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Aims: To evaluate, describe and quantify the diversity in postoperative antimetabolite administration and bleb needling practices among glaucoma specialists performing trabeculectomy surgery within the UK and Ireland., Methods: A cross-sectional online survey was distributed to all consultant glaucoma specialists who are on the United Kingdom and Eire Glaucoma Society (UKEGS) contact list. Participants were asked specific questions about their current practices for post-trabeculectomy antimetabolite administration followed by questions directly related to bleb needling procedures., Results: 60 (83%) of UKEGS glaucoma subspecialty consultants completed the survey. 70% of respondents administered 5-fluorouracil (5-FU) in their clinic room while 30% used a separate treatment room. Doses of 5-FU varied considerably but 70% used 5 mg as standard. Techniques used to reduce corneal toxicity included precipitation with amethocaine (44%) or benoxinate (14%), saline wash (14%) and modified injection technique (8%). Topical antibiotics and/or betadine were used to prevent infection following 5-FU injection in just over 50%. Bleb needling was exclusively performed in operating theatre by 56% of respondents and solely at the slit lamp in the clinic room by 12%. A further 30% used a combination of both theatre and outpatient clinic rooms. Anti-metabolites used were 5-FU (72%) and mitomycin C (22%) with 12% using either of the two substances., Conclusions: There is a significantly wide variety of current practices for antimetabolite administration and bleb needling within the UK and Ireland. This may be influenced by a glaucoma surgeon's specific experience and audit results as well as particular clinical set-up, availability of antimetabolite and clinic room space., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To compare mean endothelial cell loss in patients of primary open angle glaucoma undergoing trabeculectomy with and without mitomycin C., Study Design: Randomised control study., Place and Duration of Study: Institute of Ophthalmology, Mayo Hospital, Lahore, from May 2016 to April 2017., Methodology: Patients with primary open angle glaucoma, not controlled with medication, were selected from the outpatient department. Patients with secondary glaucomas and concomitant ocular disease were excluded. Selected patients were divided into two groups of 30 each. Group A patients underwent trabeculectomy with adjunctive mitomycin C while group B patients underwent trabeculectomy alone. Pre- and post-trabeculectomy endothelial cell counts were recorded with the help of specular microsope and entered on proforma., Results: Median cell loss was 283 (66.50) when trabeculectomy was done with the use of adjunctive mitomycin C in group A while median endothelial cell loss was 72.50 (19.25) when the trabeculectomy was done without the use of adjunctive mitomycin C in group B., Conclusion: Use of mitomycin C causes more endothelial cell loss during trabeculectomy as compared to when done without it.

Introduction: Trabeculectomy is considered the standard for glaucoma surgery. Postoperative scarring is one the factors associated with surgery failure. Different antimetabolites have been used in order to reduce this risk, particularly 5-fluorouracil and mitomycin C. Although both are considered effective, it is not clear if they are different in terms of success of trabeculectomy and adverse effects., Methods: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified four systematic reviews including 17 studies overall, of which 12 were randomized trials. We concluded mitomycin C might be more effective in reducing intraocular pressure and increasing qualified success compared to 5-fluorouracil. However, its use might be associated to a higher risk of complications.

The aim of the study was to assess the effects of bevacizumab in augmenting trabeculectomy for glaucoma. We searched the databases of Cochrane Library, PubMed, Embase, CNKI, and VIP. All the databases were retrieved from the time databases established to September, 2015. The keywords we used were as follows: "bevacizumab," "anti-VEGF," "avastin," "trabeculectomy," "glaucoma," and so on. We used a method of the freedom word search and the MeSH search combined, which was recommended by Cochrane Systematic Review Manual 5.1.2. Randomized controlled trails (RCTs) of frequently used bevacizumab in trabeculectomy for glaucoma were included. Study selection, data extraction, quality assessment, and data analysis were performed according to the Cochrane standards. Eight randomized controlled trails involving 212 eyes in the experimental (bevacizumab or bevacizumab + mitomycin C) groups and 214 eyes in the control (mitomycin C or placebo) groups were selected. Compared with placebo, bevacizumab significantly increased the complete success rate [OR = 2.79, 95%CI, (1.47, 5.29), P = 0.002], what else, bevacizumab also significantly decreased the intraocular pressure (IOP) [MD = 3.07, 95% CI, (0.87, 5.27), P = 0.006] at the 6-month after trabeculectomy and the number of antiglaucoma medications [MD = 1.23, 95% CI, (0.66, 1.80), P < 0.0001]. Additionally, it also increased the risk of bleb leak [OR = 5.24, 95% CI, (1.30, 21.10), P = 0.02]. When compared with mitomycin C (MMC), bevacizumab significantly increased the rate of encysted blebs [OR = 4.62, 95% CI, (1.02, 20.91), P = 0.05]. However, there was no significantly difference between the bevacizumab + MMC groups and MMC groups whatever the items were. Bevacizumab was an effective way in trabeculectomy concerning the complete success rate, IOP, and anti-glaucoma medications reduction when compared with placebo; however, it increased the risk of bleb leakage. And it significantly increased the rate of encysted blebs compared with MMC.

Current techniques for the delivery of antimetabolites, such as mitomycin C, tend to be very variable among surgeons and risk uncontrolled contact with the conjunctivae, which may result in delayed wound healing, wound dehiscence, and wound leakage postoperatively. We describe a novel technique which appear to allow a more precise and reproducible delivery of antimetabolite to the target area with minimal contact with the conjunctival edge. The technique involves the injection of an antimetabolite-soaked wick into the subconjunctival space posterior to the scleral flap using an intraocular lens injector system.

Purpose: To assess the success of needling in failed filtration blebs and the potential benefit of using either 5-fluorouracil (5-FU) or mitomycin C (MMC)., Methods: In this retrospective, comparative observational case series, 107 eyes that underwent needle revision with either 5-FU or MMC between July 2003 and May 2008 at Wills Eye Institute were selected. Exclusion criteria included follow-up less than 1 month and a history of glaucoma drainage device. Intraocular pressure (IOP) and number of glaucoma medications were recorded preoperatively and postoperatively. Success was defined as >20% decrease in IOP if glaucoma medications were resumed or <10% decrease in IOP if medications were not resumed post needling or fewer medications than pre needling., Results: Sixty-five patients received 5-FU and 42 patients received MMC for needling. Mean IOP changed from 23.9 mmHg to 13.8 mmHg in the MMC group and from 23.3 mmHg to 13.02 mmHg in the 5-FU group (both p<0.001). Mean glaucoma medications changed from 1.7 to 0.7 in the MMC group and 2.0 to 0.8 in the 5-FU group (both p<0.001) at the end of follow-up. After a mean follow-up of 14.5 months, overall survival was 49.5%. Mean time to failure was 7.7 months. There was a moderately weak association between survival and the immediate postoperative IOP (r=0.262, p=0.01). In comparing MMC and 5-FU, there was no statistically significant difference in survival rate (p=0.267)., Conclusions: Bleb needling may be a safe and effective means of prolonging bleb survival. The only factor associated with success was the immediate postoperative IOP. There was no apparent difference between the use of 5-FU and MMC in this population. A prospective study may provide further confirmation of this finding.

Objective: To compare the long-term efficacy of intraoperative 5-fluorouracil (5-FU) and mitomycin C (MMC) in primary trabeculectomy., Design: Comparative case series and extension of a prospective, randomized controlled trial., Participants: One hundred fifteen eyes of 103 subjects undergoing primary trabeculectomy with either intraoperative 5-FU or MMC., Methods: This study is an extension of a 12-month, prospective, double-masked, randomized trial that previously was reported. Subjects were randomized to receive either intraoperative 5-FU (50 mg/ml for 5 minutes) or MMC (0.2 mg/ml for 2 minutes) during primary trabeculectomy. Follow-up data were collected from patient medical records after informed consent was obtained from the study patient. Attempts were made to contact subjects who had been lost to follow-up, and some consented to reexamination., Main Outcome Measures: The primary measure was Kaplan-Meier survival function, with failure defined as intraocular pressure (IOP) of more than 21 mmHg or less than 6 mmHg on 2 consecutive visits, less than 20% reduction from baseline IOP, loss of light perception vision, or additional glaucoma surgery to lower IOP (except bleb revision). Secondary measures included IOP, number of glaucoma medications, visual acuity, additional surgeries, and number and type of complications., Results: Mean follow up was 53.4+/-31.4 months (interquartile range, 34-82 months) in the 5-FU group and 45.3+/-28.0 months (interquartile range, 19-70 months) in the MMC group (P = 0.15, t test). Kaplan-Meier success was 0.83 at 3 years and 0.76 at 5 years in the 5-FU group and 0.79 at 3 years and 0.66 at 5 years in the MMC group (P = 0.18, log-rank test). Bleb leakage was the most common complication in each group and developed in approximately 4% of subjects in each group per year (P = 0.33, log-rank test)., Conclusions: There were no significant differences between topical 5-FU and topical MMC in reducing IOP of eyes undergoing primary trabeculectomy. Both antifibrosis agents may contribute to the development of bleb leakage., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To compare the long-term efficacy and safety of intraoperative 5-fluorouracil (5-FU) versus mitomycin-C (MMC) used adjunctively with primary trabeculectomy in a Black West African population., Design: Retrospective comparative study supplemented with cross-sectional follow-up data., Methods: Review of 68 eyes of 68 Black West African subjects that underwent primary trabeculectomy with the use of intraoperative 5-FU or MMC between January 1, 1988 and January 1, 2002 and had at least 3 years postoperative follow-up. Postoperative outcome measures included intraocular pressure (IOP) control, number of glaucoma medications, visual acuity, and complications., Results: Thirty-eight of sixty-eight eyes received 5-FU and 30 received MMC. Mean postoperative follow-up was 7.5 and 6.5 years in the 5-FU and MMC groups, respectively (P=0.17). A higher proportion of eyes in the MMC group achieved "qualified" (with or without medical therapy) success with varying IOP targets relative to the 5-FU group, but the differences were not statistically significant. "Complete" (without medical therapy) postoperative success was greater in the MMC group with a significantly higher proportion achieving an IOP <21 mm Hg (P=0.02). MMC use was also associated with a lower likelihood of receiving IOP-lowering medications postoperatively (P=0.01). Baseline demographic characteristics, preoperative and postoperative IOP, visual acuity, and complications did not differ significantly between the 2 groups., Conclusions: Intraoperative MMC use is associated with a lower likelihood of requiring postoperative medications and a greater likelihood of achieving IOP lowering without medications relative to the use of 5-FU in a Black West African population.

Purpose: To compare the intermediate-term efficacy of 5-fluorouracil (5-FU) and Mitomycin C (MMC) as adjunctive antimetabolites in neovascular glaucoma (NVG) filtration surgery., Methods: Forty consecutive eyes of 40 patients with NVG refractory to medical therapy were randomized to receive antimetabolite-augmented trabeculectomy. Eighteen eyes received postoperative 5-FU (5-FU group) and 22 eyes received intraoperative, low-dose (0.2 mg/ml) MMC for 2 mins (MMC group). The main outcome measure was intraocular pressure (IOP). Surgical success was defined as IOP < 21 mmHg with topical treatment (qualified success) or without topical treatment (complete success). Surgical failure was defined as IOP > or = 21 mmHg, despite postoperative topical treatment, and by postoperative blindness., Results: The mean follow-up period was 35.8 +/- 22.6 months in the 5-FU group and 18.6 +/- 17.2 months in the MMC group. This difference was not significant. Mean IOP decreased from 40.4 +/- 10.3 mmHg to 14.7 +/- 3.4 mmHg (p < 0.0001) in the 5-FU group and from 42 +/- 11.3 mmHg to 22.9 +/- 13.3 mmHg (p = 0.0006) in the MMC group; however, the difference between the 5-FU and MMC groups was not significant at any point. The success rate in the 5-FU group was 55.5% (44.4% complete, 11.1% qualified), compared with 54.5% (9.1% complete, 45.4% qualified) in the MMC group. This difference was not significant., Conclusions: The percentage of patients who achieved postoperative IOP < 21 mmHg was similar in both groups, although a larger proportion of patients treated with MMC-augmented trabeculectomy required topical treatment in comparison with the 5-FU group.

Background: To describe the results of a novel postoperative management approach for patients undergoing combined cataract and glaucoma surgery supplemented with early needle revision and antimetabolites., Methods: Consecutive retrospective chart review identified 66 patients who had undergone combined cataract and glaucoma surgery with early needling and antimetabolite injections between January 2002 and May 2003; 8 patients were excluded from analysis because of missing data or inadequate follow-up time. Single-site phacotrabeculectomy was performed followed by subconjunctival antimetabolite injections of 5-fluorouracil (5-FU). Needling was performed as an office procedure if early evidence of subconjunctival scarring was observed 2-6 weeks after surgery. Additional subconjunctival 5-FU injections were administered after needling, and repeat needling was performed with 5-FU or mitomycin-C if subconjunctival scarring recurred. A complete success was defined as a reduction in intraocular pressure (IOP) to <18 mm Hg without the use of antiglaucoma medications or further surgical procedures to control IOP. The outcome was considered a qualified success when antiglaucoma medications were required to achieve the same result., Results: The mean preoperative IOP was 21.9 (SD 6.3) mm Hg, and the mean postoperative IOP at 6 months was 13.0 (SD 6.7) mm Hg. The mean number of medications was reduced from 2.9 (SD 1.3) preoperatively to 0.5 (SD 0.9) postoperatively at 6 months. Needling was performed because of early evidence of subconjunctival scarring in 34 patients. The 6-month outcomes of 37 patients (64%) were a complete success and of 47 patients (81%) were a complete or qualified success. A longer follow-up of 10-23 months was attained in 25 of the 58 patients. At latest visit, the mean postoperative IOP of this group was 13.0 (SD 5.5) mm Hg, the mean number of postoperative medications was 0.7 (SD 1), and 21 of the 25 (84%) had achieved a complete or qualified success. The most common complication for all 58 patients was an early, self-limited postoperative wound leak that was unrelated to the needling intervention and was observed in 26 patients (45%)., Interpretation: Phacotrabeculectomy supplemented with early needle revision and antimetabolites may improve outcomes of combined cataract and glaucoma surgery.

Background: Regeneration/proliferation of lens material within the capsular bag still is the most frequent complication after cataract surgery. We aimed to evaluate the effects of hydrodissection with low doses of antimitotics on the overall regeneration/proliferation of lens material in rabbit eyes, using a model allowing the lens material to be confined to the equatorial region of the capsular bag, facilitating its quantification., Methods: Twelve albino rabbits underwent bilateral phacoemulsification. Their eyes were randomized to receive 0.4 cc of balanced salt solution, 5-fluorouracil (12.5 mg/mL) or mitomycin C (0.1 mg/mL) during hydrodissection. They were left aphakic, so the capsulorhexis would fuse with the posterior capsule postoperatively. After 4 weeks, killing/enucleation was performed. Regeneration/proliferation of lens material within the equatorial capsular bag (Soemmering's ring) was graded from the Miyake-Apple view (0-4). Its area was also calculated (microm(2)) from direct measurements performed on histological sections., Results: The capsulorhexis margin fused with the peripheral posterior capsule, so the central posterior capsule remained clear. There was no significant difference among the groups (Kruskal-Wallis test) regarding Soemmering's ring gross grading (P = 0.511), number of lens epithelial cell layers lining the inner surface of the capsular bag (P = 0.310) and Soemmering's ring microscopic cross-sectional area (P = 0.638)., Conclusions: The effect of different solutions on after-cataract should be assessed in terms of overall regeneration/proliferation of lens material within the capsular bag, in addition to posterior capsule opacification. When administered in low doses during hydrodissection, 5-fluorouracil and mitomycin C did not show a significant inhibitory effect on after-cataract formation in rabbit eyes.

Purpose: To study the long-term effectiveness and factors involved in successful needling of failed filtration blebs with mitomycin C (MMC)., Materials and Methods: We conducted a prospective, nonrandomized comparative trial that included 34 consecutive patients (34 eyes) who underwent mitomycin C needling of a failed filtering bleb after trabeculectomy followed by a 0.01 mL injection of mitomycin C (0.2 mg/ml). The success of the needling revision was defined as absolute if the intraocular pressure (IOP) was < 21 mm Hg without antiglaucoma medications and qualified if the IOP was < 21 mm Hg with antiglaucoma medications. Preoperative and perioperative factors were evaluated for an association with postoperative success using Kaplan-Meier survival analysis., Results: The mean follow-up was 14.2 +/- 9.8 months. The mean preoperative IOP was 25.5 +/- 4.4 mm Hg, which decreased to 11.1, 13.4, 15.8, 16.7, 14.9, 14.1, 13.9, and 13 on postoperative day 1, postoperative week 1, and after 1, 3, 6, 9, 12, and 24 months, respectively (P = 0.001 for each comparison). At the final visit, success was absolute in 15 eyes (44.1%) and qualified in 14 eyes (41.2%). The success rates were 90% and 75% at 1 and 2 years, respectively. The success of the needling procedure was highly correlated with glaucoma filtration surgery performed less than 4 months previously (Kaplan-Meier analysis, log-rank test P = 0.006)., Conclusions: Mitomycin C needling revision appears to have a high long-term success rate. Surgery performed less than 4 months previously contributes to the success of the initial mitomycin C needling procedure.

Purpose: Antimetabolites, especially mitomycin C (MMC), increase the incidence of late bleb-related endophthalmitis in trabeculectomy. This is related to a higher incidence of avascular, thin, cystic, translucent blebs, which may be caused by a toxic effect on conjunctival tissue. An MMC dose-response study was carried out focusing on bleb morphology and function., Patients and Methods: In a retrospective, comparative case series study, 2 successive groups of patients with complicated glaucoma were compared 2 years after a special, minimally invasive, filtering procedure (intrastromal holmium laser keratostomy). Preoperative local subconjunctival injections of a fixed MMC dose (4 microg) were used in group A, and lower MMC doses, calculated individually (1 or 2 microg), were used in group B. Bleb vascularity and morphology were evaluated by masked grading of photomicrographs. Bleb function was evaluated by intraocular pressure (IOP)., Results: Total bleb avascularity occurred in 63% of the blebs in group A and 0% in group B (P < 0.01). In eyes with IOP < or = 20 mmHg without medical treatment, the mean IOP was significantly lower in group 1 (8 vs 15 mm Hg, P < 0.002). A translucent cystic bleb without conjunctival stroma was observed in only 1 eye in group A. An optimal spongy stromal bleb was observed in all other eyes (96%) despite the different MMC doses. The numbers of complications in the 2 groups were nearly equal., Conclusions: Bleb avascularity after 4 microg MMC could be avoided by the use of 1 or 2 microg MMC on the basis of preoperative prognosticators for failure, but at the expense of some of the IOP-lowering effect. This indicates that the therapeutic index (clinical safety margin) of MMC seems to be narrow. An MMC dose-response relation was not observed for the thin, cystic, and translucent bleb. The low incidence of this bleb (4%) indicates that the operative technique, apart from the vascularity, may be the most essential determinant of bleb morphology.

Purpose: To probe the results of trabeculectomy with human amniotic membrane (HAM) or mitomycin(MMC) in the treatment of glaucoma., Methods: In a randomized control clinical trial, 48 eyes of 28 glaucoma patients were divided into two groups, each group has 24 eyes, and each group was divided into two sub-groups according to the age. The former was underwent trabeculectomy with HAM transplanted, the later was administrated intra operatively with MMC, 0.2-0.4mg/ml, for 2-4 minutes, the follow-up was 6 months., Results: The operation success rate of both groups was higher than the standard trabeculectomy, and the difference between the two groups was not significant. Complications induced by HAM were mainly shallow anterior chamber, whereas by MMC were thin wall bleb, bleb leaking, persistent hypotony and hypotonous maculopathy., Conclusion: Application properly HAM or MMC can improved the operation success rate, maintain the functional bleb long time and decreased the complications.

Objective: The effects of topical application of Mitomycin-C (MMC) and 5-fluorouracil (5-FU) for maintaining myringotomy patency were investigated in this experimental study., Study Design: We performed simple myringotomy with a knife on 140 tympanic membranes of 70 rats. Rats were divided in two study groups and a control group. Each study group had 60 tympanic membranes, and the control group had 20. We applied Mitomycin-C (0.4 mg/ml) in Group A, 5-fluorouracil (50 mg/ml) in Group B topically, and sterile saline in the control group for 10 minutes. Examination was made with otoendoscope on days 1, 3, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, and 70, and patency rates were recorded., Results: MMC and 5-FU Groups remained open for a mean of 46.17 days and 14.62 days, respectively. The control ears healed within 10.4 days. Fibrosis of the MMC-treated group was the same as that of 5-FU-treated groups. Fibrosis of both study groups was significantly lower than that of the control group., Conclusions: MMC is more effective than 5-FU, which is more effective than the simple myringotomy procedure in extending the patency of myringotomies in rat tympanic membranes (p < 0.05). Both medications are useful as an adjunct in preventing myringotomy closure.

Purpose: Owing to its technical refinements, "modern" trabeculectomy aims to reduce the incidence and severity of early postoperative complications while increasing postop IOP success. The purpose of our study was to evaluate namely the safety of "modern" trabeculectomy, the quality of the filtration blebs, the influence on the quality of life and secondarily IOP reduction according to the surgical procedure whether augmented with peroperative application of antimetabolites or not., Material-Methods: Retrospective study including our 45 first consecutive procedures in 38 patients (mean age: 61.1 years) with medically uncontrolled various glaucomas. All procedures were performed according to a modified P. Khaw's protocol. Antimetabolites were applied peroperatively in 28/45 eyes (62.2%) with a history of previous filtering surgery (12/28 eyes) and/or advanced glaucomatous damage (22/28 eyes). Antimetabolites were not used in the 17/45 other eyes with lower surgical risk factors and higher target IOP, surgical procedure was not augmented with antimetabolites. Postoperative management included laser suture lysis, withdrawal of adjustable sutures and 5-FU injections when needed. Complete ocular examination was carried out preoperatively and postoperatively at day 1, 7, at 1, 2 and 3 months and every 3 months thereafter. All patients were questioned for symptoms associated with filtration bleb dysesthesia at the last visit., Results: The mean follow-up was 7.9 +/- 3.3 in the group without antimetbolites and 5.3 +/- 2.2 months in the group with antimetabolites (p < 0.05). Final mean IOP (+/-SD) was significantly lower in the group augmented with antimetabolites (11.2 +/- 4.5 mmHg) compared with the group without antimetabolites (14.9 +/- 3.7 mm Hg) (p < 0.05). Complete and qualified success were respectively 64.3% and 89.3% in the group with antimetabolites and 70.6% and 82.4% in the subgroup without antimetabolites (p > 0.05). 1st month postoperative complications were transient and minor. They occurred in 59% in the group without antimetabolites and in 68% in the subgroup augmented with antimetabolites. Complications had comparable frequency of distribution between the 2 subgroups (p > 0.05). 84% of the filtration blebs (30/45) were diffuse and mildly vascularized. Avascular blebs were noticed in 7 eyes (15.5%) and were not related with the intraoperative application of mitomycin C (p > 0.05). Subjective comfort was good to excellent in 42/45 eyes (93.3%). Mean final visual acuity was not altered compared with preop level (p > 0.05)., Conclusions: Our short term results suggest that the safety of "modern" trabeculectomy augmented with antimetabolites is comparable to those without intraoperative antimetabolites. Filtration blebs were very well tolerated in most patients. The peroperative use of antimetabolites precludes to appreciate if the success rates are due to the use of antimetabolites and/or the technique per se.

Objective: To evaluate the effect of temporal corneal phacoemulsification on intraocular pressure (IOP) in eyes after primary trabeculectomy with intraoperative fluorouracil (5-FU) or mitomycin C (MMC)., Design: Retrospective case-control study., Patients: Twenty-nine patients who were participants in a prospective randomized double-masked trial comparing the efficacies of intraoperative 5-FU and MMC and who underwent temporal corneal phacoemulsification after the primary trabeculectomy were matched to 29 patients enrolled in the same study who did not undergo cataract surgery. The 2 groups were matched for length of follow-up after the trabeculectomy and the antimetabolite used at the time of trabeculectomy., Methods: Comparisons of IOP, visual acuity (VA), and the number of glaucoma medications were made between the 2 groups and within the groups at various follow-up intervals to detect any statistically significant differences., Main Outcome Measures: Intraocular pressure before phacoemulsification and at various times postoperatively were compared with IOP in the control group at the matched follow-up times., Results: The mean of all IOP measurements beyond 3 months after phacoemulsification for each subject was significantly higher than the prephacoemulsification IOP (11.8+/-4.2 vs. 8.7+/-4.5 mmHg; P = 0.00003, paired t test). In contrast, the mean IOP remained stable in the control group during the equivalent time period (9.6+/-3.5 vs. 9.1+/-3.1 mmHg; P = 0.42, paired t test). Postphacoemulsification IOP was significantly higher than the corresponding IOP in the time-matched control group (P<0.003, analysis of covariance). Mean VA improved significantly after the phacoemulsification (P = 0.0002) but remained stable in the control group., Conclusion: Temporal corneal phacoemulsification can affect long-term IOP control after trabeculectomy with 5-FU or MMC.

We evaluated the change of corneal endothelium after trabeculectomy with mitomycin-C soaking (0.2 mg/ml, 2.4 +/- 1.2 minutes) and the effect of viscoelastic material in reducing this change. In randomly selected cases, 0.05 ml of sodium hyaluronate(Healon) was injected into anterior chamber (Healon group, n = 20), and same amount of balanced salt solution was injected in the other eyes (Control, n = 18) at the beginning of surgery. There were no differences in clinical variables and specular microscopy result between 2 groups before surgery. After surgery, the change of endothelial cells were significantly reduced in Healon group (cell density; -2.5 +/- 1.6%, variability of cell area; 5.8 +/- 2.5%, and percentage of hexagonal cell; -2.2 +/- 0.7%) compared to control group (-7.7 +/- 6.0%, 8.9 +/- 4.4%, and -4.8 +/- 3.5% respectively, p < 0.01). In trabeculectomy with mitomycin-C, the damage to the corneal endothelium was reduced significantly by injecting the viscoelastic material without significant complication.

Purpose: To compare the safety and efficacy of intraoperative 5-fluorouracil (5-FU) or Intraoperative mitomycin C (MMC) in eyes undergoing primary trabeculectomy., Design: Prospective double-masked randomized clinical trial., Methods: One hundred fifteen eyes of 103 patients with uncontrolled intraocular pressure (IOP) despite maximally tolerated medical therapy or laser were prospectively randomized in a double-masked fashion to one of two treatment groups in a single institution setting. Subject's eyes underwent primary trabeculectomy with either topical 5-FU (50 mg/ml for 5 minutes) or topical MMC (0.2 mg/ml for 2 minutes). Primary outcome measures included the number of eyes achieving target pressures of 21, 18, 15, and 12 mm Hg at 6 and 12 months postoperatively. Secondary outcome measures included IOP, best-corrected visual acuity, complications, and interventions., Results: Of the 115 eyes, 57 received 5-FU while 58 received MMC. A target IOP of 21 mm Hg at 6 months was achieved in 53 of 56 (95%) eyes in the 5-FU group and 54 of 57 (95%) eyes in the MMC group (P = 1.00). At 12 months, 45 of 48 (94%) eyes in the 5-FU group met a target IOP of 21 mm Hg while 48 of 54 (89%) eyes in the MMC group did (P =.49). The most common complications in each group were persistent choroidal effusions and bleb leak., Conclusion: Our study suggests that intraoperative topical 5-FU is at least as effective as intraoperative topical MMC in reducing IOP of eyes undergoing primary trabeculectomy.

Purpose: To observe the long term success of antimetabolites used in glaucoma filtering surgery in eyes with high risc of failure., Material and Method: Two groups of patients undergone trabeculectomy with the use of antimetabolites 5-Fluorouracil (5-FU) and Mitomycin C (MMC) are included in this retrospective study. 5-FU was administered postoperatively 1-10 times in the dose of 5 mg/ml in subconjunctival injection on 32 eyes. Follow up time ranged from 8 months to 9 years. Mitomycin C was administered intraoperatively in the dose of 0.2 mg/ml, on subconjunctival sponge with application time from 3 to 5 minutes on 15 eyes. Follow up time ranged from 7 month to 4.5 years., Results: Intraocular pressure (IOP) before operation with the use of 5-FU was in average 28.8 mmHg (22-50 mmHg) at the end of therapy with 5-FU was 17.6 mmHg (10-30 mmHg) and in the last examination was on average 19.5 mmHg (14-28 mmHg). IOP before operation with the use of MMC was in average 30.3 mmHg (22-40 mmHg), the seventh day after administration of MMC 12.7 mmHg (6-20 mmHg) and in the last examination was in average 18 mmHg (9-28 mmHg). During the long term observation of IOP values in the 5-FU group there was 79.2% success and in the MMC group there was 83.3% success (IOP up to 20 mmHg with or without therapy). Decrease of IOP was statistically significant., Conclusion: Antimetabolites improve the success of filtering surgery in high risc glaucomas. The long term follow up shows that failure of filtration in these types of glaucomas is still a serious clinical problem.

For evaluation of the effect of topical mitomycin-C on vocal fold healing and return of function after surgical excision of mucosa, 6 dogs underwent suspension microlaryngoscopy with bilateral microflap excision of vocal fold mucosa. Topical mitomycin-C, a chemotherapeutic agent and a fibroblast inhibitor, was applied randomly to one side, with the contralateral side serving as the control. Laryngeal videostroboscopy (LVS) was performed on each animal before the operation, at 2 weeks, and before sacrifice at 4 weeks. Both functional analysis with LVS and histologic analysis were performed in a blinded fashion to determine the effect of mitomycin-C on healing. Histologic analysis was augmented with computer morphometrics. The LVS revealed diminished mucosal wave vibration in the vocal folds treated with mitomycin-C, as well as a more atrophic appearance to the vibratory surface. The vocal folds treated with mitomycin-C showed fewer fibroblasts and less collagen within the superficial layer of the lamina propria than the control vocal folds (p < .05, Student's t-test, paired analysis). Inflammatory infiltrate was not significantly different between the two sides. Consistent with the known suppression of fibroblast proliferation by mitomycin-C, the treated vocal folds showed less connective tissue response to the surgical injury. In contrast to the reported positive effects of mitomycin-C on tracheal and glottic stenosis, the observed decrease in the healing response in the present study had negative consequences on the vocal fold vibratory pattern.

The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis.

A prospective, randomized study was performed to examine the effects of subconjunctival retention of 5-fluorouracil (5-FU) microparticles or 5-FU microparticles combined with mitomycin-C (MMC) on the success of trabeculectomy procedure in 32 New Zealand white rabbits. Drug-loaded microparticles were prepared using a biodegradable polymer, 50:50 ploy (D,L-lactide-co-glycolide) (50:50, PLG, MW 9000), by an oil-in-oil emulsification/solvent extraction technique. Each rabbit underwent trabeculectomy on both eyes, then one of the 5-FU and/or MMC preparations was placed at the site of the filtering surgery intraoperatively in the right eye, while the left eye was used as a control. The rabbits were randomly allocated to one of four treatment groups: group 1 rabbits received 5% 5-FU microparticles 10 mg; group 2 rabbits received 10% 5-FU microparticles 10 mg; group 3 rabbits received 10% 5-FU microparticles 5 mg and MMC 0.01 mg (5-FU/MMC); and group 4 rabbits received MMC 0.02 mg. Postoperatively, intraocularpressure (IOP), bleb survival, complications and IOP dynamics were compared during a follow-up period of 42 days. The results showed that IOPs were significantly lower in the eyes that received groups 3 and 4 treatments, while the eyes that received low concentrations of 5-FU microparticles resulted in no difference in IOPs as compared with those of controls. At 42 days, blebs were present in 100% of the eyes treated with 5-FU/MMC and MMC, but 0% of the eyes treated with 5-FU microparticles. The blebs in the eyes treated with MMC 0.02 mg were thinner, and significant complications (endophthalmitis, transient corneal opacification and neovascularization) occurred. In addition, the IOP dynamics study revealed that the eyes treated with 5-FU/MMC and MMC resulted in less IOP spikings after intravenous infusion of 0.9% NaCl solution. Our study suggested that the use of 5-FU microparticles in promoting the success of trabeculectomy in rabbits is dose-dependent, and its effect is less potent than a single intraoperative application of MMC.

Background and Objective: This study was undertaken to compare the efficacy and safety of low-dose intraoperative application of mitomycin-C (MMC) with that of 5-fluorouracil (5-FU) in primary trabeculectomy., Patients and Methods: A non-randomized prospective study was performed between August 1994 and November 1995. Thirty-two eyes of 16 consecutive patients who underwent trabeculectomy for uncontrolled glaucoma of various causes form the study group. The mean age was 46.8 +/- 9.9 years. The first eye received MMC (0.2, 0.4 mg/ml), fellow eye received 5-FU (50 mg/ml), for 1 minute intraoperatively. Bleb characteristics and intraocular pressure (IOP) control were analyzed. Success of surgery based on IOP control was measured by 3 different criteria: IOP less than 21 mm Hg; IOP less than 21 mm Hg with more than 30% reduction; and IOP less than 16 mm Hg with more than 30% reduction., Results: Mean preoperative IOP was 31.4 +/-12.7 mm Hg in MMC group and 27.8+/- 8.8 mm Hg in 5-FU group. Mean follow-up in MMC group was 16.12 +/- 8.17 months; in 5-FU group 13.37 +/- 8.19 months. At last follow-up all 5-FU blebs were nonischemic, while 4 eyes in the MMC group showed nonischemic blebs, and 12 eyes had ischemic blebs. There was no statistically significant difference between MMC group and 5-FU group success rates with all 3 criteria. Success rates were: IOP less than 21 mm Hg; 100% in both groups; IOP less than 21 mm Hg with more than 30% reduction; MMC group 93.8%, 5-FU group 75%; less than 16 mm Hg with more than 30% reduction; MMC group 87.5%, 5-FU group 68.8%., Conclusions: Low-dose intraoperative MMC and 5-FU can provide control of IOP in primary trabeculectomy, 5-FU group showed more non-ischemic blebs.

Purpose: To evaluate the efficacy and safety of augmented trabeculectomy with 5-fluorouracil (5-FU) and mitomycin C (MMC) compared to 5-FU only for the treatment of pediatric glaucoma., Patients and Methods: In a prospective randomized clinical trial, 8 children (12 eyes) with pediatric glaucoma, either congenital or secondary to: lens aspiration, Sturge-Weber syndrome, or steroids underwent augmented trabeculectomy. Six patients (8 eyes) underwent augmented trabeculectomy with 5-FU plus MMC and 2 patients (4 eyes) underwent augmented trabeculectomy with 5-FU only., Main Outcome Measures: Between-group comparison of postoperative parameters: change in intraocular pressure (IOP), dependence on antiglaucoma medication, number of 5-FU injections, cup-disc ratio, corneal diameter, drug-induced complications., Results: In the 5-FU/MMC group, 7/8 eyes showed good control of postoperative IOP (9-16 mm Hg), which was independent of antiglaucoma therapy; only 2 injections of 5-FU were needed. By contrast, in the 5-FU group, no control of the postoperative IOP (21-23 mm Hg) was achieved in 4/4 eyes, and these patients remained dependent on antiglaucoma medication; up to 6 injections of 5-FU were used. There was no deterioration in the cup-disc ratio or the corneal diameter in either group. Results were maintained on follow-up (23-27 months). No significant drug-induced complications were noted., Conclusion: Augmented trabeculectomy with adjunctive 5-FU/MMC may be an option for the control of pediatric glaucoma in patients with a poor surgical prognosis.

Purpose: This study was conducted to review outcomes in eyes following primary trabeculectomy supplemented intraoperatively with 5-fluorouracil (5-FU) or lower dose mitomycin-C (MMC)., Patients and Methods: We retrospectively reviewed the medical records of 73 eyes of 63 patients with progressive, far advanced open angle glaucoma who had undergone initial trabeculectomy with intraoperative application of 5-FU, 50 mg/mL for 5 min (N = 37), or MMC, 200 micrograms/mL for 3-5 min (N = 36), and with at least 12 months follow-up., Results: Mean preoperative intraocular pressures (IOPs) in the MMC and 5-FU groups were 24.3 +/- 7.6 and 24.6 +/- 9.3 mm Hg, respectively. Postoperatively, IOPs were similar at 6-month interval follow-up examinations in the MMC and 5-FU groups. At an average follow-up of 20.9 months, mean final visit postoperative IOPs were 10.2 +/- 3.6 (p < 0.001) and 9.7 +/- 3.4 mm Hg (p < 0.001) in the MMC and 5-FU groups, respectively, requiring an average of 0.25 and 0.22 antiglaucoma medications per eye, respectively. Interval follow-up complications were similar between groups and included four bleb leaks in the MMC group, and three bleb leaks in the 5-FU group. Visual acuity remained stable in 71 of 73 eyes., Conclusions: Both antifibrosis agents provide good intermediate term IOP control and may be appropriate for use in those eyes requiring final "target" IOPs in the low teens or single digits.

Purpose: The purpose of this study was to estimate the quantity of mitomycin-C contained in sponges prepared by different surgeons as compared to that in applicators of the type used in Schirmer's test graduation (5 x 5 mm)., Materials and Methods: Four surgeons each cut and prepared 10 sponges for intraoperative use according to their usual method. The same procedure was performed with 10 Schirmer's test graduations. Each sponge and each graduation was immersed in a solution of mitomycin-C 0.2 mg/ml, and the quantity of antibiotic (microgram) in each was calculated as the difference between wet and dry weight., Results: The mean quantity (+/-SEM) of mitomycin-C contained in cut sponges was 9.6 +/- 4.4 micrograms (range 1.9-17.3), and differences between surgeons were statistically significant (p < 0.0001). The mean quantity of antibiotic in Schirmer's test graduation was 1.7 +/- 0.3 micrograms (range 1.1-2.5), and the differences between surgeons were not statistically significant (p = 0.79)., Conclusion: The quantities of mitomycin-C contained in sponges prepared for glaucoma surgery differed for a given surgeon and between surgeons. Thus, variations in the doses applied to the sclera could account for certain complications due to mitomycin-C. The use of a Schirmer's test graduation improves predictability for the quantity of mitomycin-C applied to the sclera.

To improve the function of filtering blebs after trabeculectomy, we divided randomly 44 patients (60 eyes) with moderate or late glaucoma into mitomycin C and control groups (30 eyes per group). Two small surgical sponges were soaked with 0.2 mg.ml-1 mitomycin C solution. One sponge was put on the top of the superficial scleral flap, the other was placed underneath the scleral flap and contacted with the bed of the scleral flap. After 5 minutes the wound was then irrigated with normal saline. All patients were followed up from 1 to 12 months (7.9 +/- 4.0 months). We found that: (1) functional filtering blebs were 92.9% in the mitomycin C group and 55.2% in the control group (P < 0.01), (2) the decreasing percentage of intraocular pressure (IOP) in the mitomycin C group was much more than that in the control group (P < 0.05), (3) the successful rates of the operation in MMC group were higher than that of the control group, and the visual field was effectively maintained in MMC group.

This prospective, randomized clinical trial assessed the effects of mitomycin C and cyclosporin A used as antimetabolites in trabeculectomy on the post-operative IOP and success rate. Eighty-six consecutive patients were randomly allocated to three treatment groups. There were 30 patients in the mitomycin C group, 28 in the cyclosporin A group and 28 in the control group. The follow-up periods were different for the three groups and ranged from 6 to 30 months. The treatment groups consisted of primary open-angle glaucoma, closed-angle glaucoma, various secondary glaucomas and prior failed trabeculectomy. There were no significant differences pre-operatively with respect to IOP and number of medications used (p > 0.05). Postoperative IOP was considered to be successfully reduced when it was reduced by more than 25% from baseline or when it was lower than 20 mmHg. According to these criteria, IOP was under control in 90% of the mitomycin C treated eyes, 85.7% of cyclosporin A treated eyes and 71.4% of the control eyes. Postoperatively there was a significant decrease in IOP (p < 0.01) and in the number of medications need to control IOP (p < 0.01) in the mitomycin C and cyclosporin A groups. Post-operative IOP and number of medications in the mitomycin C and cyclosporin A group were similar. Complications encountered in the three groups were similar. There were no serious complications like hypotonus maculopathy. Our study highlights the utility of mitomycin C as an adjunct in glaucoma filtering surgery and indicated that cyclosporin A may also be used as an antimetabolite.

Antimetabolites such as 5-fluorouracil and mitomycin C are known to delay wound healing. Epidermal growth factor (EGF) has been shown to accelerate corneal epithelial wound healing. This study was designed to investigate the effects of EGF on corneal epithelial healing that has been modified by antimetabolite treatment. New Zealand White rabbits were pretreated with either saline (controls) or 5-fluorouracil (5FU) injected subconjunctivally, or mitomycin C (MMC) applied topically. Circular anterior stromal wounds were created, followed by a 6-hour perfusion of normal saline or 50 micrograms/ml of EGF. Subconjunctival saline or 5FU, or topical MMC treatments were continued after wounding for a total of 6 days. Corneas were photographed and quantitative morphometry of the wound site was performed. Compared with saline controls, MMC significantly delayed wound healing (P < 0.05) whereas 5FU did not (P > 0.05). Compared with 5FU, MMC significantly delayed wound healing with either normal saline or EGF perfusion (P < 0.05). In the presence of either 5FU or MMC, EGF perfusion had no significant effect on the corneal wound-healing rate (P > 0.05). Corneal wound healing is not affected by subconjunctivally injected 5FU while it is delayed by topically applied MMC. EGF treatment does not overcome the inhibitory effects of MMC. EGF therapy may not be useful in the treatment of complications related to antimetabolite therapy.