2--7--bis-(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethyl-ester and Fibrosis

To evaluate the safety, tolerability, and clinical effect on intraocular pressure (IOP) of a carboxyfluorescein ester as an adjunctive antifibrotic therapy in human glaucomatous eyes to control postoperative wound healing after trabeculectomy.. In 10 human glaucomatous eyes with high IOPs that underwent 1 to 3 previous surgical procedures for glaucoma, 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester was applied 15 minutes prior to trabeculectomy via a subconjunctival injection followed by intraoperative illumination with diffuse blue light (450-490 nm; approximately 51.9 x 10(3) candelas/m(2)) for 8 minutes. Antifibrotic efficacy was established by clinical response, postoperative IOP reduction, slitlamp examination, and filtering bleb site photographs. Success was defined as an IOP less than 21 mm Hg from baseline without the eye receiving any antiglaucomatous medication or an application of antimetabolites.. The mean (SD) IOP on the day before surgery was 37.2 (11.2) mm Hg. The IOP was 16.6 (3.8) mm Hg in 8 successful eyes after a mean (SD) follow-up of 400.1 (38.1) days (P<.001). Two eyes showed scarring at the site of the filtering bleb within 1 month. In 1 eye with pseudoexfoliation glaucoma IOP decreased to 17 mm Hg but needed topical antiglaucomatous medication. Clinical examination revealed none of the following: blebitis, uveitis, endophthalmitis, or toxic damage of the adjacent tissues.. We report our findings about the first 10 consecutive human glaucomatous eyes treated with a single dose of 80 microg of 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester during trabeculectomy. In contrast to chemotherapeutic agents, cellular photoablation acts only on cells having incorporated 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester and having been exposed to light of an appropriate wavelength. Though safety and efficacy demand a controlled randomized study, our method seems to be an effective therapeutic approach to control postoperative fibrosis in human glaucomatous eyes with a poor surgical prognosis. Multiple factors such as dose of light, means of application, wavelength, irradiation area, total dose of the dye, and multiple dosing may be altered in the future to improve the antifibrotic effect of photodynamic therapy during surgery for glaucoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Exfoliation Syndrome; Female; Fibrosis; Fluoresceins; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Postoperative Complications; Safety; Sclera; Trabeculectomy; Treatment Outcome; Wound Healing

To evaluate the feasibility of cellular photoablation using fluorescence generated photoreaction products as a method to control postoperative fibrosis.. The fluorescent probe, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) is a cell membrane permeable compound rendered membrane impermeable and fluorescent upon cleavage by intracellular esterases. Rabbits (ChBB:CH; n=20) received a unilateral subconjunctival injection of BCECF-AM (40, 70, 80, or 100 microg) 30 minutes before surgery followed by intraoperative illumination with diffuse blue light (450-490 nm; 51.9 x 10(3) cd/m(2)) for 10 minutes. Controls received either the probe or illumination. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by comparing intraocular pressure (IOP) between the treated experimental eye and the fellow eye, which served as control. Success was defined by >20% difference in IOP.. IOP was significantly decreased in all groups within 4 days postoperatively. In control groups IOP rose within 10 days to normal levels. This was similar in the group receiving 40 microg of BCECF-AM. In the other groups (subconjunctival injection of 70-100 microg BCECF-AM) IOP was significantly (p < 0.02) decreased for 2-3 weeks. Clinical and histological examination revealed no toxic damage to adjacent tissues.. Cellular photoablation in contrast with chemotherapeutic agents acts on cells that have incorporated BCECF-AM and have been exposed to light at the appropriate wavelength. Though safety and reliability demand further studies this method might be an useful therapeutic approach to control postoperative fibrosis in humans undergoing filtration surgery.

Topics: Animals; Disease Models, Animal; Evaluation Studies as Topic; Fibrosis; Fluoresceins; Intraocular Pressure; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Rabbits; Trabecular Meshwork; Trabeculectomy