[Clinical efficacy of travoprost-timolol fixed combination on ocular hypotensive agents and ocular surface agents in Japanese glaucoma patients].

PURPOSE: To investigate the clinical effects of travoprost-timolol fixed combination on ocular hypotensive agents, ocular surface agents and adherence in Japanese glaucoma patients. METHODS: 28 Japanese glaucoma patients, who had used topical prostaglandin F2alpha analogue (28 eyes; PG group), were assigned to treatment with travoprost-timolol fixed combination. Reduction of intraocular pressure (IOP), grades of conjuctival follicle, conjuctival injection and keratoepitheliopathy, as well as interviews for topical administration, were evaluated. 38 patients, who switched from the topical prostaglandin F2alpha analogue and a beta-blocker to travoprost-timolol fixed combination (38eyes: PG+BB group) were also evaluated in the same manner. RESULTS: While IOP was significantly reduced in the PG group, IOP was not changed in the PG+BB group. Both groups showed no significant changes in scores for conjuctival follicle, keratoepitheliopathy, or interview. CONCLUSION: These results suggest that travoprost-timolol fixed combination reduces IOP and produces low toxicity on the ocular surface.

Recovery of reliability by retest after a 5-minute interval in frequency doubling technology perimetry.

PURPOSE: In frequency doubling technology (FDT) perimetry, the incidence of tests classified as unreliable is higher in the second-tested left eye than in the first-tested right eye when perimetry is performed without a rest period. The purpose of this study was to determine whether the incidence of unreliable results was reduced when the retest began after a 5-min rest period. METHODS: The subjects were 978 residents of Miyoshi City, Japan, who underwent FDT perimetry during a medical checkup. FDT perimetry was always performed first on the right eye and then on the left eye without a rest interval. When the results were determined to be unreliable, FDT perimetry was repeated after a 5-min rest interval. RESULTS: The perimetric results were determined to be unreliable in one eye of 119 subjects; the results of the first-tested right eye were unreliable in 24 (20.2%), and the results of the second-tested left eye were unreliable in 95 (79.8%) subjects. This difference in the incidence of reliability was significant (P<0.001). After a 5-min rest interval, the percentage of eyes with reliable results recovered to 92% of the right eyes and to 86% of the left eyes. CONCLUSIONS: The incidence of unreliable results in FDT perimetry of the second-tested left eye was higher than that of the first-tested right eye when tests were performed without a rest interval. However, the incidence of unreliability in the eye was decreased when the retest was performed after a 5-min rest interval.

The efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in combination therapy with latanoprost, timolol, and dorzolamide.

PURPOSE: The aim of this study was evaluate the efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in patients with glaucoma treated by latanoprost, timolol, and dorzolamide. METHODS: An 8-week, prospective, randomized, open-label, comparative study was performed in 58 patients with primary open-angle glaucoma treated by latanoprost, timolol, and dorzolamide. These patients were randomly enrolled into two groups: (1) dorzolamide three times daily was substituted with brinzolamide twice-daily (substituting group); and (2) dorzolamide three times daily was continued (control group). Intraocular pressure (IOP) was measured at baseline, 4, and 8 weeks after the enrollment. Subjective ocular discomfort (irritation and blurred vision) at the time of the instillation of the patient was noted with interview. RESULTS: The IOPs at baseline, 4 and 8 weeks after the enrollment were 17.7 +/- 2.7 mmHg, 17.5 +/- 2.6 mmHg, and 17.4 +/- 2.9 mmHg in the substituting group, and 18.0 +/- 2.5 mmHg, 17.8 +/- 2.5 mmHg, and 17.9 +/- 2.6 mmHg in the control group, respectively. There were no significant differences in IOP changes between the two groups (P = 0.74). In the substituting group, ocular irritation was decreased significantly (P = 0.0014) from 63% to 20%. The slight increase of blurred vision from 27% to 37% that occurred in the substituting group was not significant (P = 0.58). In the control group, neither ocular irritation (P = 0.58, from 68% to 57%) nor blurred vision (P = 0.99, from 25% to 21%) was changed. CONCLUSIONS: Substituting brinzolamide for dorzolamide maintained stable IOP with improvement in ocular comfort in patients with glaucoma.

Reliability of the first eye and second eye in frequency doubling technology perimetry.

PURPOSE: To compare the reliability of the perimetry results of the first eye and the second eye with frequency doubling technology (FDT). METHODS: The subjects were 328 residents who underwent the C-20-5 mode of FDT at a city in central Japan. FDT perimetry was always performed first in the right eye and then in the left eye without any time between tests. When more than 33% fixation loss or false-positive error was detected, the result was judged unreliable. RESULTS: Of the 328 subjects, the bilateral perimetry results were reliable in 255 subjects (77.7%), the unilateral results were reliable in 57 (17.4%), and there was not a reliable result in either eye in 16 (4.9%) subjects. Of the 57 subjects whose unilateral result was unreliable, the result of the second eye was unreliable in 50 (88%) subjects, and the result of the first eye was unreliable in 7 (12%). This difference in the reliability between the first eye and second eye was significant (P < 0.001). There were no differences in the age, sex, visual acuity, refractive error, test duration, or number of glaucoma suspects between the two groups whose unilateral result was unreliable in the first eye or the second eye. CONCLUSIONS: The FDT perimetry result of the second eye was less reliable than that of the first eye.

Improvement in cognitive impairment after cataract surgery in elderly patients.

PURPOSE: To evaluate whether cognitive impairment improves in elderly patients who have cataract surgery with intraocular lens (IOL) implantation. SETTING: Kouki Hospital, Yamaguchi, Japan. METHODS: A prospective observational study evaluated patients' scores on the Revised Hasegawa Dementia Scale (HDS-R) and the HDS-R minus 1 item regarding immediate regeneration (ie, function of vision and memory). Twenty patients (6 men, 14 women) with cognitive impairment had cataract surgery in 1 eye between March 1996 and July 2001 at Kouki Hospital, Japan. The mean age of the patients was 81.8 years (range 61 to 90 years). Twenty patients (4 men, 16 women) with cognitive impairment who did not have cataract surgery were selected as a control. The mean age in the control group was 84.3 years (range 70 to 93 years). The HDS-R was administered twice between March 1996 and July 2001. RESULTS: The mean HDS-R scores in the cataract surgery group improved from 12.5 points +/- 5.3 (SD) preoperatively to 16.6 +/- 6.2 points postoperatively; the improvement was significant (t = -5.02; P<.0001). After cataract surgery, the grade of cognitive impairment improved in 12 patients (60%), was unchanged in 7 (35%), and was worse in 1 (5%). CONCLUSION: Cataract surgery improved cognitive impairment in elderly Japanese patients.

Additive effect of bunazosin on intraocular pressure when topically added to treatment with latanoprost in patients with glaucoma.

PURPOSE: To investigate whether an alpha-1 blocker, bunazosin, has an additive effect on lowering intraocular pressure (IOP) when topically added to latanoprost treatment in patients with glaucoma. METHODS: Bunazosin twice a day was added topically to the treatment for 12 patients with glaucoma who had been instilling latanoprost once a day for more than 1 month. IOP was measured and adverse events were checked 2, 4 and 8 weeks after the addition of bunazosin to their treatment. RESULTS: One of the 12 patients dropped out in the course of the study. Therefore, 11 patients were included for the analysis of IOP, and 12 for the analysis of adverse events. IOPs were decreased significantly (P=.008, Wilcoxon signed rank test) from 18.2+/-3.4 mm Hg to 16.6+/-3.5 mm Hg 8 weeks after the addition of bunazosin. Adverse events were seen in 5 of the 12 patients. CONCLUSION: Bunazosin has an additive effect on lowering IOP when topically added to latanoprost treatment in glaucoma patients.

Existence of ionotropic glutamate receptor subtypes in cultured rat retinal ganglion cells obtained by the magnetic cell sorter method and inhibitory effects of 20-hydroxyecdysone, a neurosteroid, on the glutamate response.

Glutamate and neurosteroids are known to exist in retinal ganglion cells (RGC). Therefore, patch clamp studies using the whole-cell recording method were performed to determine whether or not ionotropic glutamate receptor subtypes, i.e., N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors, were present on RGC obtained by the magnetic cell sorter (MACS) method and cultures. In addition, the effects of 20-hydroxyecdysone (20-HE), a neurosteroid, on inward currents induced by NMDA, AMPA and kainate were examined at a holding potential of -60 mV. The current-voltage relationship for NMDA in the presence of glycine and Mg2+-free, as well as those for AMPA and kainate were linear, with a reversal potential of around 0 mV. NMDA-induced currents were blocked by MK-801, while both AMPA- and kainate-induced currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Application of 20-HE in the bath resulted in significant inhibitions on NMDA-, AMPA- and kainate-induced currents. Thus, NMDA, AMPA and kainate receptors were confirmed to exist on MACS-separated cultured RGC. Moreover, 20-HE inhibited NMDA receptor-mediated currents most prominently and AMPA- and kainate-mediated currents moderately, suggesting that neurosteroids may be playing a role in modulating glutamate-mediated transmission in RGC, and 20-HE might be useful for preventing glutamate neurotoxicity.

In situ localization of nitric oxide synthase and direct evidence of NO production in rat retinal ganglion cells.

The expression of isoforms of nitric oxide synthase (NOS), enzymes responsible for NO production, and the synthesis of nitric oxide (NO) in rat retinal ganglion cells (RGCs) during synaptogenesis for various phases of the pre- and postnatal developmental periods were investigated. The retinas from prenatal, lactating, young, and adult rats were fixed in paraformaldehyde. The cryosections or paraformaldehyde-fixed ganglion cells purified from rat pups were immunostained for constitutive isoforms of NOS (n and eNOS) and observed with a confocal laser scanning microscope. Synthesis of NO in the RGCs was achieved by in vitro stimulation with glutamate. The intracellular NO levels were measured in real time using diaminofluorescein-2 diacetate, a fluorescence indicator of NO. Immunohistochemical analysis revealed nNOS and eNOS expressed in retinal ganglion cells during the first 2 postnatal weeks. Cultured RGCs also expressed nNOS and eNOS in vitro. Intracellular NO levels in cultured RGCs showed spontaneous fluctuation during a 20-min observation. The presence of both a non-specific NOS inhibitor, L-NAME, and a specific nNOS inhibitor, 7-NI, significantly inhibited (P<0.001) the increase of intracellular NO 6 and 8 min after the introduction of L-arginine and glutamate to the medium. This study revealed that all constitutive NOS isoforms are expressed in RGCs and demonstrated that NO is produced by nNOS mainly through stimulation by glutamate in cultured RGCs.