Visual Function at the Atrophic Border in Choroideremia Assessed with Adaptive Optics Microperimetry

Abstract

Recent advances in retinal imaging allow visualization of structural abnormalities in retinal disease at the cellular level. This study used adaptive optics (AO) microperimetry to assess visual sensitivity with high spatial precision and to examine how function varies across 2 phenotypic features observed in choroideremia: atrophic lesion borders and outer retinal tubulations (ORTs). Cross-sectional study. Twelve choroideremia patients. A custom AO scanning light ophthalmoscope (AOSLO) equipped with both confocal and nonconfocalsplit-detection imaging methods was used to image the photoreceptor inner and outer segment mosaics. For AO microperimetry, circular 550-nm stimuli were presented through the AOSLO system; stimuli were either 9.6 or 38.3 arcmin2 (approximately 60 or 15 times smaller than a Goldman III stimulus). Test locations were identified in structural images and stimuli were targeted to these locations using real-time retinal tracking combined with measurements of transverse chromatic aberration. Psychophysical detection thresholds were measured at the atrophic border in 12 patients. Additionally, visual sensitivity was probed along ORTs in 4patients. Visual sensitivity thresholds measured with AO microperimetry at retinal locations corresponding to structural phenotypes observed on AOSLO retinal images. In choroideremia, sharp borders between intact central islands of the photoreceptor mosaic and complete atrophy of the outer retina and retinal pigment epithelium were observed in both split-detection and confocal structural images. Adaptive optics microperimetry at locations spanning these borders showed a commensurately sharp decrease in function, with readily measurable visual sensitivity on one side and dense scotoma on the other. These functional transitions often occurred over a distance smaller than the diameter of the Goldman III stimulus. Thresholds measured along ORTs showed dense scotoma over the tubule in all 4 participants, despite the visibility of remnant cone inner segments on the AO images. Choroideremia patients exhibited sharp functional transitions that collocated with structural transitions from intact to severely degenerated retina. We found no evidence of visual sensitivity over ORTs. Measuring cone function with high resolution offered insight into disease mechanisms and may enable precise assessment of whether experimental therapies, such as gene therapy, provide a functional benefit.