Ocular Hypertension Glaucoma Research Articles

ORAL STEROIDS INCREASE GLAUCOMA RISK.

Ocular hypertension and open-angle glaucoma are well known side-effects of topical ophthalmic glucocorticoids, but there is little evidence about the risk associated with oral glucocorticoids. This case-control study assessed oral glucocorticoid use among 9,793 patients (aged 65 and over) with …

A complex interaction between topical verapamil and timolol on intraocular pressure in conscious rabbits

Calcium channel blockers have complex actions on aqueous humour dynamics that seem to depend on the route of drug administration. When applied topically, verapamil and nifedipine effectively lower intraocular pressure. However, these drugs also produce a slight reduction in aqueous humor outflow through the trabecular meshwork whereby they could modify the effect of other drugs on intraocular pressure. As calcium channel blockers could be effective in the management of ocular hypertension and low-tension glaucoma, the aim of the present work was to assess the interaction between verapamil and timolol when both drugs are topically applied to the eye of albino rabbits. Intraocular pressure was measured with a manual applanation tonometer. The effects of 5-6 different doses of each drug alone and the effects of five mixtures of both drugs at fixed concentration ratios (timolol: verapamil 4:1, 2:1, 1:1, 1:2 and 1:4) were evaluated. After measuring baseline intraocular pressure, one 50 microliters drop of the different solutions was instilled in the left eye. Measures of the intraocular pressure were repeated at intervals of 30 min until the maximal effect was reached. Each set of experiments was carried out in a group of 9-11 rabbits. Dose-response curves were fitted with a nonlinear regression microcomputer programme. The median effect plot was constructed as proposed by Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the interaction between both drugs, the observed effect was compared with the theoretically expected one and the combination indices, that relate the doses of verapamil and timolol present in the mixtures with the doses of both drugs separately which are equieffective with the combination, were calculated. The effects of verapamil and timolol followed the principle of the mass action law when administered alone. Nevertheless, no adequate dose-response relationship was obtained when the mixtures of both drugs were applied. In general, the observed effects were lower than the expected ones. Combination indices also indicate the presence of antagonism, except for the lowest concentrations of mixtures where verapamil predominates. In this case, combination indices suggest summation of effects or synergy. Both drugs seem to decrease intraocular pressure by reducing aqueous humor secretion through different mechanisms. However, due to the reduction of aqueous humor outflow caused by verapamil, the ocular hypotensive effect of timolol may be antagonized when high doses of verapamil are administered.

Intraocular pressure after a two-week washout following long-term timolol or levobunolol.

The effect on intraocular pressure (IOP) of a 2-week washout following long-term ocular therapy with topical levobunolol or timolol for an average period of 30 months was investigated in 20 patients (11 whites and 9 blacks) with early primary open-angle glaucoma or ocular hypertensive glaucoma suspect status. The 2-week washout IOP was significantly lower than the pretreatment baseline IOP in the total 20 patients (P < 0.001), and in the 9 black patients (P = 0.004), but not in the 11 white patients (P = 0.065). However, the washout IOP was found to be significantly lower than the baseline IOP in the 5 whites with brown irides (P = 0.024) but not in the 6 whites with blue irides (P = 0.574). Thus, the 2-week washout following long-term ocular therapy with a topical beta 1-, beta 2-blocker appears insufficient to restore IOP to the pretreatment baseline level in blacks and in the whites with brown irides, whereas it may be adequate in the majority of the whites with blue irides.

Intraocular pressure reduction with topically administered pilocarpine, timolol and betaxolol in normal tension glaucoma

The IOP-lowering effect of topical glaucoma medication has been studied mainly in eyes with ocular hypertension or high tension glaucoma. We tested the IOP-lowering effect of the commonly used topical medications (pilocarpine, timolol and betaxolol) in eyes with normal tension glaucoma. Instillation of 2% pilocarpine hydrochloride three times a day had no statistically significant lowering effect on the IOP level (F test, P = 0.0596, n = 18). 0.5% timolol maleate administered twice a day (n = 16) and 0.5% betaxolol hydrochloride administered twice a day (n = 17) led to statistically significant lowering of the IOP level (F test, P < 0.0001 for timolol and P = 0.0001 for betaxolol). There was no statistically significant difference in IOP-reducing effect whether topical IOP-lowering medication had been used previously or not. The results for 11 eyes participating in all three tests were similar to the results for the other eyes in the three test groups.

Early Treatment of Ocular Hypertension and Glaucoma Suspects (5)

In the late 1970s, a prospective study was initiated in an attempt to clarify the effects of early treatment of ocular hypertension and primary open-angle glaucoma suspects with topical timolol.

Contrast sensitivity in ocular hypertension and glaucoma.

Forty-eight patients aged from 60 to 69 years (58 eyes) with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) and a control group of 16 persons of the same ages (26 eyes) were studied with a clinical contrast sensitivity test, the Vistech 6500 test. No significant differences could be found between the normal and OHT or POAG eyes in any of the spatial frequencies. The group of newly found POAG eyes showed the greatest difference from the normals, but this difference did not reach the level of significance in any of the spatial frequencies.

Pattern electroretinogram and chronic ocular hypertension

Pattern-reversal electroretinograms to sinusoidal gratings of variable spatial frequency (0.6–4.8 cycles/degree) have been recorded in 28 normal subjects and 23 patients with ocular hypertension or early glaucoma who were previously treated with timolol maleate during a 12–24 months clinical follow-up. A multivariate analysis of variance showed that pattern electroetinogram amplitude was significantly reduced in patients as compared to control. This reduction was evident only in the low-medium spatial frequency range and was more marked (and progressive) in eyes with abnormal intraocular pressure (22–30 mmHg) as compared to eyes with normal intraocular pressure (14–21 mmHg) during the follow-up period. These results suggest that the pattern electroretinogram may detect the progression of neurosensory deficits associated with ocular hypertension in eyes with inadequate response to medical treatment.

Color pattern-reversal visual evoked potential in eyes with ocular hypertension and primary open-angle glaucoma

Color pattern-reversal visual evoked potential testing was performed in 99 normal eyes, 27 eyes with ocular hypertension and 30 eyes with primary open-angle glaucoma with the use of black-white, black-red and black-blue color checkerboard stimuli. The P1 wave peak time and amplitude of the eyes with ocular hypertension and glaucoma were significantly different from those of age-similar normal eyes, especially on the black-red and black-blue checkerboards (p less than 0.001). The differences between the ocular hypertensive and glaucomatous eyes were of less significance. The P1 peak time difference between black-white and black-red checkerboards may serve as an important parameter in the early diagnosis of glaucoma.

Individually consistent (tolerable) intraocular pressure in glaucoma

The author has devised a technique for determining tolerable intraocular pressure; after the intake of hypotensive drugs the intraocular pressure and the optic functions (size of the blind spot, visual fields, visual acuity) are periodically checked. The lowered tonometric value which coincides with the maximum improvement in visual function is considered the individually compatible level of intraocular pressure. Determination of the individually tolerable pressure is important for diagnosis, prognosis, and treatment. Actual intraocular pressure must not exceed the tolerable pressure by more than 5 mm Hg, otherwise the prognosis will be poor. Differential diagnosis between glaucoma, ocular hypertension, and low-tension glaucoma can be established by determining the tolerable pressure.

First round-table: A) Mass screening for simple glaucoma B) The differentiation between ocular hypertension and early glaucoma with normal fields

In order to study the value of the ‘cortisone test’ for the diagnosis of doubful cases of open-angle glaucoma 52 eyes of 27 patients were submitted to topically applied steroid for 6 weeks. They were divided into 3 groups according to the increased level of the intraocular pressure. As soon as the intraocular pressure was back to its pre-steroid values every eye was submitted to tonography and daily curve of pressures.

Dynamic studies of collagen and structural glycoproteins of connective tissue in the course of diabetes. Correlation with basement membrane modifications in capillaries

Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, interact in the juxtacanalicular tissue (JCT) region of the conventional outflow tract to regulate outflow resistance. Unlike endothelial cells lining the systemic vasculature, endothelial cells lining the inner wall of SC support a transcellular pressure gradient in the basal to apical direction, thus acting to push the cells off their basal lamina. The resulting biomechanical strain in SC cells is quite large and is likely to be an important determinant of endothelial barrier function, outflow resistance and intraocular pressure. This review summarizes recent work demonstrating how biomechanical properties of SC cells impact glaucoma. SC cells are highly contractile, and such contraction greatly increases cell stiffness. Elevated cell stiffness in glaucoma may reduce the strain experienced by SC cells, decrease the propensity of SC cells to form pores, and thus impair the egress of aqueous humor from the eye. Furthermore, SC cells are sensitive to the stiffness of their local mechanical microenvironment, altering their own cell stiffness and modulating gene expression in response. Significantly, glaucomatous SC cells appear to be hyper-responsive to substrate stiffness. Thus, evidence suggests that targeting the material properties of SC cells will have therapeutic benefits for lowering intraocular pressure in glaucoma.

Effects of epinephrine and progesterone on the ocular hypertensive response to intravenous infusion of prostaglandin A 2

Intravenous infusion of prostaglandin A 2 (0.24 μg/min) increased intraocular pressure and decreased mean arterial blood pressure in rabbits. This ocular hypertensive response was antagonized by a single topical pretreatment with 0.1 ml of a 1% 1-epinephrine and by pretreatment with intramuscular injections of progesterone (25 mg/kg, twice daily for a total of five injections). These results and others suggested that plasma prostaglandin A or E or both might be involved in the pathogenesis of ocular hypertension in glaucoma.

Fluorescein angiography during induced ocular hypertension in glaucoma.

Fluorescein angiography during induced ocular hypertension in glaucoma.