Postoperative 5-fluorouracil versus intraoperative mitomycin C in high-risk glaucoma filtering surgery: extended follow up

Purpose: To compare the long‐term efficacy and safety of postoperative subconjunctival 5‐fluorouracil (5‐FU) injections with that of intraoperative mitomycin C (MMC) in eyes at high risk for failure of trabeculectomy. Methods: In a retrospective, non‐randomized comparative trial, 36 eyes of 36 consecutive patients at high risk for failure of trabeculectomy underwent glaucoma filtering surgery with either postoperative subconjunctival 5‐FU injections (19 eyes) or intraoperative application of MMC (17 eyes). Intraocular pressure, number of postoperative antiglaucoma medications, postoperative visual acuity, interventions, and complications were evaluated. Results: Overall success (intraocular pressure ≤21 mmHg) at 1 year was 73.6% in the 5‐FU group and 82.3% in the MMC group. The cumulative 4‐year success was 52.6% in the 5‐FU group and 60.5% in the MMC group (P = 0.6). At 4‐year follow up, mean ± SD intraocular pressures were 17.58 ± 4.01 mmHg in the 5‐FU group and 13.33 ± 3.36 mmHg in the MMC group (P = 0.01). There was no significant difference in the number of post­operative medications (P = 0.84), appearance of blebs (P = 0.20), final visual acuity (P = 1.00), and complications (P > 0.05) between the groups. Conclusions: These results suggest that both postoperative 5‐FU injections and intraoperative MMC application have long‐term success in high‐risk patients. However, MMC results in a greater decrease in intraocular pressure than 5‐FU.     

Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil

We studied four patients who, having received postoperative 5-fluorouracil after glaucoma filtering operations, developed serious corneal complications. All four patients had preexisting corneal abnormalities including keratoconjunctivitis sicca, exposure keratopathy, and bullous keratopathy. All of the patients developed epithelial defects in the postoperative period. The complications included bacterial corneal ulceration (two patients), sterile corneal ulceration and corneal perforation (one patient), and a keratinized corneal plaque with underlying sterile stromal infiltrate (one patient). The use of 5-fluorouracil, which is an antimetabolite with considerable corneal epithelial toxicity, after glaucoma filtering surgery frequently causes corneal epithelial defects that may lead to secondary complications. Patients receiving this drug should have their corneal status closely monitored. In patients with corneal epithelial disease, 5-fluorouracil should be used with caution.     

Intraoperative application versus postoperative mitomycin C eye drops in pterygium surgery.

PURPOSE: Postoperative recurrence of pterygium occurs in many patients. Intraoperative and postoperative mitomycin therapy are two adjuvant treatment methods shown to lessen the high pterygium recurrence rate seen with simple excision alone. The authors designed a prospective, randomized study to explore the recurrence rate of pterygium after a single dosage of mitomycin C at the completion of pterygium excision, comparing it to postoperative mitomycin C therapy. METHODS: Thirty-six patients with 40 primary and recurrent pterygia were randomized to 1 of 2 treatment groups: intraoperative mitomycin 0.2 mg/ml for 5 minutes (group 1) and postoperative mitomycin 0.2 mg/ml four times a day for 7 days (group 2). The mean follow-up time was 15 months (range, 6 to 24 months). RESULTS: The pterygium recurred in 3 (15%) of 20 eyes in group 1 and in 4 (20%) of 20 eyes in group 2 (p=0.41). One patient in group 1 had a mild scleral melting (1 x 1 mm) and a delay of reepithelialization for three weeks. Moderate superficial punctate keratitis (two eyes) and mild anterior chamber reaction (one eye) developed in group 2. CONCLUSION: This study indicates possible advantages of administration of a single dosage of 0.02% mitomycin C over postoperative mitomycin therapy. If the decision is made to use adjunctive mitomycin, the authors recommend intraoperative over postoperative administration.     

Reducing corneal toxicity of 5-fluorouracil in the early postoperative period following glaucoma filtering surgery

To gain a better understanding of the relationship between postoperative 5-fluorouracil administration and corneal complications associated with its use, we analysed 43 consecutive filtering procedures in which it had been employed. Nine of the 43 eyes had corneal complications during that period. At the end of the three-month period, these corneal complications had all resolved. There was no correlation between postoperative intraocular pressure lowering and incidence of corneal complications. A low dose of 5-flourouracil, and early recognition and treatment of corneal toxicity associated with its use may reduce corneal complications while maintaining filtration in eyes with poor surgical prognosis.     

5-fluorouracil and glaucoma filtering surgery. II. A pilot study

5-Fluorouracil (5-FU) was injected subconjunctivally after glaucoma filtering surgery in a pilot study of eyes with poor surgical prognoses. Twenty-seven (79%) of the 34 aphakic eyes with glaucoma achieved an intraocular pressure (IOP) of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 91 -468 days). Nine (69%) of 13 eyes with neovascular glaucoma achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 120-379 days). Eight (89%) of nine phakic eyes with glaucoma following unsuccessful filtering procedures achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 134-394 days). Visual acuities remained within one line of their preoperative levels or improved in 32 (94%) of the 34 aphakic eyes with glaucoma, eight (62%) of the 13 eyes with neovascular glaucoma, and six (67%) of the nine phakic eyes with glaucoma following unsuccessful filtering procedures. Postoperative corneal epithelial defects occurred in 45% of the cases. Conjunctival wound and conjunctival needle tract leaks were observed in 41% of the cases, but only one eye required wound revision. No other serious side effects that we attributed to 5-FU were observed. It seems that postoperative subconjunctival 5-FU increases the likelihood of achieving IOP control following filtering surgery in eyes with poor surgical prognoses; however, a randomized clinical trial is necessary to confirm this.     

Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery.

INTRODUCTION: To determine whether 5-fluorouracil is effective in reducing scarring after strabismus surgery we used rectus muscle surgery in experimental animals to compare a single intraoperative dose of 5-fluorouracil with mitomycin C and to compare results in similarly treated controls not receiving these antimetabolites. METHODS: Muscle resections were performed on eight rabbits (16 eyes). Four eyes had 5-fluorouracil (50 mg/ml), and four eyes received mitomycin C (0.2 mg/ml), each of which was applied during surgery on an ophthalmic sponge for 5 minutes. Eight eyes served as controls. Six weeks after surgery conjunctival vascularity, muscle length-tension curves, muscle disinsertion force, and the histologic degree of scarring were assessed. RESULTS: The mitomycin C-treated eyes clearly had more conjunctival avascularity and a lower disinsertion force. Both treated groups had flatter length-tension curves and less scarring on histologic examination than the control eyes. CONCLUSIONS: Antifibroproliferative therapy with intraoperative sponge 5-fluorouracil appears as effective as, and is possibly safer than, mitomycin C. It may be a useful adjunct in recurrent strabismus surgery or in other situations where a risk of excessive postoperative scarring exists.     

5—氟尿嘧啶与丝裂霉素C在青光眼滤过术中的合理应用

目的 探讨青光眼滤过手术抗代谢药物丝裂霉素C（MCC）与5－氟尿嘧啶（5－Fu）的合理应用。方法 对108只需手术的青光眼随机分成3组。5－Fu组术后球结下注射5－Fu6－8次,MMC组术中一次性给予质量浓度为0.2mg/ml的MMC,对照组则不用任何药物,观察各组术后的疗效及并发症。结果 随访3－34个月（平均28．2月）,5－Fu和MMC组手术成功率明显高于对照组,P＜0．05。术后并发症5－Fu组角膜上皮点状损害18只眼（45％）,MMC组低眼压2例（6．7％）,与对照组比有显著差异（P＜0．05）。结论 5－Fu与MMC能提高青光眼手术的成功率,但有一定的毒副作用。临床上应根据病人的年龄、病情及青光眼类型选择用药。     

5-fluorouracil and glaucoma filtering surgery: I. An animal model

Failure of a glaucoma filtering procedure commonly results from scarring at the surgical site. Fibroblasts play an important role in the scarring process. 5-fluorouracil is an antimetabolite capable of inhibiting fibroblast proliferation. We tested the ability of 5-fluorouracil to inhibit cicatrization at the filtering site in an experimental model. Posterior lip sclerectomies were performed in each eye of ten normal owl monkeys. Postoperatively, one eye of each animal received subconjunctival injections of fluorouracil and the fellow eye received saline injections in a randomized, masked fashion. Two animals died of undetermined causes. None of the control eyes developed blebs, but six of the eight treated eyes in surviving animals developed blebs. The difference between intraocular pressures in fluorouracil-treated and control eyes was statistically significant (P less than 0.05). Signs of ocular toxicity included persistent corneal epithelial defects and delayed healing of the conjunctival incision. These results are considerably more favorable than those previously reported with experimental filtering procedures in non-human primates. Pharmacologic modulation of wound healing may decrease the risk of failure of filtering operations.     

比较5-Fu和MMC缓释膜在青光眼滤过手术中应用的实验研究

目的 评估生物缓释膜在青光眼滤过手术中的安全性和作用,比较5-氟尿嘧啶(5-Fu)和丝裂霉素(MMC)缓释膜在青光眼滤过手术中的抗增殖的疗效.方法 以5-Fu和MMC作为模型药物,壳聚糖作为载体,溶剂挥发法成膜;通过共价交联的方式将12μg的5-Fu或MMC结合到生物缓释膜上.未植入缓释膜作为对照组,其余3组植入空白、5-Fu和MMC缓释膜.四组均行青光眼滤过手术,静脉留置针作为引流管,空白缓释膜、5-Fu缓释膜、MMC缓释膜缝于巩膜瓣下.滤过手术前和手术后1、3、5、714、21和28d,以Tonopen眼压计记录兔眼压,以裂隙灯观察滤过泡大小和眼前节的变化并照相;分别于术后28d每组处死两只兔,总共8只眼标本行病理组织学检查;用扫描电子显微镜检测每组术后28d的角膜和晶状体标本.结果 术前各组平均眼压无差异,MMC组手术前和手术后28d内比较差异有统计学意义(F值为26.866 P＜0.01),5-Fu组和单纯引流管组手术前和手术后14d内比较差异有统计学意义,(F值分别为13.467,6.567 P＜0.01),空白缓释膜组手术前和手术后7d内比较差异有统计学意义(F值分别为11.426 P＜0.01);MMC、5-Fu组滤过泡生存时间优于单纯引流管组、空白缓释膜组.5-Fu和MMC组,术后28d角膜内皮细胞和晶状体前囊无异常改变.结论 5-Fu和MMC生物缓释膜能明显提高滤过手术成功率并且是安全的,在降低眼内压和延长滤过泡减少眼前节并发症方面,MMC缓释膜比5-Fu缓释膜能更有效地提高滤过手术成功率.     

Glaucoma filtering surgery with postoperative 5-fluorouracil in patients with intraocular inflammatory disease.

Twenty-one eyes of 18 patients with uncontrolled glaucoma and intraocular inflammatory disease had glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil (5-FU). Follow-up for eyes in which intraocular pressure was controlled ranged from 6 to 53 months (mean, 34 months; median, 35 months). Fifteen of 21 eyes (71%) had controlled intraocular pressure (21 mmHg or less). Control was achieved in 9 of 10 (90%) phakic eyes and in 6 of 11 (55%) aphakic or pseudophakic eyes with or without glaucoma medication. Four of six filter failures had a second filtering procedure with 5-FU, and of these four procedures, three were successful. Cataract progression occurred in 9 of 10 phakic eyes, leading to cataract surgery in 7 eyes. Other complications included corneal epithelial defects in 13 eyes, bleb leaks in 3 eyes, choroidal effusions in 13 eyes, 1 choroidal hemorrhage, 1 serous retinal detachment and macular retinal pigment epithelial disturbance associated with hypotony and choroidal effusion. Filtering surgery with postoperative subconjunctival 5-FU can successfully control intraocular pressure in eyes with ocular inflammatory disease.     

Glaucoma filtering surgery with 5-fluorouracil

A life-table analysis of surgical outcomes was performed on the first eye of 155 patients who were enrolled in a pilot study of glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil (5-FU) injections. The success rates at 1-, 2-, and 3-year intervals were 68, 63, and 63%, respectively, for 88 patients with non-neovascular glaucoma in aphakia; 82, 75, and 75% for 39 patients with non-neovascular glaucoma after unsuccessful filtering surgery; and 68% at each yearly interval for 28 patients with neovascular glaucoma. Complications which resulted from filtering surgery and the 5-FU injections included corneal epithelial defects (55.5%), conjunctival wound leaks (36.8%), suprachoroidal hemorrhage (5.8%), rhegmatogenous retinal detachment (2.6%), endophthalmitis and phthisis (1.9% each), and corneal scarring, late bleb leak, malignant glaucoma, and traction retinal detachment (1.3% each). A Cox Model regression analysis failed to demonstrate a correlation between surgical success and age, race, type of filtering procedure, or total dose of 5-FU received. Postoperative subconjunctival 5-FU may increase the operative success rate for selected patients with a high risk for failure after glaucoma filtering surgery.     

Limbus-based versus fornix-based conjunctival flap in glaucoma filtering surgery.

Eighteen consecutive patients suffering from the same type of glaucoma in both eyes were treated with bilateral trabeculectomy. Surgery with both fornix-based and limbus-based flap was performed on each patient, one procedure in each eye. Pre- and postoperative intraocular pressure, morphology of the fistulation bleb, anterior chamber depth and need for additional treatment were recorded. Half a year after surgery, the fornix-based flap procedure was superior (p < 0.05) concerning high success rate, little additional therapy and good morphology of the bleb.     

Dose,timing and frequency of subconjunctival 5-fluorouracil injections after glaucoma filtering surgery

BACKGROUND: Although adjunctive postoperative 5-fluorouracil (5-FU) injections are known to improve the success rate of glaucoma surgery, it is still unknown what dose, timing and frequency of application will give the best results with respect to the inhibition of postoperative scarring and intraocular pressure regulation. We therefore designed the following retrospective investigation. METHODS: We studied 172 eyes from 172 patients who had undergone trabeculectomy with adjuvant 5-FU-therapy. Variations of dosage, timing and frequency were analysed retrospectively. Surgery was defined as a complete success when the patient reached an intraocular pressure under 21 mmHg and a reduction of 20% 12 months after the operation. A relative success was achieved with these criteria under additional local medication. Not reaching these postoperative criteria for a complete success was classified as failure. RESULTS: On average, adjunctive 5-FU-treatment was started 4.6+/-5.85 days postoperatively. The injections contained between 2 mg and 5 mg FU, and the mean total dose was 26.6+/-13.2 mg (range 5-65 mg). Surgery on 94 patients (54.65%) was classified as "complete success", that on 25 patients (14.53%) was classified as "relative success" and that on 53 eyes (30.81%) was classified as "failure" 12 months (+/-3 months) postoperatively. The best results were obtained when the treatment started on or before the first postoperative day (68.0-71.4% complete success; P<0.05). In contrast, an increase in 5-FU dosage did not result in an increased success rate of trabeculectomy. None of the 172 patients suffered from vision-threatening complications such as endophthalmitis or hypotony maculopathy. CONCLUSION: Early treatment with 5-FU significantly increases the success rates of filtering surgery.     

抗青光眼滤过术中应用5-氟尿嘧啶和丝裂霉素C对泪膜的影响

目的　观察抗青光眼滤过术中应用5-氟尿嘧啶（5-fluourouracil,5-Fu）和丝裂霉素C（mitomycinC,MMC）对泪膜的影响。方法　回顾性分析难治性青光眼71例,其中使用5-Fu组24例（24只眼）,MMC组17例（17只眼）,对照组（未用药）30例（30只眼）,观察指标包括眼部异物感、干涩、畏光、痒感、结膜充血、分泌物、角膜荧光素染色及结膜、角膜虎红染色、泪膜破裂时间、Schirmer试验及眼压测量值。结果　5-Fu组患者的眼部症状和体征明显,泪膜功能受损,与对照组比较差异有显著性（P<0.05）,MMC组患者眼部干涩症状明显（P<0.05）,而其他观察指标与对照组相比差异无显著性。结论　抗青光眼滤过术后应用5-Fu可明显损害泪膜的功能。     

Use of 5-fluorouracil in the surgery of glaucoma

63 eyes (46 patients) with different types of glaucoma have been operated by filtering surgery with subconjunctival 5 fluoro-uracil (5-FU) injections. The mean follow up is 7 months. Two groups of patients have been studied: In the 33 eyes with previous unsuccessful glaucoma surgery, the result was very good: 73% of complete success (IOP less than or = 20 mmHg without additional therapy) 18% of qualified success (IOP less than or = 20 mmHg with additional therapy) 8% of failure. The other group included 30 eyes without previous glaucoma surgery, but with a bad surgical prognosis. In all the cases, the result was good, only one eye required additional therapy. The corneal complications are the most frequent, but do not last long. The other complications depend upon the indications, there are many in the aphakic patients. The durable flat anterior chamber must also be quoted.     

Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil. Prospective randomized clinical trial

OBJECTIVE: To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN: Prospective multicenter, randomized clinical trial. PARTICIPANTS: One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS: One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS: Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS: 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.     

Upper eyelid retraction after glaucoma filtering surgery and topical application of mitomycin C

PURPOSE: To describe 3 cases of upper eyelid retraction after glaucoma filtering surgery and topical application of mitomycin C and to highlight possible causes. METHODS: A report of 3 patients, identified over an 8-year interval period, who had development of upper eyelid retraction a few months after undergoing trabeculectomy with mitomycin C in the ipsilateral eye. RESULTS: Testing for Graves disease, including second-generation thyrotropin receptor antibodies (TRAb), was negative in all cases. A complete physical examination was performed by an internist: Orbital and intracranial neuroimaging studies were ordered when necessary, and all were negative. One patient underwent surgical repair of the eyelid retraction and had a satisfactory result. CONCLUSIONS: Upper eyelid retraction after filtering surgery is a rarely reported entity. Müller muscle overaction, independent of Graves disease, is a likely cause and has been pointed out as a possible factor in one previous report. Müller muscle fibrosis, euthyroid Graves disease, and mechanical hindrance to an elevated bleb are other possible factors.