Association Between Visual Acuity and Residual Retinal Fluid Following Intravitreal Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration

Abstract

IMPORTANCEThe association between residual subretinal fluid (SRF) and intraretinal fluid (IRF) and visual acuity following anti-vascular endothelial growth factor (VEGF) treatment is not well understood.OBJECTIVE To examine the association of residual retinal fluid, SRF, and IRF with visual acuity following anti-VEGF treatment in patients with neovascular age-related macular degeneration (nAMD).DATA SOURCES A systematic literature search was performed from January 2005 to August 2021 using Ovid MEDLINE, Embase, and the Cochrane Library.STUDY SELECTION Peer-reviewed articles reporting on visual acuity stratified by the presence or absence of any residual SRF, IRF, or any retinal fluid at last study observation after intravitreal bevacizumab, ranibizumab, aflibercept, or brolucizumab in patients with nAMD were included. Studies that were noncomparative, included fewer than 10 eyes, or reported on other anti-VEGF agents were excluded.DATA EXTRACTION AND SYNTHESIS Two independent reviewers conducted data extraction and synthesis. The Cochrane risk of bias tool 2 and ROBINS-I were used to assess risk of bias and GRADE evaluation was conducted to assess certainty of evidence.MAIN OUTCOMES AND MEASURES Primary outcomes were BCVA at last study observation, change in BCVA from baseline, and retinal thickness at last study observation. RESULTSIn this systematic review and meta-analysis, 11 studies (6 randomized clinical trials [RCTs]) comprising 3092 eyes were included in our analysis. Across all included studies, the BCVA of eyes with residual SRF was better than eyes without SRF (weighted mean difference [WMD], 3.1 letter score; 95% CI, 0.05 to 6.18; P = .05; GRADE, low certainty of evidence; 6 studies; 1931 eyes) but similar in RCTs (WMD, 2.7 letter score; 95% CI, −2.40 to 7.84; P = .30; GRADE, low certainty of evidence; 3 studies; 1406 eyes). The BCVA of eyes with residual IRF was worse than that of eyes without IRF (WMD, −8.2 letter score; 95% CI, −11.79 to −4.50; P < .001; GRADE, low; 7 studies; 2114 eyes). CONCLUSIONS AND RELEVANCEThe findings suggest that the presence of residual SRF was associated with slightly better BCVA at last study observation; however, baseline differences in BCVA existed and this conclusion was primarily driven by 1 study. The presence of residual IRF was associated with substantially worse BCVA at last study observation and less improvement of BCVA from baseline. The conclusions are limited by the inclusion of data from observational studies, heterogeneity, and a low certainty of evidence.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study

“…Most eyes (274/294 eyes, 93.2%) had chronic retinal fluid and were switched from other anti-VEGF agents because of insufficient response with 19.97 ± 13.87 mean number of anti-VEGF injections, which might have affected the visual recovery and restoration of photoreceptors. Several studies have reported an association between the presence of residual fluid after the anti-VEGF injection and VA, suggesting that persistent IRF is related to poor visual outcomes [28][29][30]. Although most included eyes had longstanding residual fluid, the baseline BCVA (logMAR) was 0.518 ± 0.356, similar to those recruited in pivotal studies (mean baseline BCVA: 60.6 letters [HAWK] and 61.2 [HARRIER]) and better than those in other real-world studies.…”

Maximal Extension Interval and Visual Outcomes in a Treat-and-Extend Protocol: A Post Hoc Analysis of the CANTREAT Randomized Trial

“…The cohort of patients with a maximum extension interval of 4 weeks likely had persistent choroidal neovascularization requiring treatment, which may be protective against macular atrophy [12]. In other studies, patients with nAMD and persistent residual SRF were found to have better BCVA at last study observation when compared to those without residual SRF [13, 14].…”

“…The lack of baseline BCVA, inability to discern between persistent and transient IRF/SRF, and small sample sizes in these subgroups limit the inferences of our findings. Other studies have suggested that SRF can be protective for photoreceptors and can prevent macular atrophy [13, 14, 18].…”

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

“…Currently, numerous clinical studies have shown that anti-VEGF agents have achieved good therapeutic effects in inhibiting pathological ocular neovascularization [20][21][22] . Despite the extensive clinical applications, there were still several deficiencies that have not been filled, such as frequent injection or drug resistance 23,24 . In this study, we designed and synthesized a new multi-target kinase inhibitor, DCZ19931, which could suppress ocular neovascularization by targeting endothelial angiogenic effects.…”