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.     

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.     

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.     

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     

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.