Vascular and glial changes of the retrolaminar optic nerve were studied in monkey eyes with increased intraocular pressure (IOP) from 1 to 4 years and with different stages of optic nerve atrophy. In histological cross-sections of retrolaminar optic nerves of 11 rhesus and 6 cynomolgus monkeys the entire area, number of axons and vessels and area of pial septa were quantitated and three different kinds of nerve degeneration classified. Ultrathin sections of these different stages were performed and the number of open and occluded vessels was determined. In addition, in cynomolgus monkey optic nerves immunohistochemical staining for alphaB-crystallin, glial fibrillary acidic protein (GFAP) and vimentin was performed. Even in animals with the same duration of glaucoma and comparable mean IOP values the axon degeneration varied considerably. Independently of axon loss the number of capillaries in the rhesus monkeys remained constant, whereas there was a slight decrease in the cynomolgus monkeys. Some of the vessels, especially in the most severely damaged regions, were occluded. The density of glial cells increased whereas the total number remained nearly constant. In control sections all astrocytes stained for GFAP and alphaB-crystallin. In the glaucomatous optic nerves the density of alphaB-crystallin- and GFAP-positive cells was significantly increased. The vascular reaction in the retrolaminar glaucomatous optic nerves differs from that described in the prelaminar region. We assume that in the postlaminar region in areas with diminished nutritional needs vessels occlude and finally degenerate.

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A pooled-data analysis of three randomized, double-masked, six-month clinical studies comparing the intraocular pressure reducing effect of latanoprost and timolol.

PURPOSE: To compare the intraocular pressure (IOP) reduction by latanoprost and timolol, and to study factors of prognostic value for assessing this reduction. METHODS: We analyzed 829 patients included in three phase 111 studies comparing six months' treatment with 0.005% latanoprost once daily and 0.5% timolol twice daily in patients with open-angle glaucoma or ocular hypertension. Analysis of covariance controlled for differences in baseline IOP and sex was used to assess the IOP reduction. RESULTS: Latanoprost reduced diurnal IOP (average of morning, noon and afternoon assessments) by 7.7 mmHg (31%) and timolol by 6.5 mmHg (26%) after six months of treatment. Thus the diurnal IOP was reduced 1.2 mmHg (18%) more with latanoprost than with timolol (p<0.001). Latanoprost-treated patients showed a further decrease in morning IOP of 0.7 mmHg (9%, p<0.001) from the initial morning IOP reduction obtained at two weeks. No such further decrease in IOP was seen with timolol. Higher baseline diurnal IOP resulted in a larger diurnal reduction during treatment with both drugs (p<0.001). Diurnal IOP in women was reduced 0.7 mmHg (11%) less than males with both drugs (p<0.001). CONCLUSIONS: Latanoprost was more effective than timolol in reducing mean diurnal IOP. The effect after two weeks was maintained for timolol while with latanoprost there was a further, significant IOP reduction from two weeks to six months. Baseline IOP was the only factor of clinical importance found to be of prognostic value for assessing the IOP reduction.

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