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1.  Effects of topical bevacizumab application on early bleb failure after trabeculectomy: observational case series 
The aim of this study was to evaluate the influence of topical bevacizumab on the formation and function of filtering blebs in eyes with early bleb failure after antiglaucoma surgery.
Of all patients who underwent mitomycin-augmented trabeculectomy for glaucoma in the Department of Ophthalmology at the Medical University in Lublin, Poland, between March 2009 and March 2010, a total of 21 eyes from 20 patients with injected filtration bleb 9.8 ± 4.7 days after surgery were included in this observational case series. All patients were treated with standard steroid therapy and topical bevacizumab 5 mg/mL five times a day for 20.9 ± 9.8 days. Patients were followed up every other day, and a full eye examination was performed 14, 30, 60, and 180 days after initiation of treatment. Blebs were evaluated for vascularity by slit-lamp examination with concomitant photographic documentation and intraocular pressure measurement.
Elevated functional bleb with significantly reduced vascularity was present in 16 eyes, and was flat and nonfunctional in five eyes. Intraocular pressure in all eyes decreased from a mean of 26.6 ± 9.6 mmHg before surgery to 14.6 ± 7.7 mmHg and 15.8 ± 8.3 mmHg at 2 and 6 months after surgery, respectively. Filtration bleb leak was noted in three eyes while on treatment with bevacizumab.
Topical application of bevacizumab might favor functional bleb formation after trabeculectomy in eyes with a high risk of failure.
PMCID: PMC3792922  PMID: 24109173
glaucoma; trabeculectomy; bleb failure; bevacizumab
2.  Office-based Slit-lamp Needle Revision with Adjunctive Mitomycin-C for Late Failed or Encapsulated Filtering Blebs 
The purpose of this study was to assess the results of bleb needling in glaucomatous patients with late failed filtering blebs.
Materials and Methods:
A retrospective case series of 27 eyes of 27 patients was considered. All patients underwent needle bleb revision with adjuvant mitomycin-C performed at the slit lamp, during an office visit. Complete success was defined as postneedling intraocular pressure (IOP) ≤ 21 mmHg without any antiglaucoma medications and qualified success was IOP ≤ 21 mmHg with topical antiglaucoma medications.
There were 12 eyes with encapsulated blebs and 15 eyes with flat blebs. The mean interval between index filtering surgery and bleb revision was 32.74 ± 15.36 months. Mean IOP was 25.07 ± 4.80 mmHg before surgery and 19.66 ± 4.97 mmHg at last postoperative follow-up. The mean follow-up was 20.31 ± 15.63 months. Complete and qualified successes were 7.4% and 51.9%, respectively. Cumulative rates of success at 1, 2, 3, and 4 years were 76%, 65%, 49%, and 37%, respectively. The mean number of antiglaucoma medications was reduced from 3.15 ± 0.36 preoperatively to 2.33 ± 1.21 postoperatively (P<0.001).
Slit-lamp needle revision in office is a simple and effective method for treating late encapsulated or flat filtering blebs without significant complications even for late bleb failure.
PMCID: PMC3353671  PMID: 22623862
Bleb Needling; Bleb Revision; Filtering Surgery; Glaucoma; Mitomycin-C
3.  Surgical Repair of Leaking Filtering Blebs Using Two Different Techniques 
To report the outcomes of two different surgical techniques for the repair of late onset bleb leakage following trabeculectomy.
This retrospective study includes 21 eyes of 20 patients with prior trabeculectomy and late-onset bleb leaks; 14 eyes underwent excision of the filtering bleb together with conjunctival advancement while in the other 7 eyes the bleb was retained but de-epithelialized before conjunctival advancement. Success was defined as resolution of leakage with no need for additional glaucoma surgery together with intraocular pressure (IOP) of 5-21 mmHg. Complete and qualified success was considered when the above mentioned was achieved without or with glaucoma medications, respectively.
Mean duration of follow-up was 20.3±14.4 months. No significant difference was observed between the two groups in terms of complete, qualified and overall success rates (P>0.05), however more antiglaucoma medications were necessary in the bleb excision group (P=0.02).
Both surgical techniques of bleb repair were comparably effective, however the bleb de-epithelialization technique was associated with less need for glaucoma medications after the procedure.
PMCID: PMC3595588  PMID: 23503604
Bleb Leakage; Bleb Repair; Conjunctival Advancement; Trabeculectomy
4.  Subconjunctival bevacizumab to augment trabeculectomy with mitomycin C in the management of failed glaucoma surgery 
To provide a feasible solution to the problem of failed glaucoma surgery. The aim was to evaluate the efficacy and safety of the additional effects of a combined surgical approach. This approach augments the application of trabeculectomy with mitomycin C (MMC) by adding subconjunctival bevacizumab injection. The results were compared with those of trabeculectomy with only adjunctive MMC.
A randomized controlled prospective clinical trial included 28 eyes diagnosed with failed scarred bleb of a previous trabeculectomy. The eyes were divided into two equal groups: combined group A, “trabeculectomy with adjunctive MMC and subconjunctival bevacizumab,” and control group B, “trabeculectomy with adjunctive MMC only.” The main outcome results included the cumulative probability of surgical success, intraocular pressure (IOP) values, and number of IOP-lowering medications needed to achieve the target IOP.
Group A achieved a cumulative probability of complete success of 0.769 and of qualified success of 0.231 at the end of the 24 month study period; group B achieved cumulative probabilities of 0.538 and 0.308, respectively. Group A achieved a lower mean IOP value than group B, with fewer antiglaucoma drugs at all postoperative visits, but this lower value did not reach a statistically significant level (P>0.05). There was no statistically significant difference between both groups regarding best corrected visual acuity, visual field parameters, operative and/or postoperative complications, and additional interventions. No significant adverse effects were caused by this combined approach.
Bevacizumab was not found to add much to the favorable long-term outcome of conventional trabeculectomy with MMC as a solution to the problem of scarred failed bleb.
PMCID: PMC4168860  PMID: 25246758
glaucoma; bevacizumab; mitomycin C; failed trabeculectomy; bleb failure; scarred bleb
5.  Morphology of functioning trabeculectomy blebs using anterior segment optical coherence tomography 
Indian Journal of Ophthalmology  2014;62(6):711-714.
To image trabeculectomy blebs using anterior segment optical coherence tomography (AS-OCT), and to correlate the bleb morphologic features at one month postoperatively with bleb function at six months.
Materials and Methods:
This prospective, observational study included 56 eyes undergoing trabeculectomy with MMC, followed up for minimum of six months. Postoperatively, bleb imaging was done using AS-OCT at one and six month. Bleb morphology was assessed for bleb wall reflectivity, bleb pattern in multiform reflectivity, visibility of drainage route and presence of hyper-reflectivity area. Bleb function was considered successful if IOP was <18 mmHg without medication at six month. Bleb morphology one month postoperatively was correlated with bleb function at six months.
At six months successful bleb function was noted in 44 (81.5%) eyes. Morphology of bleb at one month showed uniform bleb wall reflectivity in 6 eyes (11%) and multiform wall reflectivity in 48 eyes (89%). In eyes with multiform wall reflectivity, microcysts with multiple layers was seen in 26 eyes (48%), microcysts with subconjunctival separation in 12 eyes (22%) and only microcyst in 10 eyes (19%). When bleb features at one month were correlated with the bleb function at six months, logistic regression analysis revealed that blebs with multiform reflectivity with multiple internal layers with microcysts were associated with higher chances of success (P < 0.001).
AS-OCT demonstrated early bleb morphological features that may be used to predict the functioning of a bleb. Multiform bleb wall reflectivity with a pattern of multiple internal layers and microcysts was associated with increased chances of success of a bleb.
PMCID: PMC4131325  PMID: 25005200
AS-OCT; bleb morphology; trabeculectomy
6.  Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment 
AIMS/BACKGROUND—The introduction of the adjunctive use of antiproliferatives to trabeculectomy has greatly improved the success rate of this operation. Trabeculectomy with antiproliferative treatment, however, is usually associated with a cystic and thin walled filtering bleb, which may be more susceptible to infection. The objective of this study was to evaluate the incidence, clinical findings, and risk factors of delayed onset, bleb related infection after trabeculectomy with adjunctive mitomycin C (MMC) or 5-fluorouracil (5-FU) treatment.
METHODS—The records of 632 glaucoma patients who underwent 966 trabeculectomies, with and without the use of adjunctive MMC or 5-FU treatment, between January 1985 and February 1995 were analysed. The mean follow up period was 3.5 (2.4) years (range 0.1 to 11.2 years). The mean patient age was 54.8 (18.8) years (range 0 to 88 years).
RESULTS—Bleb related infection occurred in one of 76 trabeculectomies that did not receive antiproliferatives (1.3%), three of 228 treated with 5-FU (1.3%) trabeculectomies, and seven of 662 treated with MMC (1.1%). Five eyes developed blebitis; six eyes developed endophthalmitis. Bleb related infection developed an average of 3.1 (1.6) (range 0.4 to 6.0) years after trabeculectomy. All eyes had avascular or hypovascular blebs that were cystic in shape before infection and all eyes had reduced intraocular pressure. Early wound leaks and chronic, intermittent bleb leaks were identified to be risk factors for the bleb related infection.
CONCLUSION—The incidence of delayed onset, bleb related infection after trabeculectomy with antiproliferative treatment is similar to that after trabeculectomy without antiproliferatives.

PMCID: PMC1722033  PMID: 9486030
7.  Autologous Transplantation of a Free Tenon's Graft for Repairing Excessive Bleb Leakage after Trabeculectomy: A Case Report 
Case Reports in Ophthalmology  2014;5(3):297-301.
To report a case of autologous transplantation of a free Tenon's graft to repair excessive bleb leakage after trabeculectomy.
Case Report
A 39-year-old Japanese woman presented with severe hypotony in her left eye. She had undergone trabeculectomy with mitomycin C 14 years ago. Slit-lamp examination showed an ischemic and ruptured bleb, excessive bleb leakage, and an extremely shallow anterior chamber. A large scleral defect was vaguely observed through the bleb conjunctiva. The hypotony was attributed to excessive bleb leakage. A surgical revision was required. First, the avascular bleb conjunctiva and the melted scleral flap were excised. A scleral defect was observed. Thick fibrotic tissue, i.e., the autologous Tenon's graft, was separated from the underlying sclera, cut to the desired size to cover the defect, and sutured to the sclera with 10-0 nylon sutures. Irrigation with balanced salt solution through the paracentesis confirmed deepening of the anterior chamber with no bleb leakage. In the current case, a layer of amniotic membrane was applied to cover the largely exposed sclera. Two weeks postoperatively, the surgical site was totally re-epi-thelialized with no aqueous leakage. Three months postoperatively, vascularization into the surgical site was observed. The intraocular pressure remained within normal levels without recurrent bleb leakage.
Autologous transplantation of a free Tenon's graft successfully repaired excessive bleb leakage through a scleral defect after trabeculectomy. This technique is easier, safer, and may be more cost effective for repairing excessive bleb leakage after trabeculectomy than conventional management techniques.
PMCID: PMC4224260  PMID: 25408669
Autologous Tenon's graft; Bleb leak; Trabeculectomy; Hypotony
8.  Comparative study between trabeculectomy with photodynamic therapy (BCECF-AM) and trabeculectomy with antimetabolite (MMC) in the treatment of primary open angle glaucoma 
Various methods have been investigated to avoid postoperative scarring of the filtering bleb in modern glaucoma surgery. Most deal with the application of antimetabolic drugs such as mitomycin C (MMC). 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) is a locally acting intracellular photosensitizer which could control and decrease postoperative fibrosis at the trabeculectomy site.
To compare the effect of photodynamic therapy in combination with trabeculectomy to the effect of MMC combined with the same procedure in controlling postoperative intraocular pressure (IOP) in patients with medically uncontrolled primary open angle glaucoma (1ry OAG).
A randomized controlled clinical trial was conducted on 76 eyes of 76 patients divided into three groups undergoing trabeculectomy, trabeculectomy with BCECF-AM (group A), trabeculectomy with MMC (group B), and trabeculectomy only as a control group (group C). Patients were reviewed postoperatively for clinical evaluation and photo documentation of the blebs with a fundus camera and ultrasonic biomicroscopy (UBM). The desirable effect of the adjunctive material was evaluated according to the clinical efficacy, tolerability, and safety by comparison with the control group.
Benha University Hospital, Benha, Egypt.
After a mean follow-up of 24 months, all procedures succeeded in lowering IOP. The cumulative probability of complete success at the 24 month follow-up was 91% for group B, compared to 82% and 81.5% for group A and group C, respectively. The percentage of complete success was highest for group B, second highest for group A, and lowest for group C over the follow-up period; however, these differences were not statistically significant (P > 0.05). Regarding the bleb morphology and UBM reflectivity, the differences were not statistically significant (P > 0.05). The mean bleb height and breadth were larger in groups A and B in comparison to group C over the study period. The mean aqueous drainage route was similar in groups A and C, but less than in group B at 3 and 12 months postoperatively. Complications were generally mild and less marked in group A and C than group B.
Cellular photoablation using BCECF-AM seems to be a feasible new method to use in combination with glaucoma filtration surgery. Although MMC might be considered a more potent adjunctive to trabeculectomy in promoting IOP reduction, photodynamic therapy carries relatively less risk of adverse effects and complications. Cellular photoablation using BCECF-AM could be considered efficient, tolerable and relatively safer in managing patients with 1ry OAG. Further studies are necessary to determine the safety and the reliability of this therapy.
PMCID: PMC3474271  PMID: 23109802
photodynamic therapy; mitomycin C; trabeculectomy; open angle glaucoma; ultrasonic biomicroscopy
9.  Recurrent bleb infections 
AIM—To report the patient characteristics, causative organisms, and clinical outcomes in patients with recurrent bleb related ocular infections.
METHODS—The medical records of all patients diagnosed with bleb related ocular infection at the New York Eye and Ear Infirmary over a 10 year period were reviewed. Recurrent bleb infection was defined as at least two episodes of bleb purulence with or without associated intraocular inflammation separated by a quiescent period of at least 3 months.
RESULTS—Recurrent bleb infections developed in 12 eyes of 12 patients (10 men, two women) a mean of 16.3 (SD 17.9) months (range 3-51 months) after the initial infection. Two patients developed a third episode 3 and 20 months, respectively, after the second infection, yielding a total of 14 recurrent infection episodes. Recurrent infection developed after trabeculectomy in 11 eyes (adjunctive 5-fluorouracil, nine eyes; mitomycin C, one eye; no antifibrosis agent, one eye) and following cataract extraction with inadvertent bleb formation in one eye. Four (36.4%) of the filtered eyes had undergone trabeculectomy at the inferior limbus. The mean follow up time from filtering surgery to the first bleb related infection was 28 months for the nine patients treated with 5-fluorouracil and 14 months for the single patient treated with mitomycin C. 11 (78.6%) cases had a documented bleb leak in the 4 week period before or at the time of recurrent infection. Topical, prophylactic antibiotics had been used in 7/14 (50%) cases. The same organism was cultured from the initial and recurrent infections in 2/14 (14.3%) cases.
CONCLUSION—Eyes that have been successfully treated for bleb related infection remain at risk for recurrent infection. No apparent correlation exists between organisms responsible for the initial and recurrent infections. The increased rate of recurrent bleb related infection in patients receiving adjunctive 5-fluorouracil compared to mitomycin C may have been related to the longer follow up of the 5-fluorouracil eyes.

 Keywords: blebs; ocular infections; 5-fluorouracil; mitomycin C
PMCID: PMC1722708  PMID: 9828779
10.  Effects of Honghua preserved amniotic membrane on scar healing in experimental glaucoma surgery 
To investigate the efficacy and safety of Honghua preserved amniotic membrane (AM) for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.
Totally 36 rabbits (36 eyes) were randomly divided into 3 groups: the experimental group (ocular trabeculectomy in combination with Honghua preserved AM transplantation), the control group (ocular trabeculectomy surgery in combination with AM implantation), and the blank group (single trabeculectomy). Clinical observations [including intraocular pressure (IOP), filtering blebs and complications], Masson-Trichrome staining, real-time quantitative reverse transcription-polymerase chain reaction (real-time PCR), Western blot were performed on different time points (D1, D7, D14, D21 and D56) after the surgery.
After operated for 14d, there were statistically significant differences in the filtering blebs compared to the situation before operation (P<0.05), whereas no statistically difference on that among three groups (P>0.05). After 21d, the IOP of experimental group was lowest (P<0.05). There was significant difference between control group and blank group (P<0.05). On postoperative D14, the mean number of fibroblasts in the experimental group was significantly lower (40.6±10.2) compared to those in the control group (54.4±10.8) and blank group (68.2±11.6) (P<0.05, respectively). The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group (P<0.05, P<0.05, respectively). Compared to that in blank group, the level of transforming growth factor-β (TGF-β1) expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level (P<0.05), but not significant difference between these two groups (P>0.05).
The trabeculectory surgery with Honghua preserved AM can control IOP, sustain the functional filtration bleb, inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.
PMCID: PMC4003074  PMID: 24790862
amniotic membrane; trabeculectomy; Honghua injection; implant; transforming growth factor-β; scar formation
11.  Augmentation of Filtering Blebs with Viscoelastics in Trabeculectomy 
To evaluate the clinical outcome of viscoelastics (VE, sodium hyaluronate)-augmented trabeculectomy (VAT, 66 eyes) and conventional trabeculectomy (CT, 57 eyes) for glaucomatous eyes.
In the VAT group, half of the anterior chamber space was filled with VE via the paracentesis site at the end of CT and a balanced salt solution was injected into the anterior chamber. This procedure induced migration of VE from the anterior chamber into the bleb space; thus the bleb was elevated with underlying VE. Follow-up examinations were performed until 1 year after surgery. Success was defined as the attainment of an intraocular pressure (IOP) greater than 5 mmHg and less than 22 mmHg. If IOP was in the range of success without antiglaucoma medication, it was regarded as a complete success.
The mean postoperative IOP was significantly lower in the VAT group at postoperative 1 day, 1 week, and 1 month. The complete success rate was significantly higher in the VAT group (89%) than in the CT group (75%), though the qualified success rate was not different between the two groups. The number of IOP-lowering medications at postoperative 1 year was significantly higher in the CT group (1.30 ± 1.08 vs. 0.73 ± 0.98, p = 0.003). Among postoperative procedures, laser suture lysis was required less frequently in the VAT group (p < 0.001).
Placing VE within the bleb at the end of surgery may result in better IOP control and less need for IOP-lowering medication without any additional materials, cost, or time.
PMCID: PMC4179116  PMID: 25276081
Anti-fibrotic agent; Glaucoma; Hyaluronic acid; Trabeculectomy; Viscoelastics
12.  A comparative study of the safety and efficacy effect of 5-fluorouracil or mitomycin C mounted biological delivery membranes in a rabbit model of glaucoma filtration surgery 
To investigate the potential usage of biological delivery membranes containing mitomycin C (MMC) or 5-fluorouracil (5-FU) in the construction of glaucoma-filtering blebs, and to evaluate their safety and efficacy.
Chitosan was selected as the biological membrane carrier to prepare sustained-released membranes. Twelve micrograms of 5-FU or MMC was covalently conjugated onto the membranes by solvent volatilization. Rabbits underwent glaucoma filtration surgery and were randomly allocated into one of the four treatment regimens: glaucoma filtration operation with no implantation of chitosan membrane group (as control), drug-free chitosan membrane implantation group (blank/placebo group), membrane containing 5-FU treatment group (5-FU group), and membrane containing MMC treatment group (MMC group). Each group consisted of 12 rabbits. Intraocular pressure (IOP) was measured and evaluated over a 28-day period follow-up preoperatively, then after surgery on days 1, 3, 5, 7, 14, 21, and 28 by Tono-Pen. The aqueous humor was analyzed in each experimental and control groups at days 4, 6, 8, 10, 12, 14, 16, and 20 after operation. Bleb survival and anterior segment were examined with a slit lamp microscope and photographed simultaneously. Two rabbits from each group were killed on day 28 and eight eye samples obtained for histopathological study. Corneas and lenses were examined by transmission and scanning electron microscopy.
Both 5-FU and MMC significantly prolonged bleb survival compared with control groups. The filtering bleb’s survival period was significantly more prolonged in the MMC and 5-FU groups (maintained 14 days) than the other two groups (maintained 7 days). Significantly lower IOP was observed within the control, blank, and 5-FU groups after surgery on day 14 compared with that before operation, with F-values of 6.567, 11.426, and 13.467, respectively (P < 0.01). The most significant lower IOP was recorded in the MMC group on day 28 postoperation (F-value 26.866, P < 0.01). No obvious abnormalities were found in cornea or anterior lens capsule 28 days after surgery.
The study provided evidence that 5-FU and MMC biological delivery membranes could significantly improve the outcome of filtering procedures, the survival of the bleb, and maintenance of lower IOP. MMC membrane is superior to 5-FU, with regard to the more effective reduction of IOP. The results indicated a safe and effective treatment strategy in glaucoma surgery.
PMCID: PMC3616693  PMID: 23576864
chitosan; biological delivery; mitomycin C (MMC); 5-fluorouracil (5-FU); glaucoma
13.  Post-trabeculectomy topical bevacizumab preventing bleb failure: a preliminary study 
This study aims to evaluate the efficacy and safety of post-trabeculectomy topical bevacizumab, in preventing bleb failure. A total of 11 females and 12 males were enrolled for the study. After a complete ophthalmic evaluation, the patients underwent trabeculectomy. Full ophthalmic examination was done the next day, which included visual acuity, intraocular pressure (IOP), and bleb morphology. Next, two drops of bevacizumab [0.25 mg (0.01 ml)] were instilled over the wound area with a tuberculin (1 ml) syringe. Pressure was applied at the medial canthus to prevent it from going into the lacrimal passage. Similar postoperative procedures were repeated at 1, 2, 3, and 4 weeks. So in all, five instillations of bevacizumab were completed. Later, the patients were followed at 1-month interval for 6 months. Target IOP was achieved in all eyes and was maintained during the study period of 6 months without any anti-glaucoma medication. Average IOP before trabeculectomy was 27.27 ± 8.92 mmHg, which decreased postoperatively to 8.77 ± 0.97 mmHg at 3 months and 9.27 ± 1.16 mmHg at 6 months. This drop in IOP was statistically significant on both occasions (p = 0.00). A nice low filtering bleb was formed after the surgery, and it remained the same during the study period. The other parameters like cup-to-disc ratio and visual field did not change during the 6 months of study as expected because glaucoma is a slow progressive disease. Modulating the wound at multiple sites by bevacizumab (inflammation, proliferative, and remodeling stages) can lead to success of trabeculectomy.
PMCID: PMC3709035  PMID: 24596946
Trabeculectomy; Topical bevacizumab; Wound healing
14.  Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy 
Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU) injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP) outcome, bleb morphology, postoperative medications, and complications was evaluated.
Glaucoma patients (N = 61) who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months). Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab.
Group 1 had 6.4 ± 3.3 (0–15) (mean ± standard deviation and range, respectively) 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12) (mean ± standard deviation and range, respectively) 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005). There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU), yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008). No significant difference in best corrected visual acuity (P = 0.852) and visual field testing (P = 0.610) between preoperative to last follow-up could be found between the two groups.
The postoperative injection of bevacizumab reduced the number of subconjunctival 5-FU injections significantly by 2.4 injections. A significant difference in postoperative IOP reduction, bleb morphology, and postoperative medication was not detected.
PMCID: PMC3693864  PMID: 23814458
bevacizumab; 5-fluorouracil; glaucoma; trabeculectomy; bleb failure; bleb scarring
15.  Tear fluid signs associated with filtration blebs, as demonstrated by three-dimensional anterior segment optical coherence tomography 
To determine the clinical features of tear fluid signs associated with filtration blebs via three-dimensional anterior segment optical coherence tomography (3D AS-OCT).
In total, 152 eyes (130 patients) with glaucoma that underwent trabeculectomy with mitomycin C were evaluated retrospectively. We investigated tear fluid signs associated with filtration blebs, using 3D AS-OCT with custom software, and compared the findings of lower tear meniscus. We also analyzed postoperative intraocular pressure and the bleb parameters of filtration blebs between eyes with and without tear fluid signs.
We found tear fluid signs associated with filtration blebs in 45 (30%) of 152 eyes. The mean postoperative intraocular pressure of the eyes with the tear fluid sign in a filtration bleb was significantly lower than that in eyes without the tear fluid sign (P<0.001). Blebs with tear fluid signs have more frequent identifiable filtration openings, greater total height, increased fluid-filled cavity height, and less wall intensity compared with blebs without these signs.
We identified tear fluid signs in AS-OCT images on or along filtration blebs that depended on bleb morphology. The occurrence of these signs may be related to the presence of functional blebs, which may thereby control postoperative intraocular pressure.
PMCID: PMC4000242  PMID: 24790405
filtration bleb; trabeculectomy; 3D AS-OCT; tear fluid sign
16.  Blunt needle revision with viscoelastic materials via the anterior chamber for early failed filtering blebs after trabeculectomy 
To report a new technique of blunt needle revision with viscoelastic materials via the anterior chamber for the treatment of early failed filtering blebs and elevated intraocular pressure after trabeculectomy, in which digital ocular massage and laser suture lysis have been ineffective.
A 27-gauge blunt needle attached to a syringe containing viscoelastic material was inserted into the anterior chamber from the inferior paracentesis. The needle tip was inserted into the subscleral flap space from the filtering fistula at the anterior chamber side, and the scleral flap was lifted bluntly. The needle tip was then inserted into the subconjunctival space where the viscoelastic agent was injected and the adhesion between the sclera and conjunctiva was separated bluntly. Blunt needle revision via the anterior chamber was performed 14 times in six eyes of six patients at Saitama Medical Center, Jichi Medical University from January 2007 to May 2009. All procedures were performed within 1 month after trabeculectomy.
The intraocular pressure remained 21 mmHg or lower for more than 6 months in three of six eyes. Slight bleeding from the iris occurred in one of the 14 procedures, and hypotony (intraocular pressure below 5 mmHg) occurred in one of the 14 procedures. No serious complications developed.
Blunt needle revision via the anterior chamber for early failed filtering blebs is a new, simple, and safe procedure.
PMCID: PMC3392926  PMID: 22791972
glaucoma; trabeculectomy; filtering bleb; needle revision; blunt needle
17.  Analysis of bleb morphology after trabeculectomy with Visante anterior segment optical coherence tomography 
To describe the use of anterior segment optical coherence tomography (OCT) in imaging intrableb morphology after trabeculectomy.
14 post‐trabeculectomy eyes from 11 primary open angle glaucoma and 3 primary angle closure glaucoma subjects were studied. The blebs were classified with reference to slit lamp morphology and bleb function. They included diffuse filtering (n = 7), cystic (n = 2), encapsulated (n = 2) and flattened (n = 3) bleb types. One eye in each patient was imaged with the Visante anterior segment OCT. A vertical scan line of 10 mm consisting of 512 A‐scans was positioned at the centre of the bleb. The images were then analysed by built‐in software. Intrableb morphologies and structures, including bleb wall thickness, subconjunctival fluid collections, suprascleral fluid space, scleral flap thickness, intrableb intensity (low, medium or high) and the route under the scleral flap were characterised and measured.
Diffuse filtering blebs were found by subconjunctival fluid collections. Suprascleral fluid space and the route under the scleral flap were identified in four of the seven cases. Cystic blebs were composed of a large hyporeflective space with multiloculated fluid collections covered by a thin layer of conjunctiva. Encapsulated blebs had a thick bleb wall with high reflectivity and an enclosed fluid filled space. Flattened blebs demonstrated high scleral reflectivity and no bleb elevation.
Visante anterior segment OCT can be used for bleb imaging. The different patterns of intrableb morphology identified by OCT were related to slit lamp appearance and bleb function. This information may be useful to study the different surgical outcomes and the process of wound healing in trabeculectomised eyes.
PMCID: PMC1857643  PMID: 17005548
18.  Human pericardium graft in the management of bleb's complication performed in childhood: a case report 
BMC Ophthalmology  2011;11:27.
To report a case with hypotony due to late leakage of the filtering bleb performed during childhood and treated surgically using human pericardium graft.
Case Presentation
A man with hypotony related to bleb's leakage in his right eye was presented. During his childhood trabeculectomy was performed to manage ocular hypertension due to pediatric glaucoma. Biomicroscopy revealed choroidal tissue incarcerated in the sclerectomy under the conjunctiva. Bleb revision was performed. Human pericardium graft was used to cover the sclerectomy and a new bleb with controlled outflow was created. The intraocular pressure (IOP) and Seidel test represent the main outcomes. Intraoperative and postoperative complications were recorded. Fifteen days postoperatively the IOP was of 7 mmHg and the bleb seemed to filter properly. Five months later the IOP was 9 mmHg and no complications were noticed. During the follow up time, the Seidel test was negative.
We used human pericardium graft with no complications in a case of bleb leakage performed for pediatric glaucoma.
PMCID: PMC3189896  PMID: 21933427
late bleb leakage; human pericardium; bleb revision; pediatric glaucoma
19.  Inhibitory effect of biopolymer materials on scar formation following trabeculectomy 
To investigate the inhibitory effects of amniotic membrane, polylactic acid membrane and chitosan membrane on scar formation following trabeculectomy.
A total of 24 New Zealand white rabbits (48 eyes) were randomly divided into 4 groups: amniotic membrane group, polylactic acid membrane group, chitosan membrane group, and control group, with 6 rabbits (12 eyes) in each group. The left eyes underwent routine trabeculectomy, and the right eyes were considered as controls. Amniotic membrane, polylactic acid membrane and chitosan membrane were respectively installed under sclera flap in three groups, but any treatment was not applied in control group. Intraocular pressure, conjunctival filtering bleb, and anterior chamber inflammation responses were monitored at day 1, 3, 7, 14, 28 and 56 post-operatively. Eyeball tissue underwent histopathological examination at day 56 post-operatively.
Fibrocytes and inflammatory cells were reduced in amniotic membrane, polylactic acid membrane and chitosan membrane groups compared to that in control group. At day 1 post-operatively, intraocular pressure was decreased in three membrane groups compared to that in control group. At day 14 post-operatively, the intraocular pressure was decreased significantly, while it of three membrane groups was significantly lower than that of preoperative (P<0.01). There were no significant differences among three membrane groups (P>0.05). Filtering bleb of four groups was clearly observed at day 7 post-operatively, but there was no significant difference in pair-wise comparison. At day 28 and 56 post-operatively, filtering bleb in control group was significantly narrowed compared to that in three membrane groups (P<0.05), but there was no significant difference in pair-wise comparison of three membrane groups.
All amniotic membrane, polylactic acid membrane and chitosan membrane can effectively inhibit scar formation following trabeculectomy, the effect of amniotic membrane is the best.
PMCID: PMC3340860  PMID: 22553685
amniotic membrane; polylactic acid membrane; chitosan membrane; glaucoma; filtration surgery
20.  Suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor 
Molecular Vision  2010;16:1880-1892.
Transforming growth factor-β (TGF-β) activity has been implicated in subconjunctival scarring in eyes following glaucoma filtration surgery (GFS). The purpose of this study is to determine whether an inhibitor for activin receptor-like kinase (ALK) 5 (also known as TGF-β receptor type I) could suppress TGF-β activity and thereby promote filtering bleb survival after GFS in a rabbit model.
An ALK-5 inhibitor, SB-505124, was used. A docking study was performed to investigate the interaction between the inhibitor and the receptor. Immunofluorescence for connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) was performed in cultured rabbit subconjunctival fibroblasts. Immunoblotting for phosphorylated Smad2 (pSmad2), CTGF, and α-SMA was also performed. In an in vivo rabbit GFS model, SB-505124 was delivered in a lactose tablet during surgery. Eyes were examined by slit-lamp and intraocular pressure (IOP) was measured until the time of bleb failure or up to 28 days after surgery. Tissue sections on day 5 after surgery were histologically evaluated after staining with hematoxylin and eosin. The sections were also immunostained for CTGF and α-SMA. In addition, cell outgrowth from dissected subconjunctival tissues placed in a cell culture flask with media was investigated.
The docking study indicated hydrogen bond interactions between SB-505124 and amino acids His-283 and Ser-280 of ALK-5. Suppression of pSmad2, CTGF, and α-SMA by SB-505124 was observed in cultured fibroblasts. Filtering blebs in the GFS with SB-505124 group were maintained for more than 10 days, and the period of bleb survival was significantly longer than that in controls. IOP levels after surgery seemed to be related to bleb survival. Histologically, subconjunctival cell infiltration and scarring at the surgical site in the GFS with SB-505124 and mitomycin C (MMC) groups were much subsided compared to controls. Suppression of CTGF and α-SMA by SB-505124 was also observed by immunofluorescence. Cell outgrowth from explants dissected from eyes to which SB-505124 was applied during GFS was robust while outgrowth was poor from those treated with MMC.
The ALK-5 inhibitor SB-505124 was efficacious both in vitro and in vivo in suppressing the TGF-β action. The inhibitor may provide a novel therapy for preventing ocular inflammation and scarring.
PMCID: PMC2956700  PMID: 21031133
21.  Photodynamic modulation of wound healing in glaucoma filtration surgery 
Aim: To report a clinical pilot study investigating photodynamic therapy (PDT) in combination with glaucoma filtration surgery. BCECF-AM was used as the photosensitising substance. The clinical safety and tolerability of BCECF-AM, and its efficacy in controlling postoperative intraocular pressure (IOP) were assessed.
Methods: Before trabeculectomy (TE), 42 consecutive eyes of 36 glaucoma patients received one subconjunctival injection of 80 μg BCECF-AM (2,7,-bis- (2-carboxyethyl) -5- (and-6) -carboxy-fluorescein, acetoxymethyl-ester) followed by an intraoperative illumination with blue light (λ = 450–490 nm) for 8 minutes. Antifibrotic efficacy was established as postoperative IOP reduction of >20% and/or an IOP constantly < 21 mm Hg without antiglaucomatous medication. Follow up of the filtering bleb was documented by slit lamp examination.
Results: Eyes had mean 1.1 preoperative surgical interventions (filtration and non-filtration glaucoma surgery). Mean preoperative IOP was 31.6 (SD 9.7) mm Hg. Patients were followed for mean 496 days (range 3.5–31.8 months). Of the 42 eyes, 25 eyes had an IOP decreased to 15.8 (3.4) mm Hg without medication (complete success: 59.5%; p<0.001; t test). Seven eyes showed good IOP reduction < 21 mm Hg under topical antiglaucomatous medication (qualified success: 16.7%). 10 eyes failed because of scarring within 2–67 weeks (23.8%). Clinical follow up examinations revealed no local toxicity, no uveitis, and no endophthalmitis.
Conclusions: This method is a new approach in modulating postoperative wound healing in human eyes undergoing glaucoma filtration surgery. The data of the first human eyes combining TE with PDT underline the clinical safety of this method and its possible potential to prolong bleb survival.
PMCID: PMC1771734  PMID: 12812889
wound healing; glaucoma filtration surgery
22.  Pars plana vitrectomy for malignant glaucoma in nonglaucomatous and in filtered glaucomatous eyes 
To assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery.
Patients and methods
Data of 15 patients developing malignant glaucoma after trabeculectomy (60%) or following ophthalmic interventions other than filtration surgery (40%) were recorded retrospectively. Pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor. The main outcome measures were the postoperative intraocular pressure (IOP), the frequency of complications, and success rate based on the following criteria: IOP reduction by ≥20% and to ≤21 mmHg (definition one) or an IOP < 18 mmHg (definition two) with (qualified success) and without (complete success) glaucoma medication.
Vitrectomy reduced IOP from baseline in eyes with and without previous trabeculectomy during a median follow-up of 16.4 months (range 7 days to 58 months); although the majority of patients required glaucoma medication to reach desired IOP. The complete success rates were 11% (both definitions) for patients with filtering blebs and none of the patients without previous trabeculectomy had complete success at the 12-month visit. Complications were few and included transient shallowing of the anterior chamber, choroidal detachment, corneal decompensation, filtering bleb failure, and need for further IOP-lowering procedures.
Pars plana vitrectomy is equally effective for malignant glaucoma caused by trabeculectomy or interventions other than filtration surgery, although IOP-lowering medication is necessary in nearly all cases to maintain target IOP.
PMCID: PMC3514060  PMID: 23226000
ciliolenticular block glaucoma; malignant glaucoma; pars plana vitrectomy; trabeculectomy
23.  A Review of Trabeculectomies at a Nigerian Teaching Hospital 
Ghana Medical Journal  2007;41(4):176-180.
Trabeculectomy is the commonest surgical procedure for glaucoma. The outcome of trabeculectomy in the treatment of all types of glaucoma over a 4-year period in a Nigerian population was reviewed.
To determine the surgical rate and effectiveness of trabeculectomy in lowering of intra ocular pressure (IOP) and preservation of visual acuity.
Retrospective review of all trabeculectomies (TEs) done at the Obafemi Awolowo University Teaching Hospital, Ile-Ife between January 1999 and December 2002. The outcome of trabeculectomy was correlated with the biomicroscopic appearance of the filtering bleb, visual acuity and IOP levels. Descriptive statistics were applied to the data.
Of the 647 glaucoma patients only fifty-three (8.2%), 34 males and 19 females, had trabeculectomy done during the study period. Seventy-two consecutive eyes of these 53 Nigerian patients were operated upon. Majority, 63 (87.5%) were in the primary glaucoma group of which 46 (63.9%) were open angle glaucoma type. Nine eyes (12.5%) belonged to the secondary glaucoma group (neovascular, uveitic and traumatic angle recession). Successful control of intra-ocular pressure with medical therapy was recorded only in 13.9% of the patients. The mean pre-operative and first post-operative day IOP were 32.5+/− 6.2mmHg and 10.6+/− 2.3mmHg respectively. Mean post-op IOP at 3 months and one year were 14.6+/− 4.2mmHg, and 13.5+/− 5.8mmHg respectively. One year after surgery 34 eyes (61.8%) had intraocular pressure (IOP) of 20mm Hg or less without glaucoma medication. Hyphema 11 (15.3%) was the commonest post-operative complication documented.
Surgical intervention in the management of glaucoma, especially trabeculectomy is not commonly done in this Teaching Hospital. IOP control with medication alone is not adequate in the long term. A significant proportion of the eyes (61.8%) had complete success in IOP control following trabeculectomy.
PMCID: PMC2350112  PMID: 18464899
Glaucoma; Trabeculectomy; Intra-ocular pressure; Nigeria
24.  A randomised, prospective study comparing trabeculectomy with viscocanalostomy with adjunctive antimetabolite usage for the management of open angle glaucoma uncontrolled by medical therapy 
The British Journal of Ophthalmology  2004;88(8):1012-1017.
Aims: To compare trabeculectomy with viscocanalostomy augmented with adjunctive antimetabolite use for the control of intraocular pressure (IOP) in open angle glaucoma (OAG).
Methods: 45 patients (50 eyes) with uncontrolled OAG were randomised to either trabeculectomy (25 eyes) or a viscocanalostomy technique (25 eyes). Preoperatively, all eyes were graded in terms of risk factors for drainage failure and were given intraoperative antimetabolites (5-fluorouracil 25 mg/ml (5-FU), mitomycin C (MMC) 0.2 mg/ml and 0.4 mg/ml) according to a standard protocol.
Results: There were no significant differences between the groups in age, sex, type of OAG, preoperative medications, risk factors for drainage failure, and preoperative IOP. Mean follow up was 20 months (range 3–24 months). It was 12 months or longer in all eyes, except two lost to follow up at 3 months. At 12 months, complete success (IOP<21 mm Hg without antiglaucoma medications) was seen in 91% of eyes undergoing trabeculectomy, but in only 60% of eyes undergoing viscocanalostomy (p<0.02). Similarly, at the last follow up visit (mean 20 months) complete success was seen in 68% of eyes undergoing trabeculectomy and 34% with viscocanalostomy (p<0.05). In terms of qualified success (IOP<21 mm Hg with or without glaucoma medications) and mean IOP measurements postoperatively there were no difference between the groups, although the mean number of antiglaucomatous medications required postoperatively was less with trabeculectomy (0.39) than viscocanalostomy (1.04) (p<0.05). Needling procedures were more commonly required after trabeculectomy (p<0.02). YAG goniotomy was required in three eyes (13%) after viscocanalostomy. Early transient complications such as anterior chamber shallowing and encysted blebs were more common in the trabeculectomy group (p<0.05). Late postoperative cataract formation was similar between the two groups.
Conclusion: In terms of complete success and number of antiglaucomatous medications required postoperatively, IOP control appears to be better with trabeculectomy. Viscocanalostomy is associated with fewer early transient postoperative complications.
PMCID: PMC1772277  PMID: 15258016
trabeculectomy; viscocanalostomy
25.  The use of amniotic membrane in trabeculectomy for the treatment of primary open-angle glaucoma: a prospective study 
To investigate the effectiveness of amniotic membrane transplantation (AMT) on improving the outcomes of trabeculectomy in primary open-angle glaucoma (POAG).
Fifty-nine eyes affected by primary open-angle glaucoma were enrolled in this prospective randomized study. Thirty-two eyes underwent amnion-shielded trabeculectomy (study group) and 27 eyes underwent trabeculectomy without any antimetabolites (control group). Success was defined as intraocular pressure (IOP) <21 mmHg without any medications at 24 months follow-up. The two groups were compared in terms of IOP, bleb morphology, bleb survival and risk of failure, glaucoma medications, and complications.
There was no statistically significant difference in terms of postoperative IOP between the two groups and at 24 months median IOP was 15.5 mmHg for the AMT group and 16 mmHg for the control group. IOP postoperative reduction was 8 mmHg for the AMT group versus 6 mmHg for the non AMT group (P = 0.276). Two patients from the study group developed IOP >21 mmHg in contrast to seven patients from the classic trabeculectomy group. The study group had 61.0% less risk of developing IOP >21 mmHg (P = 0.203). No major complications in the AMT group were observed. AMT blebs were diffuse with mild vascularization.
In patients with POAG, AMT showed favorable effects on bleb survival, however data failed to provide firm evidence that AMT could be used as a routine procedure in trabeculectomy.
PMCID: PMC3280101  PMID: 22347791
amniotic membrane; trabeculectomy; primary open-angle glaucoma; glaucoma filtering bleb

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