Postoperative fibrosis suppression

The use of antimetabolites to modulate wound healing post-trabeculectomy has been a major advance in glaucoma filtering surgery. Initially, 5-fluorouracil and, more recently, mitomycin C, have been used to dramatically improve success rates in patients at high risk for trabeculectomy failure, reducing the need for postoperative glaucoma medications. However, the use of antimetabolites has been accompanied by an increased risk of complications, including early and late bleb leaks, hypotony, maculopathy, and endophthalmitis. An alternative treatment that could be applied after surgery to rescue those blebs that appear at increased risk to fail would be valuable, especially if it would obviate the need for mitomycin C.

Fuller et al’s study in this issue of the BJO (p 1352) highlights a different approach to fibrosis suppression post-trabeculectomy. Their regimen involves the use of three agents taken orally: prednisone, a non-steroidal anti-inflammatory agent, and colchicine. They used these drugs in a series of 77 of 551 eyes that had undergone trabeculectomy between 1978 and 1998. In none of these operations was an antimetabolite used. All patients had either primary open angle glaucoma or exfoliation syndrome and only two patients had a previous trabeculectomy.

These 77 eyes were selected for antifibrosis treatment because of an exaggerated postoperative healing response with increased bleb vascularity, a Tenon’s cyst formation with elevated intraocular pressure, or a reduction in bleb size with visible fibrosis and threatened bleb failure. The antifibrosis regimen was started, on average, 11 days after surgery; the range was 7–30 days. The best response was in patients started within 2 weeks of surgery and six of the eyes required subsequent bleb needling. No cases of endophthalmitis, hypotony, maculopathy, late bleb leak, or serious systemic side effects from the postoperative regimen occurred.

Long term success results are very impressive as defined by their criteria. Sixty nine of 77 eyes (89.6%) were classified as successful with an IOP of less than or equal to 21 mm Hg. The Kaplan-Meier probability of success was 0.91 at 8 years. This compares quite favourably with the 52% success rate at 4 years, reported by Ehnrooth et al.¹ However, today in a similar group of primary trabeculectomies, a pressure of 21 mm Hg post-trabeculectomy without consideration of disc and field status over time would not be classified a success by many ophthalmologists. The Advanced Glaucoma Intervention Study showed that patients required eye pressures less than 18 mm Hg for all follow up visits to prevent progressive damage.²

Fuller et al recommend that the oral medications be taken three times a day to be maximally effective. Given their potential side effects, the use of three systemic agents in an older age group population is somewhat worrisome. Dosages were tailored to patients’ size, age, general health, and degree of possible bleb failure and they were reported to be well tolerated, with only seven patients requiring an oral histamine-2 blocker (ranitidine) to counteract gastrointestinal upset. One wonders why this regimen has not been more widely embraced.³

This series is noteworthy because of its unique therapeutic approach which may help to reduce the growing incidence of complications associated with the use of mitomycin C. This regimen of fibrosis suppression has particular appeal in primary trabeculectomies. Bindish et al reported 123 eyes that underwent primary trabeculectomy with varying concentrations and durations of mitomycin C application.⁴ Their complications included hypotony (IOP <6 mm Hg) in 42.2% of eyes with a mean follow up of 26.1 months and hypotony maculopathy in 8.9% of eyes. It also could be used after mitomycin C trabeculectomy as adjunctive therapy to try to rescue a potentially failing filter if there were signs of early bleb failure.

For many eyes, this “exaggerated” healing phase may be part of an encapsulated bleb phase which responds well to conservative topical aqueous suppressant therapy.⁵ For others, it may represent a scarring process leading to bleb failure. We do not know how many of these blebs would fail and how many would function if this antifibrosis regimen was not initiated. A prospective randomised study comparing conventional postoperative topical therapy versus the antifibrosis regimen of postoperative prednisone, a non-steroidal anti-inflammatory, and colchicine would clarify its true benefit.