The actual mechanisms producing the clinical picture of central retinal vein occlusion may be roughly divided into those conditions that produce a physical blockage at the level of the lamina cribrosa, and those conditions in which hemodynamic factors result in an obstruction to the flow of blood. These mechanisms probably coexist in many patients with Central Vein Occlusion.

Etiology

• An increased risk of central retinal vein occlusion was found in patients with systemic hypertension, diabetes mellitus, and open-angle glaucoma; the risk of central vein occlusion was decreased for patients with increasing levels of physical activity and increasing levels of alcohol consumption.
• For women, the risk decreased with the use of postmenopausal estrogen and increased with a higher erythrocyte sedimentation rate.

Two types of CRVO

• Ischemic CRVO - Patients with an ischemic pattern are usually aware of a sudden, painless decrease in visual acuity. Vision ranges from 20/400 to hand movements.
• The onset, however, is generally not as rapid or the visual loss as extensive as in central retinal artery occlusion.
• Exceptional cases have been noted in which patients with an acute onset had reasonably good vision and yet demonstrated a picture of ischemic central retinal vein occlusion.
• Non Ischemic CRVO - Nonischemic central retinal vein occlusion is a much milder and more variable disease in appearance, symptoms, and course compared with ischemic central retinal vein occlusion

Ophthalmic Features

Confluent hemorrhages are the most prominent ophthalmoscopic feature of an acute ischemic central retinal vein occlusion These hemorrhages occur in a wide variety of shapes and sizes; they are usually concentrated in the posterior pole, but may be seen throughout the retina. Many hemorrhages are flame shaped, reflecting the orientation of the nerve fibers. Dot and punctate hemorrhages are interspersed and indicate involvement of the deeper retinal layers. Bleeding may be extensive, erupting through the internal limiting membrane to form a preretinal hemorrhage or extending into the vitreous. Small dot hemorrhages may be seen either isolated or clustered around small venules. The entire venous tree is tortuous, engorged, dilated, and dark. The retina is edematous, particularly in the posterior pole; some of this edema may obscure portions of the retinal vessels. Cotton-wool patches (soft exudates) are often present.

The disc margin is blurred or obscured, and the precapillary arterioles appear engorged. Splinter hemorrhages and edema are present on the disc surface and extend into the surrounding retina. The physiologic cup is filled, and the venous pulse is absent. The arterioles, often overlooked because of the other more striking pathologic features, are frequently narrowed. Sometimes in central retinal vein occlusion of acute onset, the fundus picture is less dramatic, and all of the findings previously discussed may be present, but to a lesser degree. Vision depends on extent of macular involvement

Investigations

• All patients with central retinal vein occlusion should have a comprehensive ophthalmic evaluation, including an appropriate evaluation for glaucoma. In addition, they should be referred to their primary care physician for an evaluation of cardiovascular risk factors, including hypertension and diabetes
• Standard investigations-FBC, PV, ESR
• U+E, Creatinine
• LFT, Protein Electrophoreseis
• Random Glucose, Lipid
• Urine analysis
• Ophthalmic investigations – FFA, Colour Doppler

FFA

• The intravenous fluorescein angiogram pattern of an ischemic central retinal vein occlusion is usually characterized by a delayed filling time of the venous tree of the retina, capillary and venous dilation, and extensive leaking of fluorescein into the retina, particularly in the macular area and in the area adjacent to the larger venous trunks and capillary nonperfusion may not be noted at the time of initial occlusion, but are usually manifest shortly thereafter. Late-phase photographs show patchy extravascular areas of fluorescence and staining of the retinal veins.
• Microaneurysms may not be noted at the time of initial occlusion, but are usually manifest shortly thereafter.
• Late-phase photographs show patchy extravascular areas of fluorescence and staining of the retinal veins. Fluorescence in the macula indicates capillary leakage and edema; this not only may account for much of the initial visual loss in the acute phase, but may eventually result in permanent structural changes.
• Fluorescence in the macula indicates capillary leakage and edema; this not only may account for much of the initial visual loss in the acute phase, but may eventually result in permanent structural changes
• The most serious complication of central retinal vein occlusion is neovascularization.
• Neovascularization elsewhere (NVE) occurs less frequently than neovascularization of the iris (NVI), and usually only in ischemic occlusions.

Treatment

1. Medical management- No known effective medical treatment is available for either the prevention of or the treatment of central retinal vein occlusion (CRVO). Identifying and treating any systemic medical problems to reduce further complications is important. Because the exact pathogenesis of the CRVO is not known, various medical modalities of treatment have been advocated by multiple authors with varying success in preventing complications and in preserving vision.
2. Intravitreal Bevacizumab- In patients with macular edema, injection of bevacizumab (0.05 mL/1.25 mg) into the vitreous cavity through pars plana has been shown to be effective not only in resolving the edema but also in corresponding improvement in vision.
• Also, in patients with neovascular glaucoma, a similar dose has shown significantly decreased angle neovascularization and improved intraocular pressure control, both medically and surgically.
• Even though the exact mechanism of action of intravitreal injections of bevacizumab is not known, bevacizumab probably reduces VEGF concentrations in the vitreous cavity. This leads to a reduction in capillary permeability and macular edema. The main drawback of these injections is post treatment recurrences of macular edema, requiring repeat injections.
• Significant complications reported due to the injection of bevacizumab include cataract, glaucoma, retinal detachment, vitreous hemorrhage, and endophthalmitis
3. Intravitreal injection of ranibizumab -
• Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia and was noted to be elevated in the ocular fluids of patients with CRVO. One of the potent effects of VEGF is to increase vascular permeability in the macula leading to visually significant macular edema.
• Ranibizumab is a humanized, affinity-matured VEGF antibody fragment that binds to and neutralizes all isoforms of VEGF. Ranibizumab showed improved visual outcomes in patients with neovascular age-related vascular degeneration due to its anti-VEGF activity. The role of ranibizumab in the management of CRVO was reported in multiple studies. Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events.Long-term follow-up of these patients is needed to know the persistence of these gains for more than 6 months.
4. 4) Dexamethasone intravitreal implant
• Dexamethasone is a potent, water-soluble corticosteroid that can be delivered to the vitreous cavity by the dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan; Irvine, Calif). A DEX implant is composed of a biodegradable copolymer of lactic acid and glycolic acid containing micronized dexamethasone. The drug-copolymer complex gradually releases the total dose of dexamethasone over a series of months after insertion into the eye through a small pars plana puncture using a customized applicator system.

                     

5. Intravitreal injection of triamcinolone
• In patients with macular edema, injection of triamcinolone (0.1 mL/4 mg) into the vitreous cavity through pars plana has been shown to be effective not only in resolving the edema but also in corresponding improvement in vision.
• Even though the exact mechanism of action of intravitreal injections of corticosteroids is not known, the triamcinolone crystals in the vitreous cavity probably reduce VEGF concentrations in the vitreous cavity. This leads to a reduction in capillary permeability and macular edema. The main drawback of an injection of triamcinolone was post treatment recurrences of macular edema, requiring repeat triamcinolone injections, typically every 3-6 months.
• In addition, significant complications reported due to the injection of triamcinolone include cataract, glaucoma, retinal detachment, vitreous hemorrhage, and endophthalmitis.
6. Laser photocoagulation-
• Laser photocoagulation is the known treatment of choice in the treatment of various complications associated with retinal vascular diseases (eg, diabetic retinopathy, branch retinal vein occlusion). Panretinal photocoagulation (PRP) has been used in the treatment of neovascular complications of CRVO for a long time. However, no definite guidelines exist regarding exact indication and timing of PRP
• Argon green laser usually is used. Laser parameters should be about 500-µm size, 0.1-0.2 second duration, and power should be sufficient to give medium white burns. Laser spots are applied around the posterior pole, extending anterior to equator. They should be about 1 burn apart and total 1200-2500 spots.
• If ocular media is hazy for laser to be applied, cryoablation of the peripheral fundus is performed. About 16-32 transscleral cryo spots are applied from ora serrata posteriorly