Vector alkaline phophatase substrate Blue III: one substrate for brightfield histochemistry and high-resolution fluorescence imaging by confocal laser scanning microscopy

OBJECTIVE: To compare the intraocular pressure (IOP)-reducing effect of the fixed combinations of timolol 0.5% and latanoprost 0.001% or 0.005% after 4 weeks' treatment. DESIGN: Following a 1-week run-in period on timolol 0.5% once daily, 139 patients were randomized to once-daily treatment with a fixed combination of timolol 0.5% and latanoprost 0.001% (comb. 10) or latanoprost 0.005% (comp. 50) or to the individual monotherapies. The IOP was measured at inclusion and at 8 a.m., noon and 4 p.m. on days 1, 7 and 28. RESULTS: Comb. 10, comb. 50, latanoprost and timolol reduced IOP by 3.7, 6.1, 4.9 and 2.1 mmHg, respectively, from a baseline mean diurnal IOP (+/- SEM) of 24.8 +/- 0.5, 24.1 +/- 0.4, 25.2 +/- 1.2 and 24.8 +/- 0.9 mmHg, respectively. The difference in IOP reduction was significant between comb. 50 and comb. 10 (P < 0.001), latanoprost (P = 0.046) and timolol (P < 0.001) in favor of comb. 50. There was also a significant difference between latanoprost and timolol (P = 0.007), in favor of latanoprost. All treatments were generally well tolerated. CONCLUSION: This study indicates that a fixed combination of latanoprost 0.005% and timolol 0.5% could be useful in the treatment of glaucoma.     

The effects of unoprostone isopropyl 0.12% and timolol maleate 0.5% on diurnal intraocular pressure

PURPOSE: To compare the effect of unoprostone isopropyl 0.12% to that of timolol maleate 0.5% solution given twice daily on the diurnal curve of intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In this investigator-masked, single-center, parallel-group comparison, 36 patients with primary open-angle glaucoma or ocular hypertension were randomized in a 2:1 ratio to receive either unoprostone isopropyl 0.12% or placebo/timolol maleate 0.5% solution, respectively. A placebo-controlled diurnal curve on day 0 and active-controlled diurnal curves at weeks 2 and 4 were performed at 0, 2, 4, 6, 8, 10, 12, and 24 hours. At week 2, administration of unoprostone isopropyl twice daily was compared with administration of timolol maleate twice daily. At week 4, administration of unoprostone isopropyl three times daily was compared with administration of timolol maleate twice daily. RESULTS: At the 24-hour 8:00 AM trough at week 2, administration of unoprostone isopropyl twice daily decreased IOP from 23.4 +/- 2.0 mmHg at baseline to 19.3 +/- 4.4 mmHg, and timolol maleate reduced IOP from 24.4 +/- 2.6 mmHg to 17.5 +/- 2.9 mmHg. At the 8:00 AM trough at week 4, unoprostone isopropyl given three times daily produced an IOP of 19.6 +/- 3.3 mmHg and timolol maleate resulted in an IOP of 19.4 +/- 3.0 mmHg. No statistical differences between groups were observed at any time point during either diurnal curve. Safety was similar in the two treatment groups, with no differences between groups in conjunctival hyperemia, anterior segment inflammation, or iris color change. CONCLUSION: Results of this short-term pilot trial indicate that unoprostone isopropyl may be safe and effective in reducing IOP from baseline when given twice or three times daily.     

The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group

OBJECTIVE: To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. DESIGN: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. PARTICIPANTS AND INTERVENTION: In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months. MAIN OUTCOME MEASURES: The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. RESULTS: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. CONCLUSIONS: The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.     

Inverted duplication/deletion of chromosome 8p: mild clinical phenotype

PURPOSE: To report an adverse side effect associated with topical latanoprost usage. METHOD: Case report. A 76-year-old woman with primary open-angle glaucoma developed an iris cyst 5 weeks after beginning treatment with latanoprost. Clinical examinations and slit-lamp photographs were performed. RESULTS: Latanoprost was discontinued. Periodic examinations disclosed that the iris cyst gradually diminished and finally disappeared within 3 weeks. CONCLUSION: The formation of an iris cyst is a possible complication of topical latanoprost therapy.     

Seroneutralization of porcine reproductive and respiratory syndrome virus correlates with antibody response to the GP5 major envelope glycoprotein

PURPOSE: To compare the long-term efficacy and safety of brimonidine 0.2% twice daily with timolol 0.5% twice daily in patients with glaucoma or ocular hypertension. METHODS: Of the 926 patients enrolled in the study, 837 met the protocol entry criteria and received either brimonidine 0.2% twice daily (n = 466) or timolol 0.5% (n = 371) twice daily in each eye for 1 year. RESULTS: Brimonidine and timolol significantly reduced mean intraocular pressure (P < .001) from baseline levels at every scheduled follow-up visit, both at hour 2 (peak) and hour 12 (trough). At weeks 1 and 2 and months 3 and 12, significantly greater mean decreases in intraocular pressure (P < .040) at peak were observed in patients treated with brimonidine than those treated with timolol. The mean intraocular pressure decrease at trough was significantly greater for timolol than for brimonidine at each follow-up visit (P < .001). With the exception of ocular allergy (in 11.5% of patients using brimonidine and less than 1% using timolol), fewer than 3% of patients in either treatment group withdrew from the study prematurely as a result of a specific adverse event. Patients receiving timolol experienced significant decreases in heart rate (P < .001) from baseline at all follow-up visits. No significant changes in heart rate were seen in patients treated with brimonidine. Neither medication produced clinically significant changes in blood pressure. CONCLUSION: Brimonidine is safe and effective in the long-term lowering of intraocular pressure in patients with glaucoma or ocular hypertension, with efficacy comparable to that of timolol but without a notable negative chronotropic effect on the heart.     

Timolol gel versus acetazolamide in the prophylaxis of ocular hypertension after phacoemulsification

PURPOSE: To compare postoperative intraocular pressure (IOP) after administration of acetazolamide and timolol following phacoemulsification and intraocular lens implantation. SETTING: Ophthalmic Consultants of Long Island, Rockville Centre, New York, USA. METHODS: Sixty patients were included in a prospective, randomized, masked trial. The patients received either two doses of oral, sustained-release acetazolamide (Diamox Sequels) or a single dose of topical timolol 0.5% gel (Timoptic XE). Intraocular pressure was measured by Goldmann applanation tonometry preoperatively and 1 day postoperatively. RESULTS: Mean preoperative IOP was 16.4 mm Hg. One day postoperatively, it was 19.5 mm Hg in the oral acetazolamide group and 15.9 mm Hg in the timolol gel group. One patient in the acetazolamide group developed significant adverse reactions. CONCLUSION: Prophylactic use of topical timolol 0.5% gel for viscoelastic-induced ocular hypertension after cataract extraction appears to offer better IOP control than oral acetazolamide and has potentially fewer adverse systemic effects.     

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.     

Four new drugs for glaucoma: apraclonidine, brimonidine, dorzolamide and latanoprost

Glaucoma is in most of cases initially treated with drugs, viz. beta-blocking agents, miotics, sympathicomimetics and carbonic anhydrase inhibitors. The therapy of first choice is a beta-blocking agent, but in approximately 50% of the patients treated the effect becomes inadequate with time and combination therapy is necessary. Recently, four new antiglaucomatous agents have become available: apraclonidine, brimonidine, dorzolamide and latanoprost. Apraclonidine, an alpha 2-adrenergic agonist, is indicated for brief episodes of postlaser rise of the intraocular pressure. Longer treatment may lead to tolerance. Brimonidine, another alpha 2-adrenergic agonist, is indicated for long-term treatment of glaucoma; tolerance does not often occur. Dorzolamide is a local carbonic anhydrase inhibitor which lacks the systemic side effects seen after oral administration of carbonic anhydrase inhibitors. Latanoprost, a prostaglandin F2 alpha-derivative induces an effective decrease of the intraocular pressure if administered as monotherapy and has a good efficacy when combined with other drugs lowering the intraocular pressure. The new antiglaucomatous agents are a welcome addition to the pharmacotherapy, since in many cases they make it possible to postpone or avoid surgery.     

Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy

BACKGROUND: Cystoid macular edema is a common clinical finding following intraocular surgery. Certain medications have been associated with an increased incidence of cystoid macular edema. This article describes the clinical findings in two eyes of two patients in whom cystoid macular edema developed directly following treatment with the anti-glaucoma medication latanoprost, and assesses the possible causal relationship. CASE REPORTS: Clinical correlative and angiographic studies of two patients in a referral practice are presented. The main outcome measurement was visual acuity and fundus examination on discontinuation of latanoprost. RESULTS: Cystoid macular edema developed in two pseudophakic patients after the use of latanoprost. CONCLUSION: Latanoprost should be used with caution in pseudophakic and aphakic patients--especially those with retinal vascular fragility, any inflammatory uveal disease, or other factors that may predispose to the breakdown of the blood-retinal barrier.     

Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia

PURPOSE: To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. RESULTS: Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. CONCLUSION: Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.     

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.     

Levobunolol 0.5% and timolol 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy

PURPOSE: To evaluate the prophylactic effect of levobunolol 0.5%, timolol 0.5%, or vehicle in reducing the incidence of postoperative intraocular pressure (IOP) spikes of 5 and 10 mm Hg or more in patients having neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Miami Vision Center, Coral Gables, Florida; Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Cincinnati Eye Institute, Cincinnati, Ohio; South Texas Cataract and Glaucoma Center, San Antonio, Texas; Mid-South Eye Foundation, Memphis, Tennessee, USA. METHODS: This prospective, double-masked, randomized study comprised 144 patients having Nd:YAG laser posterior capsulotomy in one eye. One drop of the test medication was administered preoperatively and one drop on the evening after surgery; IOP was measured preoperatively and 1,2,3 and 24 hours postoperatively. RESULTS: Intraocular pressure elevations of 5 mm Hg or more were seen in 1 of 60 patients (2%) in the levobunolol group, 4 of 54 (7%) in the timolol group, and 10 of 28 (36%) in the vehicle group. These elevations occurred significantly more frequently in the vehicle group than in the levobunolol (P < .001) or timolol (P < .004) groups. Elevations of 10 mm Hg or more were found in 2 of 28 patients (7%) treated with vehicle but were not observed in the patients treated with levobunolol or timolol. CONCLUSIONS: Levobunolol 0.5% or timolol 0.5% administered preoperatively and again in the evening after Nd:YAG laser capsulotomy effectively blunted the IOP rise that frequently follows laser surgery.     

Cytotoxicity of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine and 1-amino-4-phenylpyridinium ion, 1-amino analogues of MPTP and MPP+, to clonal pheochromocytoma PC12 cells

AIMS: To compare the tolerability and efficacy of a fixed combination solution of dorzolamide/timolol (Cosopt), administered twice daily with the concomitant administration of its components, dorzolamide (Trusopt) twice daily and timolol (Timoptic) twice daily. METHODS: After a 2 week timolol run in, patients with open angle glaucoma or ocular hypertension were randomised (1:1) to receive treatment with either the dorzolamide/timolol combination solution twice daily (combination) or the dorzolamide solution twice daily plus timolol maleate solution twice daily (concomitant) for 3 months. RESULTS: 299 patients were entered and 290 patients completed the study. Compared with the timolol baseline, additional IOP lowering of 16% was observed at trough (hour 0) and 22% at peak (hour 2) at month 3 in both the concomitant and combination groups. The IOP lowering effects of the two treatment groups were clinically and statistically equivalent as demonstrated by the extremely small point differences (concomitant--combination) observed in this study--0.01 mm Hg at trough and 0.08 mm Hg at peak. The safety variables of the concomitant and combination groups were very similar. Both combination and concomitant therapy were well tolerated and few patients discontinued due to adverse effects. CONCLUSIONS: The dorzolamide/timolol combination solution administered twice daily is equivalent in efficacy and has a similar safety profile to the concomitant administration of the components administered twice daily.     

The pharmacokinetics of a new antiglaucoma drug, latanoprost, in the rabbit

Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha-1-isopropyl ester) is a unique prostaglandin analogue developed for the treatment of glaucoma. To investigate the pharmacokinetics, tritium-labeled latanoprost was administered topically on the eyes of rabbits and intravenously. About 7.7% of the applied dose was found in the cornea at 15 min after the drug administration. The following Cmax and elimination half-life (interval 1-6 hr) values of the total radioactivity in the eye tissues were found: aqueous humor, 0.09 ng eq/ml and 3.0 hr; anterior sclera, 1.49 ng eq/mg and 1.8 hr; cornea, 1.59 ng eq/mg and 1.8 hr; ciliary body, 0.39 ng eq/mg and 2.8 hr; conjunctiva, 1.41 ng eq/mg and 1.4 hr; and iris, 0.39 ng eq/mg and 2.1 hr. Latanoprost was rapidly hydrolyzed, and most of the radioactivity found in the aqueous humor, anterior eye tissues, and plasma corresponded to the pharmacologically active acid of latanoprost. The initial plasma elimination half-life of the acid of latanoprost was 9.2 +/- 3.2 min after iv and 2.3 +/- 1.9 min after topical administration on the eyes. The plasma clearance of the acid of latanoprost was 1.8 +/- 0.3 liters/hr.kg, and the volume of distribution was 0.4 +/- 0.1 liter/kg after iv administration. Based on the retention times on HPLC and GC-MS, the main metabolite in urine and feces was identified as the 1,2,3,4-tetranor metabolite of acid of latanoprost. This acid existed in equilibration with the corresponding delta-lactone. The AUC of radioactivity in the eye tissues was approximately 1000 times higher than in plasma AUC. The recovery of radioactivity was complete.     

Trabeculectomy with releasable sutures: a prospective, randomized pilot study

OBJECTIVE: To compare the short-term and long-term efficacy of using releasable sutures vs conventional interrupted sutures for scleral flap suturing in trabeculectomy. DESIGN: A prospective randomized study. SETTING: A university-affiliated referral eye hospital. PATIENTS: Thirty consecutive patients requiring trabeculectomy for uncontrolled primary glaucoma. INTERVENTION: Fifteen patients underwent trabeculectomy with permanent interrupted sutures; the same number underwent trabeculectomy with releasable sutures. MAIN OUTCOME MEASURES: Incidence of short-term shallowing of anterior chamber or hypotony and related complications, and long-term intraocular pressure control and bleb score. RESULTS: The mean percentage reduction in intraocular pressure on day 1 in the group with releasable sutures was 55.2%, while only a 0.8% reduction in anterior chamber depth was noted. This compared with figures of 59.3% and 10.1%, respectively, in the group without releasable sutures. Hypotony (intraocular pressure < or =6 mm Hg) was noted in 8 (53%) of cases without releasable sutures and 3 (20%) of cases with releasable sutures. Shallow anterior chamber (central anterior chamber depth, < or =1 mm) was noted in 5 (33%) of cases without releasable sutures and 1 (7%) of cases with releasable sutures. The mean +/- SD final bleb score was 5.4 +/- 0.3 in the group with releasable sutures compared with 4.2 +/- 0.6 in the group without releasable sutures (P<.001). The mean +/- SD final intraocular pressure at the end of 12 months was 16.9 +/- 1.2 mm Hg in the group without releasable sutures and 15.0 +/- 0.9 mm Hg in the group with releasable sutures (P<.001). Final intraocular pressure was controlled (intraocular pressure < or =21 mm Hg) in all patients in the group with releasable sutures, giving a success rate of 100%, and in 12 patients in the group without releasable sutures, giving a success rate of 80%. CONCLUSIONS: Use of releasable sutures is an effective way at no extra cost or instrumentation to maximize the long-term bleb score and lower intraocular pressure, and to minimize the short-term complications of trabeculectomy.     

Hypoparathyroidism--presenting 40 years after thyroid surgery

BACKGROUND: Latanoprost represents a new therapeutic option in the treatment of chronic open angle glaucoma. It has only recently been reported for the first time that latanoprost caused cystoid macular edema in pseudophakic patients. CASE REPORT: A 60-year-old pseudophakic patient who suffered from a 10-year history of glaucoma, revealed a cystoid macular edema on fluorescence angiography after 10 days of treatment with latanoprost. One week after cessation of latanoprost therapy the cystoid edema in fluorescence angiography had resolved and the vision improved from 0.4 to 0.8. CONCLUSIONS: With respect to this severe complication, latanoprost should be used with great care and in clear indications, particularly in patients with risk of blood-aqueous leakage e.g. pseudophakic patients.     

An elective-titration study of the comparative effectiveness of two angiotensin II-receptor blockers, irbesartan and losartan. Irbesartan/Losartan Study Investigators

This multicenter, randomized, double-masked, elective-titration study was designed to compare the effectiveness, safety, and tolerability of irbesartan and losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of patients with mild-to-moderate hypertension. After a 3-week, single-masked, placebo lead-in period, 432 patients with a mean seated diastolic blood pressure (SeDBP) of 95 to 115 mm Hg were randomly allocated to receive either irbesartan 150 mg once daily (n = 213) or losartan 50 mg once daily (n = 219). At week 4, if SeDBP at trough (i.e., 24 +/- 3 hours after the previous dose) was > or = 90 mm Hg, the daily dose was doubled (to irbesartan 300 mg or losartan 100 mg). At week 8, if trough SeDBP was > or = 90 mm Hg, hydrochlorothiazide 12.5 mg once daily was added to the regimen; consistent with the prescribing information for losartan, the dose of losartan was reduced to 50 mg once daily on the addition of hydrochlorothiazide. A total of 370 patients (178 irbesartan and 192 losartan) were evaluable for efficacy. The mean change in trough SeDBP at week 8, the primary efficacy end point, was significantly greater in patients receiving irbesartan monotherapy than in those receiving losartan monotherapy (-10.2 mm Hg vs -7.9 mm Hg, respectively). At week 12, reductions in trough SeDBP and seated systolic blood pressure were greater with irbesartan treatment than with losartan treatment (-13.8 mm Hg vs -10.8 mm Hg and -18.0 mm Hg vs -13.9 mm Hg, respectively), and a greater proportion of irbesartan patients responded to therapy (i.e., trough SeDBP < 90 mm Hg or reduction in trough SeDBP > or = 10 mm Hg) compared with losartan patients (78% vs 64%, respectively). Both regimens were well tolerated.     

Change in optic disk topography after trabeculectomy

PURPOSE: To investigate the relationship between optic disk topography and intraocular pressure before and after trabeculectomy with confocal scanning laser ophthalmoscopy. METHODS: The eyes of 49 consecutive patients undergoing trabeculectomy at a university-based glaucoma practice underwent preoperative and postoperative imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph). Three images of one eye of each patient were obtained with a 15-degree field of view. Preoperative images were obtained approximately 2 months before surgery (mean +/- SD, 2.4 +/- 1.6 months). Postoperative images were obtained at least 3 months after surgery (mean, 4.5 +/- 2.6 months). RESULTS: Mean preoperative intraocular pressure, postoperative intraocular pressure, and percent change in intraocular pressure respectively were 23.1 +/- 6.8 mm Hg, 12.7 +/- 7.1 mm Hg, and 43.8% +/- 29.9%. A significant association (P < .01) was found between percent decrease in intraocular pressure and decreases in cup area, cup volume, and cup/disk area ratio as well as between percent decrease in intraocular pressure and increases in rim area, rim volume, mean height contour, retinal cross-section area, and height in contour. Between 11.7% and 31.2% of the variability (R2) in these parameters was explained by the percent change in intraocular pressure. Topography changes were more strongly associated with percent change than with mean change in intraocular pressure. We found no association between percent decrease in intraocular pressure and reference plane height or maximum cup depth. CONCLUSIONS: Changes in optic nerve topography were associated with reduction in intraocular pressure after trabeculectomy.     

Intraocular pressure in rabbits by telemetry II: effects of animal handling and drugs

PURPOSE: To measure under carefully controlled conditions the effects in the rabbit eye of commonly used therapeutic agents for glaucoma. METHODS: Rabbits were outfitted in one eye with an implantable telemetric pressure transducer and monitored for several months under controlled conditions of light/ dark and handling. Effects of tonometry, handling, water drinking, and instillation of topical ophthalmic medications on intraocular pressure were recorded during each 24-hour day/night cycle. RESULTS: Pneumatonometry, animal handling, and water drinking all had an effect on intraocular pressure that in many instances was of the same magnitude as the effects of pharmacologic agents. Dorzolamide and timolol caused a sustained reduction of intraocular pressure during the nocturnal period. Epinephrine had a biphasic effect, causing an immediate pressure elevation followed by a prolonged depression. Apraclonidine, latanoprost, and pilocarpine had no measurable effect. CONCLUSIONS: Continuous telemetric measurement of intraocular pressure in rabbits permits the measurement of uncontrollable artifacts that occur with tonometric measurements and animal handling. If environmental conditions are rigidly controlled, this method is very sensitive for detecting therapeutic effects of candidates for ocular hypotensive drugs. When healthy animals are used, the method appears to be more sensitive for drugs that affect aqueous humor formation than for drugs that affect aqueous humor outflow resistance.     

Effect of local administration of mitomycin C on intraocular pressure

BACKGROUND: Animal studies suggest that the decrease of intraocular pressure after application of mitomycin C is particularly mediated by toxic effects on the substance of ciliary body. Moreover it has been shown that the concentration of mitomycin C after topical application in the aqueous humour is as high when performing fistulating surgery. In this prospective study we wanted to investigate whether the topical application of mitomycin C would result in a significant decrease of intraocular pressure. PATIENTS AND METHODS: Forty-one eyes of 41 patients underwent pterygium surgery using a bare sclera technique. Afterwards phototherapeutic keratectomy with the excimer laser (193 nm) was performed in the area of the excision. In hospital mitomycin C eye drops (0.02%) were given twice daily for four days. The intraocular pressure of treated and untreated eyes was measured with applanation tonometry at least three times per day preoperatively, postoperatively at the fourteenth day and after 6 month. RESULTS: Mean intraocular pressure of the treated eyes was preoperatively 15.73 +/- 2.35 mm Hg, 14 days postoperatively 15.92 +/- 2.79 mm Hg and at the last examination 15.86 +/- 2.39 mm Hg. For untreated eyes the mean intraocular pressure was preoperatively 15.70 +/- 2.04 mm Hg, after 14 days 15.76 +/- 2.96 mm Hg and at the last examination 15.89 +/- 2.67 mm Hg. Consequently there was no statistically significant change of intraocular pressure in the eyes treated with mitomycin C. Furthermore there were no significant differences of intraocular pressure between treated and untreated eyes at any time of postoperative check-up. CONCLUSION: The short-term local application of mitomycin C did not result in a detectable change of intraocular pressure and is therefore probably an alternative to intraoperative application during filtration surgery.