Long-Term Bleb-Related Infections After Trabeculectomy: Incidence, Risk Factors, and Influence of Bleb Revision


To report the incidence of late-onset bleb-related infections and to identify risk factors for bleb-related infections after trabeculectomy for the treatment of glaucoma.


Retrospective case series.


Bleb-related infections were defined as blebitis, endophthalmitis, or blebitis with endophthalmitis. A total of 1959 eyes of 1423 patients who underwent trabeculectomy and who were followed for ≥1 year were included.


Twenty-four eyes were diagnosed with bleb-related infections; 15 eyes were found to have blebitis and 9 eyes presented with endophthalmitis during the follow-up period of 5.4 ± 3.5 years (mean ± standard deviation). Among 15 eyes with blebitis, 2 eyes developed endophthalmitis under treatment. The Kaplan-Meier estimated incidence of bleb-related infections was 2.0% ± 0.5% (mean ± standard error) at 10 years. A Cox multivariate analysis showed the significant risk factors for a bleb-related infection to be diagnoses of pigmentary glaucoma or juvenile glaucoma, history of bleb leak, intraocular pressure sustained below the target pressure, chronic blepharitis, and the presence of punctal plugs. Surgical bleb revision demonstrated a protective effect against bleb-related infections ( P < .01) when risk factors were present.


This large case series with long-term follow-up demonstrates the incidence of bleb-related infections to be less than 2%, and describes the risk factors associated with bleb-related infections. A protective effect of surgical bleb revision was demonstrated. Clinicians should be constantly vigilant for, and patients made aware of, the possibility of bleb-related infections long after trabeculectomy, especially in the presence of identified risk factors.

Late-onset bleb-related infection is a potentially devastating complication after trabeculectomy. While the overall incidence varies among different studies according to the study design, follow-up period, surgical technique, and statistical methods, the incidence of late postoperative infections is higher than with most other intraocular surgeries. With the widespread use of antiproliferative agents like mitomycin C (MMC) or 5-fluorouracil (5-FU) to enhance surgical success rates, a higher incidence of bleb-related infections has been noted compared to before their introduction, which had been reported to be 0.2%–1.5%. The incidence reported for MMC-augmented trabeculectomy with follow-up periods of 1–12 years varies between 1.1% and 13.8% and that for intraoperative 5-FU-augmented trabeculectomy with follow-up of 16 months – 18 years ranges from 0.8% to 13.0%. The Kaplan-Meier estimated incidence at 5 years varies from 1.5% to 6.3% for blebitis and from 1.1% to 7.5% for bleb-related endophthalmitis in several studies. Although it is evident that bleb-related infections can develop long after trabeculectomy (up to 42 years after), and the cumulative incidence seems to increase linearly with time, the estimated risks of this complication have not been reported beyond 5 years.

Many investigators have evaluated presumed risk factors for the occurrence of bleb-related infections through case-control studies, case series without survival analysis, or case series with survival analysis. In a number of case-control studies, use of postoperative antibiotics, late-onset bleb leak, younger age, black race, and inferior location of the filtering bleb were shown to be associated with a significant risk of bleb-related infections. The largest retrospective case series so far has been reported by Sharan and associates. An analysis of 521 cases in a mean follow-up of 5.3 years revealed that bleb leak, black race, and bleb manipulation were important risk factors for bleb-related infections. A notable study that used survival analysis was the Collaborative Bleb-Related Infection Incidence and Treatment Study by Yamamoto and associates. It was a prospective, multicenter study including 1098 eyes of 1098 patients who underwent a superior trabeculectomy with MMC, and it demonstrated a 5-year incidence of 2.2%, with significant risk factors being bleb leak and younger age.

Since many complications after trabeculectomy are known to be associated with bleb-related infections, surgical bleb revision might affect the cumulative incidence of late complications. No published studies have reported the influence of surgical bleb revision on the incidence of bleb-related infections.

We report the long-term estimated incidence of late-onset bleb-related infections at 10 years with survival analysis of a large case series. We estimate the hazard ratios for presumed risk factors of bleb-related infections and investigate the influence of surgical bleb revision on bleb-related infection risk, based on a survival analysis of long-term results in patients who underwent trabeculectomy with adjuvant MMC or 5-FU at a single tertiary glaucoma care center.


Eligibility Criteria and Determination of Follow-up Period

This retrospective case series was conducted in accordance with the tenets set forth in the Declaration of Helsinki and was approved by the Institutional Review Board at UCLA before the study began. Eyes that underwent trabeculectomy with intraoperative use of either MMC or 5-FU during the time interval between December 1993 and March 2013 and that were followed up for ≥1 year at the Jules Stein Eye Institute were included in the study. Eyes that underwent subsequent implantation of a glaucoma drainage device within the first postoperative year and those with a history of previous endophthalmitis or blebitis were excluded.

The follow-up period was determined as the interval between trabeculectomy and the last office visit. Intraocular surgeries such as the insertion of a glaucoma drainage device, scleral buckling, vitrectomy, combined surgery, or development of malignant glaucoma or phthisis marked the end of follow-up (ie, that eye was censored). The occurrence of a bleb-related infection was the event of interest (ie, failure), and the follow-up period was determined to be less than 1 year for those eyes that developed bleb-related infections during the first postoperative year. If both eyes of the same patient were eligible, both eyes were included in the study.

Surgical Technique

All eyes were operated with peribulbar anesthesia with 2–4 mL of 2% lidocaine. A conjunctival flap was created superiorly in either a fornix-based or limbus-based manner. The location of the bleb was determined from the operative notes. Typically, a superior peritomy was created about 4 clock hours (from 10 o’clock to 2 o’clock) wide for fornix-based flaps. For limbus-based flaps, the conjunctiva just anterior to the superior rectus insertion was elevated and cut, then the incision was extended temporally and nasally for a total of 8–10 mm. The Tenon capsule was then elevated and incised in a similar fashion. Exceptions occurred in 5 eyes where the blebs were made in the superonasal quadrant and in 1 eye where the bleb was made in the superotemporal quadrant. A scleral rectangular flap (approximately 3 × 3 mm) was outlined with light wet-field cautery. The episcleral bed was dried and a large (approximately 6 × 12 mm) Merocel sponge(Beaver-Visitec International Inc, Waltham, MA) soaked in either MMC (0.2–0.4 mg/mL) or 5-FU (50 mg/mL) was applied to the episcleral bed for 0.25–5 minutes.

After removal of the sponge, the exposed episcleral and Tenon areas were copiously irrigated with balanced salt solution. A partial-thickness scleral flap hinged at the superior limbus was made. A trabecular meshwork/corneal block 1 × 2 mm in size was resected under the anterior-most portion of the scleral flap. A basal iridectomy was performed and the scleral flap was sutured with 2–5 interrupted sutures to approximate the scleral flap onto the scleral bed. The conjunctiva was placed back and sutured in a watertight fashion. A paracentesis was made and the bleb was elevated by injecting balanced salt solution into the anterior chamber. The eye was inflated to a physiologic pressure with the anterior chamber completely formed. All surgery was performed by 5 glaucoma specialists at Jules Stein Eye Institute. Topical antibiotic eye drops were prescribed for 1 week after surgery and topical corticosteroids were used for 4–6 weeks postoperatively. Laser suture lysis was performed as needed with a diode laser from 1 to 6 weeks postoperatively. All patients were advised to avoid the use of contact lenses postoperatively.

Bleb revision was performed for the treatment of high thin blebs, bleb dysesthesia, bleb leak, and overfiltering blebs with hypotony maculopathy. The technique of surgical bleb revision followed a method previously reported. Resuturing of the trabeculectomy flap was performed in most of the revisions; in some cases a pericardial graft was required to reinforce the sclera. When indicated, drainage of choroidal effusions and reformation of the anterior chamber was also performed.

Data Collection and Definition of Parameters

Data were collected by retrospective review of medical records. Table 1 describes the clinical and demographic characteristics of the patients. Those with a history of any organ transplantation, chronic administration of oral corticosteroid or immunosuppressant, who were on chemotherapy, who were diagnosed as having seropositive human immunodeficiency virus (HIV), end-stage renal disease, or diabetes mellitus were considered to be immunocompromised.

Table 1

Results From Survival Analysis of Eyes That Underwent Trabeculectomy

Parameter Total Number of Eyes Number of Bleb-Related Infections (%) Log-Rank Test Generalized Estimating Equation
Demographic characteristics
Sex a
Male 857 7 (0.8) .159 .151
Female 1102 17 (1.5)
Age a
≥50 years 1761 18 (1.0) .044 .074
<50 years 198 6 (3.0)
Race .298 .210
White 1160 17 (1.5)
Asian 276 5 (1.8)
Black 185 1 (0.5)
Hispanic & others 338 1 (0.3)
Systemic conditions
Diabetes mellitus
No 1766 21 (1.2) .524 .546
Yes 193 3 (1.6)
No 1396 18 (1.3) .895 .895
Yes 563 6 (1.1)
Immunocompromised state (diabetes included)
No 1756 21 (1.2) .634 .646
Yes 203 3 (1.5)
Types of glaucoma a .000 .000
POAG 1411 15 (1.1)
PACG 141 1 (0.7)
Pigmentary glaucoma 39 4 (10.3)
Juvenile glaucoma 18 2 (11.1)
All other secondary 350 2 (0.6)
Lens status
Phakic 1309 19 (1.5) .311 .293
Pseudophakic, aphakic 650 5 (0.8)
OD 977 11 (1.1) .657 .656
OS 982 13 (1.3)
Surgical factors
Antimetabolites a
MMC 1926 22 (1.1) .019 .084
5-FU 33 2 (6.1)
Application duration of MMC (min)
MMC <3 1804 19 (1.0) .365 .397
MMC ≥3 122 3 (0.2)
Type of conjunctival flap
Fornix 968 11 (1.1) .597 .601
Limbus 991 13 (1.3)
Two or more filtration surgeries
No 1663 21 (1.3) .422 .398
Yes 296 3 (1.0)
Previous trabeculectomy
No 1857 24 (1.3) NA NA
Yes 102 0 (0.0)
Postoperative interventions
Laser suture lysis
No 1183 18 (1.5) .371 .359
Yes 776 6 (0.8)
Needling and/or 5-FU injection
No 1843 23 (1.2) .717 .703
Yes 116 1 (0.9)
Bleb revision
No 1791 22 (1.2) .759 .752
Yes 168 2 (1.2)
Surgical complications
Early leak a
No 1797 18 (1.0) .003 .013
Yes 162 6 (3.7)
Shallow or flat anterior chamber
No 1861 24 (1.3) NA NA
Yes 98 0 (0.0)
Hypotony maculopathy
No 1899 23 (1.2) .905 .906
Yes 60 1 (1.7)
Choroidal effusion a
No 1693 17 (1.0) .056 .082
Yes 266 7 (2.6)
Hyphema a
No 1751 17 (1.0) .018 .037
Yes 208 7 (3.4)
Hypotony a
No 1581 15 (0.9) .127 .145
Yes 378 9 (2.4)
Prolonged hypotony
No 1880 22 (1.2) .516 .384
Yes 79 2 (2.5)
Late leak (positive Seidel) a
No 1854 8 (0.4) .000 .000
Yes 105 16 (15.2)
Cataract surgery during follow-up
No 1215 12 (1.0) .707 .707
Yes 744 12 (1.6)
Bleb morphology
Avascular bleb
No 1177 2 (0.2) .000 .000
Yes 782 22 (2.8)
High bleb
No 1909 20 (1.0) .001 .012
Yes 50 4 (8.0)
Thin-walled bleb
No 1441 5 (0.3) .000 .000
Yes 518 19 (3.7)
Low bleb
No 1282 22 (1.7) .006 .002
Yes 678 2 (0.3)
Fully functioning bleb a
No 841 2 (0.2) .000 .000
Yes 1118 22 (2.0)
Total blepharitis
No 1741 18 (1.0) .082 .115
Yes 218 6 (2.8)
Chronic blepharitis a
No 1917 21 (1.1) .001 .016
Yes 42 3 (7.1)
Episodic blepharitis
No 1783 21 (1.2) .798 .801
Yes 176 3 (1.7)
Chronic use of oral steroid
No 1929 24 (1.2) NA NA
Yes 30 0 (0.0)
Use of punctal plugs a
No 1921 22 (1.1) .011 .068
Yes 38 2 (5.3)
Groups a .000 .000
Group 1 b 1661 10 (0.6)
Group 2 c 167 1 (0.6)
Group 3 d 131 13 (9.9)

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Jan 7, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Long-Term Bleb-Related Infections After Trabeculectomy: Incidence, Risk Factors, and Influence of Bleb Revision

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