Intravitreal anti-VEGF therapy

The initial studies of anti-VEGF therapy of RVO were BRAVO (Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion) and CRUISE (Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion). In these studies, monthly injections of either 0.5- or 0.3-mg ranibizumab or sham injections were administered for the treatment of macular edema secondary to venous occlusions. At 6 months, 15 or more ETDRS letters were gained in BRAVO in 61.1%, 55.2%, and 28.8% of eyes treated with 0.5- or 0.3-mg ranibizumab or sham injection, respectively; in CRUISE, the letters were gained in 47.7%, 46.2%, and 16.9% of eyes.

Similar results were achieved with intravitreal aflibercept (also called VEGF-Trap) in the VIBRANT (Study to Assess the Clinical Efficacy and Safety of VEGF Trap-Eye in Patients With Branch Retinal Vein Occlusion), COPERNICUS (Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion; conducted within North America), and GALILEO (similar protocol, but conducted outside North America) studies. The benefits were maintained during the second 6 months of these aflibercept studies, during which as-needed treatment was administered.

Bevacizumab is also effective for the management of CME secondary to RVO, as demonstrated in several controlled and uncontrolled studies (Fig 6-13). In SCORE2 (Study of Comparative Treatments for Retinal Vein Occlusion 2) bevacizumab was shown to be noninferior to aflibercept in the treatment of macular edema secondary to CRVO. In CRAVE (Comparison of Anti-VEGF Agents in the Treatment of Macular Edema from Retinal Vein Occlusion), the 98 patients who were randomized to receive either monthly bevacizumab or ranibizumab treatment for macular edema secondary to CRVO and BRVO showed no significant differences in central foveal thickness reduction or visual acuity improvement. As a result of these comparative efficacy studies and the general clinical impression of the equivalency of the anti-VEGF agents in the treatment of RVO, many practitioners use the 3 anti-VEGF drugs interchangeably. In practice, anti-VEGF agent administration strategies for RVO treatment include monthly dosing, as-needed treatment, and treat-and-extend approaches.

Figure 6-13 CME secondary to CRVO, before and after treatment. A, SD-OCT scan shows severe CME with foveal detachment in a patient with a nonischemic CRVO. Visual acuity was 20/200. B, One month after intravitreal injection of bevacizumab, 1.25 mg, the cystic changes and foveal detachment resolved, and the visual acuity was 20/25.

(Courtesy of Colin A. McCannel, MD.)

• Brown DM, Campochiaro PA, Bhisitkul RB, et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology. 2011;118(8):1594–1602.

• Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011;118(10):2041–2049.

• Scott IU, VanVeldhuisen PC, Ip MS, et al; SCORE2 Investigator Group. Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial. JAMA. 2017;317(20): 2072–2087.

Intravitreal corticosteroids

Intravitreal corticosteroids were the first pharmacological therapy that appeared efficacious for retinal vein occlusion; however, their specific risks include cataract formation (common) and steroid-induced elevation of IOP (in 20%–65% of individuals). When making patient care decisions, clinicians must weigh these risks against the benefits as well as any available alternative treatments. SCORE (Standard Care Versus Corticosteroid for Retinal Vein Occlusion) found that intravitreal triamcinolone injection in eyes with BRVO was comparable in efficacy to macular grid laser treatment with respect to 3 or more lines of visual acuity gain. Because eyes receiving triamcinolone were more likely to develop a cataract or experience elevated IOP, the study investigators concluded that macular grid laser therapy remained the benchmark against which other treatments should be compared. In the CRVO arm of the SCORE study, at 1 year follow-up, 27% of eyes treated with 1 mg of triamcinolone and 26% of eyes treated with 4 mg of triamcinolone had improved by 15 ETDRS letters or more, compared with 7% of eyes in the observation group.

The GENEVA study (Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients With Macular Edema due to Retinal Vein Occlusion) explored the use of a dexamethasone (0.7-mg) intravitreal implant to treat macular edema secondary to venous occlusive disease. A statistically significant 15-letter or more improvement from baseline corrected distance visual acuity (CDVA) was achieved between 30 and 90 days, with the greatest response (29%) at day 60. At day 180, there was no longer a significant difference between the sham (18%) and treatment groups (22% for the dexamethasone 0.7 mg group). The COMRADE (Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion) study compared the dexamethasone (0.7-mg) implant with monthly ranibizumab treatment. At the first 3 monthly follow-up visits, the efficacy of the two treatments was similar; however, at months 4–6, the eyes treated with ranibizumab had significantly better visual acuity scores, and at month 6, the mean ETDRS letters gained for the ranibizumab group and the dexamethasone (0.7-mg) implant group were 12.86 versus 2.96 letters, respectively (P < .001).

• Haller JA, Bandello F, Belfort R Jr, et al; OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134–1146.

• Hoerauf H, Feltgen N, Weiss C, et al; COMRADE-C Study Group. Clinical efficacy and safety of ranibizumab versus dexamethasone for central retinal vein occlusion (COMRADE C): a European label study. Am J Ophthalmol. 2016;169:258–267.

• Scott IU, Ip MS, VanVeldhuisen PC, et al; SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol. 2009;127(9):1115–1128.

Systemic anticoagulation

Systemic anticoagulation is not recommended for the treatment of RVO. Case series suggest the patient may experience worse outcomes due to increased bleeding in the retina.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.