Effect of oral ketanserin administration on intraocular pressure in glaucomatous patients

We evaluated the effect of the antihypertensive drug ketanserin, a 5-HT antagonist, on intraocular pressure (IOP) in 20 patients with ocular hypertension. IOP, pupil diameter, systolic arterial pressure (SBP), diastolic arterial pressure (DBP) and heart rate (HR) were recorded at baseline and at 1-hr intervals for 3 hr after oral administration of 20 mg ketanserin or placebo, given in a randomized, double masked, cross-over fashion. The alternative treatment was given a week later. In all patients, ketanserin significantly lowered IOP and SBP, while no variations in pupil diameter, DBP and HR were found. Moreover, after drug administration, total outflow facility, measured by conventional tonography, increased significantly. These findings indicate that oral ketanserin could represent a new antiglaucomatous drug.     

Effect of ketanserin administration on intraocular pressure.

PURPOSE: We evaluated the effect of oral single-dose (20 mg) ketanserin on intraocular pressure (IOP) in normotensive and hypertensive eyes. METHODS: This study included 15 healthy volunteers and 16 patients with ocular hypertension. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, IOP and pupil diameter were recorded at baseline and at 1-hour intervals for 6 h, in addition, tonographic outflow facility was studied at the third hour after the administration of placebo or an oral single dose of 20 mg ketanserin given in a randomized double-blind crossover fashion. The alternative treatment was applied a week later. RESULTS: In both groups, oral single-dose (20 mg) ketanserin significantly lowered IOP and SBP (p < 0.01). No variation was observed in DBP, heart rate and pupil diameter (p >0.01). Moreover, after drug administration, the total outflow facility measured by conventional tonography increased in a statistically significant way (p < 0.01). Placebo did not induce any significant reduction in IOP and SBP in either group. CONCLUSION: The results showed that systemic ketanserin can be used in the treatment of glaucoma patients to reduce IOP.     

Ocular hypotensive effect of topical ketanserin in timolol users

Background: Ketanserin is a specific antagonist of 5-HT2 and 5-HT1c receptors. These receptors are linked to the stimulation of phosphoinositide metabolism and are involved in IOP controls. Orally and topically administered ketanserin reduces IOP in normotensive and glaucomatous eyes. Methods: Ketanserin 0.5% eye drops were administered to 20 patients with primary open-angle glaucoma in a randomised, crossover, double-masked fashion to evaluate the effect of ketanserin in glaucomatous patients already receiving timolol who did not have controlled IOP (>21 mmHg). Mean and range of IOP curve (8.00 a.m.–8.00 p.m.), pupil diameter, Schirmer 1, basal secretion test and BUT values were recorded at baseline and after 2 weeks of topical administration of ketanserin or placebo twice daily. The alternative treatment was given 2 weeks later and the same protocol was repeated. Results: When patients received placebo no significant variations were found in the analysed parameters. Ketanserin significantly reduced mean IOP (19.5%) and was effective for up to 12 h without inducing variations of tear secretion or pupil diameter. No systemic side effects were observed, and no significant variations in ocular symptoms and signs were reported. Conclusion: These results indicate that topical administration of ketanserin may be useful to reduce IOP in patients not controlled with beta-blockers.     

Diurnal variations in outflow facility

Tonography was carried out at 8 AM, 2 PM, and 8 PM on 43 normal eyes, 58 open-angle glaucomatous eyes and 10 ocular hypertensive eyes. Diurnal variations in outflow facility and their relation to those in intraocular pressure (IOP) were studied. Diurnal variations in outflow facility were present in almost all eyes, with approximately a 10% exception. The average diurnal variation in true outflow facility (deltaCtrue) was 0.10 microliter/min/mm Hg in normal eyes and 0.07 microliter/min/mm Hg in glaucomatous eyes. The average rate of diurnal variation in true outflow facility: formula: (see text) was 43.6% in normal eyes and 69.1% in glaucomatous eyes. The value was greater in glaucomatous eyes than in normal eyes. The curve of diurnal variations in true outflow facility was divided into 5 types, and in glaucomatous eyes the value of outflow facility was apt to increase in the morning and decrease in the evening. In 42% of the normal and 45% of the glaucomatous eyes, inverse relation was seen between diurnal variations in outflow facility and diurnal rhythm in IOP. It is thought that diurnal variations in outflow facility, along with diurnal fluctuations in the rate of aqueous formation, are one of the factors responsible for the diurnal rhythm found in IOP.     

Effect of oral losartan potassium administration on intraocular pressure in normotensive and glaucomatous human subjects

The effects of the type 1 angiotensin II receptor antagonist Losartan potassium on intraocular pressure (IOP) were studied. Four groups of subjects were analysed: group A, ten controls; group B, ten patients with essential arterial hypertension and with IOP within the normal range; group C, ten patients with primary open angle glaucoma (POAG), but without essential arterial hypertension; group D, ten patients with arterial hypertension and POAG. The study design was held in a randomized crossover double-blind fashion. Systolic and diastolic arterial pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1 hr intervals up to 6 hr, following the oral administration of 50 mg of Losartan potassium and/or placebo. The alternative treatment was given a week later. Drug administration significantly reduced IOP in all subjects. No variation in heart rate and pupil diameter was observed during the follow-up period. Blood pressure dropped only in arterial hypertensive patients (groups B and D). Total outflow facility increased significantly in all groups. Placebo did not induce any variation in all groups. These findings demonstrate that the mechanism by which Losartan potassium reduces intraocular pressure is not mediated by a decrease in blood pressure, but rather it is more specific, confirming the role of the renin-angiotensin system also in the regulation of intraocular pressure in man.     

Corneal thickness in congenital glaucoma

PURPOSE: To compare central corneal thickness between eyes with congenital glaucoma and normal controls and to correlate this parameter with corneal diameter and axial length. METHODS: Eyes of consecutive children with congenital glaucoma with previous glaucoma surgery and eyes of children with inadequacy of lacrimal drainage system with age less than 3 years old were examined under inhalatory general anesthesia. Complete ophthalmologic examination, central corneal thickness, axial length, and corneal diameter measurements were performed. All patients presented with intraocular pressure (IOP) less than 21 mm Hg and no clinical sign of corneal edema. RESULTS: Fifty-five eyes of 55 patients (30 congenital glaucoma and 25 controls) were examined (mean age = 16.6 +/- 10.6 months; 20 female/ 35 males). There was no significant difference in age and gender between glaucoma patients and normal subjects. Mean IOP was higher in glaucomatous eyes (P = 0.02). Corneal diameter and axial length between glaucomatous eyes and controls were significantly different (P < 0.0001 for both). Central corneal thickness was significantly thinner in glaucomatous eyes (P = 0.01). There was a significant correlation between corneal diameter and central corneal thickness and also between central corneal thickness and axial length (r2 = 0.32 and r2 = 0.18, respectively; P < 0.0001 for both). CONCLUSION: Central corneal thickness was significantly thinner in children with congenital glaucoma. This finding may be another confounding factor when measuring IOP in those patients. Pachymetry should be considered during their examination.     

动态轮廓眼压计在正常人群中的应用及其影响因素分析

目的评价动态轮廓眼压计（DCT）与Goldmann压平眼压计（GAT）测量值之间的关系,寻找DCT眼压测量值的影响因素;分析DCT所测眼压脉动振幅（OPA）与DCT眼压值、中央角膜厚度（CCT）、角膜屈光力（CCV）、眼轴长度（AL）、前房深度（ACD）、收缩压（SBP）、舒张压（DBP）和心率（HR）的关系。方法分别测量正常人60例60眼的DCT眼压、GAT眼压、CCT、CCV、AL、ACD以及HR、SBP、DBP等指标,比较GAT、DCT2种眼压计测量的相关性及DCT测量值的影响因素。结果 DCT与GAT所测眼压平均值分别为（16.04±2.57）mmHg和（14.20±2.93）mmHg。DCT眼压值较GAT眼压值高,差异有统计学意义（t=6.454,P〈0.01）。DCT眼压值与GAT眼压值呈正相关（r=0.684,P〈0.01）。DCT眼压值与CCT不相关（r=0.212,P=0.105）,GAT眼压值与CCT呈正相关（r=0.291,P=0.024）。60例正常人的OPA均值为（2.50±0.89）mmHg,OPA与年龄、DCT眼压值、CCT、SBP、DBP、HR均不相关（P〉0.05）,与CCV呈正相关（r=0.343,P=0.007）。结论在正常人群中DCT眼压值与GAT眼压值有较好的相关性,DCT的眼压测量值不受CCT、CCV等因素的影响。DCT眼压值、CCT、SBP、DBP、HR等对OPA无明显影响。     

The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma.

The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.     

The influence of isoglaucon on the hydrodynamics and haemodynamics of the eye (author's transl)]

By animal experiments and clinically we could prove that isoglaucon instillation caused the decrease in IOP due to both increase in outflow and reduction of humor secretion; the IOP decrease and changes in hydrodynamics being manifested more markedly in the fellow-eye. As reoophthalmography demonstrated "Isoglaucon" produced lumen narrowing in the anterior portion of the uveal tract. "Isoglaucon" was prescribed to 20 patients having open-angle-glaucoma, Two hours after instillation the 23 decreased in 26 eyes (of 28) by 9.3 +/- 1.0 mm Hg. When prescribed regularly "Isoglaucon" raised the outflow facility coefficient from 0.10 +/- 0.01 to 0.20 +/-0.02. The secretion decreased from 2.0 +/- 0.2 to 0.9 +/- 0.15. Thus, IOP decrease after "Isoglaucon" is accounted for by both improved outflow and reduction of aqueous humor secretion. The "isoglucon" instillation produced a rather moderate decrease in the total arterial pressure, though no expected parallelism in arterial and intraocular pressure was marked.     

Effect of pindolol on intraocular pressure.

Pindolol, a strong beta-adrenergic blocking agent, instilled into the conjunctival sac of normal and glaucomatous eyes, produced a significant drop in intraocular pressure. This was not, at first, accompanied by any variation in outflow facility; only after prolonged treatment did an increase in facility appear, which accounted only for one-third of the tension-lowering effect. The drug was well tolerated, and did not affect either pupil motility or corneal sensitivity. It seems suitable for a trial use in the treatment of glaucoma.     

Effect of topical pergolide on aqueous dynamics in normal and glaucomatous monkeys

The effects of pergolide mesylate, an ergoline derivative, were studied on intraocular pressure (IOP), outflow facility, aqueous humor flow, and pupil size in monkeys. Unilateral topical administration of two 20-microliters drops of 0.1% pergolide significantly lowered IOP in the treated- and contralateral eye in both normal- and glaucomatous monkeys. In 12 normal monkeys, the baseline IOP of 18.3 +/- 0.4 mmHg [mean +/- S.E.(M.)] was maximally reduced to 14.4 +/- 0.7 mmHg in the treated eye (P less than 0.001) and 14.6 +/- 0.6 mmHg in the contralateral eye (P less than 0.001) at 2 hr after drug administration. In 10 monkeys made bilaterally glaucomatous by argon laser treatment of the trabecular meshwork, the baseline IOP of 33.9 +/- 3.0 mmHg [mean +/- S.E.(M.)] in the treated eyes and 31.7 +/- 3.3 mmHg in the untreated eyes maximally decreased to 23.9 +/- 2.2 mmHg (P less than 0.05) and 26.2 +/- 3.3 mmHg (P less than 0.005), respectively, at 5 hr. No significant change (P greater than 0.7) in outflow facility occurred in either eye of 11 normal monkeys 2 hr after unilateral 0.1% pergolide treatment. In six normal monkeys, the baseline aqueous humor flow of 1.58 +/- 0.20 microliter min-1 in treated eyes and 1.44 +/- 0.18 microliter min-1 in untreated eyes was reduced to 0.92 +/- 0.08 microliter min-1 (P less than 0.02) and 1.09 +/- 0.11 microliter min-1 (P greater than 0.10), respectively, from 0.5- to 3.5 hr after drug administration. A mydriatic response was observed in both eyes after unilateral treatment from 1- to 2 hr in eight normal monkeys. By the third day of treatment, bilateral twice a day 0.1% pergolide drops in eight glaucomatous monkey eyes no longer significantly (P greater than 0.05) decreased IOP.     

Effect of 15-keto latanoprost on intraocular pressure and aqueous humor dynamics in monkey eyes

PURPOSE: To compare the ocular hypotensive effects of 15-keto latanoprost (KL) with the commercial preparation of latanoprost (Xalatan; Pfizer, New York, NY) in monkey eyes with laser-induced unilateral glaucoma and to evaluate the effects of topical 0.005% KL on aqueous humor dynamics in normal monkey eyes. METHODS: Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:30 AM on day 1 (untreated baseline); day 2 (vehicle only); and treatment days 1, 3, and 5 (topical, 30 microL of study drug) in the glaucomatous eyes of four to eight monkeys with unilateral laser-induced glaucoma. KL concentrations of 0.0001%, 0.001%, and 0.01% and latanoprost at 0.005% were studied separately, with a minimum washout period of 2 weeks between studies. Tonographic outflow facility (C) and fluorophotometric aqueous humor flow rates (F) were measured in nine normal monkeys before and after a single topical dose of 0.005% KL in one eye, with a vehicle-only control in the fellow eye. RESULTS: When applied once daily to glaucomatous monkey eyes, all three concentrations of KL and a 0.005% concentration of latanoprost produced significant (P < 0.05) reductions in IOP, with the maximum reduction on treatment day 5, regardless of the drug or concentration studied. The maximum reduction (P < 0.001) from vehicle-only baseline IOP was (mean +/- SEM) 3.0 +/- 0.3 mm Hg (9%) for 0.0001% KL, 7.6 +/- 0.6 mm Hg (23%) for 0.001% KL, 6.3 +/- 0.4 mm Hg (18%) for 0.01% KL, and 6.6 +/- 0.6 mm Hg (20%) for 0.005% latanoprost. After application of a single dose of 0.005% KL in nine normal monkey eyes, neither C nor F was altered (P > 0.80) when compared with untreated baseline values or vehicle-treated control eyes. CONCLUSIONS: The reduction in IOP produced by 0.001% KL was equivalent to, and at some measured time points, greater than the effect produced by 0.005% latanoprost. The IOP reduction by KL in normal monkeys appeared to have no effect on aqueous humor production or tonographic outflow facility and may thus indicate a drug-induced increase in uveoscleral outflow.     

Decreased intraocular pressure in the hypertensive human eye with betaxolol, a beta 1-adrenergic antagonist

In a double-masked randomized prospective study, 19 adult white subjects with primary open-angle glaucoma or ocular hypertension were treated twice daily with drops of 0.25% betaxolol (a relatively selective beta 1-adenoceptor antagonist) or placebo for six weeks. The nine betaxolol-treated subjects demonstrated a statistically significant average decrease in intraocular pressure of 3.8 +/- 5 mm Hg, evident after one week and persisting throughout the entire six-week treatment period. The ten placebo-treated subjects exhibited a statistically nonsignificant increase in intraocular pressure of 0.4 +/- 2.4 mm Hg. Mean systemic arterial blood pressure, pulse rate, corneal sensitivity, pupil diameter, and basal tear secretion remained unchanged in both groups. Transient stinging upon instillation of the eyedrops was the only side effect in the betaxolol-treated subjects but in no case did it necessitate cessation of therapy.     

Central corneal thickness in congenital glaucoma

PURPOSE: The aim of this study was to compare central corneal thickness between eyes with congenital glaucoma and normal fellow eyes in unilateral glaucoma or less affected fellow eyes in bilateral glaucoma. METHODS: Eyes of consecutive phakic children with congenital glaucoma and previous glaucoma surgery were examined under chloral hydrate. Complete ophthalmologic examination, central corneal thickness (CCT), axial length, and corneal diameter measurements were performed. Patients were included in the study if presented with intraocular pressure (IOP) less than 21 mm Hg and no biomicroscopic signs of corneal edema. RESULTS: Nine patients were included in the study. The mean CCT in the more affected eye/glaucomatous eye was 522.3 +/- 65.2 microm and in the less affected eye/healthy eye was 579.7 +/- 44.5 microm. This difference was statistically significant (P = 0.0013). CONCLUSION: CCT was significantly thinner in glaucomatous eyes than in normal fellow eyes in phakic children with congenital glaucoma. This finding may be another confounding factor when measuring IOP in these patients.     

The effect of timolol eye drops on the intraocular pressure in simple glaucoma (author's transl)

The intraocular pressure response to timolol ophthalmic solution, a beta-adrenergic blocking agent, was tested in two groups of open angle glaucoma patients using the 0,1% and the 0,5% solution. The 0.5% concentration gave a mean IOP reduction of 13 mm Hg in 39 glaucomatous eyes, corresponding to 46% of the pretreatment pressure level. The 0,1% concentration resulted in an average pressure decrease of 11,5 mm Hg in 22 glaucomatous eyes, corresponding to 40% of the pretreatment pressure levels. With both solutions a reduction of the first day's response was noted after repeated administration of timolol. In all patients tested timolol was tolerated well subjectively and objectively without any side effects. Timolol did not affect blood pressure or pulse rate. Tear production was not reduced after topical application of timolol. Pupillary diameter and facility of outflow were not changed significantly under therapy. It is concluded, that timolol acts primarily by reduction of aqueous inflow. The advantages of timolol as antiglaucomatous drug not affecting visual functions like miotics are discussed.     

The influence of hemodialysis on intraocular pressure: III. Aqueous humor dynamics and tissue hydration

Intraocular pressure, aqueous flow, outflow facility, outflow resistance, and both corneal and lens thickness were measured in patients receiving regular hemodialysis three times a week to test for induced variations of these parameters. No statistically significant differences occurred in any of the measurements taken. This study confirms that patients undergoing hemodialysis are not susceptible to glaucomatous disease.     

Glaukomrisiko und Hornhautdicke

Intraocular pressure is still the most important risk factor for the development of glaucomatous optic nerve damage. There is growing evidence that corneal thickness is a risk factor for the development of glaucoma. This might be caused by the effect of corneal thickness on intraocular pressure (IOP) measurements. Goldmann applanation tonometry measurements are correlated with corneal thickness. Thick corneas lead to false high readings whereas thin corneas lead to false low readings. If corneal thickness as a risk factor for glaucoma is only related to the dependency of IOP measurements on corneal thickness or is related to possible different biomechanical tissue properties in glaucomatous eyes is not known. However, a large proportion of the corneal thickness effect seems to be related to the effect on IOP readings by applanation tonometry. Neglecting corneal thickness can lead to false measurements of IOP with consequent misdiagnosis and false treatment. Therefore, measurements of corneal thickness should be performed in glaucoma patients and suspects.     

A myosin light chain kinase inhibitor,ML-9, lowers the intraocular pressure in rabbit eyes

The role of myosin light chain kinase (MLCK) in regulating the intraocular pressure (IOP) and outflow facility in rabbit eyes were studied. The IOP and pupil diameter were determined before and after intracameral and intravitreal administration of ML-9, a specific MLCK inhibitor. Total outflow facility and uveoscleral outflow facility was determined 3hr after intracameral administration of ML-9. Immunoblotting was performed to identify MLCK and the 20-kDa light chain of myosin (MLC) isoforms in human trabecular meshwork (TM) cells. The phosphorylation status of MLC was examined following ML-9 treatment. The effects of ML-9 on the morphology and actin and vinculin distribution in cultured TM cells were also studied. In rabbit eyes, administration of ML-9 resulted in a dose-dependent decrease in IOP. An increase of the outflow facility was also observed. Immunoblot analysis revealed the presence of MLCK in human TM cells. Exposure to ML-9 dose-dependently inhibited MLC phosphorylation/activation. The inhibitor caused retraction and dissociation of cells, disruption of actin bundles and impairment of focal adhesion formation in TM cells. ML-9 induces a reduction in IOP and an increase in the outflow facility in rabbit eyes. The IOP-lowering effects may be related to alterations in TM cell shapes. Inhibitors of MLCK may potentially be developed into novel medications for glaucoma.     

The risk of glaucoma and corneal thickness

Intraocular pressure is still the most important risk factor for the development of glaucomatous optic nerve damage. There is growing evidence that corneal thickness is a risk factor for the development of glaucoma. This might be caused by the effect of corneal thickness on intraocular pressure (IOP) measurements. Goldmann applanation tonometry measurements are correlated with corneal thickness. Thick corneas lead to false high readings whereas thin corneas lead to false low readings. If corneal thickness as a risk factor for glaucoma is only related to the dependency of IOP measurements on corneal thickness or is related to possible different biomechanical tissue properties in glaucomatous eyes is not known. However, a large proportion of the corneal thickness effect seems to be related to the effect on IOP readings by applanation tonometry. Neglecting corneal thickness can lead to false measurements of IOP with consequent misdiagnosis and false treatment. Therefore, measurements of corneal thickness should be performed in glaucoma patients and suspects.     

Inter-instrument agreement and influence of central corneal thickness on measurements with Goldmann, pneumotonometer and noncontact tonometer in glaucomatous eyes

PURPOSE: This study was conducted to compare the intraocular pressure (IOP) measurements by the Goldman applanation tonometer (GAT), non contact tonometer (NCT) and the ocular blood flow (OBF) pneumotonometer in different IOP ranges in glaucomatous eyes. The effect of central corneal thickness (CCT) on IOP measurement in chronic glaucomatous eyes using the three different tonometers was also evaluated. MATERIALS AND METHODS: IOP measurements of 130 eyes of primary glaucoma patients were performed using GAT by an ophthalmologist while NCT and OBF-pneumotonometer measurements were performed by an experienced optometrist. The IOP values were compared amongst the three instruments in the three different IOP ranges (0-18 mmHg, > 18 to 25 mmHg, > 25 mmHg). CCT was also measured in all patients. RESULTS: The mean of paired difference between GAT and NCT was 0.9 +/- 3.1 mmHg while that between GAT and OBF-pneumotonometer was 0.3 +/- 3.4 mmHg. The OBF-pneumotonometer and NCT were more affected by corneal thickness (0.41 mmHg and 0.4 mmHg / 10 micro corneal thickness respectively) while GAT was the least affected by corneal thickness (0.3 mmHg / 10 micro corneal thickness) though the difference was not statistically significant ( P =0.42). CONCLUSION: With appropriate correction for corneal thickness the NCT and OBF-pneumotonometer can be used as reliably as GAT in following up glaucomatous patients.