Gauging how well your patients are doing following corneal collagen crosslinking (CXL) may one day be as simple as looking at their tears. Turkish researchers examined changes in the levels of organic acids, which are important tear metabolites, in patients’ tears after CXL treatment for keratoconus. Their findings, published in Eye Contact Lens, suggest metabolite tear studies could help determine the prognosis of patients following treatment and aid in better understanding diseases such as keratoconus.

The prospective non-randomized interventional case series included 24 patients who were scheduled to receive CXL treatment (Dresden protocol) for progressive keratoconus. Investigators collected tears in one eye before CXL treatment and six months after the procedure.

The study separated patients into four groups: males, females, subjects aged 18 and younger and those older than 18. The researchers used mass spectrometry to analyze organic acid profiles of the tear samples.

Following CXL treatment, the team observed the greatest increase (66%) in N-acetyl-L-aspartic acid, a derivative of aspartic acid known to have antioxidant effects. 

Conversely, they noted the greatest decrease (61%) in 3-OH butyric acid, a marker of impaired ketone body and glucose metabolism. It is believed that an increase in 3-OH butyric acid in urine is a significant marker of impaired glucose use in fasting and diabetes, and it may be used as a marker of subclinical ketoacidosis, insulin sensitivity and diabetic complications, the researchers said in their study. These results suggest corneal glucose metabolism improved in keratoconic eyes after CXL treatment, they added.

Additionally, investigators reported a 46% decrease in the lactic acid/malic acid ratio.

The determination of organic acids in tears is an indicator of changes in cell metabolism occurring in the cornea after CXL treatment, and a similar course of organic acid levels was not observed in all groups after CXL treatment, the researchers noted. Moreover, although the lactic acid level increased, the reduction in the lactic acid/malic acid ratio could be an indicator that cellular antioxidant processes started after CXL treatment, the investigators wrote in the study.

The researchers noted limitations of their study included the small patient cohort and short follow-up of only six months. Organic acid levels can also be evaluated according to post-CXL topographic results, but the six-month follow-up would be too soon to determine the effects of CXL treatment on corneal topography, they added. In future studies, metabolic data from patients should be examined at different stages of keratoconus, the researchers suggested.

Sağlık A, Koyuncu İ, Soydan A. Tear organic acid analysis after corneal collagen crosslinking in keratoconus. Eye Contact Lens. August 13, 2019. [Epub ahead of print].