In Vivo corneal confocal microscopy study of keratoendotheliitis fugax hereditaria caused by a pathogenic variant in the NLRP3 gene

Purpose To elucidate by using in vivo corneal confocal microscopy (IVCM) the pathogenesis of keratoendotheliitis fugax hereditaria, an autosomal dominant cryopyrin‐associated periodic keratitis associated with a pathogenic variant in NLRP3, in its acute and chronic phase. Methods Cross‐sectional, hospital‐based study of 7 patients during an acute attack and 18 patients in the chronic phase. Corneal photography, IVCM and Sanger sequencing to confirm NLRP3 variant c.61C>G were performed. Results During the acute attack, the stroma was transiently infiltrated with hyperreflective small roundish bodies consistent with inflammatory cells. Other layers of the cornea were essentially normal. With multiple recurring attacks, a central corneal stromal opacity gradually develops. IVCM revealed that the opacities correspond to hyperreflective needle‐shaped structures in the extracellular matrix of the stroma. Conclusions Keratoendotheliitis fugax hereditaria mainly involves the middle layers of the corneal stroma, and is stromal keratitis rather than a true keratoendotheliitis. IVCM shows that inflammatory cells invade only the stroma during an acute attack. With repeated attacks, needle‐shaped hyperreflective extracellular matrix elements emerge and cause a persistent opacity. The disease will be excellent in vivo human model to study the activation of the NLRP3 inflammasome and the tissue specificity in cryopyrin‐associated periodic syndromes.