The origin of keratonocus (KC) has often been linked to genetics, but new research that looked into environment’s influence suggests mechanical manipulation, such as rubbing or hand palm compression, is the reason behind the vast majority of cases.

“The literature shows that mechanical manipulation may be the common underlying factor or the indispensable act precipitating the cascade of events leading to permanent corneal deformation,” the authors wrote in their paper that was published in Current Opinion in Ophthalmology.

Genetic-related connective tissue disorders demonstrate the inconsistency of theories regarding KC pathogenesis since no corneal steepening was noted in the majority of these patients, the authors explained. Despite recent advances and decades of research into the genetics of the condition, the identification of disease-causing KC genes has been frustrating, they added.

Additionally, variants found on genome-wide and next-generation sequencing only seemed to account for a small number of cases or play a limited role in KC pathogenesis.

Beside mechanical manipulation, the authors considered several potential causative factors, including inflammatory pathways, contact lenses, atopy, blepharitis and dry eye, sleeping positions, unilateral and very asymmetrical KC, associated genetic disorders and genetic updates of the condition, acute corneal hydrops and KC reemergence after transplant.

Other key study findings included:

  • Inflammatory markers were observed in KC patient tears, especially IL-6, tumor necrosis factor-a and matrix metalloproteinases 9 and 13.

  • A significant number of patients with KC had a positive history of allergic rhinitis.

  • Recent next-generation sequencing testing studies have mostly focused on small KC families, which fail to show significant results throughout monogenic research strategies, the authors suggested.

  • Osteogenesis imperfecta (brittle bone disease) and Marfan syndrome represent a perfect counter example to explain the irrelevance of current theories on the pathogenesis of KC, which describe it to be an unknown collagen dystrophy, researchers said.

  • A small number of patients were not aware of eye manipulation and did it unconsciously while their attention was focused elsewhere or while they were asleep.

“Although we cannot explain the entire pathophysiology of KC, it must be emphasized that it is primarily a mechanical disorder,” the investigators wrote in their paper. “Hence, we have the opportunity to increase patient awareness about eye manipulation repercussion and treat ocular surface disorders.”

As a direct result, they recommend that  corneal collagen crosslinking should be reserved for patients with reduced compliance and persistence of unconscious eye manipulation, especially in children and patients with infectious diseases.

de Azevedo Magalhães A, Gonçalves MC, Gatinel D.  The role of environment in the pathogenesis of keratoconus. Curr Opin Ophthalmol. 2021;32(4):379-384.