Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2

Research output: Contribution to journalArticlepeer-review


Purpose: The p.(Leu450Trp) substitution in Collagen, Type VIII, Alpha 2 (COL8A2) is associated with an early-onset corneal dystrophy. Here we identify distinct anterior corneal and keratorefractive changes associated with this disease and replicate its distinguishing endothelial characteristics in a new family. Methods: We reviewed clinical data from a large family associated with the p.(Leu450Trp) COL8A2 mutation. We compared clinical photographs and keratometry over an 11-year period. We sought to replicate these findings, and after a 40-year-old male subject presented similarly, we obtained a peripheral blood sample and sequenced COL8A2. Results: Of 10 individuals with the p.(Leu450Trp) substitution, clinical records noted corneal edema in 6, of which 4 showed epithelial microcystic edema. Eleven-year progression data reveal a marked increase in subepithelial corneal edema and gradual, profound increase in anterior corneal astigmatism. Sequencing of genomic DNA from the unrelated individual predictably identified a c.1349T.G [p.(Leu450Trp)] heterozygous variation in COL8A2. Confocal microscopy confirmed attenuated endothelium, and histopathology revealed no guttae, consistent with findings from a previously identified family. Conclusions: Peripheral, anterior microcystic corneal edema represents a characteristic aspect of the phenotype associated with the p.(Leu450Trp) substitution in COL8A2, in at least 2 of 3 known affected families worldwide. We describe long-term progression and Descemet stripping endothelial keratoplasty for this disease for the first time.

Original languageEnglish (US)
Pages (from-to)587-591
Number of pages5
Issue number5
StatePublished - 2016


  • COL8A2
  • Scheimpflug imaging
  • corneal dystrophy
  • corneal edema

ASJC Scopus subject areas

  • Ophthalmology


Dive into the research topics of 'Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2'. Together they form a unique fingerprint.

Cite this