Cone Photoreceptor Structure in Achromatopsia

Abstract

Purpose: : Achromatopsia (ACHM) is considered to be a stationary cone disorder with animal studies suggesting it may be a good candidate for gene replacement therapy. Recent clinical studies have suggested that progressive cone loss may occur with age. This study further investigates the integrity of cone photoreceptors in ACHM.

Methods: : 60 eyes of 30 patients with ACHM underwent spectral domain optical coherence tomography (SDOCT) imaging (49 B-scans, 20°x20°, 12 frames per B-scan). SDOCT retinal appearance was classified as (1) normal outer retinal structure, (2) inner segment/outer segment disruption, (3) hyporeflective zone presence and (4) complete cone and RPE cell layer disruption.

Results: : Mean age of subjects was 26.3 years (range 8-53 years). 20% of eyes had normal outer retinal structure, 30% had inner segment/outer segment disruption, 37 % had a hyporeflective zone present, and 13 % had complete cone and RPE cell layer disruption. There was high inter-eye correlation of SDOCT changes. There was no significant difference in age of subjects (p=0.760) or visual acuity (p=0.152) between the SDOCT change categories.

Conclusions: : SDOCT changes in ACHM can vary from apparently normal outer retinal structure to complete cone loss with RPE involvement. These changes were not present in an age-dependent manner, or associated with visual acuity; implying that the window of opportunity for gene therapy intervention may extend into adulthood, and prospective patients need to be assessed on an individual basis, irrespective of age.

Keywords: gene transfer/gene therapy • photoreceptors • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)