Tear Organic Acid Analysis After Corneal Collagen Crosslinking in Keratoconus

Abstract

Objectives: This study examined changes in the levels of organic acids, which are important tear metabolites, after corneal collagen crosslinking (CXL) treatment for keratoconus. Methods: This prospective, nonrandomized, interventional case series included a single eye from 24 patients who were scheduled to receive CXL treatment (Dresden protocol) for progressive keratoconus. Before CXL treatment and at 6 months after treatment, tears were collected in capillary tubes. The patients were separated into four groups as males, females, and ages 18 years younger and >18 older. The organic acid profiles of the tear samples were analyzed using mass spectrometry. Results: An evaluation was made of 12 females and 12 males with a mean age of 19.20±4.06 years (range: 12‒27 years). The greatest percentage increase in organic acids after CXL treatment was observed for N-acetyl-L-aspartic acid (66% increase). The organic acid showing the greatest decrease was 3-OH butyric acid (61% decrease). A decrease of 46% was found (P=0.263) in the lactic acid/malic acid ratio. Conclusion: Metabolomic studies of tears could facilitate a new and objective process in the follow-up period or in the determination of prognosis after CXL treatment for diseases such as keratoconus, which has a multifactorial etiology.

Metabolomics and lipidomics approaches in human tears: A systematic review

“…Two studies did not report any significant age-related effect on the ω3:ω6 (proinflammatory/antiinflammatory) lipid ratio in tears 88 nor on amino acids 53 whereas most studies found that concentrations of both lipids 48,3,5 and metabolites 76,43 were influenced by age.Other factors (e.g.…”

“…Cross-linking is part of the therapeutic arsenal, but its efficacy remains controversial 69 . One study investigated the metabolomics profile using LC-MS/MS in the pre-and 6 months post-cross-linking basal tears of patients with keratoconus based on the Rabinowitz diagnosis criteria 76 . In total, 24 metabolites were identified, among which 7 were significantly up-regulated (univariate analyses: 4-OH phenylacetic acid (p<0.01), fumaric acid (p<0.05), glycolic acid (p<0.01), homogentisic acid (p<0.05), N-acetyl-Laspartic acid (p<0.0001), 2-OH phenylacetic acid (p<0.01), and suberic acid (p<0.01)) and 4 were significantly down-regulated (univariate analyses: 3-OH butyric acid (p<0.01), pyruvic acid (p<0.05), 2-OH-3-methyl pentanoic acid (p<0.05), and 2-ketoglutaric acid (p<0.01)).…”

Role of Oxidative Stress in Ocular Diseases: A Balancing Act

“…Riboflavin-mediated crosslinking is an FDA-approved treatment for KC that also promotes lower lactate/malate levels in tears [ 99 ] and reduced lactate production by corneal fibroblasts [ 100 ], providing a degree of stabilization to the metabolic phenotype observed in KC, in addition to stiffening the collagen matrix to blunt progressive thinning. Moreover, basal arginase activity and hydroxyproline levels have been found to be lower in KC-derived keratocytes [ 101 ], correlating with a reduction in collagen deposition associated with these cells [ 102 ].…”

Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects

“…The tear metabolic status of patients who had progressive keratoconus was also examined before and after CXL. An increase was found in 16 organic acids and a decrease in 8 organic acids 6 months after CXL treatment [ 86 ]. The organic acid that showed the greatest percentage increase before and after CXL was N-acetyl-L-aspartic acid, a derivative of aspartic acid that has anti-oxidant effects.…”