Predictive factors for the efficacy of brolucizumab in refractory polypoidal choroidal vasculopathy following aflibercept resistance

TL;DR

The study identifies factors that predict whether patients with a specific eye condition can extend treatment intervals after switching medications.

Contribution

A predictive model using choroidal thickness changes and pachychoroid status is proposed for brolucizumab efficacy in refractory eye disease.

Findings

Eyes without significant early choroidal thinning were more likely to extend treatment intervals.

A ≥40% choroidal thickness reduction strongly predicted difficulty in extending treatment intervals.

The model showed good discrimination with an AUC of approximately 0.97.

Abstract

To identify predictors of extension of the injection interval beyond 8 weeks at the 24-month visit after switching to brolucizumab in aflibercept-resistant polypoidal choroidal vasculopathy (PCV).

Retrospective observational study

17 eyes of 16 patients with persistent or recurrent exudation on aflibercept were switched to intravitreal brolucizumab and managed with a treat-and-extend (T&E) regimen with a minimum 8-week interval after loading. The primary outcome contrasted extension (>8 weeks) versus non-extension (≤8 weeks) at month 24. Prespecified predictors were early central choroidal thickness (CCT) change from baseline to the switch visit (A0 to A1; ≥ 40% reduction) and pachychoroid. Associations were tested with Fisher’s exact tests and Firth-penalized logistic regression with the event defined as extension.

At 24 months, 6 of 17 eyes (35%) achieved extension. A ≥ 40% early CCT reduction occurred in 0 of 6 extension eyes versus 7 of 11 non-extension eyes (Fisher exact two-sided P ≈ 0.035). In the Firth model (event = extension), < 40% CCT reduction strongly predicted extension (odds ratio 38.5; profile-likelihood 95% CI 2.0–10,000; LR P = 0.004). Non-pachychoroid showed the same direction with wide CIs (odds ratio 14.3; 95% CI 0.99–2,174; LR P = 0.006). Model fit was significant (LR χ² = 15.19, P = 0.0005) and discrimination was good (apparent AUC ≈ 0.97). We prespecified a parsimonious two-predictor model to limit overfitting; adding age, sex, prior photodynamic therapy, or number of prior aflibercept injections did not materially change coefficients or improve AICc (ΔAICc < 2).

Eyes without marked early choroidal thinning (<40% CCT reduction at A1) were more likely to extend, whereas marked thinning (≥40%) signaled difficulty extending under T&E regimen after switching to brolucizumab. Given the small sample and few events, estimates should be interpreted cautiously and considered hypothesis-generating, and warrant prospective external validation studies.

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