To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT.

Image analysis of a double-masked, sham-controlled, randomized clinical trial.

55 eyes of 55 treatment-naïve participants with symptomatic macular PCV completing 52 weeks of follow-up.

Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52.

Longitudinal OCTA changes and predictors of PL closure at week 52.

We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 ± 3.01mm ² at baseline, 2.86 ± 2.50mm ² at week 12, 3.59 ± 3.26mm ² at week 52; monotherapy: 3.77 ± 2.23mm ² at baseline, 3.27 ± 2.36mm ² at week 12, and 3.47 ± 2.58mm ² at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 ± 2.08 mm ² at baseline, 1.46 ± 1.36mm ² at week 12, and 1.53 ± 1.32mm ² at week 52; monotherapy: 2.39 ± 1.85mm ² at baseline, 1.87 ± 1.68mm ² at week 12, and 1.82 ± 1.38mm ² at week 52). BNN VD reduction was greater in the combination arm at week 12 (−10 ± 15% vs − 3 ± 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52).

In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (β=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (β=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03).

Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.