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Pallak Nikhil Kusumgar, Nimisha R Kumar, Rohit Shetty, Abhijit Sinha Roy, Arkasubhra Ghosh, Natasha Pahuja; Predicting optimal CXL outcomes with cone-specific lysyl oxidase and other tissue factors’ expression in keratoconus patients. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1402.
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© ARVO (1962-2015); The Authors (2016-present)
In Keratoconus (KC), the cornea is deformed and weakest at the corneal cone area while the surrounding cornea is of normal thickness. Alteration in gene expression patterns may be specific to the “cone” and hence treatment outcomes may be dependent on levels of molecular markers within the ectatic zone. This study evaluated the gene expression changes at the corneal “cone” normalized to the corneal “periphery” of each subject to rule out individual specific expression patterns.
Corneal epithelium from 35 eyes (18 and 60 years) undergoing accelerated collagen crosslinking (9 mW/cm2 for 10 minutes (KXL) or customized beam profile based crosslinking, KXLII) was separately obtained from the cone and periphery for each subject. Ratio of gene expression [for lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP 9), bone morphogenic protein (BMP7), tissue inhibitor of metalloproteinase (TIMP1), collagens (COL IA1 and COL IVA1)] from the cone vs peripheral cornea was correlated with the outcome of crosslinking. Clinical parameters like keratometry, refraction, visual acuity and corneal densitometry was done for patients, before and 12 months after surgery. Surgical outcomes were classified based on the change in corneal flattening, as positive (improvement of >1 D) or sub-optimal. Exclusion criteria includes patients with any allergic or inflammatory eye disease, pregnancy, diabetes, glaucoma or corneal scarring.
Both the surgical procedures (KXL and KXLII) show improved visual acuity which correlates with reduction in keratometric values. 80% of KXLII and 70% of KXL subjects had a positive outcome. Higher LOX levels in the cone epithelium correlated significantly with positive (p>0.05). Subjects with sub-optimal outcome show the trend of reduced COL IVA1, BMP7 and TIMP1 gene expression at the ectatic cone. Patients with positive outcomes had relatively reduced MMP9 levels
The level of LOX and other tissue factors within the tissues may be a direct indicator of the ability of the tissue to be crosslinked. Thus tear measurement of LOX activity may be a useful screening tool for patient selection.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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