vitreous hemorrhage

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

Optic disc swelling

Venous tortuosity

Macular edema

NFL hemorrhage

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

Retinal vein occlusion

Macular edema

Periphlebitis

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

Targeted enzymatic posterior vitreous detachment enzyme selectively cleaves the anatomic

attachment between the posterior hyaloid and the inner surface of the retina

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 indirect-acting 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.