AL-2512, a novel corticosteroid: preclinical assessment of anti-inflammatory and ocular hypertensive effects.

The anti-inflammatory efficacy and ocular hypertensive effect of AL-2512 were characterized in rodent and feline models of ocular inflammation. Neutrophil influx into ocular tissue following topical ocular administration of test drugs was evaluated in models of endotoxin-induced uveitis. In rats, the anti-inflammatory efficacy of AL-2512 was compared with that of 0.1% dexamethasone. Test drug or vehicle was administered topically before subplantar injection of endotoxin. Neutrophil influx was assessed at 24 hours. Feline eyes, injected intravitreally with endotoxin, were treated topically with 0.1% AL-2512, 1.0% prednisolone acetate or vehicle at various timepoints before and after endotoxin injection. At 12 hours, protein concentration and leukocyte count in aqueous humor were determined. In the feline intraocular pressure (IOP) model, after baseline IOP values were established, AL-2512, dexamethasone, or vehicle was administered topically to both eyes of cats. IOP was measured daily before and during treatment. Topical ocular administration of AL-2512 inhibited endotoxin-induced leukocyte influx in rodent and feline models of uveitis. In rats, AL-2512 significantly inhibited neutrophil influx by 89%, compared with 93% by dexamethasone. In feline eyes, AL-2512 significantly (p < 0.05) inhibited leukocyte infiltration of aqueous humor by 59%, compared to 37% inhibition by prednisolone acetate. Intraocular pressure in cats treated for 32 days with AL-2512 or dexamethasone increased 6% and 18%, respectively. The ocular anti-inflammatory effect of AL-2512 was equivalent to dexamethasone and superior to prednisolone acetate in rat and feline models of ocular inflammation, respectively. This steroid provides anti-inflammatory efficacy equivalent to dexamethasone with a reduced risk of inducing ocular hypertension.     

Ocular changes in rabbits with corticosteroid-induced ocular hypertension.

Rabbit eyes with steroid-induced ocular hypertension were investigated in order to evaluate the histochemical abnormalities in the chamber angle region. The right eye of 14 rabbits was treated by dexamethasone 1% 3 times daily for 3 to 5 weeks. The eyes were stained by haematoxylin-eosin, periodic acid Schiff, fibrin, colloidal iron, and alcian blue with and without hyaluronidase. All treated eyes developed elevated intraocular pressure up to 4 weeks after treatment. These globes showed alcian-blue-positive hyaluronidase-sensitive staining in the amorphous material adjacent to Schlemm's canal and in the cytoplasmic granules of trabecular endothelial cells. There was no increase in incorporation of radioactive thymidine into nuclei of endothelial cells as seen by autoradiography. These results provide further support for the idea that there is abnormal accumulation of acid mucopolysaccharides in the chamber angle in steroid-induced ocular hypertension.     

The short-term IOP-lowering effect of brimonidine 0.2% and dorzolomide 2% combination in primary open-angle glaucoma

PURPOSE: To evaluate the ocular hypotensive effect of dorzolamide 2% in primary open-angle glaucoma (POAG) patients with intraocular pressure (IOP) of at least 22 mmHg despite ongoing twice daily treatment with brimonidine 0.2%. PATIENTS AND METHODS: Nineteen eyes of 19 patients with POAG and IOP >or= 22 mmHg, on twice daily brimonidine therapy, were included in the study. Intraocular pressure and adverse effects were recorded on days 2, 7, 14 and 30 after adding dorzolamide three times daily to the treatment. RESULTS: Mean pretreatment IOP was 27.6 +/- 2.2 mmHg. This decreased to 24.2 +/- 2.2 mmHg after a mean duration of 23.8 +/- 12.1 days. After dorzolamide was added to the treatment, mean IOP was 20.8 +/- 2.3 mmHg on day 2, 19.3 +/- 2.2 mmHg on day 7, 18.0 +/- 2.5 mmHg on day 14 and 17.2 +/- 2.3 mmHg on day 30. The differences between pre- and post-treatment IOP values were statistically significant (p < 0.0001, anova test). CONCLUSION: Dorzolamide administered three times daily has significant additive ocular hypotensive effect in POAG patients whose IOP is elevated despite ongoing treatment with brimonidine.     

A randomized double-masked crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients with primary open-angle glaucoma and ocular hypertension

PURPOSE: To compare the intraocular pressure)-lowering effect and side effects of latanoprost 0.005% once daily with unoprostone 0.12% twice daily. METHODS: Sixty patients with primary open-angle glaucoma or ocular hypertension were randomized to receive either latanoprost once daily in the evening and placebo once daily in the morning, or unoprostone twice daily in the morning and evening. The study was double masked and followed a crossover design with two treatment periods of 1 month separated by a 3-week washout period. The intraocular pressure was measured at 9 AM and 5 PM on the baseline and day 28 visits, and at 9 AM on day 2 and day 14 visits of each treatment period. The 9 AM measurement was taken 2 hours and 13 hours after the last drop of unoprostone and latanoprost, and the 5 PM measurement was at 10 and 21 hours, respectively. The mean of the measurements was calculated. Safety parameters were also recorded. RESULTS: Fifty-six patients completed both treatment periods and had intraocular pressure data available for evaluation. After 1 month of treatment, latanoprost significantly reduced intraocular pressure (mean +/- SEM) by 6.1 +/- 0.5 mm Hg (P <.001) and unoprostone by 4.2 +/- 0.4 mm Hg (P <.001) adjusted from an overall baseline of 22.3 +/- 0.5 mm Hg and 23.2 +/- 0.4 mm Hg, respectively. The difference of 1.9 mm Hg between treatments was statistically significant in favor of latanoprost [P =.003, analysis of covariance (ANCOVA)]. Unadjusted analysis of responders using the percentage decrease in intraocular pressure showed that the proportion of responders in the latanoprost-treated group was greater than in the unoprostone-treated group. Adverse ocular symptoms and findings were mild in both treatment groups. Eye redness and ocular irritation were the most frequently reported events. CONCLUSIONS: Latanoprost once daily was significantly more effective in reducing intraocular pressure compared with unoprostone twice daily after 1 month of treatment in patients with primary open-angle glaucoma and ocular hypertension. Both drugs were well tolerated with few ocular adverse events.     

Intraocular pressure-lowering effects of latanoprost and brimonidine therapy in patients with open-angle glaucoma or ocular hypertension: a randomized observer-masked multicenter study

PURPOSE: To compare the effect of treatment with latanoprost or brimonidine on intraocular pressure in patients with glaucoma or ocular hypertension and intraocular pressure inadequately controlled by monotherapy or dual therapy. PATIENTS AND METHODS: Three hundred seventy-nine patients with primary open-angle glaucoma or ocular hypertension were recruited for this 6-month prospective, randomized, observer-masked multicenter study involving 30 eye clinics. All patients were receiving monotherapy or dual therapy that did not adequately control intraocular pressure. After appropriate washout periods, patients were randomized to treatment with latanoprost once daily or brimonidine twice daily. The main outcome measure was change in mean diurnal intraocular pressure after 6 months of treatment compared with baseline. RESULTS: Of the 379 randomized patients, 375 were included in the intent-to-treat analysis. From an overall baseline mean intraocular pressure of 25.0 mm Hg, latanoprost monotherapy reduced mean diurnal intraocular pressure by 7.1 +/- 3.3 mm Hg (mean +/- SD, P < 0.001), whereas brimonidine monotherapy yielded an intraocular-pressure reduction of 5.2 +/- 3.5 mm Hg (P < 0.001). This 1.9 mm Hg difference in intraocular-pressure reduction was significantly in favor of latanoprost (P < 0.001). Ocular allergy (P < 0.001) and systemic side effects (P = 0.005) were reported significantly less frequently by latanoprost-treated patients compared with brimonidine-treated patients. CONCLUSIONS: Both latanoprost and brimonidine reduced intraocular pressure in patients with glaucoma or ocular hypertension after 6 months of treatment. However, latanoprost once daily was significantly more effective than brimonidine twice daily in reducing mean diurnal intraocular pressure. Latanoprost was better tolerated with less frequently occurring ocular allergy and systemic side effects.     

Inhibition of the epinephrine-induced reduction of intraocular pressure by systemic indomethacin in humans

In a prospective, randomized, double-masked study, 2% epinephrine applied topically twice each day for two weeks to the eyes of patients with glaucoma or ocular hypertension caused an 8.1 +/- 1.4-mm Hg (mean +/- S.E.M.) reduction of intraocular pressure in placebo-treated patients, but only a 1.9 +/- 0.6-mm Hg decrease in patients treated with 25 mg of orally administered indomethacin four times each day (P less than .0005). Systemic treatment with indomethacin for one week did not significantly increase intraocular pressure by itself (baseline, 19.7 +/- 0.6 mm Hg, vs 20.1 +/- 1.4 mm Hg after indomethacin treatment). When indomethacin treatment was discontinued in those patients receiving topical epinephrine, there was a further significant (P less than .05) reduction in intraocular pressure compared with the placebo-treated group. Since the ocular hypotensive effect of topically applied epinephrine is inhibited by indomethacin, a cyclo-oxygenase inhibitor, these results suggest that this reduction of intraocular pressure is at least partially mediated by the endogenous production of prostaglandins, or other cyclo-oxygenase products, and that the intraocular pressure of glaucoma patients undergoing epinephrine therapy may increase when systemic cyclo-oxygenase inhibitors such as indomethacin or aspirin are taken.     

Ocular hypertensive response to topical dexamethasone in children: a dose-dependent phenomenon

OBJECTIVE: To investigate the ocular-hypertensive response to different dosages of topical dexamethasone eye drops in Chinese children. DESIGN: Prospective, randomized clinical trial. PARTICIPANTS: Thirty-one consecutive children undergoing bilateral strabismus surgery. INTERVENTION: Topical dexamethasone (0.1%) was administered to children undergoing bilateral strabismus surgery. They were all less than 10 years of age. One eye was randomized to receive a regimen of four times daily, and another received a twice daily regimen. Intraocular pressure (IOP) was serially measured in the postoperative period for 4 weeks or more. Topical steroids were discontinued if IOP was 30 mmHg or more. MAIN OUTCOME MEASURES: Intraocular pressure was measured on the day before the surgery, on postoperative days 1, 3, 5, 8, 12, 15, 22, 29, and 2 weeks thereafter until the IOP reached preoperative levels. Peak IOP, IOP net increase, and time to reach an IOP more than 20 mmHg in the two study groups were analyzed. RESULTS: A total of 31 patients (20 male, 11 female) were examined. The mean age was 5.8 +/- 2.0 years (range, 2-10 years). Preoperative IOP in groups treated twice daily and four times daily were similar. After topical dexamethasone treatment, both groups showed a significant rise in peak IOP compared with preoperative values (twice daily, 25.2 +/- 6.8 mmHg vs. 14.3 +/- 2.4 mmHg, P < 0.001; four times daily, 28.7 +/- 6.9 mmHg vs. 14.3 +/- 2.9 mmHg, P < 0.001). The peak IOP was significantly higher in the four times daily group (P < 0.001), as was the net increase in IOP (twice daily, 10.9 +/- 5.8 mmHg vs. four times daily, 14.5 +/- 6.4 mmHg; P < 0.001). There was no difference in time for both groups to achieve the peak IOP, but the time to exceed its upper normal value (20 mmHg) was shorter in the four times daily group (twice daily, 12.3 +/- 9.1 days vs. four times daily, 10.0 +/- 7.4 days; P < 0.05). CONCLUSIONS: In children treated with topical dexamethasone, ocular hypertension occurs in a dose-dependent manner. Children in the four times daily group had a quicker onset and more severe ocular hypertensive response than the twice daily group. Nevertheless, even the twice daily regimen produced significant IOP rise, suggesting that dexamethasone use in children should be avoided if possible, and it would be desirable to monitor the IOP twice weekly when it is administered to children.     

Intraocular pressure profile of a child on a systemic corticosteroid

PURPOSE: To report the ocular hypertensive response to high-dose systemic corticosteroid in a pediatric patient. DESIGN: Observational case report. METHODS: A 9-year-old patient with leukemia received oral prednisolone at a dosage of 2.3 mg/kg/d for 5 weeks, followed by a 4-month break and then a 4-week course of oral dexamethasone at 10 mg/d. Detailed ocular examination was performed for both eyes before and regularly throughout the two courses of treatment. RESULTS: The intraocular pressure in both eyes rose to almost 40 mm Hg after only 8 days of oral corticosteroid. On stopping systemic corticosteroid, the intraocular pressure rapidly returned to baseline level within 2 days. A similar intraocular pressure profile was recorded for both eyes during the course of oral dexamethasone. The patient remained largely asymptomatic throughout. CONCLUSIONS: Systemic corticosteroid may give rise to significant but asymptomatic ocular hypertension in pediatric patients.     

Is it worthwhile to add dipivefrin HCl 0.1% to topical beta 1-, beta 2-blocker therapy?

In a prospective study, the addition of dipivefrin hydrochloride 0.1% twice daily to one eye of 32 patients with early primary open-angle glaucoma or ocular hypertension, maintained on a bilateral beta 1-, beta 2-blocker twice daily, resulted in a significant decrease of mean intraocular pressure (IOP) from 22.7 +/- 3.9 to 20.2 +/- 3.4 mmHg at 1 week (P = 0.0001) and to 21.0 +/- 3.8 mmHg at 12 weeks (P less than 0.02) in the dipivefrin-treated eyes. On the other hand, no significant change was noted in the fellow eyes (from 21.7 +/- 4.1 to 21.6 +/- 4.0 mmHg at 1 week and to 21.3 +/- 4.2 mmHg at 12 weeks). The addition of dipivefrin resulted in an IOP reduction of 2 mmHg or more in 50% and 3 mmHg or more in 19% of the eyes throughout the 12-week therapy. The result of the current study provides a realistic guideline as to what to expect from the common practice of adding dipivefrin hydrochloride to a beta 1-, beta 2-blocker regimen.     

The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open-angle glaucoma or ocular hypertension

PURPOSE: To evaluate the efficacy and safety of latanoprost 0.005% given topically every evening versus brimonidine 0.2% given topically twice daily in primary open-angle glaucoma or ocular hypertensive patients. METHODS: This was a multicenter, crossover, double-masked comparison. After a 28-day treatment-free period, patients with primary open-angle glaucoma or ocular hypertension were randomized for 6 weeks to brimonidine or latanoprost and then crossed over to the opposite treatment. At baseline and after each treatment period, patients underwent intraocular pressure measurements every 2 hours from 08:00 to 20:00. RESULTS: In 33 patients the mean baseline trough (08:00) was 23.2 +/- 2.1 mm Hg and the diurnal curve pressure was 19.8 +/- 2.7 mm Hg. The trough and diurnal intraocular pressures for brimonidine were 19.6 +/- 3.4 mm Hg and 17.6 +/- 2.2 mm Hg, respectively. Brimonidine statistically reduced the pressure from baseline at each time point except hours 10 and 12 (P =.14 and P =.21, respectively). For latanoprost, the trough and diurnal pressures were 16.2 +/- 2.9 mm Hg and 15.4 +/- 2.5 mm Hg, respectively, and the pressure was statistically reduced at each time point (P <.001) and for the diurnal curve (P <.001). When compared directly, the intraocular pressure level for latanoprost was lower than brimonidine for the diurnal pressure and at each time point (P <.05). One patient was discontinued early from latanoprost treatment because of eyelid swelling; also, latanoprost caused more hyperemia than brimonidine (P =.04). CONCLUSION: This study suggests latanoprost dosed daily in the evening statistically reduces intraocular pressure more during daytime and evening hours than brimonidine dosed twice daily. Brimonidine may not consistently decrease the pressure 10 and 12 hours past dosing from nontreated levels.     

Five-year follow up of selective laser trabeculoplasty in Chinese eyes

PURPOSE: To study the effectiveness and safety of selective laser trabeculoplasty (SLT) on primary open-angle glaucoma and ocular hypertension in Chinese eyes. METHODS: This was a prospective randomized controlled clinical study in which 58 eyes of 29 patients with primary open-angle glaucoma or ocular hypertension were included. One eye of each patient was randomized to receive SLT (Group 1) and the fellow eyes received medical treatment (Group 2). Patients were evaluated after laser treatment at 2 h, 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, and then yearly. RESULTS: All patients (13 male, 16 female) were Chinese. The mean age was 51.9 +/- 14.7 years. The mean baseline intraocular pressure was 26.8 +/- 5.6 mmHg in group 1 and 26.2 +/- 4.2 mmHg in group 2 (P = 0.62). The failure rate, defined as intraocular pressure >21 mmHg with maximal medications, was 17.2% in group 1 and 27.6% in group 2 at 5-year follow-up (P = 0.53). Eight eyes (27.6%) in group 1 required medications to control the intraocular pressure to below 21 mmHg. There was no statistically significant difference in the intraocular pressure reductions between the two groups at all time intervals (P > 0.05). The mean number of antiglaucoma medications was significantly lower in the SLT than the medical treatment group up to 5 years of follow up (P < 0.001). Transient post-SLT intraocular pressure spike >5 mmHg was observed in three eyes (10.3%). CONCLUSION: With fewer medications, SLT gives similar intraocular pressure reduction to medical therapy alone in Chinese patients with primary open-angle glaucoma or ocular hypertension.     

The effect of selective laser trabeculoplasty on intraocular pressure in patients with intravitreal steroid-induced elevated intraocular pressure

PURPOSE: To assess effectiveness of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in patients with steroid-induced elevated IOP. METHODS: Retrospective review of 7 patients (7 eyes) with IOP elevation after intravitreal triamcinolone acetonide (4.0 mg/0.1 mL) injections for macular edema (6 patients) or central retinal vein occlusion (1 patient). Three patients had preexisting open angle glaucoma; 2 patients had preexisting ocular hypertension. Time between intraocular corticosteroid injection and subsequent increased IOP ranged from 5 to 29 weeks. After unsuccessful maximum tolerated medical therapy, patients underwent unilateral SLT between April 2003 and June 2005. IOP was measured 4 weeks prelaser; on the day of laser; within 3 weeks, and at 1, 3, and 6 months postlaser. Two-sample t test was used for analysis. RESULTS: The pre-SLT and post-SLT IOP measurements were the major outcome measures used to define the relative success of the SLT procedure. Seven patients were taking 4.0+/-0.8 ocular hypotensive medications before SLT. Preoperative IOP (mm Hg+/-SD) 38.4+/-7.3 decreased postoperative to 25.6+/-7.1 within 3 weeks (P<0.003), 25.9+/-8.8 at 1 month (P<0.007), 23.9+/-10.6 at 3 months (P<0.006), and 15.7+/-2.2 at 6 months (P<0.001). Four patients underwent a second SLT procedure. Two patients failed after the 3-month visit. IOP in fellow eyes of all patients was unchanged (P>0.080). CONCLUSIONS: SLT lowered (P<0.007) IOP in 5 eyes of 7 patients with steroid-induced increased IOP from 3 weeks to 6 months postoperative. Two patients required additional surgical procedures. Repeat SLT treatments may be necessary. SLT is a temporizing procedure to consider in patients with steroid-induced elevated IOP.     

Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid

PURPOSE: To report the ocular manifestations and clinical course of eyes developing interface fluid after laser in situ keratomileusis (LASIK) surgery from a steroid-induced rise in intraocular pressure. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS/INTERVENTION: We examined six eyes of four patients who had diffuse lamellar keratitis develop after uneventful myopic LASIK surgery and were treated with topical corticosteroids. PRINCIPAL OUTCOME MEASURE: Slit-lamp findings, intraocular pressure measurements, and visual field loss. RESULTS: All eyes had a pocket of fluid develop in the lamellar interface between the flap and the stromal bed associated with a corticosteroid-induced rise in intraocular pressure. However, because of the interface fluid, intraocular pressure was normal or low by central corneal Goldmann applanation tonometry in all eyes. The elevated intraocular pressure was diagnosed by peripheral measurement in several cases after months of elevated pressure. All six eyes had visual field defects develop. Three eyes of two patients had severe glaucomatous optic neuropathy and decreased visual acuity develop as a result of undiagnosed steroid-induced elevated intraocular pressure. CONCLUSIONS: A steroid-induced rise in intraocular pressure after LASIK can cause transudation of aqueous fluid across the endothelium that collects in the flap interface. The interface fluid leads to inaccurately low central applanation tonometry measurements that obscure the diagnosis of steroid-induced glaucoma. Serious visual loss may result.     

Effect of changing from concomitant timolol pilocarpine to bimatoprost monotherapy on ocular blood flow and IOP in primary chronic angle closure glaucoma.

The aim of the present prospective masked study was to assess the effect of bimatoprost monotherapy on ocular blood flow and intraocular pressure (IOP) in eyes of primary chronic angle closure glaucoma patients already on concomitant timolol and pilocarpine. Thirty two patients of bilateral primary chronic angle closure glaucoma (PCACG) on topical timolol 0.5% twice a day and pilocarpine 2% three times daily were switched over to bimatoprost 0.03% once daily in both eyes. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) were recorded before and after starting bimatoprost and were followed up every four weeks for three months. Bimatoprost had statistically significant (p < 0.05) mean IOP reduction from 19.3 +/- 6.6 to 13.5 +/- 4.5 mmHg (30.5%) and there was improvement from 858 +/- 260 to 1261 +/- 321 microL/min (46.8%) in mean pulsatile ocular blood flow (p < 0.05). Conjunctival hyperemia (32%) was the most common adverse effect of bimatoprost. Bimatoprost 0.03% monotherapy improved ocular blood flow and provided a better diurnal IOP control than concomitant timolol-pilocarpine in eyes with primary chronic angle closure glaucoma and was found to be well tolerated.     

Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce intraocular pressure

PURPOSE: To evaluate the efficacy and safety of brimonidine compared with dorzolamide given three times daily as monotherapy in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In a double-masked, multicenter, crossover comparison in 40 patients, qualified patients were washed out from their previous medication and randomized to dorzolamide 2% or brimonidine 0.2% for the first 6-week treatment period. Patients then were washed out for 2 weeks and started on the opposite medication for the second 6-week period. RESULTS: Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 +/- 2.0 mm Hg. This study found that the 8:00 AM trough intraocular pressure after 6 weeks of therapy for dorzolamide was 20. 7 +/- 3.1 mm Hg and for brimonidine 20.8 +/- 3.2 mm Hg (P =.99). The peak intraocular pressure (2 hours after dosing) for dorzolamide was 18.6 +/- 3.4 mm Hg and for brimonidine 17.8 +/- 2.7 mm Hg (P =.10 ). Dorzolamide caused more stinging upon instillation (P <.01) and brimonidine more itching (P =.01). No statistical differences existed between groups for systemic adverse events. Six patients, all on brimonidine, were discontinued from a treatment period early. Of these, two were discontinued for inadequate pressure control, two with dizziness and fatigue, one with ocular pain, and one for lifestyle reasons (P =.07). CONCLUSIONS: This study found similar efficacy and safety between monotherapy treatment with dorzolamide or brimonidine when each was given three times daily to patients with ocular hypertension or primary open-angle glaucoma.     

The effect of corynanthine on intraocular pressure in clinical trials

A single drop, dose-response, double-masked study of the effect corynanthine, a selective alpha 1 adrenergic antagonist, on intraocular pressure (IOP) was carried out in 10 symmetrically ocular hypertensive patients. Corynanthine 1% had no significant pressure lowering effect. Topical application of a 2% solution significantly (P less than 0.05) reduced IOP for at least eight hours; at five hours, mean IOP (+/- SEM) was 20.6 +/- 2.0 mmHg and 26.0 +/- 4.9 mmHg, comparing treated and control eyes, respectively. The 5% solution caused a significant (P less than 0.05) bilateral reduction in IOP, comparing treated and control eyes to baseline IOP respectively. Two percent corynanthine applied topically two or three times daily for one, two, or three weeks to seven patients with symmetrical ocular hypertension did not reduce IOP. Alpha adrenergic antagonists may have a role in the treatment of glaucoma.     

Twenty-four-hour diurnal curve comparison of commercially available latanoprost 0.005% versus the timolol and dorzolamide fixed combination

PURPOSE: To evaluate the efficacy and safety of commercially available latanoprost 0.005% given every evening versus timolol 0.5% and dorzolamide 2% fixed combination (TDFC) given twice daily to white Greeks with primary open-angle glaucoma and ocular hypertensive patients. DESIGN: A single-masked, two-center, crossover comparison with two 6-week treatment periods occurring after at least a 3-week medicine-free period. Diurnal curve intraocular pressures were taken at 2:00 AM, 6:00 AM, 10:00 AM, 2:00 PM, 6:00 PM, and 10:00 PM. PARTICIPANTS: Thirty-four subjects with primary open-angle glaucoma or ocular hypertension were enrolled. INTERVENTIONS: Latanoprost 0.005% given every evening and TDFC twice daily. MAIN OUTCOME MEASURES: The primary efficacy variable was diurnal intraocular pressure. RESULTS: Thirty-three patients completed the study. On the last day of treatment, the mean diurnal intraocular pressure for latanoprost was 15.9 +/- 2.3 mmHg and for TDFC was 15.3 +/- 2.0 mmHg (P = 0.05). Individual time points for intraocular pressure were not statistically different between groups except at the 10:00 PM time point, when the mean for TDFC was 14.6 +/- 2.7 mmHg and for latanoprost was 16.6 +/- 3.1 mmHg (P < 0.006). Eighteen patients overall preferred latanoprost versus 2 patients for the fixed combination, generally because of the greater convenience of once daily dosing. Adverse events were not significantly different between groups except that a bitter taste was found more frequently with TDFC (n = 9) than with latanoprost (n = 0; P = 0.009). Despite screening to exclude intolerance to beta-blockers, a single patient had to discontinue the TDFC because of new-onset asthma. CONCLUSIONS: This study indicates that the 24-hour diurnal intraocular pressure is lowered more, by a small but statistically significant amount, with TDFC compared with latanoprost in primary open-angle glaucoma and ocular hypertensive patients.     

Effect of inverted body position on intraocular pressure

We evaluated changes in intraocular pressure in eyes with primary open-angle glaucoma after inversion into a totally dependent position with the head down and compared them with the changes intraocular pressure in healthy nonglaucomatous eyes. Five minutes after inversion, intraocular pressure increased from 16.8 mm Hg +/- 2.8 (sitting) to 32.9 mm Hg +/- 7.9 in normal eyes and from 21.3 mm Hg +/- 2.3 (sitting) to 37.6 mm Hg +/- 5.0 in glaucomatous eyes. Although visual fields were unchanged after inversion, glaucomatous eyes may be particularly susceptible to such changes and unable to withstand the transient but significant increase in intraocular pressure that occurs after assuming an inverted position. We recommend that patients with ocular hypertension or glaucoma refrain from this activity.     

Comparison of topical brinzolamide 1% and dorzolamide 2% eye drops given twice daily in addition to timolol 0.5% in patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: The aim was to compare topical brinzolamide 1% twice daily with dorzolamide 2% twice daily, each given with timolol 0.5% twice daily, for safety and effects on intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension. METHODS: This double-blind, randomized, active controlled, parallel group study was conducted multinationally at 31 sites, in 241 patients as above, with assessments at baseline and monthly during 3 months of treatment. The primary end point was a diurnal reduction of trough/peak intraocular pressure from a timolol 0.5% twice daily baseline. RESULTS: Both treatment regimens reduced intraocular pressure significantly at all time points (P <.001): brinzolamide plus timolol by -3.6 to -5.3 mm Hg (-14.2 to -21.9%), dorzolamide plus timolol by -3.6 mm Hg to -5.1 mm Hg (-14.1 to -21.2%). Clinically relevant intraocular pressure reductions (decreases 5 mm Hg or greater or absolute intraocular pressure values 21 mm Hg or less) were manifested by 50.0% to 89.3% of patients under brinzolamide plus timolol and by 43.9% to 85.4% under dorzolamide plus timolol. The treatments were equivalent in mean intraocular pressure-lowering. In general, both regimens were well tolerated. However, more patients (P =.001) experienced at least one adverse event with dorzolamide plus timolol (32.8%) as compared with brinzolamide plus timolol (14.7%); also, more patients (P =.001) experienced ocular discomfort (stinging and burning) after dorzolamide plus timolol (13.1%) than after brinzolamide plus timolol (1.7%). CONCLUSIONS: In terms of intraocular pressure reduction, brinzolamide 1% twice daily was equivalent to dorzolamide 2% twice daily, each added to timolol 0.5% twice daily, but brinzolamide produced significantly less ocular burning and stinging.     

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.