FP914 : Outcomes of Bleb Repair for Delayed Bleb Leaks and Sweating Blebs

Dr. Rashmi Krishnamurthy, K16848, Dr. Chandra Sekhar G, Dr. Arpita Basia, Dr. Sirisha Senthil

Abstract:

Purpose: To report the outcomes of bleb repair for delayed onset leaking blebs and sweating blebs following glaucoma filtering surgery.

Methods: Medical records of 76 eyes of 76 subjects that underwent bleb repair for either leaking bleb or sweating bleb between 1990 and 2015 were reviewed. Complete success was resolution of bleb leak and or hypotony with intraocular pressure (IOP) ≥5 and ≤21 mmHg with no anti-glaucoma medication (AGM).

Results: There were 45 eyes with leaking bleb and 31 eyes with sweating bleb that underwent bleb repair by either conjunctival autograft or conjunctival advancement (p=0.11). Prior to bleb repair, complications like blebitis and hypotony maculopathy were significantly higher in sweating bleb group (13/31) compared to bleb leak group (5/45) (p=0.002). Median follow up after bleb repair was > 2 years in both groups (p=0.69). Post repair, eyes in leaking bleb group had higher immediate (p=0.01) and long term IOP elevation (p=0.06) compared to sweating bleb group. Complete success probability in sweating bleb group was significantly better (88%, 78% and 71%) compared to leaking bleb group (54%, 45% and 40%) at 1, 3 and 6 years respectively (p=0.01). One eye in each group had blebitis, two eyes in leaking bleb group and one eye in sweating bleb group needed repeat glaucoma intervention.

Conclusion: Higher complication rate prior to bleb repair in eyes with sweating bleb warrants early bleb repair. Bleb repair helped retain bleb function in 71% eyes with sweating blebs at the end of 6 years, strengthening our recommendation.

Key words: Late leaking blebs; conjunctival advancement; conjunctival autograft; bleb leak; bleb repair; sweating blebs; post trabeculectomy complication; bleb-related complication;

Introduction:

Bleb leak is a known complication following glaucoma filtering surgery (GFS),1 both in the early and late postoperative period. Thin ischemic blebs may leak months or years later and are known as delayed or late leaking blebs.2 Bleb leaks can be high flow leaks that are siedel’s positive or can be low flow pin point leaks or may present with bleb sweating or trans conjunctival ooze. These complications were more common with full thickness procedures3, 4 and are seen increasingly with adjunctive antimetabolite augmented trabeculectomies.5-9 Chronic or late bleb leaks are more commonly seen with thin cystic and avascular blebs (5.2%-6%) compared to thick walled blebs (1.1- 1.3%).1, 3, 10-12 In a prospective study by Anand et al, changes in the bleb characteristics over 24 months were observed in 125 eyes following glaucoma filtering surgery with Mitomycin C (MMC).13 At the end of 24 months, bleb avascularity was noted in 73% eyes, transconjunctival ooze in 95% eyes and bleb leak in 26% eyes and these complications were more common following trabeculectomy compared to deep sclerectomy or combined surgery.13

Leaking blebs predispose the eyes to complications, like hypotony maculopathy, choroidal detachment, shallow or flat anterior chamber, corneal decompensation, cataract formation and can be a risk factor for bleb failure too.1, 3, 14, 15 Bleb leaks and avascular blebs are more prone to serious vision threatening complications like blebitis and bleb related endophthalmitis. 8, 9, 14, 16, 17Treatment of delayed leaking blebs is challenging and successful closure of the leak often requires surgical repair.18, 19 The two surgical procedures commonly used for bleb repair are free conjunctival autograft,20-23 and conjunctival advancement.10, 15, 21 The technique of repair depends on the nature and extent of the bleb leak, site of leak, and the health and mobility of the adjacent conjunctiva.

Currently the indications for bleb repair are bleb dysesthesia, large sweating bleb with hypotony maculopathy, bleb leak or blebitis.15, 18, 22 Various studies have evaluated outcomes of bleb repair in eyes with one or more of these complications.8,10, 15, 20, 22-25 Although avascular blebs and sweating blebs are more prone to blebitis and hypotony maculopathy,10 and are clinical indications for bleb repair, the outcomes of bleb repair in these eyes before a serious complication develops is not evaluated so far. Our objective was to evaluate the outcomes of bleb repair in eyes with delayed leaking blebs and non leaking or sweating blebs using either conjunctival advancement or conjunctival autograft.

Materials and Methods: We retrospectively reviewed the medical records of all consecutive glaucoma patients who underwent bleb repair between 1990 and 2015 at our institute for a delayed onset leaking bleb or sweating bleb following a glaucoma filtering surgery (GFS). The Institutional review board of L.V. Prasad Eye Institute approved the study. Some of the patients in this study were also included in smaller case series published earlier.25

We included eyes with late bleb leak with definite aqueous streaming in one group and those blebs with bleb sweating into another group. Patients with bleb leak within 3 months of GFS, those with obvious trauma causing bleb leak and those with less than 6 weeks follow up were excluded from the study. Eyes that underwent bleb repair for dysesthetic blebs or eyes that needed scleral patch graft during bleb repair were excluded.

The clinical details collected were: age, gender, type of glaucoma, date and type of the primary GFS, use of anti-fibrotics, interval between trabeculectomy and bleb leak or hypotony, bleb characteristics and anterior segment details, optic disc and retinal evaluation surgical technique of bleb repair, complications and their management, re-surgeries if any, intra ocular pressure (IOP), visual acuity and number of anti glaucoma medications (AGM) before and after bleb repair.

Presence of positive Seidel’s test (fluorescein dye washed away by the aqueous leaking from the bleb) constituted a ‘leaking bleb’. Increase in the fluorescence of the bleb area typically appearing as slowly enlarging dots or ooze, without any defect in the conjunctival tissue with no obvious aqueous streaming on Seidel’s test constituted a ‘sweating bleb’. Hypotony was defined as IOP ≤5 mmHg on two consecutive occasions. Hypotony maculopathy was defined as hypotony with loss of 2 or more lines of visual acuity in the presence of macular folds. Conservative treatment in the form of large diameter soft bandage contact lens (15-20 mm) and topical aminoglycoside eye drops (to incite conjunctival inflammation and stimulate healing) were tried in a few patients before the surgical repair.

Choice of surgical repair was based on the dimension of leak, status of the surrounding conjunctiva and the surgeon’s discretion. All surgeries were performed by one of the 6 glaucoma specialists (AKM, GCS, HLR, NKL, SD, SIR). All surgeries were performed under peribulbar anesthesia with 2% lidocaine and 0.5% bupivacaine. Superior rectus or corneal traction suture was applied as required during the surgery.

Surgical procedure:

Conjunctival Advancement: Conjunctival advancement was preferred in the presence of a small avascular bleb or a small anterior leak (less than 2-3 mm from the limbus) with surrounding healthy and mobile conjunctiva. A fornix based conjunctivo-tenon incision was made delineating the bleb, peritomy was carried out to free the adjacent conjunctiva to allow adequate anterior advancement. The anterior ischemic bleb was either debrided of the epithelium following a gentle cautery or was completely excised. The underlying sclera was examined for presence and the intensity of leak. If there was excess leakage, additional scleral suture with 10’0 nylon (ETHICON, Somerville, NJ) was applied. The conjunctiva was then anteriorly advanced and sutured at the limbus ensuring a watertight closure with interrupted 10’0 nylon sutures.

Conjunctival Autograft: In the presence of large avascular bleb or a small bleb with surrounding scarred conjunctiva, a conjunctival autograft was preferred. The dimensions of the bleb were measured using a calipers and an oversized conjunctival autograft (by 2 mm) was harvested from adjacent or inferior bulbar conjunctiva. Slightly oversized graft was planned to prevent traction on the wound edges and also to account for the postoperative tissue shrinkage and bleb elevation. After debriding the bleb wall or excising the avascular bleb, additional scleral sutures with 10’0 nylon were applied if there was excess leakage from the underlying sclera. Maintaining the limbal orientation, the harvested conjunctiva was placed over the bleb area and anchored with interrupted 10’0 nylon sutures.

The standard postoperative regimen was followed, which was topical antibiotic and cycloplegic eye drops for 1-2 weeks and tapering dose of topical steroids for 4-5 weeks. Postoperative reviews were on day one, week 1, week 6 and 4-6 monthly thereafter.

The primary outcome measure was cumulative probability of success. Success was defined as complete in the presence of resolution of bleb leak or hypotony with IOP ≥5 and ≤21 mmHg without any AGM and as qualified in the presence of resolution of bleb leak or hypotony with AGM required for IOP control. Failure was defined as one or more of the following: a) presence of persistent bleb leak, which required repeat surgery b) persistent hypotony (IOP≤5 mm Hg) or c) IOP>21mm Hg despite medical treatment or need for repeat glaucoma surgery.

Statistical analysis: Snellen visual acuity measurements were converted to logarithm of minimum angle of resolution (Log MAR) equivalents for the purpose of analysis. Descriptive statistics for continuous variables included mean and standard deviation for normally distributed variables and median, first quartile, and third quartile values for non-normally distributed variables. Normally distributed variables were compared using ‘t’ test and non-normally distributed variables using Wilcoxon ranksum test. Categorical variables were summarized as percentages and compared using Chi square test. Kaplan-Meier survival analysis was used to assess cumulative probability of success. Statistical analyses were performed using commercial software (Stata ver. 11.0; Stata Corp, College Station, TX). A p value of 0.05 or less was considered statistically significant.

Results:

Demographic data, preoperative characteristics and surgical details: A total of 116 eyes underwent bleb repair for late leaking blebs from the year 1990 to 2015 at our Institute. Bleb repair for overhanging blebs (dysesthetic blebs) or those eyes requiring scleral patch graft during bleb repair together constituted 40 eyes, which were excluded. We included 76 eyes of 76 subjects that underwent bleb repair for either late leaking bleb or non-leaking sweating bleb. The demographic, preoperative characteristics of the study subjects are given in Table 1.

Of the 76 eyes that underwent bleb repair, the indication for bleb repair was leaking bleb in 45 eyes and sweating bleb in 31 eyes. The median age of subjects was similar in the two groups (p=0.17). More than half of the eyes had trabeculectomy without antimetabolites as primary glaucoma surgery (29 eyes in leaking bleb group and 17 eyes in sweating bleb group) and one third had trabeculectomy with MMC (13 eyes in leaking bleb group and 10 eyes in sweating bleb group).

The type of glaucoma was similar in both the groups. In the sweating bleb group, 4 eyes had hypotony maculopathy, 6 eyes had previous blebitis and 3 eyes had shallow anterior chamber (AC) with corneal edema. In the leaking bleb group, 2 eyes had hypotony maculopathy and 3 eyes had previous blebitis. Bleb related or hypotony related complications were seen more frequently in sweating bleb group compared to leaking bleb group (42% vs. 11%; p=0.002). Median duration from trabeculectomy to bleb repair in eyes with sweating bleb was more than twice the duration compared to eyes with leaking bleb, (116.4 months vs. 51.7 months), however this difference did not reach statistical significance(p=0.18).

Median preoperative visual acuity (VA) was better in eyes with leaking bleb group compared to those with sweating blebs (0.3 vs. 0.6), this although was not statistically significant (p=0.11) but was clinically significant. This difference was apparent even after excluding eyes with bleb related complications, in eyes with no preexisting complications, the median VA was 0.25 (0.1, 0.7) in the leaking bleb group and was 0.6 (0.3, 0.8) in the sweating bleb group.

Bleb repair was either performed with conjunctival advancement or conjunctival autograft. Both groups had more eyes managed with conjunctival autograft compared to conjunctival advancement. Four of the eyes with leaking blebs had scleral flap suture during bleb repair and one eye with sweating bleb had a scleral suture during bleb repair. There was a vitreous tag noted intra-operatively which was cleared with an automated vitrector in an eye with bleb leak that underwent conjunctival autograft.

Three eyes in sweating bleb group, which had preexisting corneal edema had worsening of corneal edema and decompensation needing intervention. Although this was not a complication of bleb repair, long-standing shallow AC in these eyes with sweating blebs resulted in this complication. Of these 3 eyes, one eye underwent penetrating keratoplasty, one eye underwent anterior stromal puncture and the third patient was advised keratoplasty but was lost to follow up.

Postoperative characteristics: Table 2 shows the post-operative characteristics and complications. The median postoperative visual acuity was 0.2 (0.1, 0.6) in eyes treated for leaking blebs and was 0.4 (0.1, 1.1) in eyes treated for sweating blebs (p=0.31). Visual acuity change (by Log MAR) post bleb repair in eyes with sweating blebs was 0.09 (-0.2, 0.48) and in eyes with leaking blebs was 0 (-0.1, 0.18), the change in VA was not different between the two groups, p=0.38. In eyes with sweating bleb, 14 eyes had no change in VA, 10 eyes had improvement of more than 2 lines and 7 eyes had 2 or more lines deterioration. In eyes with bleb leak, 25 eyes had no change in VA, 10 eyes had 2 or more lines of improvement in VA and 10 eyes had 2 or more lines deterioration.

Early post bleb repair complications: In the leaking bleb group 4 eyes had persistent leak, 2 of these resolved with use of bandage contact lens (BCL) and 2 eyes required re-suturing.  In the eyes with sweating blebs, one eye had persistent leak with hypotony that resolved with BCL. Elevated IOP immediately after bleb repair was higher in leaking bleb group (9 eyes) compared to sweating bleb group (2 eyes), (p 0.01).                                                                                      Late post bleb repair complications: The median follow up post bleb repair was more than 2 years in both the groups. During the follow up, more number of eyes (40% eyes) in the leaking bleb group needed AGM for IOP control compared to (19% eyes) those with sweating bleb (p=0.06). Two eyes in the leaking bleb group needed repeat glaucoma intervention for IOP control (1 repeat trabeculectomy with MMC after 2 years and one TSCPC after 1 month of bleb repair) and one eye in sweating bleb group needed repeat trabeculectomy 4 months after bleb repair.

One eye in leaking bleb group and 2 eyes in sweating bleb group had persistent hypotony, without hypotony maculopathy. As all the three eyes had visual acuity improvement both for distance and near (better than 20/40 for distance and N6 for near) no further intervention was needed. Post bleb repair, 7 eyes in leaking bleb group (15.5%) and 8 eyes in sweating bleb group (25.8%) developed significant cataract. One eye in each group developed overhanging/ dysesthetic bleb. One eye in leaking bleb group had blebitis and one eye in sweating bleb group had blebitis with endophthalmitis. The eye in sweating bleb group developed blebitis and endophthalmitis 3 years after bleb repair. This eye needed bleb excision with pars plana vitrectomy and intraocular antibiotics. The infection resolved and vision improved to 20/200 with IOP of 11mmHg with no AGM until last follow up (at 38.3 months). The eye in the bleb leak group developed blebitis 3 months following conjunctival autograft. This eye resolved with intensive medical treatment and did not require any surgical intervention.

Kaplan-Meier survival probability: Following bleb repair, complete success was seen in 54% at 1 year, 45% at 3 years and 40% at 6 years in bleb leak group as compared to 88% at 1 year, 78% at 3 years and 71% at 6 years in the sweating bleb group (Figure 1); the difference was statistically significant at all time points (p=0.01). The qualified success probability was 94% at 1 year in bleb leak group and 100% in sweating bleb group, which decreased to 83.7% and 82% at 6 years in the bleb leak group and sweating bleb group respectively (Figure 2). The qualified success probability was similar between the two groups (p=0.55).

Discussion: Intuitively, leaking blebs are likely to be associated with higher rates of bleb related and hypotony related complications. However, our data shows that the complications like blebitis, hypotony maculopathy and shallow AC with corneal edema were more common in eyes with sweating blebs compared to leaking blebs (42% vs 11%, p=0.002%). The eyes with sweating blebs also had worse visual acuity compared to the eyes with leaking blebs. This difference could not be explained by the preoperative factors like type of glaucoma or use of antimetabolites (which was similar between the two groups). The one parameter that was significantly different was the, longer duration from primary glaucoma surgery to bleb repair in the sweating bleb group. It is possible that the longer the presence of avascular and sweating blebs, the higher the chance of bleb related complications like hypotony with associated maculopathy, cataract and corneal edema. The longer duration before diagnosis and the greater incidence of complications in the sweating bleb group may also be a result of greater difficulty in diagnosing sweating blebs, which is subtle compared to a frank leak.                    Ocular complications like hypotony maculopathy and blebitis are definite indications for bleb repair in eyes with delayed leaking blebs or sweating blebs.15, 18, 22, 24 however, uncommon indications for bleb repair are thin cystic or sweating blebs without ocular complications.21 In our study evaluating the outcomes of bleb repair for delayed bleb leaks and sweating blebs, the complete success probability was significantly better (88% versus 54% at 1 year and 71% versus 40% at 6 years) in the sweating bleb group compared to the leaking bleb group respectively (p=0.01). The possible reason for the significant difference in the success rates between the two groups could be the difference in the bleb function between the two groups. It is possible that in eyes with frank bleb leak, the bleb was flat with less sub-conjunctival aqueous, predisposing them to sub-conjunctival fibrosis. In these eyes when the bleb leak is repaired, the IOP may elevate significantly, often needing medications or surgery for IOP control. On the other hand, in eyes with sweating blebs, the blebs are cystic and elevated and functional. Hence when repaired with adequate precautions; the bleb function would be preserved providing better IOP control. From our results, we would consider leaking bleb a strong risk factor for failure after bleb repair. The technique of bleb repair is unlikely to have contributed to the difference in success rates of the two groups as similar number of eyes in both the groups underwent bleb repair with conjunctival advancement and conjunctival autograft.The reported overall success rates of bleb repair with various techniques were 80-86% at 1 year, which decreased to 50% at 5 years.18, 21 The variability in the outcomes across studies is due to the differences in the indications, type of intervention, definition of success and the follow up duration. There is limited literature comparing the outcomes of bleb repair in leaking and non-leaking blebs. In the study by Catoira et al, following bleb repair with conjunctival advancement, leaking blebs showed 47% success (8/17 eyes) versus 80% success (8/10 eyes) in eyes with non-leaking cystic blebs with hypotony, similar to our results. Although they did not compare the two indications in their study, their results clearly show that the eyes with leaking blebs had higher tendency to scar and fail and required AGM for IOP control compared to the eyes with non-leaking blebs.

In our study, bleb leak closure was achieved in 95% eyes in the leaking bleb group. Most studies have reported similar success rates ranging from 80-100% for bleb leak closure.18, 20-22, 24 The aim of bleb repair is not only closure of bleb leak or resolution of hypotony, but also to preserve the bleb function. Early postoperative increase in IOP is an expected complication following bleb repair as was noted in 2-13.7% eyes in previous reports.21, 24, 26 This complication was seen in majority of eyes that underwent scleral flap tightening in Radhakrishnan et al study.21 The number of eyes with elevated IOP was higher in the leaking bleb group (9 eyes, 20% eyes, 95% CI: 9.6-34.6) compared to sweating bleb group (2 eyes, 6.5%, 95% CI: 0.8-21.4%) at one-month. However, in our series, there was no association noted between high post op IOP and additional scleral flap sutures. Two out of 5 eyes (1 in 4 eyes in leaking bleb group and 1 in 2 eyes in sweating bleb group) that had scleral flap suture during bleb repair needed AGM for IOP control and one of these eyes also needed TSCPC for IOP control 3 months after bleb repair. On the other hand, 19 out of 71 eyes without the scleral flap suture had raised IOP.                            Early bleb leaks are reported in 10.7-46% eyes following bleb repair,15, 22, 24 and persistent hypotony or recurrent bleb leaks are reported in 3.5-8% eyes.18, 22, 24 Persistent or recurrent bleb leaks following bleb repair can occur secondary to flap retraction or leakage between the sutures. This can be avoided with slightly oversized graft to achieve traction free conjunctival closure. We had 2 eyes in the leaking bleb group with persistent leak needing resuturing. There were no recurrent bleb leaks noted in both the groups. In our series, 3 eyes had persistent hypotony (3.9% eyes, 2 eyes in sweating bleb group and one eye in leaking bleb group), however all 3 eyes had good visual recovery hence no further intervention was attempted. If these eyes were considered successful as in Radhakrishnan et al study21 (who considered resolution of hypotony either by IOP criteria of  >5 mm Hg or by visual recovery despite not satisfying the IOP criteria) our success rates would further increase.

Long term IOP elevation needing AGM for IOP control or repeat glaucoma surgery following bleb repair is reported in 12- 50% of the eyes.15, 18, 21-24 In our study, post bleb repair, long-term AGM was needed in 18 (40%, 95% CI: 25.7, 55.7) eyes in the leaking bleb group compared to 6 (19.4%, 95% CI: 7.5, 37.5) in the sweating bleb group (p=0.06). Repeat glaucoma surgery was needed in 4.2% eyes in leaking bleb group and 3.2% eyes in sweating bleb group.

Blebitis and endophthalmitis are complications that can occur few months to many years after bleb repair. Radhakrishnan et al reported blebitis in 5% of cases (9/177) after bleb revision surgery with a mean interval between the revision surgery and diagnosis of blebitis of 3.0±2.4 years.21Pandey et al in a series of 58 eyes with bleb repair reported 1 case of recurrent blebitis with endophthalmitis 6 months following bleb repair. This eye had prior episode of blebitis with endophthalmitis prior to bleb repair and resulted in phthisis despite treatment with vitrectomy and intravitreal antibiotics.22 Two eyes in our series developed blebitis in the late postoperative period. One eye developed blebitis after 3 months of bleb revision, which resolved with intensive topical antibiotics. The other eye developed blebitis and endophthalmitis after 3 years of bleb revision and required bleb excision with vitrectomy and intraocular antibiotics.  Both the eyes maintained stable vision and well controlled IOP and both these eyes did not have prior blebitis.

Bleb dysesthesia following bleb repair is a rare complication. Following bleb repair, 5/177 eyes had bleb dysesthesia in a study by Radhakrishnan et al21 and 3/30 eyes in Catoira et al series had bleb dysesthesia.11 In our series, one eye in each group had overhanging bleb. Apart from the discomfort the dysesthetic blebs cause, these eyes are also prone for complications like blebitis as was seen in one of the eyes in our series.

Close to 15.5% and 25.8% eyes in the two groups developed significant cataract. This could be related to shallow AC, low-grade inflammation and post operative steroid use. Although corneal complications are rare following bleb repair, preexisting ocular condition and anterior segment status would contribute to corneal edema and decompensation. In our series, 3 eyes in sweating bleb group had worsening of preexisting corneal edema needing keratoplasty. All the 3 eyes had hypotony with shallow AC before bleb repair that resulted in this complication.

The limitations of our study are inherent to the retrospective nature. Bleb function before the development of the bleb leak, duration of bleb leak and bleb morphology are important factors that could determine the functional success of filtering surgery after a bleb repair. However, these details were not available in our study. There were two techniques of bleb repair performed in our study, the conjunctival autograft and conjunctival advancement; the choice of which was at surgeons’ discretion. The difference in the technique of bleb repair could have influenced our results, however on subgroup analysis, the technique of bleb repair did not contribute to the difference in the success rates of bleb repair in both the groups. There were multiple surgeons who performed the surgeries, which could have influenced our results. However, all the surgeons were fellowship trained glaucoma specialists and the surgical technique followed was similar, hence unlikely to have contributed to the difference in the surgical success.

The prevalence of higher preoperative complications in the sweating bleb group and better bleb survival following bleb repair, we recommend early intervention in eyes with sweating blebs, rather than wait for an obvious bleb leak or a complication to intervene. The importance of careful examination to diagnose sweating blebs cannot be overemphasized.

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Legends to figures:

Figure: 1 Kaplan-Meier survival analysis showing complete success probability of bleb repair in eyes with leaking and sweating blebs.

Figure: 2 Kaplan-Meier survival analysis showing qualified success probability following bleb repair in eyes with leaking and sweating blebs.