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.