Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis

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Objective: To determine the effect of subretinal fluid (SRF) resolution on visual acuity in patients with neovascular age-related macular degeneration (nAMD) from the HARBOR trial.

Design: Post hoc analysis, carried out from January 2020 to July 2021, of the HARBOR trial, a phase 3, double-masked, randomized, active treatment-controlled trial of ranibizumab conducted between July 2009 and August 2012 (NCT00891735).

Participants: Treatment-naïve patients with nAMD and active subfoveal choroidal neovascularization (N = 1097); intervention arms were pooled for this analysis if SRF was present at baseline and intraretinal fluid/SRF resolved during the study, based on spectral-domain OCT (n = 349).

Intervention: Three monthly loading doses were followed by intravitreal ranibizumab 0.5 mg and 2.0 mg injections, administered monthly or pro re nata over 24 months.

Main outcome measures: Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between the month before SRF resolution and the month of SRF resolution detection. Visual outcomes at months 12 and 24 were analyzed in eyes without SRF recurrence after SRF resolution. Eyes losing up to 4 letters were considered vision gainers/maintainers and eyes losing 5 or more letters were considered vision losers.

Results: Of 349 patients, 32 (9%) lost 5 or more ETDRS letters (mean [95% confidence interval (CI)], -9.9 [-12.0, -7.9] letters) and 317 (91%) of eyes gained/maintained BCVA (mean, 6.1 [5.3, 6.8] letters) between the month before SRF resolution and the month of SRF resolution. There were no differences in baseline ocular characteristics between patient groups. Among eyes without SRF recurrence after SRF resolution (64%; 224/349), those losing 5 or more ETDRS letters versus those that gained/maintained letters at the time of SRF resolution had reduced visual outcome gains from baseline at month 12 (1.4 vs. 12.9 letters) and month 24 (0.0 vs. 12.6 letters).

Conclusions: In ranibizumab-treated eyes with nAMD, most gained/maintained visual acuity at SRF resolution. However, 9% of eyes lost vision at SRF resolution; those eyes had reduced final visual acuity gains at 12 and 24 months. Further analyses are needed to assess the factors potentially underlying this finding and, if confirmed, the treatment implications.