Shetty Rohit, Kumar Nimisha Rajiv, Khamar Pooja, Francis Matthew, Sethu Swaminathan, Randleman J Bradley, Krueger Ronald R, Sinha Roy Abhijit, Ghosh Arkasubhra
J Refract Surg. 2019 Jan 1;35(1):6-14. doi: 10.3928/1081597X-20181128-01.
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.
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.
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.
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. [J Refract Surg. 2019;35(1):6-14.].
评估一名患者在小切口飞秒透镜切除术(SMILE)后发生角膜扩张的情况,尽管其术前断层扫描和生物力学评估结果正常,分析其细胞外基质调节因子和炎症因子。
从发生角膜扩张的患者双眼以及三名年龄、性别和随访时间匹配的对照患者(5只眼)中获取SMILE透镜,用于赖氨酸氧化酶(LOX)、基质金属蛋白酶9(MMP9)、I型胶原蛋白α1链(COLIA1)和IV型胶原蛋白α1链(COLIVA1)、转化生长因子-β(TGF-β)、骨形态发生蛋白7(BMP7)、白细胞介素-6(IL-6)、组织蛋白酶K、分化簇68、整合素β-1和金属蛋白酶组织抑制剂-1(TIMP1)的基因表达分析。此外,通过研究在原代人角膜成纤维细胞中过表达LOX的胶原蛋白凝胶收缩效率,在体外评估LOX的功能作用。
术前,右眼的明显屈光度数为-9.25屈光度(D),左眼为-10.00 D。角膜厚度、Pentacam(德国韦茨拉尔市OCULUS Optikgeräte GmbH公司)断层扫描和Corvis生物力学指标(OCULUS Optikgeräte GmbH公司)均正常。与未发生角膜扩张的对照相比,发生角膜扩张的眼睛(左眼)的透镜中LOX和COLIA1的表达降低。与对照相比,发生角膜扩张的左眼TGF-β、BMP7、IL-6、组织蛋白酶K和整合素β-1的mRNA倍数变化表达增加;然而,MMP9和TIMP1水平未改变。人角膜成纤维细胞中异位LOX表达显著诱导更多的胶原蛋白凝胶收缩,证实了LOX在强化角膜基质中的作用。
术前已存在的LOX和胶原蛋白水平降低可能使接受屈光手术的临床健康眼睛易发生角膜扩张,推测是由于交联不足的胶原蛋白导致角膜基质减弱。术前分子检测可能在不存在断层扫描或生物力学危险因素的情况下揭示角膜扩张易感性。[《屈光手术杂志》。2019年;35(1):6 - 14。]