Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits

purpose?To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. methods?Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (10 animals), one eye of each animal received topical application of MMC (0.2?mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50?mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. results?MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. conclusions?MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.     

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.     

Histologic effect of mitomycin C on strabismus surgery in the rabbit

PURPOSE: To evaluate the efficiency of mitomycin C (MMC) in limiting the postoperative inflammatory response and scarring after strabismus surgery. METHODS: A prospective, two-stage, masked, controlled trial was conducted. In the first stage, the inflammatory response at the extraocular muscle reattachment site was increased after inferior rectus recession in eight rabbits. In the second stage, MMC (0.4 mg/ml) was applied during surgery to the eyes of 22 rabbits with inferior rectus recession. As a control, contralateral eyes were treated with saline solution. Seven weeks later, exenteration was performed, and the sites of muscle reattachment were processed for histologic examinations. The sums of the areas of the granulomas in the extraocular muscle reattachment sites of control and treated eyes were compared. RESULTS: There was no significant inhibitory effect of MMC on the inflammatory response of treated eyes compared with that of control eyes. CONCLUSIONS: The intraoperative use of MMC (0.4 mg/ml) was not effective in controlling the postoperative inflammatory response in rabbit eyes after extraocular muscle surgery. These data do not support the hypothesis that MMC reduces postoperative adhesions after strabismus surgery.     

丝裂霉素C在斜视手术中应用的实验研究

目的 通过在斜视手术中使用丝裂霉素C（MMC），观察MMC对减少术后肌肉与周围粘连的效果。方法 手术后徙家兔2眼上下直肌并缝合于浅层巩膜上，右眼在术中使用MMC而左眼不用，术后6周观察肌肉与周围组织粘连和附着情况。结果 实验眼肌肉与周围的粘连情况较对照组明显减少（P＜0．01），肌肉附着点张力也较对照眼减少（P＜0．05）。结论 在实验性斜视手术中使用MMC可明显减少术后肌肉与周围粘连，而不影响肌肉与巩膜的愈合。     

Wound modulation after trabeculectomy by different formulations of antimetabolites in rabbits.

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.     

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.     

Combined effect of Interceed and 5-fluorouracil on delayed adjustable strabismus surgery

AIMS/BACKGROUND: To discover a more reliable method of performing delayed suture adjustment as a basis to investigate whether delayed adjustment actually provides more stable results. In order to prevent the formation of postoperative adhesions and delay the time of adjustment, an animal study was performed to determine the combined effect of physical barriers, Viscoat and Interceed, and a pharmacological agent, 5-fluorouracil (5-FU). METHODS: 38 rabbit eyes were divided into three groups. After recession of the superior rectus muscle (SRM), 5-FU was applied beneath and over the SRM in group 5-FU. Group I-f had Interceed and 5-FU and group I-fv, Interceed, 5-FU, and Viscoat. Delayed adjustment was performed once on each SRM at 1, 2, and 3 weeks postoperatively. The possible length and the necessary force to adjust as well as the degree of adhesions were recorded. RESULTS: 5-FU delayed the adjustment for up to 1 week after surgery in three out of four eyes. Combined use of Interceed and 5-FU could delay the adjustment for up to 1 week after surgery in three out of five eyes. Addition of Viscoat could delay the adjustment for up to 1 week after surgery in four out of five eyes. Adjustment was possible on only one of four eyes thereafter. CONCLUSIONS: Combined use of Interceed, 5-FU, and Viscoat could delay the adjustment in rabbits until 1 week postoperatively.     

Holmium YAG laser sclerostomy ab externo for refractory glaucoma

Ab externo thermal sclerostomy was performed with the holmium YAG (thulium, holmium, chromium-doped YAG crystal) laser in 21 eyes of 20 patients with refractory glaucoma. We used either the 5-fluorouracil (5-FU) or mitomycin C (MMC) antimetabolites in all cases. The rate of intraocular pressure (IOP) control defined as IOP < 21 mmHg regardless of whether antiglaucoma medication was applied postoperatively) was estimated by the life-table methods of Kaplan-Meier. The postoperative IOP control rate was 47.1% in the MMC-treated group at 57 months, and 14.3% in the 5-FU-treated group at 52 months. There were statistically significant differences in success rates between the MMC- and 5-FU-treated groups. We observed no clinically significant complications except excess filtration associated with a shallow anterior chamber in one case. This procedure is thought to have several advantages over more conventional filtration surgery; the operation time is shorter, and there is no need for intraocular manipulation, which means conjunctival trauma is minimal. However, the IOP control rate was substantially lower than that achieved via conventional trabeculectomy. Our results suggest that the selection of patients and the use of MMC is an important factor in maintaining successful filtration.     

Comparison of the effectiveness of mitomycin-C and Viscoat on delayed adjustable strabismus surgery in rabbits

PURPOSE: To determine a way to prevent the formation of adhesions and delay the time of suture adjustment in the course of adjustable strabismus surgery, an animal study was performed to assess and compare the effects of mitomycin C (Mit-C) and viscoelastic material Viscoat (sodium hyaluronate 3% and chondroitin sulphate 4%, Alcon, Fort Worth, TX). METHODS: Right eyes of 47 rabbits were divided into three groups. After recession of the superior rectus muscle (SRM), Mit-C was administered beneath and over the SRM in Group M (16 eyes), Viscoat was administered beneath and over SRM in Group V (16 eyes), and ringer lactate was administered in Group C (15 eyes). SRM then recessed 5 mm with adjustable strabismus surgery technique. Animals in each group were subdivided into 1 and 2, where 1 = adjustment 1 week postoperatively and 2 = adjustment 3 weeks postoperatively. Delayed adjustment was performed in M1 group (6 eyes), V1 group (6 eyes), and C1 group (7 eyes) after 1 week; in M2 group (6 eyes), V2 group (6 eyes), and C2 group (6 eyes) after 3 weeks. Histopathologic examinations were performed for the remaining 10 eyes without suture adjustment at the end of first and third weeks after adjustable strabismus surgery. The possible length and the necessary force to adjust and the degree of adhesions were recorded. RESULTS: When length and strength of the adjustment, adhesions between muscle and sclera, and adhesions between muscle and conjunctiva were taken into consideration, there was no statistically significant difference among M, V, and C groups at postoperative weeks 1 and 3. The force needed for adjustment in M1 group was statistically lower than M2 group. CONCLUSIONS. The intraoperative use of Mit-C (0.4 mg/mL) may decrease adhesion formation in the early postoperative period, especially in the first week. The intraoperative use of Viscoat was not effective in reducing postoperative adhesions and delaying adjustment.     

The effect of mitomycin-C on the healing process in rabbit extraocular muscle surgery

BACKGROUND AND OBJECTIVE: One of the most serious complications following extraocular muscle surgery is formation of postoperative adhesions that may result in restrictive ocular motility dysfunction. The effect of mitomycin-C (MMC) on postoperative wound healing in extraocular muscle surgery was investigated. MATERIALS AND METHODS: Sixteen albino rabbits (24 eyes) were used and anesthetized with ketamine and xylazine. These rabbits were divided into 3 groups; (1) control group (balanced salt solution (BSS) exposure for 5 minutes), (2) Group 1 (0.5 mg/ml MMC exposure for 1 minute) and (3) Group 2 (0.5 mg/ml MMC exposure for 5 minutes). After 3 mm recession of superior rectus muscle, MMC or BSS was applied using Weck-Cel sponge (Solan, Jacksonville, FL). The reduction of fibroblast and collagen fiber proliferation were evaluated histopathologically with light microscope at 1, 2, 4 and 8 weeks after operation. We also evaluated the amount of basic fibroblast growth factor (bFGF) by immunohistochemical study at the same time. RESULTS: Histopathologically, there was a more significant reduction of fibroblast and collagen fiber proliferation in Group 1 and 2 than the control group. Immunohistochemically, Group 1 and 2 showed lesser expression of bFGF than the control group. But, there was no difference between Group 1 and 2. CONCLUSIONS: Topical intraoperative application of mitomycin C in extraocular muscle surgery may reduce postoperative adhesions.     

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.     

Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C

Background

Avascularity of the bleb is regarded as a risk of bleb infection, which is the most serious complication after filtration surgery with mitomycin C (MMC). There is no perfect way to prevent avascular bleb formation. We hypothesized that keeping the conjunctiva away from direct exposure to aqueous filtration may suppress avascular bleb formation after filtration surgery with MMC. In order to prove our hypothesis, we investigated whether a thin biodegradable, honeycomb-patterned film (HPF) can reduce bleb avascularity in a rabbit model of filtration surgery with mitomycin C (MMC).

Methods

A fornix-based full-thickness filtration surgery was performed in one eye of each of five rabbits (control group). The same surgery with intraoperative MMC treatment was done in both eyes of six rabbits, with one eye receiving a 14-μm-thick HPF made from poly(L-lactide-co-ε-caprolactone), which was placed subconjunctivally over the filtration site with the honeycomb surface facing up. Intraocular pressure (IOP) measurements, bleb evaluations using ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM) were performed periodically for 4?weeks postoperatively followed by histological examination.

Results

The postoperative IOP decrease and bleb survival were significantly greater in MMC-treated eyes than in control eyes, and were similar between MMC-only and MMC + HPF eyes. The avascular area in the bleb persisted for 4?weeks in MMC-only eyes. Postoperative IVCM showed morphological changes of the conjunctival epithelial cells (i.e., enlarged and variable in size and shape) and epithelial defects in MMC-only eyes, and significantly lower density of connective tissue and vascularity in the subepithelial space in MMC-only eyes compared to the control eyes. These IVCM findings agreed with those by UBM and histology. Bleb avascularity shown by clinical bleb appearance, IVCM and histology, conjunctival epithelial damage shown by IVCM and histology, and loose subepithelial connective tissue shown by UBM, IVCM, and histology were all reduced in MMC + HPF eyes compared to MMC-only eyes.

Conclusions

IVCM successfully showed the characteristic conjunctival damage in MMC-treated blebs. The concomitant use of a thin biodegradable HPF reduced avascularity and conjunctival damage in blebs, without compromising filtration in rabbits following filtration surgery with MMC.     

Polydiaxonon prevents adhesions in the rabbit model: a pilot report.

PURPOSE: Restrictive strabismus is a common and difficult problem confronted by strabismologists. Several materials have been used to minimize the formation of adhesions after strabismus surgery with varying degrees of success. Polydiaxonon (PDS, Ethicon) is an absorbable, nontoxic, nonporous material. We used it as 25 and 50 microm thick sleeves to study its effectiveness in the prevention of adhesions. METHOD: Eight eyes of four adult New Zealand White rabbits were used. To simulate the adhesions, a raw scleral bed was created under the superior rectus insertion in study animals and the muscle capsule facing the sclera was opened. Four study eyes had PDS sleeves inserted around the superior rectus; the other four served as controls. After 4 months the animals were killed. The surgical sites were inspected for adhesions. Light microscopy was also performed. RESULTS: Virtually no adhesion formation was noted in the study eyes. In the control group, however, dense adhesions were seen. Light microscopy confirmed these results. No significant amount of foreign material was found. There was no toxicity resulting from PDS. CONCLUSIONS: This demonstrated nearly complete prevention of adhesions in the rabbit model. PDS sleeves appear to have potential in surgery for restrictive strabismus.     

Morphologic proof of the toxicity of mitomycin C on the ciliary body in relation to different application methods

· Background: Since postoperative hypotony has been a frequent complication of glaucomatous filtration surgery with adjunctive use of mitomycin C (MMC), the question arises of whether there may be another application method which can minimize this side effect. The purpose of this study was to establish the morphologic side effects of different application methods. · Methods: MMC 0.2 mg/ml was applied to the episclera of nine eyes of six pigmental rabbits at random via collagen shield (CS), soft contact lens (CL), or lyophilisate (20 μg; LY) for 5 min. Two eyes (controls) had a subconjunctival injection of BSS only. Another control eye was left untreated (no injection). No trabeculectomy was performed. One hour later the amounts of MMC in the conjunctiva and aqueous were analyzed by reverse-phase high-pressure liquid chromatography. Ciliary bodies were dissected from the enucleated eyes, embedded and investigated by transmission electron microscopy (TEM). Cell height of the nonpigmented ciliary epithelium was morphometrically assessed by means of computer-assisted image analysis. · Results: The light-microscopic analysis of the sectioned cell area revealed reduction of the cell height of the non-pigmented ciliary epithelium (NPCE) after application with soft contact lens (foufold) and collagen shield (2.5-fold) but not with lyophilisate compared to the untreated eye. The following ultrastructural changes were seen: loss of apical microvilli (CS, CL, LY), disintegrating melanin granules within NPCE (CS), lysis of entire areas with NPCE cells (CS), myelin figures within mitochondria (LY), intracellular vacuoles (CS, CL), lysis of myelinated nerves (CS), myelin figures in mitochondria of endothelial cells (LY), and lysis of stromal fibrocytes (CS). In the control eyes (injection of BSS) none of these ultrastructural changes were detected in the cylindrical NPCE cells. The concentration of mitomycin in the aqueous humor after topical application of MMC on the episclera for 5 min were all below the detection limit (<10 ng/ml). The concentration of MMC in the conjunctiva ranged from 2.1 to 3.7 μg/g. · Conclusion: Severe morphologic alterations were seen at the electron-microscopic level after application of MMC 0.2 mg/ml with a collagen shield and with a soft contact lens. They were mildest with lyophilisate and absent in the BSS controls. A new administration device is needed if trabeculectomy is to be performed successfully using MMC in human glaucomatous eyes. Received: 28 September 1998 Revised version received: 17 November 1998 Accepted: 17 November 1998     

Effects of an Anti-transforming Growth Factor-β Agent (Pirfenidone) on Strabismus Surgery in Rabbits

Purpose: To evaluate the usefulness of an anti-transforming growth factor-β (TGF-β) agent, pirfenidone (PFD) on postoperative inflammation and fibrosis following strabismus surgery in rabbits. Methods: Both eyes of 16 New Zealand white rabbits underwent reinsertion of the superior rectus muscle (SRM). After reinsertion of the SRM, PFD-loaded liposomes (0.5 mg/ml) were injected into the right eye (PFD group) and normal saline-loaded liposomes was injected into the left eye (control group), subconjunctivally (0.4 ml). To assess the postoperative inflammatory changes and fibrosis of the SRM, immunofluorescence staining with anti-CD11b antibody was performed at 3 days postoperatively, and Masson's trichrome staining was performed at 4 weeks postoperatively. To evaluate the toxicity of PFD on muscle fibers, the integrity of the muscle fibers was examined by transmission electron microscopy (TEM) at 3 days and 4 weeks postoperatively. Results: CD11b protein expression was significantly reduced in the PFD group compared with the control group at 3 days postoperatively (p = 0.012). Masson trichrome staining, which stains collagen, was diminished in the PFD group at 4 weeks postoperatively. TEM revealed disorganized muscle fibers and vacuoles in both groups, but this was less prominent in the PFD group. Conclusions: Intraoperative injection of PFD may be effective as an adjunctive treatment to decrease inflammation and fibrosis resulting from strabismus surgery.     

Polytetrafluoroethylene/polylactide-co-glycolide laminate containing dexamethasone allows delayed adjustable strabismus surgery in a rabbit model

PURPOSE: To determine the usefulness of polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate containing dexamethasone in delayed adjustable strabismus surgery. METHODS: A prospective, masked-observer, controlled study was performed in rabbits. Fifty-two rabbit eyes were divided into three groups. After a recession of the superior rectus muscle (SRM), a PTFE/PLGA containing or not containing dexamethasone or balanced saline solution was applied beneath and over the SRM in the three treatment groups: the PTFE/PLGA-dexamethasone group (the P-D group), the PTFE group (the P group), and the control group (group C). Delayed adjustment was performed once on each SRM at 3 or 5 weeks after surgery by a masked observer. Adjustment lengths, the forces required, and degrees of adhesions were evaluated. RESULTS: In the control group, adjustment was possible in no eyes at 3 or 5 weeks after surgery. In group P, adjustment was possible in 6 of 10 eyes at 3 weeks after surgery and in 4 of 9 eyes at 5 weeks after surgery. In group P-D, adjustment was possible in 7 of 9 eyes at 3 and 5 weeks after surgery. CONCLUSIONS: PTFE/PLGA containing dexamethasone was found to allow delayed adjustment in most eyes for up to 5 weeks after surgery without instillation of anti-inflammatory agent.     

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

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

Efficacy of various drugs in the prevention of posterior capsule opacification: experimental study of rabbit eyes

PURPOSE: To assess the efficacy of various drugs in the prevention of posterior capsule opacification (PCO) in a closed capsular bag technique. SETTING: Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA. METHODS: Lens material was removed using phacoaspiration or phacoemulsification through a microcapsulorhexis according to the hardness of the crystalline lens correlated with the weight and age of the rabbits. A mixture of an ophthalmic viscosurgical device (sodium hyaluronate 1.4% [SHA]) and a drug was injected into the empty capsular bag, allowed to remain inside for 3 minutes, and removed. The capsular bag was rinsed with balanced salt solution (BSS) and refilled with SHA. In a group of rabbits, the capsulorhexis was sealed with a minicapsulorhexis valve (MCV). Rabbits were treated with 1 of the following: SHA (control), BSS, mitomycin-C (MMC, 0.2 mg/mL), ethylenediaminetetraacetic acid (EDTA) (10 mM and 15 mM), 5-fluorouracil (5-FU, 33 mg/mL), acetic acid (3%, 0.3%, and 0.003%), and distilled water. RESULTS: Upon completion of the study, the control and treated eyes had PCO and new lens material (not residual). Anterior capsule proliferation was observed in eyes treated with 5-FU. The order of PCO appearance (earliest to latest) was as follows: 15 mM EDTA, SHA, MMC, acetic acid 0.3%, acetic acid 3%, BSS, distilled water (small animals; no MCV), acetic acid 0.003%, 5-FU, 10 mM EDTA, and distilled water (large animals; MCV). The earliest appearance was day 1 postoperatively and the latest, day 47. CONCLUSIONS: Distilled water and 10 mM EDTA treatments were the most efficient in retarding the appearance of PCO.     

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.     

The use of sodium hyaluronate as a biologic sleeve in strabismus surgery

Strabismus surgery sometimes fails because of the mechanical restriction caused by the development of fibrous adhesions between the operated muscle and the surrounding tissues. Reoperation increases the frequency and severity of mechanical restriction significantly because of additional scar formation. Attempts to isolate the muscle from other tissues using gelatin sponges or Supramid plastic sleeves have been unsuccessful because of the body's reaction to these permanent foreign bodies. We used an ultra-pure fraction of sodium hyaluronate to study whether this nonantigenic, noninflammatory, viscoelastic substance could function as a temporary sleeve to prevent or reduce scarring and mechanical restriction following strabismus surgery. We resected the superior rectus muscle of 14 eyes from seven 5- to 7-pound white rabbits. In one eye, we instilled sodium hyaluronate 1% around the muscle. The other eye served as a control. The rabbits were killed at five, seven, ten, 14, 21, 28, and 42 days. Ante mortem length-tension measurements and post mortem histologic examinations of the operated muscles were performed in a blinded fashion. The results suggested, but did not definitely demonstrate, that sodium hyaluronate may reduce postoperative adhesions.