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.     

Clinical experience with the single-plate Molteno implant in complicated glaucomas

Ninety patients with medically uncontrollable glaucomas and poor surgical prognoses received single-plate Molteno implants (Optomat Supplies, Dunedin, New Zealand) without postoperative adjunctive systemic antifibrosis therapy. Eleven patients had insufficient follow-up for assessment of intraocular pressure (IOP) or visual acuity outcome. The initial Molteno implant procedures in the remaining 79 patients were successful (IOP less than or equal to 21 mmHg with at least 6 months' follow-up) in 26 (63%) of the 41 patients older than 12 years of age with non-neovascular glaucomas in aphakia/pseudophakia; 7 (70%) of the 10 patients older than 12 years of age with non-neovascular glaucomas in phakic eyes after failed filtering surgery; 7 (47%) of the 15 patients with neovascular glaucomas; and 7 (54%) of the 13 patients younger than 13 years of age with non-neovascular glaucomas. The visual acuities remained within one line of their preoperative levels or improved in 31 (76%) of the 41 aphakic or pseudophakic eyes with non-neovascular glaucomas; 3 (30%) of the 10 phakic eyes with non-neovascular glaucomas after failed filtering surgery; 10 (67%) of the 15 eyes with neovascular glaucomas; and 9 (100%) of the 9 eyes with non-neovascular glaucomas in patients younger than 13 years of age on whom Snellen acuity was available.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects

The antimetabolite 5-fluorouracil (5-FU) was used as adjunctive treatment in glaucomatous eyes with poor prognoses undergoing filtering surgery. By adjusting the frequency of postoperative 5-FU subconjunctival injections according to the clinical response, the author thought it might be possible to reduce episcleral fibroproliferation and maintain a patent filter while reducing complications. Sixty-three eyes underwent filtering surgery with subsequent subconjunctival injections of 5.0 to 7.5 mg 5-FU for 14 days. The antimetabolite was not administered if there was evidence of corneal toxicity as demonstrated by epithelial defects or filaments, flat anterior chamber, or a conjunctival wound leak. By adjusting the injections in this fashion, the total amount of 5-FU administered ranged between 17.5 and 62.5 mg (34.4 +/- 11.6 mg). After 1 year, successful surgical outcomes were observed in 13/15 eyes with aphakia (87%), 11/17 eyes with neovascular glaucoma (65%), 11/12 eyes with at least two previous failed filters (92%), and 5/6 eyes with inflammatory glaucoma (83%). Eyes with epithelial downgrowth and cicatrizing diseases of the conjunctiva also were treated. Overall, conjunctival wound leaks were observed in 24% of the eyes and 29% had detectable changes in their corneal epithelium with corneal defects and filaments. Although adjusting the dose of 5-FU appears to be safe and effective, this can be determined clearly only by a controlled randomized clinical trial.     

Trabeculectomy with 5-fluorouracil.

The effect of subconjunctival injection of 5-fluorouracil (5-FU) after trabeculectomy was studied retrospectively in 205 eyes of 168 patients. A life table analysis of the surgical outcome was based on the type of glaucoma and age related differences, and a comparison was made with patients who had trabeculectomy without subconjunctival 5-FU. The success rate at 30 months after trabeculectomy with 5-FU therapy was considerably higher in primary open-angle glaucoma at 93.6% (72.7%), secondary glaucoma at 88.9% (72.4%), and refractory glaucoma at 72.2% (32.5%) with (or without) the use of ocular hypotensive drops when compared with historical control groups treated without 5-FU (60.0% (41.7%), 35.5% (24.0%), and 18.0% (8.0%), respectively). In patients aged over 70 years, no statistically significant improvement could be demonstrated with the use of 5-FU after trabeculectomy in primary open-angle glaucoma. Our study may provide data on the appropriate dosage and indications for the use of this drug after glaucoma surgery.     

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 5-fluorouracil subsequent to circular buckling operation and cataract extraction.

Six patients, each with one eye that had previously undergone circular buckling surgery for the repair of retinal detachment before or followed by cataract extraction with or without intraocular lens implantation, underwent trabeculectomy with 5-fluorouracil (5-FU) for intractable glaucoma. Surgery was done through scarred subconjunctival tissues that were excised partially. The total doses of 5-FU ranged from 65 to 100mg (mean +/- standard deviation, 84.2 +/- 13.2mg) Eight to 47 months later, intraocular pressures were 18mmHg in five eyes, two of which were not receiving hypotensive medications. In the sixth eye, the intraocular pressure was 26mmHg with maximum hypotensive treatment. Intraocular pressures in the six eyes were significantly lower postoperatively than preoperatively (P < .05). This preliminary study suggests that filtering surgery with 5-FU may be beneficial after intraocular operations even in eyes where it is done through postoperative scarred subconjunctival tissues.     

Filtration procedures supplemented with mitomycin C in the management of childhood glaucoma

AIMS: To evaluate the outcome of filtering procedures supplemented with mitomycin C in children with glaucoma. METHODS: All patients aged 17 or younger with glaucoma who underwent filtering surgery supplemented with mitomycin C at a tertiary care centre (n = 21) during a 5 year interval (1992 and 1996) were included. One eye for each patient was entered into the analysis. The postoperative intraocular pressure (IOP), use of antiglaucoma medications, clinical stability of glaucoma, complications, and visual acuity were retrospectively evaluated. Kaplan-Meier survival curves were used to estimate the probability of success. RESULTS: At the time of surgery mean age was 5.7 (SD 5.0) years. The most common diagnoses were trabeculodysgenesis (n = 6) and aphakic glaucoma (n = 8). Mean IOP before surgery was 35.7 (10.5) mm Hg. Average length of follow up was 18.6 (14.7) months. The probability of having IOP less than 21 mm Hg with no antiglaucoma medications and with clinically stable glaucoma 1 year after surgery was 76.9% in phakic eyes (n = 13) and 0% in aphakic eyes (n = 8). A phakic patient with Sturge-Weber's syndrome had choroidal effusion after surgery that resolved spontaneously. In the aphakic group one patient had retinal detachment and another developed an encapsulated bleb. Visual acuity deteriorated in one patient. CONCLUSION: A guarded filtration procedure with mitomycin C is relatively successful in phakic children with glaucoma, but unsuccessful in aphakic ones.     

Long-term results of 5-fluorouracil trabeculectomy for primary open-angle glaucoma

The effect of 5-fluorouracil (5-FU) subconjunctival injection on the bleb formation and intraocular pressure (IOP) following trabeculectomy was studied in 27 primary open-angle glaucoma patients (33 eyes) who had never been operated upon (25 eyes) or had undergone single trabeculectomy that failed to reduce IOP (8 eyes). The results were analyzed by means of life table analysis and compared with those of 65 primary open-angle glaucoma eyes that had undergone trabeculectomy without postoperative administration of 5-FU as the first or the second filtering surgery. The surgical techniques and postoperative care were virtually identical between the eyes treated with 5-FU and the eyes that had undergone trabeculectomy without 5-FU. At the end of 28-month follow-up, the success probability was 74.8% without any postoperative antiglaucoma medication, and 100% with antiglaucoma medication. Whereas, the success probability with postoperative antiglaucoma medication was as low as 60.8% for the first, and 51.5% for the second trabeculectomy without 5-FU at the 24-month follow-up. Postoperative, subconjunctival injection of 5-FU appears to improve the prognosis following trabeculectomy in primary open-angle glaucoma patients.     

Primary trabeculectomy with 5-fluorouracil for glaucoma secondary to uveitis

Raised intraocular pressure occurs in a significant proportion of patients with uveitis, and may lead to glaucomatous visual loss. Medical therapy often proves inadequate in controlling intraocular pressure, necessitating surgical intervention but conventional filtering procedures such as trabeculectomy are known to fail more frequently in this group than in non-inflamed eyes. Adjunctive subconjunctival 5-fluorouracil (5-FU) has been shown to improve the success of trabeculectomy in a variety of secondary glaucomas. This retrospective study examined the effect of postoperative 5-FU administration on the outcome of trabeculectomy in uveitis-related glaucoma in 28 eyes of 26 patients. Eyes treated with adjunctive 5-FU showed a more prolonged control of intraocular pressure, and a longer median time to failure of control than untreated eyes. Trabeculectomy failure was more common and occurred earlier when a limbus-based conjunctival flap had been used, in patients of black ethnic origin, and if there had been previous intraocular surgery. Additional hypotensive therapy with topical ?-blockers was required more frequently in eyes which had not received 5-FU, and where a limbus-based conjunctival flap had been employed, all eyes in the latter group requiring ?-blockers one year after surgery. Intraocular inflammation was under satisfactory control in all patients at the time of surgery, and no deleterious effect on control of uveitis in relation to surgical intervention was observed.     

After-cataract and secondary glaucoma in the aphakic infant rabbit

PURPOSE: To study the association between after-cataract and secondary glaucoma after lensectomy and 5-fluorouracil treatment in an experimental infant rabbit model. SETTING: St Erik Eye Hospital, Karolinska Institute, Stockholm, Sweden. METHODS: Lensectomy was performed in both eyes of 16 3-week-old rabbits. One randomly selected eye in each rabbit was injected with 2.5 mg of 5-fluorouracil (5-FU) at surgery and 5.0 mg the day after surgery to reduce the formation of after-cataract. Axial length, corneal thickness, corneal diameter, and intraocular pressure were measured preoperatively and 4 times during the 6 months following surgery. Six months after surgery, the wet weight of the after-cataract was determined. RESULTS: In 16 aphakic eyes treated with 5-FU, no or a minimal amount (<0.001 g) of after-cataract developed. None of the eyes showed signs of secondary glaucoma. Of 16 aphakic eyes not treated with 5-FU, 10 developed considerable amounts of after-cataract (>0.10 g); 8 of these developed glaucoma. The other 6 eyes had no or minimal after-cataract and did not develop secondary glaucoma. The relationship between after-cataract and secondary glaucoma was statistically significant. CONCLUSION: A significant relationship between the amount of after-cataract and the development of secondary glaucoma was found in aphakic infant rabbit eyes.     

Mitomycin C-augumented trabeculectomy with postoperative wound modulation in pediatric glaucoma.

PURPOSE: The purpose of this study was to evaluate mitomycin C-augmented trabeculectomy combined with postoperative subconjunctival 5-fluorouracil and laser suture lysis in the treatment of refractory pediatric glaucoma. METHODS: Twenty-one consecutive cases (17 patients) with refractory pediatric glaucoma treated with mitomycin C trabeculectomy (0.4 mg/mL for 3 to 5 minutes) and postoperative 5-fluorouracil, laser suture lysis, or both were retrospectively reviewed. Success was defined as intraocular pressure between 4 and 16 mm Hg without further glaucoma surgery or devastating complication. RESULTS: The median age of the study population was 2.6 years (range, 0.05 to 16 years). The overall success rate was 52.4%, with a median follow-up of 23 months for successful cases. Success rates for patients older than 1 year of age versus those younger than 1 year of age at surgery were 73% and 30%, respectively. Success rates for phakic versus aphakic eyes were 64% and 29%, respectively. Age and lens status, taken together, were significant predictors of outcome (P = .013). Reasons for failure in this study were uncontrolled intraocular pressure (8 cases), persistent wound leak (1 case), and endophthalmitis (1 case); the latter 2 cases required bleb excision. Other complications encountered included chorioretinal detachment, shallow anterior chamber, 5-fluorouracil toxicity, and cataract formation. No irreversible visual deficits could be attributed to the trabeculectomy procedure or subsequent complications in any of these cases. CONCLUSIONS: Mitomycin C-augmented trabeculectomy combined with postoperative suture lysis and 5-fluorouracil is a viable option for older phakic children with refractory glaucoma. This procedure has a lower success rate in infants and in aphakic eyes. Both early and late postoperative complications are common, and diligent lifelong long-term follow-up is needed to detect bleb leaks and infection. The addition of postoperative suture lysis and 5-fluorouracil to mitomycin C-augmented trabeculectomy did not provide any convincing improvement in the success of this procedure in pediatric patients with refractory glaucoma and may have increased the complication rate.     

Needling with intra-bleb 5 fluorouracil for intractable neovascular glaucoma

BACKGROUND AND OBJECTIVE: Trabeculectomy for neovascular glaucoma (NVG) often results in filtering bleb scarring. The outcome of a needling procedure with intra-bleb 5-fluorouracil (5-FU) administration in NVG eyes is presented. PATIENTS AND METHODS: Following trabeculectomy with mitomycin C (MMC), intraocular pressures (IOPs) ranged between 36 to 56 mm Hg in 3 painful, neovascular glaucomatous eyes despite treatment. Each eye was then injected subconjunctivally with 1.0 mg of 5-FU, adjacent to and within the filtering bleb. The needle was advanced and penetration into the anterior chamber through the bled, anterior to the scleral flap, followed. RESULTS: In each eye, the IOP dropped immediately. After 18 to 29 months, IOPs were 11 to 22 mm Hg, and in two eyes-without hypotensive medications. Cataract progression was evident in the 2 eyes that had had cataracts preoperatively. CONCLUSION: The postoperative needling, in conjunction with the dual effect of intraoperative MMC and intra-bleb 5-FU, was found efficacious and saved further surgery in these intractable cases.     

反复针刺分离联合结膜下注射5-FU治疗青光眼术后滤过泡功能不良

目的:评估以反复针刺分离联合结膜下注射5-FU的方法处理青光眼术后功能不良滤过泡的效果。方法:回顾性分析2009-03/2013-02在我院以反复针刺分离联合结膜下注射5-FU的方法处理因青光眼术后滤过泡功能不良而眼压升高的连续病例34例34眼。分析治疗后眼压、滤过泡形态的变化及眼部并发症。结果:治疗后平均眼压从35.51mmHg降至14.43mmHg(P<0.05),成功率达91%。常见并发症包括角膜上皮损伤、结膜撕裂和脉络膜脱离等。结论:反复针刺分离联合结膜下注射5-FU的方法处理青光眼术后滤过泡功能不良安全有效。     

Further experience with trabeculectomy.

Trabeculectomies performed on 33 eyes were compared to 28 standard filtering procedures done at the same institution during a 4 year period. The success rates in the two groups of patients whether white or black were statistically comparable, 92% in the trabeculectomy group and 77% in the standard filtering surgical group. Only cases of phakic open angle glaucoma, chronic angle closure and combined mechanism glaucoma were considered. Cases of secondary glaucoma, previous surgical failure and aphakic nonpupillary block glaucoma did uniformly poorly. When trabeculectomy was performed with "enhanced cyclodialysis" early results in a few cases were successful. The incidence of flat anterior chamber and cataracts with permanent reduction in visual acuity was significantly less in the trabeculectomy group than in the standard filtering procedure group. These results support previous studies which support trabeculectomy as successful as standard filtering procedures with the advantage of having fewer permanent serious complications.     

针刺分离联合5-FU治疗青光眼术后早期滤过泡功能不良

目的探讨对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU的治疗效果。方法青光眼滤过术后3月内25眼功能不良的滤过泡采用针刺分离滤过泡周围纤维瘢痕,联合结膜下注射5-FU 5mg/次,隔日1次,最多5次,分析治疗后眼压和滤过泡形态的变化及治疗后的眼部并发症。结果 25眼中,21眼眼压控制在21mmHg以下,其中18眼在15mmHg以下;滤过泡形态：有19眼表现为功能性滤过泡;并发症：常见并发症有结膜下出血、角膜上皮损伤、滤过泡损伤等。结论对于青光眼术后早期功能不良的滤过泡采用针刺分离联合结膜下注射5-FU是安全、有效的。     

Endoscopic diode laser cyclophotocoagulation in the management of aphakic and pseudophakic glaucoma in children.

INTRODUCTION: Endoscopic cyclophotocoagulation (ECP) has been shown to be a useful adjunct in the management of a variety of difficult pediatric and adult glaucomas. This study reports the efficacy and safety of this procedure for pediatric aphakic and pseudophakic glaucoma. METHODS: ECP was performed on 34 eyes of 25 patients under 16 years of age with aphakic or pseudophakic glaucoma between April 1994 and November 2004. Patients were followed for a minimum of 12 months or until a treatment failure had been declared. Treatment failure was defined as postoperative intraocular pressure (IOP) of >24 mm Hg and IOP lowering of less than 15% despite the addition of glaucoma medications or the occurrence of any visually significant complications. Aphakic eyes of patients with congenital glaucoma or an anterior segment dysgenesis were not included in the study group. RESULTS: Pretreatment IOP averaged 32.6 mm Hg in the 34 eyes, compared with a final postoperative average of 22.9 mm Hg. Mean follow-up period for study eyes was 44.4 months, and the average number of procedures per eye was 1.5. Overall success rate was 53% (18/34). Thirteen of the 34 eyes (38%) received one treatment only and were deemed a success. Retinal detachments developed in two eyes within the first postoperative month. CONCLUSIONS: ECP is a useful tool in the treatment of aphakic and pseudophakic glaucoma, with a low rate of visually significant complications. Retreatment of eyes improved the overall success rate, although experience with cases beyond two treatment sessions is limited. Hypotony was not encountered despite 8 of the 34 eyes receiving 360 degrees of total endocyclophotoablation to the ciliary processes.     

Wound healing in glaucoma filtering surgery

Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success.     

Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery.

In a randomized clinical trial, the authors compared the use of postoperative subconjunctival injections of 5-fluorouracil (5-FU) in 19 eyes with a single intraoperative application of subconjunctival mitomycin (MMC) at the filtering site in 20 eyes at high risk for failure of glaucoma filtering surgery. Six months after surgery, intraocular pressures averaged 10.9 +/- 5.3 mmHg (mean +/- standard deviation) in the MMC-treated eyes versus 14.2 +/- 5.5 mmHg in the 5-FU-treated eyes (P = 0.08) and were less than or equal to 12 mmHg in 60.0% of MMC-treated eyes and 21.1% of 5-FU-treated eyes (P = 0.03). Mitomycin-treated eyes were receiving an average of 0.3 +/- 0.5 medications for intraocular pressure control, and 5-FU-treated eyes were receiving an average of 1.1 +/- 1.1 medications (P = 0.01). Drug-induced corneal epithelial defects were seen in nine 5-FU-treated eyes and in no MMC-treated eyes (P = 0.0004). These results suggest that intraoperative MMC may be a viable alternative to postoperative 5-FU, with lower overall intraocular pressures, decreased dependence on postoperative ocular antihypertensive medications, and decreased corneal toxicity.