Proposed Article Structure
To interpret this study in a clinically useful way, the article is organized into: Highlights; Clinical Background and Unmet Need; Study Design and Methods; Key Results; Mechanistic and Clinical Interpretation; Strengths and Limitations; Practice Implications; Conclusion; Funding, Registration, and Citation.
Highlights
A single intraoperative intravitreal dose of bevacizumab given during trabeculectomy with mitomycin-C was associated with better 3-year surgical survival than placebo.
The benefit was seen for both complete success, defined as achieving target intraocular pressure without topical therapy, and qualified success, defined as achieving target pressure with topical therapy if needed.
Patients in the placebo group were more likely to require postoperative glaucoma drops, with differences evident as early as 3 months and persisting through 36 months.
The findings support vascular endothelial growth factor inhibition as a potentially useful adjunct to wound modulation in filtration surgery.
Clinical Background and Unmet Need
Trabeculectomy remains a key pressure-lowering operation for patients with glaucoma whose disease is progressing despite medical therapy, laser treatment, or both. Its goal is to create a guarded fistula that allows aqueous humor to exit the anterior chamber into the subconjunctival space, thereby lowering intraocular pressure (IOP). The long-term success of the procedure depends heavily on wound healing. Excessive postoperative fibrosis can lead to bleb failure and loss of pressure control.
Because fibrosis is central to surgical failure, adjunctive antimetabolites such as mitomycin-C (MMC) are routinely used to suppress fibroblast proliferation. MMC has substantially improved outcomes, but it does not eliminate failure, and its use comes with trade-offs, including thin avascular blebs, hypotony-related complications, and infection risk. Therefore, there remains a strong interest in identifying adjunctive therapies that can improve bleb survival without adding undue toxicity.
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF). In ophthalmology, it is widely used intravitreally for retinal vascular diseases, although its role in glaucoma surgery is less established. The rationale for bevacizumab in trabeculectomy is biologically plausible: VEGF is involved not only in angiogenesis but also in inflammatory and fibroproliferative wound-healing pathways. Modulating VEGF activity might reduce vascularity and scarring in the bleb region, potentially prolonging filtration function. Shorter-term studies have explored anti-VEGF strategies as alternatives or complements to antimetabolites, but robust long-term randomized data have been limited. This makes the present 3-year follow-up especially relevant.
Study Design and Methods
This was a single-centre, parallel-group, double-blinded, randomized, placebo-controlled trial conducted in an ophthalmic outpatient referral centre within a tertiary teaching hospital. The trial enrolled patients requiring primary trabeculectomy, redo-trabeculectomy, or combined phaco-trabeculectomy for progressing glaucoma.
A total of 131 patients were randomized to receive either intraoperative intravitreal bevacizumab 1.25 mg in 0.05 mL (n=65) or placebo with balanced salt solution 0.05 mL (n=66). The injection was given as a single intraoperative dose during trabeculectomy with MMC.
The primary outcome was treatment success. The investigators used two clinically relevant definitions. Complete success required IOP to remain below a predefined target pressure without topical glaucoma medication. Qualified success required IOP to remain below the predefined target with the aid of topical medication. This dual framework is important because, in glaucoma surgery, a reduction in medication burden is meaningful in itself, but pressure control remains the core therapeutic objective.
Of the 131 randomized participants, 111 completed 36 months of follow-up, corresponding to an 85% retention rate. For a surgical glaucoma trial with long follow-up, this is a reasonably strong completion rate and supports the reliability of the longitudinal outcome assessment.
Key Results
Trabeculectomy survival at 36 months
At 36 months, trabeculectomy survival was significantly higher in the bevacizumab group than in the placebo group. For complete success, the reported hazard ratio was 0.17 with P=0.015. For qualified success, the hazard ratio was 0.07 with P=0.03.
These hazard ratios indicate a markedly lower risk of surgical failure over time in the bevacizumab-treated cohort. Although the abstract does not provide confidence intervals, the effect sizes are numerically substantial. A hazard ratio well below 1 suggests that the addition of bevacizumab was associated with a durable separation in survival curves rather than only a transient postoperative effect.
Need for postoperative topical therapy
The placebo cohort had a higher requirement for topical glaucoma therapy at multiple follow-up points: 3 months (P=0.008), 6 months (P=0.009), 12 months (P=0.007), and 36 months (P<0.005). This pattern suggests that the benefit of bevacizumab may have emerged early and remained clinically relevant over time.
From a practical standpoint, reduced need for topical therapy matters for several reasons. First, fewer drops may improve adherence, which is often imperfect in chronic glaucoma care. Second, reducing exposure to topical preservatives may help preserve conjunctival health. Third, patients often judge surgical success partly by whether they can reduce or stop glaucoma medications after surgery. The findings therefore have both physiological and patient-centered importance.
Retention and follow-up
Eighty-five percent of randomized patients completed 36 months of follow-up. While some attrition is unavoidable in long-term surgical studies, this level of retention is acceptable and helps support the validity of the long-term survival analysis. However, the abstract does not detail whether losses to follow-up were balanced between groups or whether sensitivity analyses were performed to test the influence of missing data.
Safety reporting
The abstract provided does not report adverse events, bleb-related complications, visual outcomes, or additional surgical interventions. This is an important gap for interpretation. An intervention that improves survival but increases hypotony, avascular blebs, endophthalmitis risk, or retinal complications would require a different clinical calculus. Therefore, the full publication should be reviewed carefully for safety data before the findings are translated into routine practice.
Mechanistic and Clinical Interpretation
The biological rationale for this result is credible. Wound healing after trabeculectomy involves a tightly linked cascade of inflammation, angiogenesis, and fibroblast activation. VEGF contributes to vascular remodeling and may also influence scar formation. By suppressing VEGF intraoperatively, bevacizumab may blunt the postoperative angiogenic response and reduce the vascular scaffold that supports fibroblast-driven bleb failure. In theory, this could complement the antiproliferative effects of MMC rather than simply duplicate them.
Notably, the drug in this study was delivered intravitreally rather than subconjunctivally. That route is familiar to retina specialists and widely used in practice, but in the context of filtration surgery it is less conventional than perioperative subconjunctival anti-VEGF approaches. The intravitreal route may offer a more standardized dose and delivery technique, though it also raises distinct safety considerations, including rare but serious injection-related complications.
The magnitude of benefit suggested by the hazard ratios is striking. If reproduced, these findings could indicate that VEGF modulation meaningfully alters long-term bleb biology. The persistent reduction in medication need strengthens the impression that the effect is clinically substantive rather than statistically marginal.
At the same time, the result should be interpreted with appropriate caution. Surgical outcomes in glaucoma are highly sensitive to operative technique, bleb management strategy, case mix, and postoperative intervention thresholds. A single-centre study can achieve excellent internal consistency, but it may also reflect local expertise not easily generalized to other settings.
Strengths of the Trial
This study has several important strengths. First, it used a randomized, placebo-controlled, double-blinded design, which remains the gold standard for evaluating an adjunctive surgical therapy. Second, the 3-year follow-up is a major asset. Many wound-modulation strategies show early promise but fail to translate into durable benefits. Third, the trial addressed clinically meaningful endpoints, especially treatment survival and postoperative medication burden. Fourth, the inclusion of patients undergoing primary, redo-, and combined phaco-trabeculectomy increases real-world relevance, since glaucoma surgeons frequently manage a heterogeneous surgical population.
Key Limitations
The most important limitation is the single-centre design. External validity may therefore be limited, particularly if perioperative and postoperative management protocols differ across practices. The sample size, while respectable for a surgical randomized trial, remains modest, especially for subgroup analyses. The abstract also does not provide confidence intervals, absolute survival percentages at 36 months, or detailed baseline characteristics, all of which are needed to judge the precision and balance of treatment effect.
Another limitation is the absence of safety data in the abstract. For clinicians considering adoption, efficacy alone is not enough. Data on hypotony, shallow anterior chamber, bleb leak, needling rates, infection, cataract progression in standalone cases, visual acuity trajectories, and intravitreal injection-related adverse events are essential.
The enrolled population included primary trabeculectomy, redo-trabeculectomy, and phaco-trabeculectomy cases. This broad inclusion improves applicability, but it also introduces heterogeneity. These subgroups can have materially different baseline risks of failure. Without subgroup analyses, it is difficult to know whether the apparent benefit was consistent across surgical indications or driven by one subgroup.
Finally, contemporary glaucoma practice is evolving. In some regions, minimally invasive glaucoma surgery and tube shunts are increasingly used in selected patients. Even so, trabeculectomy remains indispensable for patients needing low target pressures, so optimization of its long-term success remains highly relevant.
How This Fits With Existing Evidence
Previous work on anti-VEGF agents in trabeculectomy has produced mixed results, often limited by short follow-up, small sample size, differing routes of administration, and varied comparators such as MMC or 5-fluorouracil. Some studies have suggested that anti-VEGF therapy can reduce bleb vascularity and may improve early postoperative outcomes, but durable superiority over established antimetabolites has not been consistently shown. The current study is notable because bevacizumab was used in addition to MMC and still appeared to improve long-term survival.
This adjunctive rather than replacement strategy may be the most clinically plausible path forward. MMC targets fibroblast proliferation broadly, whereas bevacizumab may specifically modify angiogenesis-related wound signaling. The combination could theoretically widen the therapeutic window if it improves efficacy without substantially increasing complications. Whether that is truly the case depends on the full safety profile and on replication in multicentre settings.
Current glaucoma guidelines emphasize achieving individualized target IOP and recognizing the need for durable pressure control in progressive disease. They do not currently endorse routine intravitreal bevacizumab during trabeculectomy. This trial alone is unlikely to immediately change guidelines, but it provides a strong signal that merits confirmation and may stimulate larger multicentre trials.
Practice Implications for Clinicians
For glaucoma surgeons, this study suggests that a single intraoperative intravitreal bevacizumab injection may enhance the durability of trabeculectomy performed with MMC. The potential advantages are clinically meaningful: higher probability of sustained surgical success and lower dependence on postoperative topical therapy.
However, practice change should be measured rather than immediate. Several questions remain before widespread incorporation into routine surgery: Which patients benefit most, primary versus redo cases? Does the effect differ in phakic versus pseudophakic eyes or by glaucoma subtype? What is the complication profile compared with standard MMC trabeculectomy alone? Is the benefit maintained beyond 3 years? And how does this strategy compare with or complement intensified postoperative bleb management?
For clinicians in high-volume tertiary centres, the findings may justify close attention to the full text and consideration of local protocol review, especially in patients at high risk of bleb failure. For broader adoption, replication in a multicentre randomized trial with detailed safety reporting, standardized failure definitions, and patient-reported outcomes would be highly valuable.
Conclusion
This randomized double-blinded placebo-controlled trial provides persuasive long-term evidence that a single intraoperative intravitreal dose of bevacizumab can improve trabeculectomy survival when added to MMC. At 36 months, bevacizumab was associated with better complete and qualified surgical success and with a lower need for topical glaucoma medication from early postoperative follow-up through 3 years.
The study addresses a central challenge in glaucoma surgery: durable control of wound healing without compromising safety. Its findings are biologically plausible and clinically important, but they should be interpreted in the context of single-centre design, modest sample size, and limited safety detail in the abstract. Overall, the trial strengthens the case for VEGF inhibition as a potentially useful adjunct in filtration surgery and sets the stage for confirmatory multicentre research.
Funding, Registration, and Citation
Funding information and a ClinicalTrials.gov registration number were not provided in the abstract or citation details supplied here. These details should be verified in the full article.
Citation: Landers J, Mullany S, Hassall MM, Craig JE. Intravitreal Bevacizumab Improves Trabeculectomy Survival at 3 Years: Long-term Follow-up from The ‘Bevacizumab in Trabeculectomy Study’. Ophthalmology. 2026-05-13. PMID: 42134554. URL: https://pubmed.ncbi.nlm.nih.gov/42134554/
Selected References
Landers J, Mullany S, Hassall MM, Craig JE. Intravitreal Bevacizumab Improves Trabeculectomy Survival at 3 Years: Long-term Follow-up from The ‘Bevacizumab in Trabeculectomy Study’. Ophthalmology. 2026-05-13. PMID: 42134554.
European Glaucoma Society. Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2021;105(Suppl 1):1-169.
Cairns JE. Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol. 1968;66(4):673-679.
Wilkins M, Indar A, Wormald R. Intra-operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev. 2005;(4):CD002897.
Medeiros FA, Lisboa R, Weinreb RN, et al. A randomized clinical trial of mitomycin C versus bevacizumab as adjunctive treatments for trabeculectomy. Although anti-VEGF adjunct studies exist, readers should verify individual reports directly in PubMed when comparing methodologies and outcomes.