Confirmation of the rat model of chronic, moderately elevated intraocular pressure.

We have confirmed the usefulness of the rat model of chronic, moderately elevated intraocular pressure (IOP) for studying loss of retinal ganglion cells, and as a model for pharmacological neuroprotection studies that may be relevant to treating human glaucoma. By unilaterally cauterizing three episcleral vessels, as described previously in the literature by another laboratory, we observed an approximately 1.6-fold increase in IOP compared to the contralateral eye (18.6 vs 11.5 mm Hg, respectively). Elevated IOP persisted for 6 months without re-treatment. Cupping of the optic disk was observable by examination, in vivo. In 6 months, there was an approximately 40% loss of retinal ganglion cells in the peripheral retina. This model provides a reproducible and quantitative model for pharmacological experiments using neuroprotective agents.

Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma.

Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP. We previously demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP. Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde labeling with Fluoro-Gold. When compared with their contralateral control eyes with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.

Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies.

PURPOSE: To investigate practice patterns among glaucoma subspecialists in the American Glaucoma Society (AGS) and the Japanese Glaucoma Society (JGS), regarding use of antifibrosis agents and glaucoma drainage devices. METHODS: An anonymous survey incorporating 10 clinical situations was mailed to all AGS and JGS members in December 1995. RESULTS: Half of the AGS (105 of 210), and JGS (25 of 50) members returned surveys. Most respondents (51-87%) preferred trabeculectomy with adjunctive mitomycin for all 10 clinical situations. Mitomycin concentrations varied from 0.1 to 0.8 mg/ml (range of means for 10 situations 0.31-0.39 mg/ml) and intraoperative application times ranged from 5 s to 7 min (range of means for 10 situations 2.5-4.6 min). Preferences for either no antifibrosis agent (up to 39%) or 5-fluorouracil (up to 29%) were highest in primary trabeculectomy. Thirty-seven percent to 64% of AGS members used glaucoma drainage devices, especially after complicated postsurgical glaucomas (after penetrating keratoplasty, scleral buckling, or pars plana vitrectomy) and in neovascular glaucoma, but few JGS members used them. Large differences between university- and private practice-based AGS members were found only in mitomycin use for primary trabeculectomy (33% vs. 52%, respectively; p = 0.07) and for complicated postsurgical glaucomas (46% vs. 70%, respectively; p = 0.03). CONCLUSIONS: Trabeculectomy with mitomycin was the preferred surgical procedure among AGS and JGS members in the clinical situations surveyed. Mitomycin concentration and time of application varied widely. Many respondents used 5-fluorouracil or no antimetabolite in primary trabeculectomy. Glaucoma drainage devices were widely used for complicated glaucomas in the United States.