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Intraocular pressure measurement in cynomolgus monkeys. Tono-Pen versus manometry.

PURPOSE: In living cynomolgus monkey eyes, the authors compared manometrically set and measured intraocular pressure (IOP) with simultaneous IOP readings obtained with the Tono-Pen (TP), a handheld applanation tonometer based on the Mackay-Marg principle. METHODS: In three pentobarbital-anesthetized cynomolgus monkeys, IOP was set and measured manometrically after anterior chamber cannulation through the peripheral cornea with a 26-gauge needle connected to a vertically adjustable reservoir and a pressure transducer. Intraocular pressure was raised in approximately 5 mm Hg steps from 5 mm Hg to 60 mm Hg and then lowered in 5 mm Hg steps to 5 mm Hg, with TP measurements taken at each increment and decrement in open and stopcock modes. RESULTS: Linear regression analysis of TP on manometric readings for grouped data from all six eyes, with each data point representing the average of all the TP readings from one eye at each manometric pressure setting, showed a slope 0.692 +/- 0.016 and 0.683 +/- 0.023 (both significantly different from 1; P < 0.001), intercept 1.21 +/- 0.60 and 1.64 +/- 0.82 mm Hg (both significantly different from 0.0, P < 0.05), and correlation coefficient 0.981 and 0.96 in open stopcock and closed stopcock mode, respectively. There were no striking differences when the data were analyzed for individual eyes or animals, for open versus closed stopcock manometry, or for increasing versus decreasing manometric IOP. CONCLUSIONS: The TP provides reproducible measurements of IOP in cynomolgus monkeys, with measurement accuracy dependent on the generation of an appropriate calibration curve.

Animals↗

Intraocular pressure in myopic anisometropia.

The authors studied the intraocular pressure, scleral rigidity and outflow facility of 137 anisometropic subjects with unilateral high myopia. The contralateral eyes were emmetropic, hyperopic or slightly myopic (less than 5 diopters). No difference was found between the intraocular pressure on the two sides. The scleral rigidity was lower and the outflow facility higher on the myopic side. It is concluded that high myopia is not, in itself, a cause of ocular hypertension, nor is caused by it.

Adolescent↗

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.

Administration, Topical↗

Effect of intracameral carbachol on intraocular pressure after cataract extraction.

Thirty-two patients were randomly assigned to a treatment or a control group to determine the dose-response and duration of action of intracameral carbachol on immediate postoperative intraocular pressure after extracapsular cataract extraction using a viscoelastic substance. Patients in the treatment group received 0.5, 0.25, or 0.1 ml of 0.01% intracameral carbachol. Patients in the control group received 0.1 or 0.5 ml of balanced salt solution. Intraocular pressures of all patients were measured preoperatively and at three, six, 12, 24, and 48 hours postoperatively. The control group as a whole showed a 9.5-mm Hg intraocular pressure rise at three hours, a 10.0-mm Hg rise at six hours, a 9.0-mm Hg rise at 12 hours, and a 7.2-mm Hg rise at 24 hours postoperatively. The group treated with 0.5 ml of carbachol maintained stable intraocular pressures through the 48-hour measurement period. The groups treated with 0.25 and 0.1 ml of carbachol maintained stable intraocular pressures through 24 hours postoperatively. The differences in intraocular pressure were statistically significant for all treated groups through the 24-hour measurement.

Carbachol↗

The reproducibility of the intraocular pressure response to dexamethasone.

The reproducibility of the intraocular pressure response to topical dexamethasone was investigated in 162 persons previously classified as low (NN), intermediate (NG), or high (GG) responders. The concordance of first and second test results was 71% for NN, 74% for NG, and 79% for GG responders, exceeding chance significantly for the NG and GG categories. Quantitative assessment revealed significant correlation of final pressure achieved on first and second tests (r equals .747, P LESS THAN .001). In the course of the study applications of dexamethasone to one eye were noted to have no effect on the intraocular pressure in the contralateral untreated eye, nor did testing of one eye influence the response of the contralateral eye in simultaneous bilateral testing. Using our data to estimate the reproducibility of topical testing in a general population, a value of 73% was obtained. That value was similar to the 65% concordance reported in an identical twin study, suggesting that the limited precision of topical testing accounts for the relatively low concordance found in that study.

Administration, Topical↗

Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine.

We performed a double-masked, crossover study comparing the cardiovascular and intraocular pressure effects of 0.5% and 0.25% topical apraclonidine hydrochloride and 0.5% timolol maleate in 20 healthy female volunteers. The contralateral effects of unilateral apraclonidine and the plasma concentrations of apraclonidine were also assessed. All measurements were done 2, 5, and 8 hours after drop instillation. A 15-minute treadmill test was performed after the 2-hour measurements. All three active medications lowered intraocular pressure comparably. There was no significant contralateral intraocular pressure effect seen with apraclonidine. The apraclonidine plasma concentrations were variable and unrelated to the amount of intraocular pressure lowering and cardiovascular parameters measured. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. Timolol, however, blunted exercise-induced tachycardia. There were no significant differences in pupillary diameters or interpalpebral fissure widths among treatment groups.

Administration, Topical↗

The Glaucoma Laser Trial. I. Acute effects of argon laser trabeculoplasty on intraocular pressure. Glaucoma Laser Trial Research Group.

The Glaucoma Laser Trial Research Group has examined the acute effects of argon laser trabeculoplasty on immediate change in intraocular pressure and the formation of peripheral anterior synechiae among the 271 eyes assigned to argon laser trabeculoplasty as initial treatment for primary open angle glaucoma. Argon laser trabeculoplasty was administered in two sessions. Intraocular pressure rises of greater than 5 mm Hg occurred in 34% of eyes after one or both of the treatment sessions; intraocular pressure rises of greater than 10 mm Hg occurred in 12%. Eyes that had an intraocular pressure rise after the first session were more likely to have a rise after the second session than eyes with no rise after the first session. Among the many patient, eye, and treatment characteristics examined, only pigmentation of the trabecular meshwork was strongly associated with intraocular pressure rises. Forty-six percent of eyes developed greater than or equal to 1 degree of peripheral anterior synechiae. Brown iris color and posterior placement of laser burns were associated with higher rates of peripheral anterior synechiae formation.

Adult↗

Decrease of intraocular pressure after fat-removal orbital decompression in Graves disease.

PURPOSE: To address the efficacy of fat-removal orbital decompression to reduce intraocular pressure in patients with Graves disease. METHODS: This cohort study included 64 eyes of 39 patients with Graves disease. Thirteen men and 36 women, with a mean age of 52.5 years (range, 27 to 80 years), underwent fat-removal orbital decompression. Intraocular pressure (applanation) and proptosis (Hertel exophthalmometry) were prospectively investigated before surgery and 1 week and 6 months after surgery. RESULTS: The volume of resected fat was 6.4+/- 4.5 (3 to 12) ml. The intraocular pressure in primary position decreased from 19.3+/- 4.4 mm Hg to 17.0+/- 2.9 mm Hg at 1 week (p<0.001) and 15.9+/- 3.7 mm Hg at 6 months (p<0.001). Mean proptosis dropped from 24.3+/- 2.5 mm before surgery to 19.9+/-3.0 mm at 1 week (p<0.01), and 19.9+/-3.1 mm at 6 months (p<0.01). Intraocular pressure decrease neither correlated to the volume of resected fat nor to proptosis reduction. CONCLUSIONS: Fat removal reduces intraocular pressure in patients with Graves disease, with no correlation to the volume of resected fat.

Adipose Tissue↗

Intraocular pressure control with twice-daily pilocarpine in two vehicle solutions.

In a double-blind study no significant difference was found in intraocular pressure control, mean pressure or comparative binocular intraocular pressure difference between pilocarpine in Adsorbobase compared to pilocarpine in 0.5% hydroxypropl-methylcellulose solution. Intraocular pressure control was achieved on fewer than 60% of visits using pilocarpine twice daily in either of the 2 vehicles. While pilocarpine retained some residual hypotensive effect 12 hours after application, twice-daily dosage with the solutions tested gave inadequate control for clinical usefulness.

Adult↗

Apraclonidine and anterior segment laser surgery. Comparison of 0.5% versus 1.0% apraclonidine for prevention of postoperative intraocular pressure rise.

PURPOSE: To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy. METHODS: This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery. RESULTS: Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine). CONCLUSION: The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.

Adrenergic alpha-Agonists↗

Intraocular pressure and retinal vascular changes during transient exposure to microgravity.

We measured intraocular pressures and retinal vascular diameters from 11 subjects during 20 seconds of microgravity produced by parabolic flight on board a KC-135 aircraft. Intraocular pressures increased 58% during parabolic flight compared to baseline values (19 +/- 1 mm Hg vs 12 +/- 1 mm Hg, respectively; P < .001). A 4% reduction in the caliber of retinal arteries was also noted during microgravity, but this change did not achieve statistical significance (7.8 +/- 0.3 pixels at zerogravity vs 8.1 +/- 0.3 pixels at 1g; P = .07). The increase in intraocular pressure and trend of arteries to constrict are thought to result from cephalad shifts in intravascular and extravascular body fluids as a result of the absence of the 1g hydrostatic gradient. The results of our study confirm that this fluid shift and its effects on the eye occur rapidly, within 20 seconds of exposure to microgravity.

Adult↗

[Intraocular pressure ten weeks after cataract surgery].

The effect of phacoemulsification and extracapsular cataract extraction on the intra-ocular pressure is analysed for several intra-operative factors. The mean intraocular pressure is significantly reduced ten weeks after the operation in comparison with the preoperative intraocular pressure. This reduction of the intraocular pressure is most significant for eyes with preoperative ocular hypertension and those eyes where leakage of the aqueous humour was evidenced during the immediate postoperative period.

Cataract Extraction↗

New experimental model system to study central regulation of intraocular pressure.

To elucidate the mechanisms of intraocular pressure (IOP) regulation by the central nervous system (CNS), the change in IOP following microiontophoretic application of oxytocin (OXT) onto the cat hypothalamus was investigated. Under sodium pentobarbital anesthesia, the experimental cat was fixed in a stereotaxic apparatus, immobilized and ventilated artificially through a tracheal cannula. The intraocular and blood pressures were continuously recorded using an electromanometer. A 3- to 5-barreled glass microelectrode was used; OXT and, as a control, saline were applied iontophoretically onto the hypothalamus according to the stereotaxic coordinates. On completion of the experiment, the animal was deeply anesthetized and perfused transcardially. Frozen sections of the brain were cut and stained with neutral red, and the tracks of the electrodes were reconstructed. The IOP was elevated gradually when OXT was applied onto the supraoptic nucleus. The latency and the amplitude of this response were 171 +/- 25 seconds and 0.99 +/- 0.46 mmHg (mean +/- SD; N = 4), respectively. The IOP showed no change after saline application to the same site. It was concluded that OXT-sensitive cells in the cat hypothalamus may play a role in regulating IOP. The combination of iontophoretic application of peptide and simultaneous IOP-monitoring as presented in this study provides a useful model system to study the mechanisms of IOP regulation by the CNS.

Animals↗

Hypotensive effect of carteolol on intraocular pressure elevation and secondary glaucoma associated with endogenous uveitis.

The therapeutic effects of carteolol hydrochloride were evaluated in the treatment of 44 uveitis patients (51 eyes) with intraocular pressure elevation or secondary glaucoma. Carteolol ophthalmic solutions, either 1% or 2%, were given twice day for more than 4 weeks in glaucomatocyclitic crisis and for more than 8 weeks in other forms of uveitis. Intraocular pressure significantly decreased from week 1 of treatment and persisted within normal limits until week 8 in glaucomatocyclitic crisis. Similarly, intraocular pressure decreased significantly from week 2 in other forms of uveitis. Intraocular pressure was well controlled in patients with open-angle glaucoma, but the control was insufficient in patients with angle-closure glaucoma. No adverse reactions such as systemic hemodynamic effects or exacerbations of intraocular inflammation were observed during this study. Carteolol therefore seems to be effective for the treatment of intraocular pressure elevation and secondary glaucoma associated with endogenous uveitis.

Adolescent↗

The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure.

Sodium hyaluronate (Healon), chondroitin sulfate, and methylcellulose have been used to protect the corneal endothelium from intraocular lens trauma. A study of the efficacy and toxicity of these compounds showed that 1% sodium hyaluronate, 0.4% methylcellulose, and 20% chondroitin sulfate were nontoxic to the corneal endothelium, but that 20% chondroitin sulfate caused a marked decrease in corneal thickness because of its hypertonicity. Anterior chamber injection of these viscous substances resulted in an increase in intraocular pressure. Within one to four hours the maximum intraocular pressure with 1% sodium hyaluronate was 67 +/- 4.1 mm Hg and that with 20% chondroitin sulfate was 55 +/- 3.5 mm Hg. The intraocular pressure did not increase to these high levels with 10% chondroitin sulfate or 0.4% methylcellulose or when the test substances were washed out of the anterior chamber. The corneal endothelium was protected from injury with 1% sodium hyaluronate and 20% chondroitin sulfate, but 10% chondroitin sulfate and 0.4% methylcellulose provided only minimal protection.

Animals↗

Comparative efficacy of the beta-blockers for the prevention of increased intraocular pressure after cataract extraction.

We conducted a randomized, double-masked study of intraocular pressure in 80 patients treated with betaxolol, levobunolol, timolol, or placebo after extracapsular cataract extraction. Intraocular pressures were measured preoperatively and early (four to seven hours) and late (20 to 24 hours) postoperatively. There was a significant mean increase in pressure from the preoperative period to the early postoperative period for the placebo group (5.35 mm Hg), betaxolol group (6.73 mm Hg), and the timolol group (3.83 mm Hg). However, the levobunolol group had a mean decrease in pressure (0.43 mm Hg). There was no significant difference between preoperative and late postoperative pressures for any of the groups. One-way analysis of covariance of the changes in pressure from the preoperative to early postoperative period showed a significant increase for the placebo and betaxolol groups compared to the levobunolol group, without significant difference between the levobunolol and timolol groups. Overall, levobunolol proved most effective in preventing an increase in intraocular pressure after extracapsular cataract extraction; timolol was partially effective.

Adrenergic beta-Antagonists↗

[Effect of intraocular administration of acetylcholine and carbachol on postoperative intraocular pressure after cataract surgery].

In a consecutive series of 90 patients we examined the effect of intracameral acetylcholine and carbachol on intraocular pressure following extracapsular cataract surgery. In all cases phacoemulsification and implantation of a folded polyhema intraocular lens under healon was performed. After evacuation of the viscoelastic substance from the capsular bag behind the inserted lens and wound suturing we instilled 0.5 ml 1% acetylcholine, 0.5 ml 0.01% carbachol or 0.5 ml balanced salt solution respectively into the anterior chamber. Without the influence of antiglaucomatous drugs applanation tonometry was performed 6 and 18 hours postoperatively. When compared with preoperative values intraocular pressure decreased in the carbachol group (-2.8 mm Hg) but increased in the acetylcholine group (+0.6 mm Hg) and control group (+4.7 mm Hg). 18 hours postoperatively the mean change was -3.0 mm Hg in the carbachol group, +0.8 mm Hg in the acetylcholine group and +2.3 mm Hg in the control group. Intraocular pressure exceeding 22 mm Hg at 6 hours was observed in 33% of the control group and 13% of the acetylcholine group but none of the carbachol group. At 18 hours intraocular pressure was still elevated in 13% of the control group, 10% of the acetylcholine group and 3% of the carbachol group. Reviewing our results we conclude that the evacuation of viscoelastic substances from the capsular bag behind the implanted lens reduces the incidence of pressure rises in the early postoperative period. This effect can be enhanced by the use of acetylcholine and, the more potent, carbachol.

Acetylcholine↗

Acute effects of sildenafil on Humphrey visual field and intraocular pressure.

PURPOSE: To evaluate the effects of sildenafil on visual field and intraocular pressure in a group of healthy subjects. METHODS: Twenty-eight healthy male volunteers with normal eyes were included in the study. Visual field examinations were performed using FASTPAC 30-2 program (white-on-white and blue-on-yellow) with the Humphrey field analyzer before and one hour after receiving oral 50 and 100 mg sildenafil citrate. RESULTS: The mean age was 51.1 +/- 8.9 years. Mean deviation, pattern standard deviation, short-term fluctuation and corrected pattern standard deviation did not differ significantly among tests both in white-on-white and blue-on-yellow visual field examinations. Changes in intraocular pressure were not statistically significant. CONCLUSIONS: No significant effect of sildenafil was seen on visual field and intraocular pressure in healthy subjects.

3',5'-Cyclic-GMP Phosphodiesterases↗