Visible-to-near-infrared spanning Optical Coherence Tomography for retinal imaging at the half-micron scale

New York University School Of Medicine, New York NY

Investigators

Abstract

Abstract: Historically there have been no effective treatments for geographic atrophy, the end stage of dry age-related macular degeneration (AMD). Recently, two complement inhibition treatments were shown to slow atrophic AMD progression, leading to FDA approval last year. Ideally, these and other promising treatments would be applied even earlier, before atrophy has begun. In this endeavor, early, high-risk biomarkers are needed. While the Classification of Atrophy Meetings (CAM) scheme provides staging of atrophy and nascent atrophy, it lacks granularity in the intermediate AMD stage, when these and other treatments are likely to be most effective. Macular pigments (MPs) and retinal pigment epithelium (RPE) melanosomes are beneficial for vision and protect against the development of advanced AMD. MPs are the target of Age-Related Eye Disease Study (AREDS)/AREDS2 dietary supplements, and until recently, the only accepted intervention for dry AMD. However, accurate measurement of MPs in the living eye has been challenging, and for this reason large-scale MP assessment was omitted from the landmark AREDS/AREDS2 studies. Likewise, there is no accepted method to measure RPE melanosomes/melanolipofuscin (RPEMs) in humans, so the CAM scheme assesses RPEM loss indirectly, by OCT hyper-transmission. Over the past several years, our group has pushed the axial resolution of visible light Optical Coherence Tomography (OCT) to 1 micrometer, demonstrating a multitude of bands which are not quantifiable by other techniques, including important substrates of AMD within the photoreceptors, retinal pigment epithelium (RPE), and Bruch's membrane (BM). Recently we showed quantification and localization of MPs to Henle's fiber layer for the first time in vivo, along with preliminary data showing the ability to distinguish lutein and zeaxanthin, the two major MPs. We also demonstrated direct RPEM imaging in vivo via a new spectral red-shift technique. In this proposal, the utility of the above advances for studying aging and AMD will be further bolstered with finer axial resolution and broader spectral coverage. Specifically, we will develop visible-to-near-infrared spanning OCT to image depth-resolved MPs, RPEMs and other novel outer retinal structural biomarkers for the first time, with up to 0.5 micrometer axial resolution, ~6x finer than the best commercial NIR OCT systems (Aim 1). We will investigate the spatiotemporal relationship of these biomarkers with aging (Aim 2) and early AMD (Aim 3a). Finally, we will determine whether MPs and RPEMs (or lack thereof) could serve as early biomarkers for risk of progression to atrophy, by determining association with other high-risk biomarkers (Aim 3b). If borne out by subsequent longitudinal studies, visible light OCT assessment of retinal morphology and MPs/RPEMs could identify potential beneficiaries of early dry AMD treatment.