Multimodal adaptive optics SLO/OCT imaging in eyes with geographic atrophy reveals the cellular status of the photoreceptor – retinal pigment epithelium complex

Abstract

Purpose : Age-related macular degeneration (AMD) is a leading cause of vision loss, but controversy remains as to the status of cells during disease progression. In this study, we imaged the photoreceptor-retinal pigment epithelium (PR-RPE) complex in patients with geographic atrophy (GA) associated with AMD using a custom-built multimodal adaptive optics (AO) retinal imager in combination with established clinical imaging modalities.

Methods : A multimodal retinal imager that combines AO scanning light ophthalmoscopy (AOSLO, λ=790nm) and optical coherence tomography (AO-OCT, λ=1077nm) was used to enable simultaneous collection of images revealing different information. Images were acquired in 3 patients with juxtafoveal GA. Split detection, confocal reflectance, and AO-OCT were used to assess cone photoreceptor inner segments (IS), waveguiding, and outer PR-RPE bands. Near-infrared autofluorescence (AO-IRAF) and late phase indocyanine green fluorescence (AO-ICG) were used to assess RPE viability. Cone IS and RPE spacings were quantified at various locations and compared to published normative data.

Results : There was good overall agreement across imaging modalities. Cone IS spacings measured at GA margins (n=12 ROIs) were generally within normal ranges, suggesting overall cone IS preservation. Colocalization of atrophy seen by AO-IRAF and AO-ICG suggested that intact RPE cells were present up to the boundary. Reduced (confocal) reflectivity was sometimes observed perilesionally, indicating possible disruption of cone outer segments (OS). This was corroborated by AO-OCT images which showed the preservation of cone IS/OS reflections with absence of corresponding cone outer segment tip (COST) reflections. In one eye, abnormally enlarged RPE cells (2.7-4.8X increase in RPE spacing, n=6) were observed in some areas well outside of GA margins as seen on AO-ICG, indicating that RPE pathological changes may extend into the macula outside of GA. In these areas, normal cone IS spacing was observed.

Conclusions : We demonstrate the capability of multimodal ophthalmoscopy to simultaneously visualize and quantify the PR-RPE complex at the cellular level in eyes with GA. These new advances provide insights into the changes in cellular physiology and cell-cell interactions underlying the pathobiology of GA.

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