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The use of a liposome-encapsulated 5-fluoroorotate for glaucoma surgery: I. Animal studies.

We have considered the wound-healing and tissue-repair process as it applies to glaucoma filtration surgery. Information derived from classical histologic studies of functioning and failed blebs has been considered in view of the new ideas based on modern cell biology concepts of the wound healing process. These evaluations provide a rationale for the use of adjunctive chemotherapy for glaucoma filtration surgery. A study is described using posterior-lip sclerectomies, an experimental monkey model, a liposomal-drug delivery system and the potent pyrimidine analog L5FO. Results of the clinical evaluation, IOP measurements, and histologic examination of L5FO treated and untreated eyes are reported. We found that the wound healing response at the surgical limbus after a posterior sclerectomy appears similar to that described for other vascularized soft tissues. The macrophage appeared to play an important role in the healing of the episcleral tissues (including Tenon's capsule and the conjunctival stroma), which proceeds rapidly resulting in the deposition of a fibrovascular scar by 2 weeks in most cases. The administration of the L5FO is highly effective in preventing the formation of such scars and thereby promoting development of functioning blebs. The administration of this wound healing retardant 1 week prior to surgery, compared to its administration at the time of surgery, shows that both methods are effective, but the use of L5FO prior to surgery is most effective. The use of the experimental monkey model described by Parrish et al offers many research opportunities to develop better adjunctive chemotherapies for glaucoma filtration surgery.