Progression Dynamics of Early versus Later Stage Atrophic Lesions in Nonneovascular Age-Related Macular Degeneration Using Quantitative OCT Biomarker Segmentation

Purpose: To investigate the progression of geographic atrophy secondary to nonneovascular age-related macular degeneration in early and later stage lesions using artificial intelligence-based precision tools.Design: Retrospective analysis of an observational cohort study.Subjects: Seventy-four eyes of 49 patients with =1 complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to age-related macular degeneration were included. Patients were divided between recently developed cRORA and lesions with advanced disease status.Methods: Patients were prospectively imaged by spectral-domain OCT volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recent cRORA-converted lesions were compared with lesions in an advanced disease status using mixed effect models.Main Outcome Measures: The progression of retinal pigment epithelial loss (RPEL) was considered the primary end point. Secondary end points consisted of external limiting membrane disruption and ellipsoid zone loss. These pathognomonic imaging biomarkers were quantified using validated deep-learning algorithms. Further, the ellipsoid zone/RPEL ratio was analyzed in both study cohorts.Results: Mean (95% confidence interval [CI]) square root progression of recently converted lesions was 79.68 (95% CI,-77.14 to 236.49), 68.22 (95% CI,-101.21 to 237.65), and 84.825 (95% CI,-124.82 to 294.47) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss respectively. Mean square root progression of advanced lesions was 131.74 (95% CI,-22.57 to 286.05), 129.96 (95% CI,-36.67 to 296.59), and 116.84 (95% CI,-90.56 to 324.3) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss, respectively. RPEL (P = 0.038) and external limiting membrane disruption (P = 0.026) progression showed significant differences between the 2 study cohorts. Further recent converters had significantly (P < 0.001) higher ellipsoid zone/RPEL ratios at all time points compared with patients in an advanced disease status (1.71 95% CI, 1.12-2.28 vs. 1.14; 95% CI, 0.56-1.71).Conclusion: Early cRORA lesions have slower growth rates in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of nonneovascular age-related macular degeneration and for the interpretation of clinical trials in geographic atrophy. Individual disease monitoring using artificial intelligence-based quantification paves the way toward optimized geographic atrophy management.

Automated summary

This study investigated the progression of geographic atrophy secondary to nonneovascular age-related macular degeneration using artificial intelligence-based precision tools. The findings revealed that early lesions have slower growth rates and there are differences in growth dynamics compared to atrophic lesions in advanced stages.