uf-021 and Glaucoma--Open-Angle

Optic nerve and retinal diseases such as glaucoma, age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are significant public health concerns and have a momentous impact on patients' functional status and quality of life. These diseases are among the most common causes of visual impairment worldwide and account for billions of dollars in healthcare expenditures and lost productivity. The importance of adequate treatment of these conditions and the need for efficacious therapeutic drugs cannot be overstated. Unoprostone continues to be developed as a potential treatment for these debilitating diseases.. This review provides background information on unoprostone isopropyl (unoprostone), a prostanoid and synthetic docosanoid approved for the treatment of open-angle glaucoma and ocular hypertension, and recapitulates safety and efficacy data as it relates to this indication. Additionally, this review describes potential new uses of unoprostone as therapy for dry AMD and RP. A literature search of peer-reviewed publications was performed utilizing PubMed. Searches were last updated on 10 September 2012.. Current data indicate that unoprostone does significantly lower intraocular pressure (IOP) and has a favorable safety and tolerability profile. However, the IOP-lowering effects of unoprostone do not compare with other commercially available prostanoids and it has the disadvantage of a twice-daily rather than once-daily dosing regimen. Nonetheless, recent data suggest that unoprostone may improve neuronal survival and increase ocular blood flow, indicating that it may have some value as a therapy for glaucoma, RP and dry AMD. Further studies are needed to confirm whether unoprostone provides any clinically significant advantage over the other commercially available prostanoids.

Topics: Antihypertensive Agents; Dinoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Macular Degeneration; Ocular Hypertension; Retinitis Pigmentosa; Treatment Outcome

It is still uncertain whether travoprost has comparable or better efficacy compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension. The authors performed a meta-analysis of randomized controlled trials to evaluate the incidence of reported side-effects and intraocular pressure (IOP)-lowering effect of travoprost versus other prostaglandin analogues (latanaprost, bimatoprost, unoprostone) or timolol.. Systematic literature retrieval was conducted in Pubmed, EMBASE, Chinese Bio-medicine Database and Cochrane Controlled Trials Register to identify the potentially relevant randomized controlled trials. The statistical analysis was performed by RevMan 4.1 software that was provided by the Cochrane Collaboration. The outcome measures were the incidence of reported side-effects (hyperaemia, iris pigmentation, eyelash changes) and mean IOP pooled over treatment visits.. In total, 12 articles involving 3048 patients with open-angle glaucoma or ocular hypertension were included in this meta-analysis. The combined results showed that travoprost 0.004% was more effective than timolol or travoprost 0.0015% in lowering IOP, but not more effective than bimatoprost or latanoprost. Travoprost 0.004% caused a higher percentage of hyperaemia than timolol, latanoprost, or travoprost 0.0015%. There was an increased incidence of pigmentation with travoprost than timolol. Travoprost 0.004% caused a higher percentage of eyelash changes than timolol, latanoprost, or travoprost 0.0015%.. According to data available, travoprost is more effective than timolol in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Compared with other prostaglandin analogues, travoprost appears to be equivalent to bimatoprost and latanoprost. Although a limited number of local side-effects were reported, no serious treatment-related side-effects were reported.

Topics: Aged; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Lipids; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Timolol; Travoprost

Latanoprost became the first line therapeutic agent in glaucoma treatment being the best sold worldwide anti-glaucoma medication. When adequate intraocular pressure decrease can not be achieved with latanoprost monotherapy, then its combinations are to be used. Latanoprost combinations are grouped in to non-fixed and fixed variants. Non-fixed combinations mean concomitant therapy,that is giving the two or more medications using different bottles. The medications used for latanoprost non-fixed combinations are represented by timolol 0.5%, pilocarpine 2%, acetazolamide dispensed systemically and locally, dipivefrin 0.1%, unoprostone 0.12% and brimonidine 0.2%. Fixed combinations mean administering the two mixed medications using one single bottle. At the present time there is only one fixed combination of latanoprost i.e. its combination with timolol 0.5% whose trading name is Xalcom.

Topics: Acetazolamide; Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Dinoprost; Drug Combinations; Drug Therapy, Combination; Epinephrine; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Pilocarpine; Prostaglandins F, Synthetic; Quinoxalines; Timolol

This review summarises the safety of unoprostone isopropyl (both at the 0.12 and 0.15% concentrations) instilled twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). For unoprostone 0.15%, combined data from two 12-month comparative monotherapy studies are reported, as well as data from three adjunctive therapy studies and two special population studies. With unoprostone monotherapy, most adverse events were mild or moderate and transient in nature. Less than 7% of unoprostone-treated patients discontinued therapy due to an adverse event. The most common adverse events associated with unoprostone were burning/stinging, burning/stinging directly upon drug instillation, ocular itching, and conjunctival hyperaemia. Unoprostone had no clinically notable effects on vital signs, laboratory profiles, or comprehensive ophthalmic examinations. One of 659 unoprostone 0.15%-treated patients had a change in iris colour after 12 months of monotherapy. Except for a higher incidence of burning/stinging and burning/stinging upon instillation, unoprostone was comparable to timolol 0.5% twice daily and betaxolol 0.5% twice daily. No safety concerns were raised with use of unoprostone as adjunctive therapy. Unoprostone had no significant effect on exercise-induced heart rate in healthy subjects or on pulmonary function in patients with mild-to-moderate asthma. The safety profile of unoprostone 0.15% was consistent with published information on the 0.12% formulation. In conclusion, unoprostone has an excellent safety profile in patients with POAG or OH.

Topics: Antihypertensive Agents; Chemotherapy, Adjuvant; Demography; Dinoprost; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Ocular Hypertension

To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma.. Primary and review articles were identified from a MEDLINE search (1966-May 2001) and requested information from product manufacturers.. All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date.. The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with beta-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes.. Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Drug Storage; Glaucoma, Open-Angle; Humans; Latanoprost; Lipids; Ocular Hypertension; Prostaglandins; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Travoprost

Latanoprost and unoprostone (isopropyl unoprostone) represent the first commercially available prostaglandin analogues to be used for the treatment of glaucoma. Both compounds reduce intraocular pressure by enhancing uveoscleral outflow. Latanoprost, when used once daily in the evening, produces a greater reduction in pressure than timolol. Latanoprost produces mild conjunctival hyperaemia compared with timolol in some patients. Darkening of the irides has been reported, especially in green-brown, yellow-brown and blue/grey-brown irides. Hypertrichosis and hyperpigmentation of the eyelashes have also been demonstrated. Although latanoprost has not been proven to cause uveitis or cystoid macular oedema, case reports of an association exist. Latanoprost does not produce systemic adverse effects nor does it alter routine blood analyses. Unoprostone, when given twice daily, produces less of a reduction in intraocular pressure than timolol or latanoprost. Three times daily use may be required to approach the effectiveness of timolol. Unoprostone may have a similar adverse effect profile to latanoprost, but may to cause more corneal epithelial problems. Unoprostone is also not known to cause systemic adverse effects. Both agents are welcome additions to the treatment of glaucoma. However, additional studies and more experience are needed with each agents.

Topics: Dinoprost; Drug Administration Schedule; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Latanoprost; Ocular Hypertension; Pigment Epithelium of Eye; Prostaglandins F, Synthetic; Risk Assessment

To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily.. In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period.. In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey.. Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Dinoprost; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quinoxalines; Timolol; Treatment Outcome

To investigate the effects of prostaglandin analogues on the blood-aqueous barrier and to evaluate the occurrence of cystoid macular edema in aphakic or pseudophakic patients with glaucoma.. In this randomized, masked-observer, 6-month clinical trial, patients with primary open-angle, pseudophakic, or aphakic glaucoma were treated once daily with bimatoprost (n = 16), latanoprost (n = 15), or travoprost (n = 17) or twice daily with unoprostone (n = 16) or lubricant drops (control group) (n = 16). Blood-aqueous barrier status, which was assessed using a laser flare meter; intraocular pressure; the occurrence of angiographic cystoid macular edema; and conjunctival hyperemia were evaluated.. Mean flare values were significantly higher in the bimatoprost, latanoprost, and travoprost groups throughout follow-up (P < .02). Four latanoprost-treated eyes, 1 bimatoprost-treated eye, and 1 travoprost-treated eye developed cystoid macular edema; all cases resolved after discontinuation of the prostaglandin analogue and treatment with topical diclofenac sodium. Mean intraocular pressure reductions after 6 months were higher for the latanoprost (26%), bimatoprost (28%), and travoprost (29%) groups than for the control (3%) and unoprostone (14%) groups (P< .05). Bimatoprost induced significantly higher hyperemia scores than latanoprost, unoprostone, and placebo (P< .01).. Bimatoprost, latanoprost, and travoprost use may lead to disruption of the blood-aqueous barrier in patients with pseudophakia and aphakia.

Topics: Aged; Amides; Antihypertensive Agents; Aphakia, Postcataract; Bimatoprost; Blood-Aqueous Barrier; Cloprostenol; Dinoprost; Female; Fluorescein Angiography; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Lipids; Macular Edema; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Pseudophakia; Safety; Travoprost

To assess the efficacy and safety of unoprostone isopropyl as an adjunctive treatment to topical beta-blocker in patients with primary open angle glaucoma (POAG).. This was a prospective, open-label clinical study.. A total of 44 eyes of 22 eligible patients whose intraocular pressure (IOP) was inadequately controlled by topical beta-blocker were enrolled. Inclusion criteria consisted of patients with primary open angle glaucoma who either had IOP measurements > or = 22 mmHg while on topical beta-blocker monotherapy or had IOP measurements > or = 18 mmHg while on dual therapy (topical beta-blocker and a second drug of a different class which was to be discontinued prior to the study to allow washing out of its effects).. Baseline IOP, pupil size, blood pressure and pulse rate were initially measured; the patients were then examined at 2nd, 4th, 8th, 12th, 18th and 24th weeks of following commencement of topical unoprostone isopropyl therapy (given twice daily).. IOP pupil size, blood pressure and pulse rate were measured and were compared to baseline values.. In 44 eyes of 22 eligible patients, unoprostone isopropyl resulted in a statistically significant IOP reduction of 24.6% (p < 0.02). The mean systolic blood pressure decreased from 132.79 +/- 22.11 mmHg (range 100-180 mmHg) at baseline to 125.77 +/- 18.40 mmHg (range 80-160 mmHg) at 24th week after unoprostone isopropyl administration. This reduction was statistically significant (p = 0.002) but was unlikely to have clinical importance. Both mean diastolic blood pressure (p = 0.344), pulse rate (p = 0.306), and pupil diameter (p = 0.107) were not significantly affected.. Topical unoprostone isopropyl beneficially provides additive IOP lowering effect to topical beta-blocker in patients with primary open angle glaucoma. No serious systemic side effects were found in the present study.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Dinoprost; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method; Tonometry, Ocular; Treatment Outcome

To evaluate long-term efficacy and safety of treatment combining topical beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal-tension glaucoma patients.. A prospective, open-label, parallel-group clinical comparison trial was performed to evaluate efficacy and safety of treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5% timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which were matched in the aging and the stage of glaucomatous visual field defect, were studied. Twenty patients were treated with B&U and the other twenty patients with T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey automated perimetry, blood pressure, heart rate, and peak flow were done every six months in each group.. In the B&U treatment group, mean IOP was 21.2 mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The cases in which MD value decreased over 2 dB were one in the B&U treatment group and three in the T&U treatment group. The average MD value was significantly improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05), but there was no difference with the T&U treatment. None of the patients stopped combined therapy because of side effects, though heart rate was significantly reduced only in T&U treatment group.. Both combined treatments were effective for IOP reduction in glaucoma patients, and the data from the B&U treatment group suggested that B&U was more effective in maintaining visual field than T&U.

Topics: Adult; Aged; Antihypertensive Agents; Betaxolol; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Timolol; Visual Fields

To compare the efficacy and safety of unoprostone versus brimonidine both given twice daily in ocular hypertensive or primary open-angle glaucoma subjects.. After a 1-month washout period a baseline diurnal curve was measured every 2 hours from 08:00 hours (trough) to 20:00 hours in subjects with a trough intraocular pressure (IOP) and the pressure 24 mmHg. Qualified subjects were randomized to either brimonidine or unoprostone. After 6 weeks of treatment the period 1 diurnal curve was performed. Subjects were then switched to the opposite treatment for 6 weeks and the period 2 diurnal curve was performed.. A total of 33 subjects were included in this study. In the brimonidine-treated group the trough IOP 20.1 +/- 2.8 mmHg was reduced from baseline up to 8 hours after dosing. In the unoprostone-treated group the trough IOP was 19.5 +/- 3.0 mmHg, which was statistically equal to that of brimonidine (p = 0.21), was reduced from baseline for 12 hours after dosing. Brimonidine decreased the IOP statistically more than unoprostone at 10:00 and 12:00 hours (p < 0.0001 and p = 0.02, respectively), while unoprostone reduced the IOP more than brimonidine at 18:00 and 20:00 hours (p = 0.002 and p = 0.05, respectively). Safety levels were similar between groups, but unoprostone caused more ocular stinging than brimonidine (p = 0.008).. This study suggests that twice daily brimonidine demonstrates a statistically greater peak reduction in IOP than unoprostone. However, unoprostone, but not brimonidine, decreased IOP over the complete 12-hour daytime dosing cycle.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Cross-Over Studies; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Quinoxalines; Safety; Treatment Outcome

To evaluate the effect of substituting latanoprost(LAT) 0.005% for unoprostone(UNO) 0.12% after a trial of unilateral treatment.. We treated 30 patients with primary open-angle glaucoma(n = 8), ocular hypertension (n = 1), or normal-tension glaucoma(n = 21) with UNO for 4 weeks in one eye and then substituted LAT for UNO. Four weeks later we measured the intraocular pressure(IOP) in the ipsilateral eye.. The mean baseline IOP level was 18.6 +/- 3.8(mean +/- standard deviation) mmHg. The mean IOP levels(reduction rates) after UNO and LAT therapy were 16.7 +/- 3.1 mmHg (16.6%) and 14.1 +/- 3.2 mmHg (28.9%), respectively(p < 0.001). All patients who responded to UNO also responded to LAT; however, 55% of those who did not respond to UNO responded to LAT.. If LAT is substituted for UNO, it can be predicted that 63.3% of the patients will respond.

Topics: Adult; Aged; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Treatment Outcome

To assess whether iris color and eyelash changes occur with the use of unoprostone for 2 years.. The 2 clinical trials described herein were prospective, randomized, double-masked, active-controlled, parallel group, multicenter studies.. A total of 1131 patients with primary open-angle glaucoma or ocular hypertension participated in 2 clinical trials and received either unoprostone isopropyl 0.15% (659), timolol maleate 0.5% (331), or betaxolol hydrochloride 0.5% (141), 1 drop per eye twice daily for up to 24 months.. Color photographs (1:1 magnification) were taken of the iris and eyelid of each patient at baseline and at regular intervals thereafter through month 24 using a standardized camera system. Photography included 7 views of each eye plus a calibration photograph and a patient identification photograph, for a total of 16 photographs per patient per visit. Two independent (masked) readers subjectively compared baseline iris colors to subsequent visits. Side view photographs of the upper and lower eyelashes were used for the eyelash length analysis, with each having sufficient depth of field and a sufficient number of eyelashes in focus. Similarly, frontal eyelash views were used for the eyelash density analysis.. Changes from baseline in iris color and eyelash length and density within and between treatment groups.. Seven cases of iris color change (1.06%) were confirmed in patients treated with unoprostone for up to 24 months; no confirmed cases were reported in the timolol or betaxolol groups. In the unoprostone group, cases of iris color change were confirmed at months 12 (1 case), 18 (2 cases), and 24 (4 cases). No clinically relevant differences were observed among treatment groups for changes from baseline in eyelash length or density.. Although iris hyperpigmentation and abnormal eyelash changes may occur after treatment with unoprostone, the incidence of these events appears to be low in the 2-year clinical study.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Betaxolol; Dinoprost; Double-Blind Method; Eye Color; Eyelashes; Female; Glaucoma, Open-Angle; Hair Color; Humans; Hyperpigmentation; Incidence; Intraocular Pressure; Iris; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Photography; Timolol

To determine the mechanism by which 0.15% unoprostone isopropyl reduces intraocular pressure (IOP) by studying 33 patients with ocular hypertension or primary open-angle glaucoma.. At baseline, IOP was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, episcleral venous pressure by venomanometry, and uveoscleral outflow by mathematical calculation. Unoprostone was administered to one eye and placebo to the fellow eye of each patient twice daily in a randomized masked fashion. In patients who demonstrated an IOP reduction of 3 mm Hg or more in either eye on day 5 +/- 1 (n = 29), determinations were repeated on that day and on day 28 +/- 2. Treated eyes were compared with control eyes, and treatment days were compared with baseline by paired t tests.. Compared with baseline, unoprostone significantly (P<.001) reduced IOP by a mean +/- SEM of 5.6 +/- 0.4 mm Hg and 4.8 +/- 0.6 mm Hg on days 5 and 28, respectively. The change from baseline with unoprostone was significantly (P<.001) greater than with placebo by 2.8 +/- 0.4 mm Hg on day 5 and by 3.2 +/- 0.5 mm Hg on day 28. Compared with baseline, unoprostone significantly (P

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Aqueous Humor; Dinoprost; Double-Blind Method; Female; Fluorophotometry; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Tonometry, Ocular

Impairment of outflow facility in glaucoma causes large intraocular pressure (IOP) fluctuations that have been shown to be a risk factor for disease progression. The water-drinking provocative test (WDT) has been proposed as an indirect measurement of outflow facility to compare intraocular pressure responses of glaucoma eyes to different drugs. This study was a double-masked, randomized, parallel-group clinical trial comparing the IOP fluctuations in response to the WDT in patients using latanoprost versus unoprostone. After completing a wash-out of ocular hypotensive medications, patients with primary openangle glaucoma or ocular hypertension were randomized to receive either latanoprost (N=40) or unoprostone (N=42). IOP was measured before treatment and at 8 weeks after treatment (baseline IOP for WDT), followed by the WDT. IOP fluctuations and maximum IOP after water ingestion were compared between the two groups. Analysis of covariance was used to adjust for the effects of baseline IOP and treatment efficacy. The mean percentage reduction of IOP was 27% in patients using latanoprost, as compared to 13% in patients using unoprostone (p<0.001). Patients on treatment with latanoprost had significantly less IOP fluctuations in response to the WDT, compared to patients using unoprostone. From an overall baseline IOP of 20.0 mmHg and an overall treatment efficacy of 20%, the mean+/-standard error of the mean (SEM) of the IOP fluctuation during the WDT was 5.3+/-0.4 mmHg in the unoprostone group, and 3.6+/-0.4 mmHg in the latanoprost group (p=0.005, ANCOVA). This could represent an additional benefit of latanoprost over unoprostone in controlling the intraocular pressure of glaucomatous patients.

Topics: Antihypertensive Agents; Dinoprost; Double-Blind Method; Drinking; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Tonometry, Ocular; Water

To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily.. Prospective multicenter, randomized, double-masked, crossover comparison study.. Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days.. Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial.. This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Cross-Over Studies; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome; Visual Acuity

To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension.. This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy.. Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101).. Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Chemotherapy, Adjuvant; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Timolol

To compare, in paired eyes of open-angle glaucoma patients and glaucoma suspects, hydrodynamic and visual changes after 1 month of topical latanoprost in one eye and unoprostone in the other.. Single-center, institutional randomized clinical trial.. After completing a washout period off all topical medication, 25 adults (mean age 54 +/- SEM 2 years) with bilateral open-angle glaucoma or glaucoma suspect status underwent morning (8 to 10 AM) and afternoon (1 to 3 PM) measurements of intraocular pressure (IOP), pulsatile ocular blood flow (POBF), contrast, sensitivity, frequency doubling technology, and Humphrey 10-2 perimetry (HVFA II) in both eyes. Each then started unoprostone 0.15% (Rescula) in one randomly assigned eye and latanoprost 0.005% (Xalatan) in the other. Unoprostone was administered at 8 AM and 8 PM and latanoprost at 8 PM with placebo at 8 AM, both from masked bottles. After 28 days, differences were determined for each measured variable by two-tailed paired t test.. Starting from similar baseline IOP levels, after 1 month of treatment, the mean morning IOP values differed according to the topical agent received (16.2 +/- SEM 0.6 mm Hg for latanoprost vs 17.9 +/- 0.7 mm Hg for unoprostone; P =.001). These morning pressures were 2.6 mm Hg lower than baseline in the eyes receiving latanoprost (P <.0001), and 1.6 mm Hg lower in unoprostone-treated eyes (P =.02). Afternoon values were 3.1 +/- SEM 0.6 lower than corresponding baseline in eyes receiving latanoprost, and 2.4 +/- SEM 0.6 mm Hg in unoprostone-treated eyes (P <.0001 from baseline for both medications; interdrug mean IOP difference; P =.04). Eyes receiving unoprostone showed a 1.7-db improvement in frequency doubling mean deviation (P =.03), the only significant visual function change observed. Pulsatile ocular blood flow increased 30% relative to baseline in eyes receiving latanoprost, (P <.0001) and 16% in eyes receiving unoprostone (P =.05) by the morning of day 28. That afternoon, mean POBF had increased 30% (P <.0001) relative to afternoon baseline values among eyes receiving latanoprost and 18% (P =.03) among those receiving unoprostone (interdrug change difference, P =.05). Humphrey perimetry and contrast sensitivity remained stable with both prostanoids.. Both latanoprost and unoprostone produced significant reductions in IOP and increases in POBF, with stable central and perimacular visual function. Latanoprost once daily produced IOP reduction and POBF increases nearly twofold greater than those obtained with unoprostone twice daily. These differences in IOP and POBF change between unoprostone and latanoprost were statistically significant.

Topics: Adult; Aged; Antihypertensive Agents; Contrast Sensitivity; Dinoprost; Double-Blind Method; Eye; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Pulsatile Flow; Regional Blood Flow; Visual Fields

To compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost 0.005% once daily with that of unoprostone 0.15% twice daily for patients with primary open-angle glaucoma or ocular hypertension.. Randomized clinical trial.. In a prospective, 8-week, investigator-masked, parallel-group study conducted at numerous centers in the United States, 165 previously treated patients with IOP >or= 25 mm Hg in one or both eyes after washout were randomly assigned to receive either latanoprost 0.005% once daily in the evening or unoprostone 0.15% twice daily. Observations procedures were Goldmann applanation tonometry, best-corrected visual acuity, slit lamp biomicroscopy, and ophthalmoscopy. The main outcome measure was change in the mean of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM between baseline (before treatment) and after 8 weeks of treatment.. The change in the mean +/- SD of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM was -7.2 +/- 3.2 mm Hg (28%) for latanoprost (25.3 +/- 2.8 mm Hg at baseline to 18.2 +/- 2.8 mm Hg at 8 weeks) and -3.9 +/- 2.6 mm Hg (15%) for unoprostone (25.5 +/- 3.3 mm Hg at baseline to 21.6 +/- 4.0 mm Hg; P

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Ophthalmoscopy; Prospective Studies; Prostaglandins F, Synthetic; Tonometry, Ocular; Treatment Outcome; Visual Acuity

To compare the efficacy and safety of latanoprost versus isopropyl unoprostone (unoprostone) in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).. An 8-week, multicenter, randomized, comparative study was performed in 48 Japanese patients with POAG or OH. Four patients (two in each group) withdrew from the study, but their data were included in the safety assessment but not in the intraocular pressure (IOP) evaluation. The patients were randomly treated with latanoprost 0.005% once daily or unoprostone 0.12% twice daily for 8 weeks. IOP was measured at baseline and 2, 4, and 8 weeks after treatment. In addition, ocular and systemic adverse events were recorded.. The baseline IOPs were similar between the latanoprost (n = 25) and unoprostone (n = 19) groups (24.3 +/- 2.4 mm Hg vs 23.3 +/- 2.1 mm Hg, respectively, = 0.18). The IOP reductions from baseline at 2, 4, and 8 weeks after treatment were 5.8 +/- 2.4, 6.6 +/- 2.5, and 6.7 +/- 2.0 mm Hg in the latanoprost group, and 3.8 +/- 2.0, 3.5 +/- 2.3, and 3.3 +/- 3.0 mm Hg in the unoprostone group, respectively. The IOP reduction in the latanoprost group at 8 weeks was larger than that in the unoprostone group ( < 0.001, analysis of covariance). Five adverse events were observed in 4 (15%) of 27 patients in the latanoprost group, and five adverse events were observed in 4 (20%) of 21 patients in the unoprostone group. There was no difference in the incidence of adverse events between groups ( = 0.71).. Latanoprost produced a statistically greater reduction in IOP than unoprostone in Japanese patients with POAG or OH.

Topics: Antihypertensive Agents; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Japan; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety

A long-term comparison of the ocular hypotensive efficacy and safety of unoprostone isopropyl 0.15% twice daily with that of timolol maleate 0.5% twice daily and betaxolol HCl 0.5% twice daily.. This was a randomized, multicenter, double-masked, active-controlled 24-month clinical trial involving 27 centers in Europe and Israel.. The study population was composed of patients with primary open-angle glaucoma (including pseudoexfoliation) or ocular hypertension. After washout of antiglaucoma medications, intraocular pressure (IOP) was measured at 0, + 2, + 8, and + 12 hours. Patients were randomized in a 2:1:1 ratio to unoprostone, timolol, or betaxolol. Patients returned for examinations at 2 and 6 weeks and 3 and 6 months.. 556 patients were randomized. Each drug produced a clinically and statistically (P <.001) significant reduction from baseline in 12-hour diurnal IOP at month 6 (- 4.3 mm Hg, unoprostone; - 5.8 mm Hg, timolol; - 4.9 mm Hg, betaxolol). Differences in adjusted treatment means between unoprostone and timolol and unoprostone and betaxolol were 1.57 mm Hg (95% CI: 1.00, 2.13) and 0.53 mm Hg (95% CI: - 0.03, 1.09), respectively. Unoprostone was clinically equivalent to betaxolol but did not have as great an IOP-lowering effect as timolol. Discontinued for inadequate control of IOP were 7%, 1%, and 4% of the patients for unoprostone, timolol, and betaxolol, respectively. There were no changes of note in visual acuity, pupil size, cup-to-disk ratio, visual fields, or iris color. Changes in heart rate and blood pressure were small, with no clinically significant differences between groups.. Unoprostone provided a clinically significant IOP-lowering effect equivalent to betaxolol but not to timolol. The side effect profile of unoprostone appears to be comparable to other established IOP-lowering agents.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Betaxolol; Dinoprost; Double-Blind Method; Exfoliation Syndrome; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pupil; Safety; Timolol; Visual Acuity; Visual Fields

To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) METHODS: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measurements was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used.. 28 patients completed both treatment periods and had IOP data available for evaluation. After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg and 24.4 (1.1) mm Hg respectively (p = 0.18). When latanoprost once daily was given to patients treated with unoprostone, there was additional IOP lowering of 1.9 (0.6) mm Hg (p = 0.012). However, adding unoprostone to those being treated with latanoprost produced an IOP change of +0.4 (0.5) mm Hg (p = 0.42). Ocular symptoms and findings were mild and equally distributed between treatment groups, and after combined therapy. Hyperaemia and ocular irritation were the most frequently reported events. Over a third of patients experienced ocular irritation with the combination of medications.. Latanoprost once daily causes additional IOP lowering in eyes which were being treated with unoprostone twice a day. However, there was no additional IOP lowering when unoprostone was added to eyes which were being treated with latanoprost. Both drugs were well tolerated together with few ocular adverse events.

Topics: Adult; Aged; Antihypertensive Agents; Dinoprost; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic

To compare the intraocular pressure (IOP) reducing effect and safety of latanoprost 0.005% once daily with unoprostone 0.12% twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).. An 8-week, double-masked, randomized, parallel-group, single-center clinical trial.. A total of 108 patients with POAG or OH were enrolled.. After completing a wash-out of ocular hypotensive medications, patients were randomized to receive either latanoprost once daily in the evening plus placebo once daily in the morning, or unoprostone twice daily (morning and evening).. IOP was measured at 10:00 AM and at 5:00 PM at baseline and at week 8, and before 12:00 noon at week 2. Ocular and systemic safety assessments were performed.. From an overall baseline of 24.1 mmHg, latanoprost reduced IOP by 6.7 mmHg (28%) and unoprostone reduced IOP by 3.3 mmHg (14%). The difference between the groups of 3.4 mmHg was significant (P: < 0.001, analysis of covariance; 95% confidence interval [CI]: -4.7 to -2.1) in favor of latanoprost. A >/=30% reduction in mean IOP from baseline was achieved by 44% of latanoprost-treated patients compared with 8% of unoprostone-treated patients. The incidence of adverse events was low and comparable between the groups.. Latanoprost administered once daily was significantly more effective in reducing IOP compared with unoprostone administered twice daily in patients with POAG and OH.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety; Treatment Outcome

To evaluate the safety and efficacy of adding unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening.. We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment.. Twenty patients were treated in the placebo group and 21 in the unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 +/- 3.2 and 19.1 +/- 2.2 mm Hg, respectively. In the unoprostone isopropyl group the pressures were 19.4 +/- 3.3 and 18.0 +/- 1.7 mm Hg (P =.22 and P =.042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough (P <.01) and a 2.1 mm Hg greater decrease in diurnal pressure (P =.030) after adding unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P <.001). In addition, the range of the pressures throughout the diurnal curve was reduced from 2.7 mm Hg on latanoprost alone to 1.4 mm Hg after adding unoprostone isopropyl. Adverse events were similar between groups, and no patients were discontinued because of safety reasons.. This study suggests that unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.

Topics: Antihypertensive Agents; Dinoprost; Double-Blind Method; Drug Synergism; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety; Treatment Outcome

We investigated the intraocular pressure (IOP)-lowering potential of latanoprost in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). This prospective study included 59 NTG and 20 POAG patients treated with the following four dosing regimens of latanoprost: patients on no previous medication received latanoprost as initial therapy (Group 1, n=31), patients on beta-blocker therapy received latanoprost as adjunctive therapy (Group II, n=9), patients on unoprostone monotherapy were switched to latanoprost monotherapy (Group III, n=14), and patients previously on dual therapy with isopropyl unoprostone and beta-blocker were switched to a combined treatment of latanoprost and beta-blocker (Group IV, n=25). IOP significantly decreased 8 weeks after initiation of latanoprost therapy by 19.9% in Group I, 20.5% in Group II, 16.6% in Group III, and 12.2% in Group IV. In Groups I and II, there was a significant positive correlation between the magnitude of IOP reduction induced by latanoprost and the IOP level before latanoprost therapy. The IOP level before latanoprost therapy is a contributing factor in the IOP-lowering efficacy of latanoprost. Latanoprost is more effective in lowering IOP than isopropyl unoprostone.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Dinoprost; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Tonometry, Ocular

To compare the intraocular pressure)-lowering effect and side effects of latanoprost 0.005% once daily with unoprostone 0.12% twice daily.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Cross-Over Studies; Dinoprost; Double-Blind Method; Drug Evaluation; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Treatment Outcome

Because intraocular pressure-lowering agents should have a good safety profile with regard to ocular hemodynamics, the innocuousness of unoprostone isopropyl 0.15% with regard to ocular hemodynamics in vasospastic patients with normal-tension glaucoma was assessed in a pilot study.. Corneal temperature as a parameter of ocular blood flow and choroidal and optic nerve blood flow as assessed by means of laser Doppler flowmetry techniques were evaluated in 12 vasospastic normal-tension glaucoma patients in a prospective, randomized, observer-masked, two-period crossover, placebo-controlled pilot trial.. Statistical analysis in 2 x 2 two-way analysis of variance models with two treatments (placebo and unoprostone isopropyl) and two assessments (baseline and after 1 week of treatment) as within-subject factors disclosed a lack of difference between eyes, between the treatment (placebo/unoprostone isopropyl) periods, and between baseline and after 1 week of treatment in corneal temperature, choroidal blood flow, and optic nerve blood flow. The differences between the results at baseline and after 1 week of treatment in these parameters were not significantly different between the placebo treatment period and the unoprostone isopropyl treatment period, and this was comparable in fellow eyes for all the parameters.. Unoprostone isopropyl did not induce any alterations in ocular hemodynamics in this pilot study with vasospastic normal-tension glaucoma patients.

Topics: Antihypertensive Agents; Blood Flow Velocity; Body Temperature; Choroid; Cornea; Cross-Over Studies; Dinoprost; Double-Blind Method; Drug Evaluation; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser-Doppler Flowmetry; Male; Middle Aged; Ophthalmic Solutions; Optic Nerve; Pilot Projects; Prospective Studies

To evaluate the effects of latanoprost and unoprostone on the intraocular pressure (IOP) and on the tonographic outflow facility in glaucoma patients when used alone or in combination.. Open label randomized clinical study.. Fifty-two patients (52 eyes) with primary open-angle glaucoma were randomly divided into two groups. One group initially received only latanoprost 0.005% once daily and the other group, only unoprostone 0.12% twice daily. The study period was 12 weeks: in the first 6 weeks, latanoprost or unoprostone was given as monotherapy, and in the last 6 weeks, patients received both drugs. IOP was measured every 2 weeks by one investigator masked to the medication received by patients during the study period in the same hour as on the baseline day. At Weeks 0, 6, and 12, the coefficient of aqueous outflow was measured by tonography.. With latanoprost monotherapy, the baseline IOP of 22.9 +/- 2.4 mm Hg (mean +/- SD) decreased to 16.9 +/- 2.1 mm Hg (P<.01). When unoprostone was added to latanoprost, the IOP remained at 16.7 +/- 2.5 mm Hg. With unoprostone monotherapy, the baseline IOP of 22.7 +/- 2.1 mm Hg decreased to 19.4 +/- 2.4 mm Hg (P<.01). When latanoprost was added to unoprostone, the IOP decreased to 16.8 +/- 1.7 mm Hg (P<.01). There was no significant change in the coefficient of aqueous outflow with monotherapy or the combined use of the drugs.. The combination of latanoprost and unoprostone does not result in a more potent hypotensive effect than latanoprost alone.

Topics: Adult; Aged; Antihypertensive Agents; Aqueous Humor; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Tonometry, Ocular; Treatment Outcome

To investigate the clinical characteristics of docosanoid derivative, isopropyl unoprostone in the treatment of primary open angle glaucoma (POAG).. In 17 patients (22 eyes) with POAG we analysed prospectively the effect of Rescula upon intraocular pressure, aqueous flare, pupil size, ocular signs and symptoms. Patients were followed up every 2 weeks for at least 8 weeks with complete ocular examination. Concomitant topical therapeutics were used in the study: 0.5% Timolol--group I (16 eyes), and 0.5% Timolol + 2% Dorzolamide--group II (6 eyes).. Mean (+/- SD) pretreatment pressure was 24.7 +/- 4.3 mm Hg in group I and it was reduced by 3.7 mm Hg (13.5%) (p < 0.05) at the end of the follow up. In group I Rescula was very effective (delta T% > 25%) in 6/16 eyes (37.5%) and it was ineffective (delta T% < 10%) in the same number of eyes. In group II pretreatment pressure was 24.8 +/- 2.6 mm Hg and it was reduced by 2.6 mm Hg (10.6%) (p = 0.1). Rescula induced no elevation of the aqueous flare during the treatment. No effect on pupil size was observed, either. Eye stinging/conjunctival hyperaemia was noted in 2/17 patients and punctate epitheliopathy in 1 patient (5.9%) that caused discontinuation of drops.. Unoprostone produced significant additive effect to Timolol. Thus, it may be a valuable option for adjunctive therapy. However, interindividual differences need to be considered, as in some patients the response was insignificant.

Topics: Administration, Topical; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol

Topics: Antihypertensive Agents; Dinoprost; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Treatment Outcome

To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion.. 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment.. Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group.. While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.

Topics: Adrenergic beta-Antagonists; Aged; Dinoprost; Epithelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Optic Disk; Prospective Studies; Tears; Timolol; Visual Acuity

The efficacy of 0.5% timolol was compared with that of the prostaglandin derivative unoprostone in maintaining control of intraocular pressure (IOP) in subjects with chronic open angle glaucoma (COAG) or ocular hypertension (OH) already responding satisfactorily to beta-blocker monotherapy. In a two-centre, double-masked, randomised parallel group study, 40 subjects were placed on 0.5% timolol eyedrops twice daily for two weeks. They were then randomised either to continue with 0.5% timolol or to switch to 0.12% unoprostone, applied twice daily for six weeks. IOP was measured at two-weekly intervals. The status of the conjunctiva, iris, cornea and anterior chamber was kept under observation. Ocular safety was monitored by measurements of visual acuity, and any systemic adverse events were recorded. After six weeks' treatment, there were no statistically significant differences in mean change from baseline IOP within or between treatment groups. For the subjects treated with unoprostone, mean IOP increased by 0.69 mm Hg (p = 0.368) while that of the timolol-treated subjects fell by 0.47 mm Hg (p = 0.287). The difference in mean IOP between groups was 1.16 mm Hg (p = 0.211, 95% confidence interval [CI] -0.69 to 3.02). The most common complaint was a mild and transient burning sensation on instillation which occurred more frequently in the unoprostone group. In conclusion, an aqueous solution of 0.12% unoprostone isopropyl, applied topically to the eye twice daily for six weeks, was as effective as 0.5% timolol in maintaining control of IOP in subjects with chronic open angle glaucoma or ocular hypertension. Both treatments were safe and well tolerated.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Chronic Disease; Depression, Chemical; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Statistics, Nonparametric; Time Factors; Timolol

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.. 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.. 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.. 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.

Topics: Circadian Rhythm; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Safety; Timolol; Visual Acuity

We have reviewed two Phase III clinical studies of isopropyl unoprostone conducted in Japan: a 12-week comparative study of 0.12% isopropyl unoprostone and 0.5% timolol, and a 52-week administration of two concentrations of isopropyl unoprostone in ocular hypertensive and primary open-angle glaucoma patients. These studies showed a similar ocular hypotensive effect of 0.12% isopropyl unoprostone to 0.5% timolol and a sustained ocular hypotensive effect of the drug for up to one year. Adverse reactions of isopropyl unoprostone were minor and similar to those of timolol. No pigmentary changes of the irides were noticed. In view of these results, isopropyl unoprostone seems to be a useful antiglaucoma medication.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Dinoprost; Drug Evaluation; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Timolol; Treatment Outcome

We investigated the ocular hypotensive effect of concomitant use of pilocarpine and UF-021, a prostaglandin-related compound, in 10 cases (20 eyes) of primary open-angle glaucoma or ocular hypertension. Following a 2- to 4-week-washout of all anti-glaucoma medication, 0.12% UF-021 was instilled twice daily into both eyes of 5 patients and 1% pilocarpine four times daily in 10 eyes of the remaining 5 patients for 2 weeks. Then both eye-drops were used concomitantly for the subsequent 2 weeks. Intraocular pressure (IOP) measurement and slit-lamp examination were carried out from one hour prior to the instillation to 4 hours after the instillation at the end of the washout period, the single-use period, and the concomitant-use period. Although no significant difference was found between IOPs of the single-use and concomitant use periods at each measurement time point, a significant difference was found between them when all the measured IOP values were pooled. No changes in episcleral venous pressure nor adverse effects were noted. We concluded that the concomitant use of pilocarpine and UF-021 causes an additive ocular hypotensive effect in clinical settings.

Topics: Adult; Aged; Dinoprost; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Middle Aged; Ophthalmic Solutions; Pilocarpine; Prospective Studies

A double-masked comparative clinical study of UF-021 (Rescula), a unique prostaglandin-related compound, was carried out at 18 centers with timolol maleate 0.5% ophthalmic solution as an active reference drug. After a wash-out period, UF-021 (0.12%) or timolol (0.5%) was given topically twice a day for 12 weeks to 158 patients with primary open-angle glaucoma or ocular hypertension, in a randomized double-masked manner. Both groups showed a significant reduction in intraocular pressure from the second week to the end of the study. In overall improvement rating, 91.4% of the cases (64/70) in the UF-021 group and 88.3% (68/77) in the timolol group were judged to be "Extremely improved" or "Improved". Five and 4 cases reported having side effects in the UF-021 and timolol groups, respectively, but none of the cases required any change or discontinuation of treatment. While UF-021 did not affect blood pressure, both systolic and diastolic blood pressures in the timolol group were significantly decreased. These results suggest that UF-021 (0.12%) has the potential to lower intraocular pressure equivalent to timolol (0.5%), while having no effect on cardiovascular functions.

Topics: Administration, Topical; Blood Pressure; Dinoprost; Double-Blind Method; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Timolol

UF-021 ophthalmic solution, a novel prostaglandin-related therapeutic agent for glaucoma, was additionally applied to the eyes in intractable cases of primary open angle glaucoma (14 cases, 21 eyes) and ocular hypertension (1 case, 2 eyes) in which intraocular pressure (IOP) had not been kept under satisfactory control even with combined drug therapy by conventional, existing anti-glaucoma agents including sympathetic beta-blockers. Decrease of IOP by UF-021 ophthalmic solution (0.12%) in the treated eyes was observed from not less than one month after the initial application by 3 mmHg and more in about 85%, and by 5 mmHg and more in about 76% of the enrolled patients, respectively. The IOP reduction induced by the additional application of UF-021 was sustained for more than 6 months, resulting in successful avoidance of surgical operations in many patients. When UF-021 ophthalmic solution was applied concurrently with various anti-glaucoma agents including carbonic anhydrase inhibitors, it caused no controversial side-effects and yielded therapeutic efficacy for a prolonged period. These findings suggest that UF-021 can yield IOP-reducing activity through a novel pharmacological mechanism different from other existing drugs. In conclusion, UF-021 ophthalmic solution is extremely useful for the treatment of glaucoma.

Topics: Dinoprost; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ophthalmic Solutions

We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs.. This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire.. There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001).. The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Eyelashes; Eyelid Diseases; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Skin Pigmentation; Surveys and Questionnaires; Travoprost

We retrospectively investigated the long-term effects of isopropyl unoprostone monotherapy on intraocular pressure and visual field for normal-tension glaucoma and primary open-angle glaucoma patients. Among 80 eyes of 49 subjects receiving isopropyl unoprostone monotherapy for 2 years or more, 32 eyes of 32 subjects were analyzed because of the good reliability of their visual acuity and visual field (age, 68.1 +/- 10.1 yrs, follow-up period 47.8 +/- 14.7 months). The mean values of intraocular pressure and visual field indices were compared with baseline data before medication. The visual field changes were also analyzed using the Kaplan-Meier life-table method. The mean intraocular pressure decreased for 4 years from 14.7 +/- 4.3 mmHg (mean +/- SD) at baseline, to 12.7 +/- 4.4mmHg at 4 years. The global index of visual field (mean defect, loss variance) did not change significantly during the 4 years. The accumulative probability of survival was 80.7 +/- 8.0% after 4 years when the endpoint was defined as 3dB progression in mean defect. Isopropyl unoprostone might have the possibility of stabilizing the visual field for a long period of time.

Topics: Aged; Dinoprost; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Retrospective Studies; Visual Fields

The changes in intraocular pressure (IOP) and pupil size (PS) after instillations of 0.15% unoprostone isopropyl (Rescula, Novartis Ophthalmics, Duluth, GA) were investigated in the spontaneous glaucoma Beagle model. From the first-day baseline IOP of 27.3+/-3.2 mmHg placebo eye and 32.8+/-5.1 mmHg control eye, the mean+/-standard error of the mean (SEM) diurnal changes after 0.15% unoprostone, at 8 AM once-daily for the next 4 days, were 15.5+/-1.3 mmHg, 14.7+/-1.9 mmHg, 16.1+/-1.1 mmHg, and 17.0+/-1.5 mmHg, respectively, and were significantly different from the control eye. After 0.15% unoprostone was instilled at 8 PM, the mean+/-SEM baseline changes from the baseline IOP (insert drug eye 9 AM) in the drug eyes were 5.9+/-2.5 mmHg, 5.2+/-4.1 mmHg, 9.7+/-2.5 mmHg, and 3.6+/-3.6 mmHg, respectively. When 0.15% unoprostone was instilled twice-daily, the mean+/-SEM baseline IOP (insert drug eye 9 AM) changes were 13.6+/-0.7 mmHg, 13.9+/-1.4 mmHg, 11.3+/-1.0 mmHg, and 9.3+/-1.4 mmHg, respectively, and were significantly different from the control eyes. Miosis occurred within 2 hours and lasted several hours. Unoprostone isopropyl instilled once-daily (AM or PM), as well as twice-daily, produces significant decreases in IOP and PS in the glaucomatous Beagle.

Topics: Animals; Antihypertensive Agents; Dinoprost; Dog Diseases; Dogs; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Intraocular Pressure; Male; Pupil; Tonometry, Ocular

To evaluate the ocular factors contributing to keratoepitheliopathy in glaucoma patients treated with or without anti-glaucomatous eyedrops, and the influences of each anti-glaucomatous eyedrop to keratoepitheliopathy.. The presence and severity of keratoepitheliopathy was investigated in 193 eyes of 110 glaucoma patients. The ocular factors examined were the status of the lipid layer of the tear fluid as assessed by a specular reflection video-recording system, tear volume assessed by Schirmer's test, and tear film stability assessed by tear break-up time. The influences of combined anti-glaucomatous eyedrops and each anti-glaucomatous eyedrops to keratoepitheliopathy were investigated.. The overall occurrence of superficial punctate keratitis was 29.0%. Superficial punctate keratitis was more frequently observed in patients who used more than two anti-glaucomatous eyedrops (35.9%) than in those who used without (19.7%) and one (30.9%). Results of Schirmer's test and break-up time were worse in patients who used combined medication. The occurrence of superficial punctate keratitis in patients who used timolol (46.2%) was significantly more frequent than in those who used carteolol (4.2%). Severity of superficial punctate keratitis and break-up time in patients who used timolol were significantly worse than in those who used carteolol. There were no differences of keratoepitheliopathy and ocular factors between patients who used latanoprost and unoprostone.. The usage of multiple anti-glaucomatous eyedrops induces keratoepitheliopathy by reducing the tear volume and the tear film stability. Carteolol may be used more safely for corneal epithelium.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Carteolol; Dinoprost; Drug Therapy, Combination; Epithelium, Corneal; Female; Glaucoma, Open-Angle; Humans; Keratitis; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prostaglandins F, Synthetic; Risk Factors; Sulfonamides; Tears; Thiophenes; Timolol

Topics: Antihypertensive Agents; Data Interpretation, Statistical; Dinoprost; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic

Topics: Antihypertensive Agents; Data Interpretation, Statistical; Dinoprost; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic