Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. II. Slit-lamp biomicroscopy, aqueous humor analysis, and fluorescein angiography

Prostaglandin (PG) F2 alpha (250 micrograms in 50 microliters saline) or epinephrine 2% solution (50 microliters) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. A trace aqueous humor flare response occurred in some PGF2 alpha-treated eyes, which reached significance (P less than 0.05) only when observed 4 hr after the first or seventh dose. No significant anterior chamber cellular response was observed in treated as compared to control eyes. Slit-lamp biomicroscopic evaluation of the cornea, iris, and lens showed no differences in treated as compared to control eyes throughout the study. Aqueous humor samples were obtained from all eyes 4 hr after the ninth consecutive dose. Soluble protein concentration was significantly (P less than 0.01) greater in the PGF2 alpha-treated eyes (1.22 +/- 0.30 mg/ml) as compared to control (0.56 +/- 0.17 mg/ml) or to epinephrine-treated eyes (0.59 +/- 0.18 mg/ml). Microscopic examination of sediments obtained after centrifugation of the aqueous humor revealed no cells in experimental or control samples. Both PGF2 alpha and PGE2 levels were significantly (P less than 0.025) greater in PGF2 alpha-treated eyes, and showed a trend towards being greater in epinephrine-treated compared to control eyes. Neither cystoid macular edema nor other retinal abnormalities were evident by fluorescein angiography in any eyes during the second week of treatment. Multiple dosing of PGF2 alpha in monkey eyes does not appear to produce clinically significant adverse effects in either the anterior or posterior segment which would contraindicate its use in a multiple-dose clinical trial in glaucoma patients.