Identification and Quantification of the Angiofibrotic Switch in Neovascular AMD

Purpose: We quantify volumetric changes of subretinal hyperreflective material (SHRM) and determine the conversion toward subretinal fibrosis, the angiofibrotic switch, under anti-VEGF therapy using polarization-sensitive optical coherence tomography (PS-OCT). Methods: A total of 50 eyes of 50 patients with treatment-naïve neovascular age-related macular degeneration (AMD) were included in this prospective observational study: 26 diagnosed with type 1 choroidal neovascularization (CNV), seven with type 2 CNV, 11 with mixed type CNV, three with a retinal angiomatous proliferation (RAP) lesion and three with a polypoidal choroidal vasculopathy (PCV). Patients were imaged at baseline and at the end of the loading phase (after treatment with three intravitreal anti-VEGF injections) using a PS-OCT system with a scanning angle of 30° × 30° and a scan pattern of 1024 × 250 A-scans. The device is capable of detecting fibrosis based on birefringence and the RPE based on depolarization. The volume of SHRM was quantified by manual delineation in each PS-OCT B-scan and interpolation between B-scans using proprietary reading center certified software. The occurrence of fibrosis detected by PS-OCT was compared to the clinical presentation of subretinal fibrosis. Results: Of 50 eyes, 28 had SHRM at baseline. Seven of these eyes had subretinal fibrosis within 3 months, six of which could be detected unambiguously based on PS-OCT imaging. SHRM thickness and volume at month 3 (P = 0.001 and P = 0.02) were significantly larger and the reduction of SHRM thickness and volume (P = 0.002 and P = 0.027) in response to therapy were significantly less pronounced in eyes with fibrosis. Conclusions: SHRM volume decreases significantly under anti-VEGF therapy. However, lesions unresponsive to therapy may progress to fibrosis as early as 3 months. Reduction in SHRM thickness may be a prognostic marker for treatment response.