Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma.

PURPOSE:Our purpose was to compare, in a crossover design,the hypotensive effect of oral acetazolamide (Diamox) and topical dorzolamide (Trusopt) in patients with pediatric glaucoma. METHODS: All patients less than 18 years old who were switched from acetazolamide to dorzolamide without other intervention were reviewed. Intraocular pressures were obtained with either a Tono-Pen (Mentor Ophthalmics, Santa Barbara, Calif.) or applanation tonometer. Minimum follow-up times on acetazolamide and on dorzolamide were 1 month (mean 12.2 +/- 19.7 months) and 2 months (mean 8.2 +/- 5.1 months), respectively. The average dose of acetazolamide was 9.9 +/- 1.8 mg/kg/day. RESULTS: Eleven eyes (11 patients) were included. Indications for crossover from oral to topical carbonic anhydrase inhibitor (CAI) therapy were intolerance to acetazolamide (6 eyes) and surgical intervention in the fellow eye (5 eyes). The mean age at the time of crossover was 7.4 +/- 3.0 years. A comparison of intraocular pressure (IOP) before addition of a CAI was made in 8 eyes. The mean IOP off of a CAI was 27.8 +/- 4.9 mm Hg. The mean 10P was reduced to 18.5 +/- 4.3 mm Hg on acetazolamide (mean percent IOP reduction 35.7% +/- 15.6%, p < 0.01) and to 22.2 +/- 5.4 mm Hg on dorzolamide (mean percent IOP reduction 27.4% +/- 17.1%, p < 0.01). All 11 eyes showed an increase in IOP when switched from acetazolamide to dorzolamide, with a mean increase of 3.7 +/- 2.5 mm Hg (20.2% -/+ 13.7%, p < 0.01). Five eyes have remained controlled on dorzolamide and a topical beta-blocker. Five eyes required further intervention for the control of glaucoma. One eye was switched back to acetazolamide for better IOP control. CONCLUSION: Although not as effective as oral acetazolamide, topical dorzolamide causes a significant IOP reduction in this group of pediatric glaucoma patients and appears to be well tolerated.     

The role of sympathetic cervical ganglion in the effect of clonidine for lowering intraocular pressure]

The contribution of sympathetic cervical ganglion to the mechanism of action of clonidine for lowering intraocular pressure (IOP) was investigated. Pigmented rabbits were used. The animals were divided into 3 groups: normal control group (group 1), animals in which the bilateral cervical sympathetic trunks had been amputated presynaptically (group 2), animals in which the superior cervical ganglion (SCG) had been bilaterally dissected (group 3). Changes in IOP were measured after topical application of clonidine unilaterally. In group 1, IOP was significantly decreased in eye treated by clonidine and contralateral eyes compared to pretreatment values. Decrease of IOP in the contralateral eye was greater than that in the treated eye. In group 2, IOP was decreased in the contralateral eye but increased in the eye treated by clonidine. Pretreatment of yohimbine administered orally antagonized the ocular hypotensive effect of clonidine in a dose-related manner. In group 3, where SCGs were dissected, no changes in IOP were observed in both eyes by unilateral administration of clonidine. These results suggested that the bilateral ocular hypotensive effect of clonidine administered unilaterally is in part due to direct action on the SCG and that the alpha 2 receptor in the SCG plays some role in the regulation of IOP.     

Effect of flunarizine, a calcium channel blocker, on intraocular pressure and aqueous humor dynamics in monkeys

PURPOSE: To evaluate the effects of flunarizine, a nonselective calcium channel blocker, on intraocular pressure (IOP) in monkeys with laser-induced unilateral glaucoma and on aqueous humor dynamics in normal monkeys. METHODS: The IOP was measured before and hourly for 6 hours after single-dose administration of 0.5%, 1%, or 2% flunarizine to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. In a separate multiple-dose study, 0.5% flunarizine was applied twice daily for 5 consecutive days to the glaucomatous eye of the same 8 monkeys. IOP was measured at untreated baseline, after treatment with vehicle only, and on treatment days 1, 3, and 5. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 7 normal monkeys before and after the fifth dose of twice-daily treatment with 0.5% flunarizine. RESULTS: Unilateral application of 50 microL of 0.5%, 1%, or 2% flunarizine reduced IOP bilaterally. In the treated glaucomatous eyes, flunarizine reduced the IOP for 2, 3, or 5 hours, with a maximum reduction of 2.5+/-0.5 (mean+/-SEM) mm Hg (9%), 3.0+/-0.4 mm Hg (10%), and 5.0+/-0.8 mm Hg (18%) following the 0.5%, 1%, and 2% concentrations, respectively (P<0.01). The maximum reductions in IOP in the contralateral untreated eyes were 1.3+/-0.5 mm Hg, 1.5+/-0.3 mm Hg, and 2.9+/-0.7 mm Hg following the 0.5%, 1%, and 2% concentrations, respectively (P<0.05). Both the magnitude and duration of the ocular hypotensive effect of 0.5% flunarizine were enhanced with twice-daily administration for 5 days. Outflow facility in normal monkey eyes was increased (P<0.05) by 39% in the treated eyes compared with vehicle-treated contralateral eyes and by 41% compared with baseline values, and aqueous humor flow rates were unchanged (P>0.30). CONCLUSIONS: Flunarizine reduces IOP in a dose-dependent manner when administered to glaucomatous monkey eyes, but also has an ocular hypotensive effect on the contralateral untreated eyes. An increase in tonographic outflow facility seems to account for the IOP reduction in normal monkey eyes.     

Medical control of intraocular pressure after phacoemulsification

PURPOSE: To compare the effectiveness of oral acetazolamide, topical brinzolamide 1%, and no ocular hypotensive medication after phacoemulsification. SETTING: Adnan Menderes University Department of Ophthalmology, Aydin, Turkey. METHODS: This prospective randomized double-blind study comprised 60 eyes of 52 patients having phacoemulsification under topical anesthesia. There were no intraoperative complications. Eyes were randomized to receive oral acetazolamide 500 mg 1 hour preoperatively followed by 250 mg acetazolamide every 6 hours, 1 drop of brinzolamide 1% every 12 hours starting immediately after speculum removal, or no ocular hypotensive medication. Intraocular pressure (IOP) was measured using a Perkins tonometer preoperatively and 4 to 6 hours and 18 to 24 hours postoperatively. RESULTS: The preoperative IOP was not significantly different between the 3 groups. Four to 6 hours postoperatively, the acetazolamide group (P=.002) and brinzolamide group (P=.001) had significantly lower IOP than the control group. The same trend was observed at 18 to 24 hours in the brinzolamide group (P=.001) but not the acetazolamide group (P=.018). The IOP levels were not significantly different between the acetazolamide group and brinzolamide group at any postoperative time point. No eye receiving medication and 2 eyes (10%) in the control group had an IOP of 30 mm Hg or higher 4 to 6 hours postoperatively. Compared with preoperatively, an IOP increase of more than 5 mm Hg was seen at 4 to 6 hours in 3 eyes (15%), 2 eyes (10%), and 14 eyes (70%) in the acetazolamide, brinzolamide, and control group, respectively. CONCLUSION: Brinzolamide was as effective as acetazolamide in preventing IOP elevation 4 to 6 hours after phacoemulsification and more effective than acetazolamide at 18 to 24 hours.     

Ocular hypotensive effects of topically applied bunazosin, an alpha 1-adrenoceptor blocker, in rabbits and cats]

Effects of topically applied bunazosin, an alpha 1-adrenoceptor blocker, on intraocular pressure (IOP) and pupillary diameter were investigated in normotensive rabbits and cats, in addition to experimentally hypertensive rabbits. Bunazosin (0.005% to 0.1%) applied to both eyes significantly lowered IOP in a concentration-dependent manner in normotensive rabbits and cats. The unilateral application of 0.1% bunazosin significantly lowered the IOP in the treated eye, whereas it caused no significant change in the contralateral eye, suggesting that the effect of bunazosin is due mainly to a direct and local action and is not systemic. Bunazosin was also effective in experimentally hypertensive models induced both by water-loading and by alpha-chymotrypsin in rabbits. There was a significant correlation between the IOP decrease caused by bunazosin and the IOP value before the application, indicating that the IOP-lowering action of bunazosin is dependent on the height of the original IOP level. Bunazosin had no influence on pupillary diameter even when 0.5% was applied to rabbits. Topically applied bunazosin may be useful as a new antiglaucoma agent.     

Ocular hypotensive effect of alpha-adrenoceptor agonist and antagonist in the conscious pigmented rabbit]

It has been reported that some of the topically-used antiglaucomatics have a central ocular hypotensive effect. In this study, the influence of topical and intracerebroventricular (i.c.v.) administration of phenylephrine, clonidine, guanfacine, prazosin, yohimbine on the intraocular pressure (IOP) was investigated in the rabbit. Male pigmented rabbits were used throughout the experiments. For measurement of IOP, an applanation pneumatonograph was used. By unilateral topical administration of phenylephrine, an increase in IOP in the eye in which instillation was performed was observed. On the other hand, a slight decrease in IOP was observed by similar treatment of prazosin and yohimbine. No significant change of IOP in the contralateral eye was observed with these drugs. On the contrary, unilateral topical administration of clonidine or guanfacine decreased the IOP of both eyes. Furthermore, the decrease of IOP was more remarkable in the contralateral eye compared to the eye which received instillation. The IOP of both eyes was decreased in a dose-related fashion by i.c.v. administration of clonidine or guanfacine. The ocular hypotensive effects of clonidine were diminished by the pretreatment by i.c.v. administration with yohimbine. These results suggest that the ocular hypotensive effect of clonidine and guanfacine is due to their alpha 2-adrenoceptor stimulation in the central nervous system.     

A new procedure for the measurement of the outflow facility in conscious rabbits

A new procedure for measuring the outflow facility in conscious rabbits is described. The Langham pneumatic tonometer is applied horizontally against the eye; the intraocular pressure (IOP) is recorded before, during and immediately following 2 min of a pre-determined increased ocular pressure that is maintained at a fixed value by digital pressure applied through the eyelids. An increased volume of aqueous humor outflow resulting from the IOP increase is evaluated from the initial and final IOP values and the pressure volume relation for eyes of living rabbits. Close agreement in values of the outflow facilities in pairs of eyes of individual rabbits and excellent reproducibility of the procedure were found in repeated measurements made over a 24-hr period. The mean values of the IOP and the total outflow facility in 60 eyes of 30 rabbits were 20.5 +/- 0.2 mmHg and 0.17 +/- 0.01 microliter min-1 mmHg-1 respectively. Thirty minutes after an intravenous injection of acetazolamide, the IOP had decreased in both eyes of individual rabbits. This was associated with a decrease in the outflow facility and with a decrease of more than 50% in the rate of aqueous humor formation. One hour after the unilateral application of epinephrine the IOP had decreased in the treated eyes while the outflow facility remained unchanged.     

Effects of topical mitomycin C on the ciliary body and intraocular pressure after PRK: an experimental study

PURPOSE: To investigate the effects of the application of mitomycin C (MMC) after photorefractive keratectomy (PRK) on the ciliary body and intraocular pressure (IOP) in an experimental model. METHODS: Forty eyes of 20 rabbits underwent PRK to correct -8.00 diopters (D) in a 5-mm optical zone. Sterile surgical sponges (5 mm) soaked with 0.02% MMC were applied to corneas with the epithelium removed. Eyes were randomly chosen to receive MMC for 2 minutes (study group), and sponges soaked with balanced salt solution were applied on the contralateral eye (control group) for 2 minutes. Histological evaluation of the ciliary body was performed in a masked fashion by light and transmission electron microscopy. RESULTS: Histological examination of the morphology of the ciliary body structures revealed no differences between the two groups. Tonometric measurements of the IOP remained stable during the follow-up period with no significant changes (P=.75). CONCLUSIONS: Adjuvant application of MMC after PRK does not appear to induce alterations on the ciliary body or changes in IOP measurements.     

白细胞介素-1α对兔眼压的影响及其眼内毒副作用的观察

目的探讨白细胞介素1α(IL1α)降眼压的有效性及安全性。方法雌性新西兰白兔35只,随机分为7组,每组5只兔。A～D组分别随机一只眼结膜下注射重组人IL1α15ng(A组),前房内注射IL1α1.5ng(B组)、15ng(C组)及40ng(D组);A～D组对侧眼相应部位注射等体积的0.1%PBS。E组随机一只眼滴用噻吗心安,对侧眼滴用人工泪液。F和G组用药方法和剂量同D组,但G组双眼用药。A～D组于用药前及用药24h后连续4d分别进行眼压测量、眼前节裂隙灯显微镜及直接检眼镜检查。E组于用药前和用药后7d进行眼压测量。F组于用药24及48h后分别行双眼房水涂片,寻找炎性细胞。G组于用药前及用药后30～40h分别行角膜内皮细胞计数和闪光视网膜电图(ERG)检查,最后行组织学检查。结果A～D组用药后眼压均低于用药前(P=0.001～0.003),其中降眼压高峰期在用药后72～96h,药效持续96h以上;C、D组高峰期的降眼压幅度均高于E组(P<0.05);除局部稍充血外,A～D组采用裂隙灯显微镜和直接检眼镜检查未见明显异常。F组双眼房水炎性细胞计数比较,差异无统计学意义(P>0.05)。G组用药前后角膜内皮细胞计数和闪光ERG检测结果比较,差异无统计学意义(P>0.05),组织切片观察未见异常。结论IL1α具有降眼压效果好、幅度大、作用持续时间长、用药安全等特点,有较好的应用前景。     

A submicron emulsion of HU-211, a synthetic cannabinoid, reduces intraocular pressure in rabbits

Purpose: To study the ocular hypotensive effect of a nonpsychotropic cannabinoid, HU-211 (11-hydroxy-Δ⁸-tetra-hydrocannabinol, dimethylheptyl), an N-methyl-D-aspartate (NMDA) agonist, in normotensive rabbits. Methods: The cannabinoid HU-211, being lipophilic, was incorporated into a stable oil-in-water submicron sterile emulsion, consisting of 0.12% (w/w) HU-211. A single- dose, randomized and double-masked study was designed, using a Digilab 30R pneumotonometer to measure intraocular pressure (IOP) in normotensive rabbits. Results: Application of a single dose of HU-211 ophthalmic preparation resulted in an IOP reduction of 5.3 mmHg (24% of baseline), first evident at 1.5 h post application and persisting for over 6 h. A small but significant lowering of pressure (12.5% of baseline) occurred in the contralateral eyes of HU-211 treated rabbits, lasting for 4 h post treatment. Conclusion: Our work demonstrated that HU-211, incorporated into submicron emulsion, caused a 6-h-long reduction in IOP in the treated eye, with a lesser reduction in the contralateral untreated eye. Received: 30 March 1999 Revised: 10 June 1999 Accepted: 10 June 1999     

Intraocular pressure changes in the contralateral eye after trabeculectomy with mitomycin C

AIM: To assess intraocular pressure (IOP) changes of the contralateral eyes of eyes undergoing trabeculectomy with mitomycin C (MMC). METHODS: Non-comparative retrospective study of 24 consecutive patients who underwent trabeculectomy with MMC that led to more than 45% reduction in IOP. In the contralateral eyes, IOP before surgery was compared with IOP 1 day and 1 month after surgery. 11 fellow eyes were under topical hypotensive therapy while 13 contralateral eyes were not (12 contralateral eyes had previous filtering surgery and one had normal tension glaucoma). No patients had systemic ocular hypotensive therapy. RESULTS: Mean IOP in all contralateral eyes decreased from 15.5 (SD 5.5) mm Hg to 12.5 (3.8) mm Hg (p<0.01), and 13.0 (4.7) mm Hg (p<0.001) 1 day and 1 month after surgery, respectively. In the 11 fellow eyes under topical ocular hypotensive therapy mean IOP was reduced from 19.5 (4.0) mm Hg to 13.5 (2.2) mm Hg (p<0.01), and 16.5 (2.8) mm Hg (p<0.05) 1 day and 1 month after surgery, respectively. In the 13 fellow eyes not under topical ocular hypotensive therapy mean IOP was reduced from 12.1 (4.2) mm Hg to 11.6 (4.7) mm Hg (p not significant) and 9.8 (3.8) mm Hg (p0.01) 1 day and 1 month after surgery, respectively. CONCLUSIONS: In the present population, a month after trabeculectomy, mean IOP in the contralateral eyes decreased independently of whether these contralateral eyes were undergoing topical ocular hypotensive therapy or not.     

Effect of antiglaucoma agents on postoperative intraocular pressure after cataract surgery with Viscoat

PURPOSE: To compare the effectiveness of brinzolamide 1%, brimonidine 0.2%, acetazolamide 250 mg, intracameral acetylcholine, and timolol 0.5% in preventing intraocular pressure (IOP) peaks during the early period after phacoemulsification in which sodium chondroitin sulfate 4%-sodium hyaluronate 3% (Viscoat) was used as the ophthalmic viscosurgical device (OVD). SETTING: Department of Ophthalmology, Baskent University Medical Faculty, Ankara, Turkey. METHODS: This prospective randomized study comprised 185 eyes of 185 patients with uncomplicated cataract scheduled for phacoemulsification using Viscoat as the OVD. Patients were randomly assigned to 1 of 6 groups: postoperative application of topical brinzolamide 1%, brimonidine 0.2%, oral acetazolamide 250 mg, intracameral acetylcholine, timolol 0.5%, or no ocular hypotensive agent (control group). The IOP was measured at baseline (preoperatively) as well as 6 hours, 20 to 24 hours, and 1 week after surgery. RESULTS: The mean preoperative IOP values were not significantly different between the groups. Six hours and 20 to 24 hours postoperatively, the mean IOP was significantly lower in all groups receiving an ocular hypotensive agent than in the control group (P<.01). Six hours after surgery, the mean IOP significantly increased in all groups but was higher in the control group. At 20 to 24 hours, the mean IOP decreased significantly in all ocular hypotensive agent groups but remained significantly high in the control group. One week after surgery, there were no significant differences between the groups. CONCLUSION: Brinzolamide, brimonidine, acetazolamide, intracameral acetylcholine, and timolol had similar effects in reducing IOP increases after phacoemulsification performed using Viscoat.     

Prostaglandin analogues and mouse intraocular pressure: effects of tafluprost, latanoprost, travoprost, and unoprostone, considering 24-hour variation

PURPOSE: To establish a mouse model for the pharmacological analysis of antiglaucoma drugs, considering the effect of variations in IOP during 24 hours on the drugs' effects, and to evaluate the effect of a newly developed FP agonist, tafluprost, on mouse IOP, in comparison with three clinically available prostaglandin (PG) analogues. METHODS: Inbred adult ddY mice were bred and acclimatized under a 12-hour light-dark cycle. With mice under general anesthesia, a microneedle method was used to measure IOP. A single drop of 3 muL of either drug or vehicle solution was topically applied once into one eye in each mouse, in a blinded manner, with the contralateral, untreated eye serving as the control. IOP reduction was evaluated by the difference in IOP between the treated and untreated eyes in the same mouse. First, to determine the period feasible for demonstrating a larger magnitude of ocular hypotensive effect, the 24-hour diurnal variation in mouse IOP was measured, and 0.005% latanoprost was applied at the peak or trough time of variation in 24-hour IOP. The time point of the most hypotensive effect was selected for further studies, to evaluate the effects of PG analogues. Second, mice received tafluprost (0.0003%, 0.0015%, 0.005%, or 0.015%), latanoprost (0.001%, 0.0025%, or 0.005%), travoprost (0.001%, 0.002%, or 0.004%), or isopropyl unoprostone (0.03%, 0.06%, or 0.12%), and each corresponding vehicle solution. IOP was then measured at 1, 2, 3, 6, 9, and 12 hours after drug administration. The ocular hypotensive effects of the other three PG analogues were compared with that of tafluprost. All experiments were conducted in a masked study design. RESULTS: The IOP in the untreated mouse eye was higher at night than during the day. Latanoprost significantly lowered IOP at night (21.4%), compared with the IOP in the untreated contralateral eye 2 hours after administration. The maximum IOP reduction was 20.2% +/- 2.0%, 18.7% +/- 2.5%, and 11.2% +/- 1.8% of that in the untreated eye 2 hours after administration of 0.005% tafluprost, 0.005% latanoprost, and 0.12% isopropyl unoprostone, respectively, whereas it was 20.8% +/- 4.6% at 6 hours with 0.004% travoprost (n = 7 approximately 17). The order of ocular hypotensive effects of three clinically used PG analogues in mice was comparable to that in humans. Area under the curve (AUC) analysis revealed dose-dependent IOP reductions for each PG analogue. Tafluprost 0.005% decreased IOP more than 0.005% latanoprost at 3, 6, and 9 hours (P = 0.001-0.027) or 0.12% unoprostone at 2, 3, and 6 hours (P = 0.0004-0.01). CONCLUSIONS: The 24-hour variation in mouse eyes should be taken into consideration when evaluating the reduction of IOP. The mouse model was found to be useful in evaluating the pharmacological response to PG analogues. A newly developed FP agonist, 0.005% tafluprost, lowered normal mouse IOP more effectively than did 0.005% latanoprost.     

Different Effects of Topical Prazosin and Pilocarpine on Uveoscleral Outflow in Rabbit Eyes

Purpose:To investigate the effects of topical prazosin and pilocarpine on uveoscleral outflow(Fu) in rabbits.Methods:Sixteen rabbits were randomly divided into the control group (5 rabbits, only topical application of normal saline in the fight eye of each rabbit), Prazosin (PZ) treated group (6 rabbits, only 0.1％ Prazosin eyedrop 0.1％ in the right eye of each one) and Pilocarpine (PC) treated group (5 rabbits, 1％ Pilocarpine eye drop in each fight eye). Intraocular pressure (IOP) of bilateral eyes of each rabbit was measured before and 1h after topical application of the eye drop. And the bilateral eyes were perfused with Fluorescein-isothiocyanate bovine serum albumin (FITC-BSA) as the tracer into the anterior chamber of each rabbit for 30 min at 90 min after topical treatment. Then the rabbits were killed for Fu measurement.Results:IOP of PZ-treated eyes decreased [(0.71±0.07)kPa] in 1 hour after PZ application. IOP of PC-treated eyes decreased [(0.70±0.08)kPa] in 1 hour after PC application. Th     

Intraocular pressure effects of timolol after unilateral instillation

Beta-adrenergic antagonists are generally considered to lower intraocular pressure (IOP) of both eyes after unilateral instillation. In order to determine whether timolol also lowers IOP in the contralateral eye and to what extent, pressure curves were established in 14 normal, young subjects. Eye pressure curves on both eyes of each subject were measured before and 1 week after timolol 0.5% instillation twice daily in one eye. All subjects had an IOP decrease in the treated eye, but no subjects had a statistically significant IOP decrease in the contralateral eye. The mean IOP reduction was 26% in the treated eye, and only 3% in the contralateral eye. These results suggest that, in most cases, timolol does not lower IOP in the contralateral eye after unilateral instillation in normal subjects in contrast to certain glaucoma patients. These results suggest two different actions for timolol: (1) a local action in the treated eye, and (2) a systemic action where the pressure-lowering effect in the untreated eye is significant only in some pathologic conditions.     

Topical rivastigmine, a selective acetylcholinesterase inhibitor, lowers intraocular pressure in rabbits.

Non-selective acetylcholinesterase (AChE) inhibitors are known hypotensive agents. The purpose of the present investigation was carried out to ascertain whether rivastigmine, a selective carbamate-type inhibitor of AChE, which inhibits selectively an isoform of this enzyme found almost exclusively in the central nervous system, is able to depress the intraocular pressure (IOP) in normotensive rabbits. IOP was monitored with a TonoPen XL in conscious adult rabbits before and hourly up to 8 hr after administration of the drug. Baseline measurements without treatment and after one single topical application of rivastigmine [1% (n=8); 2% (n=4); and 5% (n=6)] to the right eye and of the vehicle alone to the left one were performed. Rivastigmine reduced the IOP of treated eyes significantly (p<0.05) in a dose-independent manner. Maximal effects of 23.2% (5% rivastigmine), 19.6% (2% rivastigmine) and 15.2% (1% rivastigmine) were achieved 1, 3 and 5 hr after application of the drug. A non-significant reduction of IOP in the contralateral eye was also observed. Rabbits evidenced no signs of discomfort after administration of rivastigmine. No conjunctival discharge or other signs of drug related local toxicity were found. Rivastigmine, a selective antagonist of AChE, lowers IOP significantly and may thus be of potential use in glaucoma therapy.     

Central imidazoline (I(1)) receptors modulate aqueous hydrodynamics

The purpose of this work is to determine the relative contributions of central imidazoline (I(1)) receptors to the ocular hydrodynamic action of moxonidine. Moxonidine (MOX), an alpha(2) and I(1) receptor agonist, and efaroxan (EFA), a relatively selective I(1) antagonist, were utilized to study alterations in intraocular pressure (IOP) and aqueous flow in New Zealand white rabbits subjected to intracerebroventricular (i.c.v.) cannulation and sympathectomy. Intracerebroventricular administration of MOX (0.033, 0.33 and 3.33 microg) to normal rabbits produced dose-dependent, bilateral IOP decreases of 3, 6, and 8 mmHg, respectively. The ocular hypotensive response to MOX was immediate (10 min. post drug), lasted for one hour, and was inhibited by prior administration of efaroxan (3.33 microg i.c.v.). In unilaterally sympathectomized (SX) rabbits, the ocular hypotensive response induced by i.c.v MOX in the denervated eye was attenuated approximately 50%, but the duration of ocular hypotension in the surgically altered eye was longer than that of the normal eye. MOX (0.33 microg i.c.v.), caused a statistically significant decrease (2.24 to 1.59 ml/min.) in aqueous flow in normal eyes. In SX eyes, there was no change in aqueous flow by MOX, suggesting that IOP effect in i.c.v. MOX observed in the SX eye might be mediated by changes in outflow resistance. Sedation was observed in all the rabbits treated with MOX (i.c.v.) and was dose-dependent. These in vivo data support the suggestion that centrally located I(1) receptors modulate the early contralateral response to topically administered MOX and are involved in lowering of IOP and aqueous flow in rabbit. In addition, expression of the full ocular hypotensive effect of centrally applied MOX depends on intact sympathetic innervation. Ocular hypotension induced by MOX in the SX eye may involve an effect on uveoscleral outflow.     

Prostaglandin F2 alpha isopropyl ester versus iloprost phenacyl ester in rabbit and beagle eyes

One and 2 micrograms of prostaglandin F2 alpha isopropyl ester (PGF2 alpha -IE) applied topically to the rabbit eye caused a biphasic response. The hypotensive phase was dose-dependent with a maximum reduction in intraocular pressure (IOP) of 9.4 +/- 1.7 mmHg at a dose of 2 micrograms. In beagles, 0.4 to 2 micrograms topical PGF2 alpha-IE resulted in a sustained IOP reduction; 2 micrograms produced the maximum reduction of 7-9 mmHg. No initial hypertensive response was observed. Iloprost phenacyl ester (Iloprost-PE) caused a greater decrease in IOP when dissolved in 0.5% hydroxypropyl methylcellulose (AT) than in saline. In rabbits, doses of 0.1 to 1 microgram in AT caused a biphasic response with a sustained IOP decrease fluctuating between 7 and 8 mmHg. In beagles 1 and 2 micrograms Iloprost-PE resulted in a mean IOP reduction of 5.8 +/- 0.4 mmHg and 5.8 +/- 0.5 mmHg (P less than 0.005), respectively; the decrease persisted for 5 hrs. No initial hypertensive response was observed. In beagles PGF2 alpha-IE induced a strong miosis lasting more than 6 hours; Iloprost-PE had no effect on pupil size. Both PG-esters induced a slight hyperemia in rabbit and beagle eyes. In rabbits Iloprost-PE affects the blood-aqueous barrier more than PGF2 alpha-IE, since higher protein concentrations are seen in the aqueous humor after application of Iloprost-PE. Neither PG-ester had a noticeable effect on aqueous protein in beagles. In rabbits, both PG-esters led to slightly increased aqueous humor cyclic-AMP concentrations. In beagles aqueous humor cyclic-AMP was elevated only after Iloprost-PE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study

PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered beta-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical beta-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the beta-blocker-treated eyes was -5.9 +/- 3. 4 mm Hg (-22% +/- 12%; Student t test, P <.0001). In the contralateral eyes, mean intraocular pressure reduction was -1.5 +/- 3.0 mm Hg (-5.8% +/- 12%; P <.0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective beta-blocker betaxolol did not differ from that of any of the nonselective beta-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical beta-blocker is evaluated by means of a one-eyed therapeutic trial.     

Involvement of nitric oxide in the ocular hypotensive action of nipradilol

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.