This week's column is the first of a series covering the recent meeting of the Association for Research in Vision and Ophthalmology, in Fort Lauderdale, and concerns the prevention of wound healing after glaucoma filtration surgery. The use of 5-FU by injection, introduced in the early 1980s, was applied in a fairly standard manner, modifications consisting of the number and site of injections. With mitomycin C, however, the comparison of various concentrations and durations of application lose nothing without some measure of how and for how long it is applied. A surgical wipe holds fluid much better than the same sized piece of Weck-cel sponge. What does blood penetrating the sponge do to the effect? One can use different sizes and numbers of sponges. How thick is the tenon's and how injected and fibrotic the episclera? For now, it would seem best that each surgeon work out a method based on a combination of published outcomes and his or her own cumulative experience.

Eve J. Higginbotham, M.D.

Karen Shelton, M.D.

From the Department of Ophthalmology, University of Maryland at Baltimore, Baltimore, Maryland

In spite of our best efforts, even with the use of the antifibrotic agents 5-fluorouracil (5-FU) and mitomycin C (MMC), maintaining long-term success after filtration surgery remains a challenge. To attain successful long-term filtration, we need to better understand and be able to manipulate the wound healing process. Teleologically, there is an obvious advantage to having wounds heal quickly, and the processes involved in wound healing are most likely genetically determined. Rapid wound healing in glaucoma surgery, however, becomes a potent adversary of surgeon and patient alike. As much as 5-FU and mitomycin C (MMC) improve bleb survival and enhance IOP reduction after glaucoma filtration surgery, they are still not a panacea. What remains puzzling is why patients' responses to MMC vary even with the same concentrations of MMC. Assuming that not all patients are alike, what are the ideal concentrations of MMC that we should be using? Should we concentrate our efforts on manipulating the growth factor profile, instead of relying on antifibrotic agents? Also, by using these, are we only changing the sequence of events in the wound healing process, but not preventing the inevitable?

A minisymposium on wound healing, moderated by Drs. Jeffrey Freedman and Peng T. Khaw, included Drs. G.L. Skuta, D.A. Lee, P.T. Khaw, D.L. Minckler, A.C.B. Molteno, M.W.J. Ferguson, D. Goddard, and G.S. Schultz as participants. The symposium began with an overview of the conjunctival effects of MMC in filtration surgery. A subconjunctival injection of 0.2 cc or 0.4 mg MMC/ml produces intracellular vacuolization. Potential complications include ciliary body and rod outer segment toxicity, more prounced hypotony than occurs with 5-FU, wound and bleb leaks, bleb infection and endophthalmitis.

Animal models and in vitro studies help us better understand the wound healing process, specifically the role of fibroblasts in scar formation. Useful devices include the Boyden Chamber to determine cell migration and motility, the Coulter Counter to measure cell numbers, and an ELISA Plate Reader. Models can be effective, efficient and economical, and good tools for screening antifibrotic agents, but remain limited for studying complex interactions between different cell types and functions and for duplicating immunologic responses.

The effects of 5-FU are short-term compared to those of MMC. When rabbits undergoing filtration surgery were injected with 5-FU, scarring was initially inhibited but failure was seen at 14 days, while MMC was still successful at 30 days. When MMC 0.5 mg was applied for 5 minutes in drainage implant surgery (Baerveldt) in rabbits, using a closed manometer system to study pressure effects, resistance to flow was transiently decreased with significantly lower IOP only up to ten weeks. In an attempt to determine a relationship between bleb structure and functional efficacy, histochemical studies of cadaver eyes with prior Molteno seton implantation showed establishment of a dynamic equilibrium after 3 months. Studies of tissue around the blebs showed collagen breakdown inside and collagen deposition outside the inner lining of the bleb. Factors producing a favorable response after drainage surgery include normal IOP, a quiet eye, older patients, vasoconstrictors, beta-blockers, acetazolamide and systemic steroids.

Growth factors and their interactions with one another play a key role in scar formation in both skin and conjunctiva. Decreasing growth factors at the wound site might lead to decreased wound healing. When growth factor antibodies were applied to skin wounds at days 7 and 14, there was a decrease in the number of monocytes and macrophages. Activated TGF-§1 appears to increase scar formation, while TGF-§3 may decrease it. Our understanding of wound healing in the conjunctiva may be helped by studies of wound healing in the skin and synovial inflammation.

Modulation of healing after glaucoma surgery is crucial in maintaining bleb survival. It remains unclear why patients vary in response to the same doses of MMC. Is it simply because we are not all delivering the same doses of MMC? Are fibroblasts activated by use of topical drugs, such as beta-blockers, and miotics? Does the initial fibroblast activity affect postoperative activity? What role do growth factors play? Can we develop a consistent method for the use of MMC? We still need to determine the role of MMC in combined cataract and glaucoma surgery, the relative roles of 5-FU and MMC in primary and "high-risk" surgery, and to further determine the short and long-term effects of MMC if it is to continue to be in our armamentarium. Although currently used antifibrotic agents have improved surgical outcomes, their associated complications, ocular toxicity and lack of standardization in terms of concentrations and duration will limit their use. Continual search for wound healing inhibitors which are safer as well as effective is paramount.

Papers Presented at the Session

1. Skuta GL. Adjunctive mitomycin in glaucoma filtering surgery. Invest Ophthal Vis Sci, 1996;37(Suppl):S422

2. Lee DA. Animal models and cellular studies of wound healing. Invest Ophthal Vis Sci, 1996;37(Suppl):S422

3. Khaw PT. Animal models of wound healing: lessons from the laboratory to the clinic. Invest Ophthal Vis Sci, 1996;37(Suppl):S422

4. Minckler D. Antifibrosis agents in drainage implant surgery. Invest Ophthal Vis Sci, 1996;37(Suppl):S422

5. Molteno ACB, Dempster AG, Cunliffe IA. Light and ultrastructural microscopy of molteno drains. Invest Ophthal Vis Sci, 1996;37(Suppl):S422

6. Ferguson MWJ. Control of dermal scarring by manipulation of TGFS. Invest Ophthal Vis Sci,1996;37(Suppl):S423.

7. Goddard D. Mechanisms of inflammatory fibrosis in glaucoma. Invest Ophthal Vis Sci, 1996;37(Suppl):S423.

8. Schultz GS, Khaw P. Sherwood M, Doyle W. Role of growth factors in glaucoma surgery. Invest Ophthal Vis Sci, 1996;37(Suppl):S423.

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