University of São Paulo, São Paulo, SP, Brazil; University of Southern California, Los Angeles, CA, USA.
Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, USA; Cole Eye Institute, Cleveland Clinic, USA.
Exp Eye Res. 2021 Jan;202:108355. doi: 10.1016/j.exer.2020.108355. Epub 2020 Nov 7.
Over the past 20 years, corneal crosslinking (CXL) has been used by surgeons to halt progression in eyes with keratoconus. We reviewed the literature regarding the mechanism of action of CXL, the role of each of its components the strong biologic reaction, and their effects on cell interaction, proteins involved, wound healing, and cytotoxic reaction. CXL surgery involves a photochemical response in which ultraviolet light at a given wavelength and riboflavin participate. The combination of irradiation with UVA light and riboflavin leads to an intense process of apoptosis of keratocytes in the anterior stroma. Differences in light irradiation, as well as the importance of riboflavin and its vehicle, were also detailed. The surgery creates additional chemical bonds between the amino terminals of the collagen side chains and the proteoglycans of the extracellular matrix. A photosensitization reaction catalyzed by riboflavin classically involves the production of singlet oxygen. Microstructure studies show changes in the size of the fibril and potentially in the interfibrillar space, that the most significant changes related to the stiffening effect of CXL occur in the anterior third of the cornea and that short irradiation times, especially below 5 min, may not have the same biological effect. Changes in the riboflavin vehicle, with the incorporation of Hydroxypropyl methylcellulose as a carrier, can lead to faster diffusion and a more intense photochemical reaction. These are findings that can impact the optimal adjustment of irradiation time according to the riboflavin (and its carrier) used. Many studies have suggested that CXL is safe and effective in the standard and accelerated protocols that have been used by surgeons. After the initial depletion of anterior keratocytes, keratocyte density seems to return to average 6-12 months after surgery when corneas are examined with the confocal microscope.
在过去的 20 年中，角膜交联术（CXL）已被外科医生用于阻止圆锥角膜的进展。我们回顾了关于 CXL 的作用机制、其各个组成部分的作用、强烈的生物反应及其对细胞相互作用、涉及的蛋白质、伤口愈合和细胞毒性反应的影响的文献。CXL 手术涉及一种光化学反应，其中特定波长的紫外线和核黄素参与其中。紫外线 A 光和核黄素的照射组合导致前基质中角膜细胞强烈凋亡。还详细介绍了光照射的差异以及核黄素及其载体的重要性。该手术在胶原侧链的氨基末端和细胞外基质的蛋白聚糖之间创建了额外的化学键。核黄素经典地催化的光致敏反应涉及单线态氧的产生。微观结构研究表明，纤维原纤维的大小和潜在的纤维间空间发生变化，与 CXL 僵硬效应相关的最显著变化发生在角膜前 1/3 处，并且较短的照射时间（尤其是低于 5 分钟）可能不会产生相同的生物学效应。核黄素载体的变化，通过将羟丙基甲基纤维素作为载体掺入其中，可导致更快的扩散和更强烈的光化学反应。这些发现可能会影响根据所用核黄素（及其载体）最佳调整照射时间。许多研究表明，在外科医生使用的标准和加速方案中，CXL 是安全有效的。在前角膜细胞初始耗竭后，当使用共聚焦显微镜检查角膜时，手术后 6-12 个月，角膜细胞密度似乎恢复到平均水平。
