Histologically-guided metrics for atrophy progression in age-related macular degeneration (AMD) tested via clinicopathologic correlation.

Abstract

Purpose : To analyze the correlation of histologic findings at the border of atrophy with in vivo optical coherence tomography (OCT) features in a patient with atrophy due to AMD. We evaluated in OCT scans the visibility and reproducibility of two metrics suggested by histology of GA – the external limiting membrane (ELM) descent towards Bruch’s membrane (BrM) as a border of atrophy and a thickening of the retinal pigment epithelium (RPE)-basal laminar deposit (BLamD) band towards this border as a progression marker.

Methods : Eye-tracked OCT scans were analyzed including qualitative and quantitative parameters, and histologic correlates were assessed. On the in vivo OCT scans, the border of the atrophy was identified based on 2 different criteria: the ELM descent (histologic definition), and the presence of choroidal hypertransmission (tomographic definition, increased reflectivity within the underlying choroid). The status of the RPE-BLamD-BrM complex was also analyzed at 500 and 100 µm on the non-atrophic and atrophic sides of this border, at the nasal and temporal sides of the central atrophic area, and then correlated with the histology.

Results : Borders defined by the ELM descent delineated a smaller area of atrophy than the area defined by the presence of hypertransmission. The RPE-BLamD layer significantly thickened towards the ELM descent in histology (p<0.001) and in the OCT scans (p<0.005). A significant progressive thickening of the RPE-BLamD band over time (5 months) was observed at the 500 and 100 µm locations using eye-tracked OCT scans (p=0.015 and 0.043). Measurement of BrM thickness was difficult using OCT.

Conclusions : A multimodal imaging approach is recommended for the diagnosis and follow-up of the atrophic changes in AMD, however different information on the atrophic status is provided by each imaging modality, and no comparison is possible between modalities and, even between different devices. In our study, the ELM descent is visible in every OCT scan, and may constitute a good anatomical definition of the border of the atrophy on OCT with direct correlation with histology. Further analysis of the ELM descent correlation with other imaging modalities, the visibility of these landmarks in other image datasets, and automatic measurements of the atrophic area is warranted.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.