Photo Credit: 1001gece

The following is a summary of “Clinical characteristics of patients with less common causes of Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy,” published in the April 2025 issue of American Journal of Ophthalmology by Balbirsingh et al. 

Researchers conducted a retrospective study to analyze the clinical characteristics, natural history, and genetics of Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy (LCA / EOSRD) associated with rare genes.  

They reviewed the clinical notes, ophthalmic images, and genetic testing results of 19 individuals with disease-causing variants in genes representing less than 1% of all LCA / EOSRD cases: ALMS1, CABP4, KCNJ13, and OTX2.  

The results showed that 6 patients had ALMS1-LCA, 7 had CABP4, and 3 had OTX2 or KCNJ13 while 9 previously unreported variants were identified. Photophobia was observed in those with ALMS1 and CABP4, while nyctalopia was seen in KCNJ13 and OTX2. Using the World Health Organization (WHO) visual impairment criteria, 68% of patients were severely sight impaired at presentation and progressed to blindness during follow-up. The worst vision was noted earliest in patients with ALMS1 and KCNJ13, with a mean LogMAR visual acuity of 2.2 and 2.8, respectively, in the second decade of life. Macular atrophy was found in all patients with KCNJ13, and peripheral retinal pigment deposits were densest in KCNJ13, followed by OTX2. Minimal retinal deposition was observed in patients with ALMS1 and CABP4. Adult patients with CABP4 showed a foveal hyporeflective zone along with generalized retinal involvement.  

Investigators concluded that the detailed genetic and phenotypic characterization of patients with LCA resulting from 4 rare genes enhanced the understanding of these conditions and had the potential to improve patient diagnosis, prognostication, and management through cross-sectional and longitudinal analysis. 

Source: ajo.com/article/S0002-9394(25)00200-4/fulltext