Vitreous Hemorrhage

Vitreous hemorrhage
Presence of extravasated blood within the space outlined by the internal limiting membrane of the retina posteriorly and laterally, the nonpigmented epithelium of the ciliary body antero-laterally and the lens zonules and the posterior lens capsule anteriorly

Pathogenesis
Retinal vascular disorders that cause retinal ischemia Retinal vascular abnormality not associated with retinal ischemia Rupture of a normal retinal vessel Breakthrough bleeding

Retinal vascular disorders that cause retinal ischemia Proliferative diabetic retinopathy Ischemic retinal vein occlusion Eales' disease Familial exudative vitreoretinopathy (FEVR)

Proliferative diabetic retinopathy

HARD EXUDATES

Central retinal vein occlusion

Venous tortuosity Macular edema

NFL hemorrhage

Optic disc swelling

Eales disease
an idiopathic retinal periphlebitis that primarily affects the peripheral retina in young adults characterized by avascular areas in the retina periphery, followed posteriorly by microaneurysms, dilatation of capillary channels, tortuosity of neighboring vessels, and spontaneous chorioretinal scars

Eales disease

Macular edema

Periphlebitis

Retinal vein occlusion

Familial exudative vitreoretinopathy

an inherited disease characterized by aberrant retinal development in non-premature infants Hallmark features:
peripheral

retina non-perfusion retinal neovascularization subretinal exudation formation of an abnormal vitreoretinal interface retinal detachment

Familial exudative vitreoretinopathy

temporal macular dragging

Familial exudative vitreoretinopathy

Peripheral nonperfusion

Retinal vascular abnormality not associated with retinal ischemia Rupture of retinal arteriole macroaneurysm associated with systemic hypertension Hemorrhage from a retinal angioma

Rupture of retinal arteriole macroaneurysm

Rupture of a normal retinal vessel

Retinal tears Retinoschisis
Tersons' syndrome Valsalva retinopathy

Retinal tear

Horshoe retinal tear

Vitreous hemorrhage

Tersons syndrome
originally defined by the occurrence of vitreous hemorrhage in association with subarachnoid hemorrhage now encompasses any intraocular hemorrhage associated with intracranial hemorrhage and elevated intracranial pressures
development

of subretinal, retinal, preretinal, subhyaloidal (classic presenation), or vitreal blood

Tersons syndrome

Valsalva retinopathy
Immediately following a Valsalva maneuver, a sudden rise in intraocular venous pressure causes retinal capillaries to spontaneously rupture. The prognosis for Valsalva retinopathy is generally good, with newer treatment modalities speeding recovery time.

Valsalva retinopathy

Breakthrough bleeding
Subretinal haemorrhage following choroidal neovascular membrane secondary to age-related macular degeneration
Choroidal malignant melanoma

Choroidal neovascular membrane

Choroidal malignant melanoma

Fate of vitreous hemorrhage

Rapid clot formation Slow lysis of fibrin Extracellular lysis of RBCs Persistence of intact RBCs for months Lack of early polymorphonuclear response

Fate of vitreous hemorrhage

Spontaneous clearance of blood from the vitreous is a slow and constant process, and is much more common in cases which have no tendency of recurrent bleeding, syneresis of the vitreous gel, and in elderly and pahakic patients. Vitreous blood does not clear as spontaneously in patients with diabetic retinopathy.

Fate of vitreous hemorrhage

Long-standing vitreous hemorrhage with the accumulated red cells and red cell debris suspended in and mixed with vitreous collagen ochre membrane

Fate of vitreous hemorrhage

Complications occurring due to non-clearing vitreous haemorrhage
retinal

damage glial and fibrovascular proliferation glaucoma

Evaluation of a patient with vitreous hemorrhage

Symptoms
sudden

painless decrease in vision sudden appearance of floaters

flashes of light visual haze cloudy vision photophobia perception of shadows and cobwebs

Evaluation of a patient with vitreous hemorrhage

Past Medical History
diabetes

mellitus systemic hypertension drug intake cerebral stroke

Ocular Examination

Best-corrected visual acuity Anterior segment evaluation

iris and angle neovascularisation keratic precipitates cells

RAPD Tonometry Fundus evaluation B-scan

Khaki-colored cells

Management
Factors to consider:

patient's age duration of disease visual acuity intraocular pressure amount of haemorrhage retinal status presence or absence of neovascularisation of iris adequacy of photocogaulation if done before the onset of haemorrhage lens status (phakic or aphakic/pseudophakic) presence or absence of posterior vitreous detachment (PVD)

Principles of Management
Observation Laser photocoagulation Vitrectomy

Observation
Unknown etiology, attached retina on B-scan
Rest

the head in an elevated position. Reevealuate after 3-7 days to ascertain the possible source of hemorrhage.

Observation
Known cause and source of hemorrhage, attached retina
Reevaluate

after 3-4 weeks Post laser or post-virectomy recurrent vitreous hemorrhage, vitreous hemorrhage in Tersons syndrome or after acute PVD and hemorrhage associated with bleeding diathesis

Observation
Attached macula
Wait

for 2-3 weeks for PVD to occur to enhance technical ease and outcomes of surgery

Macula-off
Immediate

surgery

Laser photocoagulation
Should start as soon as possible as any part of retina is visible in proliferative vasculopathies

Vitrectomy

Attached retina, good PVD, non-clearing vitreous hemorrhage over 2-3 months Advanced proliferative retinopathy with non-clearing vitreous hemorrhage in 6-8 weeks after adequate laser therapy Vitreous hemorrhage in RD especially when associated with giant retinal tears or open globe injury and vitreous hemorrhage due to AMD and IPCV

Vitrectomy

In general, early vitrectomy is indicated in situations where the underlying pathology is likely to progress fast if left untreated. Surgery can be delayed in eyes with well lasered proliferative retinopathy and attached retina where the reurrent hemorrhage is due to traction on elevated vessels and not secondary to active proliferation.

Enzymatic Vitreolysis for Retinal Disorders

Vitreous liquefaction
in

which the drug causes central liquefaction of the vitreous gel, collapse of the vitreous body, and secondary separation of the posterior hyaloid from the neural retina selectively cleaves the anatomic attachment between the posterior hyaloid and the inner surface of the retina

Targeted enzymatic posterior vitreous detachment

enzyme

Enzymatic Vitreolysis for Retinal Disorders

Plasmin Microplasmin Chondroitinase Hyaluronidase Dispase

Plasmin
an autologous serum protease that is a key component of the fibrinolysis cascade a non-specific protease usually present in human serum, and it is responsible for degrading a variety of plasma proteins specific physiologic role is to degrade fibrin clots

Microplasmin
truncated form of plasmin contains the active site of plasmin and has a similar mechanism of action in vitreolysis

Microplasmin
Unlike TPA, microplasmin is a direct acting thrombolytic, as compared to most other thrombolytics which dissolve clots indirectly by activating the plasmin precursor, plasminogen. May have neuroprotective features and have a reduced risk of bleeding compared to indirectacting thrombolytics.

Microplasmin
Once microplasmin enters into the systemic circulation, it is rapidly inactivated by a blood protein (alpha-2 anti-plasmin) thus reducing the risk of bleeding in locations away from the intended treatment area.

Hyaluronidase
substrate-specific enzyme that induces synchisis by acting on proteoglycans in the vitreous appears to alter the diffusion and movement of substances through the vitreous and, simultaneously, is important in the development of posterior vitreous detachment

Hyaluronidase
Intravitreal injection of 1 IU of intravitreal hyaluronidase is sufficient for partial vitreolysis andis non-toxic to the rabbit retina (Gottlieb et al., 1990). Intravitreal injection of hyaluronidase in doses of 10 IU or higher induces posterior vitreous detachment in rabbits over a period of 5 weeks. Intravitreal doses of 20 IU or less do not appear to affect the microscopic morphology or function of ocular structures adversely.

Hyaluronidase
Ovine hyaluronidase accelerated the clearing of vitreous hemorrhage. No serious safety issues were reported after a single intravitreal injection of ovine hyaluronidase. Kuppermann et al., 2005a

Chondroitinase
Proteolytic enzyme with specificity for chondroitin sulfate proteogylcan Despite the presence of chondroitin sulfate proteoglycan in human vitreous, there is conflicting evidence on the ability of chondroitinase to induce a posterior vitreous detachment.

Chondroitinase
Chondroitinase failed to induce a posterior vitreous detachment in the porcine eye, which is known to have a particularly thick and tenacious posterior hyaloid; plasmin was able to induce a posterior vitreous detachment in this animal model Hermel and Schrage, 2006

Chondroitinase
Although chondroitinase was not sufficient to induce a posterior vitreous detachment acting on its own, simultaneous intravitreal injection of chondroitinase ABC and matrix metalloproteinase-3 has been used in an experimental study of 24 rabbit eyes to induce posterior vitreous detachment. Meng and Zeng, 2004

Dispase
The only agent that has been used to specifically attack the surface between the posterior hyaloid and inner limiting membrane with the goal of cleaving this attachment.

Dispase
35.9 kD protease obtained from Bacillus polymyxa which cleaves the basal membrane in various tissues including skin, testis, and retinal pigment epithelium acts on type IV collagen and fibronectin, whereas other components of the extracellular matrix such as laminin, type V and VII collagens are resistant to the enzyme

Thank you.