Characterisation and clinical impact of hypertransmission alterations in neovascular age-related macular degeneration using en face OCT

Objectives To (1) evaluate a method for analysing hypertransmission alterations (HTAs) in eyes with neovascular age-related macular degeneration (nAMD) using en face optical coherence tomography (OCT) images, and (2) investigate associations between HTA phenotypes and best-corrected visual acuity (BCVA). Methods HTAs were manually annotated on en face OCT projections (images from eyes with active nAMD from cross-sectional biomarker study) and classified into 3 qualitative phenotypes based on homogeneity, reflectivity, and border delineation. HTA quantitative metrics and associations between HTA phenotypes, metrics, clinical characteristics and BCVA were assessed. Results Images from 186 eyes were evaluated. Among gradable eyes (n = 136), HTA lesions were present in 88% (119/136) and classified as homogeneous (19%), heterogeneous (25%), and indeterminate (56%). Heterogeneous HTAs had highest foveal involvement; homogeneous HTAs exhibited higher reflectivity, border delineation, and multifocality; indeterminate HTAs were more common in younger patients with shorter disease duration. Significant associations with lower BCVA (R ²  = 0.46) were found for HTA phenotype, larger square root HTA total area (− 5.1 letters/mm, 95% confidence interval [CI] − 7.9, − 2.3) and intraretinal fluid volume (− 1.3 letters/log2-transformed µm ³ ; 95% CI − 1.9, − 0.8). After adjusting for other variables, heterogeneous HTAs were associated with a reduction of 19.0 letters (95% CI 9.8, 28.2; p < 0.001) and 16.8 letters (95% CI 9.3, 24.3; p < 0.001) compared with homogeneous and indeterminate phenotypes, respectively. Conclusions HTAs are prevalent in eyes with nAMD and can be objectively classified into distinct phenotypes associated with differences in morphology, demographics, spatial distribution in the macula, and BCVA.