Bilaterally asymmetric corneal ectasia following SMILE with asymmetrically reduced stromal molecular markers

PURPOSE: To evaluate extracellular matrix regulators and inflammatory factors in a patient who developed ectasia after small incision lenticule extraction (SMILE) despite normal preoperative tomographic and biomechanical evaluation. METHODS: The SMILE lenticules from both eyes of the patient with ectasia and three control patients (5 eyes) matched for age, sex, and duration of follow-up were used for gene expression analysis of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), collagen types I alpha 1 (COLIA1) and IV alpha 1 chain (COLIVA1), transforming growth factor-beta (TGF-beta), bone morphogenetic protein 7 (BMP7), interleukin-6 (IL-6), cathepsin K, cluster of differentiation 68, integrin beta-1, and tissue inhibitor of metalloproteinase-1 (TIMP1). Furthermore, the functional role of LOX was assessed in vitro by studying the collagen gel contraction efficiency of LOX overexpressing in primary human corneal fibroblast cells. RESULTS: Preoperatively, manifest refraction was -9.25 diopters (D) in the right eye and -10.00 D in the left eye. Corneal thickness, Pentacam (OCULUS Optikgeräte GmbH, Wetzlar, Germany) tomography, and Corvis biomechanical indices (OCULUS Optikgeräte GmbH) were normal. The ectatic eye lenticule (left) had reduced expression of LOX and COLIA1 compared to controls without ectasia. Increased mRNA fold change expression of TGF-beta, BMP7, IL-6, cathepsin K, and integrin beta-1 was noted in the ectatic left eye compared to controls; however, MMP9 and TIMP1 levels were not altered. Ectopic LOX expression in human corneal fibroblast induced significantly more collagen gel contraction, confirming the role of LOX in strengthening the corneal stroma. CONCLUSIONS: Reduced preexisting LOX and collagen levels may predispose clinically healthy eyes undergoing refractive surgery to ectasia, presumably by corneal stromal weakening via inadequately cross-linked collagen. Preoperative molecular testing may reveal ectasia susceptibility in the absence of tomographic or biomechanical risk factors.