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Applying ranibizumab injections to fellow eyes of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, to prevent intermediate disease from becoming exudative, does not effectively ward off advancing disease, according to a report from the PREVENT study group that was published in Ophthalmology Retina.1
In several pivotal trials, the risk for a nonexudative eye to progress to nAMD in 2 to 5 years when the fellow eye is already diagnosed with nAMD was approximately 16.6% to 35.1% The only current preventive options are oral supplements.
The PREVENT pilot trial (ClinicalTrials.gov Identifier: NCT02140151) included 108 participants, mean age 78 years, with established nAMD in the non-study eye. Patients were randomized 1:1 to receive either ranibizumab intravitreal 0.5 mg injections or sham injection every 3 months in the high-risk study eye with intermediate signs — multiple medium drusen, or 1 or more large drusen, or hyperpigmentation.1
At 24 months, 7 of 54 eyes in each group, 13% converted to a neovascular state; and between the 2 cohorts, no significant difference in final best corrected visual acuity (BCVA) resulted. The mean change in BCVA for the ranibizumab group was -2.1 ± 5.4 letters, and in the control group -1.4 ± 7.7 letters (P =.62). “We did not detect a reduction in the incidence of nAMD in the study eyes receiving prophylactic quarterly ranibizumab, but the 95% confidence interval for the hazard ratio ranged from a one-third reduction in the risk of nAMD to a 2.5-fold increase in the risk of nAMD with prophylactic ranibizumab,” the investigators explain.1 The analysis may be underpowered to completely preclude preventive impact, the study authors suggest.
Conversion to nAMD occurred for the 7 ranibizumab-treated eyes at points from 3 months until 24 months, compared with onset in 7 sham-treated eyes from the 3-month visit until 12 months. Also, among 10 baseline variables controlled for the treatment group, none were significantly associated with progression to a neovascular state.
An analogous 24-month trial, PRO-CON (ClinicalTrials.gov Identifier: NCT02462889), examined the prophylactic effect of quarterly aflibercept 2.0 mg injections in vulnerable fellow eyes, finding conversion at 9.5% in the aflibercept cohort, compared with 10.9% for the sham injection group (P =.98).2 A majority, 70% of eyes, in the PREVENT trial were diagnosed with neovascular disease in the non-study eye less than 2 years prior.1 Notably, PRO-CON participants in this category converted at higher rates than patients with nAMD in the contralateral, non-study eye for longer than 2 years.2
Ninety individuals completed PREVENT, and none experienced any serious ocular adverse events. Approximately 90% of those in this study were concurrently undergoing injection therapy with ranibizumab or other anti-VEGF to the eye with already established nAMD.1
Limitations of the investigation include a possible crossover effect from the non-study eye’s medication. Also, no optical coherence tomography angiography (OCT-A) imaging was performed. Researchers speculate that, with a 13% event rate in the control group, the sample size needed is more than “800 patients for 90% power to detect a 50% reduction in progression to nAMD.”1
Disclosures: This research was supported by Roche-Genentech.
References
1. Chan CK, Lalezary M, Abraham P, et al. Prophylactic ranibizumab to prevent neovascular age-related macular degeneration in vulnerable fellow eyes: a randomized clinical trial. Ophthalmol Retina. Published online February 1, 2022. doi:10.1016/j.oret.2022.01.019
2. Heier JS, Brown DM, Shah SP, et al. Intravitreal aflibercept injection vs sham as prophylaxis against conversion to exudative age-related macular degeneration in high-risk eyes: a randomized clinical trial. JAMA Ophthalmol. 2021;139(5):542–547. doi:10.1001/jamaophthalmol.2021.0221
