High resolution structural phenotyping of intermediate and advanced non-neovascular age-related macular degeneration

Abstract

Purpose : Non-neovascular age-related macular degeneration (AMD), accounting for ~90% of prevalence, is currently untreatable. Adaptive optics ophthalmoscopy (AOO) offers promise to define and monitor microscopic and progressive changes in AMD, yet limited data on high resolution AMD structural phenotypes and their relationship to conventional imaging metrics limits the power of this approach. We hypothesize that AOO can characterize different phenotypes in AMD that may correlate with short and long-term progression patterns. As a first step, we define the cellular level structural phenotypes associated with intermediate and advanced AMD and their relationship to clinical imaging biomarkers in a large cohort.

Methods : We recruited 118 patients with intermediate and advanced AMD from the Quinze-Vingts National Ophthalmology Hospital and the University of Pittsburgh Department of Ophthalmology. All participants underwent color fundus photography, spectral-domain optical coherence tomography (SD-OCT), confocal scanning laser ophthalmoscopy (near-infrared (NIR) reflectance; blue fundus autofluorescence (FAF) and NIR FAF), and flood-illumination adaptive optics (FIAO) ophthalmoscopy (rtx1, Imagine Eyes, France). Select patients were imaged with adaptive optics scanning light ophthalmoscopy (AOSLO). Multi-modal en face images were registered and structural phenotypes were evaluated and compared across multi-scale images.

Results : Several distinct cellular level structural phenotypes were identified. Though some structures, such as drusen, were visible in clinical images and in AOO, their appearance and spatial extent differed markedly between modalities. Geographic atrophy (GA) lesions, visible in 21 patients, presented in AOO with several discrete forms, including either distinct or indistinct borders, marginal hyper- or hypo-reflectance and heterogenous distribution of pigmented cellular aggregates along the GA border.

Conclusions : Multi-modal and multi-scale imaging provides unprecedented insight into the in vivo tissue and cellular-level morphological alterations associated with intermediate and advanced AMD. Longitudinal follow-up imaging will provide insight into potential differences in progression rate amongst phenotypes. Ongoing work will evaluate the relationship between cellular phenotypes, disease progression rate, genotype and clinical characteristics.

This is a 2020 ARVO Annual Meeting abstract.