Photoreceptor and RPE Disruptions Observed Outside Clinically Visible Geographic Atrophy Lesions in the Living Eye with Fluorescence Adaptive Optics Scanning Laser Ophthalmoscopy (FAOSLO)

Abstract

 

Purpose:

 

To determine the microscopic anatomical retinal changes that precede and/or accompany geographic atrophy (GA) development and progression in the living human eye.

 

Methods:

 

Patients completed full clinical exams, including imaging of retinal structure using fundus photography, SD-OCT (Heidelberg Engineering Spectralis & Bioptigen) and confocal scanning laser ophthalmoscopy (cSLO) (Heidelberg Engineering HRA). Patients were imaged using near infrared (NIR) light at the initial FAOSLO imaging session. Imaging was targeted to extend into areas well outside the clinically visible lesion. Select patients returned for follow up imaging sessions to evaluate disease progression. Several of these patients underwent simultaneous NIR reflectance and autofluorescence (AF) imaging in FAOSLO, exploiting the intrinsic AF of lipofuscin to examine RPE, using 561 nm light for excitation and 604 to 644 nm for imaging.

 

Results:

 

Major disruptions to the photoreceptor mosaic were seen well outside the clinically visible GA lesion(s) in all patients. These photoreceptor disruptions were observed in some patients as far from the margin of the GA lesion as we have looked (~680 μm). Changes in the photoreceptor mosaic were observed in patients who underwent repeat imaging, including variations in the reflectivity of individual photoreceptors. Individual RPE cells were not resolved; however, AF imaging in FAOSLO revealed microscopic regions of hyper-AF and hypo-AF that matched photoreceptor reflectance changes. These AF patterns did not appear visible in commercial cSLO. Hypo-AF areas co-localized with decreased reflectivity from the overlying photoreceptors, while hyper-AF areas co-localized with increased reflectivity from overlying photoreceptors.

 

Conclusions:

 

FAOSLO can provide unique insight into the pattern and time course of changes to the cellular mosaics of the retina as a result of AMD in the living eye. The exquisite resolution of FAOSLO allows for small changes, such as modulations in the reflectivity of individual cone photoreceptors, to be seen in periods as short as a few months. The improved resolution of FAOSLO reveals microscopic patterns of AF that are invisible to commercially available instruments; future work will further improve this method to reveal individual RPE cells in GA. These abnormal AF patterns co-localize with photoreceptors disruptions, suggesting that these areas are undergoing degeneration.

 

Keywords: age-related macular degeneration • retina • imaging/image analysis: clinical