The Evolving Role of Mitomycin C in Surface Ablation

Few adjunctive treatments in refractive surgery have become as routine—and as rarely questioned—as mitomycin C (MMC). For years, its use during surface ablation has been widely accepted as an effective strategy for reducing postoperative corneal haze, particularly in higher corrections and deeper stromal ablations. Yet with the evolution of refined single-step transepithelial photorefractive keratectomy (trans-PRK), an important question deserves renewed attention: should MMC still be used routinely in every case?

Refined trans-PRK may have fundamentally changed the biological equation. Compared with conventional PRK, modern transepithelial approaches appear to produce smoother stromal surfaces, reduced tissue dehydration, and decreased keratocyte activation. These changes may contribute to a lower inflammatory response and, consequently, a lower intrinsic tendency towards postoperative haze formation.

This evolving perspective was reflected in a study my team and I previously published in the Journal of Refractive Surgery evaluating single-step transepithelial PRK performed with and without intraoperative MMC in eyes with mild-to-moderate myopia and total ablation depths of 160 μm or less. Visual, refractive, contrast sensitivity, and higher-order aberration outcomes were comparable between the two groups. Most importantly, postoperative haze remained similarly low regardless of MMC application.¹

At the same time, however, MMC-treated eyes demonstrated less favourable endothelial findings, including greater endothelial cell loss and increased variation in cell size. Although these changes were not clinically dramatic, they raised an important concern: if refractive and haze outcomes are already comparable, even subtle biological costs deserve careful consideration.

The conclusion of the study reflected this concern directly: routine MMC application in this subgroup of patients ‘may be reconsidered.’

Importantly, the low haze incidence observed in both groups was unlikely to result from a single factor. In addition to the smoother biological profile associated with transepithelial ablation, several adjunctive measures were consistently incorporated into perioperative management, including prolonged low-dose topical corticosteroids, intraoperative use of a chilled balanced salt solution, and rigorous postoperative ultraviolet protection.

Rather than a rigid protocol, this approach represented a practical strategy aimed at minimising unnecessary biological stress while preserving excellent refractive outcomes. In this context, refined trans-PRK became not merely a technical modification but part of a broader effort to improve the biological behaviour of surface ablation.

Perhaps the most important shift arising from this experience was conceptual rather than technical. Historically, refractive surgery has focused primarily on maximising visual outcomes and minimising haze incidence. However, when different approaches achieve similar refractive results, the biological price of adjunctive treatments becomes increasingly relevant.

This is particularly true for MMC. Its antifibrotic efficacy is undeniable in selected cases, and it remains valuable in eyes at elevated risk for haze formation, including higher myopia, deeper ablations, retreatments, and irregular corneas. Yet MMC is also a potent cytotoxic agent. Concerns regarding endothelial safety have already been raised, and potential effects on the ocular surface environment—including limbal stem cell integrity—should encourage thoughtful and selective use rather than automatic routine application.

The issue, therefore, is not whether MMC works. Clearly, it does. The more relevant question is whether advances in surface ablation technology now allow refractive surgeons to reserve MMC for situations in which its benefits clearly outweigh its biological cost.

In refractive surgery, progress is often associated with new lasers, algorithms, or platforms. Sometimes, however, progress comes from re-examining established habits. The future of surface ablation may depend not only on achieving excellent visual outcomes but also on doing so with the least possible biological compromise.

Soheil Adib-Moghaddam MD is an ophthalmologist at Bina Eye Hospital, Tehran, Iran. 2dr.soheil@gmail.com

1. Adib-Moghaddam S. J Refract Surg, 2018 Apr 2; 34(6): 400–407.