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Wound Healing Modulation 2026: Anti-fibrotics in Filtering Surgery · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Wound Healing Modulation.
• 0:01
  SPEAKER_00: 2026, Antifibrotics in Filtering Surgery.
• 0:05
  SPEAKER_00: Glaucoma filtering surgeries like trabeculectomy or tube shunts lower eye pressure by draining fluid out of the eye into a tiny reservoir or bleb under the conjunctiva.
• 0:16
  SPEAKER_00: After surgery, the eye's natural wound healing response, scarring, can close off this drainage, causing the surgery to fail.
• 0:23
  SPEAKER_00: To prevent excessive scarring, surgeons use antifibrotic medications during or after surgery.
• 0:28
  SPEAKER_00: The most common agents are mitomycin C, MMC, and FIFLOracil, 5FU.
• 0:34
  SPEAKER_00: These drugs help keep the drainage channel open, improving long-term success.
• 0:38
  SPEAKER_00: For example, in one study, about 95% of eyes reached targets at 6 to 12 months after trabeculectomy with either MMC or 5FU.
• 0:48
  SPEAKER_00: In other words, both drugs greatly boost the chances of success.
• 0:51
  SPEAKER_00: Over the past decades and into 2026, new strategies have appeared alongside MMC and 5FU.
• 0:57
  SPEAKER_00: Rokinase, ROC inhibitors, and anti-VGF injections are emerging as wound-healing modulators.
• 1:04
  SPEAKER_00: Research in animals and small trials suggests these may further reduce scarring and filtration surgery.
• 1:10
  SPEAKER_00: In all cases, surgeons balance the benefits of better pressure control against risks of a very thin or leaking bleb, which can lead to infection.
• 1:19
  SPEAKER_00: Below we summarize the evidence on dosing, outcomes, and safety of these therapies through mid-2026.
• 1:26
  SPEAKER_00: Antifibrotic medications, how and how much mitomycin C MMC.
• 1:31
  SPEAKER_00: Mitomycin C MMC is a potent anti-scarring drug originally used in chemotherapy.
• 1:36
  SPEAKER_00: In glaucoma surgery, it is applied as eye drops or soaked sponges under the conjunctiva at the time of surgery.
• 1:42
  SPEAKER_00: Standard practice, for many years, is to use MMC at about 0.2 to 0.4 milliliter concentration for 1 to 3 minutes on sponges covering the scleral flap area.
• 1:52
  SPEAKER_00: For example, the FDA-approved kit mitosol provides 0.2 mg per milliliter and directs surgeons to apply saturated sponges for two minutes.
• 2:01
  SPEAKER_00: In practice, surgeons tailor the dose.
• 2:04
  SPEAKER_00: A routine case might get 0.2 mg for two minutes, while a high-risk case, see risk section below, might get 0.4 to a 0.5 mg per milliliter.
• 2:13
  SPEAKER_00: After soaking, the area is rinsed with fluid to stop the drug's action.
• 2:17
  SPEAKER_00: Example dosing.
• 2:18
  SPEAKER_00: In one clinical trial, surgeons applied MMC 0.2 mg millimeter for two minutes versus 5FU50 mg per millimeter for 5 minutes during trabeculectomy.
• 2:28
  SPEAKER_00: Another study on the new Preserflow micro shunt used 0.2.4 mg MMC, lowering mean eye pressure from 21.7 to 14.mil grams at two years.
• 2:39
  SPEAKER_00: Patients given the higher 0.4 mg dose were more likely to be off all medications at two years.
• 2:44
  SPEAKER_00: MMC is very effective at keeping the bleb draining, giving excellent long-term pressure control in many patients.
• 2:50
  SPEAKER_00: In the five-year study above, average pressure with MMC was 9.9 millimeterhergrams from 25.8 preop and success was high.
• 2:59
  SPEAKER_00: However, MMC carries notable risks because it creates a thin vascular, poorly blood-supplied bleb.
• 3:05
  SPEAKER_00: In that same study, about 15% of eyes developed late bleb leaks and 5.7% had blebitis, infection of the bleb, by five years.
• 3:13
  SPEAKER_00: Very low pressure, hypotony 6 mmhergrams, occurred in 42% of eyes.
• 3:19
  SPEAKER_00: In another study, most MMC-treated blebs became avascular, lack normal blood vessels within a year, and leak risk increased over time.
• 3:26
  SPEAKER_00: Patients must be warned, a thin bleb can leak fluid and even harbor germs.
• 3:31
  SPEAKER_00: Overall, bleb-related infection after MMC augmented filtering surgery is uncommon but real, roughly 1 to 2% per year.
• 3:39
  SPEAKER_00: For example, one survey found 1.1% infection in MMC eyes at follow-up versus 1.3% without MMC.
• 3:46
  SPEAKER_00: Key points for MMC.
• 3:47
  SPEAKER_00: Standard practice is 0.2 point milligrams per milliliter for 1 to 3 minutes.
• 3:52
  SPEAKER_00: Higher doses give more pressure lowering but a higher chance of complication.
• 3:56
  SPEAKER_00: The doctor always rinses thoroughly afterward.
• 3:59
  SPEAKER_00: 5 fluororacyl 5FU.
• 4:01
  SPEAKER_00: 5 fluororacyl 5U is another anti-scarring drug used in glaucoma surgery.
• 4:06
  SPEAKER_00: It is a chemotherapy agent too, but less potent than MMC when used in the eye.
• 4:11
  SPEAKER_00: In contrast to MMC's sponge application, 5FU is often given by injections under the conjunctiva either during or after surgery.
• 4:19
  SPEAKER_00: A common regimen has been 5 mg in 0.1 milliliters injected once daily for 5 to 10 days postoperatively.
• 4:26
  SPEAKER_00: Some older studies also used 5FU on sponges at surgery.
• 4:31
  SPEAKER_00: Evidence shows 5FU significantly reduces scarring.
• 4:34
  SPEAKER_00: In one randomized trial, trabeculectomy success rates using interoperative 5FU were essentially the same as with MMC, demonstrating that 5FU can be nearly as effective.
• 4:44
  SPEAKER_00: A Cochrane review found that 5FU injections significantly lowered the risk of surgical failure in high-risk eyes.
• 4:51
  SPEAKER_00: For example, adding peroperative 5FU to repeat glaucoma surgery cut failure risk by about one-third, relative risk wise.
• 5:01
  SPEAKER_00: In high failure risk eyes, like after a prior surgery, they calculated needing to treat only four eyes to prevent one reoperation.
• 5:09
  SPEAKER_00: 5FU also produced substantial IOP drops.
• 5:12
  SPEAKER_00: In the same review, high risk, patients getting 5FU had mean IOP 16 mm Herograms lower than controls at one year.
• 5:20
  SPEAKER_00: Because 5FU tends to cause less severe thinning of the bleb wall than MMC, it is sometimes preferred for patients at very high risk of complications.
• 5:30
  SPEAKER_00: Its side effects include corneal irritation, toxicity to the front of the eye, shallow anterior chamber, and bleb leak.
• 5:38
  SPEAKER_00: The Cochrane summary noted that things like wound leaks and low pressures were more common with 5FU, though the overall infection risk was low.
• 5:46
  SPEAKER_00: In practice today, 5FU is often used in follow-up clinic if a newly formed bleb shows too much scarring.
• 5:52
  SPEAKER_00: The surgeon may inject 5FU in the office or perform needling, bleb revision, with 5FU to improve flow.
• 5:58
  SPEAKER_00: Key points for 5FU.
• 6:00
  SPEAKER_00: Common regimen is 5 mg daily for 5 days post-op.
• 6:04
  SPEAKER_00: It boosts success in tough cases.
• 6:06
  SPEAKER_00: It causes less of vascular thinning than MMC, but blebs can still leak or stay flat.
• 6:12
  SPEAKER_00: Rock, rokinase inhibitors, and other emerging drugs.
• 6:16
  SPEAKER_00: Rock inhibitors are a newer class of glaucoma medications originally developed to lower pressure by relaxing eye outflow channels.
• 6:24
  SPEAKER_00: Preclinical studies suggest they also have anti-scarring effects.
• 6:27
  SPEAKER_00: Rock inhibitors, like ripseudal or nitarsudal drops, can slow down fibroblast activity in the conjunctiva.
• 6:34
  SPEAKER_00: Animal models of glaucoma surgery have shown that adding a rock inhibitor to the eye reduces postoperative scarring.
• 6:41
  SPEAKER_00: Commercially available rock inhibitor eye drops, e.g., nitarsudal, are not yet standard in surgery, but researchers are testing whether such drops or injections could be given around the time of filtering surgery to improve bleb outcomes.
• 6:55
  SPEAKER_00: Other agents under investigation include anti-VF drugs like bevisizumab and experimental molecules that block fibrotic growth factors.
• 7:06
  SPEAKER_00: For example, a recent randomized clinical trial 2023 found that a single intravitreal bevisizumab injection at the time of trabeculectomy significantly improved results.
• 7:17
  SPEAKER_00: Only 6% of eyes in the befisumab group needed glaucoma medications at one year versus 17% of controls, and only 2% needed additional surgery versus 10% of controls.
• 7:29
  SPEAKER_00: Bleb appearances were also better, larger blebs, less redness in the bevisizumab group.
• 7:35
  SPEAKER_00: These findings suggest anti-VGF can help modulate wound healing.
• 7:40
  SPEAKER_00: Ongoing trials are comparing various drugs, topical or injected in surgery, but as of 2026, these are still emerging and not yet routine in most practices.
• 7:50
  SPEAKER_00: Sustained release and targeted delivery.
• 7:53
  SPEAKER_00: Because continuous exposure to antifibrotic agents might improve outcomes, researchers are developing sustained release formulations.
• 8:00
  SPEAKER_00: For example, a novel gel implant containing MMC was tested in rabbits with a tiny drainage stent.
• 8:07
  SPEAKER_00: Eyes that got the MMC sustained release implant maintained a 20% IOP drop for a median of 30 weeks, compared to only 6.5 weeks in eyes given a one-time MMC injection and one week in untreated eyes.
• 8:22
  SPEAKER_00: This shows how a slow release system can keep the bleb functioning much longer.
• 8:26
  SPEAKER_00: Other approaches include microparticles or coatings on drainage devices.
• 8:30
  SPEAKER_00: In lab research, scientists coated a glaucoma tube shunt with microparticles of MMC.
• 8:36
  SPEAKER_00: The microparticles slowly release the drug locally to the surrounding tissue, aiming to prevent fibrosis around the shunt.
• 8:43
  SPEAKER_00: Such designs are experimental but promising.
• 8:46
  SPEAKER_00: Similarly, there is interest in MMC-loaded biodegradable gels or pads that could be placed during surgery or injected to deliver drug over days rather than minutes.
• 8:57
  SPEAKER_00: As of 2026, these sustained release products are mostly in animal or early human testing, but they represent a future strategy to make antifibrotics safer and more effective.
• 9:08
  SPEAKER_00: Bleb morphology and infection risks.
• 9:11
  SPEAKER_00: The goal of using antifibrotics is to create a well-formed, functioning bleb that continues to drain fluid.
• 9:17
  SPEAKER_00: Typical bleb appearance with MMC is often a large, thin-walled, leaky bleb.
• 9:22
  SPEAKER_00: This cystic bleb can be ideal for lowering pressure but also precarious.
• 9:27
  SPEAKER_00: A large multilobed bleb covering much of the upper sclera with few surface blood vessels is often seen.
• 9:33
  SPEAKER_00: With 5FU, blebs may be a bit thicker and less avascular than with high-dose MMC, but can still be cystic.
• 9:40
  SPEAKER_00: Few studies have looked at bleb shape by treatment, but one analysis showed that eyes treated with MMC often became avascular neck, with leaks developing months later.
• 9:50
  SPEAKER_00: In that series, 71% of MMC blebs were avascular by one year.
• 9:55
  SPEAKER_00: Larger avascular blebs were roughly four times more likely to ooze or leak than smaller ones.
• 10:01
  SPEAKER_00: In contrast, bleb leaks in unclamped, normal pressure blebs were rare.
• 10:06
  SPEAKER_00: In practice, surgeons monitor bleb anatomy with tools like slit lamp exams and imaging, looking for excessive thinning or leaks.
• 10:14
  SPEAKER_00: If a bleb looks too thin or is leaking, they may intervene, sealing the leak, applying soft contact lenses, or using preventative antibiotics.
• 10:22
  SPEAKER_00: Because thin-edged blebs can allow bacteria inside, infection risk is a major concern.
• 10:28
  SPEAKER_00: A leaking bleb can become infected, blebitis, and even cause eyewide infection, endophthalmitis.
• 10:34
  SPEAKER_00: Studies report bleb-related infection occurs in roughly 2-8% over five years of follow-up.
• 10:40
  SPEAKER_00: For example, the collaborative BRI study found a five-year infection rate of 2.2% overall.
• 10:46
  SPEAKER_00: However, if a bleb had any leak in its history, the five-year infection rate jumped to 8% versus 1.7% if there was never a leak.
• 10:55
  SPEAKER_00: In simpler terms, a single episode of bleb leakage greatly raises infection risk.
• 11:00
  SPEAKER_00: Interestingly, comparing antifibrotics to no antifibrotics, the infection rates are similar in many studies.
• 11:06
  SPEAKER_00: One Japanese report saw infections in 1.3% of eyes with 5FU, 1.1% with MMC, and to 1.3% without any drug.
• 11:16
  SPEAKER_00: This suggests that it is the bleb characteristics, thin flat, rather than the drug itself that drive infection.
• 11:22
  SPEAKER_00: Studies also show that things like use of a limbal versus fornix conjunctival flap or combining cataract surgery did not significantly change infection rates.
• 11:32
  SPEAKER_00: In summary, while antifibrotics improve surgical success, patients must be alert for signs of bleb problems.
• 11:39
  SPEAKER_00: Worrisome signs include redness or pain around the bleb, sudden pressure drop, or any discharge.
• 11:45
  SPEAKER_00: Any suspected bleb infection is an urgent emergency requiring prompt antibiotic treatment.
• 11:51
  SPEAKER_00: Surgeons try to minimize this risk by using the lowest effective drug dose and by advising careful hygiene, e.g., avoid rubbing eyes, use antibiotic washes if drains leak.
• 12:02
  SPEAKER_00: Long-term success rates.
• 12:03
  SPEAKER_00: Antifibrotic agents greatly boost the long-term success of filtering surgery.
• 12:08
  SPEAKER_00: Success is usually defined as keeping pressure below a target, often 15 to 18 millimeter Herg, with or without medications.
• 12:16
  SPEAKER_00: Many studies show that using MMC or 5FU roughly doubles the five-year success rate compared to surgery without them.
• 12:24
  SPEAKER_00: For instance, one large series without comparator found mean IOP of 10 mm gangs at 5 years with MMC and maintained pressure reduction in the majority of eyes.
• 12:34
  SPEAKER_00: Another randomized trial, TCP study, found that trabeculectomy with MMC was significantly more likely to succeed at 5 years than tube shunt surgery.
• 12:44
  SPEAKER_00: In general, modern outcomes with MMC augmented trabeculectomy show 70 to 90% success at 3 to 5 years in many reports.
• 12:52
  SPEAKER_00: However, success comes with caveats.
• 12:54
  SPEAKER_00: As noted, long-term complications are higher with antifibrotics.
• 12:58
  SPEAKER_00: Late hypotany, very low pressure, is a particular issue.
• 13:02
  SPEAKER_00: Some series re 30 to 40% of eyes with prolonged low pressure.
• 13:07
  SPEAKER_00: Chronic low pressure can cause maculopathy, swelling in the retina, vision loss, or cataract progression.
• 13:13
  SPEAKER_00: Patients often need careful follow-up for several years.
• 13:16
  SPEAKER_00: In one report, 4.9% of eyes lost four or more lines of vision over five years, partly due to such issues.
• 13:24
  SPEAKER_00: Randomized trials and real-world studies both confirm the general picture.
• 13:29
  SPEAKER_00: Antifibrotics improve IOP control and reduce need for reoperation, but increase early and late complications.
• 13:36
  SPEAKER_00: For example, a classic trial comparing trabeculectomy with MMC versus without found far higher success with MMC, but also more flat anterior chambers and thin blebs.
• 13:47
  SPEAKER_00: Similarly, the tube versus trabeculectomy trial, 2016, showed that in eyes with previous surgery, tube implants and trabeculectomy with MMC had similar five-year success, 70 to 80%, but each had its own set of complications.
• 14:02
  SPEAKER_00: Tube had more early hypotony, TRAB had more bleb leaks.
• 14:05
  SPEAKER_00: These findings underscore the need to tailor therapy.
• 14:08
  SPEAKER_00: Perioperative protocols and risk stratification surgeons use a risk-based approach to decide on antifibrotic use.
• 14:16
  SPEAKER_00: Key risk factors for scarring include young age, African descent, a history of glaucoma surgery, or other concil surgery, uveitis or inflammation, neovascular glaucoma, and use of many glaucoma drops.
• 14:29
  SPEAKER_00: If these risks are present, they tend to use more aggressive antifibrotic therapy.
• 14:33
  SPEAKER_00: For low-risk eyes, older patients, mild glaucoma, no prior surgery, some surgeons may even skip antifibrotics to avoid complications.
• 14:42
  SPEAKER_00: One guideline suggests stratifying patients as follows: low risk, virgin conjunctiva, minimal meds, elderly, often no antifibrotic.
• 14:50
  SPEAKER_00: Moderate risk, some prior drops or cataract surgery, use either 5FU or a low-dose MMC, 0.2 mg.
• 14:56
  SPEAKER_00: High risk, e.g., multiple surgeries, uveitis, neovascular glaucoma, combined cataract trabeculectomy, use high dose MMC, 0.4 to 0.5 mg liters, and close monitoring.
• 15:07
  SPEAKER_00: The timing also matters.
• 15:09
  SPEAKER_00: Occasionally, surgeons give a small MMC injection during surgery instead of sponges or a few preoperative steroid eye drops to quiet inflammation.
• 15:17
  SPEAKER_00: Postoperatively, a heavy steroid regimen, hourly drops initially, is routine, and many surgeons use antibiotics for a week or two to prevent early infection.
• 15:27
  SPEAKER_00: Perioperative care tips include application technique.
• 15:30
  SPEAKER_00: Fully saturate the sponge with the correct concentration, e.g.
• 15:34
  SPEAKER_00: 0.2 mg per millet MMC, and spread it evenly.
• 15:38
  SPEAKER_00: Adhere strictly to the planned duration, often two minutes.
• 15:42
  SPEAKER_00: Then rinse the area well, typically with balanced salt solution to remove excess drug.
• 15:47
  SPEAKER_00: Post-op follow-up.
• 15:49
  SPEAKER_00: The surgeon will check the bleb frequently in the first weeks.
• 15:52
  SPEAKER_00: If the bleb becomes flat or shows early scarring, they may perform bleb needling in clinic, reopening the fistula, often with a small injection of 5FU to boost success.
• 16:03
  SPEAKER_00: If a leak is seen, often with sytle testing, measures like a bandage contact lens or tissue glue may be used.
• 16:10
  SPEAKER_00: Patient counseling.
• 16:12
  SPEAKER_00: Patients are instructed to recognize warning signs, redness, pain, change in vision or pressure, and to report them immediately.
• 16:19
  SPEAKER_00: Those with thin blebs may be given prophylactic antibiotic eye drops for long-term use.
• 16:24
  SPEAKER_00: By mid-2026, practice is increasingly evidence-based.
• 16:29
  SPEAKER_00: Surgeons rely on published rates to inform patients.
• 16:32
  SPEAKER_00: For example, they know that giving MMC might raise success from 660% to 80% at five years, but also know the numbers for leaks and infection from studies.
• 16:43
  SPEAKER_00: This helps them explain expected outcomes in simple terms to patients.
• 16:47
  SPEAKER_00: Conclusion.
• 16:48
  SPEAKER_00: In summary, careful wound healing modulation is vital for successful glaucoma filtering surgery.
• 16:54
  SPEAKER_00: Adjunctive antifibrotic drugs have transformed outcomes.
• 16:58
  SPEAKER_00: Mitomycin C and 5FU remain the standards, each with well-characterized dosing and effects.
• 17:04
  SPEAKER_00: Newer approaches, rock inhibitors, anti-VEGF, and drug release technologies, show promise and may further improve results in the coming years.
• 17:13
  SPEAKER_00: Through July 2026, data continue to reinforce that these strategies significantly improve IOP control, but require skillful use to avoid complications.
• 17:22
  SPEAKER_00: Patients should understand that any filtering bleb needs long-term care.
• 17:27
  SPEAKER_00: By working together with their doctor, following post-op instructions, and attending regular checkups, patients can maximize the benefits of these powerful antifibrotic treatments while minimizing risks.
• 17:40
  SPEAKER_00: All links to sources are available in the text version of this article.
• 17:44
  SPEAKER_00: You can find the full article at Visualfieldtest.com.
• 17:48
  SPEAKER_00: Thanks for listening.
• 17:50
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