This study aimed to report the clinical, electrophysiological, and genetic findings in two siblings of an Egyptian family with type 2 Oguchi disease, with multimodal imaging performed for proper evaluation. Two siblings of consanguineous parents presented with poor night vision underwent full ophthalmological examination, ultra-widefield fundus photography, fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) of the macula, repeated fundus photography following dark adaptation for 3 hours and electroretinogram (ERG). Exome sequencing (ES) was performed for one patient and Sanger sequencing was then used for segregation analysis. The clinical findings and investigations were suggestive of the Oguchi disease phenotype. The ES revealed a homozygous stop gain variant, first time to be detected in Ouchi II patient, in exon 6 of the G-protein receptor kinase 1 (GRK1) gene, c.1338c>A: p.Cys446Ter. These are the first molecularly confirmed patients from Egypt with Oguchi disease type 2. In addition, we identified a pathogenic GRK1 variant first time to be detected in Oguchi II patients expanding both the phenotypic and mutational spectrum of Oguchi disease.

Oguchi disease, a rare form of congenital stationary night blindness (CSNB), is an autosomal recessive inherited retinal disorder (IRD) caused by pathogenic variants in the SAG gene, which encodes arrestin-1, a key protein in the phototransduction cascade. We present a case of a 35-year-old male with nyctalopia, progressive central vision loss, and refractory CME. A 35-year-old male presented with nyctalopia and progressive central vision loss. Evaluation revealed attenuated retinal vessels, peripheral pigmentary changes, and severe CME bilaterally. Despite treatment with carbonic anhydrase inhibitors and NSAIDS, CME persisted. Initial genetic testing identified a heterozygous pathogenic SAG variant (p.Arg193*), raising suspicion for autosomal dominant RP. However, advanced long-read sequencing revealed a second pathogenic intronic SAG variant (c.-29+3A>G) in trans with the initial variant, confirming a diagnosis of autosomal recessive Oguchi disease.

In the past, only Oguchi disease was reported as a hereditary retinal disease from Japan. Dr. Chuuta Oguch was a Professor of Nagoya University in Japan. During the past 40 years, four new clinical entities in hereditary retinal disorders have been detected by the Miyake group from Nagoya, Japan. All disorders show essentially normal fundi, and the diagnosis was made mainly by the analysis of an electroretinogram (ERG). Gene mutations are detected in three of them. Bipolar cell (BP) dysfunction syndrome: Congenital stationary night blindness (CSNB) with negative ERG (a-wave is larger than b-wave) was named as the Schubert-Bornschein type in 1952 and considered to be an independent clinical entity. In 1986, Miyake group classified ninety patients with the Schubert-Bornschein type into two types (complete and incomplete type). The complete type of CSNB (CSNB1) showed no rod function, but the incomplete type CSNB (CSNB2) showed remaining rod function in both subjective dark adaptation and rod ERG. In order to investigate the pathogenesis, these two types of CSNB were analyzed by comparing the monkey ERGs using different glutamate analogs to the retina. The ERG analysis demonstrated that CSNB1 has a complete functional defect in the ON type BP, while CSNB2 has incomplete functional defects in the ON and OFF type BP in both rod and cone visual pathways. Evidence of several different genetic heterogeneities was reported in both diseases, indicating CSNB1 and CSNB2 are independent clinical entities. Another entity, showing total complete defect of both ON and OFF BP, was detected in 1974 and was reported by Miyake group in a brother and younger sister, showing severe photophobia, nystagmus, extremely low visual acuity, and disappearance of color vision (total color blindness). This disorder is a congenital stational condition, and subjective visual functions were severely deteriorated from birth but remained unchanged through life. This disease was termed "Total complete bipolar cell dysfunction syndrome (CSNB3)". The relationship between BP and subjective visual function was unknown. These three kinds of BP diseases can provide information on how BP relates to subjective visual functions. Occult macular dystrophy (OMD): Occult macular dystrophy (OMD) was discovered by Miyake group in 1989. This disease shows an unusual, inherited macular dystrophy characterized by progressive decrease visual acuity due to macular dysfunction, but the fundus and fluorescein angiography are essentially normal. The full-field rod and cone ERG do not show any abnormality, but the focal macular ERG (FERG) or multifocal ERG is abnormal and the only method for diagnosis. Many pedigrees of this disorder suggest autosomal dominant heredity, showing a genetic mutation of RP1L1. This disease was termed "occult macular dystrophy". "Occult" means "hidden from sight". Recently, it has been called "Miyake disease".

This case report discusses a diagnosis of Oguchi disease found incidentally on routine diabetic retinopathy screening in a 55-year-old patient.