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.

In the scotopic flash response of the full-field electroretinogram (ffERG), the downward a-wave reflects photoreceptor response and the upward b-wave is indicative of bipolar cell function. If the b-wave is equal to or smaller than the a-wave, the waveform (and the ffERG) is termed electronegative. For pediatric inherited retinal disorders this finding narrows the differential diagnosis to certain conditions, most commonly congenital stationary night blindness if multimodal imaging is grossly normal. We describe 2 siblings with reduced vision in the setting of normal multimodal imaging. Inherited retinal disorder was suspected, and ffERG was performed. Both had electronegative ffERGs, suggesting an incomplete form of congenital stationary night blindness (cone-rod synaptic disorder). However, genetic testing (biallelic RGS9 pathogenic variants) and phenotypic reassessment confirmed an actual diagnosis of bradyopsia. This report expands the differential diagnosis for an electronegative ffERG to include bradyopsia and highlights features of this underdiagnosed pediatric inherited retinal disorder.

Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically suspected ACHM in the United Arab Emirates. Retrospective case series (January 2016-December 2023) of patients with (1) clinically suspected ACHM or (2) mutations in ACHM-associated genes ( CNGA3 , CNGB3 , GNAT2 , PDE6C , PDE6H , AT6 ). Twenty-two clinically suspected patients (19 probands) were identified. Biallelic disease genes and the number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Some mutant alleles were recurrent across different families. Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP -related bradyopsia and CNNM4 -related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review-one each related to PDE6C , to AT6 , and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM. CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Recurrent mutant alleles may represent founder effects. Macular discoloration on presentation can occur in PDE6C -related disease, AT6 -related disease, and triallelic CNGB3 / CNGA3 -related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.

Inherited retinal dystrophies encompass a diverse group of disorders affecting the structure and function of the retina, leading to progressive visual impairment and, in severe cases, blindness. Electrophysiology testing has emerged as a valuable tool in assessing and diagnosing those conditions, offering insights into the function of different parts of the visual pathway from retina to visual cortex and aiding in disease classification. This review provides an overview of the application of electrophysiology testing in the non-macular inherited retinal dystrophies focusing on both common and rare variants, including retinitis pigmentosa, progressive cone and cone-rod dystrophy, bradyopsia, Bietti crystalline dystrophy, late-onset retinal degeneration, and fundus albipunctatus. The different applications and limitations of electrophysiology techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP), in the diagnosis and management of these distinctive phenotypes are discussed. The potential for electrophysiology testing to allow for further understanding of these diseases and the possibility of using these tests for early detection, prognosis prediction, and therapeutic monitoring in the future is reviewed.

Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population. The advances in ocular genetics, retinal imaging and molecular biology, have conspired to create the ideal environment for establishing treatments for IRD, with the first approved gene therapy and the commencement of multiple therapy trials. The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD. Herein we present in a comprehensive and concise manner the imaging findings of: (I) macular dystrophies (MD) [Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), pattern dystrophy (PRPH2), Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)], (II) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4 and RPGR), (III) cone dysfunction syndromes [achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6], blue-cone monochromatism (OPN1LW/OPN1MW array), oligocone trichromacy, bradyopsia (RGS9/R9AP) and Bornholm eye disease (OPN1LW/OPN1MW), (IV) Leber congenital amaurosis (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (V) rod-cone dystrophies [retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)], (VI) rod dysfunction syndromes (congenital stationary night blindness, fundus albipunctatus (RDH5), Oguchi disease (SAG, GRK1), and (VII) chorioretinal dystrophies [choroideremia (CHM), gyrate atrophy (OAT)].