Retinal Architecture in ​RGS9- and ​R9AP-Associated Retinal Dysfunction (Bradyopsia).
OBJECTIVE
To 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.


METHODS
Observational case series.


METHODS
setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA).


METHODS
Six eyes of 3 subjects with disease-causing variants in ​RGS9 or R9AP.


METHODS
Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy.


RESULTS
Cone density at 100 μm from foveal center ranged from 123 132 cones/mm(2) to 140 013 cones/mm(2). Cone density ranged from 30 573 to 34 876 cones/mm(2) by 600 μm from center and from 15 987 to 16,253 cones/mm(2) 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.


CONCLUSIONS
Bradyopsia 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.
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom.
Rupert W
RW
Strauss
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom.
Adam M
AM
Dubis
Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin.
Robert F
RF
Cooper
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom.
Rola
R
Ba-Abbad
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, University of California San Francisco, San Francisco, California.
Anthony T
AT
Moore
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom.
Andrew R
AR
Webster
Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin.
Alfredo
A
Dubra
Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin.
Joseph
J
Carroll
Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom. Electronic address: michel.michaelides@ucl.ac.uk.
Michel
M
Michaelides
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009887:Ophthalmoscopy; D020710:RGS Proteins / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D020710:RGS Proteins; C464657:RGS9BP protein, human; C116925:regulator of g-protein signaling 9