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Year : 2012  |  Volume : 19  |  Issue : 2  |  Page : 216-221  

Office-based slit-lamp needle revision with adjunctive Mitomycin-C for late failed or encapsulated filtering blebs

1 Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Razavi Hospital, Mashhad, Iran

Date of Web Publication21-Apr-2012

Correspondence Address:
Ramin Daneshvar
Farabi Eye Hospital, Qazvin Sq., South Kargar St., Tehran 1336616351
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-9233.95255

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Purpose: 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.
Results: 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).
Conclusion: 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.

Keywords: Bleb Needling, Bleb Revision, Filtering Surgery, Glaucoma, Mitomycin-C

How to cite this article:
Amini H, Esmaili A, Zarei R, Amini N, Daneshvar R. Office-based slit-lamp needle revision with adjunctive Mitomycin-C for late failed or encapsulated filtering blebs. Middle East Afr J Ophthalmol 2012;19:216-21

How to cite this URL:
Amini H, Esmaili A, Zarei R, Amini N, Daneshvar R. Office-based slit-lamp needle revision with adjunctive Mitomycin-C for late failed or encapsulated filtering blebs. Middle East Afr J Ophthalmol [serial online] 2012 [cited 2022 Dec 8];19:216-21. Available from: http://www.meajo.org/text.asp?2012/19/2/216/95255

   Introduction Top

Trabeculectomy in the era of adjunctive antifibrotic agents is highly successful. However, gradual failure is common, as more than 80% of early successes drop to almost 50% after 5-year follow-up with 5-flurouracil (5-FU) filtration. [1] Subconjunctival and episcleral fibrosis could result in failure of filtration bleb with a thick or localized bleb having low or no filtration. [2],[3]

Filtration bleb failure can result in an increase in intraocular pressure (IOP) and if maximal tolerable medical therapy could not control the rise in IOP, surgical intervention including laser trabeculoplasty, repeated trabeculectomy, glaucoma drainage device surgery, or rescue of filtration bleb with revision of a previous surgical site, is necessary. Each surgical modality has inherent advantages and disadvantages. A second trabeculectomy at a new site may not necessarily be the optimum initial choice, as surgery in an area with scarred conjunctiva is usually more difficult and has an increased chance of failure, even with the use of 5-FU or MMC. [4],[5],[6] Shunting procedures with a glaucoma drainage device may not adequately lower the IOP for severe glaucoma, and have their own set of associated risks and complications. [7] Cyclodestructive procedures are associated with even greater unpredictability and carry a significant risk of visual loss and phthisis bulbi. [8] Hence, the choice of intervention should be individualized according to patient status and surgeon preference.

Needling bleb revision is a simple approach for rescuing failed filtration and is feasible both at the slit lamp and under operating microscope. Although multiple studies have been published regarding the efficacy and safety of needle bleb revision for failed trabeculectomies, [9],[10],[11],[12],[13],[14],[15],[16],[17] comparison of results is tenuous at best, due to variations of surgical technique, dosage of antimetabolites, time elapsed between filtration surgery and revision, length of follow-up period and racial differences of the study cohort. Adding any reliable results to the current pool of data would help to perform future meta-analyses and allow surgeons to compare techniques to select a procedure. The purpose of current study was to examine the safety and efficacy of office-based, needle bleb revision at slit-lamp for late failed (flat or encapsulated) bleb with adjuvant mitomycin-C.

   Materials and Methods Top

A comprehensive chart review was performed to collect data on all patients who underwent needle bleb revision at slit lamp with adjunctive mitomycin-C (MMC), between October 2003 and November 2008. Only glaucomatous eyes with late failed (flat or encapsulated) filtration bleb that received adjunctive MMC during initial filtering surgery were reviewed. From October 2003 to November 2008, 142 needling bleb revisions were performed with only 27 being performed at more than 6 months following initial trabeculectomy surgery that were suitable for inclusion in this study. The study adhered to the tenets of declaration of Helsinki.

For performing needling revision, visibility of the scleral flap border through overlying conjunctiva was a prerequisite and was attempted in encapsulated cases after compressing the bleb. Patients with advanced conjunctival scar and invisible flap border and those with a history of blebitis were excluded. All patients were on maximally tolerable antiglaucoma medications and the IOP was considered above the target pressure, conducive to further optic nerve damage.

Surgical technique

One of authors (H.A.) performed all needle bleb revisions in his private practice. Patients signed an informed written consent prior to the procedure. Two drops of tetracaine 1% (Anestocaine® , Sina Darou, Tehran, Iran) were instilled in the eye and after 5 minutes three drops of povidone-iodine 5% were placed in the inferior cul-de-sac of the eye. The eyelids were cleansed with a 5% povidone-iodine solution in a sterile manner. After an additional 5 minutes, the eye was rinsed with artificial tears (SinaTears® , Sina Darou, Tehran, Iran) to remove residual povidone-iodine. The patient was positioned at the slit lamp and a sterile speculum was inserted, a disposable insulin syringe with a 27-gauge needle was inserted into the subconjunctival space adjacent to bleb site with a temporal approach. This procedure was performed with the surgeon's right hand for the patient's left eye and vice versa for the right eye. Subconjunctival scarring was disrupted with a sweeping movement as the needle advanced toward the scleral flap. In encapsulated blebs, faint aqueous flow along with bleb enlargement was often notified during the procedure. The needle was advanced under the sclera flap and the flap was lifted with gentle side-to-side movement, breaking episcleral adhesions. If simple flap dissection failed to form a noticeable bleb, the needle was inserted into the anterior chamber through the ostium site to ensure sufficient filtration. The needle was then removed and hand-held cautery was applied to the conjunctival entry site to seal the conjunctiva. Subconjunctival injection of 0.1 ml of 0.2 mg/ml MMC (Mitomycin-C Kyowa, Kyowa Hakko Kogyo Co Ltd., Tokyo, Japan) was given via a separate injection site superior to the bleb, approximately 10 mm from the sclera fistula. A cotton-tip applicator was used to compress the entry site, allowing for more complete closure. At the conclusion of the procedure, one drop each of chloramphenicol 0.5% (Chlobiotic® , Sina Darou, Tehran, Iran) and betamethasone 0.1% (Betasonate® , Sina Darou, Tehran, Iran) were instilled in the eye and the eye was patched.

At one day follow up, the patient was re-examined and chloramphenicol 0.5%, betamethasone 0.1%, and atropine 1% (Atrin® , Sina Darou, Iran) eye drops were administered four-times daily and tapered slowly over the next 4 weeks. Follow-up visits were scheduled for postoperative week 1, the 1st month, at 6 months, at 12 months and every 6 months thereafter. At each follow-up visit, Snellen visual acuity testing, intraocular pressure measurement with Goldmann applanation tonometry, and anterior and posterior segment evaluation were performed and postoperative complications were documented. Further needling was considered if the first procedure failed to achieve the desired target pressure. "Complete success" was defined as an IOP ≤ 21 mmHg and > 5 mmHg without any antiglaucoma medication and "qualified success" was defined as a postneedling IOP ≤ 21 mmHg and > 5 mmHg with antiglaucoma medications usage. The procedure was considered "failed" if the IOP was > 21 mmHg or < 5 mmHg or if additional surgery (except repeated needling) was required.

Statistical analysis

Statistical analysis was performed with SPSS software (Ver. 15, SPSS Inc, Chicago, Illinoise, USA). The paired t-test was used to compare IOP and number of medications before and after the procedure along with Kaplan-Meier survival analysis of the success. Final IOP was compared between encapsulated and flat blebs, using independent sample t-test. Fisher's exact test was used to compare success rates based on preoperative bleb morphology. Statistical significance was set at P<0.05.

   Results Top

In the study period, needling bleb revision was performed in 27 eyes of 27 patients. The mean age of the patients was 56.5 ± 16.2 years (range, 27-80 years). Nineteen patients (70.4%) were female. There were 15 right eyes (55.6%). Various types of glaucoma were included, with primary open angle glaucoma being the most frequent [Table 1]. Mean preoperative intraocular pressure was 25.07 ± 4.80 mmHg (range, 17-40 mmHg). The average interval between initial trabeculectomy and first revision was 32.74 ± 15.36 months (range, 6-60 months). Mean follow-up was 20.31 ± 15.63 months (range, 6-61 months; median, 13 months; more than 11 months in 20 (74.07%) eyes). Mean pre- and postoperative logarithm of the minimum angle of resolution (logMAR) uncorrected visual acuity were 0.48 ± 0.33 and 0.42 ± 0.34, respectively; however, best-corrected visual acuity was unavailable for a substantial proportion of the patients.
Table 1: Type of glaucoma in the study population (n=27)

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Failed blebs were encapsulated in 12 eyes (44.44%) and flat or fibrotic in 15 eyes (55.55%). Mean needling number was 1.37 ± 0.79 (range, 1-4; median and mode: 1). Only six eyes underwent more than one needling; of these, three patients had two, two patients had three, and one patient had four needling procedures.

The reduction in IOP after the procedure was statistically significant (P<0.05) [Table 2]. Final IOP reduction was not significantly different between the two bleb groups (P=0.955). The mean number of preoperative antiglaucoma medications was 3.15 ± 0.36 and reduced to 2.33 ± 1.21 postoperatively (P<0.001). Complete success and qualified successes were achieved in 2 (7.4%) and 14 (51.9%) eyes, respectively, summing up to an overall success rate of 59.3%. The procedure failed to revive the proper filtration in 11 (40.7%) eyes. Success and failure rates, based on different types of blebs, are presented in [Table 3]. There was no statistically significant difference in success rates based on preoperative bleb morphology (P=0.619).
Table 2: Intraocular pressure before and after bleb needling at slit lamp for late failed filtering bleb

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Table 3: Success and failure rates of needling bleb revision, based on preoperative bleb morphology (percent in parenthesis)

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Using Kaplan-Meier survival analysis, the estimated mean time to failure following needling was 34.32 ± 5.43 months with a 95% confidence interval of 23.67 to 44.97 months [Figure 1]. Estimated mean times to failure following needling bleb revision, based on preoperative bleb morphology, are represented in [Table 4] and cumulative rates of successes at 60 months are represented in [Table 5].
Figure 1: Kaplan Meier plot of the cumulative probability of success following office-based bleb needling for late trabeculectomy failure (n=27)

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Table 4: Estimated mean time to failure following needling bleb revision, based on preoperative bleb morphology (months)

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Table 5: Survival table of success at various intervals following office-based bleb needling for late bleb failure

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The only postoperative complication was a small hyphema in two patients, which resolved spontaneously. In addition, we had conjunctival avascularity at the site of MMC injection in one patient, which did not progress to a scleral melt and was managed conservatively with frequent topical lubrications [Figure 2].
Figure 2: Conjunctival avascularity at the site of mitomycin-C injection in a patient who underwent needle bleb revision at the slit lamp for late filtering bleb failure

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   Discussion Top

There are several management options for failed filtering blebs including bleb revision (excisional or needling), additional filtering surgery and shunting procedure. Compared to other techniques, needling bleb revision has advantages including the simplicity of the procedure, the low cost and the comfort for both patient and surgeon.

Since the first description by Ferrer, [18] there have been several reports on needling bleb revision with various methods; however, the principles are similar. Most importantly, different studies have used 5-fluorouracil (5-FU) or MMC for needle bleb revision. Compared to 5-FU, MMC has several advantages including greater potency, lower risk of bleb encapsulation, and better IOP control. [19] In a comparative study, Anand and associates compared the efficacy of 5-FU versus MMC for bleb revision. [20] Their results suggested that MMC is more effective than 5-FU for needle revision of failed trabeculectomy blebs. There was no statistically significant difference in the complication rates between groups. With this in mind, we usually use MMC in our trabeculectomies and bleb revisions.

Comparison of studies on bleb-needling revision is difficult, because of demographic differences, type and severity of glaucoma, timing of needling following initial filtration, MMC concentration, needle gauge size, extent of subconjunctival dissection, and whether entrance to the anterior chamber via the ostium is performed or not.

In a study with technical similarities to our study, Shetty et al.[11] performed slit lamp needle bleb revision on 44 patients to revive failed filtering blebs after one year. They used high dose subconjunctival MMC (0.4 mg/ml), dissected subconjunctival fibrosis and lifted the scleral flap with 27-gauge insulin needle, and entered the anterior chamber in all patients. Their criterion for [complete] success was postneedling IOP greater than 4 mmHg and less than 21 mmHg without any antiglaucoma medications or further surgery, and qualified success was an IOP in this same range above, with the use of antiglaucoma medications. [11] The case "failed" if another filtration procedure was required. [11] Their [complete] success rate was 39% and qualified success was 25%. [11] The IOP after 1 year was 13.6 ± 4.0 mmHg with an average of 0.5 ± 0.8 medications. [11] There was no case of postoperative blebitis, endophthalmitis, or suprachoroidal hemorrhage. [11] The authors [11] suggested that needle bleb revision with high dose MMC was effective in reducing IOP in 64% of eyes with a failed filtering bleb. However, in our study with a considerably longer follow-up (mean, 20 months) and lower MMC concentration, the overall success was 59.3%. Hence, it seems that a high MMC concentration may not be always necessary for rescuing a failed bleb. However, we had fewer cases with complete success, which may be due to the more diverse types of glaucoma included in our study, racial differences, or technical problems. In addition, we did not insert the insulin needle into the anterior chamber in all cases. More importantly, almost 40% of Shetty et al.'s [11] cases were needled within 4 months of the initial trabeculectomy whereas all of our cases had an interval of at least 6 months - this is an important predictor of success.

In a prospective, nonrandomized comparative trial on 34 patients, Gutierrez-Ortiz et al.[21] evaluated long-term effectiveness and factors involved in successful needling bleb revision with MMC. Their mean time from trabeculectomy to needling was 4.4±9.3 months (range, 1-24 months). [21] Their success rate was 90% and 75% at 1 and 2 years, respectively. [21] They identified one independent preoperative factor for success of the initial MMC needling bleb revision; a lapse of less than 4 months between trabeculectomy and the needling procedure. [21] Gutierrez-Ortiz et al.[21] proposed that application of MMC during the cellular phase of healing is most effective which concurs with other studies. [22],[23] In our study, the mean interval between initial needling and initial trabeculectomy was 32.74 ± 15.36 months (range, 6-60 months) with an overall success of 59.3%. Our success rate is obviously lower, which as proposed by Gutierrez-Ortiz, may be due to the long interval between initial and revision surgery. The differences between studies may also be due to diversity of glaucoma types in our patients, racial differences, and technical problems. However, it is noteworthy to emphasize that according to our findings, even late needling has an acceptable success rate in reviving failed filtering bleb.

Predicting which patients are likely to do well after needling bleb revision is not easy and there is no consensus regarding the determinants of success. Several factors have been linked to a poor outcome in previous reports. Some of the reported risk factors are the interval between filtration surgery and needling, [11],[14],[21],[24],[25] high pre-needling IOP, [12],[15],[26] multiple needlings, [12],[15],[26] lack of MMC usage during the previous filtration surgery, [26] and high IOP immediately after needling. [16],[26] Other factors associated with needling failure include young age, [17] aphakia or pseudophakia, [27] fornix-based conjunctival flap trabeculectomy, [28] previous surgery involving a conjunctival incision, [11],[12],[29] and long-term previous exposure to topical sympathomimetic. [28] Among these, the long interval between index trabeculectomy and revision, high initial IOP, and young age of some patients may contribute to our lower success rates. It should be emphasized that there is no agreement on the interval between initial and revision surgeries and some authors reported higher success rate with longer intervals. [11],[14] In addition, we used small gauge insulin needle for the revision, which is not stiff enough to dissect subconjunctival scarring adequately. We believe that the needle size and stiffness were inadequate, and the tract was not sufficiently large and closed readily, even in cases where we entered the anterior chamber. Using larger and stiffer needles or specifically designed bleb-knives may help address this problem.

Most of the reported complications have been minor and include temporary conjunctival wound leaks, [29],[30] transient shallowing of the anterior chamber, [26] small hyphema, [15],[26] and corneal epithelial toxicity (mainly due to 5-FU). [15],[26] The incidence of minor complications has been reported between 20% and 38%. [29],[15] The potential for more serious complications should not be underestimated. Few serious complications are ever divulged, although significant hypotony, [29] suprachoroidal hemorrhage, [20],[30] malignant glaucoma, [20],[31] and endophthalmitis [12] have been reported after bleb needling.

In the present study, we had a small hyphema in two cases, which resolved spontaneously. No other complications were seen in our series that may be due to our more conservative approach to the needling. Conjunctival avascularity at the site of MMC injection was seen in only one patient and was not progressive and treated with topical lubrication to reduce the foreign body sensation.

Improvement in mean uncorrected visual acuity following needling in our patients was not clinically significant (less than one Snellen line); this may be due to vision improvement following decreasing IOP, especially in younger patients, or due to the known visual fluctuation of glaucoma patients.

Our study has several limitations including its retrospective nature, small sample size, and lack of a control group. A prospective, randomized controlled trial with a larger number of cases could resolve these problems.

In conclusion, the bleb-needling procedure with MMC at the slit lamp during an office visit can successfully rescue a late failed filtration procedure without increasing the risks associated with more invasive procedure in the operating room; in addition, it is relatively easy and is less time consuming. Hence, although the success rate is lower than early needling, we recommend needle bleb revision to be considered prior to a repeat trabeculectomy or another major surgery.

   References Top

1.The Fluorouracil Filtering Surgery Study Group. Five-year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1996;121:349-66.  Back to cited text no. 1
2.Skuta GL, Parrish RK. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987;32:149-70.  Back to cited text no. 2
3.Swan KC. Reopening of nonfunctional filters-simplified surgical techniques. Trans Am Acad Ophthalmol Otolaryngol 1975;70:342-8.  Back to cited text no. 3
4.Palmer SS. Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology 1991;98:317-21.  Back to cited text no. 4
5.The Fluorouracil Filtering Surgery Study Group. Fluorouracil Filtering Surgery Study one-year follow-up. Am J Ophthalmol 1989;108:625-35.  Back to cited text no. 5
6.Skuta GL, Beeson CC, Higginbotham EJ, Lichter PR, Musch DC, Bergstrom TJ, et al. Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery. Ophthalmology 1992;99:438-44.  Back to cited text no. 6
7.Noureddin BN, Wilson-Holt N, Lavin M, Jeffrey M, Hitchings RA. Advanced uncontrolled glaucoma: Nd:YAG cyclophotocoagulation or tube surgery. Ophthalmology 1992;99:430-6.  Back to cited text no. 7
8.Bloom PA, Tsai JC, Sharma K, Miller MH, Rice NS, Hitchings RA, et al. "Cyclodiode": Trans-scleral diode laser cyclophotocoagulation in the treatment of advanced refractory glaucoma. Ophthalmology 1997;104:1508-19.  Back to cited text no. 8
9.Rotchford AP, King AJ. Needling revision of trabeculectomies bleb morphology and long-term survival. Ophthalmology 2008;115:1148-53.  Back to cited text no. 9
10.Allen LE, Manuchehri K, Corridan PG. The treatment of encapsulated trabeculectomy blebs in an out-patient setting using a needling technique and subconjunctival 5-fluorouracil injection. Eye (Lond) 1998;12:119-23.  Back to cited text no. 10
11.Shetty RK, Wartluft L, Moster MR. Slit-lamp needle revision of failed filtering blebs using high-dose mitomycin C. J Glaucoma 2005;14:52-6.  Back to cited text no. 11
12.Greenfield DS, Miller MP, Suner IJ, Palmberg PF. Needle elevation of the scleral flap for failing filtration blebs after trabeculectomy with mitomycin C. Am J Ophthalmol 1996;122:195-204.  Back to cited text no. 12
13.Iwach AG, Delgado MF, Novack GD, Nguyen N, Wong PC. Transconjunctival mitomycin-C in needle revisions of failing filtering blebs. Ophthalmology 2003;110:734-42.  Back to cited text no. 13
14.Mardelli PG, Lederer CM Jr, Murray PL, Pastor SA, Hassanein KM. Slit-lamp needle revision of failed filtering blebs using mitomycin C. Ophthalmology 1996;103:1946-55.  Back to cited text no. 14
15.Hodge W, Saheb N, Balazsi G, Kasner O. Treatment of encapsulated blebs with 30-gauge needling and injection of low-dose 5-fluorouracil. Can J Ophthalmol 1992;27:233-6.  Back to cited text no. 15
16.Broadway DC, Bloom PA, Bunce C, Thiagarajan M, Khaw PT. Needle revision of failing and failed trabeculectomy blebs with adjunctive 5-fluorouracil: Survival analysis. Ophthalmology 2004;111:665-73.  Back to cited text no. 16
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18.Ferrer H. Conjunctival dialysis in the treatment of glaucoma recurrent after sclerectomy. Am J Ophthalmol 1941;24:788-90.  Back to cited text no. 18
19.Azuara-Blanco A, Bond JB, Wilson RP, Moster MR, Schmidt CM. Encapsulated filtering blebs after trabeculectomy with mitomycin-C. Ophthalmic Surg Lasers 1997;28:805-9.  Back to cited text no. 19
20.Anand N, Khan A. Long-term outcomes of needle revision of trabeculectomy blebs with mitomycin C and 5-fluorouracil: A comparative safety and efficacy report. J Glaucoma 2009;18:513-20.  Back to cited text no. 20
21.Gutierrez-Ortiz C, Cabarga C, Teus MA. Prospective evaluation of preoperative factors associated with successful mitomycin C needling of failed filtration blebs. J Glaucoma 2006;15:98-102.  Back to cited text no. 21
22.Costa VP, Spaeth GL, Eiferman RA, Orengo-Nania S. Wound healing modulation in glaucoma filtration surgery. Ophthalmic Surg 1993;24:152-70.  Back to cited text no. 22
23.Tahery MM, Lee DA. Review: Pharmacologic control of wound healing in glaucoma filtration surgery. J Ocul Pharmacol 1989;5:155-79.  Back to cited text no. 23
24.Gillies WE, Brooks AM. Restoring the function of the failed bleb. Aust N Z J Ophthalmol 1991;19:49-51.  Back to cited text no. 24
25.Fitzgerald JR, McCarthy JL. Surgery of the filtering bleb. Arch Ophthalmol 1962;68:453-67.  Back to cited text no. 25
26.Shin DH, Kim YY, Ginde SY, Kim PH, Eliassi-Rad B, Khatana AK, et al. Risk factors for failure of 5-fluorouracil needling revision for failed conjunctival filtration blebs. Am J Ophthalmol 2001;132:875-80.  Back to cited text no. 26
27.Hawkins AS, Flanagan JK, Brown SV. Predictors for success of needle revision of failing filtration blebs. Ophthalmology 2002;109:781-5.  Back to cited text no. 27
28.Pederson JE, Smith SG. Surgical management of encapsulated filtering blebs. Ophthalmology 1985;92:955-8.  Back to cited text no. 28
29.Potash SD, Ritch R, Liebmann J. Ocular hypotony and choroidal effusion following bleb needling. Ophthalmic Surg 1993;24:279-80.  Back to cited text no. 29
30.Howe LJ, Bloom P. Delayed suprachoroidal haemorrhage following trabeculectomy bleb needling. Br J Ophthalmol 1999;83:757.  Back to cited text no. 30
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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