Bleb Leaks and Bleb-Related Infection

Understanding the relevant literature is essential to managing these conditions..

By Jeffrey M. Zink, MD, and Francisco E. Fantes, MD
 
Bleb leaks are a common problem encountered by glaucoma specialists and general ophthalmologists. A cross-sectional analysis reported a 1.4% to 3.7% incidence of late-onset bleb leaks following filtration surgery.1 Higher rates of late-onset bleb leaks are seen with the use of antimetabolites (eg, mitomycin C [MMC] and 5-fluorouracil [5-FU]).2-4 The treatment of late-onset bleb leaks presents a difficult management problem with many described treatments.

A potentially devastating complication of a leaking bleb is the development of blebitis and bleb-associated endophthalmitis. The incidence of the former has been reported at 3% of superior and 9% of inferior filtration surgeries performed with 5-FU.5 The term blebitis refers to a limited form of infection around or inside a filtering bleb that is often associated with anterior chamber inflammation. In contrast, bleb-associated endophthalmitis is blebitis in the setting of inflammatory cells in the vitreous cavity. A thorough understanding of bleb leaks, blebitis, and bleb-associated endophthalmitis is important to the proper management of these patients and the prevention of permanent visual loss.

BLEB LEAKS
Clinical Treatment
Conservative measures for the treatment of bleb leaks have had variable success. Some of these methods include tamponade with an 18-mm bandage contact lens, compression sutures, a cyanoacrylate tissue adhesive, aqueous suppressants, and direct suturing with a microvascular needle.6-9 Based on our clinical experience, another conservative treatment that is reasonably successful is a mildly irritating antibiotic such as gentamicin, which can be combined with a bandage contact lens.

Other, slightly more invasive techniques have been proposed. For example, the injection of autologous blood10,11 involves drawing a small amount of blood with a 27-gauge needle and injecting 0.5 mL into the bleb’s periphery. It is believed that the red blood cells and plasma fibrin provide a temporary plug, possibly allowing subsequent fibroblastic transformation.10,11

Some practitioners advocate a bleb-needling technique. This approach involves elevating the conjunctiva off the surface of the globe with balanced salt solution and a 27-gauge needle. The surgeon then incises the underlying scarring of the Tenon’s capsule with a 30-gauge needle to create a more diffuse bleb that is decompressed. It is thought that creating a larger bleb space reduces the focal stress on the area of the leak.12

Alternatively, some success has been reported with procedures using argon and Nd:YAG lasers, although these methods have not gained widespread acceptance.13,14

Important considerations regarding management include recognizing the cause of the leak and determining the characteristics of the tissue at the site of the leak. For example, leaks in the suture line generally occur either because of a loose suture that is causing the wound to gape or because the suture itself “claws” through the conjunctiva to cause a buttonhole. Oftentimes, leaks caused by inadequate conjunctival closure will cease with time (due to later closure) and conservative treatment. Those caused by a suture-related buttonhole usually do not stop until the suture stretching the wound open is removed. In general, bleb leaks that occur early in the postoperative period and in vascular conjunctiva have a better chance of closing with the conservative treatments mentioned earlier. Leaks in avascular bleb tissue are less likely to close with conservative treatment and often require a compression suture or bleb revision (described later).

Surgical Revision
If conservative treatments fail, it is often necessary to return to the OR to revise a leaking bleb. One of a number of surgical strategies is the bleb-decompression technique in which the surgeon dissects the fibrous walls of the focal cystic bleb, thus releasing scar tissue to make the bleb more diffuse. This technique has the advantage of minimizing corneal astigmatism, decreasing the risk of postoperative IOP spikes, and creating a more diffuse bleb. Its disadvantages include leaving the ischemic bleb intact and increasing the risk of future bleb leak and infection.15

The technique of conjunctival advancement involves the excision or de-epithelialization of avascular bleb tissue. After dissecting posteriorly between the conjunctiva and Tenon’s capsule, the surgeon advances and sutures the conjunctiva to the limbus.15-17 This procedure sometimes requires autologous conjunctival transplantation from the inferior conjunctiva or fellow eye if there is not adequate adjacent conjunctiva present for advancement.18 One may place additional flap sutures or a patch graft (sclera, cornea, pericardium) if there is excessive flow through the scleral flap.19,20 Conjunctival advancement eliminates the avascular bleb tissue but can cause astigmatism, ptosis, and postoperative IOP spikes.15

Bleb revision with amniotic membrane transplantation was studied by Budenz et al,21 who compared the technique with conjunctival advancement surgery for leaking blebs in a randomized clinical trial. The cumulative bleb survival rate for amniotic membrane transplantation was 46% at 2 years versus 100% for conjunctival advancement surgery. Other investigators have described a double-layered technique for amniotic membrane transplantation, in which the membrane is folded upon itself with the basement membrane side outward. The modified technique for amniotic membrane transplantation may be useful in certain situations where a patient does not have healthy autologous conjunctiva to harvest for transplantation.22

BLEBITIS
Background
Blebitis is characterized by pain, mildly reduced vision, redness, and discharge. There are inflammatory cells present within the bleb that are often associated with anterior chamber inflammation or hypopyon. Many physicians view conjunctivitis, blebitis, and endophthalmitis as a continuum of diseases. Patients who previously underwent trabeculectomy surgery and have conjunctivitis are at risk of developing more focal inflammation within the filtering bleb that will lead to blebitis. Patients with conjunctivitis and a history of filtering surgery require close follow-up to ensure they do not develop a bleb-related infection.

Some of the reported risk factors for blebitis include the use of MMC, full-thickness procedures, filtration surgery performed without cataract surgery, late-onset bleb leakage, young age, and inferior blebs.5,23,24

The most common pathogens in blebitis are Staphylococcus epidermidis and Staphylococcus aureus25,26 (Figure 1). Haemophilus influenzae is a frequent pathogen with inferior blebs. In most series, Staphylococcus and Streptococcus are common causes of bleb-related endophthalmitis.27-29 The number of bleb-related endophthalmitides associated with staphylococcal species ranges from 7.0% to 58.2%, whereas the number caused by streptococcal species ranges from 19% to 57%.30-34

Figure 1. This patient’s left eye developed Serratia marcescens blebitis in the setting of a bleb leak many years after undergoing trabeculectomy with MMC. Serratia marcescens is a gram-negative rod that is a relatively rare cause of bleb-related infection.

Management
Once a patient has been clinically diagnosed with blebitis, it is a good idea to perform a culture of the bleb to determine the pathogen responsible for the infection. The initial treatment of blebitis usually involves aggressive dosing with fortified topical antibiotics (Figure 2) or a topical fourth-generation fluoroquinolone. Subconjunctival antibiotics should be considered in patients with severe blebitis (presence of a hypopyon) or potentially noncompliant patients. A minority of glaucoma specialists will use oral or intravenous antibiotics in the setting of blebitis.35

Figure 2. After treatment with intensive, fortified, topical antibiotics, the blebitis resolved in the eye shown in Figure 1, and a brisk bleb leak was observed 3 weeks later. Because of the persistent leak, the patient was taken to the OR for bleb revision and the placement of an inferonasal Baerveldt glaucoma drainage device (Advanced Medical Optics, Inc., Santa Ana, CA).

When there is severe anterior chamber inflammation with fibrin or vitreous cells present, the surgeon should consider the infection to be endophthalmitis and promptly inject intravitreal antibiotics and possibly a steroid. In cases of advanced visual loss with light-perception-only vision, the results of the Endophthalmitis Vitrectomy Study (EVS) may support more aggressive treatment with a pars plana vitrectomy. The EVS included patients who had undergone cataract surgery or the implantation of a secondary IOL. The study found that individuals with light-perception-only vision achieved better final visual outcomes with pars plana vitrectomy compared with vitreous biopsy. In addition, the EVS showed no difference in final visual acuity with the use of intravenous antibiotics. Pars plana vitrectomy or immediate vitreous biopsy had equal outcomes in patients presenting with hand motion or better vision.36 It is important to keep in mind that bleb-associated endophthalmitis may differ from that following cataract surgery or the implantation of a secondary IOL. It is probably wise to consult a vitreoretinal specialist for advice on the appropriate course of treatment in such advanced cases.

Examining the practice patterns of glaucoma physicians can be useful when developing treatment guidelines for patients with bleb leaks and blebitis. Reynolds et al35 conducted a survey of glaucoma specialists in the American Glaucoma Society regarding their practice patterns for managing blebitis. In this survey, 48% of respondents indicated that they usually or almost always saw blebitis in the context of a leaking bleb. For a persistently leaking bleb following the resolution of blebitis, 77% of the specialists indicated they would attempt to revise the bleb surgically, usually in the form of conjunctival advancement or autograft.

Recurrence
The blebs in patients with recurrent episodes of blebitis exhibit generalized or focal thinning as well as a depletion of goblet cells. Mucin, produced by goblet cells, serves an important function as a physical and biological barrier to foreign bodies and microorganisms. Poor immune response due to a lack of mucin and mechanically thin blebs are pathologic characteristics that are associated with infected blebs, especially in the setting of antimetabolite use.37

ADVANCED TRABECULECTOMY TECHNIQUES
Bleb leaks, blebitis, and bleb-associated endophthalmitis are difficult problems to manage. One hopes that methods will be developed to reduce the incidence of these complications following filtration surgery with antimetabolites. Newer trabeculectomy techniques such as those pioneered by Peng Khaw, PhD, FRCS, FRCOphth, may reduce the rate of complications from filtering procedures with adjunctive antimetabolites.38 Dr. Khaw utilizes a fornix-based conjunctival flap and a broad application of antifibrotic agents. This technique extends the posterior bleb and minimizes the formation of thin-walled cystic blebs, which are associated with an increased risk of bleb-related infection.38 In addition, methods for meticulous corneal-conjunctival closure with fornix-based flaps may result in fewer leaks at the limbus.38 A fornix-based conjunctival closure technique using a 9–0 nylon vertical mattress suture running the length of the conjunctival edge and anchored to an intact limbus at each end has been described. This technique can produce a leak-resistant closure for fornix-based conjunctival flaps in filtering surgeries with mitomycin C.39

CONCLUSION
It is to be hoped that continued advances in the techniques of filtration surgery will result in fewer bleb leaks and bleb-related infections. Ophthalmologists must remain vigilant, however, in order to detect bleb-related infections early and thereby minimize the visual consequences to their patients.

Francisco E. Fantes, MD, is Associate Clinical Professor of Ophthalmology at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. He acknowledged no financial interest in the product or company mentioned herein. Dr. Fantes may be reached at (305) 326-6000; ffantes@med.miami.edu.

Jeffrey M. Zink, MD, is a member of the Glaucoma Service at the Cincinnati Eye Institute and Volunteer Assistant Professor of Ophthalmology at the University of Cincinnati College of Medicine. He acknowledged no financial interest in the product or company mentioned herein. Dr. Zink may be reached at (513) 984-5133; jzink@cincinnatieye.com.

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