A bleb leak is a condition in which aqueous humor leaks out of the eye through the wall of a filtering bleb formed after glaucoma filtration surgery (such as trabeculectomy or Ex-PRESS shunt surgery). It is confirmed by a positive Seidel test using fluorescein. This is a complication specific to filtration surgery and is not typically seen in other ophthalmic surgeries.
Based on the time of onset, bleb leaks are broadly classified as follows.
Furthermore, based on persistence, leaks are divided into transient and persistent leaks. Persistent leaks carry a high risk of infection and may progress to hypotony maculopathy, thus requiring more aggressive treatment.
The incidence of aqueous humor leakage from the conjunctival wound in the early period after trabeculectomy is reported to be 3.4–14% 1). When mitomycin C (MMC) is used, the risk of leakage over 5 years after surgery reaches 15% 2). The incidence of hypotony maculopathy occurring 1 month or more after surgery is 0.9–5% 1).
Bleb leak is the greatest risk factor for bleb infection, increasing the infection risk by 26 times. The cumulative incidence of bleb-related infection within 5 years after trabeculectomy with MMC is reported to be 2.2%2).
Trabeculectomy is the most established filtering surgery for glaucoma, offering excellent long-term intraocular pressure reduction, but complications related to the filtering bleb can occur throughout the patient’s life. Bleb leak is one of the representative complications, and early detection and appropriate management of the leak determine the long-term postoperative prognosis.
This article covers the management of bleb leak (the leak itself). For details on infections secondary to leakage, see Bleb-related infections.
Bleb leak refers to the leakage of aqueous humor through the bleb wall, confirmed by a positive Seidel test. In contrast, bleb infection (bleb-related infection) is an infectious complication caused by bacterial entry through the leak site. Bleb leak is the greatest risk factor for infection, but many cases involve leakage without infection. Prompt closure of the leak is key to preventing infection.
Bleb leak itself is often asymptomatic, but may be accompanied by the following symptoms.
Observation of the bleb appearance is primarily performed using slit-lamp microscopy, and the following five items are assessed.
Persistent aqueous humor leakage leads to hypotony and may present the following findings1).
Multiple factors contribute to the development of bleb leak.
Antimetabolites such as mitomycin C (MMC) and 5-FU are used to suppress scar formation around the filtering bleb, thereby maintaining long-term intraocular pressure reduction. However, they also promote thinning and avascularity of the bleb wall and reduce mucin production due to decreased goblet cells. These changes weaken the conjunctival barrier and increase the risk of aqueous humor leakage.
The Seidel test is used for definitive diagnosis of bleb leak. It is recommended to perform this test routinely at each examination after trabeculectomy to assess for leakage. The procedure is as follows.
Representative bleb classification systems based on appearance include the Moorfields Bleb Grading System (MBGS) and the Indiana Bleb Appearance Grading Scale (IBAGS). These systems score bleb extent, height, vascularity of the wall, and wall thickness, and are used for functional evaluation of filtering blebs and stratification of leakage risk. Recording scores over time allows objective tracking of morphological changes and progression of thinning.
Anterior segment OCT can evaluate bleb wall thickness, cavity status, and subconjunctival tissue characteristics in cross-sectional images 4). It is useful for detecting subtle wall thinning that is difficult to assess by slit-lamp examination and for longitudinal evaluation of treatment effects.
Conditions that require differentiation from bleb leak are shown below.
| Differential Diagnosis | Seidel Test | Features |
|---|---|---|
| Bleb Leak | Positive | Aqueous humor outflow confirmed |
| Filtering bleb infection | Positive to negative | Hyperemia, white-on-red, pain |
| Overfiltration | Negative | Low intraocular pressure but no leakage from conjunctiva |
| Conjunctivochalasis | Negative | Epiphora due to conjunctival laxity |
In bleb infection, debris may temporarily occlude the leakage site, causing the Seidel test to be negative. If an opaque, white, cloudy bleb surrounded by hyperemic conjunctiva (so-called “white-on-red”) is observed, infection should be suspected, and a detailed examination including conjunctival swab and aqueous humor culture should be performed. Overfiltration is excessive aqueous outflow from the scleral flap, leading to hypotony and shallow anterior chamber, but it is distinguished from bleb leak by the absence of conjunctival leakage.
Treatment for bleb leak is selected based on the degree of leakage, bleb vascularity, and presence of complications. Since aqueous leakage is a significant risk factor for bleb infection, it must be promptly controlled 2).
Leaks occurring in vascularized conjunctiva have a relatively high chance of closure with conservative treatment.
Non-invasive Treatment
Pressure patch: Accurately compress the scleral flap with gauze, etc. Also effective for improving overfiltration.
Bandage contact lens (BCL): A large-diameter soft contact lens of 18 mm is worn to promote wound closure.
Aqueous humor suppressants: Reduce leakage by decreasing aqueous humor production via eye drops.
Atropine sulfate hydrate eye drops: Suppress aqueous humor production by relaxing the ciliary body, and are also expected to have anti-inflammatory effects1).
Minimally Invasive Procedures
Autologous blood injection: A method of injecting the patient’s own blood into and around the filtering bleb. Improvement of hypotony maculopathy has been reported3).
Cyanoacrylate tissue adhesive: Applied locally to small leakage sites to seal them.
Intracameral injection of viscoelastic material or air: Forms the anterior chamber and temporarily suppresses leakage.
If conservative treatment does not improve the condition or if hypotony maculopathy develops, surgical intervention is performed.
The Glaucoma Practice Guidelines (5th edition) recommend the following regarding antibiotic use after trabeculectomy1)2).
Autologous blood injection is a treatment in which the patient’s own blood is collected and injected into and around the filtering bleb3). The clotting action of the blood promotes closure of the leakage site. While improvement of hypotony maculopathy has been reported, it can cause a sudden rise in intraocular pressure3), so strict postoperative intraocular pressure monitoring is necessary.
If conservative treatment does not improve the condition, surgical treatment is performed. Excision of the avascular filtering bleb and conjunctival advancement have been reported to stop leakage in about 90% of cases with a single surgery, and recurrence is rare3). The use of amniotic membrane transplantation in combination has also been reported to be effective3). The indication for surgery is determined by the degree of leakage, bleb characteristics, and presence of complications.
Trabeculectomy is a surgery that creates a window in the limbal corneosclera, establishing a non-physiological aqueous humor outflow pathway from the anterior chamber to the subconjunctival tissue 1). Postoperative intraocular pressure is determined by the balance between aqueous humor production and outflow through the scleral flap into the filtering bleb.
During the postoperative wound healing process, scar tissue forms in the subconjunctival tissue. Since this scarring can lead to reduced bleb function (elevated intraocular pressure), the standard management involves using MMC to suppress early excessive tissue reactions and increase the likelihood of long-term bleb maintenance 1). However, MMC also induces the following changes.
These changes act in combination, sustaining the risk of bleb leak from the early to late postoperative period. Particularly during the first few months after surgery, when scarring progresses rapidly, the outflow resistance of the scleral flap and bleb morphology change dynamically, requiring timely intervention.
Early leakage is mainly due to mechanical failure of the surgical wound. The main causes are suture insufficiency of the scleral flap, dehiscence of the conjunctival incision, or excessive filtration due to a sudden change in the balance of aqueous humor production and outflow. It has been shown that additional postoperative subconjunctival injection of 5-FU increases the frequency of aqueous humor leakage in addition to corneal epithelial damage 1).
Late leakage occurs as a result of chronic tissue degeneration caused by antimetabolites. Progressive thinning of the bleb wall over a long period exceeds a critical point at some time, and transmural leakage of aqueous humor becomes apparent. Mechanical trauma (such as rubbing the eye) may also trigger it.
Persistent aqueous humor leakage causing hypotony can lead to the following series of changes 1).
These combined factors lead to severe visual impairment (hypotony maculopathy). Transient postoperative hypotony does not affect long-term intraocular pressure, but persistent hypotony can cause irreversible macular changes.
Aqueous humor leakage from the filtering bleb provides a route for tears and periocular commensal bacteria to enter the eye through the leak site 2). The normal conjunctiva has multilayered defense mechanisms including epithelial tight junctions, mucin from goblet cells, and lysozyme and IgA in tears; however, in blebs weakened by antimetabolites, bacteria can easily invade through the leakage site.
The longer the leakage persists, the higher the infection risk. Once infection occurs, it may progress through the stage of blebitis (infection localized to the filtering bleb) to spread into the anterior chamber and further into the vitreous (bleb-associated endophthalmitis) 2). Bleb-associated endophthalmitis has been reported to result in visual acuity of 0.1 or worse in 94% of cases despite aggressive treatment, so prompt management at the bleb leak stage greatly affects prognosis.
For filtering blebs with leakage or hypotony, surgical repair such as avascular bleb excision or conjunctival advancement aims to achieve both leak closure and intraocular pressure control3).
In reoperation cases with insufficient healthy conjunctiva, repair methods combining conjunctival advancement with auxiliary materials such as amniotic membrane may be considered3).
Minimally invasive glaucoma surgery (MIGS), which has become increasingly popular in recent years, includes many devices that do not form blebs, unlike traditional trabeculectomy. Because they drain aqueous humor via Schlemm’s canal or the suprachoroidal space, they do not create subconjunctival filtering blebs, structurally avoiding the risk of postoperative hypotony or bleb leak. However, the intraocular pressure-lowering effect is more limited than trabeculectomy, and indications are often restricted to mild to moderate glaucoma. Some MIGS devices that form subconjunctival blebs exist, but since they do not use antimetabolites, the leakage risk is reduced compared to traditional trabeculectomy.
Kojima et al. (2015) reported the evaluation of filtering bleb internal structure using anterior segment OCT4). Since it allows quantitative assessment of wall thickness, low-reflectivity areas in the lumen, and subconjunctival tissue characteristics, it is expected to be applied for predicting microleaks and leakage risk that are difficult to detect with Seidel testing alone. In the future, AI-based OCT image analysis is expected to enable automatic detection of progressive bleb wall thinning and prediction of the optimal timing for preventive intervention before leakage occurs.
In addition to amniotic membrane transplantation, reports on bleb repair methods using biomaterials such as collagen matrix and fibrin glue are accumulating. For cases where healthy conjunctiva is insufficient for conventional conjunctival advancement, the development of conjunctival substitutes through tissue engineering approaches is also under research.
