Investigators did not observe a benefit with the anti-VEGF in preventing intermediate AMD eyes from converting to neovascular disease versus sham.
A quarterly dose of 0.5 mg ranibizumab was not associated with reduced incidence of neovascular age-related macular degeneration (nAMD) versus sham injections among patients with intermediate AMD, according to new findings.
In research seeking to interpret the potential prophylactic benefits of the anti-VEGF injection therapy, a team of investigators from the PREVENT Study Group reported that an altered dose regimen of ranibizumab intravitreal injection did not provide neither reduction in patient progression to nAMD nor benefit of visual acuity over 2 years.
That said, the team also observed data indicating the PREVENT findings may have been underpowered.
Led by Clement K. Chan, MD, of Southern California Desert Retina Consultants, investigators sought to interpret the preventive effect of ranibizumab on nAMD development in eyes with intermediate AMD for patients patients with preexisting nAMD in their contralateral eye. They conducted a multi-center, randomized trial involving patients ≥50 years old with eligible nAMD and AMD disease; eligible eyes required multiple intermediate drusen of ≥63 μm and <125 μm, or ≥1 large drusen of ≥125 μm, plus pigmentary changes.
Patients were randomized to either intravitreal ranibizumab 0.5 or sham injections every 3 months for 24 months. Chan and colleagues sought a primary outcome of conversion of eyes from AMD to nAMD, and a secondary outcome of change in best corrected visual acuity (BCVA), each from baseline to 24 months.
The final trial population included 108 participants split 1:1 to either treatment arm. Mean patient age was 78 years old at baseline, with a majority (56%) being female; 106 (98.1%) patients were non-Hispanic White. Mean BCVA score was 77.7 letters.
Investigators observed 7 eyes (13%) convert from AMD to nAMD in both treatment arms from baseline to 24 months, indicating no observed benefit of ranibizumab in preventing disease progression (hazard ratio [HR], 0.91; 95% CI, 0.32 - 2.59; P = .86). Even after adjusting for patients lost to treatment follow-up, cumulative nAMD indigence was 14% in the ranibizumab arm (95% CI, 4 - 23) versus 15% in the sham injection arm (95% CI, 4 - 25) at 24 months.
Chan and colleagues observed only an -0.8 adjusted difference in BCVA letter change (95% CI, -3.7 to 2.2; P = .62) in the ranibizumab arm (mean change, -2.1 letters; SD, 5.4) versus sham injection arm (mean change, -1.4 letters; SD, 7.7).
The team also observed 2 of 39 (5%) eyes from the ranibizumab arm that lost ≥10 letters in VA from baseline to 24 months, versus 4 of 40 (10%) eyes from the sham arm. No serious ocular adverse events were observed in either group.
The team concluded that both primary and secondary endpoints were not met with preventive ranibizumab in eyes with AMD versus sham injection. They stressed the need for other strategies that may reduce progression from AMD to nAMD in this vulnerable population, while also pointing to weaknesses in the PREVENT trial.
“Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded,” they wrote.
The study, “Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial,” was published online in Ophthalmology Retina.