Clinical features, retinal detachment (RD) rates, and RD prophylaxis in patients with genetically confirmed Knobloch...

Knobloch syndrome is a rare autosomal recessive condition characterized by lack of functional collagen type XVIII (COL18A1), occipital defects, high myopia, and vitreoretinal degeneration. Clinical features, retinal detachment (RD) rates, and role of prophylactic treatment are not well established. The purpose is to 1) report clinical/systemic features, 2) RD rates and 3) the role of prophylactic treatment in a U.S.-based genetically confirmed cohort.

Retrospective, nonrandomized multi-center case cohort SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Genetically confirmed Knobloch patients from 12 US -based pediatric retina tertiary referral centers MAIN OUTCOMES MEASURES: Baseline characteristics, RD rates, risk of RD with or without a history of prophylactic treatment RESULTS: 72 eyes (36 patients) were included. Mean follow up was 5.2 years. 14 patients (38.9%) were female. Most common systemic features included 1) occipital defects (n=17 (47.2%)), 2) intracranial abnormalities (n=10 (27.8%); polymicrogyria, plagiocephaly, cortical dysplasia, encephalomalacia, periventricular heterotopia), and 3) skin (n=5 (13.9%)); hemangioma, eczema). Mean +/-SE refractive error was - 9.85 (range -20.12 - +7.50). 18 eyes (25.0%) had cataracts, 16 (20.0%) iris defects (transillumination defects, absent crypts, pupillary membrane), 40 (57.1%) optically empty/vitreous condensations, and 64/70 eyes (91.4%) had macular abnormalities ranging from tessellated fundus to generalized macular atrophy.Of 72 eyes, 23 (31.9 %) experienced an RD, 12 (52.2%) at baseline. Two eyes (8.7%) had a concurrent macular hole. Mean age at RD was 6.24 years and time to RD was 18.6 months (0 - 86). 20 eyes (87.0%) underwent RD surgery (laser, SB, PPV, or PPV/SB). Single and final anatomic success was 60% and 85%. 21/72 eyes (29.2%) received laser or scleral buckle prophylaxis - only two of which (9.0%) developed an RD. Age-adjusted GEE logistic model demonstrated lower odds of RD in eyes that received prophylaxis than not (OR 0.20, P = 0.022). 4/19 fellow eyes (21%) developed an RD (n=1 with previous RD prophylaxis). There was a nonsignificant lower odds of RD in fellow eyes that received RD prophylaxis versus no prophylaxis (OR = 0.42, p = 0.41).

In genetically confirmed Knobloch, RD rates are high, and RD prophylaxis appeared to reduce risk of RD. Early diagnosis and prophylaxis should be considered in this population.