Multimodal imaging and electrophysiological features in bradyopsia associated with homozygous variants (c.895T>C) in Regulator of G-protein Signaling 9 (RGS9)

To report multimodal imaging findings and natural history of clinical features in two probands with bradyopsia harboring homozygous variants (c.895T>C) in Regulator of G-protein Signaling 9 (RGS9). Ophthalmic history, clinical examination, fundus autofluorescence (FAF), optical coherence tomography (OCT), microperimetry, flood-illuminated adaptive optics (AO) imaging, and electroretinogram (ERG) were obtained. A 37-year-old male and a 67-year-old female from non-consanguineous parents had normal fundus examination, FAF, and OCT. ERGs for the male case between the age of 4 and 38 years showed no progression. Both probands had flat International Society for Clinical Electrophysiology of Vision (ISCEV) Standard full-field ERG light-adapted (LA) responses but dark-adapted (DA) red x-wave and S-cone responses were present. DA 30 Hz flicker was present after 2 but not after 10 seconds. The reduced amplitude and b:a ratio of the DA10 response improved with increasing interstimulus interval. AO and microperimetry demonstrated preservation of foveal cone density and subnormal retinal sensitivity, respectively. Both measures remained stable over 3 years. The c.895T>C variant was classified as pathogenic. Bradyopsia associated with homozygous RGS9 c.895T>C variants is characterized by normal retinal structure but subnormal macular sensitivity. Extended ERG protocols can be used to confirm delayed phototransduction recovery.