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Multimodal
Imaging in Uveitis

H. Nida Sen
Russell W. Read
Editors

123
Multimodal Imaging in Uveitis
H. Nida Sen • Russell W. Read
Editors

Multimodal Imaging
in Uveitis
Editors
H. Nida Sen Russell W. Read
National Eye Institute Ophthalmology
National Institutes University of Alabama at Birmingham
of Health Birmingham, AL
Bethesda, MD USA
USA

ISBN 978-3-319-23689-6    ISBN 978-3-319-23690-2 (eBook)

https://doi.org/10.1007/978-3-319-23690-2

Library of Congress Control Number: 2017962971

© Springer International Publishing AG 2018

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Preface

Ophthalmology is one of the fields in medicine, in which there has been rapid prog-
ress in the availability and widespread acceptance of several new modalities of diag-
nostic imaging. Over the past decade, there have been advances in ophthalmic
imaging, including wider angle, improved resolution, quicker scan times, and
enhanced depth imaging to allow more detailed visualization and better comprehen-
sion of the extent of disease and closer scrutiny of the structural changes which
improved the understanding of pathophysiology of disease.
The gold standard of imaging as an adjunct to clinical care is taking on a new
form, and the ophthalmology community must continually keep abreast of these
advances and be able to appropriately incorporate them into clinical practice. This
is especially true with diseases of the retina and choroid in uveitis, where functional
changes may precede structural changes and having strong knowledge of the
strengths of imaging techniques can help identify disease in initial stages and permit
early institution of treatment.
In view of the considerable progress made, this book aims at providing up-to-
date comprehensive information on the most advanced imaging modalities available
for the assessment of retina and choroid, with a focus on uveitis. For each modality,
a description of the currently known applicability, role, and limitations within dis-
ease entities is reported. Among the newer imaging modalities, detailed attention is
paid to the various OCT technologies such as spectral domain OCT, enhanced depth
imaging OCT, and en face swept-source OCT. Further individual chapters focus on
imaging using adaptive optics, multiview OCT, and OCT angiography.
This book is a modern guide to the ophthalmic imaging techniques that have
revolutionized the diagnosis and management of uveitis during the past decade.

Bethesda, MD, USA H. Nida Sen, MD, MHS

Birmingham, AL, USA  Russell W. Read, MD, PhD

v
Acknowledgements

The editors warmly acknowledge all authors that contributed to make this book a
reality, and to Springer for their support and belief in the project.
Increasing use and better understanding of different modalities described in this
book are sure to improve our knowledge of the disease mechanisms involved in
uveitis and lead to better outcomes.
The challenge with this project is the continual development of newer imaging
modalities; however, the authors focused on the imaging tools that they have learnt
to be the most useful at diagnosis and monitoring of progression in uveitis.
We thank the authors who have assembled their experience and expertise into
this comprehensive and yet very timely book for all ophthalmologists dealing with
diseases of the retina and choroid.
H. Nida Sen and Russell W. Read

vii
Contents

1 Fluorescein Angiography in the Diagnosis and Management

of Uveitis ��������������������������������������������������������������������������������������������������    1
Albert T. Vitale and Nikhil N. Batra
2 Indocyanine Green Angiography in Uveitis������������������������������������������   25
Shilpa Kodati, Samuel P. Burke, and Thomas A. Albini
3 Wide-Field Imaging in Uveitis����������������������������������������������������������������   37
Benjamin P. Nicholson, Karen R. Armbrust, and H. Nida Sen
4 Imaging in Uveitis: Spectral Domain and Enhanced Depth
Imaging Ocular Coherence Tomography����������������������������������������������   51
Wendy M. Smith
5 Fundus Autofluorescence Imaging in Posterior Uveitis������������������������   69
Rubbia Afridi, Aniruddha Agarwal, Mohammad Ali Sadiq,
Muhammad Hassan, Diana V. Do, Quan Dong Nguyen,
and Yasir Jamal Sepah
6 Microperimetry in Uveitis ����������������������������������������������������������������������   87
Himanshu K. Banda, Maggie M. Wei, and Steven Yeh
7 Optical Coherence Tomography Evaluation of the Anterior
Segment in Uveitis Patients ��������������������������������������������������������������������   99
Francesco Pichi and Sunil K. Srivastava
8 Optical Coherence Tomography Angiography in Uveitis�������������������� 107
Francesco Pichi and Sunil K. Srivastava
9 En Face Optical Coherence Tomography���������������������������������������������� 117
Fabio Scarinci, Amani A. Fawzi, and Debra A. Goldstein
10 Multi-view Optical Coherence Tomography ���������������������������������������� 129
William R. Tucker, Robert B. Nussenblatt, and H. Nida Sen

ix
x Contents

11 Adaptive Optics and Its Use in Inflammatory Eye Disease ���������������� 135
Johnny Tam
12 Novel Use of Existing Imaging Modalities to Assess
Intraocular Inflammation ���������������������������������������������������������������������� 151
Alastair K. Denniston and Pearse A. Keane
Index������������������������������������������������������������������������������������������������������������������ 165
Contributors

Rubbia Afridi, MBBS Byers Eye Institute, Stanford University, Palo Alto, CA,
USA
Aniruddha Agarwal, MD Department of Ophthalmology, Advanced Eye Center,
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh,
India
Thomas A. Albini, MD Bascom Palmer Eye Institute, Miller School of Medicine,
University of Miami, Miami, FL, USA
Karen R. Armbrust Department of Veterans Affairs Medical Center University of
Minnesota, Minneapolis, MN, USA
National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Himanshu K. Banda, MD Emory Eye Center, Atlanta, GA, USA
Nikhil N. Batra, MD Vitreoretinal Division, Section of Ophthalmology, Geisel
School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon,
NH, USA
Samuel P. Burke, BA Bascom Palmer Eye Institute, Miller School of Medicine,
University of Miami, Miami, FL, USA
Alastair K. Denniston, PhD, FRCOphth Queen Elizabeth Hospital Birmingham,
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute for Inflammation and Ageing, College of Medical and Dental Sciences,
University of Birmingham, Edgbaston, Birmingham, UK
NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital
NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
Diana V. Do, MD Byers Eye Institute, Stanford University, Palo Alto, CA, USA
Amani A. Fawzi, MD Department of Ophthalmology, Northwestern University,
Chicago, IL, USA

xi
xii Contributors

Debra A. Goldstein Department of Ophthalmology, Northwestern University

Feinberg School of Medicine, Chicago, IL, USA
Muhammad Hassan, MBBS Byers Eye Institute, Stanford University, Palo Alto,
CA, USA
Pearse A. Keane, MD, FRCOphth NIHR Biomedical Research Centre for
Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
of Ophthalmology, London, UK
Shilpa Kodati, MD National Eye Institute, National Institutes of Health, Bethesda,
MD, USA
Quan Dong Nguyen, MD, MSc Byers Eye Institute, Stanford University, Palo
Alto, CA, USA
Benjamin P. Nicholson Great Lakes Eye Care, St. Joseph, MI, USA
Robert B. Nussenblatt Moorfields Eye Hospital, London, UK
Francesco Pichi, MD Cole Eye Institute, Cleveland Clinic Foundation, Cleveland,
OH, USA
Cleveland Clinic Abu Dhabi, Eye Institute, Abu Dhabi, UAE
Mohammad Ali Sadiq, MBBS Byers Eye Institute, Stanford University, Palo
Alto, CA, USA
Fabio Scarinci Department of Ophthalmology, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA
G. B. Bietti Eye Foundation-Istituto di Ricovero e Cura a Carattere Scientifico,
Rome, Italy
H. Nida Sen National Eye Institute, National Institutes of Health, Bethesda, MD,
USA
Moorfields Eye Hospital, London, UK
Yasir Jamal Sepah, MBBS Byers Eye Institute, Stanford University, Palo Alto,
CA, USA
Wendy M. Smith, MD Mayo Clinic, Rochester, MN, USA
Sunil K. Srivastava, MD Cole Eye Institute, Cleveland Clinic Foundation,
Cleveland, OH, USA
Johnny Tam National Eye Institute, National Institutes of Health, Bethesda, MD,
USA
William R. Tucker Moorfields Eye Hospital, London, UK
Contributors xiii

Albert T. Vitale, MD Member of Vitreoretinal Division, Department of

Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of
Utah, Salt Lake City, UT, USA
Maggie M. Wei, BS National Eye Institute, National Institutes of Health, Bethesda,
MD, USA
Steven Yeh, MD Emory Eye Center, Atlanta, GA, USA
Chapter 1
Fluorescein Angiography in the Diagnosis
and Management of Uveitis

Albert T. Vitale and Nikhil N. Batra

Introduction

Fluorescein angiography (FA) is an essential tool in the diagnosis and management of

both infectious and noninfectious intraocular inflammations in patients with interme-
diate, posterior, and panuveitis [1–3]. While, in clinical practice, multimodal imaging
with color fundus photography, optical coherence tomography (OCT), indocyanine
green angiography (ICGA), and fundus autofluorescence (FAF) are frequently
employed in this setting, FA remains a highly sensitive technique for the assessment
of the presence and extent of active retinochoroidal and vascular inflammation, in
monitoring the response to and threshold for anti-inflammatory therapy and the iden-
tification of ocular structural abnormalities associated with visual loss. In some
instances, the type and pattern of vascular and/or retinochoroidal involvement seen on
FA may be particular to specific uveitic entities making it diagnostically very useful.
Fluorescein angiography employs fluorescein sodium (C20H10Na2O5), an orange-­
red crystalline hydrocarbon dye, with a molecular weight of 376 Da that is 80% bound
to protein (primarily albumin). Although the unbound form readily diffuses through
most body fluids including the choriocapillaris, the tight junctions of the retinal vas-
cular endothelial cells and the zona occludens joining adjacent RPE cells normally
prevent the molecule from entering potential spaces within the vitreous cavity, retinal
tissue, and subretinal space. The normal adult dosage is 500 mg [4].

A.T. Vitale, MD (*)

Member of Vitreoretinal Division, Department of Ophthalmology
and Visual Sciences, John A. Moran Eye Center, University of Utah,
Salt Lake City, UT, USA
e-mail: [email protected]
N.N. Batra, MD
Vitreoretinal Division, Section of Ophthalmology, Geisel School of Medicine at Dartmouth,
Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
e-mail: [email protected]

© Springer International Publishing AG 2018 1

H.N. Sen, R.W. Read (eds.), Multimodal Imaging in Uveitis,
https://doi.org/10.1007/978-3-319-23690-2_1
2 A.T. Vitale and N.N. Batra

Table 1.1 Reported complications of fluorescein angiography

Nausea
Vomiting
Allergy
 • Mild: pruritis, sneezing
 • Moderate: urticaria
 • Severe: laryngeal edema, bronchospasm, anaphylaxis
Cough
Dizziness
Vasovagal reaction
 • Syncope
 • Circulatory shock
 • Myocardial infarction
Extravasation and local tissue necrosis
Thrombophlebitis
Nerve palsy
Seizure
Death

Over 50 years of experience with fluorescein angiography has proven it to be a

relatively safe procedure. The most common side effects include nausea, vomiting,
and mild vasovagal reactions, which can occur in approximately 5–10% of patients
[5, 6]. Other side effects are listed in Table 1.1. Although no known teratogenic
effects have been reported, most clinicians avoid fluorescein angiography during
pregnancy, especially in the first trimester [7]. Fluorescein sodium is expressed in
the breast milk of lactating women, a consideration to be kept in mind should angi-
ography be necessary in a breastfeeding patient [8]. Sodium fluorescein is excited
by absorbed light energy in the blue spectrum (465–490 nm) and emits green-­yellow
light (520–530 nm) [9]. Digital-based fluorescein angiography has gained wide
acceptance, replacing film-based systems allowing rapid and easy archival and
retrieval of images for monitoring inflammatory disease progression and response
to treatment [2]. In addition, fluorescein angiography can be performed using a scan-
ning laser ophthalmoscope (SLO) based system which is covered in detail in Chap. 3.

Fluorescein Angiography Interpretation

FA provides both anatomic and functional information primarily with respect to the
retinal circulation and superficial retinal structures and secondarily of the underly-
ing RPE, choriocapillaris, subretinal, and choroidal disease processes (i.e., choroi-
dal neovascular membranes) in a dynamic fashion. The normal FA is divided into
discrete phases following the intravenous injection of dye:
1. Choroidal phase: within 10–15 s of injection, fluorescein first appears in the
choroid (choroidal flush) and the optic nerve.
2. Arterial phase: rapid arterial filling within 2 s following the choroidal phase.
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 3

3. Arteriovenous phase: laminar venous filling followed by full and equally bright
veins and arteries (20–30 s).
4. Recirculation phase: intravascular fluorescence then fades gradually leaving
veins brighter than the arteries. The angiogram is usually complete by 10 min.
Abnormal fluorescence patterns on FA denote pathology and are grouped into
two major categories: hypofluorescence and hyperfluorescence. Table 1.2 lists the
various causes and anatomical basis for these abnormal fluorescein angiography
patterns.

Table 1.2 Abnormal fluorescein angiography patterns

Hypofluorescencea Blockage
 • Blood
 • Pigment
 • Vitreous debris
 • Inflammatory lesions
Vascular filling defect
 • Obstruction
 • Congenital absence
 • Capillary non-perfusion
Hyperfluorescence Increased transmission (window defect)b
 • RPE atrophy
 • Macular hole
Leakage
 • Choroidal neovascularizationc
 • Optic disc edemad
 • Cystoid macular edemae
Staining
 • Inflammatory vasculitis (perivascular staining)f
 • Chorioretinal scar
 • Drusen
Pooling
 • Pigment epithelial detachment (PED)
 • Neurosensory or exudative detachmentg
Abnormal vessel caliber and shapeh
a
The approximate anatomic location of the blocking material can usually be ascertained by the
degree to which the visibility of fluorescence from the retinal or choroidal circulations is obscured.
For example, preretinal hemorrhage would be expected to block both retinal and choroidal fluores-
cence while hemorrhage located in the subretinal space would obstruct visibility of the choroidal
but not the retinal circulation. The distinction between blocked fluorescence and that due to a
hypoperfusion is critically important and usually requires correlation between the findings seen on
FA with those on ophthalmoscopy or fundus photography. Should the area of hypofluorescence
seen on FA match substances or lesions visible on clinical exam, blocked fluorescence is present;
however, if no corresponding blocking material is observed, hypofluorescence is due to a vascular
filling defect
b
Hyperfluorescence due to window defects parallels that of the choroidal fluorescence appearing
bright early and fading late, has distinct borders and is stable in size
c
Early, lacy hyperfluorescence is observed with CNVM, often before filling of the retinal vessels,
with late leakage into the retinal tissues and subretinal space
d
Dilated capillaries associated with inflammatory papillitis hyperfluorescence early and stain the
optic disc late, obscuring the disc margins to a variable degree depending on the degree of leakage,
(continued)
4 A.T. Vitale and N.N. Batra

Table 1.2 (continued)

while frank neovascularization of the disc (NVD) and retinal neovascularization elsewhere (NVE)
characteristically produce early, intense hyperfluorescence with progressive, profuse late leakage
of dye into the vitreous cavity
e
Leakage of dye with late pooling in the outer plexiform layer of the macula render the petaloid
pattern of hyperfluorescence seen with inflammatory macular edema (ME)
f
Retinal vascular occlusion with late staining (or leakage) of the vessel walls on the FA are the
hallmarks of retinal vasculitis
g
Early pinpoint leakage with progressive and expanding leakage at the level of the RPE with late
pooling of fluorescein in the subretinal space typify inflammatory subneurosensory exudative reti-
nal detachment
h
Abnormal retinal vessels are readily apparent as early and hyperfluorescent during vascular filling
phase with variable degrees of leakage in the later stages of the FA

Clinical Utility of FA

Optic Disc Inflammation

Inflammation of the optic nerve is a very common but non-specific sign of active
intraocular inflammation manifested clinically as hyperemia, absence of the cup,
and a variable degree of blurring of the disc margin (Table 1.3). Hyperfluorescence
of dilated disc capillaries is visualized early on FA as late staining of the optic disc
with the extent of disc margin obscuration depending on the degree of dye leakage
(Fig. 1.1a, b). Optic disc inflammation as seen on FA uniformly accompanies uve-
itic macular edema (ME) and, is useful in distinguishing it from noninflammatory
causes of ME and from other forms of optic disc involvement such as neuroretinitis.
Subtle optic nerve hyperfluorescence may denote subclinical inflammation and be
useful as a sign of active disease and in monitoring the response to anti-inflamma-
tory treatment.

Inflammatory Macular Edema

Macular edema is the leading cause of central visual loss among patients with uve-
itis [10, 11]. Inflammatory macular edema is thought to arise from the breakdown
of the inner blood retinal barrier mediated by inflammatory cytokines leading to
increased vascular permeability of the perifoveal capillaries and the accumulation
of fluid within in the outer plexiform layer and sub-neurosensory retina [12].
Angiographically, there is corresponding late leakage and pooling of fluorescein
dye into these spaces with the characteristic pattern of petaloid hyperfluorescence
together with optic disc staining (Table 1.3) (Fig. 1.2). Several studies have demon-
strated that OCT, a noninvasive, quantitative, reproducible modality for the mea-
surement of retinal thickness, can be as effective as FA in demonstrating ME in
patients with uveitis with visual loss correlated with central macular thickness and
the severity of leakage [13–15]. However, it is important to note that FA and OCT
measure different manifestations of an underlying inflammatory disease, the
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 5

Table 1.3 Posterior segment abnormalities associated with vison loss: clinical findings and FA
correlates
Structural abnormality Clinical findings FA findings
Optic disc inflammation Hyperemia, absence of physiologic Early hyperfluorescence of
cup, blurring of disc margin, dilated disc capillaries, late
hemorrhage staining and leakage
Neuroretinitis Features of optic disc inflammation Early hyperfluorescence and late
as above plus: staining of optic disc, no
 • Macular star leakage from macular capillaries
 • Exudative macular detachment
Inflammatory macular Loss of foveal depression Late petaloid leakage and
edema Macular thickening pooling, perifoveal capillary
Cysts hyperfluorescence
Retinal NVD: Abnormal vascular net, Profuse late leakage
Neovascularization hemorrhage, fibrovascular (intermediate uveitis, BD,
 – Neovascularization proliferation sarcoidosis, SLE, ANCA
of the disc (NVD) NVE: Hemorrhage at border of associated uveitis)
 – Neovascularization perfused and non-perfused retina,
elsewhere (NVE) fibrovascular proliferation,
tractional retinal detachment
Retinitis Yellow white retinal necrosis, Blockage from necrosis and
Hemorrhage, Associated vasculitis hemorrhage, peri-arteriolar
(arteritis), Vitritis leakage and staining (ARN,
CMV)
Retinochoroiditis Focal yellow-white lesion, Early blockage, late staining at
Pigmented scar, hemorrhage lesion borders, periphlebitic
Vitritis, associated vasculitis leakage and staining
(phlebitis)
Chorioretinitis Deep creamy lesions (often Early hypofluorescence from
multiple discrete or placoid), deep choroidal blockage, late
associated vasculitis (arteritis or staining at borders of lesions,
phlebitis), variable vitritis perivascular staining
(toxoplasmosis)
Exudative neurosensory Multifocal exudative retinal Multiple early pinpoint
retinal detachment detachments, optic disc edema, hyperfluorescent dots within
choroidal thickening exudative detachments, late
leakage and pooling into
sub-neurosensory space (VKH,
SO, sarcoidosis, posterior scleritis)
Choroidal Gray-Green subretinal lesion, Early lacy hyperfluorescence,
neovascularization Subretinal or intraretinal fluid Late leakage which obscures
Cystoid macular edema, pigmented borders of lesion (PIC,
scar MFC-PU, serpiginous, VKH,
BSRC, toxoplasmosis)
Outer retinal, RPE, Variable presentation depending on Early hypofluorescence with
choriocapillary disease; see text for descriptions of variable late staining (BSRC,
inflammatory disease specific entities Serpiginous, APMPPE), early
wreathlike hyperfluorescence
and late staining (MEWDS)
Retinal vasculitis Perivascular cream colored cuffs, See Tables 1.4, 1.5 and 1.6
vessel sheathing, exudation, micro
and macro aneurysms
6 A.T. Vitale and N.N. Batra

a b

Fig. 1.1 Optic disc inflammation: (a) FA showing early hyperfluorescence of dilated optic nerve
capillaries. (b) Late leakage obscuring the disc borders

Fig. 1.2 Inflammatory

macular edema: FA
showing petaloid
hyperfluorescence with
optic disc staining

pathophysiologic process of vascular leakage, and the anatomic changes in retinal

thickening (or thinning), respectively. Leakage seen on FA may not always be
accompanied by an increase in macular thickness on OCT (Fig. 1.3a, b). Conversely,
macular thickening may occur in the absence of ongoing vascular leakage with
RPE pump dysfunction in the presence of chronic intraretinal or subretinal fluid.
OCT may be the best test for the initial detection and longitudinal monitoring of
inflammatory ME; however, compensated leakage may be present in the absence of
retinal thickening and vice versa.
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 7

a b

Fig. 1.3 Compensated leakage: (a) macular hyperfluorescence on FA; (b) absence of frank
thickening or cysts on OCT

Retinal Vasculitis

Clinically, retinal vasculitis appears as perivascular, creamy-colored cuffs with

varying degrees of exudation and sheathing (Table 1.3). The pattern, type, extent,
and location of retinal vascular staining and leakage may be useful diagnostically
(Tables 1.4, 1.5 and 1.6). In addition, FA is essential for the identification and treat-
ment of vasculitic complications such as retinal nonperfusion, neovascularization,
telangiectasia, arterial-venous (AV) anastomosis, and micro- and macroaneurysms.
As with inflammatory ME, staining and leakage of the vessel walls are sensitive
indicators of inflammatory activity, such as in asymptomatic patients with pars
planitis or BSRC in the absence of clinically apparent signs and in vitrectomized
eyes in which the usual surrogate markers of activity (vitreous cells/haze) may have
been removed. Finally, FA is indicated in the evaluation and management of sys-
temic diseases with retinal vascular involvement such as Behçet’s disease (BD),
ANCA-­associated vasculitides, Susac’s syndrome, and systemic lupus erythemato-
sus (SLE) [16].
Uveitic entities commonly associated with retinal phlebitis and the correspond-
ing FA findings are described in Table 1.4. In sarcoidosis-associated periphlebitis,
the pattern of vascular staining and leakage is characteristically segmental or dis-
continuous and may be associated with yellow perivascular exudates described as
“taches de bougie” (candle wax drippings) (Fig. 1.4). In contrast, a more diffuse
pattern is observed in idiopathic retinal vasculitis and with CMV-associated frosted
branch angiitis [17] (Fig. 1.5). Retinal vascular involvement in pars planitis is
common and may exhibit both segmental and diffuse staining and leakage of the
veins with small vessel hyperfluorescence in a characteristic “fern pattern”
(Fig. 1.6) [18–21]. Wide field imaging may reveal more extensive peripheral vas-
cular staining and leakage than that visualized on conventional FA, particularly
8 A.T. Vitale and N.N. Batra

Table 1.4 Uveitic entities associated with predominantly retinal phlebitis

Staining Primary
Occlusive pattern location
vs. non (segmental (posterior pole
Condition occlusive vs. diffuse) vs. periphery) Other features
Idiopathic retinal Both Diffuse Both Macular Ischemia
vasculitis
Pars planitis Non Both Periphery “Fern pattern” hyperfluorescence
occlusive Peripheral nonperfusion
NVE
Birdshot (BSRC) Non Diffuse Posterior pole Optic disc staining and leakage
occlusive
Sarcoid Both Segmental Both Macroaneurysms
NVE
Tuberculosis Non Segmental Posterior pole Neuroretinitis
occlusive Focal choroiditis
NVE
Eales’ disease Occlusive Segmental Periphery Peripheral nonperfusion
Small vessel BRVO
NVE
Toxoplasmosis Non Both Posterior pole Typical focal retinochoroiditis
occlusive lesion
HIV retinopathy Occlusive Segmental Both Microvasculopathy
CMV retinitis Both Diffuse Both Characteristic necrotic
chorioretinal lesion
Multiple sclerosis Non Both Periphery May be transient
occlusive

Table 1.5 Uveitic entities associated with predominantly retinal arteritis

Staining pattern Primary location
Occlusive vs. (segmental vs. (posterior pole
Condition non occlusive diffuse) vs. periphery) Other features
HSV (ARN) Occlusive Diffuse Both Necrotizing Retinitis
VZV (PORN)
Syphilis Non occlusive Diffuse Both Chorioretinitis
CME
Disc edema
Susac’s Syndrome Occlusive Segmental Both Multiple BRAO with
minimal leakage
IRVAN Occlusive Segmental Both Microaneurysms
Neuroretinitis
Peripheral nonperfusion
SLE Occlusive Both Both BRAO
NVE, NVD
Cotton wool spots
Peripheral nonperfusion
ANCA associated Occlusive Segmental Both Delayed choroidal
(polyarteritis filling
Nodosa, Churg
strauss)
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 9

Table 1.6 Uveitic entities associated with both retinal phlebitis and arteritis
Staining pattern Primary location
Occlusive vs. (segmental vs. (posterior pole Other
Condition non occlusive diffuse) vs. periphery) features
Behçet’s Disease (BD) Both Both Both Macular
ischemia
NVE
CME
Granulomatosis with Occlusive Both Both Rare
polyangiitis (Wegener’s)

a b

Fig. 1.4 Ocular sarcoid: (a) color photograph showing yellow, perivascular exudates (“taches de
bougie”); (b) FA with corresponding segmental periphlebitis and optic nerve leakage (Courtesy of
Ramana Moorthy, MD, FACS)

Fig. 1.5 Color photograph

showing diffuse retinal
periphlebitis (“frosted
branch angiitis”)
associated with CMV
retinitis
10 A.T. Vitale and N.N. Batra

Fig. 1.6 Wide angle FA

showing capillary leakage
in a “fern pattern”

a b

Fig. 1.7 (a) Color fundus photograph with clinically unapparent vasculitis in a birdshot retinocho-
roidopathy patient. (b) Extensive periphlebitis and optic nerve leakage on FA

when posterior pole involvement is absent [22, 23]. In the management of BSRC,
FA reveals critical components of disease activity including the extent of periphle-
bitis and optic nerve leakage which may not be appreciated on clinical exam
(Fig. 1.7a, b).
Posterior and panuveitis primarily associated with retinal arteritis are high-
lighted in Table 1.5. Occlusive arteriolar vasculopathy is invariably present
and is a diagnostic criterion for the acute retinal necrosis syndrome (ARN)
[24] (Fig. 1.8). The FA in Susac’s syndrome discloses characteristic focal, non-
perfused arterioles with multiple areas of segmental staining remote from sites
of bifurcation [25] (Fig. 1.9). The salient diagnostic features of IRVAN syndrome,
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 11

a b

Fig. 1.8 Acute retinal necrosis: (a) color photograph showing confluent retinitis and arteritis.
(b) Corresponding FA reveals occlusive arteriolitis

a b

Fig. 1.9 Susac’s syndrome: (a) color photograph depicting ischemic retinal whitening corre-
sponding to superotemporal branch artery occlusions; (b) FA showing superotemporal branch arte-
riole occlusions with multiple areas of segmental staining remote from sites of bifurcation

retinal arterial vasculitis, multiple macroaneurysms, and neuroretinitis are

highlighted by FA and may help guide treatment with laser photocoagulation
in the presence of significant capillary ­nonperfusion [26] (Fig. 1.10a, b).
Retinal arterial macroaneurysms, while uncommon in uveitis patients in gen-
eral, may be seen with peripheral multifocal chorioretinitis associated with
sarcoidosis [27–29].
The retinopathy associated with SLE and ANCA-associated vasculitides
typically arise from vaso-occlusive events primarily involving the retinal arte-
riolar and choroidal vasculature in the absence intraocular inflammation and
are considered important markers of systemic disease activity [30–32]. The
hallmarks of occlusive retinal vasculitis/vasculopathy on FA include retinal
capillary dropout, nonperfusion, and retinal vascular staining and leakage
which may involve the retinal arterioles, venules, or both. Structural complica-
tions due to consequent retinal ischemia including NVD and NVE, as well as
12 A.T. Vitale and N.N. Batra

a b

Fig. 1.10 Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN). (a) Early FA dem-
onstrating multiple arterial macroaneurysms. (b) Late leakage from optic nerve and aneurysms

Fig. 1.11 Occlusive

retinal vasculitis: FA shows
extensive peripheral
nonperfusion, retinal
vascular staining of both
arterioles and venules, and
arteriovenous anastomoses

those arising from post-occlusive vascular remodeling, such as retinal telangi-

ectasias, microaneurysms, and AV anastomoses may be identified and distin-
guished on the basis of their FA leakage patterns (Fig. 1.11).
The retinal vasculitis associated with Behçet’s disease (BD) and granulomatosis
with polyangiitis (GPA, previously known as Wegener’s Granulomatosis) may
involve both the arterioles and veins and be leaky and/or occlusive (Fig. 1.12).
Fluorescein angiography is essential in the early detection of inflammatory activity
and structural complications in BD. It is also useful to monitor the efficacy of treat-
ment modalities and can be used prognostically as macular ischemia and NVD have
been associated with increased risk of visual loss in patients with BD [33, 34].
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 13

Fig. 1.12 Behçet’s

disease: occlusive retinal
vasculitis with enlargement
of the foveal avascular
zone, temporal macular
nonperfusion, and vascular
remodeling

a b

Fig. 1.13 Retinal neovascularization: (a) FA showing inflammatory disc neovascularization in

pars planitis; (b) FA showing ischemic peripheral neovascularization in Eales’ disease. Also, note
the tortuosity and collaterals proximal to the area of neovascularization

Retinal Neovascularization

Retinal neovascularization (neovascularization of the disc or elsewhere, NVD or

NVE) may complicate the course of a variety uveitic entities and arises as a conse-
quence of retinal ischemia or may be driven by inflammatory mediators alone [35]
(Table 1.3). Peripheral retinal neovascularization typically occurs at the border of
perfused and nonperfused retina and leaks profusely in the late stages of the FA,
whereas AV anastomosis does not. The distinction between inflammatory vs. isch-
emic neovascularization by FA, as well as the identification of post-occlusive vas-
cular abnormalities, is essential as the treatment of each is markedly different
(Fig. 1.13a, b). Disc neovascularization due to persistent intraocular inflammation
14 A.T. Vitale and N.N. Batra

may respond to more aggressive anti-inflammatory therapy alone, whereas NVE

associated with peripheral nonperfusion requires laser photocoagulation, and non-­
leaky shunt vessels may be safely observed [36].

Retinitis, Retinochoroiditis, and Chorioretinitis

Fluorescein angiography is not routinely necessary in the evaluation of most infec-

tious causes of retinitis and retinochoroiditis, but may highlight more extensive
pathology than that seen on ophthalmoscopy, and the pattern seen on FA may be so
stereotypical as to be virtually pathognomonic. For example, acute posterior placoid
chorioretinitis with early hypofluorescence and typical late macular hyperfluores-
cence without exudative detachment is highly suggestive of syphilis [37] (Fig. 1.14a–c).
In West Nile virus (WNV), FA reveals early hypofluorescence with late staining of

a b

Fig. 1.14 Syphilitic posterior placoid chorioretinitis: (a) color photograph showing a pale yellow
subretinal lesion in macula with concomitant papillitis. (b) Early FA with patchy hypofluorescence
along margins of the lesion. (c) Late FA with staining of the placoid lesion with a background of
persistent hypofluorescence and optic disc leakage
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 15

the lesions, while in the subacute phase, there is central hypofluorescence with
peripheral hyperfluorescence creating a targetoid appearance secondary to central
blockage from pigment and peripheral hyperfluorescence due to atrophy (Fig. 1.15).
These angiographic findings, together with a linear clustering of chorioretinal
lesions following the course of the nerve fibers, are highly suggestive of the diagno-
sis of WNV infection [38].
Active and recurrent toxoplasmosis lesions typically block dye early and stain
late from the borders and may be associated with vascular changes primarily
involving the retinal veins but also the arterioles with plaques known as Kyrieleis
arteritis (Table 1.4) (Fig. 1.16). Active choroidal lesions such as those associated

Fig. 1.15 West Nile virus

choroiditis (subacute
phase): FA reveals
characteristic targetoid
central hypofluorescence
with peripheral
hyperfluorescence together
with linear clustering of
chorioretinal lesions

Fig. 1.16 Toxoplasmic

retinochoroiditis: color
photograph of Kyrieleis
perivascular plaques
16 A.T. Vitale and N.N. Batra

with tuberculosis typically exhibit early hypo- or isofluorescence with intense late
hyperfluorescent staining. A segmental retinal periphlebitis involving the post
equatorial veins may also be associated with tuberculosis with active or healed
focal choroidal lesions along the retinal vessels [39–42]. Inactive chorioretinal
lesions and scars typically display early hyperfluorescence with late staining or
window defects.

Exudative Neurosensory Retinal Detachment

Exudative neurosensory retinal detachment develops during the acute uveitic

phase of Vogt-Koyanagi-Harada (VKH) syndrome [43] but may also compli-
cate the course of sympathetic ophthalmia (SO) [44], sarcoidosis-associated
uveitis [45], and posterior scleritis [46] and less commonly in APMPPE [47]
and SLE [48] (Table 1.3). Fluorescein angiography in both VKH and SO dem-
onstrates optic disc leakage and a delay in choroidal perfusion seen as choroi-
dal hypofluorescence during the acute uveitic phase [49]. Multiple, bilateral,
pinpoint hyperfluorescent dots at the level of the RPE are visualized during the
early and mid-phase of the study which increase in intensity, gradually enlarge
and leak with pooling of dye in the sub-neurosensory space in the late phase of
the angiogram (Fig. 1.17a, b). Vascular staining and leakage can also be seen.
In the chronic stage of the disease, RPE atrophy and pigment hyperplasia may
develop with corresponding window and blocking defects seen on FA. These
RPE changes may evolve into a salt and pepper appearance during the conva-
lescent stage with alternating areas of hypofluorescence and hyperfluorescence
[50, 51].

a b

Fig. 1.17 Vogt-Koyanagi-Harada syndrome: (a) early FA with multiple pinpoint hyperfluorescent
dots at the level of the RPE. (b) Late FA with typical leakage and pooling of dye in the sub-neuro-
sensory space
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 17

Choroidal Neovascularization

Choroidal neovascular membrane (CNVM) may complicate both infectious and

noninfectious posterior and panuveitis, with the potential for severe visual loss.
Inflammatory CNVM develops most often in a Type 2 subretinal neovascular
pattern in which pathologic vessels penetrate through Bruch’s membrane and
proliferate above the RPE within the subretinal space [52]. Angiographically, a
lacy hyperfluorescence corresponding to pathologic vessels is observed, often
before complete filling of the retinal vessels, with late leakage of dye into the
retinal tissues and subretinal space (Table 1.3) (Fig. 1.18a, b). Uveitic entities at
highest risk for the development of CNVM include punctate inner choroidopa-
thy (PIC), multifocal choroiditis and panuveitis (MFC-PU), and VKH and is a
well-described complication of serpiginous choroiditis, BSRC, toxoplasma reti-
nochoroiditis, and other chorioretinal inflammatory entities, albeit less fre-
quently [50, 53, 54].

Outer Retinal, RPE, and Choriocapillary Inflammatory Disease

Multimodal imaging with FA, FAF, OCT, and ICG provides invaluable information
with respect to the nature and location of the pathologic process in a variety of pos-
terior uveitic entities such as those included in the white dot syndromes, posterior
scleritis, and SLE-associated vasculopathy that may affect the inner and/or outer
retina/photoreceptor complex, RPE, choriocapillaris, and choroid [55]. ICGA is the
best tool for the evaluation of the choriocapillaris and the choroid (see Chap. 2).

a b

Fig. 1.18 CNVM complicating punctate inner choroidopathy (PIC). (a) Early lacy hyperfluores-
cence with surrounding blocked fluorescence due to blood and hyperfluorescence of the PIC
lesions. (b) Late leakage of dye from the neovascular complex superior to fovea and staining of the
PIC lesions inferiorly
18 A.T. Vitale and N.N. Batra

a b

Fig. 1.19 Birdshot retinochoroidopathy: (a) late FA highlights periphlebitis, macular capillary,
and optic disc leakage; (b) ICGA reveals hypofluorescent dots more numerous than those seen on
FA or clinical exam

Similarly, ICGA may be a useful adjunct to FA in the detection of occult or recur-

rent CNVM. Likewise, OCT and FAF provide detailed anatomic information with
respect to the integrity of the outer retinal layers and RPE which complement that
obtained from FA studies.
For example, the choroidal lesions of BSRC demonstrate angiographic hetero-
geneity on FA being influenced by the age, degree of inflammatory activity, and
the presence of multiple lesions at different stages of evolution in the same eye. In
contrast, ICGA discloses multiple hypofluorescent spots which are more numer-
ous than those seen on FA and biomicroscopy (Fig. 1.19a, b). Patients with recent
active disease may have fuzzy indistinct choroidal vessels and late diffuse choroi-
dal hyperfluorescence which may respond to therapy to some degree [56, 57].
Similarly, the evaluation of toxoplasmosis retinochoroiditis with both FA and ICG
reveals multiple hypofluorescent satellite dark spots present in the majority of
eyes with active retinochoroiditis, highlighting features not evident on clinical
exam [58, 59].
In serpiginous choroiditis, the FA shows early hypofluorescence at the edge the
acute lesion with late brush fire staining and variable leakage at its margin, while on
FAF imaging, this same area of activity is visualized as hyperautofluorescent [60]
(Fig. 1.20a–c). Similarly, the hypofluorescence visualized throughout all phases of
ICGA matches the hypoautofluorescence seen on FAF, corresponds the area of RPE
and choroidal loss, and is larger than that seen on FA and may be valuable in assess-
ing and monitoring the extent of the disease activity. A localized spot of hyperfluo-
rescence in the mid-phase of the ICGA may be indicative of the presence of a
CNVM.
In the acute stages of APMPPE, both the FA and ICGA show early hypo-
fluorescence of the lesions, more numerous than the placoid lesions seen by
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THE SPELL OF SCOTLAND

THE SPELL SERIES

 Each volume with one or more
colored plates and many
illustrations from original drawings
or special photographs. Octavo,
decorative cover, gilt top, boxed.
Per volume, net $2.50; carriage
paid $2.70
By Isabel Anderson
THE SPELL OF BELGIUM
THE SPELL OF JAPAN
THE SPELL OF THE HAWAIIAN
ISLANDS AND THE PHILIPPINES
By Caroline Atwater Mason
THE SPELL OF ITALY
THE SPELL OF SOUTHERN
SHORES
THE SPELL OF FRANCE
By Archie Bell
THE SPELL OF EGYPT
THE SPELL OF THE HOLY LAND
By Keith Clark
THE SPELL OF SPAIN
THE SPELL OF SCOTLAND
By W. D. McCrackan
THE SPELL OF TYROL
THE SPELL OF THE ITALIAN
LAKES
By Edward Neville Vose
THE SPELL OF FLANDERS
By Burton E. Stevenson
THE SPELL OF HOLLAND
By Julia De W. Addison
THE SPELL OF ENGLAND
By Nathan Haskell Dole
THE SPELL OF SWITZERLAND

THE PAGE COMPANY

53 Beacon Street
Boston, Mass.
The Pass of Killiecrankie
(See page 195)
 The
Spell of Scotland
 BY
Keith Clark
Author of "The Spell of Spain," etc.

"A Traveller may lee wi authority." (Scotch Proverb)

ILLUSTRATED

BOSTON
THE PAGE COMPANY
MDCCCCXVI

Copyright, 1916, by
The Page Company

All rights reserved

First Impression, November, 1916

THE COLONIAL PRESS

C. H. SIMONDS COMPANY, BOSTON, U. S. A.
 TO

THE LORD MARISCHAL

 CONTENTS

CHAPTER PAGE
I. Hame, Hame, Hame! 1
II. Scotts-Land 24
III.Border Towns 53
IV. The Empress of the North 82
V. The Kingdom of Fife 149
VI. To the North 171
VII. Highland and Lowland 194
VIII. The Circle Round 220
IX. The Western Isles 252
X. The Lakes 277
XI. The West Country 314
Bibliography 335
Index 339
 LIST OF ILLUSTRATIONS

PAGE
The Pass of Killiecrankie (in full colour) (See page 195) Frontispiece
MAP OF SCOTLAND 1
James VI 6
Queen Mary 15
James II 25
Melrose Abbey 34
Abbotsford (in full colour) 41
The Study, Abbotsford 45
St. Mary's Aisle and Tomb of Sir Walter Scott, Dryburgh
51
Abbey
Jedburgh Abbey 63
Hermitage Castle 66
Newark Castle 74
Interior View, Tibbie Shiel's Inn 77
St. Mary's Lake 80
Edinburgh Castle (in full colour) 86
Mons Meg 90
Greyfriars' Churchyard 96
Moray House 102
Interior of St. Giles 104
John Knox's House 106
James Graham, Marquis of Montrose 108
Holyrood Palace 111
James IV 115
Margaret Tudor, Queen of James IV 124
Bothwell Castle (in full colour) 131
Princes Street 134
John Graham of Claverhouse, Viscount Dundee 142
Tantallon Castle 157
St. Andrews Castle 165
Drawing-room, Linlithgow Palace, where Queen Mary was
184
Born
Huntington Tower 190
Glamis Castle 194
Glen Tilt 197
Invercauld House 200
Balmoral Castle 205
Marischal College 207
Dunnottar Castle 212
Spynie Castle 224
Cawdor Castle (in full colour) 227
Battlefield of Culloden 232
The Old Man of Hoy 237
Earl's Palace, Kirkwall 240
Invergarry Castle 248
Kilchurn Castle 258
Aros Castle 265
Entrance to Fingal's Cave 267
Cathedral of Iona and St. Martin's Cross 273
Dumbarton Castle 282
Loch Katrine 289
The Brig o' Turk 294
The Trossachs (in full colour) 296
Stirling Castle (in full colour) 304
Doune Castle 310
Portrait of Thomas Carlyle, by Whistler 317
Ayr River (in full colour) 322
Burns' Cottage, Birth-place of Robert Burns, Ayr 328
Caerlaverock Castle 333
Click here for larger size
 THE
SPELL OF SCOTLAND
 CHAPTER I
HAME, HAME, HAME!

"It's hame, and it's hame, hame fain wad I be,

And it's hame, hame, hame, to my ain
countree!"
ime was when half a hundred ports ringing round the semi-
island of Scotland invited your boat to make harbour; you
could "return" at almost any point of entry you chose, or
chance chose for you.
To-day, if you have been gone for two hundred and fifty years, or
if you never were "of Scotia dear," except as a mere reading person
with an inclination toward romance, you can make harbour after a
transatlantic voyage at but one sea-city, and that many miles up a
broad in-reaching river. Or, you can come up the English roads by
Carlisle or by Newcastle, and cross the Border in the conquering
way, which never yet was all-conquering. There is shipping, of
course, out of the half hundred old harbours. But it is largely the
shipping that goes and comes, fishing boats and coast pliers and the
pleasure boats of the western isles.
You cannot come back from the far corners of the earth—to which
Scotland has sent such majorities of her sons, since the old days
when she squandered them in battle on the Border or on the
Continent, to the new days when she squanders them in colonization
so that half a dozen of her counties show decline in population—but
you must come to Glasgow. The steamers are second-class
compared with those which make port farther south. They are
slower. But their very lack of modern splendour and their slow speed
give time in which to reconstruct your Scotland, out of which
perhaps you have been banished since the Covenant, or the Fifteen,
or the Forty Five; or perhaps out of which you have never taken the
strain which makes you romantic and Cavalier, or Presbyterian and
canny. We who have it think that you who have it not lose
something very precious for which there is no substitute. We pity
you. More clannish than most national tribesmen, we cannot
understand how you can endure existence without a drop of Scotch.
Always when I go to Scotland I feel myself returning "home."
Notwithstanding that it is two centuries and a bittock since my
clerical ancestor left his home, driven out no doubt by the fluctuant
fortunes of Covenanter and Cavalier, or, it may be, because he
believed he carried the only true faith in his chalice—only he did not
carry a chalice—and, either he would keep it undefiled in the New
World, or he would share it with the benighted in the New World; I
know not.
All that I know is that in spite of the fact that the Scotch in me has
not been replenished since those two centuries and odd, I still feel
that it is a search after ancestors when I go back to Scotland. And, if
a decree of banishment was passed by the unspeakable Hanoverians
after the first Rising, and lands and treasure were forfeited, still I
look on entire Scotland as my demesne. I surrender not one least
portion of it. Not any castle, ruined or restored, is alien to me.
Highlander and Lowlander are my undivisive kin. However empty
may seem the moorlands and the woodlands except of grouse and
deer, there is not a square foot of the twenty-nine thousand seven
hundred eighty-five square miles but is filled for me with a longer
procession, if not all of them royal, than moved ghostly across the
vision of Macbeth.
Nothing happens any longer in Scotland. Everything has
happened. Quite true, Scotland may some time reassert itself,
demand its independence, cease from its romantic reliance on the
fact that it did furnish to England, to the British Empire, the royal
line, the Stewarts. Even Queen Victoria, who was so little a Stewart,
much more a Hanoverian and a Puritan, was most proud of her
Stewart blood, and regarded her summers in the Highlands as the
most ancestral thing in her experience.
Scotland may at sometime dissolve the Union, which has been a
union of equality, accept the lower estate of a province, an American
"state," among the possible four of "Great Britain and Ireland," and
enter on a more vigorous provincial life, live her own life, instead of
exporting vigour to the colonies—and her exportation is almost
done. She may fill this great silence which lies over the land, and is
fairly audible in the deserted Highlands, with something of the
human note instead of the call of the plover.
But, for us, for the traveler of to-day, and at least for another
generation, Scotland is a land where nothing happens, where
everything has happened. It has happened abundantly,
multitudinously, splendidly. No one can regret—except he is a
reformer and a socialist—the absence of the doings of to-day; they
would be so realistic, so actual, so small, so of the province and the
parish. Whereas in the Golden Age, which is the true age of
Scotland, men did everything—loving and fighting, murdering and
marauding, with a splendour which makes it seem fairly not of our
kind, of another time and of another world.
You must know your Scottish history, you must be filled with
Scottish romance, above all, you must know your poetry and ballads,
if you would rebuild and refill the country as you go. Not only over
fair Melrose lies the moonlight of romance, making the ruin more
lovely and more complete than the abbey could ever have been in its
most established days, but over the entire land there lies the silver
pall of moonlight, making, I doubt not, all things lovelier than in
reality.
We truly felt that we should have arranged for "a hundred pipers
an' a' an' a'." But we left King's Cross station in something of
disguise. The cockneys did not know that we were returning to
Scotland. Our landing was to be made as quietly, without pibroch, as
when the Old Pretender landed at Peterhead on the far northeastern
corner, or when the Young Pretender landed at Moidart on the far
western rim of the islands. And neither they nor we pretenders.

JAMES VI.
The East Coast route is a pleasant way, and I am certain the
hundred pipers, or whoever were the merry musicmakers who led
the English troops up that way when Edward First was king, and all
the Edwards who followed him, and the Richards and the Henrys—
they all measured ambition with Scotland and failed—I am certain
they made vastly more noise than this excellently managed railway
which moves across the English landscape with due English
decorum.
We were to stop at Peterborough, and walk out to where, "on that
ensanguined block at Fotheringay," the queenliest queen of them all
laid her head and died that her son, James Sixth of Scotland, might
become First of England. We stopped at York for the minster, and
because Alexander III was here married to Margaret, daughter of
Henry III; and their daughter being married to Eric of Norway in
those old days when Scotland and Norway were kin, became mother
to the Maid of Norway, one of the most pathetic and outstanding
figures in Scottish history, simply because she died—and from her
death came divisions to the kingdom.
We paused at Durham, where in that gorgeous tomb St. Cuthbert
lies buried after a brave and Scottish life. We only looked across the
purpling sea where already the day was fading, where the slant rays
of the sun shone on Lindisfarne, which the spirit of St. Cuthbert
must prefer to Durham.
All unconsciously an old song came to sing itself as I looked across
that wide water—
"My love's in Germanie,
Send him hame, send him hame,
My love's in Germanie,
Fighting for royalty,
He's as brave as brave can be,
Send him hame, send him hame!"
Full many a lass has looked across this sea and sung this lay—and
shall again.
The way is filled with ghosts, long, long processions, moving up
and down the land. A boundary is always a lodestone, a lodeline.
Why do men establish it except that other men dispute it? In the old
days England called it treason for a Borderer, man or woman, to
intermarry with Scotch Borderer. The lure, you see, went far. Even so
that kings and ladies, David and Matilda, in the opposing edges of
the Border, married each other. And always there was Gretna Green.
Agricola came this way, and the Emperor Severus. There is that
interesting, far-journeying Æneas Sylvius Piccolomini, the "Gil Blas of
the Middle Ages," who later became Pius II. He came to this country
by boat, but becoming afraid of the sea, returned by land, even
opposite to the way we are going. Froissart came, but reports little.
Perhaps Chaucer, but not certainly. George Fox came and called the
Scots "a dark carnal people."
With the Act of Union the stream grows steady and full. There is
Ben Jonson, trudging along the green roadway out yonder; for on
foot, and all the way from London, he came northward to visit
William Drummond of Hawthornden. Who would not journey to such
a name? But, alas, a fire destroyed "my journey into Scotland sung
with all the adventures." All that I know of Ben is that he was
impressed with Lomond—two hundred years before Scott.
And there trails Taylor, "water poet," hoping to rival Rare Ben, on
his "Pennyless Pilgrimage," when he actually went into Scotland
without a penny, and succeeded in getting gold to further him on his
way—"Marr, Murraye, Elgin, Bughan, and the Lord of Erskine, all of
these I thank them, gave me gold to defray my charges in my
journey."
James Howell, carries a thin portfolio as he travels the highway.
But we must remember that he wrote his "Perfect Description of the
People and Country of Scotland" in the Fleet.
Here is Doctor Johnson, in a post chaise. Of course, Sir! "Mr.
Boswell, an active lively fellow is to conduct me round the country."
And he's still a lively conductor. Surely you can see the Doctor, in his
high boots, and his very wide brown cloth great coat with pockets
which might be carrying two volumes of his folio dictionary, and in
his hand a large oak staff. One tries to forget that years before this
journey he had said to Boswell, "Sir, the noblest prospect that a
Scotchman ever sees is the highroad that leads him to London."
And, was there any malice in Boswell's final record—"My illustrious
friend, being now desirous to be again in the great theater of life
and animated existence"?
The poet Gray preceded him a little, and even John Wesley moves
along the highroad seeking to save Scottish souls as well as English.
A few years afterward James Hogg comes down this way to visit his
countryman, Tammas Carlyle in London; who saw Hogg as "a little
red-skinned stiff rock of a body with quite the common air of an
Ettrick shepherd."
There is Scott, many times, from the age of five when he went to
Bath, till that last journey back from Italy—to Dryburgh! And
Shadowy Jeanie Deans comes downward, walking her "twenty-five
miles and a bittock a day," to save her sister from death.
Disraeli comes up this way when he was young and the world was
his oyster. Stevenson passes up and down, sending his merry men
up and down. And one of the most native is William Winter—"With a
quick sense of freedom and of home, I dashed across the Border
and was in Scotland."
There is a barricade of the Cheviots stretching across between the
two countries, but the Romans built a Wall to make the division
more apparent. In the dawn of the centuries the Romans came
hither, and attempting to come to Ultima Thule, Picts and Scots—
whatever they were, at least they were brave—met the Romans on
the Border, as yet unreported in the world's history and undefined in
the world's geography, and sent them back into what is England.
The Romans in single journeys, and in certain imperial attempts, did
penetrate as far as Inverness. But they never conquered Scotland.
Only Scotland of all the world held them back. And in order to define
their defeat and to place limits to the unlimited Roman Empire, the
Great Wall was built, built by Hadrian, that men might know where
civilization, that splendid thing called Roman civilization, and
barbarism did meet. Scotland was barbarism. And I think, not in
apology but in all pride, she has remained something of this ever
since. Never conquered, never subdued.
The Wall was, in truth, a very palpable thing, stretching from the
Solway to the North Sea at the Tyne, with ample width for the
constant patrol, with lookout towers at regular and frequent
intervals, with soldiers gathered from every corner of the Empire,
often the spawn of it, and with much traffic and with even
permanent villas built the secure side of the barrier. If you meet
Puck on Pook's hill, he will tell you all about it.
Our fast express moves swiftly northward, through the littoral of
Northumberland, as the ship bearing Sister Clare moved through the
sea—
"And now the vessel skirts the strand
Of mountainous Northumberland;
Towns, towers, and hills successive rise,
And catch the nun's delighted eyes."

Berwick

The voyager enters Berwick with a curious feeling. It is because of

the voyagers who have preceded him that this town is singular
among all the towns of the Empire. It is of the Empire, it is of
Britain; but battled round about, and battled for as it has been since
ambitious time began, it is of neither England nor Scotland. "Our
town of Berwick-upon-Tweed," as the phrase still runs in the acts of
Parliament, and in the royal proclamations; not England's, not
Scotland's. Our town, the King's town.
For it is an independent borough (1551) since the men who fared
before us could not determine which should possess it, and so our
very own time records that history in an actual fact. I do not
suppose the present serious-looking, trades-minded people of the
city, with their dash of fair Danish, remember their singular situation
day by day. The tumult and the shouting have died which made "the
Border" the most embattled place in the empire, and Berwick-upon-
Tweed the shuttlecock in this international game of badminton.
It is a dual town at the best. But what has it not witnessed, what
refuge, what pawn, has it not been, this capital of the Debatable
Land, this Key of the Border.
The Tweed is here spanned by the Royal Border Bridge, opened in
1850, and called "the last Act of Union." But there is another bridge,
a Roman bridge of many spans, antique looking as the Roman-
Moorish-Spanish bridge at Cordova, and as antique as 1609, an Act
of Union following swiftly on the footsteps of King James VI—who
joyously paused here to fire a salute to himself, on his way to the
imperial throne.
The walls of Berwick, dismantled in 1820 and become a
promenade for peaceful townsfolk and curious sightseers, date no
farther back than Elizabeth's time. But she had sore need of them;
for this "our town," was the refuge for her harriers on retaliatory
Border raids, particularly that most terrible Monday-to-Saturday
foray of 1570, that answer to an attempt to reassert the rights of
Mary, when fifty castles and peels and three hundred villages were
laid waste in order that Scotland might know that Elizabeth was
king.
It was her kingly father, the Eighth Henry, who ordered Hertford
into Scotland—"There to put all to fire and sword, to burn Edinburgh
town, and to raze and deface it, when you have sacked it and gotten
what you can of it, as there may remain forever a perpetual memory
of the vengeance of God lighted upon it for their falsehood and
disloyalty. Sack Holyrood House and as many towns and villages
about Edinburgh as ye conveniently can. Sack Leith and burn it and
subvert it, and all the rest, putting man, woman and child to fire and
sword without exception, when any resistance is made against you.
And this done, pass over to the Fife land, and extend like extremities
and destructions in all towns and villages whereunto ye may reach
conveniently, not forgetting among the rest, so to spoil and turn
upside down the Cardinal's town of St. Andrews, as the upper stone
may be the nether, and not one stick stand by another, sparing no
creature alive within the same, especially such as either in friendship
or blood be allied to the Cardinal. The accomplishment of all this
shall be most acceptable to the Majesty and Honour of the King."
Berwick has known gentler moments, even marrying and giving in
marriage. It was at this Border town that David, son of the Bruce,
and Joanna, sister of Edward III, were united in marriage. Even then
did the kingdoms seek an Act of Union. And Prince David was four,
and Princess Joanna was six. There was much feasting by day and
much revelry by night, among the nobles of the two realms, while,
no doubt, the babies nodded drowsily.
 QUEEN MARY.
At Berwick John Knox united himself in marriage with Margaret
Stewart, member of the royal house of Stewart, cousin, if at some
remove, from that Stewart queen who belonged to "the monstrous
regiment of women," and to whose charms even the Calvinist John
was sensitive. One remembers that at Berwick John was fifty, and
Margaret was sixteen.
There is not much in Berwick to hold the attention, unless one
would dine direct on salmon trout just drawn frae the Tweed. There
are memories, and modern content with what is modern.
Perhaps the saddest eyes that ever looked on the old town were
those of Queen Mary, as she left Jedburgh, after her almost fatal
illness, and after her hurried ride to the Hermitage to see Bothwell,
and just before the fatal affair in Kirk o' Field. Even then, and even
with her spirit still unbroken, she felt the coming of the end. "I am
tired of my life," she said more than once to Le Croc, French
ambassador, on this journey as she circled about the coast and back
to Edinburgh.
She rode toward Berwick with an escort of a thousand men, and
looked down on the town from Halidon Hill, on the west, where two
hundred years before (1333) the Scots under the regent Douglass
had suffered defeat by the English.
It was an old town then, and belonged to Elizabeth. But it looked
much as it does to-day; the gray walls, so recently built; the red
roofs, many of them sheltering Berwickians to-day; the church
spires, for men worshiped God in those days in churches, and
according to the creeds that warred as bitterly as crowns; masts in
the offing, whence this last time one might take ship to France, that
pleasant smiling land so different from this dour realm. At all these
Mary must have looked wistfully and weariedly, as the royal salute
was fired for this errant queen. She looked also, over the Border,
then becoming a hard-and-fast boundary, and down the long, long
road to Fotheringay, and to peace at last and honour, in the Abbey.
It is well to stand upon this hill, before you go on to the West and
the Border, or on to the North and the gray metropolis, that you may
appreciate both the tragedy and the triumph that is Scotland's and
was Mary's. The North Sea is turning purple far out on the horizon,
and white sea birds are flying across beyond sound. The long level
light of the late afternoon is coming up over England. In the
backward of the Border a plaintive curlew is crying in the West, as
he has cried since the days of Mary, and æons before.
 Flodden

You may go westward from here, by train and coach, and carriage
and on foot, to visit this country where every field has been a
battlefield, where ruined peel towers finally keep the peace, where
castles are in ruins, and a few stately modern homes proclaim the
permanence of Scottish nobility; and where there is no bird and no
flower unsung by Scottish minstrelsy, or by Scott. Scott is, of course,
the poet and prose laureate of the Border. "Marmion" is the lay,
almost the guide-book. It should be carried with you, either in
memory or in pocket.
If the day is not too far spent, the afternoon sun too low, you can
make Norham Castle before twilight, even as Marmion made it when
he opened the first canon of Scott's poem—
"Day set on Norham's castle steep
And Tweed's fair river, broad and deep,
And Cheviot's mountains lone;
The battled towers, the donjon keep,
The loophole grates, where captives weep,
The flanking walls that round it sweep,
In yellow luster shone."
There is but a fragment of that castle remaining, and this, familiar
to those who study Turner in the National Gallery. A little village with
one broad street and curiously receding houses attempts to live in
the shadow of this memory. The very red-stone tower has stood
there at the top of the steep bank since the middle Eleven
Hundreds. Henry II held it as a royal castle, while his craven son
John—not so craven in battle—regarded it as the first of his
fortresses. Edward I made it his headquarters while he pretended to
arbitrate the rival claims of the Scottish succession, and to establish
himself as the Lord Superior. On the green hill of Holywell nearby he
received the submission of Scotland in 1291—the submission of
Scotland!
 Ford castle is a little higher up the river, where lodged the dubious
lady with whom the king had dalliance in those slack days preceding
Flodden—the lady who had sung to him in Holyrood the challenging
ballad of "Young Lochinvar!" James was ever a Stewart, and
regardful of the ladies.
"What checks the fiery soul of James,
Why sits the champion of dames
Inactive on his steed?"
The Norman tower of Ford (the castle has been restored), called
the King's tower, looks down on the battlefield, and in the upper
room, called the King's room, there is a carved fireplace carrying the
historic footnote—
"King James ye 4th of Scotland did lye
here at Ford castle, A. D. 1513."
Somehow one hopes that the lady was not sparring for time and
Surrey, and sending messages to the advancing Earl, but truly loved
this Fourth of the Jameses, grandfather to his inheriting
granddaughter.
Coldstream is the station for Flodden. But the village, lying a mile
away on the Scotch side of the Tweed, has memories of its own. It
was here that the most famous ford was found between the two
countries, witness and way to so many acts of disunion; from the
time when Edward I, in 1296, led his forces through it into Scotland,
to the time when Montrose, in 1640, led his forces through it into
England.
"There on this dangerous ford and deep
Where to the Tweed Leet's eddies creep
He ventured desperately."
The river was spanned by a five-arch bridge in 1763, and it was
over this bridge that Robert Burns crossed into England. He entered
the day in his diary, May 7, 1787. "Coldstream—went over to
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