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Could One Extra Injection Make Glaucoma Surgery Last Longer? New Evidence Points to Better Trabeculectomy Success · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Could one extra injection make glaucoma surgery last longer?
• 0:04
  SPEAKER_00: New evidence points to better trabeculectomy success.
• 0:07
  SPEAKER_00: Evidence reviewed through August 30, 2026.
• 0:11
  SPEAKER_00: Introduction.
• 0:13
  SPEAKER_00: Trabeculectomy remains one of the most powerful operations for lowering eye pressure in advanced or progressing glaucoma.
• 0:20
  SPEAKER_00: It can reduce eye pressure to levels that are difficult to achieve with eye drops, laser treatment, or many newer minimally invasive procedures.
• 0:28
  SPEAKER_00: Its main weakness is scarring.
• 0:30
  SPEAKER_00: After surgery, the body may treat the new drainage pathway as an injury that needs to be repaired.
• 0:35
  SPEAKER_00: Fibroblasts move into the area, collagen is deposited, and the filtering bleb can become thick, flat, or sealed.
• 0:43
  SPEAKER_00: When that happens, the operation may gradually lose its effect.
• 0:47
  SPEAKER_00: A new long-term report suggests that a single intravitreal injection of beviseumab given during trabeculectomy, in addition to mitomycin C, may substantially improve the chance that the operation remains medication-free three years later.
• 1:01
  SPEAKER_00: The reported difference is striking.
• 1:03
  SPEAKER_00: 92.3% medication-free success with bivicisumab plus mitomycin C, 71.2% medication-free success with mitomycin C alone.
• 1:12
  SPEAKER_00: Absolute difference.
• 1:14
  SPEAKER_00: Approximately 21 percentage points.
• 1:16
  SPEAKER_00: Approximate number needed to treat 5 patients.
• 1:19
  SPEAKER_00: The result is important, but it is not yet enough to conclude that every patient undergoing trabeculectomy should receive the injection.
• 1:27
  SPEAKER_00: The trial was relatively small, took place at one center, involved a largely European ancestry population, and has not yet been independently reproduced with the same technique.
• 1:39
  SPEAKER_00: The short answer: the new evidence is promising and biologically plausible, and it is stronger than most earlier studies of anti-vascular endothelial growth factor treatment during trabeculectomy.
• 1:51
  SPEAKER_00: However, the evidence currently supports the following conclusion.
• 1:55
  SPEAKER_00: Intravitrial bevisimab may be a useful adjunct to mitomycin C in selected trabeculectomy patients, but it is not yet established routine care.
• 2:05
  SPEAKER_00: The apparent benefit seems to come mainly from better control of the early postoperative wound healing response rather than from permanently lowering eye pressure by itself.
• 2:15
  SPEAKER_00: The injection produced larger, less inflamed blebs early after surgery, and this early advantage was associated with fewer medications and fewer failures later.
• 2:26
  SPEAKER_00: The next step should be larger, independent, multi-center trials with more diverse patients and at least five years of follow-up.
• 2:34
  SPEAKER_00: What the new randomized trial actually found?
• 2:37
  SPEAKER_00: Study design and patient population.
• 2:40
  SPEAKER_00: The study was the three-year follow-up of the Beva Sysomab in trabeculectomy study, conducted at a single tertiary ophthalmic center in South Australia.
• 2:49
  SPEAKER_00: It included adults with progressing glaucoma, for which the treating surgeon believed trabeculectomy was necessary.
• 2:56
  SPEAKER_00: Participants could undergo primary trabeculectomy, redubeculectomy, trabeculectomy combined with cataract surgery.
• 3:04
  SPEAKER_00: A total of 131 patients were randomized.
• 3:07
  SPEAKER_00: 65 patients received bevisezomab, 66 patients received placebo, the bevisezoomab group received 1.25 mg in 0.5 milliliters by intravitreal injection at the end of trabeculectomy.
• 3:21
  SPEAKER_00: The control group received an intravitreal injection of balanced salt solution.
• 3:25
  SPEAKER_00: Both groups also received trabeculectomy with mitomycin C.
• 3:29
  SPEAKER_00: The surgical protocol used mitomycin C concentration of 0.04%, 2 minutes of exposure for lower risk eyes, 3 minutes for higher risk eyes, a standardized fornix-based surgical technique, a standardized scleral flap and suturing approach.
• 3:44
  SPEAKER_00: The original trial was double-masked, randomized, and placebo controlled.
• 3:48
  SPEAKER_00: Both the patient and surgical team were masked to whether bevacismab or placebo had been injected.
• 3:54
  SPEAKER_00: The randomization was stratified by surgeon and by primary versus redu trabeculectomy in the original trial.
• 4:01
  SPEAKER_00: Intravitrial bevacizomab improves trabeculectomy survival at three years.
• 4:07
  SPEAKER_00: There were some important population details.
• 4:09
  SPEAKER_00: The average age was approximately 76 years.
• 4:12
  SPEAKER_00: About 91% of eyes underwent primary rather than redu trabeculectomy.
• 4:18
  SPEAKER_00: Nearly all participants were of European ancestry, 129 of 131 participants in the original report.
• 4:25
  SPEAKER_00: Combined cataract surgery was more common in the Bevisezumab group, approximately 34% compared with 18% in the control group.
• 4:33
  SPEAKER_00: Active retinal vascular disease, active iris neovascularization, and several unusual forms of glaucoma were excluded.
• 4:40
  SPEAKER_00: The cataract surgery imbalance is important.
• 4:43
  SPEAKER_00: Combined cataract surgery can sometimes reduce trabeculectomy success, although the investigators found that it did not independently explain the results.
• 4:52
  SPEAKER_00: How did the researchers define success?
• 4:55
  SPEAKER_00: The study used a personalized target eye pressure based on the patient's preoperative eye pressure and visual field damage.
• 5:03
  SPEAKER_00: This is more individualized than simply defining success as an eye pressure below 21 mm of mercury.
• 5:09
  SPEAKER_00: Complete success.
• 5:11
  SPEAKER_00: Complete success meant that eye pressure remained at or below the patient's target, no topical pressure-lowering medication was needed.
• 5:18
  SPEAKER_00: This is the basis for the widely reported 92% versus 71% medication-free success result.
• 5:25
  SPEAKER_00: Qualified success.
• 5:27
  SPEAKER_00: Qualified success meant that eye pressure remained at or below the target.
• 5:32
  SPEAKER_00: Additional eye drops were allowed if needed.
• 5:34
  SPEAKER_00: Failure.
• 5:35
  SPEAKER_00: Failure occurred if eye pressure was above the target on at least two occasions despite maximum medical treatment.
• 5:42
  SPEAKER_00: Further glaucoma filtration surgery was required.
• 5:46
  SPEAKER_00: Irreversible blindness resulted from glaucoma or a surgical complication.
• 5:51
  SPEAKER_00: A return to the operating room to treat early hypotenuse-related maculopathy was not automatically classified as surgical failure because it is a recognized complication of filtration surgery.
• 6:02
  SPEAKER_00: Intravitrial bevisismab improves trabeculectomy survival at three years, three-year results.
• 6:08
  SPEAKER_00: At 36 months, the reported survival estimates were for the full table.
• 6:12
  SPEAKER_00: Please open this article on VisualFieldTest.com.
• 6:15
  SPEAKER_00: The statistical results were complete success p.01, hazard ratio for complete success failure 0.17, 95% confidence interval 0.6 to 0.52, p equals 0.02.
• 6:28
  SPEAKER_00: Qualified success p equals 0.03.
• 6:31
  SPEAKER_00: Hazard ratio for qualified success failure 0.07, 90% confidence interval, 0.01 to 0.80, p equals 0.03.
• 6:41
  SPEAKER_00: A hazard ratio of 0.17 suggests that the bevasisumab group experienced approximately 83% fewer failures over the follow-up period, although hazard ratios should not be interpreted as exactly the same as an 83% reduction in individual patient risk.
• 6:56
  SPEAKER_00: Absolute risk reduction and number needed to treat.
• 6:59
  SPEAKER_00: Using the reported three-year success percentages, complete success.
• 7:03
  SPEAKER_00: Failure with bevacyzzumab, approximately 7.7%.
• 7:07
  SPEAKER_00: Failure with mitomycin C alone, approximately 28.8%.
• 7:11
  SPEAKER_00: Absolute reduction in failure, approximately 21.1 percentage points.
• 7:15
  SPEAKER_00: Approximate number needed to treat 5.
• 7:18
  SPEAKER_00: In practical terms, if the result applies to similar patients, treating about 5 patients with the additional intravitreal injection could result in one additional patient remaining medication free at three years.
• 7:29
  SPEAKER_00: Qualified success.
• 7:31
  SPEAKER_00: Failure with bevisizumab, approximately 1.5%.
• 7:35
  SPEAKER_00: Failure with mitomycin C alone, approximately 10.6%.
• 7:39
  SPEAKER_00: Absolute reduction in failure, approximately 9.1 percentage points.
• 7:44
  SPEAKER_00: Approximate number needed to treat, 11.
• 7:47
  SPEAKER_00: These numbers are approximate because the study used survival analysis with some loss to follow-up, rather than a simple comparison in which every patient was observed continuously for exactly three years.
• 7:59
  SPEAKER_00: Did bevasisumab permanently lower eye pressure?
• 8:02
  SPEAKER_00: Not clearly.
• 8:04
  SPEAKER_00: The bevacismab group had lower eye pressure at approximately one month, but later average eye pressures were similar.
• 8:11
  SPEAKER_00: This does not mean the treatment had no effect.
• 8:13
  SPEAKER_00: The control group required more rescue treatment, including additional eye drops, bleb needling with 5-fluorocil, further glaucoma surgery.
• 8:23
  SPEAKER_00: Once these rescue treatments were given, the average eye pressures in the two groups became more similar.
• 8:29
  SPEAKER_00: Therefore, the more meaningful result may be that bevasisamab helped the original operation work without additional treatment.
• 8:37
  SPEAKER_00: Did it reduce repeat glaucoma surgery?
• 8:40
  SPEAKER_00: The 12-month report found that approximately 2% of patients in the bevacyamab group required further glaucoma surgery, 10% of control patients required further glaucoma surgery.
• 8:52
  SPEAKER_00: That is an approximate absolute reduction of 8% points, corresponding to a rough number needed to treat of 13 to avoid one additional glaucoma operation during the first year.
• 9:03
  SPEAKER_00: However, the three-year publication primarily reported survival outcomes rather than a detailed, independently powered comparison of repeat operations.
• 9:14
  SPEAKER_00: It would be inappropriate to assume that the same 8 percentage point reduction continues unchanged to five years.
• 9:21
  SPEAKER_00: Intravitrial bevasisomab improves trabeculectomy survival at 12 months.
• 9:26
  SPEAKER_00: What happened to the bleb?
• 9:28
  SPEAKER_00: The study included detailed photographic assessments using the Moorefield's bleb grading system.
• 9:32
  SPEAKER_00: At one month, blebs in the bevisisamab group were larger in central area, larger in total area, taller, less inflamed around the blood vessels.
• 9:42
  SPEAKER_00: The reduction in vessel inflammation was statistically very strong, with p-values below 0.001 in several comparisons.
• 9:50
  SPEAKER_00: By later visits, many of these differences had become smaller or disappeared.
• 9:56
  SPEAKER_00: Bleb height remained greater in the bevasisomab group at 12 months, but central and total bleb size were no longer clearly different.
• 10:04
  SPEAKER_00: This pattern is important.
• 10:06
  SPEAKER_00: It suggests that bevasisamab may not permanently change the bleb.
• 10:10
  SPEAKER_00: Instead, it may help the bleb get through the dangerous early healing period in a more favorable condition.
• 10:17
  SPEAKER_00: The control group caught up to some degree because more patients underwent needling, received five fluorouracil, or restarted eye drops.
• 10:25
  SPEAKER_00: Intravitrial bevicisomab improves trabeculectomy survival at 12 months.
• 10:30
  SPEAKER_00: Why might vascular endothelial growth factor affect glaucoma surgery?
• 10:34
  SPEAKER_00: The normal healing response.
• 10:36
  SPEAKER_00: After trabeculectomy, the eye goes through overlapping stages of wound healing, inflammation, new blood vessel formation, fibroblast migration and multiplication, collagen production, scar remodeling.
• 10:50
  SPEAKER_00: A certain amount of healing is necessary.
• 10:52
  SPEAKER_00: If the conjunctiva did not heal at all, the eye could develop a persistent leak, infection, or dangerously low eye pressure.
• 10:59
  SPEAKER_00: The problem is excessive or poorly organized healing.
• 11:02
  SPEAKER_00: Too much scar tissue beneath the conjunctiva can block the movement of aqueous fluid into the bleb.
• 11:08
  SPEAKER_00: Vascular endothelial growth factor is more than a blood vessel signal.
• 11:13
  SPEAKER_00: Vascular endothelial growth factor is best known for stimulating new blood vessels and increasing blood vessel leakage, but it also appears to influence wound healing more broadly.
• 11:25
  SPEAKER_00: Research has found that vascular endothelial growth factor is increased in the aqueous fluid of some glaucoma patients.
• 11:32
  SPEAKER_00: It is increased in tenons tissue in patients undergoing glaucoma surgery.
• 11:36
  SPEAKER_00: Higher tenin' tissue levels have been associated with worse trabeculectomy outcomes.
• 11:42
  SPEAKER_00: Vascular endothelial growth factor can influence macrophage and fibroblast migration.
• 11:48
  SPEAKER_00: It may increase collagen organization, contraction, and scar formation.
• 11:52
  SPEAKER_00: A study of patients with primary open-angle glaucoma found that higher vascular endothelial growth factor levels in tenons tissue were associated with surgical failure at one year.
• 12:03
  SPEAKER_00: Other laboratory and review studies describe effects on fibroblast activity and collagen deposition.
• 12:09
  SPEAKER_00: Level of vascular endothelial growth factor in tendon tissue and results of glaucoma surgery.
• 12:15
  SPEAKER_00: Pathobiology of wound healing after glaucoma filtration surgery.
• 12:19
  SPEAKER_00: How bevisismab might help.
• 12:21
  SPEAKER_00: Bevisismab blocks vascular endothelial growth factor.
• 12:25
  SPEAKER_00: In theory, this could affect several parts of postoperative healing.
• 12:29
  SPEAKER_00: For the full table, please open this article on VisualFieldTest.com.
• 12:33
  SPEAKER_00: This mechanism is plausible, but it is not fully proven in humans.
• 12:37
  SPEAKER_00: Most of the direct evidence comes from tissue studies, animal experiments, bleb appearance, and clinical outcomes rather than repeated human biopsies demonstrating less fibrosis.
• 12:48
  SPEAKER_00: There is also a biological trade-off.
• 12:51
  SPEAKER_00: Reducing blood vessels too aggressively might impair healthy wound closure and could contribute to thin, avascular, leaking blebs.
• 12:58
  SPEAKER_00: That is one reason mitomycin C itself can create long-term complications.
• 13:04
  SPEAKER_00: Previous studies of bevasisumab and other antivascular endothelial growth factor drugs.
• 13:09
  SPEAKER_00: Earlier clinical studies were considerably less consistent than the new intravitrial trial.
• 13:14
  SPEAKER_00: Intravitrial ranobizumab, a 2010 pilot study, randomized only 10 patients with primary open-angle glaucoma to intravitrial ranobizumab plus mitomycin C.
• 13:25
  SPEAKER_00: Mitomycin C alone, all patients were classified as unqualified successes at the end of follow-up.
• 13:32
  SPEAKER_00: The ranobizomab group had more diffuse blebs and less vascularity, but the study was far too small to determine whether the drug improved long-term surgical survival.
• 13:41
  SPEAKER_00: Bleb morphology and vascularity after trabeculectomy with intravitreal rhanobismab.
• 13:48
  SPEAKER_00: Intracameral bevisisimab.
• 13:50
  SPEAKER_00: A randomized Belgian study included 138 patients who completed 12 months of follow-up.
• 13:56
  SPEAKER_00: Intracameral bevisisamab produced absolute success in 71% compared with 51% in the placebo group.
• 14:03
  SPEAKER_00: Fewer needling procedures, 12% versus 33%.
• 14:07
  SPEAKER_00: Similar average eye pressure at one year.
• 14:10
  SPEAKER_00: No major difference in reported complications.
• 14:13
  SPEAKER_00: This study suggested a possible benefit, particularly in reducing interventions, but it did not establish that intracameral bevacyMab improves long-term success.
• 14:22
  SPEAKER_00: Intracameral bevicisamab as an adjunct to trabeculectomy.
• 14:25
  SPEAKER_00: A different randomized trial compared intracameral bevisisamab directly with mitomycin C in 87 eyes.
• 14:32
  SPEAKER_00: After approximately 17 months, complete success was 61% with bevicisamab.
• 14:38
  SPEAKER_00: Complete success was 66% with mitomycin C.
• 14:41
  SPEAKER_00: The difference was not statistically significant.
• 14:44
  SPEAKER_00: Early bleb leakage was more common with bevisisamab, 29% versus 11%.
• 14:49
  SPEAKER_00: This is a useful warning against assuming that every route of bevisisamab administration has the same effect.
• 14:55
  SPEAKER_00: Short-term results of trabeculectomy using adjunctive intracameral bevicissomab versus mitomycin C.
• 15:02
  SPEAKER_00: In another prospective randomized study with three-year follow-up, intracameral bevicissomab alone performed similarly to subtenins mitamycin C.
• 15:10
  SPEAKER_00: Complete success, 66% versus 64%.
• 15:14
  SPEAKER_00: Qualified success, 90% versus 86%.
• 15:17
  SPEAKER_00: Neither difference was statistically significant.
• 15:20
  SPEAKER_00: Intracameral bevicissomab versus subtenons mitomycin C.
• 15:24
  SPEAKER_00: Subconjunctival bevicissimab, a randomized study of 46 eyes with primary open-angle glaucoma, compared a single subconjunctive bevacismab injection added to mitomycin C with mitomycin C alone.
• 15:36
  SPEAKER_00: At 12 months, success was 85% with bevisisamab.
• 15:40
  SPEAKER_00: Success was 89.5% with mitomycin C alone.
• 15:44
  SPEAKER_00: The difference was not statistically significant.
• 15:47
  SPEAKER_00: The bevisisomab group had less bleb vascularity at one month, but this difference was not maintained at later visits.
• 15:54
  SPEAKER_00: Efficacy of adjunctive subconjunctival bevisisomab.
• 15:57
  SPEAKER_00: A small study of 28 eyes undergoing surgery for a previously failed, scarred bleb reported higher numerical success with mitomycin C plus subconjunctival bevisisomab than with mitomycin C alone.
• 16:10
  SPEAKER_00: However, the difference was not statistically significant, and the study was too small to provide reliable evidence.
• 16:16
  SPEAKER_00: Subconjunctival bevicisomab to augment trabeculectomy with mitomycin C in failed glaucoma surgery.
• 16:23
  SPEAKER_00: What do systematic reviews show?
• 16:25
  SPEAKER_00: Older systematic reviews were generally cautious.
• 16:28
  SPEAKER_00: A 2016 review of randomized trials found that bevacyMab could improve some outcomes compared with placebo, but the combination of bevisisamab plus mitomycin C did not clearly outperform mitomycin C alone.
• 16:42
  SPEAKER_00: That review also raised concerns about increased bleb leakage and encapsulated blebs in some comparisons.
• 16:49
  SPEAKER_00: A 2018 meta-analysis of randomized clinical trials found no clear additional benefit when bivisysomab was combined with mitomycin C or 5-fluoroorocil.
• 16:59
  SPEAKER_00: A newer 2025 systematic review included 16 studies and 1,002 patients.
• 17:06
  SPEAKER_00: It reported higher odds of complete success at 12 months when anti-vascular endothelial growth factor treatment was added to mitomycin C.
• 17:14
  SPEAKER_00: The most consistent signal involved 1.25 mg intracameral or intravitreal bevicisamab with an odds ratio of 1.58 for complete success.
• 17:24
  SPEAKER_00: However, the studies used different routes, doses, patient groups, success definitions, and follow-up periods.
• 17:32
  SPEAKER_00: The effects of bevisisamab in augmenting trabeculectomy.
• 17:36
  SPEAKER_00: Trabeculectomy augmented with antivef improves surgical outcomes.
• 17:40
  SPEAKER_00: The overall message is the new three-year trial is not consistent with all previous studies, but it may be identifying a route-specific effect of a longer-lasting intravitreal dose.
• 17:51
  SPEAKER_00: Is the new result reproducible or could it be a study artifact?
• 17:55
  SPEAKER_00: Reasons to believe the finding is real.
• 17:57
  SPEAKER_00: Several features strengthen the result.
• 18:00
  SPEAKER_00: Randomized design, placebo control, double masking, standardized surgery, predefined target eye pressures, objective bleb photographs, a plausible biological mechanism, similar direction of benefit at 12 months and 3 years, early bleb changes that matched the proposed mechanism.
• 18:18
  SPEAKER_00: The result was also statistically unlikely to be explained by random chance alone.
• 18:22
  SPEAKER_00: The difference in complete success had a p-value of 0.001, and the confidence interval around the failure-hazard ratio remained well below 1.
• 18:32
  SPEAKER_00: Reasons to remain cautious.
• 18:34
  SPEAKER_00: It was a single center study.
• 18:36
  SPEAKER_00: Outcomes after trabeculectomy depend heavily on surgeon technique, mitomycin C concentration, and exposure time.
• 18:44
  SPEAKER_00: Suture adjustment, frequency of postoperative visits, timing of needling, threshold for restarting eye drops, management of early inflammation.
• 18:53
  SPEAKER_00: A single center may have developed a particularly effective way of combining surgery, intravitreal injection, and postoperative care.
• 19:00
  SPEAKER_00: Follow-up was incomplete.
• 19:01
  SPEAKER_00: Of the 131 randomized patients, 111 completed 36 months or approximately 85%.
• 19:08
  SPEAKER_00: Loss to follow-up was greater in the placebo group.
• 19:11
  SPEAKER_00: Many losses were caused by death or relocation, which is understandable in an older population, but unequal loss to follow-up can still influence survival analysis if the missing patients had different outcomes from those who remained.
• 19:26
  SPEAKER_00: The study population was not very diverse.
• 19:29
  SPEAKER_00: Almost all participants were of European ancestry.
• 19:32
  SPEAKER_00: Trabeculectomy success and scarring risk can vary with ancestry age, previous surgery, inflammation, ocular surface disease, glaucoma type, genetic and biological differences in wound healing.
• 19:45
  SPEAKER_00: The result may not apply equally to younger patients, people of African or Asian ancestry, or patients with severe inflammatory or secondary glaucoma.
• 19:54
  SPEAKER_00: Combined cataract surgery was imbalanced.
• 19:56
  SPEAKER_00: Combined phacotrobeculectomy was performed in approximately 34% of bevacyzumab patients compared with 18% of controls.
• 20:04
  SPEAKER_00: Because combined surgery can sometimes have lower success, this imbalance would not obviously explain the superior bevasisumab result.
• 20:13
  SPEAKER_00: If anything, it might have made the bevisisumab group look slightly worse.
• 20:18
  SPEAKER_00: However, imbalances in small studies can have complex effects and are best avoided through stratified randomization.
• 20:25
  SPEAKER_00: Complete success is a demanding but sensitive endpoint.
• 20:29
  SPEAKER_00: Medication-free success depends partly on when the surgeon decides to restart eye drops.
• 20:34
  SPEAKER_00: The trial was masked, which helps, but complete success can still be influenced by clinical judgment.
• 20:40
  SPEAKER_00: Also, similar later eye pressures between the groups do not mean the operations performed identically.
• 20:46
  SPEAKER_00: The control group needed more rescue treatment to achieve those pressures.
• 20:50
  SPEAKER_00: Overall judgment on reproducibility.
• 20:53
  SPEAKER_00: My assessment is the direction of benefit is probably real for the specific technique of a single intervitrial dose added to mitomycin C.
• 21:02
  SPEAKER_00: The very large size of the benefit may be less certain.
• 21:06
  SPEAKER_00: The result is more convincing than the earlier small anti-vascular endothelial growth factor studies, but it remains vulnerable to the limitations of a single center trial.
• 21:16
  SPEAKER_00: A larger independent study might reproduce, a clinically meaningful benefit, moderately likely.
• 21:22
  SPEAKER_00: The exact 21 percentage point advantage, possible, but not yet likely enough to assume.
• 21:28
  SPEAKER_00: No benefit at all, still plausible, particularly in a different population or with different postoperative care.
• 21:35
  SPEAKER_00: How does this compare with other ways of preventing trabeculectomy failure?
• 21:39
  SPEAKER_00: Mitomycin C.
• 21:41
  SPEAKER_00: Mitomycin C remains the established standard adjunct for high risk trabeculectomy.
• 21:46
  SPEAKER_00: It suppresses fibroblast multiplication and reduces scar formation.
• 21:50
  SPEAKER_00: Its advantages?
• 21:51
  SPEAKER_00: Strong evidence, powerful eye pressure reduction widely available, familiar to glaucoma surgeons, its disadvantages, non selective toxicity.
• 22:00
  SPEAKER_00: Hypotony, hypotany-related maculopathy, thin orovascular blebs, late bleb leakage, blebitis, and endophthalmitis, delayed conjunctival healing.
• 22:10
  SPEAKER_00: The American Academy of Ophthalmology's current guidance recognizes that antifibrotic treatment improves filtration surgery but emphasizes weighing its benefits against hypotany, bleb leakage, and infection.
• 22:21
  SPEAKER_00: Primary open-angle glaucoma, preferred practice pattern.
• 22:25
  SPEAKER_00: Five fluorooraceal injections.
• 22:27
  SPEAKER_00: Five fluorooraasol can be injected after surgery, often when the bleb becomes inflamed, vascular, or begins to scar.
• 22:33
  SPEAKER_00: It is also commonly used during bleb needling.
• 22:36
  SPEAKER_00: Its advantages, useful for early threatened failure, can be given selectively, can be combined with needling.
• 22:43
  SPEAKER_00: Its disadvantages, painful injections, corneal epithelial toxicity, possible wound healing complications.
• 22:50
  SPEAKER_00: Not usually given routinely to everyone.
• 22:53
  SPEAKER_00: A long-term randomized comparison of intraoperative 5-fluorooracyl and mitomycin C found five-year success of approximately 76% with 5-fluoroacyl and 66% with mitomycin C, but the difference was not statistically significant.
• 23:08
  SPEAKER_00: Long-term outcomes of intraoperative 5-fluoroacyl versus intraoperative mitomycin C.
• 23:14
  SPEAKER_00: Laser suture lysis.
• 23:15
  SPEAKER_00: Laser suture lysis cuts selected scleroflap sutures after surgery.
• 23:20
  SPEAKER_00: This allows more aqueous fluid to enter the bleb.
• 23:23
  SPEAKER_00: It is primarily a mechanical method of adjusting flow, not an anti-scarring treatment.
• 23:28
  SPEAKER_00: It can be highly useful during the early postoperative period but does not directly suppress fibroblast activity.
• 23:34
  SPEAKER_00: Bleb needling.
• 23:36
  SPEAKER_00: Needling mechanically breaks scar tissue around a failing bleb.
• 23:40
  SPEAKER_00: It is often combined with five-fluorouracil or mitomycin C.
• 23:44
  SPEAKER_00: The American Academy of Ophthalmology recognizes transconjunctival needling with five-fluororacyl or mitomycin C as an effective way to revive selected failing blebs.
• 23:54
  SPEAKER_00: It is a rescue treatment rather than a replacement for a successful initial operation.
• 23:59
  SPEAKER_00: Primary open-angle glaucoma, preferred practice pattern.
• 24:03
  SPEAKER_00: Steroids topical corticosteroids are routinely used after trabeculectomy to reduce inflammation.
• 24:09
  SPEAKER_00: Inflammation can contribute to scarring, but corticosteroids do not directly target the entire fibroblast and collagen pathway.
• 24:17
  SPEAKER_00: Increasing steroid treatment is not an established substitute for mitomycin C or selective postoperative bleb management.
• 24:25
  SPEAKER_00: Excessive steroid exposure may cause steroid-related eye pressure elevation, cataract progression, delayed epithelial healing, increased infection risk, oligen-collagen matrix.
• 24:37
  SPEAKER_00: Oligin is a biodegradable collagen glycosaminoglycan scaffold intended to guide healing toward less dense scar formation.
• 24:44
  SPEAKER_00: One small five-year randomized study reported higher complete and overall success with oligen than with low-dose mitomycin C.
• 24:52
  SPEAKER_00: However, the study involved only a small number of eyes, and systematic reviews have described mixed results.
• 24:58
  SPEAKER_00: Oligin has not replaced mitomycin C as the dominant approach.
• 25:03
  SPEAKER_00: Biodegradable 3D porous collagen matrix compared with mitomycin C, oligen implant versus mitomycin C.
• 25:10
  SPEAKER_00: Rhoe-associated kinase inhibitors and newer targeted agents, roe associated kinase inhibitors such as riposudil are being studied because they may reduce fibroblast contraction, collagen deposition, inflammation, and blood vessel growth.
• 25:24
  SPEAKER_00: A multi-center randomized study found that three months of postoperative riposudal reduced the number of pressure-lowering medications at two and three years, but did not significantly improve the three-year cumulative probability of surgical success.
• 25:39
  SPEAKER_00: Effective riposudal, after trabeculectomy with mitomycin C.
• 25:44
  SPEAKER_00: Other experimental approaches target transforming growth factor beta, connective tissue growth factor, lysyl oxidase-like two integrins, fibroblast-specific signaling pathways, local drug delivery systems.
• 25:57
  SPEAKER_00: These approaches may eventually be more selective than mitomycin C, but they remain investigational or lack convincing long-term clinical evidence.
• 26:05
  SPEAKER_00: Which patients might benefit most?
• 26:07
  SPEAKER_00: The trial does not establish a subgroup in which bevacizumab should definitely be used.
• 26:13
  SPEAKER_00: Still, several groups are biologically interesting.
• 26:17
  SPEAKER_00: Younger patients.
• 26:19
  SPEAKER_00: Younger people often have a stronger wound healing response and may scar more aggressively.
• 26:24
  SPEAKER_00: They also have more years during which a failed trabeculectomy could matter.
• 26:28
  SPEAKER_00: However, the new trial mostly involved older adults, and it was not designed to prove a special benefit in younger patients.
• 26:36
  SPEAKER_00: Younger patients also face a greater risk of hypotene-related maculopathy after filtration surgery.
• 26:42
  SPEAKER_00: Conclusion Plausible benefit, but unproven.
• 26:46
  SPEAKER_00: Previously operated eyes.
• 26:48
  SPEAKER_00: Previous conjunctival surgery can increase scarring and make trabeculectomy more difficult.
• 26:54
  SPEAKER_00: The trial included a small number of redu trabeculectomies, but it was too small to determine whether intravitreal bevisisomab is especially valuable in these eyes.
• 27:03
  SPEAKER_00: The subgroup results were not sufficiently reliable to guide treatment.
• 27:07
  SPEAKER_00: Conclusion.
• 27:08
  SPEAKER_00: A reasonable research target, not an established indication.
• 27:12
  SPEAKER_00: Aggressive scar formers.
• 27:14
  SPEAKER_00: Patients with previous failed trabeculectomy, extensive conjunctival scarring, multiple previous eye operations, severe inflammation.
• 27:23
  SPEAKER_00: A history of rapid bleb failure might theoretically gain the greatest absolute benefit because their baseline failure risk is higher.
• 27:30
  SPEAKER_00: But the benefit risk balance may also be more complicated.
• 27:33
  SPEAKER_00: The more aggressively mitomycin C and bevisisamab suppress healing, the greater the concern about thin blebs, hypotony, and leakage.
• 27:42
  SPEAKER_00: Conclusion.
• 27:44
  SPEAKER_00: Possibly the group most likely to benefit, but also the group requiring the greatest caution.
• 27:49
  SPEAKER_00: High baseline eye pressure.
• 27:51
  SPEAKER_00: Higher pre-operative eye pressure can indicate advanced disease and a need for substantial pressure reduction.
• 27:58
  SPEAKER_00: In the 12-month analysis, higher baseline eye pressure was associated with a greater likelihood of needing medication to reach the target.
• 28:06
  SPEAKER_00: The three-year analysis did not establish that high pressure patients receive a disproportionately greater benefit from bevisisimab.
• 28:14
  SPEAKER_00: Conclusion, no validated selection rule.
• 28:17
  SPEAKER_00: Inflammatory glaucoma.
• 28:19
  SPEAKER_00: Inflammatory glaucoma is often associated with aggressive scarring.
• 28:24
  SPEAKER_00: The study included only a small number of eyes with uveitic glaucoma, all of which happened to be in the placebo group.
• 28:31
  SPEAKER_00: Removing those eyes did not eliminate the reported treatment effect, but the number was too small for a dependable conclusion.
• 28:38
  SPEAKER_00: Activirus neovascularization and active proliferative retinal disease were excluded, so the findings should not be extended to neovascular glaucoma.
• 28:48
  SPEAKER_00: Conclusion, important potential subgroup, but essentially unanswered.
• 28:53
  SPEAKER_00: Patients requiring extremely low eye pressure head.
• 28:56
  SPEAKER_00: The trial's personalized target pressures were relatively low, around 13 millimeters of mercury on average.
• 29:02
  SPEAKER_00: This makes the findings more relevant to patients with advanced glaucoma who need very low pressure.
• 29:09
  SPEAKER_00: Still, the trial did not separately analyze patients needing a target of 10, 11, or 12 millimeters of mercury.
• 29:16
  SPEAKER_00: The most important question for these patients is not simply whether the bleb survives, but whether it reliably maintains a safe pressure without causing hypotony.
• 29:26
  SPEAKER_00: Conclusion.
• 29:27
  SPEAKER_00: Potentially relevant but individualized surgical planning remains more important than the injection alone.
• 29:34
  SPEAKER_00: Safety.
• 29:35
  SPEAKER_00: What is the trade-off?
• 29:36
  SPEAKER_00: Complications observed in the trial.
• 29:38
  SPEAKER_00: At 12 months, there was no statistically significant difference in most complications.
• 29:42
  SPEAKER_00: Reported events included hypoten-related maculopathy, approximately 3 to 6% in each group, choroidal effusion, 1.8% in the control group versus 5.8% with bevisimab, wound leak, 1.8% versus 3.8%, tenin cyst, 1.8% versus 9.6%, microbial keratitis, approximately 2% in each group.
• 30:04
  SPEAKER_00: Late hypotony-related maculopathy, approximately 4% versus 6%.
• 30:10
  SPEAKER_00: The numerical excess of choroidal effusion, wound leak, and tenin cyst in the bevisisimab group did not reach statistical significance.
• 30:17
  SPEAKER_00: The trial was not large enough to reliably detect uncommon but serious complications.
• 30:22
  SPEAKER_00: The three-year report found very few new complications after the first year.
• 30:26
  SPEAKER_00: However, the original trial did not observe enough patients to rule out late bleb leakage, infection, or a vascularity over longer periods.
• 30:35
  SPEAKER_00: Intravitrial bevisisamab improves trabeculectomy survival at 12 months.
• 30:40
  SPEAKER_00: Not just for retinal specialists.
• 30:43
  SPEAKER_00: Intravitrial bevisismab in glaucoma surgery.
• 30:46
  SPEAKER_00: Additional risks from an intravitre injection.
• 30:49
  SPEAKER_00: Adding an intravitre injection creates risks that would not exist with mitomycin C alone, including infectious endothalmitis, sterile intraocular inflammation, retinal tear, retinal detachment, vitreous hemorrhage, accidental lens injury, temporary eye pressure elevation, rare retinal vascular complications.
• 31:10
  SPEAKER_00: These events are uncommon in routine retinal practice, but a rare event can still matter when the injection is being given to an eye that does not otherwise need retinal treatment.
• 31:19
  SPEAKER_00: A large literature review found that post-injection endophthalmitis occurred in approximately 0.058% of bevisamab injections and 0.029% of randobismab injections in the studies analyzed.
• 31:32
  SPEAKER_00: These estimates vary according to injection technique, compounding, antisepsis, and study design.
• 31:38
  SPEAKER_00: Global reported endophthalmitis risk following intravitreal injections.
• 31:43
  SPEAKER_00: The safety of intravitreal bevisisamab monotherapy.
• 31:47
  SPEAKER_00: The trial itself did not observe lens touch, vitreous hemorrhage, or retinal detachment.
• 31:52
  SPEAKER_00: That is reassuring, but a sample of 65 treated patients cannot exclude a risk that occurs once in several hundred injections.
• 31:59
  SPEAKER_00: The bleb-specific safety concern.
• 32:02
  SPEAKER_00: Both mitomycin C and bevisisamab can reduce blood vessel formation.
• 32:06
  SPEAKER_00: That may be beneficial early, but an excessively avascular bleb can become thin, fragile, prone to leakage, vulnerable to infection, associated with chronic hypotany.
• 32:18
  SPEAKER_00: The new trial did not show a statistically significant increase in avascular blebs, but the possibility remains clinically important, particularly over five to ten years.
• 32:28
  SPEAKER_00: How much might it improve five-year surgical survival?
• 32:31
  SPEAKER_00: There is no direct five-year randomized result yet, so any five-year estimate must be treated as an informed projection.
• 32:39
  SPEAKER_00: Historical studies of mitomycin C trabeculectomy have reported considerable variation.
• 32:44
  SPEAKER_00: One long-term randomized comparison found approximately 66% five-year success with mitomycin C under its study definition, while a 20-year observational cohort reported approximately 57% medication-free survival at 20 years and 88% qualified survival.
• 33:02
  SPEAKER_00: These studies use different definitions and patient populations, so they cannot be directly substituted for the new trial.
• 33:09
  SPEAKER_00: Long-term outcomes of intraoperative 5-fluoroor versus intraoperative mitomycin C, a 20-year follow-up study of trabeculectomy.
• 33:19
  SPEAKER_00: My reasoned five-year estimate.
• 33:42
  SPEAKER_00: The most plausible single-point estimate, in my view, is roughly 65% with mitomycin C alone, 85% with additional intravitreal bevisumab.
• 33:52
  SPEAKER_00: That would represent an approximate absolute benefit of 20% points, similar to the three-year result.
• 33:58
  SPEAKER_00: This estimate could be wrong in either direction.
• 34:00
  SPEAKER_00: The advantage may shrink with longer follow-up if late complications or late scarring emerge.
• 34:06
  SPEAKER_00: Alternatively, if bevasisomab truly prevents early bleb failure, the early advantage could remain substantial for many years.
• 34:14
  SPEAKER_00: Could it reduce repeat glaucoma surgery?
• 34:17
  SPEAKER_00: Probably, but the reduction may be smaller than the reduction in medication use.
• 34:22
  SPEAKER_00: Many failed or borderline trabeculectomies are managed with eye drops, laser suturysis, bleb needling, five-fluorowracil injections, bleb revision.
• 34:32
  SPEAKER_00: The trial's first-year data suggest fewer additional glaucoma operations with bevacismab, but the three-year evidence is not detailed enough to calculate a firm five-year reduction.
• 34:43
  SPEAKER_00: My cautious estimate is that intravitrial bevasisamab might reduce the need for repeat glaucoma surgery by approximately 3 to 8 percentage points over five years in a similar population.
• 34:55
  SPEAKER_00: That estimate is low confidence and should not be presented to patients as an established benefit.
• 35:01
  SPEAKER_00: Probability that larger independent trials reproduce the result.
• 35:05
  SPEAKER_00: No scientific study can provide a precise probability of replication, but based on the available evidence, my estimate would be 65 to 75% chance that a larger trial finds at least some clinically meaningful benefit from intravitreal bevisisamab added to mitomycin C, 40% to 60% chance that it reproduces a benefit as large as the reported 21 percentage point difference, 25 to 35% chance that a larger or more diverse trial finds little or no important benefit.
• 35:37
  SPEAKER_00: These are reasoned estimates, not published statistical predictions.
• 35:41
  SPEAKER_00: They reflect the unusually strong new randomized result, the supportive early BLEB findings, the 2025 meta-analysis, and the inconsistent results of earlier studies using different delivery routes.
• 35:54
  SPEAKER_00: Could antivascular endothelial growth factor treatment help an existing bleb?
• 35:58
  SPEAKER_00: The evidence is much weaker for treating an already failing bleb, new trabeculectomy.
• 36:04
  SPEAKER_00: The best supported use, if future studies confirm the result, would be a single intravitreal bevisisomab injection given during a new trabeculectomy with mitomycin C.
• 36:15
  SPEAKER_00: The timing may matter because the drug appears to influence the first weeks of wound healing.
• 36:20
  SPEAKER_00: Early bleb fibrosis.
• 36:22
  SPEAKER_00: For a bleb that is becoming vascular, inflamed, or mildly scarred, the established strategies remain intensive topical corticosteroids when appropriate, bleb massage, adjustment or laser release of sutures, subconjunctival 5-fluorooracil, bleb needling with 5-fluorooracil or mitomycin C, bleb revision when necessary.
• 36:43
  SPEAKER_00: Subconjunctival bevasisumab has been studied in small trials and pilot studies.
• 36:47
  SPEAKER_00: It may temporarily reduce vascularity, but it has not consistently restored long-term bleb survival.
• 36:54
  SPEAKER_00: There is no well-established dosing schedule or treatment algorithm for injecting bevacismab into an early failing bleb.
• 37:02
  SPEAKER_00: Intravitrial bevisumab has not been shown to reopen a mature scarred filtration pathway.
• 37:08
  SPEAKER_00: Once substantial subconjunctival fibrosis is present, the mechanical component of needling or surgical revision is usually more important than simply blocking vascular endothelial growth factor.
• 37:20
  SPEAKER_00: Is this likely to become routine trabeculectomy practice?
• 37:23
  SPEAKER_00: Possibly, but not immediately.
• 37:25
  SPEAKER_00: The treatment has several attractive features.
• 37:27
  SPEAKER_00: One dose, familiar drug, relatively low cost compared with many new technologies, administration during surgery, possible reduction in postoperative medication use, possible reduction in needling and repeat surgery, a plausible effect on early wound healing, but the barriers are significant.
• 37:46
  SPEAKER_00: Intravitrial injection adds a rare but serious risk.
• 37:50
  SPEAKER_00: Use in this setting is off-label.
• 37:52
  SPEAKER_00: The evidence comes mainly from one research group and one center.
• 37:57
  SPEAKER_00: The patient population was small and not very diverse.
• 38:00
  SPEAKER_00: Earlier studies using other delivery routes were inconsistent.
• 38:04
  SPEAKER_00: Five-year safety and bleb survival are not yet established.
• 38:07
  SPEAKER_00: The precise dose, injection technique, and best patient selection remain uncertain.
• 38:12
  SPEAKER_00: A reasonable future pathway would be independent multi-center replication, inclusion of younger, racially diverse, previously operated, and inflammatory glaucoma patients, at least five years of follow-up, detailed reporting of bleb leaks, hypotony infection, and repeat surgery, cost-effectiveness analysis, comparison with optimized mitomycin C and modern postoperative needling protocols.
• 38:36
  SPEAKER_00: Until then, it may be reasonable for some surgeons to offer the technique selectively, particularly within a clinical trial or after a careful discussion of its experimental status.
• 38:48
  SPEAKER_00: Conclusion: The three-year bevisisamab and trabeculectomy study provides the strongest evidence so far that a single intravitreal injection of bevisisomab added to mitomycin C may improve trabeculectomy survival.
• 39:01
  SPEAKER_00: The headline result is clinically meaningful.
• 39:04
  SPEAKER_00: Approximately 92% medication-free success at three years, compared with approximately 71% with mitomycin C alone, roughly one additional medication-free success for every five patients treated.
• 39:18
  SPEAKER_00: The most convincing explanation is that bevisisomab suppresses part of the early inflammatory and fibroproliferative response, producing a larger and less inflamed bleb during the period when many trabeculectomies begin to fail.
• 39:31
  SPEAKER_00: However, this remains promising evidence rather than settled practice.
• 39:35
  SPEAKER_00: Earlier studies of intracameral and subconjunctival treatment were mixed, and the new trial was relatively small, single center, and largely limited to older participants of European ancestry.
• 39:47
  SPEAKER_00: For now, bevacismab should be viewed as a potentially valuable selective adjunct, not as a reason to delay needed surgery or assume that standard mitomycin C trabeculectomy is obsolete.
• 39:59
  SPEAKER_00: How big a deal is this for someone considering trabeculectomy?
• 40:03
  SPEAKER_00: Rating 6 out of 10 for immediate patient relevance.
• 40:07
  SPEAKER_00: This is an important development, but it is not yet practice changing for most patients.
• 40:12
  SPEAKER_00: For someone considering trabeculectomy today, the new evidence does not mean that standard surgery is inadequate.
• 40:19
  SPEAKER_00: It does not prove that every patient should receive an intravitreal injection.
• 40:24
  SPEAKER_00: It does suggest that asking a glaucoma surgeon whether this approach is appropriate, available through a clinical trial, or part of the surgeon's practice is reasonable.
• 40:34
  SPEAKER_00: The quality of postoperative follow-up, early bleb management, and the surgeon's experience probably remain more important than the injection alone.
• 40:44
  SPEAKER_00: The result is exciting because it targets the central weakness of trabeculectomy, scarring.
• 40:50
  SPEAKER_00: Its ultimate importance will depend on whether independent surgeons can reproduce the same benefit without increasing late bleb leakage, hypotony, or infection.
• 40:59
  SPEAKER_00: All links to sources are available in the text version of this article.
• 41:03
  SPEAKER_00: You can find the full article at visualfieldtest.com.
• 41:08
  SPEAKER_00: Thanks for listening.
• 41:10
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