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Mitomycin-C can reduce corneal haze after laser refractive surgery
Francesco Carones, MD, explains how MMC can be used to treat or prevent haze.
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Introduction
 Amar Agarwal |
Haze formation represents excessive wound healing in response to corneal tissue ablation and is characterized by stromal reaction, keratocyte activation, collagen and amorphous material deposition. Certain circumstances tend to magnify both the density of haze and the chance of its appearance. Among them, the amount of intended correction is probably the most important — the higher the correction, the worse the haze. But other factors such as sun exposure, delay in re-epithelialization and irregularity of the ablation surface are also implicated in haze formation. Dense haze may significantly impair vision by reducing best corrected visual acuity, inducing regression, inducing irregular astigmatism and provoking visual symptoms such as blurred vision, halos, glare and ghost images. Treatment of severe haze involves the use of pharmaceuticals applied topically. Corticosteroids produce some controversial results and are frequently ineffective. The second category of drugs employed are antimetabolites, of which mitomycin-C (MMC) is used the most. My special guest in this column is Francesco Carones, MD, of Carones Ophthalmology Center, Milan, Italy, to explain the use of this powerful agent.
Amar Agarwal, MS, FRCS, FRCOphth
Mitomycin-C is a systemic chemotherapeutic agent. It is commonly used topically in ophthalmology after glaucoma surgery, after pterygium excision, in the treatment of conjunctival and corneal intraepithelial neoplasia, and in the treatment of ocular pemphigoid. Rationale for its use relies on its long-term, possibly permanent, cytostatic effect on tissue. More specifically, its use after PRK is intended to inhibit subepithelial fibrosis as the result of an abnormal activation or proliferation of stromal keratocytes after laser ablation. The peculiar action of MMC on the corneal tissue allows two possible applications in the field of laser surface ablation. It can be used therapeutically in eyes already exposed to surface ablation that present significant haze, or it can be used in a prophylactic fashion to avoid haze formation in eyes at risk for haze.
MMC to treat haze
The rationale for this therapy is the removal of haze by any method (excimer laser PTK, mechanical scraping) and the application of MMC to inhibit further haze formation.
The corneal epithelium is removed using a 20% diluted alcohol solution, applied topically by filling the barrel of a 9-mm Hoffer marking trephine. The alcohol is removed with Merocel microsponges, and the epithelium is gently removed with Merocel surgical microsponges. Once the epithelium is removed, using a Desmarres sharp blade, the stromal surface is scraped vigorously in an attempt to remove as much newly generated tissue as possible. This process is complete when no material is visible on the sharp edge of the blade itself. At this point, the stromal surface should look not only much more transparent than before scraping (slit-lamp examination is mandatory for this), but also much more regular and smooth. Immediately after scraping, a circular Merocel microsponge soaked with a 0.02% (0.2 mg/mL) MMC solution is placed on top of the stromal surface (Figure 1). This is left in place for 2 minutes. The surface is then irrigated copiously with 20 cc of balanced salt solution to remove all MMC particles and remnants.
The scar can also be removed using the excimer laser in a therapeutic fashion. In this case, the surgeon may consider programming either a plano correction or a refractive procedure, depending on the patient’s refraction. It is important to note that with all approaches there will be some unpredictable refractive change due to the removal of fibrotic tissue; thus, the programmed refractive change should be conservative.
Postoperatively, a bandage contact lens is applied to both eyes and left in place until re-epithelialization is complete (usually 4 days). During this period, antibiotic drops and nonsteroidal anti-inflammatory drops are applied four times a day, together with artificial tears. The patient is also prescribed oral narcotics as needed for pain. Once the bandage contact lens is removed, topical fluorometholone drops are applied three times a day for 2 weeks and then twice a day for 2 weeks. Artificial tears are administered as needed thereafter.
Results
The results attainable with this therapy are successful. Figures 2 and 3 show a case of a patient who underwent PRK for –12 D correction in 1996 and had this therapy in 1998. The patient was in a lamellar keratoplasty waiting list at another center. The opacity was so dense that it obscured details of iris visualization at slit-lamp examination, and the irregularity generated by the scarring was so severe to determine a high irregular astigmatism on corneal topography. This case mimics the average results achievable with MMC used to avoid further haze formation once the scar is removed. Corneal transparency, once restored, is maintained over time in the majority of cases.
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Images: Carones F |
MMC to avoid haze formation
In all cases of surface ablation at risk of haze formation, MMC may be applied prophylactically to avoid such complications. Indications include not only high volumes of ablated tissue (high attempted corrections, generically speaking), but also surface ablation enhancements; ablation on top of a previous LASIK flap either for enhancement purposes or to manage a flap complication (aborted, buttonhole, irregular); ablation over previous refractive surgery (radial keratotomy) or therapeutic corneal surgery (penetrating keratoplasty); or keloid formers. The way MMC is delivered is the same as for therapeutic purposes.
Safety issues
The major criticism in the use of MMC after laser refractive surgery refers to the potential side effects and complications associated with its long-term cytostatic action on tissues when applied in a topical fashion on the corneal stroma. Several researchers have reported corneoscleral melt after MMC application after pterygium excision. Also, the long-term integrity of the endothelial layer is supposed to be at risk.
For More Information:
- Amar Agarwal, MS, FRCS, FRCOphth is director of Dr. Agarwal’s Group of Eye Hospitals. Dr. Agarwal is author of several books published by SLACK, Incorporated, publisher of Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery, and Presbyopia: A Surgical Textbook. He can be reached at 19 Cathedral Road, Chennai 600 086, India; fax: 91-44-28115871; e-mail: dragarwal@vsnl.com; Web site: www.dragarwal.com.
- Francesco Carones, MD, can be reached at Carones Ophthalmology Center, Via Pietro Mascagni, 20, 20122 Milan, Italy; 39-02-7631-8174; fax: 39-02-7631-8506; e-mail: fcarones@carones.com.
References:
- Agarwal A. Handbook of Ophthalmology. Thorofare, NJ: SLACK Incorporated; 2005.
- Agarwal A. Refractive Surgery Nightmares. Thorofare, NJ: SLACK Incorporated; 2007
- Agarwal S, Agarwal A, Agarwal A. Four volume textbook of ophthalmology. India: Jaypee; 2000.