Clinical and Genetic Characteristics of a Chinese Occult Maculopathy Cohort

To analyze the genetic basis and phenotypic features of occult maculopathy in the Chinese population.

Clinical data and venous blood from probands with occult maculopathy and available family members were collected. Variants were detected using next-generation sequencing (NGS), analyzed bioinformatically, and confirmed through Sanger sequencing.

Heterozygous pathogenic variants in RP1L1 were detected in 17 of 24 families, with c.133C>T and c.3599G>T identified in 15 and 2 families, respectively. In patients with the RP1L1 variants, best-corrected visual acuity (BCVA) showed an overall declining trend despite sporadic fluctuations, stabilizing between 0.70 and 1.0 logarithm of the minimum angle of resolution in most patients. No potential pathogenic variants were detected in the remaining seven families (7/24, 29.17%) after systematic analysis of NGS data. Comparative assessment revealed that patients lacking RP1L1 variants had significantly earlier onset and better BCVA at their first visit. A distinctive finding was universally normal optical coherence tomography (OCT) profiles in this non-RP1L1 group. Other atypical changes were detected in subsets of patients on other examinations, including OCT, fundus autofluorescence, microperimetry, and adaptive optics retinal imaging.

Heterozygous pathogenic variants in RP1L1 contributed to 70.83% (17/24) of Chinese families with occult maculopathy in our cohort. Multifocal electroretinogram (mfERG) remains the most sensitive detection modality for occult maculopathy, while bilateral OCT abnormalities might indicate a genetic etiology related to heterozygous RP1L1 variants. Other modalities, including fundus autofluorescence, visual field, and adaptive optics imaging, have been explored for diagnosis and differentiation.

This study emphasizes the importance of genetic diagnosis and mfERG for the accurate diagnosis and management of occult maculopathy.