Mitomycin C in refractive corneal surface surgery with the excimer laser: first experience and review of the literature

Haze formation with loss of corneal transparency and surface irregularities and myopic regression are the major complications after corneal refractive surface surgery. The use of mitomycin C (MMC) with its antibiotic and antineoplastic properties is intended to inhibit wound healing mechanisms leading to subepithelial fibrosis. We report the use of MMC to achieve visual rehabilitation in the re-treatment of 3 eyes of 2 patients following refractive corneal surgery. According to the literature, the local use of MMC 0.02 % for 2 minutes is safe and enables one to treat and prevent stromal haze and myopic regression and allows a reduction of the postoperative topical pharmacotherapy. Results are still limited due to small case numbers and short follow-up periods.     

翼状胬肉的不同术式对创面上皮修复及复发率的影响

目的:比较羊膜移植、羊膜移植+丝裂霉素C处理和自体带结膜瓣的角膜缘干细胞移植等三种常见辅助治疗,对胬肉切除术术后角膜创面愈合和1a复发率的影响。方法:本研究为随机、单盲的前瞻性研究。选择160例190眼进展期翼状胬肉成年患者,在行胬肉切除手术时,随机辅助三种常见治疗:A组,羊膜移植(60例68眼);B组,羊膜移植+丝裂霉素C应用(50例62眼);C组,自体带结膜瓣的角膜缘干细胞移植(50例60眼)。随访、记录术后角膜创面愈合情况和1a复发率。结果:A,B和C三组患者角膜创面愈合时间分别为2.1±1.5,2.3±1.2和2.8±1.7d,以C组较长(P<0.05);A组术后2wk内有5例(7%)出现鼻侧结膜手术创缘肉芽肿生长,剪除后无再生,而B,C组未见创缘肉芽肿生长;术后1aA组11眼(16%)复发,与B组7眼(11%)和C组4眼(7%)相比较,具有统计学差异(P<0.05)。结论:羊膜移植+丝裂霉素C处理在促进术后角膜创面愈合和降低1a复发率疗效方面更有优势。     

羊膜移植联合丝裂霉素C在复发性翼状胬肉手术中的应用

目的探讨复发性翼状胬肉手术中采用羊膜移植联合丝裂霉素C的临床疗效。方法复发性翼状胬肉21例（21眼）,彻底切除胬肉和粘连组织后,巩膜创面上应用丝裂霉素C,并分别将羊膜覆盖固定在巩膜及角膜创面。结果角膜创面覆盖的羊膜组织1周内松解脱落,角膜上皮愈合。巩膜创面羊膜植片到术后14~20 d才结膜化。术后随访1~2 a无复发者。结论复发性翼状胬肉采用羊膜移植联合丝裂霉素C是一种有效的手术方法。     

翼状胬肉撕除联合球结膜移植及丝裂霉素C的临床效果观察

目的观察翼状胬肉撕除联合球结膜移植及丝裂霉素C治疗翼状胬肉的效果。方法将69例（69眼）患者随机分为三组,A组行单纯翼状胬肉撕除术;B组为翼状胬肉撕除联合应用丝裂霉素C;C组为翼状胬肉撕除联合应用丝裂霉素C及球结膜移植术。术后观察角膜创面、移植片情况、术后并发症及胬肉复发情况。结果 A组23眼有6只眼复发（26.09%）;B组23眼有3只眼复发（13.04%）;C组23眼有1只眼复发（4.35%）复发率。C组与A组、B组比较,差异均具有统计学意义（P〈0.05）。角膜创面愈合三组差异无统计学意义（P〉0.05）。结论翼状胬肉撕除联合球结膜移植及丝裂霉素C是一种安全有效的治疗翼状胬肉的方法,且复发率低。     

原发性翼状胬肉两种治疗方法的疗效观察

目的:探讨原发性翼状胬肉两种治疗方法的疗效观察。方法:A组25例采用翼状胬肉切除联合丝裂霉素术治疗,B组10例采用自体球结膜+角膜缘干细胞移植术治疗。根据角膜创面恢复、结膜伤口愈合、胬肉有无复发进行观察。结果:A组患者术后角膜上皮第3～7d恢复,结膜充血10～15d消退,3例复发;B组患者术后角膜上皮第2d恢复,结膜充血7～10d消退,1例复发。结论:翼状胬肉切除术联合丝裂霉素和自体球结膜+角膜缘干细胞移植术都能降低胬肉复发率,二者相比较,自体球结膜+角膜缘干细胞移植术优于翼状胬肉切除联合丝裂霉素。     

Effect of topical mitomycin C on glaucoma filtration surgery in monkeys.

In this study, an experimental model of glaucoma filtration surgery was used to evaluate the clinical and histologic effects of a single intraoperative topical application of mitomycin C. Argon laser treatment to the trabecular meshwork produced sustained elevation of intraocular pressure in monkeys. Eight eyes of four animals were randomly assigned to receive topical mitomycin C or balanced salt solution at the time of full-thickness sclerostomy. Surgical success was substantially increased in four of five eyes that received mitomycin C when compared with three eyes that received topical balanced salt solution. Mitomycin C was also effective in prolonging surgical success in two eyes that had previously undergone surgery and failed. No significant ocular toxicity was observed in eyes treated with mitomycin C. Histologic examination of mitomycin C-treated eyes showed patent sclerostomies and hypocellular, well-formed bleb cavities. A single intraoperative application of mitomycin C has a marked effect on postoperative wound healing after filtration surgery in monkeys.     

Mitomycin C, ceramide, and 5-fluorouracil inhibit corneal haze and apoptosis after PRK

PURPOSE: To investigate the effects of mitomycin C (MMC), ceramide, and 5-fluororacil (5-FU) on haze after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UVB) radiation. METHODS: The right eyes of 42 New Zealand white rabbits were treated with PRK to correct -10 diopter with a 5-mm optical zone. Sponges soaked in 0.02% MMC, 10 or 40 micromol/L ceramide, or 0.5% 5-FU were applied to the right eyes of 6 rabbits each, and a tarsorrhaphy was performed. Eight weeks after complete healing, topical 0.02% MMC or 0.5% 5-FU was applied twice daily to the right eyes of 6 rabbits that had previously received PRK but no topical medication. The control group of 6 rabbits was treated only with PRK. Three weeks after PRK, all the laser-treated eyes were exposed to 100 mJ/cm UVB radiation. Corneal haze was assessed biomicroscopically every 2 weeks using the Fantes scale. Eyes were enucleated 2, 7, and 13 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with Apostain. RESULTS: Corneal haze was observed in all rabbits after PRK and was aggravated by UVB irradiation. When applied immediately after PRK, MMC induced corneal opacity and apoptosis of keratocytes, but, at later times, this reagent significantly suppressed opacity, Apostain-positive keratocytes and reactivation of keratocytes, even after UVB irradiation. In contrast, ceramide and 5-FU suppressed corneal opacity after PRK, but this effect was not sustained after UVB irradiation. CONCLUSIONS: MMC is a potent inhibitor of haze induced by PRK and UVB irradiation. Throughout the process of corneal wound healing, the severity of apoptosis and reactivation of keratocytes was closely correlated with haze formation.     

LASEK and photorefractive keratectomy for myopia: clinical and confocal microscopy comparison

PURPOSE: To compare postoperative visual acuity and corneal morphology after laser epithelial keratomileusis (LASEK) versus photorefractive keratectomy (PRK) in the correction of low to moderate myopia. METHODS: In a double-blind, randomized clinical trial, 50 myopic patients (mean: -4.5 +/- 1.35 diopters) were randomized to receive LASEK in one eye and PRK in the fellow eye. No mitomycin C eye drops were used in this study. Patients were observed daily for 4 days, then at 1 month and every 3 months up to 1 year. Uncorrected and best-corrected visual acuity (UCVA and BSCVA), manifest refraction, corneal epithelium healing time, postoperative pain, and corneal haze were evaluated. Corneal wound healing was quantified with corneal confocal microscopy. RESULTS: Refractive error, UCVA, and BSCVA were not statistically different between eyes treated with LASEK and PRK. Corneal epithelium healing time was 2.52 +/- 0.99 days in the eyes treated with PRK and 2.29 +/- 0.52 days in the eyes treated with LASEK (P=.22). The postoperative pain score was 2.17 +/- 0.87 in the eyes treated with PRK and 2.62 +/- 0.60 (P=.02) in the eyes treated with LASEK. Corneal confocal microscopy showed fewer stromal activated keratocytes and less extracellular matrix deposition in the eyes treated with LASEK than in the eyes treated with PRK at 1 month postoperatively (P=.003). CONCLUSIONS: LASEK is an effective and safe procedure for low to moderate myopia, but it seems more painful until full corneal reepithelization. In the early postoperative period, the corneal wound healing process is significantly less intense in eyes treated with LASEK than in eyes treated with PRK. The role of LASEK in corneal wound healing modulation remains controversial.     

Corneal wound healing response following different modalities of refractive surgical procedures

The corneal wound healing response following refractive procedures represents a subject of high relevance, due to its direct influence on the postoperative results. Technical modifications of current refractive procedures, like the automated flap creation with the femtosecond laser, LASEK, PRK with mitomycin C and Epi-LASIK have been proposed as alternatives to traditional LASIK and PRK. Several theoretical advantages have encouraged the diffusion of these new techniques; however, a better understanding of the corneal wound healing response following these procedures is required. The present text proposes a review of the corneal wound healing characteristics following different modalities of refractive surgical procedures.     

角膜缘干细胞移植联合术中应用丝裂霉素C防止翼状胬肉术后复发

目的探讨自体角膜缘十细胞移植联合丝裂霉素C防止翼状胬肉术后复发的效果。方法对95例（109眼）初发翼状胬肉行胬肉切除加角膜缘干细胞移植术中刚含0．02％丝裂霉素C棉片在裸露的巩膜上放置5min。随访6～48个月．结果109眼中复发2眼,复发率为1．83％。主要并发症为结膜伤口延迟愈合和浅层点状角膜炎等。结论自体角膜缘十细胞移植联合术中应用丝裂霉素C可降低翼状胬肉术后复发率,是治疗初发冀状胬肉安全有效的方法。     

多柔比星对兔眼准分子激光角膜切削术后角膜上皮下混浊（Haze)的影响

目的　通过动物实验初步观察应用多柔比星对准分子激光角膜切削术（photorefractive keratectomy,PRK）术后角膜上皮下混浊(Haze)的影响,评估其抑制PRK术后Haze的有效性和安全性,旨在探讨PRK术中多柔比星替代丝裂霉素C应用的可行性。方法　新西兰白兔10只（20眼）,其中右眼为多柔比星治疗的实验组,左眼为丝裂霉素C治疗的对照组,两组兔眼均行PRK激光切削校正-8.00 D后,分别用0.2 g·L^-1多柔比星或0.2 g·L^-1丝裂霉素C的棉片处理,分别于术后1 d、1周、2周、3周、4周在裂隙灯下观察角膜上皮愈合及Haze情况。结果　术后1周,两组所有兔眼角膜上皮均已完全愈合。实验组3眼术后1 d即出现角膜基质片状炎性浸润灶,其中2眼治疗后角膜基质炎性浸润灶消退,另1眼形成浅层斑翳;实验组其余7眼及对照组10眼均未见Haze。结论　多柔比星虽然可能引起角膜基质非感染性炎症反应,但在抑制PRK术后细胞增殖方面或具有与丝裂霉素C类似效果。     

Mitomycin C alters corneal stromal wound healing and corneal haze in rabbits after argon-fluoride excimer laser photorefractive keratectomy.

PURPOSE: To investigate the effects of mitomycin C (MMC) on rabbit cornea wound healing after photorefractive keratectomy (PRK). MATERIALS AND METHODS: Rabbit corneas were stained with dichlorotriazinyl aminofluorescein immediately after PRK. MMC was applied to the right eye and phosphate-buffered salt solution (PBS) to the left. Corneal epithelial wound healing rate and corneal haze were examined. Ultrasound pachymetry was performed. Stromal collagen regeneration was evaluated by fluorescent microscopy. We used terminal deoxyribonucleotidyl transferase-mediated D-uridine 5'-triphosphated-digoxigenin nick-end labeling (TUNEL) assay and transmission electron microscopy (TEM) to evaluate keratocyte apoptosis. RESULTS: In eyes treated with MMC, there was no delay to the healing rate of corneal epithelial wound, and less haze 4 weeks after PRK. Ultrasound pachymetry showed thinner corneal thickness in MMC-treated eyes at week 4. Corneal stromal thickness regression was less in MMC-treated eyes observed by fluorescent microscope at week 4. Keratocyte apoptosis was noted in both MMC- and PBS-treated eyes by TUNEL assay and TEM observation. This study discovered the phenomenon that MMC prolongs keratocyte apoptosis. CONCLUSIONS: Applying MMC after PRK is an effective method to decrease haze formation and corneal stromal thickness regression in rabbit corneas. The effect may be related to MMC prolonging keratocyte apoptosis.     

高海拔地区少数民族翼状胬肉治疗的临床观察

目的:探讨高海拔地区哈萨克族翼状胬肉患者不同方法治疗的效果.方法:将66例69眼患者随机分为两组,分别采用翼状胬肉显微切除加自体角膜缘干细胞移植联合丝裂霉素C术(33例34眼)和翼状胬肉显微切除+丝裂霉素C术(33例35眼),术后随诊1~2d.结果:角膜上皮愈合时间:角膜缘干细胞组为3~5(平均4.5±2.4)d,胬肉切除组5~8(平均6.5±2.6)d,两组比较差异有统计学意义(t=3.317,P<0.05).角膜缘干细胞组有1眼复发,复发率3%,胬肉切除组8眼复发,复发率为22%,两组比较差异有统计学意义(χ2=4.389,P<0.05).结论:在高海拔地区,由于气压低、风沙大、干燥、紫外线辐射强等特点,造成少数民族患病率增高.采用胬肉切除加自体角膜缘干细胞移植联合丝裂霉素C治疗,角膜创面修复快,复发率低,是一种安全、有效、值得推广应用的方法.     

Bullous keratopathy as a complication of trabeculectomy with mitomycin C

Background The routine use of mitomycin C to enhance glaucomatous filtering surgery has found wide acceptance. Complications of the application of mitomycin C have been repeatedly noticed. We now report a previously undescribed complication showing a toxic effect of mitomycin C to the corneal endothelium. Methods Patients underwent routine trabeculectomy with mitomycin C. Following surgery, the eyes were examined by biomicroscopy and specular microscopy of the corneal endothelium. Results In two cases, we observed a partial decompensation of the corneal endothelium resulting in a well-demarcated clear zone of the cornea and a second zone with thickening of the cornea and a bullous keratopathy adjacent to the filtering bleb. The specular microscopy showed marked irregularities of the endothelial cells and areas of necrosis in those parts of the cornea close to the filtering bleb. Conclusions The two cases described here demonstrate that if the corneal endothelium is already compromised before surgery, the application of mitomycin C may have an additional toxic effect on the endothelium and may result in a partial bullous keratopathy. Surgeons should be aware of this complication.     

角膜缘干细胞移植与羊膜移植治疗翼状胬肉疗效比较

目的 比较角膜缘干细胞移植联合丝裂霉素C与羊膜移植联合丝裂霉素C治疗翼状胬肉疗效.方法 将54例(65只眼)患者随机分为两组,角膜缘干细胞移植组(28例35只眼):采用角膜缘干细胞移植联合丝裂霉素C治疗翼状胬肉;羊膜移植组(26例30只眼):采用羊膜移植联合丝裂霉素C治疗翼状胬肉.术后随访6至12个月,分析不同手术复发率及角膜创面愈合时间.结果 角膜缘干细胞移植组1只眼复发,复发率为2.86%;羊膜移植组7只眼复发,复发率为23.33%,两组比较有显著性差异(x2=4.532,P<0.05).角膜创面平均愈合时间角膜缘干细胞移植组为4.67d,羊膜移植组为6.48d,两组比较有显著性差异(t=5.92,P<0.05).结论 角膜缘干细胞移植联合丝裂霉素C能有效地治疗翼状胬肉,角膜创而修复较快,复发率低,是一种安全、有效的手术方法.     

Results of intraoperative mitomycin C application in dacryocystorhinostomy

AIMS: To evaluate the long term results of intraoperative mitomycin C application in dacryocystorhinostomy (DCR) surgery compared with results of the conventional procedure. METHODS: In this prospective randomised controlled study, a total of 88 eyes diagnosed with acquired nasolacrimal duct obstruction were randomly divided into a conventional DCR group and a mitomycin C group in which mitomycin C was used during DCR surgery. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site for 30 minutes. The results of the DCR surgeries were evaluated by objective findings such as irrigation and the height of tear meniscus and subjective symptoms by asking patients the condition of tearing improvement. RESULTS: Among the 44 eyes in the mitomycin C group, 95.5% of patients remained totally symptom free after 10 months of follow up; while in the conventional group, 70.5% of patients were reported to be symptom free and 18% of patients to have an improvement in their symptoms. There was a significant difference between these two groups. As far as objective findings were concerned, there were 41 eyes in the mitomycin C group classified as having a normal and one eye with moderate tear meniscus level, compared with 32 eyes and seven eyes, respectively, in the conventional group. There was also a significant difference between these two groups. The non-patency rate in the mitomycin C group is 4.5% compared with 11.4% in the conventional group. There were no complications such as abnormal nasal bleeding, mucosal necrosis, or infection except one patient with delayed wound healing. CONCLUSIONS: Intraoperative mitomycin C application is effective in increasing the success rate of DCR surgery in standard nasolacrimal duct obstruction, and no significant complications resulted from its use.     

逆向方法联合丝裂霉素结膜瓣转移术治疗翼状胬肉

目的:探讨降低翼状胬肉复发的手术方法。方法:将95例110眼随机分成两组,A组55例63眼采取逆向方法分离翼状胬肉,术中应用丝裂霉素(MMC)及自体结膜瓣移植术,B组常规手术组40例47眼,其中男16例18眼,女24例29眼,年龄28～67(平均41.15)岁,观察两组复发率及角膜上皮愈合时间的情况。结果:随访6～12mo,A组复发率为3.2%;B组复发率为36.2%,复发率比较差异有统计学意义(χ2=9.57,P<0.01)。角膜创面上皮愈合时间:A组平均为4.6±1.2d,B组平均为8.1±0.9d,角膜创面上皮愈合时间两组差异有统计学意义(t=13.08,P<0.01)。结论:逆向方法联合MMC及自体结膜瓣转移术治疗翼状胬肉是一种取材方便,操作简单易学,术后角膜创面恢复快、透明、光滑、结膜平复、复发率低的优点,该方法疗效确切,是理想的手术方式,值得在基层医院推广。     

Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil.

PURPOSE: The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea. METHODS: Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU. RESULTS: Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing. CONCLUSION: These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.     

Permanent corneal edema resulting from the treatment of PTK corneal haze with mitomycin: a case report

A 39-year-old man underwent phototherapeutic keratectomy via excimer laser for recurrent corneal erosions secondary to basement membrane dystrophy with the subsequent development of irregular astigmatism and central stromal opacity. The cornea was scraped and treated with 0.02% mitomycin C using a total of 14 drops over a period of 6 days. Corneal edema developed as a consequence of low endothelial cell count with dysfunctional cells. A corneal transplant restored acuity of 20/20 with binocular vision. It is believed that the underlying endothelium was exposed to toxic doses of mitomycin C sufficient to damage and destroy vital cells. The author reports this case not to criticize the use of mitomycin C in visually disabling post-phototherapeutic keratectomy or photorefractive keratectomy haze but to apprize colleagues of a potential pitfall. The author believes that the use of mitomycin C as a 1-time application at the end of surgery is a safe and valuable adjunct to recover vision when no other is known. However, continued topical application of mitomycin C to the central cornea, in the face of an epithelial defect or an epithelium with inadequate barrier function, increases the risk of endothelial damage.     

Impaired corneal wound healing associated with ketorolac 0.5% after uncomplicated extracapsular cataract extraction

PURPOSE: To describe an apparent association between the use of ketorolac 0.5% (Acular; Allergan) for cystoid macular edema (CME) prophylaxis and impaired corneal wound healing in patients undergoing extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation. METHODS: A retrospective case series reviewing 7 eyes of 7 patients who underwent uncomplicated ECCE with IOL implantation and were treated postoperatively with ketorolac 0.5% 4 times daily as a prophylactic measure against CME. RESULTS: Patients were treated with ketorolac 0.5% 4 times a day for an average of 30 days (range, 20-44 days) after uncomplicated ECCE with IOL implantation. Two eyes developed postoperative endophthalmitis necessitating vitreous tap with intravitreal antibiotic injection; 1 eye went on to require pars plana vitrectomy with corneal wound resuturing. One eye developed corneal wound dehiscence that required wound resuturing in the operating room. One eye developed an inadvertent filtering bleb despite the lack of postoperative suture lysis. Three others were followed up closely postoperatively with slit-lamp evidence of impaired wound healing, manifested by wound avascularity and/or wound gape, and did not require surgical intervention. CONCLUSIONS: The use of nonsteroidal anti-inflammatory agents for prophylaxis of CME after cataract surgery is an evolving trend. This retrospective case series showed a possible link between the use of ketorolac 0.5% and impaired corneal wound healing, and caution is urged in the liberal use of this agent postoperatively after ECCE.