Tear Mediators NGF along with IL-13 Predict Keratoconus Progression

Abstract

Purpose: To find immunomediator combinations which could sensitively indicate keratoconus progression. Methods: Tear samples of 42 patients with keratoconus were collected at baseline and at the end of a one-year follow-up. The concentrations of 13 mediators were measured by CBA. Based on Pentacam HR examination, eyes were divided into a non-progressive and a progressive group. Results: At the end of the follow-up, significant differences were observed in the release of IFNγ, IL-13, IL-17A, CCL5, MMP-13 and PAI-1 between the two groups. Changes in five Pentacam parameters correlated positively with changes in IFNγ, IL-13, IL-17A, CXCL8, CCL5, TIMP-1 and t-PA. We found that tear level of IL-13 in combination with NGF can predict the progression of keratoconus with 100% specificity and 80% sensitivity. Conclusion: The findings of our longitudinal study may underscore the importance of NGF and IL-13 tear levels in the prediction of keratoconus progression.

Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile

“…IL-1β, IL-6, IL-17A, TNFα, IFNγ, IgE, MMP2, EPO, PDGF-BB, sVCAM, sL-selectin, granzyme-B and perforin were observed to be significantly increased compared to controls in two or more of KC grades. This finding is consistent with earlier observations reporting increased levels of IL-1β 26 , 40 – 42 , IL-6 24 , 26 , 30 , TNFα 41 , IL-17A 40 , 43 , IFNγ 44 and MMP2 26 in the tear fluid of KC patients. The observed variation in tear fluid expression of MMP9 24 – 33 , 45 , IL-8 26 , 33 , 46 , IL-13 40 , IL-21 40 , IL-23 40 , IFNα 40 , MCP1 40 and CCL5 31 , 32 , 44 between the current study and previous reports, may be attributed to differences in sample size and stage of KC investigated in the cohort.…”

Biochemical and molecular alterations and potential clinical applications of biomarkers in keratoconus

“…An increase in tear levels of IFN-gamma is associated with disease progression and corneal thinning. [ 89 ] Epithelial TNF-α levels from the cone region have a positive association with Belin–Ambrosio-enhanced ectasia display scores, corneal deformation, and keratometry, all of which suggest a biomechanical weakening process. [ 44 ] TGF-β tear levels indicate a profibrotic state and an increase in the tear levels correlates with corneal remodeling and scarring in advanced KC.…”

Advances in the diagnosis and treatment of keratoconus

“…Another study found higher levels of innate biomarkers, namely toll-like receptors 2 and 4, on the ocular surface of subclinical keratoconus patients, and drawing from this finding, the authors advocated their use as a biomarker in identifying keratoconus cases. 19 Interestingly, Fodor and colleagues 20 demonstrated that a concomitant increase in tear nerve growth factor and interleukin (IL)-13 predicts keratoconus progression with a sensitivity and specificity of 80% and 100%, respectively.…”