High-Resolution Imaging To Probe Retinal Integrity In RPGR Associated Rod-Cone Dystrophy

Abstract

Purpose: In preparation for gene augmentation therapies there is need to characterize retinal structure and function in patients with X-linked Retinitis Pigmentosa (RP) due to mutations in the RPGR gene to determine viability of successful intervention, window of opportunity, and sensitive and reliable end-points.

Methods: Three male patients (15, 20 and 43 years old) with molecularly confirmed RPGR-associated RP underwent clinical examination and retinal imaging including autofluorescence (AF) imaging, spectral domain optical coherence tomography (SDOCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). Retinal lamination was assessed using SDOCT and AOSLO was used to probe integrity of the photoreceptor mosaic and assess qualitative changes in reflectance.

Results: Visual acuity in the youngest patients was 20/20 and in the eldest 20/60. This was consistent with the residual island of outer retinal architecture on SDOCT and relatively normal central macular AF. All subjects had a perifoveal ring of increased AF. Foveal cone topography on AOSLO was normal in the younger subjects, deteriorating rapidly away from the foveal centre. The older subject had a disrupted mosaic throughout the foveal region. At the boundaries of the intact photoreceptor mosaic RPE-appearing cells were observed. These corresponded well with the transition zone between normal macular AF and the ring of increased AF signal, and disappeared at the outermost edge of the high-density AF ring. Consistent with previous reports, the transition zones from normal to high AF and from intact photoreceptor mosaic to RPE cells correlated well with the drop off in outer retinal architecture observed on SDOCT.

Conclusions: Despite X-linked RP being a rapidly progressive and early-onset form of RP, there is a window of opportunity for intervention that extends several decades. It will be important to undertake serial quantitative imaging to determine the rate of progression, which is likely highly variable, to identify potential participants who might be most likely to benefit and to characterise the most sensitive metrics to determine efficacy in a timely fashion. Our AOSLO imaging is currently limited to reflectance imaging of waveguiding photoreceptors, new split-detection AOSLO that can identify cone inner segments will be valuable to probe whether rescuable cones remain over regions of RPE-like cells at the edge of the photoreceptor mosaic.

Keywords: 550 imaging/image analysis: clinical • 648 photoreceptors • 696 retinal degenerations: hereditary