Zoledronic acid as adjuvant therapy in neovascular age-related macular degeneration: a randomised controlled pilot study.

Aims: To assess the feasibility of a study protocol for a randomised controlled trial of zoledronic acid (ZA) as adjuvant therapy for neovascular age-related macular degeneration (nAMD).

Methods: In this 1-year, randomised, double-blinded, placebo-controlled pilot study, nAMD patients were allocated 1:1 to receive intravenous ZA 5 mg or placebo at baseline and after 6 months in addition to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy following a treat-and-extend regimen. Bevacizumab was the first-line anti-VEGF drug, but eyes with refractory nAMD were switched to aflibercept. The primary outcome was mean change in best-corrected visual acuity (BCVA).

Results: 40 participants enrolled in the study, with 20 allocated to each treatment group. 38 participants received both study infusions, and all participants completed the final assessment. Mean (SD) change in BCVA was 7.5 (9.5) letters in the ZA group and -0.5 (11.5) letters in the control group; the between-group difference was 8.0 letters (95% CI: 1.5 to 15.0 letters). There were no between-group differences in mean change in central retinal thickness, refractory nAMD proportion or mean number of injections.

Conclusion: It is feasible to conduct a randomised controlled trial of ZA as adjuvant therapy for nAMD in terms of recruitment and adherence to the pilot study protocol. We found a possible visual benefit of ZA that is worth further investigation. To clarify the relationship between ZA and the need for intravitreal injections, we recommend amending the protocol by omitting switching of the anti-VEGF drug. Due to the limited sample size of the pilot study, the estimates of treatment effect are not meant to be confirmatory and should be interpreted with caution.

Trial registration number: 2019-001492-37 (EudraCT), 04304755 (NCT).