Congenital Hereditary Endothelial Dystrophy: A Review of the Molecular Pathogenesis, Genetic Basis, and Emerging Treatments

Abstract: Congenital hereditary endothelial dystrophy (CHED) is a rare autosomal recessive disease more common in populations with high consanguinity. This review aims to provide a comprehensive overview of CHED focusing on the underlying genetic and molecular bases, listing identified mutations, and evaluating current and future therapeutic strategies. We performed a comprehensive literature review using PubMed with the keywords “Congenital hereditary endothelial dystrophy (CHED); SLC4A11 gene; Endothelial keratoplasty (EK) and pediatric corneal disease; Genetic therapy and corneal endothelial disease” from 1988 to 2025. Of the reviewed articles (n=494), English-language studies published in the last decade were prioritized and analyzed (n=107). CHED is commonly caused by biallelic SLC4A11 mutations, causing dysfunction of the corneal endothelium, progressive stromal edema, and visual loss. It typically manifests at birth or infancy as bilateral, asymmetric corneal opacification with variable severity. Although penetrating keratoplasty and EK remain the gold standards for the recovery of corneal transparency, novel therapeutics, including gene therapies and mitochondrial-targeted antioxidants, have shown promising results in preclinical studies. Emerging therapeutic strategies are likely to markedly change the current treatment of CHED with less invasive and more effective therapeutic options on the horizon. Keywords: SLC4A11 gene, keratoplasty, gene therapy, oxidative stress, primary congenital glaucoma, pediatric corneal diseases