Occult Macular Dysfunction Syndrome: Identification of Multiple Pathologies in a Clinical Spectrum of Macular Dysfunction with Normal Fundus in East Asian Patients: EAOMD Report No. 5.

Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond , causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were in forty-seven patients from thirty families (30/50, 60.0%), in two patients from one family (1/50, 2.0%), in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.