Morphologic changes of the double-layer sign during anti-vascular endothelial growth factor therapy in eyes with neovascular age-related macular degeneration.

Purpose: To evaluate longitudinal morphologic changes of the double-layer sign (DLS) on optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (nAMD) presenting with exudative macular neovascularization (eMNV) undergoing anti-vascular endothelial growth factor (VEGF) therapy.

Methods: This retrospective study included 207 consecutive treatment-naïve eyes (207 patients) with nAMD presenting with eMNV and a DLS treated with intravitreal anti-VEGF injections and were followed for ≥ 12 months. All eyes received 3 monthly loading injections followed by either treat-and-extend (TAE) or pro re nata (PRN) retreatment, per predefined criteria. DLS area, length, and height were measured at baseline, after loading, and 12 months.

Results: All 207 eyes demonstrated significant reductions in mean (± standard deviation) DLS area, length, and height 1 month after the third monthly injection (165 ± 188 µm², 1446 ± 639 µm, and 202 ± 109 µm, respectively) compared with baseline (302 ± 264 µm², 1801 ± 573 µm, and 282 ± 150 µm, respectively) (P = 0.001, P = 0.001, and P = 0.024, respectively). At 12 months the mean change in DLS area was - 141 µm² [95% confidence interval (CI) - 185 to - 98], and median (95% CI) injection number was 8.1 (7.9 to 8.4). Eyes with subretinal and/or intraretinal fluid (SRF/IRF) at 12 months showed re-enlargement of DLS parameters, whereas eyes without SRF/IRF maintained the post-treatment decrease.

Conclusion: DLS morphology regresses after anti-VEGF therapy, and persistent or recurrent fluid is associated with less durable regression. The DLS regresses in response to anti-VEGF therapy, and its behaviour correlates with the clinical course of exudative MNV associated with a DLS. DLS monitoring may complement-but not replace-multimodal imaging when assessing MNV activity.