A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.     

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.     

The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study

BACKGROUND: It has been suggested that beta-adrenergic antagonists might have mechanisms of action other than ocular hypotensive effects affecting the visual function in glaucoma patients and that betaxolol might protect the visual field better than others. A randomized, double-blind study was conducted to compare the effects of betaxolol and timolol on visual fields of glaucoma patients. METHODS: Sixty-four glaucoma patients were treated with either 0.5% betaxolol or 0.25% timolol eyedrops twice daily. The Octopus visual field performance was followed up for 2 years and analyzed to find diffuse and localized changes. We analyzed the change in the mean sensitivity (MS) and performed a cluster analysis and clinical assessment of the visual fields in both treatment groups. RESULTS: The mean sensitivity (MS) improved significantly and equally in both treatment groups. There was a tendency towards more improved clusters in the betaxolol group than in the timolol group and more worsened cluster in the timolol group than in the betaxolol group, but the difference was not statistically significant. The clinical assessment also showed no statistically significant difference between the two groups. CONCLUSION: In the present study both betaxolol and timolol had a favorable effect on the visual fields of glaucoma patients. There was no statistically significant difference between betaxolol- and timolol-treated patients either in the change in mean retinal sensitivity or in the change in localized scotomatous areas.     

Comparison of the efficacy and safety of 2% dorzolamide and 0.5% betaxolol in the treatment of elevated intraocular pressure. Dorzolamide Comparison Study Group

A multicenter, parallel-design, randomized, double-masked study was conducted to compare the efficacy and safety of 2% dorzolamide with those of 0.5% betaxolol in the treatment of elevated intraocular pressure (i.o.p). A total of 311 adults with ocular hypertension or open-angle glaucoma were randomly allocated to receive either 2% dorzolamide administered topically TID or 0.5% betaxolol administered topically BID plus placebo administered topically QD for 12 weeks. After the washout of previous ocular hypotensive drugs, patients with IOP > or = 23 mm Hg in at least one eye at 10 AM or 4 PM on study day 1 were randomly allocated to receive one of the study treatments. Throughout the study, IOP was measured 2 and 8 hours after instillation of study medication for the morning peak effect (hour 2) and afternoon trough effect (hour 8). After 12 weeks of therapy, the mean change in IOP was not significantly different between the dorzolamide and betaxolol treatment groups at hour 8 (-3.6 mm Hg in both groups) or hour 2 (-5.4 vs -5.3 mm Hg, respectively). The differences between treatments (and 95% CIs associated with these differences) in mean IOP changes from baseline were 0.02 mm Hg (-0.870 to 0.901) for hour 8 and -0.14 mm Hg (-0.959 to 0.685) for hour 2. The ocular adverse experience (AE) most frequently reported by patients was ocular burning and/or stinging, and the most frequently reported nonocular AEs were taste perversion, upper respiratory infection, and headache. Only the incidence of taste perversion was significantly different between treatment groups (14.6% for the dorzolamide group and 0.0% for the betaxolol group). Two percent of patients in each treatment group discontinued the study due to AEs. This study confirmed the similar IOP-lowering effect of 2% dorzolamide and 0.5% betaxolol. Both treatments were generally well tolerated, and their safety profiles were similar.     

Effects of antiglaucoma drugs and corticosteroids on the cellular glucose uptake in cultured porcine corneal endothelial cells

In this study, various commercially used antiglaucoma drugs and corticosteroids were investigated in their effects on porcine corneal endothelial cells especially in cellular glucose uptake. Cellular glucose uptake directly affects the pumping efficiency in corneal endothelial cells. Following the cells' treatment with various antiglaucoma eyedrops for 100 min, the 3H-2-deoxyglucose uptake in cultured porcine corneal endothelial cells was affected by betaxolol from 3.1% (1.6 mM), 181% (0.16 mM) to 158% (0.016 mM), by timolol from 93% (0.79 mM), 227% (0.079 mM) to 151% (0.0079 mM), by carteolol from 141% (3.4 mM), 180% (0.34 mM) to 97% (0.034 mM), by levobunolol from 80% (1.5 mM), 98% (0.15 mM) to 90% (0.015 mM), by dipivefrin from 116% (0.2 mM), 176% (0.02 mM) to 108% (0.002 mM) and by pilocarpine from 115% (9.6 mM), 210% (0.96 mM) to 210% (0.096 mM) when the cells were compared with a control medium. In the presence of various corticosteroids, the glucose uptake in corneal endothelial cells was affected by fluorometholone from 160% (0.26 mM), 139% (0.026 mM) to 107% (0.0026 mM), by dexamethasone from 85% (0.25 mM), 117% (0.025 mM) to 109% (0.0025 mM) and by betamethasone from 95% (0.25 mM), 96% (0.025 mM) to 99% (0.0025 mM). These results show that the commercial eyedrops of antiglaucoma drugs and corticosteroids will not decrease the cellular glucose uptake in cultured porcine corneal endothelial cells except when incubated with high concentrations of betaxolol, levobunolol and dexamethasone.     

A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group

OBJECTIVE: To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS: This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS: The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS: Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.     

Glucose biosensors based on oxygen electrode with sandwich-type membranes

Cyclosporine is an important tool for the therapy of immunological diseases of the cornea and conjunctiva, as well as the treatment of patients with high-risk corneal grafts. However, potentially severe systemic side effects are disadvantageous. The purpose of our study was to determine if topical ocular application leads to about the same concentrations in ocular tissues as systemic application. Therefore, the concentration of cyclosporine in conjunctiva, aqueous humor and blood was measured by radioimmunoassay in six patients with systemic administration of cyclosporine and ten patients who received one drop of topical cyclosporine 2% four times prior to cataract surgery. All patients with systemic application showed measurable concentrations of cyclosporine in blood, as did four patients in the group receiving topical cyclosporine. There was no significant difference between both groups concerning cyclosporine concentration in aqueous humor. The level of cyclosporine in the conjunctiva was significantly higher after topical application (P < 0.02). In conclusion, therapy with cyclosporine eye drops results in levels in the conjunctiva and aqueous humor that are comparable to or even higher than those after systemic application if the last application was no more than 18h prior to the measurement. Therefore, topical ocular application of cyclosporine, which reduces or eliminates the drug's systemic side effects, can be used to induce local immunosuppressive activity, particularly in the treatment of superficial immunological diseases and after limbal allograft transplantation.     

Liver changes in protein malnutrition. An experimental study in rats

Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications. A worldwide rubella epidemic from 1963 to 1965 affected thousands of infants. This is a 20 year follow up study of patients with congenital rubella syndrome analysing the prevalence of ophthalmic disorders, associated systemic problems, and correlations among these defects. The authors statistically analysed 125 cases of congenital rubella seen in the Mayo clinic ophthalmology department over a 32 year interval. Most patients were young adults. Ocular disease was the most commonly noted disorder (78%), followed by sensorineural hearing deficits (66%), psychomotor retardation (62%), cardiac abnormalities (58%), and mental retardation (42%). Multiorgan disease was typical (88%). Ocular disease and hearing loss were frequently associated (53% had both) but not significantly correlated. A similar association existed between ocular and cardiac disease. Cataracts and microphthalmia were significantly correlated with poor visual acuity (each p < 0.0001). Glaucoma was significantly correlated with cataracts (p = 0.0002) and microphthalmia (p = 0.0024) but not poor visual acuity. Four patients with microphthalmia developed late onset glaucoma. No significant association was found between gestational age at time of maternal infection and the incidence of individual ocular conditions. However, several cardiac disorders were significantly associated with gestational age. Although new cases of congenital rubella are rare, surviving victims continue to challenge the ophthalmic and medical communities with a wide range of ocular and systemic disorders.     

Laparoscopic fine needle catheter jejunostomy]

AIMS: To investigate the efficacy of azithromycin in patients with ocular toxoplasmosis. METHODS: 11 immunocompetent patients with ocular toxoplasmosis were treated with azithromycin (500 mg the first day, followed by 250 mg/day for 5 weeks). Ocular and systemic examinations were performed during active retinitis episodes and all patients were followed for at least 1 year. RESULTS: The intraocular inflammation disappeared within 4 weeks in seven patients, including two cases with progressive retinitis despite previous treatment with pyrimethamine, sulphadiazine, and folinic acid. Recurrence of retinitis occurred in three patients (27%) within the first year of follow up. No systemic side effects of azithromycin were encountered. CONCLUSION: These results indicate that although azithromycin cannot prevent recurrent disease it may be an effective alternative for patients with ocular toxoplasmosis who cannot tolerate standard therapies.     

Effect of pilocarpine ocular therapeutic systems on diurnal control of intraocular pressure

The pilocarpine ocular therapeutic system is an innovative ocular drug delivery system which releases pilocarpine into the tear film at a constant rate of 20mug/hr or 40mug/hr. The system was evaluated in 22 hospitalized patients with bilateral open angle glaucoma to determine its ability to control ocular pressure throughout the diurnal interval. Only the right eye of each patient was treated with the pilocarpine ocular therapeutic system; the other eye served as a control. Twelve pressure measurements were made with a noncontacttorometer over a 34-hour test period. In general, the pilocarpine ocular therapeutic system provided satisfactory around-the-clock control of intraocular pressure and was well tolerated by the patients.     

Practical suggestions in diagnosing metachromatic leukodystrophy in probands and in testing family members

BACKGROUND: Echographic biometry of the ocular axial length is a helpful criterion in diagnosis and follow-up of primary congenital glaucoma. However, quantitative assessment of ocular growth following successful primary glaucoma surgery in the first year of life is hardly to find in literature. PATIENTS AND METHODS: In 36 eyes from 21 patients (mean age 4.4 +/- 2.4 months) with primary congenital glaucoma Ascan biometry was performed under general anesthesia before and 7.2 +/- 4.2 months following successful primary glaucoma surgery and retrospectively summarized. RESULTS: Preoperative axial length was 21.7 +/- 2.5 mm, postoperative axial length was 22.4 +/- 1.6 mm. Ocular growth was significantly stronger in eyes with a preoperative axial length < 20 mm (p = 0.0012) and in children younger than 3 months at surgery (p = 0.0004). CONCLUSIONS: Preoperative axial length and age are basic factors for the interpretation of ocular growth following glaucoma surgery in primary congenital glaucoma. Temporary cessation of ocular growth is a frequent finding after successful pressure-reducing surgery in eyes with axial length > 22 mm and in children aged 3 months or older.     

Ocular pulse amplitude and local carbonic anhydrase inhibition

Ocular perfusion is increasingly being discussed in the pathogenesis of glaucoma. The present study was designed to investigate ocular pulse amplitude (OPA) in primary open-angle glaucoma (POAG) patients with elevated intraocular pressure (HTG) and non-glaucomatous controls (CTL) following topical application of the carbonic anhydrase inhibitor dorzolamide. METHODS: OPA (Ocular Blood Flow System, OBF Labs UK) intraocular pressure (IOP), heart rate (HR), and systolic (BPsyst) and diastolic (BPdiast) bronchial artery pressures were measured before and 2 days after initiating treatment in 33 cataract patients with n = 14) and without (n = 19) POAG. RESULTS: Following application of dorzolamide, IOP (mmHg) in drug-treated HTG and CTL eyes was highly significantly reduced (p < 0.001) and in vehicle-treated HTG and CTL eyes significantly reduced (p < 0.03) compared to respective baseline measurements. OPA (mmHg) in drug-treated HTG and CTL eyes was significantly increased (p < 0.05) and in vehicle-treated eyes in affected compared to respective baseline measurements. Systemic perfusion parameters were also unchanged. CONCLUSION: Dorzolamide increased OPA in HTG and CTL eyes. An increase in OPA may improve the prognosis of HTG.     

Peritoneal dialysis in treatment of diffuse purulent peritonitis]

Hypotensive efficacy and safety of local monotherapy with 0.005% xalathane (once a day) and combined therapy with 0.5% timolol (twice a day) and 2% pilocarpine (3 times a day) are compared in 24 patients with primary open-angle glaucoma. Mean decrease of intraocular pressure was significant in both groups. No side effects of xalathane were recorded. In one case there was a slight reddening of the eye and a sensation of discomfort Pilocarpine therapy was associated with miosis in all patients; half of them complained of obscure vision and headache after instillation. Monotherapy with xalathane is safe sufficiently effective, and comparable to combined therapy with timolol and pilocarpine.     

Efficacy of silicone punctal plugs as adjuncts to topical pharmacotherapy of glaucoma--a pilot study. Punctal Plugs in Glaucoma Study Group

BACKGROUND: The concept of enhancing the ocular hypotensive effects of topical antiglaucoma medications by impeding lacrimal drainage of medication has been insufficiently studied. This investigation sought to evaluate the effect of bilateral inferior punctal occlusion using silicone punctal plugs on the ocular hypotensive effect of topically applied timolol. METHODS: A randomized, double-masked, cross-over clinical trial was conducted, comparing the ocular hypotensive effect of timolol maleate 0.25 percent, both with and without occlusion of the inferior punctum with the Freeman silicone punctal plug. Following a 2-week washout of topical medication, 17 subjects with early primary open-angle glaucoma or ocular hypertension received one drop of timolol 0.25 percent in each eye with or without punctal plugs in place. Blood pressure, resting pulse rate, and intraocular pressure were measured both before timolol instillation and at intervals of 1, 2, 4, 8, and 12 hours following drop instillation. Following a 2-week washout period, the subjects were evaluated with the alternative treatment. RESULTS: There was no statistically significant difference (p = 0.648) in IOP levels between treatment groups. CONCLUSIONS: This pilot suggests that need for a longer-term study with larger numbers of subjects to evaluate the potential role of silicone punctal plugs to enhance the ocular bioavailability of topically applied antiglaucoma medications.     

Diagnosis of malaria--an overview

PURPOSE: To examine the anterior optic nerve vasomotor effects of nonselective and relatively beta-1-selective beta-adrenergic antagonists in rabbits, because different influences on optic nerve blood flow with these medications have been suggested. METHODS: After topical therapy for 30 days with either timolol maleate 0.5% (six rabbits), betaxolol hydrochloride 0.5% (six rabbits), or placebo (two rabbits), the microvasculature of the optic nerve was examined with an intraluminal microvascular corrosion casting technique. The investigators were masked to both the medication group and the treated eye. The constriction, in percent of the downstream vessel caliber, was measured at the vascular branching point of arterioles supplying the anterior optic nerve. An average constriction was calculated and compared between the medication groups and between the treated and the contralateral, untreated eyes. RESULTS: Constriction values from a total of 218 arterioles supplying the anterior optic nerve were obtained for the 14 rabbits. The means of the average constriction on the treated side were comparable between the groups treated with timolol maleate, betaxolol hydrochloride, and placebo (one-way analysis of variance, P = .64), as well as between the treated and untreated eyes (two-tailed t-test for paired variables, P = .68 for timolol maleate and P = .42 for betaxolol hydrochloride). The statistical power to find a difference of 5% or more average constriction was at least 90%. CONCLUSIONS: Both relatively selective and nonselective beta-adrenergic antagonists produce no observable optic nerve vasomotor effects in the rabbit eye.     

Perivascular inflammatory reaction after percutaneous placement of covered stents

AIDS ocular complications have been researched in 70 hospitalised patients in the two main hospitals of Bamako (Mali) during one year (1992-1993). Men were predominant (sex ratio 1.6). HIV1 infections (67%) were most frequent than HIV1 + HIV2 (21.4%) or HIV2 infections (11.4%). Most of the patients were on the WHO's clinical stage III; 34% of them had ocular complications, quite often non infectious: cotonous nodules (10%), vascularitis (5.7%) and retineous haemorrhages (4.3%). Ocular opportunistic infections were rare: only one case of toxoplasmic chorio-retinitis was reported. Ocular complications were observed with all types of HIV. Vascular abnormalities were observed in the stage II or IV of AIDS and seemed, in Bamako, as a serious sign during the AIDS course.     

Contact allergy to eyedrops containing beta-blockers]

In six patients (4 women aged 80, 62, 43 and 52 years and 2 men aged 58 and 51 years), who used eyedrops containing beta-blockers for the treatment of glaucoma, allergic contact dermatitis of the eyelids was diagnosed. Three were allergic to metipranolol, 2 to levobunolol and 1 to timolol. In literature, less than 50 cases of hypersensitivity to beta-blockers in eye medication have been reported. There are, however, reasons to assume that sensitization is more frequent: (a) not all patients are referred by the ophthalmologist to the dermatologist; (b) false-negative reactions to patch tests with the commercial preparations and with beta-blockers are not infrequent; (c) they are not routinely tested because beta-blockers are difficult to obtain in pure form; (d) cross-reactions with other beta-blockers are infrequent, and changing to another preparation therefore usually solves the clinical problem. Nevertheless it is advisable to test a battery of beta-blockers (befunolol, levobunolol, metipranolol, timolol) in allergic patients. A test preparation of 2% in water or 3%-10% in petrolatum may be suitable. Control testing in non-exposed individuals is necessary to exclude irritation reactions.     

The rarity of clinically significant rise in intraocular pressure after laser peripheral iridotomy with apraclonidine

OBJECTIVE: To determine the incidence of intraocular pressure (IOP) rise of varying degrees after laser peripheral iridotomy (LPI) in patients with and without glaucoma treated perioperatively with pilocarpine and apraclonidine. DESIGN: A retrospective chart review. PARTICIPANTS: A total of 289 eyes in 179 patients with narrow occludable angles (NOA) (N = 148), open-angle glaucoma or ocular hypertension (OAG) (N = 115), or chronic-angle closure glaucoma (CACG) (N = 26) were reviewed. MAIN OUTCOME MEASURES: The difference between preoperative and postoperative IOP, absolute postoperative IOP, and the need for acute IOP-lowering treatment was noted. RESULTS: Only 1.1% (95% confidence interval [CI], 0.03%-5.8%; 1 of 94) of patients and 0.7% (95% CI, 0.02%-3.7%; 1 of 148) of eyes with NOA experienced a rise of more than 10 mmHg 1 to 2 hours after LPI. The incidence of postoperative IOP greater than 25 mmHg and acute postoperative IOP-lowering management was 0% (95% CI, 0%-3.8%). Intraocular pressure in 1 of 115 eyes (0.9%, 95% CI, 0.02%-4.7%) with OAG rose more than 10 mmHg, requiring acute treatment. None of the 26 CACG eyes experienced a rise of more than 10 mmHg (95% CI, 0%-13.2%). CONCLUSION: The IOP rise that requires further intervention after LPI with the perioperative use of pilocarpine and apraclonidine is very uncommon. In patients with NOA, routine postiridotomy IOP monitoring may not be required.     

Low-tension glaucoma

A retrospective study of 45 patients with low-tension glaucoma revealed the mean age at diagnosis to be 66 years. Seventeen patients had follow-up visual field examinations, the average follow-up period being 6.4 years. There was no significant difference in prognosis of the ocular course between patients with Po/C equal to or greater than 100 and those with Po/C less than 100. The presence of splinter hemorrhages at the optic disk (10% of affected eyes) or of systemic arterial hypertension (diastolic blood pressure greater than 100 mm Hg) was associated with progression of visual field defects. Patients with sudden visual loss or associated hemodynamic events (33% of the total patients) had a more favorable prognosis regarding stability (lack of progression) of visual field defects than those without such an event. Extension of visual field defects across the macula was a common finding (25% of affected eyes). No firm evidence was obtained to indicate that treatment of the low-tension glaucoma improved the prognosis of the ocular course.