Cellular-scale assessment of visual function in Choroideremia

Abstract

Purpose : Advanced retinal imaging allows identification of cellular-scale structural abnormalities in retinal disease. Here we use adaptive optics scanning laser ophthalmoscopy (AOSLO) to assess retinal function at high spatial resolution, and ask how function varies with structural changes observed in Choroideremia (CHM), an X-linked inherited retinal degeneration.

Methods : Structural images of the inner and outer segment mosaics were imaged in twelve CHM patients using a custom AOSLO equipped with both confocal and split-detection imaging modalities. The same instrument was used to make two types of functional measurements. 1) For AO microperimetry (11 of 12 patients), circular stimuli of 550 nm subtending either 9.6 or 38.3 arcmin^2 (~60 or 15 times smaller than Goldman III stimuli) were presented through the AOSLO system. Measurements of transverse chromatic aberration combined with real-time retinal tracking enabled precise targeting of stimuli to pre-identified locations and psychophysical thresholds were measured. 2) For intrinsic reflectance (7 of 12 patients), infrared confocal images were acquired before, during and following exposure to 550 nm square stimuli subtending 1 deg^2. Reflectance responses were extracted for each cone as described in Cooper et al. (2017, Biomed. Opt. Express); these signals are related to phototransduction (ibid).

Results : In CHM, both split-detection and confocal structural images show sharp borders between intact central islands of photoreceptors and complete atrophy of the outer retina. AO microperimetry at locations directed across these borders also show a sharp decrease in function, with readily measureable visual thresholds on one side and complete scotoma on the other. Thresholds measured along an outer retinal tubulation showed complete scotoma despite the presence of visible cone inner segments. The average amplitude of the intrinsic reflectance response was reduced by a factor of 6.8 in CHM compared to controls.

Conclusions : CHM patients exhibit sharp functional transitions between intact and degenerated retina. These functional transitions can occur over an area smaller than the Goldman III stimulus. In addition, the intrinsic reflectance response can provide a high throughput biomarker of local cone function in retinal disease. High resolution measures of cone function are important, in particular for assessing whether experimental therapies provide a functional benefit to patients.

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