Persistence of Retinal Fluid after Anti-VEGF treatment for neovascular age-related macular degeneration: A Systematic Review and Meta-Analysis.

Abstract

Topic: To evaluate the prognosis of retinal fluid resolution in neovascular age-related macular degeneration (nAMD) after initiating treatment in terms of the prevalence of eyes with retinal fluid, the proportion of eyes which never achieve a fluid-free retina throughout the course of treatment, and the relationship between retinal fluid and visual acuity outcome.

Clinical relevance: Retinal fluid often persists or recurs after initiating treatment for nAMD. It is unclear what proportion never achieve fluid resolution throughout their treatment course.

Methods: MEDLINE, Embase, and Web of Science were searched till May 2024 for randomized control trials (including post-hoc analyses) and prospective studies treating nAMD patients with intravitreal anti-VEGF injections (CRD42023437516). To investigate the prevalence of persistent fluid, a meta-analysis of proportions was conducted at key time-points. To estimate the proportion of poor-responding patients, iterative algorithms were used to simulate individual-patient-data from time-to-fluid fluid-resolution Kaplan-Meier curves. Cure fractions from Weibull non-mixture cure models were meta-analysed. Finally, the weighted mean BCVA difference (WMD) between patients with and without any fluid, SRF or IRF was calculated.

Results: Fifty articles were included across the meta-analysed outcomes. The pooled prevalence of retinal fluid was 41.4% (95%CI:35.0%-48.0%) at 1 year, and 47.4% (95%CI:38.5%-56.5%) at 2 years. The pooled median time-to-first fluid-resolution was 10.2 weeks (95%CI:7.66-14.59 weeks). Cure modelling suggests that 17.6% (95%CI: 11.9%-25.3%) of patients may never achieve a fluid-free finding in the long run despite prolonged treatment. Eyes with SRF had significantly higher BCVA compared to eyes without SRF at 12m (WMD 2.39 letters; 95%CI, 0.27-4.52; p<0.05). Eyes with IRF had significantly poorer BCVA compared to eyes without IRF at 12m (WMD -5.38 letters; 95% CI, -8.65 - -2.11; p<0.05). At long follow-up (>60m), eyes with SRF had significantly higher BCVA compared to eyes without SRF (WMD 7.69 letters; 95%CI, 2.79-12.59; p<0.05).

Conclusions: Notwithstanding the heterogeneity in studies included, our analysis estimates that nearly half of all treated patients have persistent retinal fluid after initiating treatment and a substantial 18% of patients may never attain complete fluid resolution. We confirm that SRF is associated with better visual outcomes, while IRF is associated with worse visual outcomes.