Mitomycin- C Mmc In Crosslinking: Bane Or Boon? A Clinical & Molecular Study

Published 2025 - 43rd Congress of the ESCRS

Reference: PP16.03 | Type: Free paper | DOI: 10.82333/egz8-sp37

Authors: Clare ODonnell* ¹ , Nabila Jones ² , Amir Hamid ³

¹Eye Sciences,Optegra Eye Health Care,Manchester,United Kingdom;Faculty of Biology, Medicine and Health,University of Manchester,Manchester,United Kingdom;College of Health and Life Sciences,Aston University,Birmingham,United Kingdom, ²Eye Sciences,Optegra Eye Health Care,Manchester,United Kingdom, ³Eye Sciences,Optegra Eye Health Care,Manchester,United Kingdom;Faculty of Biology, Medicine and Health,University of Manchester,Manchester,United Kingdom

Purpose

This study aimed to evaluate the effect of mitomycin-C (MMC) as a pro-fibrotic agent in corneal cross-linking (CXL) and assess whether tailored anti-inflammatory therapy prior to CXL reduces postoperative corneal haze.

Setting

A prospective clinical study was conducted at a tertiary ophthalmology center.

Methods

In Vitro Analysis

Human corneal epithelial cells (HCEs) were used to analyze the effect of MMC under inflammatory stress. HCEs were treated with MMC (0.01%) in the presence of tumor necrosis factor-alpha (TNF-α). The expression of extracellular matrix (ECM) remodeling markers COL1A1, LOX, and PREX1 was measured using quantitative PCR (qPCR) to evaluate the pro or anti-fibrotic effects of MMC.

Clinical: Total 200 eyes undergoing CXL with MMC were included, with 100 eyes in each group:

1: Received tailored anti-inflammatory therapy based on biomarker profiling before CXL (biological cleansing).

2: Underwent CXL with MMC with no preop treatment.

Postop corneal haze incidence and severity were assessed at 1 month, graded using a standardized scale.

Results

In Vitro Findings

MMC-treated HCEs under TNF-α stimulation demonstrated a significant increase in COL1A1, LOX, and PREX1 expression. Despite increased MMP9 expression, the upregulation of ECM remodeling markers suggests that MMC promotes pro-fibrotic molecular changes rather than exerting an anti-fibrotic effect in the presence of cellular stress.

Clinical Findings

A significantly higher incidence of corneal haze was observed in Group 2 (p < 0.01), with:

67 patients developing haze (37 with grade 1, 18 with grade 2, and 12 with grade 3 haze).

In contrast, in Group 1 (pre-treated with biological cleansing): Only 13 patients developed haze (7 with grade 1, 5 with grade 2, and 1 with grade 3).

Conclusions

MMC does not mitigate fibrosis but rather enhances pro-fibrotic changes when cellular stress is present. Preoperative biomarker-based anti-inflammatory therapy (biological cleansing) significantly reduces postoperative corneal haze following CXL with MMC. These findings highlight the importance of individualized pre-treatment strategies to minimize haze formation and improve CXL outcomes.