Abstract
Purpose: Mutations in the RPGR gene have been shown to cause both Rod-Cone and Cone-Rod dystrophies. In preparation for gene augmentation therapies, there is need to characterize retinal structure and function in patients with retinal dystrophy due to mutations in the RPGR gene, to assist with participant identification, determine the window of opportunity, and identify sensitive and reliable end-points. Methods: Molecularly confirmed RPGR subjects with Rod-Cone dystrophy (RCD) (n=14) and Cone-Rod dystrophy (CORD) (n=6) underwent clinical examination and retinal imaging, including autofluorescence (AF) imaging, spectral domain optical coherence tomography (SDOCT), and adaptive optics scanning light ophthalmoscopy (AOSLO) confocal and split detector imaging. Results: Subjects ranged in age from 15 to 57 in the CORD group. Best-corrected visual acuity in subjects with CORD was poorer (range 6/60 to light perception) than in RCD (range 6/6 – 6/20). Visual function was highly correlated with retinal integrity and autofluorescence measurements. Confocal imaging showed a variable foveal mosaic in the RCD and absent waveguidingfoveal cones in CORD. RPE-like cells were visible in the transition zones. Split detector imaging shows the existence of cone inner segments in regions void of waveguiding cones, and dark field imaging confirms RPE structures well into the transition zones. Conclusions: Both dystrophies result in severe degeneration, with a variable window of opportunity for intervention that potentially extends several decades. It will be important to undertake serial quantitative imaging to determine the rate of progression, which is likely highly variable, in order to identify potential participants who might be most likely to benefit and characterize the most sensitive metrics to determine efficacy in a timely fashion.