Optical Coherence Tomography Signs of Early Atrophy in Age-related Macular Degeneration: Inter-Reader Agreement

Abstract

Purpose : To determine the inter-reader agreement for structural features related to incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA respectively) in age-related macular degeneration (AMD).

Methods : Following formal training (reviewing literature, performing a pre-test twice and undergoing a web-based tutorial), readers qualitatively assessed 60 optical coherence tomography (OCT) B-scans from 60 eyes with AMD for nine individual features associated with early atrophy and performed seven different annotations to quantify the spatial extent of OCT features within regions-of-interests. Cases were selected to depict the entire spectrum of findings that may be observed in dry AMD eyes with and without atrophy. Inter-reader agreement based on kappa coefficients (κ) and smallest real difference (SRD) was assessed.

Results : Slight to substantial inter-reader agreement was observed for assessment of individual features associated with atrophy (κ=0.19–0.70), with lowest and highest agreement being for outer nuclear layer thinning and inner nuclear layer (INL) subsidence, respectively. The lowest SRD for horizontal annotations was observed for the zone of choroidal hypertransmission (±190.8µm). Using the qualitative and quantitative gradings to derive atrophic features, there was moderate agreement for a two-category classification of the presence or absence of at least iRORA (κ=0.53), and substantial agreement for the presence or absence of cRORA (κ=0.62). There was moderate agreement for a three-category classification of no atrophy, iRORA and cRORA (κ=0.52). Exploratory analyses suggested a significantly higher level of agreement for a three-category classification using (i) no atrophy, (ii) presence of INL and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band as a less severe atrophic grade and (iii) the latter plus an additional requirement of choroidal hypertransmission ≥250µm for a more severe atrophic grade (κ=0.68; P=0.004).

Conclusions : While current definitions of iRORA and cRORA allow for a consistent and robust assessment of early atrophy, a refined combination of individual features improved inter-reader agreement. This evaluation represents an important step towards a more detailed classification system for atrophic AMD and helps to inform the design and analysis of future early interventional clinical trials in AMD.

This is a 2021 ARVO Annual Meeting abstract.