Interreader Agreement and Longitudinal Progression of Incomplete/Complete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration

Abstract

To analyze the ability to evaluate changes over time of individual lesions of incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA, respectively) in patients with intermediate age-related macular degeneration (iAMD). OCT images from patients enrolled in Proxima B clinical trial (NCT02399072) were utilized. Patients enrolled in the Proxima B clinical trial, from the cohort with geographic atrophy (GA) in 1 eye and iAMD in the other eye at baseline, were included. Junior and senior readers analyzed OCT images for the qualitative presence of 9 distinct early atrophic features (presence of zone of choroidal hypertransmission, attenuation and/or disruption of RPE, disruption of ellipsoid zone [EZ] and external limiting membrane [ELM], outer nuclear layer [ONL] thinning, outer plexiform layer [OPL]/inner nuclear layer [INL] subsidence, and hyporeflective wedge-shaped band). If deemed "present," 7 features were quantified with a predefined tolerance level of 50 μm (diameter for the zone of choroidal hypertransmission, zone of attenuation and/or disruption of the RPE, outer retinal thickness left/right vertical diameter, outer retinal thickness thinnest vertical diameter, annotation of EZ, and ELM disruption). Interreader agreements for qualitative assessments (κ-type statistics) and quantitative measurements (Bland-Altman statistics) were assessed. Progression of the lesion features over time was described. Moderate agreement was found for presence of choroidal hypertransmission (κ= 0.54), followed by ELM disruption (κ= 0.58), OPL/INL subsidence (κ= 0.46), and a hyporeflective wedge-shaped band (κ= 0.47). Quantification measurements showed that choroidal hypertransmission had the highest agreement, whereas RPE attenuation/disruption had the lowest agreement. Longitudinal adjudicated changes for quantitative measurements of lesion progression showed that choroidal hypertransmission and ELM disruption showed significant progression, whereas EZ disruption and RPE attenuation/disruption did not. The ability to evaluate changes over time for specific features of iRORA and cRORA was explored. The most robust biomarker was found to be choroidal hypertransmission, followed by ELM disruption and the qualitative markers of OPL/INL subsidence, as well as a wedge-shaped band. Disease progression over time could be assessed by some, but not all, spectral-domain OCT features that were explored. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.