Dorzolamide, a topical carbonic anhydrase inhibitor: a two-week dose-response study in patients with glaucoma or ocular hypertension.

We investigated the dose-response relationship of the intraocular pressure-lowering activity of dorzolamide, a novel topical carbonic anhydrase inhibitor previously known as MK-507. A double-masked, randomized, multicenter study of 113 patients with either primary open-angle glaucoma or ocular hypertension was conducted; dorzolamide (0.2, 0.5, 1, or 2%) was administered three times daily for 14 days. All of the dorzolamide concentrations substantially lowered intraocular pressure from baseline measurements. The percentage change in baseline intraocular pressure with 0.5, 1, and 2% dorzolamide 2, 4, and 6 h after dosing on day 14 ranged from 12.0 to 17.0% on average, which was greater than after treatment with 0.2% dorzolamide. No dose response was seen for 0.5, 1, or 2% dorzolamide. The most frequently reported ocular symptom was transient smarting, which occurred in 35.6-74.1% of every treatment group. Smarting and mild hyperemia were most frequent with 2% dorzolamide (74.1 and 18.5%, respectively). The present results indicate that the 0.5, 1, and 2% concentrations of dorzolamide are almost equally effective and that 2% concentrations may be less well-tolerated than 0.5 or 1% concentrations.

Polysaccharides in fungi. XXX. Antitumor and immunomodulating activities of two polysaccharides from the fruiting bodies of Armillariella tabescens.

The effects of two polysaccharides, AT-HW and AT-AL obtained from the fruiting bodies of Armillariella tabescens on murine sarcoma 180 tumor and peritoneal macrophages were examined at intraperitoneal administration. AT-HW from the hot-water extract and AT-AL from the alkaline extract significantly inhibited the tumor, and the results of different administration schedule and phagocytic system blockade suggested that the mechanism of AT-AL differed from that of AT-HW and branched (1----3)-beta-D-glucans. AT-HW and AT-AL showed reticuloendothelial system-potentiating activity, increased the number of peritoneal exudate cells, activated on macrophages (acid phosphatase activity, glucose consumption, superoxide anion production), and enhanced mitogenic reaction, although AT-HW did not produce superoxide anion in vitro.

Polysaccharides in fungi. XXIX. Structural features of two antitumor polysaccharides from the fruiting bodies of Armillariella tabescens.

An antitumor polysaccharide containing peptide moieties AT-HW ([alpha]D + 31 degrees in water) and an antitumor polysaccharide AT-AL ([alpha]D + 209 degrees in 1 M sodium hydroxide) were isolated from hot-water extract and the alkaline extract of the fruiting bodies of Armillariella tabescens, respectively. Chemical structures of AT-HW and AT-AL were investigated by a combination of chemical and spectroscopic methods. The results indicate that the major constituent of AT-HW (molecular weight, 105000), a heteroglycan, is composed primarily of beta-(1----6)-linked D-glucopyranosyl and D-galactopyranosyl residues, and contains their branched residues and terminal sugar (gluco-, manno-, and fucopyranose) residues, in addition to beta-(1----3)-linked D-glucopyranosyl residues, while AT-AL (molecular weight, 93000) is chiefly composed of alpha-(1----3)-linked D-glucopyranosyl residues.

Epidemiology of glaucoma in Japan--a nationwide glaucoma survey.

A population-based, collaborative glaucoma survey was conducted in seven regions throughout Japan, during the years of 1988 and 1989. The total number of subjects examined was 8,126 out of 16,078 residents aged 40 years or older, representing a participation rate of 50.54%. There were no significant differences in background factors between participants and randomly sampled nonparticipants. A mainstay of the screening consisted of tonometry and fundus photography with nonmydriatic camera, followed by automatic perimetry as a recall examination. Overall prevalences obtained were primary open-angle glaucoma (POAG) 0.58%, low-tension glaucoma (LTG) 2.04%, primary angle closure glaucoma (PACG) 0.34%, other types of glaucomas 0.60%, and ocular hypertension (OH) 1.37% at the time of screening. The very high prevalence of LTG and extremely low prevalence of OH in the Japanese might reflect a racial peculiarity in the age-specific trend of the intraocular pressure. The prevalence of PACG was found much higher in Japanese than in Caucasians, with a predilection for women. Racial peculiarities as revealed in this study were discussed, with particular reference to the refractive status in the Japanese that showed progressive decrease in myopia with age.

Intraocular pressure: new perspectives.

Reevaluation of normal intraocular pressure (IOP) was attempted to investigate possible background factors that contribute to variations in IOP. It is well known that IOP increases with age among Western populations, while in the Japanese IOP has been confirmed to decrease with aging. Such paradoxical results can not be reasonably explained without considering systemic conditions rather than local factors peculiar to different races. Accumulated evidence indicates that IOP is positively correlated with blood pressure, obesity and other cardiac risk variables. Incorporation of these factors by stratifying the sample may provide the baseline IOP in those who are different in systemic conditions.

Hereditary macular dystrophy without visible fundus abnormality.

We found an unusual form of macular dystrophy in three patients from two generations of the same family. The fundi of these patients appeared normal by ophthalmoscopy and fluorescein angiography, even in an older patient and in patients with poor visual acuity. Results of full-field electroretinograms were also normal in both cone and rod components. Focal macular electroretinograms were severely affected, however, indicating retinal impairment in the macular region. Results of Tübingen perimetry were consistent with electroretinographic findings. Since the condition was progressive, this disease is thought to be a hereditary macular dystrophy without visible fundus abnormality.

A new approach to stratified normal intraocular pressure in a general population.

Using computer-filed data for approximately 187,000 eyes of 94,000 Japanese subjects who underwent automated multiphasic tests, we studied the mean and the upper limit of intraocular pressure by stratifying the whole sample by age, systolic blood pressure, and degree of obesity. Intraocular pressure increased when systolic blood pressure or obesity increased and intraocular pressure decreased with advancing age when systolic blood pressure and the degree of obesity were kept constant. Apparent disparities in the upper limit of intraocular pressure were noted between the "obese and hypertensive" and "lean and hypotensive" groups, who were at the highest and the lowest extremes, respectively. Stratified normal intraocular pressure is a standard specifically applied for different sex, age, or other systemic conditions; however, the values for the group with the highest intraocular pressure should eventually be modified by the data for Western populations.

The aging effect on intraocular pressure in an apparently normal population.

Statistical analysis of intraocular pressure was conducted on approximately 200,000 healthy subjects who were examined at the Aichi Prefectural Center of Health Care in Nagoya, Japan, during the last decade. The IOP was estimated with either Schl øtz or noncontact tonometers, which consistently showed a decreasing tendency of IOP with age in both sexes. Multivariate analysis on systemic values disclosed that obesity, systolic BP, and age were the most influential factors of IOP. Stratification of the sample by systolic BP, obesity index, and age indicated that young, obese, and hypertensive subjects had the highest IOP, while old, lean, and hypotensive subjects showed the lowest IOP. It was confirmed that the IOP is physiologically maintained by a counterbalance between the IOP-lowering effect of age and the IOP-raising effects of obesity and systolic hypertension, which are largely age dependent.