JF, et al. Predictive visual outcome
Foveal detachment is clinically important since it may result after macula-off retinal detachment surgery using optical coherence to-
mography. Retina. 2005; 25: 44–53.
in postoperative visual impairment or metamorphopsia. Although 5) Nakanishi H, Hangai M, Unoki N, et al. Spectral-domain optical coherence
it can sometimes be hard to identify with an biomicroscopy, its tomography imaging of the detached macula in rhegmatogenous retinal
presence can be easily determined with OCT. In RRD, retinal detachment. Retina. 2009; 29: 232–242.
detachment often appears to temporarily stop once it has reached 6) Lecleire-Collet A, Muraine M, Ménard JF, et al. Evaluation of macular changes
before and after successful retinal detachment surgery using stratus-opti-
the fovea centralis before progressing to full detachment. cal coherence tomography. Am J Ophthalmol. 2006; 142: 176–179.
Separation of the outer retinal layers (known as »intraretinal 7) Maruko I, Iida T, Sekiryu T, et al. Morphologic changes in the outer layer of
separation«) is a typical finding seen in detached retinas. This the detached retina in rhegmatogenous retinal detachment and central
finding can be considered to be cystoid spaces that have formed serous chorioretinopathy. Am J Ophthalmol. 2009; 147: 489–494.e1.
8) Schocket LS, Witkin AJ, Fujimoto JG, et al. Ultrahigh-resolution optical co-
in the Henle’s fibrous layer of the outer plexiform layer, and is
herence tomography in patients with decreased visual acuity after retinal
actually closer to retinoschisis.(2–5) detachment repair. Ophthalmology. 2006; 113: 666–672.
Additionally, cystoid space formation in the inner nuclear 9) Smith AJ, Telander DG, Zawadzki RJ, et al. High-resolution Fourier-domain
layer (5, 6) and severe undulations in the photoreceptor layer (out- optical coherence tomography and microperimetric findings after macu-
la-off retinal detachment repair. Ophthalmology. 2008; 115: 1923–1929.
er nuclear layer, photoreceptor inner and outer segments) (2–5) are
10) Wakabayashi T, Oshima Y, Fujimoto H, et al. Foveal microstructure and visual
also typical findings of RRD. As these findings are not seen in acuity after retinal detachment repair: imaging analysis by Fourier-domain
CSC, a typical form of SRD, their presence is helpful in diagnosis optical coherence tomography. Ophthalmology. 2009; 116: 519–528.
for cases where it is difficult to determine whether retinal detach- 11) Shimoda Y, Sano M, Hashimoto H, et al. Restoration of photoreceptor
ment is rhegmatogenous or serous. The formation of intraretinal outer segment after vitrectomy for retinal detachment. Am J Ophthalmol.
2010; 149: 284–290.
separation is unrelated to the length of the detachment period.(2) 12) Lai WW, Leung GY, Chan CW, et al. Simultaneous spectral domain OCT and
Defects in foveal photoreceptor inner segment can be de- fundus autofluorescence imaging of the macula and microperimetric cor-
tected with SD-OCT.(5) These findings are irreversible since the respondence after successful repair of rhegmatogenous retinal detach-
inner segment does not regenerate. Findings associated with a ment. Br J Ophthalmol. 2010; 94: 311–318.
13) Sheth S, Dabir S, Natarajan S, et al. Spectral domain-optical coherence to-
poor postoperative visual prognosis after reattachment include mography study of retinas with a normal foveal contour and thickness
outer retinal layer cystoid spaces,(2) the height of the foveal after retinal detachment surgery. Retina. 2010; 30: 724–732.
detachment,(2, 4, 5, 7) foveal photoreceptor inner and outer seg- 14) Gharbiya M, Grandinetti F, Scavella V, et al. Correlation between spectral-
ment defects,(5) and foveal(5) or parafoveal(7) outer nuclear layer domain optical coherence tomography findings and visual outcome after
primary rhegmatogenous retinal detachment repair. Retina 2012; 32: 43–53.
thinning. In contrast, »intraretinal separation« is reportedly un-
15) Delolme MP, Dugas B, Nicot F, et al. Anatomical and functional macular
related to postoperative visual acuity.(3, 5) changes after rhegmatogenous retinal detachment with macula off. Am J
Ophthalmol. 2012; 153: 128–136.
Case 183 · Rhegmatogenous retinal detachment: A case where retinal detachment has stopped at the fovea centralis
337 10
Case 183 Rhegmatogenous retinal detachment: A case where retinal detachment has stopped
at the fovea centralis
A 59-year-old male, OD, BCVA 0.7

A: Color fundus photograph in the right eye. B: Fundus photograph montage in the right eye: At initial diagnosis. A bullous retinal detachment due to
a superonasal retinal tearcan be seen in the superior fundus. The retinal detachment is extending towards the fovea centralis. The detached retina has
few folds. C: FA + OCT horizontal scan of the right eye: At initial diagnosis. A flat retinal detachment is visible from the temporal area to the fovea. Diffuse
vitreous hemorrhages thought to have occurred during retinal tear formation is apparent in the vitreous cavity. D: FA + OCT vertical scan of the right eye:
At initial diagnosis. The retinal detachment is spreading right up to the fovea centralis. The elevation of the superior detached retina is significant. The
mirror image of the detached retina that was out of the imaging flame is seen as an inverted image. E: IR + OCT vertical scan of the right eye: One month
after surgery. Best-corrected visual acuity has improved to 1.0. The retina has been reattached, and the foveal shape has almost been restored to normal.
The IS/OS line in the superior fovea centralis is weakly reflective and irregular (red dashed circle).

Image interpretation points

As in this case, patients often see a doctor when the retinal reveal few changes in the detached retina. This is consistent
detachment has reached the fovea centralis. The detachment with the lack of folds in the detached retina on fundus photo-
often appears to stop here temporarily. Once it passes this area, graphs. If the RRD is discovered at this stage and treated by
it may rapidly advance to macular detachment. OCT findings surgery, the visual prognosis is generally good.
 338 Chapter 10 · Retinal detachment

Case 184 Rhegmatogenous retinal detachment: Macular detachment

A 61-year-old male, OD, BCVA 0.5

10

A: Color fundus photograph in the right eye: At initial diagnosis. A retinal detachment including the macula and folds of detached retina are visible. A retinal
tear in the temporal fundus led to the retinal detachment. B: FA + OCT vertical scan of the right eye + enlarged version [red dashed box]: At initial diagnosis.
There are seen in the detached retina intraretinal separation in the Henle’s fiber layer of the outer plexiform layer and undulating outer nuclear layer (outer
nuclear layer and photoreceptor inner and outer segments, which are findings characteristic to rhegmatogenous retinal detachment. Small inner nuclear
layer cystoid spaces are depicted. C: IR + OCT vertical scan of right eye + enlarged version [red dashed box]: Two months after surgery. Best-corrected
visual acuity is 0.6. There is a flat retinal detachment remaining in the inferior posterior pole. This was indistinct on an biomicroscopy. A typical CME is also
seen. The ELM and IS/OS lines are visible in the fovea centralis, but the latter is irregular. D: IR + OCT vertical scan of right eye + enlarged version [red
dashed box]: Five months after surgery. Best-corrected visual acuity has improved to 1.2. CME has disappeared. Foveal IS/OS reflectivity is partially attenuated.
The extent of the residual retinal detachment in the inferior posterior pole is smaller, and thus the detachment is resolving.

Image interpretation points

Characteristic retinal folds are often observed in RRD. On OCT, are hardly seen in SRDs such as CSC. Vitreous surgery was per-
retinoschisis in the Henle’s fiber layer (HFL) of the outer plexiform formed for this patient, and the retina appeared to be reattached
layer (intraretinal separation) occurs, and the retina outer to the on an biomicroscopy; but OCT revealed a residual shallow retinal
retinoschisis is undulating. This retinal undulation corresponds to detachment. CME occurred two months postoperatively, although
the retinal folds on photo. Cystoid spaces can sometimes be seen this subsided by the fifth postoperative month. Thus, OCT allows
in the inner nuclear layer. These findings are typical of RRD and detection of abnormal features not evident on an biomicroscopy.
Case 185 · Rhegmatogenous retinal detachment: Foveal inner segment defects
339 10
Case 185 Rhegmatogenous retinal detachment: Foveal inner segment defects

A 46-year-old male, OD, BCVA 0.1

A: Color fundus photograph in the right eye: At initial diagnosis. A retinal detachment is seen in the inferior half of the fundus and the macula. This is due to
a retinal tear in the superotemporal periphery. Horizontal retinal folds are seen in the macula. B: FA + OCT horizontal scan of the right eye + enlarged version [red
dashed box]: At initial diagnosis. Retinal features characteristic to RRD, such as retinoschisis in the Henle’s fiber layer of the outer nuclear layer and undulations
of the outer retinal layers (outer nuclear layer and photoreceptor inner and outer segments) can be seen in the detached retina. A columnar structure thought
to be composed of Müller cells is apparent. Note that no reflectivity is evident outside the ELM in the foveola, which may be due to damage to the inner seg-
ment (*). Insignificant inner nuclear layer cystoid spaces are noted. C: FA + OCT vertical scan of the right eye + enlarged version [red dashed box]: At initial
diagnosis. Similar findings to B can be seen, but outer retinal folding is more severe. D: IR + OCT horizontal scan of the right eye + enlarged version [red dashed
box]: 13 months after surgery. IS/OS abnormal reflectivity is visible only in the foveola. Despite the successful retinal detachment surgery, best-corrected visual
acuity better than 0.6 has not been achieved.

Image interpretation points

Retinal folds in RRD are consistent with undulations of the which is irreversible damage. These findings can be seen in cases
retina outer to the retinoschisis of the Henle’s fiber layer of where foveal detachment is high or many days have passed
the outer plexiform layer as depicted on OCT. Close observation before surgery and often result in a poor visual prognosis. This
of the foveola reveals loss of the reflectivity outside of the ELM patient was diagnosed one week after becoming aware of
line. This suggests the disappearance of the inner segment, visual acuity decline.
 340 Chapter 10 · Retinal detachment

Case 186 Optic disc pit maculopathy

A 23-year-old male, OS, BCVA 0.4

10

A: Color fundus photograph in the left eye: At initial diagnosis. An elliptical pit is visible on the inferior temporal part of the optic disc ( ). Retinal nerve fiber
layer defect-like findings are apparent in the papillomacular bundles and are linked to a macular SRD. B: FA/IA in the left eye (14 minutes): No fluorescein leakage
is evident in the pit, and no retinal or choroidal vessel hyperpermeability findings can be found. The fovea centralis exhibits hyperfluorescence at the early to
late phase of both FA and IA imaging, but this hyperfluorescence is thought to be due to depigmentation of the retina pigment epithelium layer as a result of
prolonged detachment. C: Color fundus photograph + 1 µm SS-OCT horizontal scan of the left eye: Scan passing through the pit ( ) and fovea centralis. A SRD
is visible in the macula, and the foveal photoreceptor layer is dehisced. Retinoschisis is significant in the retinal nerve fiber layer and in the Henle’s fiber layer of
the outer plexiform layer and appears to be connected to the pit through hyporeflective vacuole or slit spaces in the optic disc rim ( ) and in the deep portion
of the optic disc rim ( ). Vacuoles are also visible in the ganglion cell layer and inner nuclear layer. D: Color fundus photograph + 1 µm SS-OCT horizontal scan
of the left eye: Scan passing through the pit. Highly reflective tissue appears to be filling the pit. The outline of the pit is clearly visible as a result of this tissue,
and we can see that the lamina cribrosa is defective.

Image interpretation points

An optic disc pit is thought to be a congenital anomaly where a accompanied by retinoschisis in the inner and/or outer retinal
round or elliptical pit forms in the temporal part of the optic layers. The laminar fluid in the gap has been speculated to derive
disc. The lamina cribrosa is defective in the pit area, which is either from cerebrospinal fluid, retinal blood vessels, or the vitreous
filled with abundant collagen. A pit can be seen on the temporal fluid. However, according to recent observational studies using
side of the optic disc in this case. This SS-OCT image succeeds OCT, cerebrospinal fluid passes through the pit and then inner
in depicting the pit filled with highly reflective fibrous tissue. and/or outer retinal layers to accumulate subretinally in the mac-
25% to 75% of eyes with an optic disc pit subsequently develop ular area. SS-OCT images reveal that vacuoles inside the sensory
a SRD in the macular area, which results in visual decline. This retina and the optic disc rim connect and communicate with the
is known as optic disc pit maculopathy. This is always pit.
 341 11

Lesion morphology index based

on OCT
 342 Chapter 11 · Lesion morphology index based on OCT

Vitreoretinal interface lesions

Perifoveal PVD with foveal deformation Macular PVD resulting in foveal deformation
(Case 2C, page 30) (Case 1C, page 29)

Stage 1 idiopathic macular hole Stage 2 idiopathic macular hole

(Case 2D, page 30) (Case 8C, page 36)

11

Macular PVD resulting in a macular microhole Vitreomacular traction syndrome

(Case 23C, page 57) (Case 35E, page 74)

Myopic foveoschisis Epiretinal membrane with PVD

(Case 37C, page 76) (Case 27D, page 64)

Epiretinal membrane without PVD Macular pseudohole without PVD

(Case 31E, page 68) (Case 34D, page 71)
11 · Lesion morphology index based on OCT
343 11
Macular thickening
Thickening due to traction

Epiretinal membrane Vitreomacular traction syndrome

(Case 28D, page 65) (Case 35E, page 74)

Macular pseudohole with PVD

(Case 33D, page 70)

Thickening with cystoid spaces

Diabetic macular edema Branch retinal vein occlusion

(Case 41 G, page 89) (Case 57C, page 114)

Sarcoidosis Macular telangiectasia Type 1

(Case 154E, page 283) (Case 64E, page 124)

Thickening with retinoschisis

Myopic foveoschisis X-linked juvenile retinoschisis

(Case 170B, page 316) (Case 131C, page 243)
 344 Chapter 11 · Lesion morphology index based on OCT

Foveal detachment and macular retinal detachment

Stage 1 idiopathic macular hole Idiopathic macular hole with spontaneous closure
(Case 4C, page 32) (Case 18E, page 50)

Vitreomacular traction syndrome Myopic foveoschisis

(Case 36B, page 75) (Case 170B, page 316)

11

Diabetic macular edema Central retinal vein occlusion

(Case 46E, page 95) (Case 55E, page 112)

Macular telangiectasia Type 1 Central serous chorioretinopathy

(Case 64E, page 124) (Case 72D, page 140)

Vogt-Koyanagi-Harada syndrome Type 1 CNV in exudative age-related macular degeneration

(Case 156E, page 287) (Case 98G, page 184)
11 · Lesion morphology index based on OCT
345 11

Polypoidal choroidal vasculopathy Inferior staphyloma

(Case 105D, page 195) (Case 182G, page 335)

Adult-onset foveomacular vitelliform dystrophy

(Case 135E, page 252)

Outer retinal layer atrophy

Retinitis pigmentosa
Atrophic age-related macular degeneration (Case 145E, page 267)
(Case 95D, page 178)

Stargardt disease
(Case 133F, page 247) Oguchi disease
(Case 149C, page 275)

Bietti’s crystalline dystrophy

(Case 143D, page 265) Cancer-associated retinopathy
(Case 142E, page 263)
 346 Chapter 11 · Lesion morphology index based on OCT

Retinal pigment epithelium protrusions and undulations

Drusen Serous pigment epithelial detachment

(Case 80C, page 158) (Case 86D, page 164)

Type 1 CNV in exudative age-related macular degeneration Polypoidal choroidal vasculopathy

(Case 98G, page 184) (Case 113G, page 208)

Choroidal thickening and thinning

11

Retinal angiomatous proliferation stage 2B Pseudoxanthoma elasticum

(Case 120D, page 217) (Case 137D, page 255)

Central serous chorioretinopathy (EDI-OCT) Vogt-Koyanagi-Harada syndrome (EDI-OCT)

(Case 74D, page 142) (Case 157D, page 289)

Myopic foveoschisis Myopic choroidal neovascularization

(Case 170B, page 316) (Case 178D, page 327)
 347

Service Part

Subject Index – 348

Case Index – 350

348 Service Part

Subject Index

A cherry-red spot 115, 116

choroid 9, 10, 137
enhanced depth imaging (EDI) 10
enlargement of blind spot 233
idiopathic juxtafoveolar retinal
telangiectasia 121
ABCA4 gene mutation 246 choroidal folds 293, 294 epiretinal membrane 60, 61, 70 idiopathic macular holes 23
acute CSC 136 choroidal imaging 9 extensibility 305 ILM detachment 307, 313
acute retinal necrosis 299, 301 – choroidal thickness 10 exudative age-related macular ILM peeling 315, 317
acute zonal occult outer retino- – EDI-OCT 9 degeneration 179 incomplete central retinal artery
pathy (AZOOR) 235 – swept source OCT (SS-OCT) 10 exudative chorioretinal spots 284 occlusion 118
adult-onset foveomacular vitelliform choroidal neovascularization eye movement 13 indocyanine angiography 134
dystrophy (AOFVD) 249 (CNV) 179, 180, 181, 182, 183, inferior staphyloma 331, 334
age-related macular degeneration 185, 186, 187, 188, 189, 190 infiltrated leukocytes 281
(AMD) 173
– and outer segment 7
choroidal permeability 134
choroidal thickening 137, 286,
F inflammatory cells 297
ink-blot 135
angioid streaks (AS) 254 289, 290 false colours 10 ink-blot pattern 135, 140
anti-VEGF treatment 326, 329 choroidal thinning 308, 313, 334 fibrin 141 inner nuclear layer cystoid edema
area of nonperfusion 110 choroidal vessel hyperpermeability fibrin membrane 285 245
arterial macroaneurysm 132 137 fibrovascular membrane 101, 102 inner nuclear layer cystoid spaces
artifacts 13, 14, 15, 16, 17 chronic central serous chorioretino- flap 24 244
– caused by the optical properties pathy 135, 144 fluorescein angiography 134 inner retinal atrophy 116
of tissue 14 chronic CSC 136 fovea centralis thinning 146 inner segment 7, 8
– high-reflectivity 14 classic CNV 324, 325, 328 foveal atrophy 99 interpretation, B-scan 2
– involuntary eye imovement 13 CME 122 foveal avascular zone (FAZ) 78 intracavity reflections 80, 81
– low-reflectivity 14 Coat’s disease 128 foveal cystoid spaces 132 intrachoroidal cavitation
– shadows 14 cone outer segment tip (COST) 6 foveal detachment 40, 42, 47, 48, (ICC) 305, 308
atrophic age-related macular cone sheath 7 49, 50, 124, 132, 279, 284, 336 intraretinal microvascular
degeneration 173, 174 contact cylinder 7 foveal detachment 344 abnormalities (IRMAs) 78, 98
atrophic AMD 173 COST line 6 foveal IS/OS reflectivity 111 intraretinal separation 336
atrophy of the photoreceptor layer cotton-wool spots 78 foveal retinal thinning 315 irregular retinal whitening 118
96 cryopexy 128 foveal retinoschisis 312, 314, 316 ischemic maculopathy 84
autoimmune 295 Curtin classification 304 foveal RPE atrophy 315 IS/OS abnormalities 235
AZOOR 237 cuticular drusen 153, 159, 160 foveal thinning 281 IS/OS defect 232, 233, 234
– complex 235 cyclosporine 296 fringe washout 14 IS/OS line 7
cystic degeneration 122 fundus albipunctatus 271, 273 IS/OS line irregularities 125
cystoid macular edema 98, 104, fundus flavimaculatus 246
B 106, 109, 110, 121, 124, 278, 280,
282, 284, 336, 338
L
Behçet disease 278, 279
Best disease 249
cystoid spaces 81, 82, 86, 95, 97,
105
G lacquer crack 305, 311, 312, 330
Bietti crystalline dystrophy 262 – intracavity reflectivity 80 Gass’s Stage 24 lamellar cystic degeneration 125,
blind spot enlargement 237 – typical locations 80 gas tamponade 131 126, 127
boundary surface 4, 6 genetic predisposition 295 lamellar macular hole 25, 46, 54
branch retinal vein occlusion granulomatous iridocyclitis 285 laser photocoagulation 137, 141
(BRVO) 106
breakdown of the outer blood-retinal
D granulomatous lesions 297, 298 leakage mechanism 79

barrier 134 dark choroid 247

Bruch’s membrane tears 241
B-scan interpretation 2
defocusing 16, 17
degenerative myopia 304, 305
H M
B-scans 10 depth resolution 2, 11, 12 hard drusen 153 macular dystrophy 246
– displaying false colours 10 – misinterpretations 11 hard exudate 84, 128, 132 macular hole 23, 24, 25, 26, 27,
– displaying reflection intensity diabetic macular edema 78, 79, 88 hemi-retinal vein occlusion 104 306
10 – injure hemorrhage 84 – Myopia 306
bullous retinal detachment 337 – photoreceptor layer 84 Henle fiber layer (HFL) 4, 25 – postoperative OCT findings
diabetic retinopathy 78 herpes simplex virus 299 26
dome-shaped macula 331, 332 HFL 4, 5 – postoperative visual prognosis
C DONFL 36, 39
drusen 153, 159, 160, 161
hyperreflective foci 82, 91, 95 26
– spontaneous closure 26
cancer-associated retinopathy drusenoid PED 153, 167 – stage classification 24
(CAR) 259
capillary aneurysms 124
I macular hole formation 319
macular hole retinal detach-
central retinal vein occlusion 104,
105, 109, 111
E idiopathic choroidal neovascular-
ization 223, 226, 228
ment 305, 320
macular microhole 25, 56, 57
central scotomas 235 EDI-OCT 9 idiopathic CNV 223, 328 macular pseudohole 55, 61
central serous chorioretinopathy Ehlers-Danlos syndrome 254 idiopathic epiretinal membrane macular retinal detachment 316,
(CSC) 56, 134, 137 ellipsoids 7 60 344
 349 A–Y
Subject Index

macular serous retinal detachment

340
P retinal macroaneurysm 130
retinal microaneurysms 83
subretinal detachment 104, 106,
109, 128, 135, 147
macular thickening Paget’s disease 254 retinal nerve fiber layer 7, 8 subretinal hemorrhage 130, 131
– thickening due to traction 343 panretinal photocoagulation 99 retinal nerve fiber layer clouded supraciliary effusion 289, 293, 294
– thickening with cystoid spaces papilledema 293 edema 79 swept source OCT 142
343 parafoveal cystoid spaces 94 retinal nerve fiber layer thinning sympathetic ophthalmia 295, 296
– thickening with retinoschisis paravascular retinal cysts 306 317
343 pathological myopia 304, 306 retinal periphlebitis 283
Malattia leventinese 220, 222
Marfan syndrome 254
perifoveal PVD 23, 26
– foveal form abnormalities 25
retinal pigment epithelium
protrusions and undulations
T
measurement principles 16 – spontaneous separation 25 346 temporal cystoid macular edema
membrane-like material 292 peripapillary atrophy 314 – Choroidal thickening and 123
MEWDS 235, 237 photodynamic therapy 137 thinning 346 thickened posterior vitreous cortex
microaneurysms (MAs) 79, 88 photoreceptor cell inner 7 retinal pigment epithelium 318
middle-aged men 134 photoreceptor cells 83 (RPE) 6, 134 third line 6
mild lacquer cracks 311 photoreceptor defects 316 retinal thickening 120, 122 thrombus 115
Müller cell cone 26, 27, 33, 35 photoreceptor dehiscence 24 retinal thinning 126, 127, 292, tilted disc syndrome with inferior
multifocal choroiditis and photoreceptor layer damage 84 299, 301 staphyloma 332
panuveitis (MCP) 238 PIC 241 retinal traction 297 toxocariasis 297
multilocular subretinal detachment pigment epithelial detachment retinal vasculitis 278 tractional posterior vitreous
287 134, 135, 147, 155, 172, 201, 205 retinal vein occlusion 104 detachment 312
multiple B-scan averaging 3 polypoidal choroidal vasculopathy retinal whitening 115, 119, 120 traumatic macular hole 52
multiple evanescent white dot (PCV) 155, 167, 191, 192, 196, retinitis pigmentosa 265, 268 Type 2 CNV 238, 240, 325, 328
syndrome (MEWDS) 232, 234 201, 202, 205, 207 retinoschisin 242
myopia 304 posterior staphyloma 304, 320 retinoschisis 319, 330, 338, 340
myopic CNV 307, 310, 325, 326,
327, 328
posterior synechia 279
posterior vitreous cortex 100
rhegmatogenous retinal
detachment (RRD) 299, 336
V
myopic foveoschisis 305, 318 posterior vitreous detachment right-angled retinal venules 126 vacuoles 340
myopic simple hemorrhage 322, (PVD) 23 rod outer segment tip (ROST) 6 varicella-zoster virus 299
323 proliferative diabetic retinopathy RPE 4, 6 vascular microfolds 306, 313
101, 102 atrophy 135 vasculitis 299
proliferative membrane 298 defects 238 venous beading 98
N prolonged subretinal detachment
144
depigmentation 237
hyperplasia 127
virtual images 16, 17
visual impairment 78
neovascularization, idiopathic pseudoxanthoma elasticum line 6 vitelliform macular dystrophy
choroidal 226, 228 (PXE) 254 thickening 296 (VMD) 249
noncaseating epithelioid granuloma punctate inner choroidopathy RS1 gene mutation 242 vitreomacular traction syndrome
282 (PIC) 238 67, 71, 72, 73, 100, 102
non-ischemia 113 PVD 23 vitreoretinal interface lesions 342
nonperfusion area 83
nonproliferative diabetic retino-
S vitreous hemorrhage 99, 129
vitreous inflammation 300
pathy 78
normal choroidal imaging 9
R sarcoidosis 282
scar contraction 298
vitreous macular traction
syndrome 318
normal retina 4 RAP scotoma 234 vitreous surgery 296
– cellular layer 4 – schematic diagram 212 SD-OCT findings 80 VKH syndrome 288
– fiber layer 4 reactive RPE hyperplasia 146 sensitivity attenuation 16, 17, 18 Vogt-Koyanagi-Harada disease
normal retinal layer structure 7 recurrence 144 serous retinal detachment (VHD)
reflection intensity 10 (SRD) 134, 181, 285 – Harada type 285
reflection of virtual images 16 shadows 14 – Vogt-Koyanagi type 285
O reflectivity 4, 5, 14, 15
reticular pseudodrusen 153, 154,
silicone oil tamponade 301
smoke-stack 134, 135
Vogt-Koyanagi-Harada disease
(VKH) 285
OCT findings 61, 136 161, 162, 163 pattern 137, 139, 143
Oguchi disease 274 retinal angiomatous proliferation soft drusen 153, 157
operculum 24
outer photoreceptor shedding
212, 213, 219
retinal arterial macroaneu-
soft exudate (cotton-wool
spots) 78
X
296, 334 rysm 129, 131 solar retinopathy 56 X-linked juvenile retinoschisis 242
outer plexiform layer edema 81, retinal artery occlusion 115 speckle noise 2, 3, 11
95, 132 retinal atrophy 280 – removal 11
outer retinal layer atrophy 345
outer retinal thinning 235
retinal capillary bed 78
retinal capillary lesions 78
– removing 3
spectral-domain OCT (SD-OCT) 2
Y
outer segment 7, 8 retinal capillary network 78 SS-OCT 10 yellowish-white dots 232
outer segment photoreceptor retinal clouding 281 Stargardt disease 246, 248 yellowish-white lesions 238
abnormalities 143, 144 retinal detachment 300, 301, 336 steroid resistance 294 yellowish-white spots 239
outer segment shedding 294 retinal edema 79 steroids 134
– classification 79 steroid therapy 288, 290, 291
retinal folds 298, 338, 339 subfoveal atrophic lesions 315
retinal granulomatous lesions 282 sub-ILM hemorrhage 130
retinal hemorrhages 110 subretinal deposits 145
350 Service Part

Case Index

A – progression from non-ischemic

to ischemic 108, 110
– Type 1 CNV with low activity
182
– Stage 1 small foveal detachment
type 34
acute bullous retinal detachment chronic central serous chorioretino- – Type 1 CNV with relatively strong – typical example of stage 2 36
– A typical example 147 pathy exudative changes 183 – typical example of stage 3 41
acute central serous chorioretino- – case of recurrence 143 – Type 2 CNV localized in the fovea – typical example of stage 4 43
pathy – changes in the photoreceptor centralis 189 ILM detachment
– a slowly leaking ink-blot pattern outer segment 145 – Type 2 CNV with strong exudative – case without foveoschisis 312
140 – choroidal thickening 142 changes 190 inferior staphyloma
– Intense leakage with ink-blot – example of poor visual acuity – Serous retinal detachment
pattern 141 146 333
– Smoke-stack pattern 139
acute retinal necrosis
Coats’ disease 128
cuticular drusen
F intrachoroidal cavitation
– connection with the vitreous
– typical example 300 – case with vitelliform detachment foveal cystoid spaces 90, 94 cavity 309
acute zonal occult outer retino- 159 foveal detachment 90 – typical example 308
pathy – fellow eye 160 foveal photoreceptor layer ischemic maculopathy
– Eye with a history of MEWDS cystoid macular edema 87 degeneration 92 – cystoid macular degeneration
236 – CME limited to layers anterior to fundus albipunctatus 98
adult-onset foveomacular vitelliform the ELM 87 – typical example 272 – thinned macula 99
dystrophy – exacerbation 89
– course 253 – foveal detachment with
– peudohypopyon stage 252
– vitelliform stage 251
recurrence 90
– ME extending to the outer retina
H L
after surgery 42, 45 88 hard exudate 88, 91, 92, 96 lacquer cracks
anti-VEGF treatment 186, 196, – microaneurysms 97 hemi-central retinal vein occlusion – mild case 311
219, 226, 326 – photoreceptor damage from – non-ischemic type 113 – typical example 310
atrophic age-related macular outer plexiform layer edema – idiopathic choroidal neovascular- lamellar macular hole 53, 54, 55
degeneration 95 ization large pigment epithelial detachment
– atrophic lesions of various sizes – subfoveal accumulation 91 – envelopment by RPE cells – case where CNV is present 171
177 – subfoveal leakage from a foveal 225 – case where CNV is suspected
– fellow eye of PCV 178 cystoid space 94 – fresh case 224 168
– typical example 176 – subretinal leakage from a para- – scarring process 227
foveal cystoid space 92
cystoid spaces 87
M
B I macular hole 29, 42, 51, 52
Behçet disease
– acute attack 281
D idiopathic epiretinal membrane
– typical example 63
– Stage 1, macular microhole
formation 48
– cystoid edema and foveal diabetic macular edema – exposure of the fibrocellular – Stage 1, spontaneous separation
detachment 279 – Early-stage case 86 membrane 64 of perifoveal PVD 47
– retinal atrophy 280 dome-shaped macula – macular PVD has been com- – Stage 2, spontaneous closure
Bietti crystalline dystrophy – typical example 332 plete 68 49
– outer retinal tubulation 264 dot and blot hemorrhages 88 – macular PVD has not been – Stage 3, Spontaneous closure
– typical example 263 drusenoid PED complete 67 50
aranch retinal artery occlusion – case where CNV is suspected – membrane with significant – Stage 4, spontaneous closure
– case of good visual acuity 119 166 whitening 65 51
– incomplete occlusion 120 – significant columnar structure – traumatic, a typical example
aranch retinal vein occlusion formation 66 52
– Significant inner retinal layer
ischemia 114
E idiopathic macular hole
– case just before progression from
macular microhole
– case without PVD 59
enlargement of hemorrhagic stage 1 to stage 2 35 – with complete PVD 58
pigment epithelial detachment – postoperative course for macular – with macular PVD 57
C 201
enlargement of the abnormal
hole closure 40
– postoperative course for
macular pseudohole 53, 70, 71
macular telangiectasia
cancer-associated retinopathy vascular network 202 macular hole closure under gas – Yannuzzi classification Type 1
– damage to the outer retinal epiretinal membrane 69 tamponade 38 123, 124
layers 260 exudative age-related macular – progression from lamellar to – Yannuzzi classification Type 2
– retinal vasculitis 261 degeneration full-thickness macular holes 46 Stage 2 125
central retinal artery occlusion – case with extensive Type 1 and 2 – progression from stage 1 30 – Yannuzzi classification Type 2
116 CNV exudative changes 185 – Stage 1 foveal cystoid space Stage 3 126
– cilioretinal artery not occluded – Type 1 and 2 CNV with cystic formation type 31 – Yannuzzi classification Type 2
117 changes 188 – Stage 1 foveal detachment Stage 4 127
– incomplete occlusion 118 – Type 1 and 2 CNV with extensive type 32 Malattia leventinese
central retinal vein occlusion serous retinal detachment 187 – Stage 1 photoreceptor – typical example 221
– ischemic type 112 – Type 1 CNV with a SRD 181 dehiscence type 33 multilayered petaloid 89
 351 A–X
Case Index

multiple evanescent white dot

syndrome
– optic disc type 206
– polypoidal lesions and pigment
T
– typical example 233 epithelial detachment 208 toxocariasis
myopic choroidal neovascularization – small lesions 194 – proliferative membrane 298
– anti-VEGF treatment 328 – tomographic notch sign 209
– foveoschisis 330 proliferative diabetic retinopathy
– Large CNV 327
– Small CNV 325
101
pseudoxanthoma elasticum
V
– typical example 324 – outer retinal tubulation 258 venous beading 98
– young example 328 – polypoidal lesions 257 vitreomacular traction syndrome
myopic foveoschisis – Type 1 CNV 255 73, 74, 75, 76, 100
– before and after surgery for – Type 2 CNV 256 Vogt-Koyanagi-Harada disease
MHRD 321 punctate inner choroidopathy – choroidal folds 293
– case with foveal detachment – atrophic pigmented scars – large foveal cystoid space 287
314 239 – prominent choroidal thickening
– case with macular retinal – case complicated by CNV 289
detachment 316 240 – reattachment process 291
– case without foveal detachment – yellowish-white spots and
313 CNV 241
– macular hole formation 319
– MHRD 320
X
– traction from the thickened
posterior vitreous cortex 318
R X-linked juvenile retinoschisis
– retinoschisis confined to the
myopic subretinal hemorrhages reticular pseudodrusen 163 macula 245
– typical example 322 – case with atrophic age-related – retinoschisis over a wide
macular degeneration (atrophic area 243
AMD) 162
N – fellow eye of RAP 161
retinal angiomatous proliferation
nonperfusion area 88, 93 – Stage 1 214
– Stage 2A 215
– Stage 2B 216, 217
O – Stage 3 218
retinal arterial macroaneurysm
Oguchi disease 132
– cystoid space formation and retinal arterial macroaneurysm
golden sheen fundus reflex – subretinal hemorrhages 130
276 retinitis pigmentosa
– typical example 275 – cystoid macular edema 269
optic disc pit maculopathy 340 – typical example 267
outer plexiform layer cystoid – vitreomacular traction syndrome
spaces 94 270
rhegmatogenous retinal
detachment
P – case where retinal detachment
has stopped at the fovea
physiological PVD centralis 337
– flattening of foveal depression – foveal inner segment defects
29 339
pigment epithelial detachment – macular detachment 338
– case with type 1 CNV 169,
170
– reactive proliferation of retinal
pigment epithelial cells 165
S
polypoidal choroidal vasculopathy sarcoidosis
– large branching vascular network – cystoid macular edema 283
199 – foveal detachment 284
– large hemorrhagic pigment serous pigment epithelial
epithelial detachment 203, detachment
204 – case without CNV 164
– massive lesion 211 soft drusen 163
– case confused with central – confluent drusen 158
serous chorioretinopathy 195 – example 157
– case where the branching soft exudate 91
vascular network has detached stargardt disease
210 – typical example 247
– fibrin deposits 197, 198 sympathetic ophthalmia
– large foveal cystoid space 200 – after vitreous surgery 296