Spatio-temporal alterations in retinal and choroidal layers in the progression of age-related macular degeneration (AMD) in optical coherence tomography

Abstract

Age-related macular degeneration (AMD) is the predominant cause of vision loss in the elderly with a major impact on ageing societies and healthcare systems. A major challenge in AMD management is the difficulty to determine the disease stage, the highly variable progression speed and the risk of conversion to advanced AMD, where irreversible functional loss occurs. In this study we developed an optical coherence tomography (OCT) imaging based spatio-temporal reference frame to characterize the morphologic progression of intermediate age-related macular degeneration (AMD) and to identify distinctive patterns of conversion to the advanced stages macular neovascularization (MNV) and macular atrophy (MA). We included 10,040 OCT volumes of 518 eyes with intermediate AMD acquired according to a standardized protocol in monthly intervals over two years. Two independent masked retina specialists determined the time of conversion to MNV or MA. All scans were aligned to a common reference frame by intra-patient and inter-patient registration. Automated segmentations of retinal layers and the choroid were computed and en-face maps were transformed into the common reference frame. Population maps were constructed in the subgroups converting to MNV (n=135), MA (n=50) and in non-progressors (n=333). Topographically resolved maps of changes were computed and tested for statistical significant differences. The development over time was analysed by a joint model accounting for longitudinal and right-censoring aspect. Significantly enhanced thinning of the outer nuclear layer (ONL) and retinal pigment epithelium (RPE)–photoreceptorinner segment/outer segment (PR-IS/OS) layers within the central 3 mm and a faster thinning speed preceding conversion was documented for MA progressors. Converters to MNV presented an accelerated thinning of the choroid and appearance changes in the choroid prior to MNV onset. The large-scale automated image analysis allowed us to distinctly assess the progression of morphologic changes in intermediate AMD based on conventional OCT imaging. Distinct topographic and temporal patterns allow to prospectively determine eyes with risk of progression and thereby greatly improving early detection, prevention and development of novel therapeutic strategies.

Biomarkers in Early Response to Brolucizumab on Pigment Epithelium Detachment Associated with Exudative Age-Related Macular Degeneration

“…The performance of fundus autofluorescence (AF) and enface scans are of particular importance in order to follow patients with atrophic AMDs. In fact, these techniques can easily identify and help predict any increase in the area of retinal atrophy [31,32]. The role of an abnormal choriocapillaris perfusion of the macular area also has been recently reported to be a contributing factor to the progression of non-exudative AMD [33].…”

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

“…Age-related macular degeneration (AMD) is a disease that damages the macular region of the retina and leads to progressive loss of central vision, which is the leading cause of blindness in the elderly population. 1 The overall prevalence in Europe was 16.2% for AMD, and the number of global population with AMD will increase to 288 million by 2040. 2,3 AMD is not simply a "macular" disease, but involves the entire retina.…”

Developing and validating a multivariable prediction model which predicts progression of intermediate to late age-related macular degeneration—the PINNACLE trial protocol

“…fast progressors versus slow progressors). We will construct a spatio-temporal atlas that enables us to compare the retinal anatomy across time for an individual subject, between subjects and between different groups of subjects [ 25 , 26 ]. It is expected that such atlas and associated representations will facilitate identification of structural changes in the outer retina over time that may shed light on the biological process by which these changes convert to late AMD.…”