Corneal haze after corneal cross-linking associated with mitomycin C

Reviewed by Dr Shady T. Awwad.

Rather than preventing the development of corneal haze after corneal cross-linking (CXL) procedures, the application of the cytotoxic agent mitomycin C (MMC) contributes to its development, according to Dr Shady T. Awwad, professor of clinical ophthalmology at the American University of Beirut Medical Center, in Lebanon.

The rationale for applying MMC after CXL is that it inhibits 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.

Dr 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 Center. 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 2015 to December 2015.

The results obtained from the patients treated with CXL alone were compared with those for the patients who underwent CXL and application of MMC. All patients were followed for 1 year and underwent periodic examinations during this time. The clinicians used Cirrus high-definition optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec AG) to monitor the stromal haze.

Optical coherence tomography (OCT) sections of haze were analysed using a patented machine learning algorithm, developed and published by the authors, to automatically detect and objectively stage areas of 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.

According to Dr Awwad, the overall anterior stromal haze was significantly (P < 0.05 for all comparisons) greater at all postoperative time points (ie, 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 versus 14.8 ± 04.7 grey scale units at 1 month and 18.4 ± 9.3 versus 13.9 vs 4.4 at 12 months.

Analysis of the middle stromal reflectivity indicated that haze was significantly greater at the 12-month time point; however, it 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 versus 23.2 ± 05.9 at 1 month and 27.1 ± 12.8 versus 20.6 ± 07.9 at 12 months for the CXL with MMC and the CXL groups, respectively (P < 0.05 for all comparisons).

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

Shady T. Awwad, MD

E: sawwad@gmail.com

Dr Awwad has no financial disclosures related to this content.