Researchers recently uncovered five genetic loci associated with corneal hysteresis (CH) and corneal resistance factor (CRF), both of which are associated with keratoconus. The finding bring us one step closer to understanding the genetics that drive these corneal biomechanical factors in keratoconus and helping catch it before it progresses to a vision-threatening stage.

The study evaluated two cross-sectional populations of 9,029 total patients for the genetic determinants associated with corneal hysteresis and corneal resistance factor. The researchers then examined the possible link between those genetic determinants and keratoconus using a case-control study. The team compared 752 keratoconus patients with 974 participants undergoing direct sequencing or 13,828 participants undergoing genotyping who were not part of the first analysis.

The team located seven genome-wide significant loci associated with corneal hysteresis or corneal resistance factor that were independently replicated. They identified two more suggestive loci after meta-analysis. They noted that five of the nine—named ANAPC1, ADAMTS8, ADAMTS17, ABCA6 and COL6A1—have not been reported as associated with corneal disease.

The study authors concluded that these findings suggest type VI collagen, extracellular matrix and connective-tissue play a role in corneal biomechanics and corneal hysteresis and corneal resistance factor are useful biomarkers for keratoconus.

Khawaja AP, Lopez KER, Hardcastle AJ, et al. Genetic variants associated with corneal biomechanical properties and potentially conferring susceptibility to keratoconus in a genome-wide association study. JAMA Ophthalmol. June 27, 2019. [Epub ahead of print].