Clinical spectrum and geographic distribution of keratitis fugax hereditaria caused by the pathogenic variant c.61G>C in NLRP3

Purpose To chart clinical findings in individuals with keratitis fugax hereditaria (KFH) and the geographic distribution of their ancestors. Methods Patient population included 84 Finnish patients (55% female) from 25 families with the pathogenic NLRP3 variant c.61G>C. Procedures and main outcome measures were Sanger sequencing, clinical examination, corneal imaging, and a questionnaire regarding symptoms, quality‐of‐life, treatment, and comorbidities. Results The oldest members in each family were born in Ostrobothnia in Western Finland or Southwestern Finland with historical ties to Sweden. One carrier was asymptomatic. Most (77%) experienced their first attack between 6 and 20 years of age. Three quarters had unilateral attacks 3‐5 times annually, primarily triggered by cold wind or air, or stress. Eighty percent reported ocular pain (median, 7 on scale 1‐10), conjunctival injection, photophobia, foreign body sensation, and tearing during attacks. Visual blur occurred 75% and 91% during and after the attack, respectively, for 1 day to 2 months (median, 10 days). Forty‐seven percent had corneal oval opacities with irregular tomography patterns and mild to moderate decrease (20/60 or better) in best‐corrected visual acuity that improved with scleral contact lenses. Except for headache in 40%, systemic symptoms were absent during the attacks. Conclusions Symptoms and signs of KFH are restricted to the anterior segment of the eye, and they vary widely between individuals. We recommend scleral contact lenses as first‐line treatment for reduced vision. Allele frequencies suggest that KFH goes unrecognized in Sweden and populations with Scandinavian heritage.