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

Participants: Treatment-naive patients with nAMD and active subfoveal choroidal neovascularization (N = 1097). Multiple 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 followed by intravitreal injections of 0.5-mg or 2.0-mg ranibizumab were administered monthly or pro re nata over 24 months.

Main outcome measures: Mean change in 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. The proportion of patients who lost ≤ 4 letters were considered as vision gainers/maintainers and those who lost ≥ 5 were considered as vision losers.

Results: Of 349 patients, 32 patients (9%) lost ≥ 5 ETDRS letters (mean [95% confidence interval (CI)], -9.9 letters [-12.0, -7.9]) and 317 (91%) of the eyes gained/maintained BCVA (mean, 6.1 letters [95% CI, 5.3, 6.8]) 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), eyes that lost ≥ 5 ETDRS letters compared with those that gained/maintained letters at the time of SRF resolution had reduced visual outcome gains from baseline to month 12 (1.4 vs. 12.9 letters) and month 24 (0.0 vs. 12.6 letters).

Conclusions: A greater proportion of ranibizumab-treated eyes with nAMD gained/maintained visual acuity at SRF resolution. Approximately 9% of eyes lost vision during SRF resolution; these eyes had reduced final visual acuity gains at 12 and 24 months. Further analyses are warranted to investigate potential underlying factors and discuss the treatment implications if confirmed.

Keywords: Fluid; macular degeneration; neovascular; ranibizumab.