Mitomycin C associated with increase in corneal haze after corneal crosslinking

Reviewed by Dr Shady T. Awwad.

During a presentation at the American Academy of Ophthalmology’s 2021 annual meeting, Shady Awwad, MD, professor of Clinical Ophthalmology at the American University of Beirut Medical Centre, Beirut, Lebanon, advised that application of mitomycin C (MMC) after corneal crosslinking (CXL) does not prevent development of corneal haze after the procedure and instead contributes to development of more corneal haze.

The rationale for applying MMC after CXL has been the inhibition of incoming keratocytes following the procedure; however, abundant cytokine release from a surge in apoptosis due to the combination of CXL and MMC seems to be responsible for the development of more haze.

Awwad and colleagues reached this conclusion based on the results of a retrospective, single-centre study of 72 patients (87 eyes with keratoconus) who underwent CXL from June 2013 to January 2015 at the American University of Beirut Medical Centre. The same surgeon performed all CXL procedures using the Dresden protocol. MMC was applied at the end of each CXL procedure as part of the routine protocol from February to December 2015.

Percent of haze area: anterior stroma

The results obtained from the patients treated with CXL alone was compared to the patients who underwent CXL and application of MMC. All patients were followed for 1 year and underwent periodic examinations during that period. The clinicians used Cirrus high-definition optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec AG) to monitor the stromal haze. OCT sections of stromal haze were analysed using a patented machine learning algorithm, developed and published by the authors, to automatically detect and objectively stage areas of stromal haze.

The visual results were slightly better without MMC but not significantly so, and the topographic results with/without MMC were significantly better compared with preoperatively.

Awwad reported that the overall anterior stromal haze was significantly (p < 0.05 for all comparisons) greater at all postoperative time points, i.e., at 1, 3, 6, and 12 months when MMC was applied compared with when CXL alone was performed. The mean gamma-decoded anterior stromal reflectivity on OCT scans was 26.0±15.0 vs 14.8± 4.7 grey scale units (GSUs) at 1 month and 18.4±9.3 vs 13.9± 4.4 at 12 months.

Analysis of the middle stromal reflectivity indicated that haze was significantly greater at the 12-month time point but did not reach significance at any time in the posterior stroma. The reflectivity of the anterior stromal haze area (which is selected by the software as displaying more haze than the surrounding area), calculated as the mean pixel intensity in a particular corneal region, was 33.1±16.6 vs 23.2+/-5.9 GSU at 1 month and 27.1±12.8 vs 20.6±7.9 GSUs at 12 months, for the CXL with MMC and the CXL groups, respectively (p<0.05 for all).

Awwad concluded by raising another area for consideration, notably the implications of this study on simultaneous PRK plus CXL candidates. where the value and potential risks of MMC should be critically appraised.

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