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Trabeculectomy patient; study indicates that that MMC & Avastin subconjunctival treatment before the end of surgery will slow aggressive wound healing in patients who’ve undergone previous failed surgeries
Source: Daljit Singh, M.D.

Despite trabeculectomy’s gold standard reputation, research suggests it doesn’t work as well after previous failed glaucoma surgery or in especially difficult glaucoma cases. “Conventional trabeculectomy is reported to be less successful in eyes that have undergone failed glaucoma surgery or have a disease with poor prognosis (i.e., neovascular glaucoma (NVG) or uveitic glaucoma), when compared to the eyes with primary disease, probably due to the aggressive wound healing process associated with excessive inflammation, adhesion, or angiogenesis,” according to a report by Jaewan Choi, M.D., HanGil Eye Hospital, Incheon, South Korea. The study was published in the February issue of the Korean Journal of Ophthalmology.
Such vigorous wound healing, which is not necessarily desirable in the case of trabeculectomy, may be significantly deterred in some regards by a drug that has gained popularity for its off-label use in the treatment of age-related macular degeneration: bevacizumab (Avastin, Genentech, South San Francisco, Calif.). This time, bevacizumab’s use was once again off-label by researchers, and once again, efficacious.
“Subconjunctival bevacizumab administration may be an effective and safe adjunct regimen to trabeculectomy in eyes with refractory glaucoma,” Dr. Choi reported. “The blockage of angiogenesis and possible fibroblast modulation with anti-VEGF agent may provide some benefits for glaucoma filtering surgery.”
Those benefits don’t come without additional risks because delayed wound healing in other respects is problematic. “While the inhibition of angiogenesis could play a beneficial role in the scleral flap healing process, also possible is that interrupted wound healing may dispose the conjunctival incision to postoperative leakage in trabeculectomy,” Dr. Choi noted.“Precise surgical skill for watertight conjunctival closure is warranted if subconjunctival bevacizumab is used as an adjunct regimen to trabeculectomy.”

Case reports

Dr. Choi analyzed six eyes of six consecutive glaucoma patients who underwent trabeculectomy with mitomycin C and received a 1.25 mg subconjunctival bevacizumab injection at the end of the surgery. Two eyes had NVG, three had uveitic glaucoma, and one had secondary glaucoma after vitrectomy. They also all previously underwent a failed glaucoma laser or surgical treatment or intraocular surgery.
Results proved promising. Overall, IOP was 37.5 mm Hg pre-op, 6.2 mm Hg at one week, 8.3 mm Hg at one month, 12.0 mm Hg at two months, 10.8 mm Hg at three months, and 12.2 mm Hg at six months.
“All eyes had functioning blebs with normal IOP at postoperative 6 months with no additional IOP-lowering medication,” Dr. Choi reported.
Dr. Choi suggested that inhibiting angiogenesis with the anti-VEGF treatment could have been the reason why these challenging glaucoma patients did so well. “Angiogenesis, the process of new blood vessel formation, is a key element in the proliferative phase of wound healing, supplying oxygen and nutrients to support the rapid growth of cell-mediated repair,” Dr. Choi noted. “[Researchers] reported that VEGF promoted angiogenesis and scar formation in early fetal skin and that a VEGF blockade influenced the organization of scar tissue. VEGF neutralization not only reduced the amount of scar tissue formed, but also improved the quality of the scar tissue that did form by shifting the collagen fibril distribution to a state more closely resembling normal skin in a mouse model.”
Topical and systemic uses of bevacizumab work against inflammation-induced angiogenesis and lymphangiogenesis in the cornea, Dr. Choi reported.
“Reducing the amount of cytokines (e.g., fibroblast growth factor, VEGF) released from the vessels to the site of injury by blocking angiogenesis with bevacizumab may indirectly render the scleral flap less adherent to its original site during the immediate postoperative period, allowing more fluid to drain through the flap,” Dr. Choi reported. “Another possible explanation could be that bevacizumab itself acts on the scleral flap’s scar formation directly through fibroblast modulation.”
Sujatha Mohan, M.D., associate medical director, Rajan Eye Care Hospital, Chennai, India, says she has doubts about whether bevacizumab would be helpful for standard trabeculectomies for glaucoma, but she has used bevacizumab for neovascular glaucoma with success. “We use it as an intracameral agent to reduce vascularity, and we have found it works very well,” Dr. Mohan said.
Dr. Mohan does not believe bevacizumab would be, on its own, a treatment for neovascular glaucoma, but rather it serves as a piece of the treatment pie. “The pressure also has other mechanisms for building up,” Dr. Mohan said. “But bevacizumab is useful for treating the neovascularization of the iris in neovascular glaucoma.”

Editors’ note: Dr. Choi reported no financial interests related to this study. Dr. Mohan has no financial interests related to her comments.