The Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
The Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
Exp Eye Res. 2020 Nov;200:108218. doi: 10.1016/j.exer.2020.108218. Epub 2020 Sep 6.
This review details the current understanding of the mechanism of action and corneal effects of mitomycin C (MMC) for prophylactic prevention of stromal fibrosis after photorefractive keratectomy (PRK), and includes discussion of available information on dosage and exposure time recommended for MMC during PRK. MMC is an alkylating agent, with DNA-crosslinking activity, that inhibits DNA replication and cellular proliferation. It acts as a pro-drug and requires reduction in the tissue to be converted to an active agent capable of DNA alkylation. Although MMC augments the early keratocyte apoptosis wave in the anterior corneal stroma, its most important effect responsible for inhibition of fibrosis in surface ablation procedures such as PRK is via the inhibition of mitosis of myofibroblast precursor cells during the first few weeks after PRK. MMC use is especially useful when treating eyes with higher levels of myopia (≥approximately 6 D), which have shown higher risk of developing fibrosis (also clinically termed late haze). Studies have supported the use of MMC at a concentration of 0.02%, rather than lower doses (such as 0.01% or 0.002%), for optimal reduction of fibrosis after PRK. Exposure times for 0.02% MMC longer than 40 s may be beneficial for moderate to high myopia (≥6D), but shorter exposures times appear to be equally effective for lower levels of myopia. Although MMC treatment may also be beneficial in preventing fibrosis after PRK treatments for hyperopia and astigmatism, more studies are needed. Thus, despite the clinical use of MMC after PRK for nearly twenty years-with limited evidence of harmful effects in the cornea-many decades of experience will be needed to exclude late long-term effects that could be noted after MMC treatment.
本文详细介绍了丝裂霉素 C（MMC）在光折射性角膜切削术（PRK）后预防基质纤维化的作用机制和角膜效应的现有认识，并包括对 PRK 中推荐的 MMC 剂量和暴露时间的讨论。MMC 是一种烷化剂，具有 DNA 交联活性，可抑制 DNA 复制和细胞增殖。它作为前体药物，需要在组织中还原，才能转化为能够对 DNA 进行烷化的活性物质。虽然 MMC 增强了前部角膜基质中的早期角膜细胞凋亡波，但它在 PRK 等表面消融手术中抑制纤维化的最重要作用是通过抑制 PRK 后最初几周内肌成纤维细胞前体细胞的有丝分裂。当治疗近视（≥约 6D）水平较高的眼睛时，MMC 的使用尤其有用，这些眼睛显示出更高的纤维化发展风险（临床上也称为迟发性混浊）。研究支持使用浓度为 0.02%的 MMC，而不是较低剂量（如 0.01%或 0.002%），以获得 PRK 后最佳的纤维化减少效果。0.02%MMC 的暴露时间超过 40 秒可能对中度至高度近视（≥6D）有益，但较短的暴露时间似乎对低度近视同样有效。尽管 MMC 治疗在 PRK 治疗远视和散光后预防纤维化方面可能也有益，但还需要更多的研究。因此，尽管 MMC 在 PRK 后已经使用了近二十年——在角膜中只有有限的有害影响证据——但还需要几十年的经验才能排除 MMC 治疗后可能注意到的晚期长期影响。
