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Pooja Khamar, Rohit Shetty, Nimisha Kumar, Tanuja Vaidya, Mathew Francis, Abhijit Sinha Roy, Swaminathan Sethu, Arkasubhra Ghosh; Altered corneal stromal molecular profile associated with post-refractive ectasia. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5980.
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© ARVO (1962-2015); The Authors (2016-present)
Refractive procedures such as SMILE (small incision lenticule extraction) are practiced for vision correction worldwide. Despite appropriate clinical patient selection criteria being followed, undesirable surgical outcomes may occur. Thus we analysed extra-cellular matrix regulators and inflammatory factors in patient samples and in vitro studies.
Corneal lenticules were collected intra-operatively from subjects undergoing SMILE surgery after approval of Institutional Ethics Committee and written informed consent. Of the 178 subjects followed up over 2-3 years, one subject presented with blurry vision 25 months post surgery and had developed bilaterally asymmetric ectasia. MRSE of right and left eyes of the subject were -1D and -3.625D and mean K was 39.8D and 43.3D, respectively. Pre-operative MRSE was -9.25D and -10D in OD and OS, respectively. BAD-D values were 0.76 and 0.94 respectively, which were well within published limits for suspect corneas. Lenticules from both eyes of the ectasia subject and 3 age, sex and duration of follow up matched control subjects (6 eyes) were used for gene expression analysis of Lysyl Oxidase (LOX), MMP9, Collagens (COL IA1, COL IVA1), TGFβ, BMP7, IL-6, CathepsinK, CD68, Integrin β1 and TIMP1. Control and LOX overexpressing human corneal fibroblasts (HCF) were seeded on collagen gel matrices to assess LOX function. LOX expression was analysed in cells treated with TNFα(10ng/ml).
The ectatic eye had reduced fold change expression of LOX (0.57), COL IA1 (0.063), COL IVA1 (0.5) compared to controls without ectasia. Increased mRNA fold change expression of TGFβ (1.5), BMP7 (1.4), IL6 (1.5), CTSK (1.37), Integrin β1 (1.4) was noted in severely ectatic eye when compared to controls. However, MMP9 and TIMP1 levels were not altered in the ectatic eye compared to controls. LOX overexpression in HCF induced significantly more collagen gel contraction (25%) indicating its role in strengthening the corneal stroma. LOX expression was also reduced to 0.5 fold upon inflammatory stimulus.
Reduced pre-existing LOX and collagen levels may predispose clinically healthy eyes undergoing refractive surgery to ectasia, possibly via weakened stroma due to lack of crosslinked collagen. Thus, diagnostic testing for molecular factors can reveal susceptibility in absence of topographical evidence.
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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