Natural History of Rod and Cone Photoreceptor Dysfunction in Choroideremia

Abstract

Purpose : To describe the natural history of central cone- and rod- photoreceptor dysfunction in choroideremia (CHM).

Methods : Visual thresholds determined by light-adapted (achromatic) and dark-adapted (chromatic) perimetry (Goldmann size V stimulus) in patients with CHM (n=40, ages 9 to 69 years). Sensitivities were determined every 2° along a horizontal meridian extending to 30° of eccentricity and were related with co-localized measures of photoreceptor structure by spectral domain optical coherence tomography (SD-OCT).

Results : 1120 retinal locations were evaluated excluding the blind spot (14-16° temporal field) and the fovea. Rod-mediated central sensitivities were measurable only in 17% of the locations (19 patients); when measurable, thresholds were elevated on average by at least 1.5 log units. Cone-mediated sensitivities were measurable in 81% of the locations; sensitivities were within normal limits (17% of the locations) or reduced (64% of the locations) on average by at least 0.3 log units. There was a strong relationship between rod and cone dysfunction in locations where both cone- and rod-mediated function could be ascertained. At least 0.5 -1 log unit of rod photoreceptor desensitization occurred before cone dysfunction was measurable. Locations within absolute rod scotomas often showed spared cone sensitivities and outer retinal structure. Locations with detectable rod and cone function, generally from younger patients, showed the best preserved outer retina.

Conclusions : CHM shows a severe rod photoreceptor dysfunction both in the near mid-periphery and central retina from the earliest stages. The relationships between rod and cone function suggest substantial loss of rod function occurs before cone dysfunction and that residual cones with relatively spared function can survive relatively well in this disease after total loss of rods.

This is a 2020 ARVO Annual Meeting abstract.