Persistence of Retinal Fluid After Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

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-resolution Kaplan-Meier curves. Cure fractions from Weibull nonmixture cure models were meta-analyzed. Finally, the weighted mean best-corrected visual acuity (BCVA) difference (WMD) between patients with and without any fluid, subretinal fluid (SRF), or intraretinal fluid (IRF) was calculated.

Results: Fifty articles were included across the meta-analyzed outcomes. The pooled prevalence of retinal fluid was 41.4% (95% confidence interval [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 modeling 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 with eyes without SRF at 12 months (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 12 months (WMD, -5.38 letters; 95% CI, -8.65 to -2.11; P < 0.05). At long follow-up (>60 months), 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).

Conclusion: 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, whereas IRF is associated with worse visual outcomes.

Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.