Subclinical Retinal Pigment Epithelium Changes Observed in Choroideremia Using Adaptive Optics Enhanced Indocyanine Green Imaging

Abstract

Purpose : Choroideremia (CHM) is an X-linked retinal degeneration that leads to progressive damage to the outer retina. Previous studies on histology and adaptive optics (AO) have reported that the photoreceptors are relatively well-preserved in areas where the RPE is intact. In this study, we investigate RPE structure in CHM using adaptive optics enhanced indocyanine green (AO-ICG) imaging to reveal the extent to which RPE is affected.

Methods : Following comprehensive ophthalmic examination, AO-ICG imaging was performed on two female carriers and two affected male patients (n=8 eyes) with molecularly confirmed CHM. Fluorescent AO images of ICG-labeled RPE cells were acquired across a range of retinal locations in which RPE cells were intact, depending on the locations of discrete RPE atrophy. Following manual identification of RPE cells, measurements of RPE spacing and density in CHM were compared to published normative data.

Results : The late phase AO-ICG fluorescence pattern, corresponding to the RPE layer, was markedly different in both carriers and patients with CHM when compared to the expected pattern observed in healthy subjects. In all eyes, areas of dramatically enlarged RPE cells were observed in areas where fundus autofluorescence and optical coherence tomography confirmed the presence of an intact RPE layer. Measurements of RPE cell spacing and density confirmed that there was lower-than-normal RPE density and higher-than-normal RPE spacing for all eyes when compared to normative data (BOE 8(10):4348-4360, 2017). Based on RPE cell spacing measurements, the affected male patients had a greater degree of RPE enlargement (z-scores: 9 to 74; spacing increased by up to 5.2) compared to female carriers (z-scores: 7 to 44; spacing increased by up to 3) across the range of retinal locations measured (0-4.5 mm).

Conclusions : AO-ICG can be used to detect subclinical changes to the RPE structure and may be useful to monitor the efficacy of future therapies in CHM. The observation of interspersed enlarged RPE cells in female carriers and contiguous enlarged RPE cells in affected males, together with previous studies support the notion that the RPE is a primary site of degeneration in CHM.

This is a 2021 ARVO Annual Meeting abstract.