Central Retinal Vein Occlusion Treatment & 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.

Advocated treatments are as follows:

• Aspirin
• Anti-inflammatory agents
• Isovolemic hemodilution
• Plasmapheresis
• Systemic anticoagulation with warfarin, heparin, and alteplase
• Fibrinolytic agents
• Systemic corticosteroids
• Local anticoagulation with intravitreal injection of alteplase
• Intravitreal injection of ranibizumab
• Intravitreal injection of triamcinolone^{[18, 19, 20, 21, 22, 23]}
• Intravitreal injection of bevacizumab^{[13, 24, 25, 26, 27]}
• Dexamethasone intravitreal implant^[28]

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 posttreatment 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.

Because most of the data available for the use of triamcinolone injection is from multiple short-term follow-up studies, a large controlled, randomized clinical trial called the SCORE (Standard Care vs Corticosteroid for Retinal Vein Occlusion) Study is now underway in about 90 centers throughout the United States. This study is funded by the National Eye Institute (NEI) to evaluate the use of intravitreal triamcinolone for macular edema in about 1,200 patients with CRVO or branch retinal vein occlusion (BRVO). All patients are being randomized to either 1 mg or 4 mg of triamcinolone versus standard care therapy (eg, observation in CRVO, laser photocoagulation in BRVO). Patients will be followed for up to 3 years to measure long-term treatment efficacy and safety; reinjections (if needed) will be performed beginning at 4 months after the initial therapy.

Based on the results of the SCORE-CRVO trial, intravitreal triamcinolone using a 1-mg dose and retreatment as needed should be considered for up to 1 year and possibly 2 years in patients with vision loss associated with macular edema secondary to CRVO. Intravitreal triamcinolone in both a 1-mg and 4-mg dose led to better visual acuity outcomes over 12 months than the untreated natural history of macular edema secondary to perfused CRVO. Owing to fewer adverse effects with the 1-mg dose, it is preferred over the 4-mg dose.^[23]

Intravitreal injection of 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.

In addition, significant complications reported due to the injection of bevacizumab include cataract, glaucoma, retinal detachment, vitreous hemorrhage, and endophthalmitis.

Significant complications were reported with high doses of bevacizumab given intravenously for the treatment of cancer. There have been no significant reports of these complications in the available small studies.

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.^{[29, 30]} Long-term follow-up of these patients is needed to know the persistence of these gains for more than 6 months.

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.

A 6-month study evaluated the safety and efficacy of DEX implant 0.35 mg and 0.7 mg compared with a sham procedure in eyes with vision loss due to macular edema associated with BRVO and CRVO.^[28] In conclusion, the results of the study demonstrated that DEX implant reduced the risk of further vision loss and increased the chance of improvement in visual acuity in eyes with CRVO.

The percentage of eyes with a greater than or equal to 15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P < .001). The results of this study further demonstrate that when these eyes were left untreated, a significant percentage will either fail to improve or will experience further loss of visual acuity. The DEX implant was well tolerated, producing generally transient, moderate, and readily managed increases in IOP in less than 16% of eyes. Overall, this study suggests that the DEX implant could be a valuable new treatment option for eyes with visual loss due to CRVO.

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. A National Eye Institute (NEI) sponsored multicenter prospective study, the Central Vein Occlusion Study (CVOS), provided guidelines for the treatment and follow-up care of patients with CRVO.^{[1, 10, 31, 32, 33]}

CVOS evaluated the efficacy of prophylactic PRP in eyes with 10 or more disc areas of retinal capillary nonperfusion, confirmed by fluorescein angiography, in preventing development of 2 clock hours of iris neovascularization or any angle neovascularization or whether it is more appropriate to apply PRP only when iris neovascularization or any angle neovascularization occurs. CVOS concluded that prophylactic PRP did not prevent the development of iris neovascularization and recommended to wait for the development of early iris neovascularization and then apply 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.

CVOS evaluated the efficacy of macular grid photocoagulation in preserving or improving central visual acuity in eyes with macular edema due to central vein occlusion (CVO) and best-corrected visual acuity of 20/50 or poorer. Macular grid photocoagulation was effective in reducing angiographic evidence of macular edema, but it did not improve visual acuity in eyes with reduced vision due to macular edema from CVO. At present, the results of this study do not support a recommendation for macular grid photocoagulation for macular edema.

Chorioretinal venous anastomosis

Chorioretinal venous anastomosis^{[34, 35, 36, 37, 38]} is performed by creating an anastomosis to bypass the site of venous occlusion in the optic disc. In this procedure, retinal veins are punctured, either using laser or by surgery, through the retinal pigment epithelium and the Bruch membrane into the choroid, thereby developing anastomotic channels into the choroid.

Chorioretinal venous anastomosis reduces macular edema and may improve vision in nonischemic CRVO. The success rate is low, and the complication rate can be quite high, including vitreous hemorrhages and choroidal neovascularization at the anastomosis site.

The exact indication and timing of the procedure has not been clearly studied.

Radial optic neurotomy

Radial optic neurotomy (RON)^{[39, 40, 41, 42, 43, 44]} is a new surgical technique in which a microvitreoretinal blade is used during pars plana vitrectomy to relax the scleral ring around the optic nerve. The central retinal artery and vein passes through the narrow openings of the cribriform plate in the optic disc.

Promoters of this technique suggest that CRVO may be due to the compression of the central retinal vein at this location creating a compartment syndrome. If this procedure is successful, it decompresses the closed compartment and leads to an improvement in venous outflow and a reduction of macular edema.

In one recent study, RON resulted in clinically relevant improvements on a long-term basis. Patients with nonischemic CRVO may respond more favorably than patients with ischemic CRVO.

In another study, significant improvements were observed in the b-to-a ratio of the standard combined ERG after surgery in eyes with CRVO.

The benefits from surgery have not been clearly documented. One study, looking into the biomechanical effect of RON, found negligible change in the space around the central retinal vein; RON is unlikely to be a procedure that could mechanically ameliorate the clinical sequelae of a central vein occlusion. The improvement of retinal function is most likely due to improved oxygenation of the retina caused by vitrectomy and not by RON.

In addition to the regular complications of vitrectomy, RON can result in significant hemorrhage and neovascularization at the incision site.

No consensus currently exists among various researchers regarding the exact criteria for the use of RON.

Vitrectomy

A vitrectomy^[45] is a technique in which the vitreous is surgically removed along with removal of the posterior hyaloid.

Some studies have shown that a vitrectomy may be beneficial for macular edema due to CRVO. One theory is that a vitrectomy may relieve traction on the macula and, thus, reduce macular edema. According to another hypothesis, removing the vitreous will also remove cytokines and VEGF associated with a venous occlusive event; thus, the stimulus for macular edema will be reduced.

At the present time, no convincing evidence indicates that a vitrectomy is the best approach.

A general ophthalmologist should consult a retinal specialist for management of CRVO complications. Other consults include an internist for proper evaluation and management of any systemic medical problems. If patients develop neovascular glaucoma, a glaucoma specialist should be consulted.

Diet should be tailored to systemic medical problems.

No restrictions usually exist. If patients develop vitreous hemorrhage, they are advised to avoid strenuous activities, sleep with few pillows, and avoid bending and lifting heavy weights.