Wound Healing Modulation 2026: Anti-fibrotics in Filtering Surgery

This audio article is from VisualFieldTest.com.Read the full article here: https://visualfieldtest.com/en/wound-healing-modulation-2026-anti-fibrotics-in-filtering-surgeryTest your visual field online: https://visualfieldtest.comSupport the show so new episodes keep coming: https://www.buzzsprout.com/2563091/supportExcerpt:Wound Healing Modulation 2026: Anti-fibrotics in Filtering Surgery 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. After surgery, the eye’s natural wound-healing response (scarring) can close off this drainage, causing the surgery to fail. To prevent excessive scarring, surgeons use anti-fibrotic medications during or after surgery. The most common agents are Mitomycin C (MMC) and 5-fluorouracil (5-FU). These drugs help keep the drainage channel open, improving long-term success. For example, in one study about 95% of eyes reached targets at 6–12 months after trabeculectomy with either MMC or 5-FU (). In other words, both drugs greatly boost the chances of success. Over the past decades and into 2026, new strategies have appeared alongside MMC and 5-FU. Rho-kinase (ROCK) inhibitors and anti-VEGF injections are emerging as wound-healing modulators. Research (in animals and small trials) suggests these may further reduce scarring in filtration surgery () (). 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). Below we summarize the evidence on dosing, outcomes, and safety of these therapies through mid-2026. Anti-Fibrotic Medications: How and How Much Mitomycin C (MMC) Mitomycin C (MMC) is a potent anti-scarring drug originally used in chemotherapy. In glaucoma surgery, it is applied as eye drops or soaked sponges under the conjunctiva at the time of surgery. Standard practice (for many years) is to use MMC at about 0.2 to 0.4 mg/mL concentration for 1–3 minutes on sponges covering the scleral flap area. (For example, the FDA-approved kit “Mitosol” provides 0.2 mg/mL and directs surgeons to apply saturated sponges for 2 minutes ().) In practice, surgeons tailor the dose: a routine case might get 0.2 mg/mL for 2 minutes, while a high-risk case (see risk section below) might get 0.4–0.5 mg/mL. After soaking, the area is rinsed with fluid to stop the drug’s action. Example dosing: In one clinical trial, surgeons applied MMC 0.2 mg/mL for 2 minutes versus 5-FU 50 mg/mL for 5 minutes during trabeculectomy (). Another study on the new PRESERFLO microshunt used 0.2–0.4 mg/mL MMC, lowering mean eye pressure from 21.7 to 14.1 mmHg at 2 years (). Patients given the higher 0.4 mg/mL dose were more likely to be off all medications at 2 years. MMC is very effective at keeping the bleb draining, giving excellent long-term pressure control in many patients (). In the 5-year study above, average pressure with MMC was 9.9 mmHg (from 25.8 pre-op) (), and success was high. However, MMC carries notable risks because it creates a thin, avascular (poorly blood-supplied) bleb. In that same study, about 15% of eyes developed late bleb leaks and 5.7% had blebitis (infection of the bleb) by 5 years (). Very low pressure (hypotony, <6 mmHg) occurred in 42% of eyes. In another study, most MMC-treated blebs became avascular (lack normal blood vessels) within a year, and leak risk increased over time (). Patients must be warned: a thin bleb can leak fluid and even harbor germs. Overall, bleb-related infection after MMC-augmented filtering surgery is uncommon but real – roughly 1–2% per year () () (for example, one survey found 1.1% infection in MMC eyes at follow-up vs 1.3% without MMC ()). Key points for MMC: Standard practice is 0.2–0.4 mg/mL for 1–3 minutes. Higher doses give more pressure lowering but a higher chance of complication. The doctor always rinses thoroughly afterward. 5-Fluorouracil (5-FU) 5-Fluorouracil (5-FU) is another anti-scarring drug used in glaucoma surgery. It is a chemotherapy agent too, but less potent than MMC when used in the eye. In contrast to MMC’s sponge application, 5-FU is often given by injections under the conjunctiva either during or after surgery. A common regimen has been 5 mg (in 0.1 mL) injected once daily for 5–10 days postoperatively. Some older studies also used 5-FU on sponges at surgery. Evidence shows 5-FU significantly reduces scarring. In one randomized trial, trabeculectomy success rates using intraoperative 5-FU were essentially the same as with MMC (), demonstrating that 5-FU can be nearly as effective. A Cochrane review found that 5-FU injections significantly lowered the risk of surgical failure in high-risk eyes. For example, adding perioperative 5-FU to repeat glaucoma surgery cut failure risk by about one-third (relative risk ~0.67) (). In high-failure-risk eyes (like after a prior surgery), they calculated needing to treat only ~4 eyes to prevent one reoperation. 5-FU also produced substantial IOP drops: in the same review, “high-risk” patients getting 5-FU had mean IOP ~16 mmHg lower than controls at 1 year (). Because 5-FU tends to cause less severe thinning of the bleb wall than MMC, it is sometimes preferred for patients at very high risk of complications. Its side effects include corneal irritation (toxicity to the front of the eye), shallow anterior chamber, and bleb leak. The Cochrane summary noted that things like wound leaks and low pressures were more common with 5-FU, though the overall infection risk was low (). In practice today, 5-FU is often used in follow-up clinic if a newly formed bleb shows too much scarring: the surgeon may inject 5-FU in the office or perform needling (bleb revision) with 5-FU to improve flow. Key points for 5-FU: Common regimen is 5 mg daily for ~5 days post-op. It boosts success in tough cases (). It causes less avascular thinning than MMC, but blebs can still leak or stay flat. ROCK (Rho-Kinase) Inhibitors and Other Emerging Drugs ROCK inhibitors are a newer class of glaucoma medications originally developed to lower pressure by relaxing eye outflow channels. Preclinical studies suggest they also have anti-scarring effects. ROCK inhibitors (like ripasudil or netarsudil drops) can slow down fibroblast activity in the conjunctiva. Animal models of glaucoma surgery have shown that adding a ROCK inhibitor to the eye reduces postoperative scarring (). Commercially available ROCK inhibitor eye drops (e.g. netarsudil) 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. Other agents under investigation include anti-VEGF drugs (like bevacizumab) and experimental molecules that block fibrotic growth factors. For example, a recent randomized clinical trial (2023) found that a single intravitreal bevacizumab injection at the time of trabeculectomy significantly improved results: only 6% of eyes in the bevacizumab group needed glaucoma medications at 1 year (versus 17% of controls), and only 2% needed additional surgery (versus 10% of controls) (). Bleb appearances were also better (larger blebs, less redness) in the bevacizumab group (). These findings suggest anti-VEGF can help modulate wound healing. 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. Sustained-Release and Targeted Delivery Because continuous exposure to anti-fibrotic agents might improve outcomes, researchers are developing sustained-release formulations. For example, a novel gel implant containing MMC was tested in rabbits with a tiny drainage stent. 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 1 week in untreated eyes (). This shows how a slow-release system can keep the bleb functioning much longer. Other approaches include microparticles or coatings on drainage devices. In lab research, scientists coated a glaucoma tube shunt with microparticles of MMC. The microparticles slowly release the drug locally to the surrounding tissue, aiming to prevent fibrosis around the shunt. Such designs are experimental but promising (). 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. As of 2026 these sustained-release products are mostly in animal or early human testing, but they represent a future strategy to make anti-fibrotics safer and more effective. Bleb Morphology and Infection Risks The goal of using anti-fibrotics is to create a well-formed, functioning bleb that continues to drain fluid. Typical bleb appearance with MMC is often a large, thin-walled, leaky bleb. This “cystic” bleb can be ideal for lowering pressure but also precarious. A large multi-lobed bleb covering much of the upper sclera with few surface blood vessels is often seen. With 5-FU, blebs may be a bit thicker and less avascular than with high-dose MMC, but can still be cystic. 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 (). In that series, 71% of MMC-blebs were avascular by 1 year. Larger avascular blebs were roughly four times more likely to ooze or leak thSupport the show