To investigate whether the spatial distribution of photoreceptor density governs the rate and directionality of geographic atrophy (GA) progression and to propose a photoreceptor density–based metric for biologically informed assessment of GA progression. A retrospective longitudinal analysis of untreated fellow eyes from a multicenter, randomized, sham-controlled clinical trial (MAHALO). A total of 103 untreated fellow eyes from 143 eyes enrolled in the MAHALO study, all with GA secondary to age-related macular degeneration. Fundus autofluorescence images obtained at baseline and 18 months were analyzed. Geographic atrophy lesion area and boundary progression distance (“front”) were quantified using rigidly registered images. The retina was divided into concentric eccentricity rings centered on the fovea. Theoretical cone and rod density models derived from histologic data were applied to generate photoreceptor density maps. Photoreceptor loss within GA lesions was estimated, and a photoreceptor-adjusted front was calculated by weighting boundary progression by local photoreceptor density. Directional progression was further evaluated using clock-hour–based analysis and a cosine-based directional metric (cosθ). Geographic atrophy area enlargement, front progression distance, photoreceptor-adjusted front, ring-wise photoreceptor loss, and directional variability of lesion expansion. Geographic atrophy enlargement differed significantly across eccentricity rings (P < 0.001), demonstrating relatively slower expansion in regions with higher modeled photoreceptor density and greater expansion in lower-density regions. Total photoreceptor loss showed a moderate positive correlation with GA area enlargement (r = 0.48; P = 0.001). Directional variability of progression was significantly reduced when using the photoreceptor-adjusted front compared with the geometric front (coefficient of variation: 0.769 vs. 1.145; P < 0.01). In extrafoveal lesions, conventional front measurements demonstrated more rapid peripheral versus foveal progression, whereas this directional asymmetry was attenuated after photoreceptor density adjustment. Geographic atrophy progression may be partly explained by the spatial distribution of photoreceptor density, among other contributing biological factors. Apparent directional and regional differences in GA expansion may reflect underlying gradients in photoreceptor density in addition to geometric and other biological influences. Photoreceptor density–based metrics provide a biologically informed framework for interpreting GA progression and may serve as complementary measures for natural history studies and clinical trials. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: Age-related macular degeneration is a major cause of vision loss, and improved visualization of macular neovascularization (MNV) on OCT angiography (OCTA) could enhance clinical assessment. This study aimed to establish a simple and accessible image enhancement method. Methods: We retrospectively analyzed 24 eyes from 22 patients with MNV at the Doheny UCLA Eye Centers. Grayscale-inverted OCTA images were generated using the basic “Invert” function in ImageJ 1.51 23. Each original and inverted image pair was assessed for seven MNV-related features: structure and area within 3 × 3 mm, 6 × 6 mm and 12 × 12 mm scans, and presence of polypoidal lesions. Twenty-one ophthalmologists graded visibility using a standardized five-point scale. Paired comparisons were performed using the Wilcoxon signed-rank test. Results: Grayscale inversion significantly improved the visualization of MNV structure in 6 × 6 mm scans (mean difference: +0.67 ± 1.02; p = 0.008), 12 × 12 mm scans (+0.62 ± 1.07; p = 0.013), and detection of polypoidal lesions (+0.43 ± 0.98; p = 0.030). No significant differences were found for 3 × 3 mm structure (p = 0.793) or area-related features (all p > 0.3). Conclusions: Grayscale inversion may enhance MNV visibility and polypoidal lesion detection on OCTA. As this study relied solely on subjective assessments, future work should incorporate quantitative image analysis.

To investigate the impact of epiretinal membrane (ERM) on the structural characteristics of acquired vitelliform lesions (AVLs) in eyes with intermediate age-related macular degeneration (iAMD). Cross-sectional study. Eyes of patients with iAMD-associated AVLs were identified from a tertiary referral center database. Multimodal imaging, including spectral-domain OCT, was reviewed. Eyes were stratified according to the presence (ERM + AVL) or absence (AVL-only) of ERM. Quantitative OCT parameters, including apical AVL height and width, and qualitative structural features such as intraretinal hyperreflective foci (IHRF), ellipsoid zone (EZ), and external limiting membrane (ELM) disruption, and AVL location relative to drusen, were assessed by masked graders. Effect sizes were calculated using Hedges' g. Group comparisons were performed using appropriate parametric or nonparametric tests. Differences in AVL structural characteristics between eyes with and without ERM. A total of 234 eyes with age-related macular degeneration (AMD)-associated AVLs were included, of which 17 eyes had concomitant ERM. Eyes with ERM demonstrated significantly greater apical AVL height compared with AVL-only eyes (169.9 ± 52.5 μm vs. 134.8 ± 55.0 μm; P = 0.016). Acquired vitelliform lesion width was greater in the ERM + AVL group, although this difference did not reach statistical significance (811.1 ± 251.0 μm vs. 676.8 ± 416.0 μm; P = 0.057). The prevalence of IHRF, EZ disruption, ELM disruption, and AVL location over drusen did not differ significantly between groups. Effect size analysis demonstrated a moderate positive effect for apical AVL height (Hedges' g ≈ 0.65; 95% confidence interval [CI] ∼0.15 to 1.10), whereas AVL width showed a small-to-moderate effect size with CIs crossing 0. In eyes with AMD-associated AVLs, the presence of ERM is associated with increased AVL height without corresponding differences in other outer retinal structural features. These findings suggest that vitreomacular traction may selectively influence AVL configuration. Longitudinal studies are needed to determine whether traction-related modulation of AVL morphology impacts AMD disease progression and AVL collapse. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.