Progressive damage to retinal pigment epithelial cells near subretinal drusenoid deposits revealed using adaptive optics

Abstract

Purpose : Retinal pigment epithelial (RPE) cell damage has been implicated in the pathogenesis of eyes with subretinal drusenoid deposits (SDD). In this study, multimodal imaging, including autofluorescence, optical coherence tomography, and adaptive optics (AO), was used to longitudinally evaluate RPE cells near SDD.

Methods : SDD were identified based on multimodal imaging performed in six subjects (three with late-onset retinal degeneration, L-ORD, and three with early/intermediate age-related macular degeneration, AMD). Fluorescently labeled RPE cells were imaged within retinal regions containing SDD using AO (PMID 30895942), from which quantitative measurements of RPE cell-to-cell spacing were obtained for comparison to normative RPE data (PMID 29082069). For a subset of subjects (two with L-ORD and two with AMD), longitudinal imaging over a period of up to 5 years was performed to evaluate whether there were any changes in either SDD or RPE across time.

Results : The hyperreflective cores of individual SDD lesions as imaged by AO were dynamic in both L-ORD and AMD, consistent with what has been previously reported using AO in AMD (PMID 28196054). We observed examples of individual SDDs located at eccentricities of 1.5 to 5 mm that were enlarged laterally as well as others that decreased in size (44% of all longitudinally-tracked lesions increased and 56% decreased). On the baseline visit, RPE spacing was increased relative to normative data in retinal regions containing SDD by 24.3±14.8% (mean±SD, n=27 retinal regions). Longitudinal imaging (up to 5 visits over 5 years) revealed that RPE spacing further worsened at a rate of 4.7±4.3% per year (% increase relative to baseline) alongside the dynamic SDD lesions, indicating that there is slow, progressive damage to the RPE that accompanies SDD.

Conclusions : RPE cell spacing is increased in retinal regions containing SDD and continues to deteriorate with dynamic changes to the individual SDD lesions. These slow progressive changes to the RPE may cumulatively contribute to more advanced disease in eyes with SDD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.