Pharmacological mechanisms, clinical effectiveness, and side-effects of prostaglandin analogues as anti-glaucoma agents

Prostaglandin (PG)-related ophthalmic solutions, which only recently became available for clinical use, are currently the most widely used solutions in the treatment of glaucoma, because they have excellent ocular hypotensive effects with little adverse effects. With respect to the pharmacological mechanism of action of these solutions, the mechanism of intraocular pressure (IOP) reduction for latanoprost, the first drug in this class to become available, is to promote the outflow of aqueous humor through the uveoscleral route, an important aqueous humor outflow tract. Molecular and cellular studies have shown that latanoprost affects the extracellular matrix metabolism in the uveoscleral route. For other PG-related ophthalmic solutions, there is no consensus opinion on their effects on the aqueous humor outflow tract, and how they reduce the IOP remains largely unclear. The docosanoid, isopropyl unoprostone, has excellent ocular hypotensive effects, despite having extremely low affinities to the known PG receptors. Many basic and clinical studies have demonstrated that PG-related ophthalmic solutions themselves cause not only a decrease in the IOP, but also induce endogenous PGs which could lead to secondary effects that may account in part for the IOP reduction. PG-related ophthalmic solutions have essentially no clinically important systemic adverse effects, but often have local adverse effects. The most characteristic is the pigment deposition in the iris or eyelid. Corneal epitheliopathy is also relatively common. In addition, as an adverse effect that affects vision, cystoid macular edema can be seen. Current studies are aimed at elucidating the mechanisms of development of these adverse effects, and thus to establish measures to prevent them. We compare the mechanisms of action of PG-related ophthalmic solutions and review the adverse effects and their mechanisms.Biomedical Reviews 2002; 13: 17-27

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

Purpose. To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods. Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results. Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P<0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions. Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events

Evaluation of intraretinal migration of retinal pigment epithelial cells in age-related macular degeneration using polarimetric imaging

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R2 = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED