Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery

PURPOSE: To determine whether postoperative application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (ilomastat), reduces scarring after glaucoma filtration surgery. METHODS: In a randomized, prospective, masked-observer study, 40 New Zealand White rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive postoperative subconjunctival injections of either phosphate-buffered saline (PBS) or 100 microM ilomastat for 10 days. The animals were killed on days 7, 14, 21, and 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (alphaSMA) and extracellular matrix components in the two groups. RESULTS: Surgical outcome was significantly prolonged in the ilomastat-treated group compared with the vehicle-treated group (P < 0.001). At day 30, all the blebs had survived except two in the ilomastat-treated group, whereas no blebs survived to day 30 with vehicle treatment (n = 11). The intraocular pressure remained significantly lower throughout the course of the experiment in the ilomastat group compared with the vehicle group (P < 0.0017). Histologically, less scar tissue was observed at the sclerostomy site with inhibition of MMP, compared with vehicle treatment. CONCLUSIONS: The data presented suggest that the healing response after surgery can be modulated by inhibiting the effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.     

Postoperative subconjunctival mitomycin-C injection after non-penetrating glaucoma surgery.

PURPOSE: To evaluate subconjunctival mitomycin C (MMC) injection efficacy and safety in patients with failing glaucoma non-penetrating filtering blebs. METHODS: Twenty-eight eyes were consecutively recruited for this study. Only one eye for each patient was randomly selected. All the recruited patients had glaucoma and uncontrolled intraocular pressure after a non-penetrating filtering glaucoma surgery and/or a pathological aspect of the filtering bleb (i.e., vascularized and/or encysted). One or more MMC injections were performed under the conjunctiva closed to the bleb to improve filtration. Local effects and complications of subconjunctival MMC injections were analyzed. RESULTS: Out of the 28 patients, 21 (75%) had MMC also applied intraoperatively. The mean postoperative IOP before MMC injections was 17 +/- 6.6 mmHg. The final IOP after MMC injections was 13.9 +/- 2.9 mmHg after a mean follow-up of 6 months. A total of 67 subconjunctival MMC injections were performed with a mean of 2.9 (ranging from 1 to 5) injections per patient. The only complication found to be possibly related to MMC injections was two cases of corneal Dellen. CONCLUSION: From these preliminary results, subconjunctival MMC injections in selected cases appear to be not only safe but also effective in promoting further the postoperative IOP drop.     

Bleb vascularity following post‐trabeculectomy subconjunctival bevacizumab: a pilot study

Background: To determine whether postoperative subconjunctival bevacizumab significantly alters bleb vascularity. Design: A randomized, prospective interventional study. Participants: Forty‐three eyes from 39 patients were recruited, with 21 eyes randomized to subconjunctival injections of 5‐fluorouracil, and 22 eyes to combined 5‐fluorouracil/bevacizumab. Methods: All patients who underwent uncomplicated primary antimetabolite augmented trabeculectomy who subsequently required postoperative subconjunctival 5‐fluorouracil injection within 4 weeks of surgery were eligible. Patients were randomized to receive subconjunctival 5‐fluorouracil only (7.5 mg/0.15 mL) or 5‐fluorouracil plus bevacizumab (1.25 mg/0.05 mL). Main Outcome Measures: Primary outcome was bleb vascularity with secondary endpoints including visual acuity, intraocular pressure, bleb morphology, complications and total numbers of 5‐fluorouracil injections were recorded at baseline, week 12 and 18 months. Results: At week 12, there was no significant difference between groups for visual acuity, intraocular pressure, bleb vascularity and morphology, or total number of 5‐fluorouracil injections. By 18 months, 47.4% of the 5‐fluorouracil/bevacizumab group exhibited central bleb avascularity compared with 21.1% of the 5‐fluorouracil group (Fisher's exact test, P = 0.17). Two bleb complications (one blebitis; one suture abscess) recorded in the 5‐fluorouracil/bevacizumab group. Conclusions: After a single combined injection, a trend for increased central bleb avascularity was observed, although this effect was not sufficient to reach statistical significance. This, in addition to the occurrence of two bleb‐related complications in the bevacizumab group, suggests the need for a larger clinical trial to further evaluate the safety and efficacy of bevacizumab as a modulating agent in glaucoma filtration surgery.     

Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model

PURPOSE: Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. To gain further understanding of the role of CTGF in the scar formation that occurs after glaucoma filtering surgery (GFS), experiments were performed in a rabbit model. METHODS:. Three experiments were performed: (1) CTGF and transforming growth factor (TGF)-beta expression were measured quantitatively after GFS, using ELISA. (2) After GFS conjunctival bleb tissues were immunostained for the presence of CTGF and TGF-beta. (3) Exogenous CTGF was injected into mitomycin-C (MMC)-treated filtering blebs and the scaring response compared to TGF-beta and physiological saline-injected blebs. RESULTS: CTGF and TGF-beta were expressed maximally by day 5 after surgery and were both shown to be present in the bleb tissues after GFS. The addition of exogenous CTGF and TGF-beta increased the rate of failure of GFS blebs. CONCLUSIONS: These data support the hypothesis that CTGF plays an important role in scarring and wound contracture after GFS. Inhibition of CTGF synthesis or its action may help prevent bleb failure and improve long-term GFS outcomes.     

Determinants of bleb morphology in minimally invasive, clear-cornea micropenetrating glaucoma surgery with mitomycin C

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.     

Co-treatment of suberoylanilide hydroxamic acid and mitomycin-C induces the apoptosis of rabbit tenon's capsule fibroblast and improves the outcome of glaucoma filtration surgery

PURPOSE: This study was undertaken to develop a new treatment modality that would be able to minimize fibrosis and provide better outcome with glaucoma filtration surgery (GFS). METHODS: We examined whether co-treatment with mitomycin-C (MMC) and histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) efficiently induces apoptosis on rabbit Tenon's capsule fibroblasts (TCF) in vitro. We further examined the effect of co-treatment with SAHA and MMC on the alteration of IOP and the bleb survival in rabbits following GFS. RESULTS: Co-treatment of MMC and SAHA efficiently induces apoptosis in TCFs via the up-regulation of p53 and increased phosphorylation of p53 on serine 15 and 392. Also, co-treatment of SAHA and low-dose MMC decreases IOP, prolongs bleb survival, and induces apoptosis of cells under the bleb area following GFS. CONCLUSION: This study shows that a co-treatment of SAHA and MMC could improve the outcome of GFS.     

Outcome of cataract extraction and posterior chamber intraocular lens implantation following glaucoma filtration surgery

PURPOSE: To evaluate the outcome of cataract extraction (CE) after glaucoma filtering surgery (GFS). METHODS: A total of 77 eyes (77 patients) who underwent CE with posterior chamber intraocular lens (PCIOL) implantation following GFS by a single surgeon were reviewed. Main outcome measures were preoperative and postoperative intraocular pressures (IOPs), visual acuities, medications, astigmatism, bleb survival, time of surgical failure, complications, and success rate. RESULTS: Mean time interval between GFS and CE was 46.8+/-50.9 months (range, 2-348 months). The mean preoperative IOP was 13.9+/-4.7 mmHg (range 3-27 mmHg) and mean postoperative IOP at 3 weeks was 13.6+/-5.5 mmHg (range, 6-44 mmHg). The mean follow-up was 19.5+/-20.1 months (range, 1.4-73 months; median 10.6 months). Complete success was achieved in 59 eyes (76.7%). The cumulative probability of complete success was 91.3+/-3.7, 82.0+/-5.6 and 78.1+/-6.5% at the end of 6 months, 1, and 2 years, respectively. Visual acuity before CE was < or =20/50 in all eyes (100%). Visual acuity at last visit was > or =20/40 in 33 eyes (42.8 %), 20/50-20/80 in 30 eyes (39.0%), < or =20/100 in 14 eyes (18.2%). Risk factors identified for qualified success included age at CE>60 years, interval of < or =5 months between GFS and CE, use of preoperative glaucoma medications, and postoperative IOP >19 mmHg within 2 weeks. CONCLUSIONS: IOP and bleb function was maintained after CE with PCIOL implantation following successful GFS with good visual recovery.     

Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery

PURPOSE: Postoperative subconjunctival wound healing remains the commonest cause of late bleb failure after glaucoma filtration surgery. This study was undertaken to investigate whether the human monoclonal antibody that neutralizes transforming growth factor-beta2 (CAT-152; lerdelimumab) could be used as a postoperative agent to prevent scarring after glaucoma surgery and compared it with 5-fluorouracil (5-FU), to benchmark its potential clinical benefit. METHODS: In a randomized, controlled, masked-observer study, after modified glaucoma surgery, 48 rabbits were randomly allocated to receive a postoperative course of seven subconjunctival injections of CAT-152 (1 mg/mL), 5-FU (50 mg/mL), or no treatment. Bleb characteristics, the presence of subconjunctival drainage, and local reaction to treatment were assessed. Animals were killed on days 10, 21, and 30. Immunohistochemistry, histologic staining and electron microscopy were performed to demonstrate the mechanism of CAT-152-mediated effects on the extracellular matrix. RESULTS: CAT-152 significantly improved surgical outcome (log rank test, P < 0.001) and reduced subconjunctival collagen deposition (P < 0.01) compared with 5-FU and control. Median bleb survival was increased in the CAT-152 group (23.5 days) compared with the 5-FU (20 days) and control (16 days) treatment groups. CAT-152 treatment improved bleb morphology (P < 0.05) and was well tolerated. 5-FU prolonged the duration of corneal epitheliopathy (P < 0.01). CONCLUSIONS: Postoperative administration of CAT-152 significantly improved surgical outcome, reduced subconjunctival scarring, and minimized the risk of corneal side effects compared with the anti-scarring agent 5-FU. These findings suggest that CAT-152 may offer therapeutic benefit as a postoperative agent to prevent subconjunctival scarring after glaucoma filtration surgery.     

Postoperative adjunctive bevacizumab versus placebo in primary trabeculectomy surgery for glaucoma

AIM: To compare the effectiveness of postoperative adjunctive use of subconjunctival bevacizumab in altering the outcome of primary trabeculectomy in terms of sustained lowering of intraocular pressure (IOP) and reduction of postoperative bleb vascularization and fibrosis. METHODS: A prospective, one center, randomized, placebo-control study. Fifty-nine patients (59 eyes) with uncontrolled IOP under maximal tolerated medical treatment (MTMT) were recruited. A primary trabeculectomy with mitomycin C (MMC) was done and the patients were randomized to either postoperative subconjunctival injection of bevacizumab (1.25 mg/0.05 mL) or balanced salt solution (BSS). Forty-seven patients (47 eyes) completed at least one year of follow up and were included in the study. The main outcome measure was the IOP, and secondary outcome measures include bleb morphology, vascularization, and fibrosis, as well as the need for glaucoma medications and 5-fluorouracil (5-FU) needling. RESULTS: At 1-year follow up, there was no significant difference between groups for IOP (P=0.65), bleb morphology (P=0.65), and the need for glaucoma medications (P=0.65) or 5-FU needling requirements (P=0.11). However, the bevacizumab group had a higher rate of success results, lower use of glaucoma medications after surgery, and optimal bleb aspect in more patients, but more 5-FU needling procedures required. CONCLUSION: A bigger sample size is needed in order to determine whether the differences found in the bevacizumab group are statistically significant.     

结膜下注射CTGF抗体对兔青光眼滤过手术后眼压和滤过泡面积的影响

目的:探讨结缔组织生长因子(connective tissue growth factor,CTGF)抗体对兔青光眼滤过手术后滤过泡瘢痕化的抑制作用。方法:家兔5只双眼制作青光眼滤过手术模型。随机选取家兔一眼作为抗体组,分别于手术完成当时和术后5d结膜下注射0.1mL浓度为50mg/L的CTGF抗体;另一眼作为对照组在相同时间点结膜下注射0.1mL磷酸盐缓冲液。术后1,3,5,7,10,14d分别观察滤过泡形态并测量其面积和眼压值。结果:术后7,10和14d抗体组滤过泡面积均大于对照组(P<0.05),眼压均小于对照组(P<0.05)。结论:结膜下注射CTGF抗体可维持兔眼滤过手术后较大的滤过泡面积和较低的眼压。     

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.     

Adjunctive use of delayed and adjustable low-dose 5-fluorouracil in refractory glaucoma

We used delayed 5-mg subconjunctival injections of 5-fluorouracil as an adjunct to filtering surgery in ten eyes with refractory glaucoma. The first 5-fluorouracil injection was made three to 15 days postoperatively and was used only when clinical signs suggested an impending bleb failure. These signs included flattening and localization of bleb, increased vascularity, early subconjunctival scarring, loss of microcystic conjunctival changes, and increased intraocular pressure. After a follow-up of ten to 17 months (mean, 13.7 months), an intraocular pressure of less than 21 mm Hg was attained in five eyes without medication and in four eyes with medication. The treatment failed in one eye. The average dose of 5-fluorouracil was 28 +/- 12 mg per eye. There were no conjunctival wound leaks. Six eyes developed transient corneal epithelial defects. The modified administration of 5-fluorouracil can result in fewer conjunctival wound leaks. Its use can be limited to those patients who show evidence of impending bleb failure.     

Single intraoperative applications of 5-fluorouracil during filtration surgery: early results.

Experimental studies from our laboratory have suggested that single exposures to 5-fluorouracil (5-FU) would have a similar effect to subconjunctival injections of 5-FU and a less permanent effect on subconjunctival fibroblasts than mitomycin C (MMC). Thirty four eyes of 33 glaucoma patients with an increased risk of filtration surgery failure were treated with a single intraoperative 5 minute exposure of sclera and subconjunctival tissues to 5-FU, 25 mg/ml. The follow up period ranged from 3-9 months, during which two high risk eyes failed completely and one required topical beta blockers to control intraocular pressure. No low/moderate risk eyes failed. Single 5 minute intraoperative exposures to 5-FU are convenient, inexpensive, have no significant corneal side effects, and may be a useful adjunctive treatment to optimise the results of glaucoma filtration surgery, particularly in the large group of low/moderate risk patients.     

Non-penetrating glaucoma surgery augmented with mitomycin C or 5-fluorouracil in eyes at high risk of failure of filtration surgery: long-term results

PURPOSE: To investigate the long-term efficacy and safety of non-penetrating glaucoma surgery (NPGS) augmented with mitomycin C (MMC) or 5-fluorouracil (5FU) in eyes at high risk of failure of glaucoma filtration surgery. METHODS: Prospective study of all eyes, undergoing NPGS with 0.04% MMC (1 to 2 min topical or 0.04 mL subconjunctival injection into the superior fornix) or 5FU (25 mg/mL topically for 5 min). Complete success was an intraocular pressure (IOP)or=20% drop in IOP or a reduction of at least two medications. RESULTS: Twenty-three eyes of 22 patients with a mean follow up of 41.4 months were reviewed. Fifteen eyes had failed trabeculectomy and seven had uveitic glaucoma. Mean preoperative IOP reduced from 25.8+/-7.8 to 15.4+/-4.9 mmHg at final visit, a mean change of 41%. Median number of preoperative medications decreased from 3 to 0 postoperatively. Cumulative probability of success was 100% at 2 years, 94% at 3 years and 85% at 4 years. No patient developed any long-term complications. Complete success was achieved in 11 eyes and qualified success in 10 eyes. Two eyes failed and required further surgery. CONCLUSION: NPGS augmented with small-volume MMC/5FU provides good long-term IOP control in eyes at high risk of failure with a lower incidence of complications compared with augmented trabeculectomy and eliminates the need for postoperative bleb or suture manipulation.     

5-Fluorouracil after trabeculectomy and the iridocorneal endothelial syndrome

Nine patients (nine eyes) with iridocorneal endothelial (ICE) syndrome underwent trabeculectomy and received postoperative subconjunctival injections of 5-fluorouracil (5-FU) to enhance bleb formation (total 5-FU dose, 30-105 mg; mean, 53.8 mg). Eight eyes had undergone prior unsuccessful trabeculectomy. Four eyes had intraocular pressure (IOP) less than or equal to 21 mmHg on zero to two glaucoma medications after 6 to 54 months of follow-up (mean, 25.3 months). Five eyes required repeat surgery within 2 to 13 months and were considered failures. All five eyes that failed received a Molteno drainage implant. Progressive endothelial proliferation may explain late onset bleb failure and the relative ineffectiveness of 5-FU in this condition.     

Partial excision with a conjunctival advancement flap after a relaxing incision for a dissecting glaucoma filtering bleb

A 65-year-old male patient developed dissecting glaucoma filtration bleb following trabeculectomy with mitomycin-C (MMC). Surgical partial excision of the bleb was performed and the tissue was subjected to histopathological evaluation. The bleb area was covered by a conjunctival flap that was advanced with the help of a relaxing incision in the superior conjunctiva fornix. The dissecting bleb was successfully managed by controlling intraocular pressure, and the patient became asymptomatic without any medication. The light microscopic examination of the bleb showed irregularly arranged collagen bundles and hypocellularity of the subconjunctival tissue with places of nodular configuration of the fibroblast in the periphery. Surgical partial excision of the dissecting glaucoma filtering bleb is a reliable, simple, and precise method. Advancing the conjunctival flap by a superior conjunctival relaxing incision facilitates easy mobilization of the flap, ensures healthy resurfacing of the bleb, and prevents postoperative transconjunctival leakage. Histopathology of the bleb is compatible with the use of MMC during original filtering surgery.     

Subconjunctival or General anaesthesia in Trabeculectomy - A Retrospective Analysis of the Bleeding Risk from a Glaucoma Surgeon's Point of View

Introduction: The aim of this study was to compare the intraoperative and early postoperative outcome of trabeculectomy with mitomycin C in glaucoma patients undergoing general anaesthesia compared to those undergoing subconjunctival anaesthesia. Methods: The perioperative results of consecutive glaucoma patients receiving a trabeculectomy with mitomycin C either under general anaesthesia (group 1, n = 60) or in subconjunctival anaesthesia (group 2, n = 60) were analysed in a retrospective study. All surgical procedures were performed by one surgeon and only one eye of each patient with no history of previous conjunctival surgery was included in the study.Results: No significant peri- and postoperative differences concerning period of hospitalisation, intraocular pressure, filtration-bleb bleedings, hyphaema, frequency of laser suture lysis, hypotony, chorioidal detachment or revision surgery could be shown between the two groups. Considering all patients together, there was a significant correlation between the occurrence of postoperative filtering bleb bleedings and the absolute number of topical antiglaucomatous substances used prior to surgery Conclusions: The perioperative risk profile of penetrating glaucoma surgery with subconjunctival anaesthesia seems to be similar to that of procedures under general anaesthesia. For prevention of postoperative filtering bleb bleedings, the administration of topical antiglaucomatous drugs should be stopped before surgery.     

Augmentation of filtering blebs with perfluoropropane gas bubble: an experimental and pilot clinical study

OBJECTIVE: To evaluate the use of perfluoropropane (C3F8) gas bubble in the augmentation of glaucoma-filtering blebs. DESIGN: Experimental animal study and a pilot clinical study. PARTICIPANTS: Twenty rabbits in the animal study and 20 humans in the pilot study participated. INTERVENTION: Twenty patients underwent trabeculectomy for medically uncontrolled glaucoma. Surgical techniques were similar to those used in standard limbus-based trabeculectomies. The Tenon's capsule and conjunctival wound were closed separately using continuous sutures. Before the final knots were tied, 0.1 to 0.2 ml of 15%:85%-C3F8:air mixture gas bubble was introduced into the subconjunctival space with a silicone tube attached to a 27-gauge Rycrof cannula. The sutures were immediately knotted on withdrawal of the tube. The patients were reviewed after surgery for the appearance, size, and location of the gas bubble. The bleb morphology and intraocular pressures were also monitored. MAIN OUTCOME MEASURES: The parameters measured were intraocular pressure control, Snellen visual acuity, appearance of the bleb in relation to its elevation and degree of inflammation of the subconjunctival tissue, and characteristics of the gas bubble (e.g., size, number, and position). RESULTS: The gas bubbles stayed in the conjunctival bleb for an average duration of 17 days (range, 13-27 days). In all cases, the gas bubbles helped to maintain the filtering bleb until their complete resolution. No excessive inflammation was noted in the filtering blebs. The mean preoperative intraocular pressure was 27.3 +/- 5.5 millimeters of mercury (mmHg), and the mean postoperative intraocular pressure was 14.5 +/- 2.3 mmHg, with only two patients requiring supplementary topical medication. All cases resulted in good filtering blebs with satisfactory intraocular pressures after 16 months of follow-up. CONCLUSIONS: Subconjunctival C3F8 gas bubbles, via a "spacer" effect, aid the maintenance of filtering blebs in the early postoperative period. This technique may be useful in augmenting or salvaging blebs at risk of failure.     

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

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

A modified model of glaucoma filtering surgery in Sprague-Dawley rats

Animal models are useful in glaucoma research to study tissue response to wound healing. Smaller animals such as rats offer additional advantages in terms of availability of detection antibodies and microarrays with cheaper maintenance costs. In this study, we describe a glaucoma filtering surgery (GFS) model in adult Sprague–Dawley rats by performing a sclerostomy using a 26-G needle and additionally placing a silicone tube (27 G) connecting the anterior chamber to the subconjunctival space to maintain a patent fistula for the flow of aqueous humor, thus providing a more definitive bleb. This technique will be useful in identifying and modifying newer targets in the wound healing process in order to improve surgical outcomes following GFS.