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Natasha Pahuja, Pooja Khamar, Rohit Shetty, Archana Padmanabhan Nair Nair, Tanuja Vaidya, Vishal Jhanji, Rajiv R Mohan, Swaminathan Sethu, Arkasubhra Ghosh; Distinct tear molecular profile of keratoconus patients with progressive disease.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4402.
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© ARVO (1962-2015); The Authors (2016-present)
Keratoconus (KC) is an ocular surface condition marked by progressive loss of vision due to ectasia induced irregular astigmatism. Certain soluble factors in KC patients’ tears have been functionally associated with pathologic corneal changes in cross-sectional studies.Yet, how the molecular milieu in progressive patients gradually changes is not known. Thus we evaluated the alterations in tear profile of KC patient during progression
A total of 19 KC patients were included after approval of Institutional Ethics Committee and written informed consent. KC patients were classified based on clinical parameters and topographical features. Serial topographical maps based changes in Kmax (ΔKmax) upon patient follow-ups were used to determine progressive form of the disease. Tear samples collected serially (2 visits) were quantified for IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-9, IL-10, IL-12, IL-17A, IL-17F, IFNα, IFNγ, TNFα, CCL2/MCP-1, CCL4/MIP-1β, CCL5/RANTES, CX3CL1/Fractalkine CXCL9/MIG, CXCL10/IP10, CXCL11/I-TAC, ICAM1, VCAM1, CD62P, CD62L, FasL, b-FGF, VEGF, Angiogenin, IgE, sTNFRI, sTNFRII, sIL-1RA, MMP1, MMP2, MMP7, MMP9 and MMP10 using flow cytometry based cytometric bead array and multiplex ELISA. Tear samples from contralateral eye with either stable disease or lower progressive disease served as controls.
The ΔKmax of the progressing group (1.77±0.4; mean±SEM) was significantly (P<0.0001) higher than the stable group (0.05±0.1). The difference in the levels of tear soluble factors IL-1β, IL-4, IL-8, IL-12, IL-17A, RANTES, MIG, IP10, ICAM1, FasL, b-FGF, MMP7, MMP9, IgE and sIL-RA between two visits showed increasing trend in eyes with progressive form of KC compared to stable group. Analytes Fractalkine, VCAM1, CD62L, VEGF, Angiogenin, MMP2, and MMP10 exhibited an inverse trend in eyes with progressive disease. The differences observed in IL-4, IL-8, Fractalkine, VEGF, bFGF and MMP9 were statistically significant.
A unique tear biomarker profile was observed in KC patients with clinically progressive disease which reveals new factors suggestive of complex underlying molecular processes. These factors may have of diagnostic utility for patient monitoring and present new therapeutic targets.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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