Ophthalmological and Genetic Profile in Knobloch Syndrome

To analyze the clinical and genetic characteristics of Knobloch syndrome (KNO) in a large cohort, with a focus on retinal detachment (RD) characteristics, surgical outcomes, and variants in the COL18A1 gene.

Retrospective, multicenter interventional/observational case series.

Thirty-four patients (68 eyes) with clinically and genetically confirmed KNO were included.

Data were collected from three institutions, including demographics, clinical findings, surgical techniques, and outcomes, and genetic testing results. Surgical success was defined as retinal reattachment after silicone oil removal. Genetic testing was performed for the COL18A1 gene to identify pathogenic variants.

The primary outcomes included the prevalence and characteristics of RD, surgical success rates, and the identification of pathogenic variants in COL18A1.

The median age at diagnosis was 24 months, with consanguinity noted in 76% of cases. RD occurred in 50% of eyes, with a median onset of 2.5 years. Macular hole (MH)-related RD accounted for 57% of cases and presented early (median age: 11 months). Surgical success after the first procedure was 54%, improving to 69% after reoperation. The use of Tenon's capsule or amniotic membrane grafts in 69% of MH-RD cases doubles the reattachment rate (82% vs 40%). Genetic testing identified 14 COL18A1 variants, including nine novel variants.

KNO presents significant diagnostic and surgical challenges: early-onset RD, small flap-shaped MHs that are easily overlooked, and an abnormally adherent vitreoretinal interface. Early recognition of MH-RD and the use of grafts during surgery can improve anatomical outcomes. While the ocular phenotype is often pathognomonic, genetic testing aids in confirming the diagnosis and guiding counseling. Understanding these clinical and surgical challenges may improve outcomes in patients with this rare disorder.