Aflibercept With vs Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial.

Abstract

Importance: The potential benefit of adding photodynamic therapy (PDT) to intravitreal aflibercept injection (IAI) in eyes with polypoidal choroidal vasculopathy (PCV) remains unclear.

Objective: To compare the functional and anatomical benefit of combination therapy using reduced-fluence PDT (RF-PDT) plus IAI vs IAI monotherapy in participants with PCV.

Design, setting, and participants: This double-masked, sham-controlled, randomized clinical trial was conducted at 2 centers in Singapore from January 2021 to June 2024 for participants aged 50 years or older with symptomatic macular PCV confirmed on indocyanine green angiography. Data were analyzed from January 2021 to June 2024.

Interventions: Randomization 1:1 to RF-PDT plus 2 mg of IAI or sham-PDT plus 2 mg of IAI at week 0. Follow-up was at 4 weeks and retreatment with IAI, per protocol pro re nata regimen.

Main outcomes and measures: The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Secondary outcomes, not adjusted for multiple analyses, included proportion of eyes with polypoidal lesion (PL) closure at week 12 per indocyanine green angiography .

Results: Only 60 (43 male [71.6%] and 17 female [28.4%]; mean [SD] age, 71.3 [5.7] years) of the planned 160 participants were enrolled between January 2021 and June 2023. Among these, 30 of 30 (100%) and 30 of 30 participants (100%) in combination and monotherapy groups, respectively, returned for the 52-week follow-up. Baseline BCVA letter score (approximate Snellen equivalent [SD]) was 62.0 (20/63 [10.6]) and 62.0 (20/63 [10.7]) in the combination and monotherapy arms, respectively. At week 52, mean gain in BCVA was 12.7 (combination) vs 11.9 (monotherapy) (difference = 0.8 letters; 95% CI, -3.0 to 6.0 letters; P = .82). At week 12, the PL closure rate occurred in 20 of 30 eyes (66.7%) vs 10 of 30 eyes (33.3%) in the combination and monotherapy arms, respectively (difference = 33.4%; 95% CI, 9.5%-57.2%; P = .02).

Conclusions and relevance: With less than half of the planned sample size enrolled, no superiority in BCVA outcomes for either arm was detected and the combination arm could not be shown to be not worse (not noninferior) to the monotherapy arm. While PL closure at week 12 was greater in the combination arm, secondary outcome results, which were not adjusted for multiple analyses, should be considered hypothesis generating and not associated with a clinically relevant functional outcome in this trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03941587.