Abstract
PurposeTo characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy.DesignObservational case series.Methodssetting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy.ResultsCone density at 100 μm from foveal center ranged from 123 132 cones/mm2 to 140 013 cones/mm2. Cone density ranged from 30 573 to 34 876 cones/mm2 by 600 μm from center and from 15 987 to 16,253 cones/mm2 by 1400 μm from center, in keeping with data from normal subjects. Adaptive-optics imaging identified a small, focal hyporeflective lesion at the foveal center in both eyes of the subject with RGS9-associated disease, corresponding to a discrete outer retinal defect also observed on spectral-domain optical coherence tomography; however, the photoreceptor mosaic remained intact at all other observed eccentricities.ConclusionsBradyopsia and oligocone trichromacy share common clinical symptoms and cannot be discerned on standard clinical findings alone. Adaptive-optics imaging previously demonstrated a sparse mosaic of normal wave-guiding cones remaining at the fovea, with no visible structure outside the central fovea in oligocone trichromacy. In contrast, the subjects presented in this study with molecularly confirmed bradyopsia had a relatively intact and structurally normal photoreceptor mosaic, allowing the distinction between these disorders based on the cellular phenotype and suggesting different pathomechanisms.
Highlights
T HE PHENOMENON OF BRADYOPSIA (‘‘SLOW VISION’’: OMIM 608415) was first described by Kooijman and associates in 4 patients from 3 unrelated Dutch families.[1]
Electroretinograms according to the protocol recommendations by the International Society for Clinical Electrophysiology of Vision (ISCEV)[8,9] do not allow for the distinction to be made between RGS9/R9AP-associated retinopathy and oligocone trichromacy, with more comprehensive electroretinograms than those mandated by the ISCEV in the electroretinogram standard document being needed
RGS9/R9AP-associated retinopathy can be distinguished from oligocone trichromacy on the basis of molecular screening and distinct electrophysiologic findings following extended assessment.[3,5,10]
Summary
AOSLO 1⁄4 adaptive-optics scanning light ophthalmoscope; MCW 1⁄4 Medical College of Wisconsin; MEH 1⁄4 Moorfields Eye Hospital. Photoreceptor topography was assessed in 3 subjects with typical oligocone trichromacy, confirmed to not harbor variants in either RGS9 or R9AP, using adaptive-optics flood-illuminated ophthalmoscopy (AOFlood).[11] These patients were all found to have a reduced number of waveguiding cones at the fovea, with no structure visible outside the central fovea—thereby confirming the original hypothesis of the underlying basis of oligocone trichromacy, that the disorder was caused by a reduction in number of otherwise functional cone photoreceptors. Spectral-domain optical coherence tomography was used to both qualitatively and quantitatively examine retinal laminar integrity and confocal adaptive-optics scanning light ophthalmoscopy was used to directly probe photoreceptor mosaic architecture in order to determine (1) whether oligocone trichromacy and RGS9/R9AP-associated retinopathy could be discerned at the cellular level, and (2) whether the generalized retinal dysfunction in RGS9/R9AP-associated retinopathy is secondary to cone cell loss/structural deficit or a functional deficit in otherwise intact receptors
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