XALATAN
(generic name: Latanoprost)

Indian J Ophthalmol. 2005 Mar;53(1):23-30.
Efficacy and safety of latanoprost for glaucoma treatment: a three-month multicentric study in India.
Thomas R, Parikh R, Sood D, Vijaya L, Sekhar GC, Sood NN, Baskaran M, Prasad KK; Latanoprost India Study Group.
L V Prasad Eye Institute, L V Prasad Marg, Banjara Hills, Hyderabad 500-034, India. ravithomas@lvpei.org

PURPOSE: To evaluate the short-term efficacy and safety of 0.005% topical latanoprost in Indian eyes. DESIGN: Prospective non-randomised open-label multicentric trial. METHODS: One hundred and fifty patients with ocular hypertension (OHT), primary open-angle, pseudoexfoliation or pigmentary glaucoma were enrolled at four centers. Each center contributed at least 20 patients. Following baseline measurements, 0.005% latanoprost was applied topically once daily in the evening for three months. Patients were examined at 2, 6 and 12 weeks. The primary outcome measure was mean intraocular pressure (IOP) reduction. The mean diurnal variation of IOP (difference between highest and lowest IOP) at baseline and at 12-weeks was compared. RESULTS: One hundred and thirty of 150 enrolled patients completed the study. One randomly selected eye of each patient was included for analysis. At three months, latanoprost reduced the mean IOP from 24.9 (+/- 3.16) mmHg at baseline to 16.10 (+/- 2.7) mmHg, a reduction of 35.25%. 83% had a reduction in IOP of > 25%. The IOP reduction was maintained throughout the study period, and was not affected by gender or age of the patient. One eye did not show any response to the drug. Daytime diurnal variation of IOP was reduced from 4.5 to 2.9 mmHg. 20 patients had conjunctival hyperemia. Six patients had side effects requiring withdrawal from the study. CONCLUSIONS: In this short-term multicentric study, latanoprost effectively reduced IOP and stabilised the diurnal curve in Indian eyes. There were no clinically significant ocular or systemic adverse effects.

Br J Ophthalmol. 2005 May;89(5):547-9.
Effects of the combination of bimatoprost and latanoprost on intraocular pressure in primary open angle glaucoma: a randomised clinical trial.
Doi LM, Melo LA Jr, Prata JA Jr.
Department of Ophthalmology, Federal University of Sao Paulo, Brazil.

AIMS: To evaluate the effect of the combination of bimatoprost and latanoprost on intraocular pressure (IOP) in primary open angle glaucoma (POAG). METHODS: An open label randomised clinical trial was conducted, which included 18 glaucomatous patients (36 eyes). In the first 4 weeks, latanoprost 0.005% was prescribed for both eyes of the patients and any other antiglaucoma medication was discontinued. In the next 4 weeks (phase 1), bimatoprost 0.03% was combined with latanoprost in one randomly assigned eye (case eye) of each patient. In the next 4 weeks (phase 2), bimatoprost was discontinued in the case eyes, while bimatoprost was substituted for latanoprost in the fellow eye (control eye). The IOP was measured at the end of the first 4 weeks (baseline measurement) and weekly during phases 1 and 2. RESULTS: In the case eyes, the mean IOP increased along the first phase (1.8 mm Hg; p = 0.006) when compared to baseline measurements. The IOP returned to previous values after discontinuation of bimatoprost in phase 2. In the control eyes, the mean IOP did not change throughout the study. CONCLUSION: The combination of bimatoprost and latanoprost in POAG increases the IOP and should not be considered as a therapeutic option.

J Ocul Pharmacol Ther. 2005 Apr;21(2):170-3.
The efficacy and safety of topical brinzolamide and dorzolamide when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma.
Tsukamoto H, Noma H, Matsuyama S, Ikeda H, Mishima HK.
Department of Ophthalmology and Visual Sciences, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. htsuka@hiroshima-u.ac.jp

PURPOSE: Brinzolamide and dorzolamide are often used as adjunctive therapy to other antiglaucoma agents. The purpose of this study was to compare the efficacy and safety of brinzolamide 1% versus dorzolamide 1% when added to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma. METHODS: An 8-week, randomized, open-label comparative study was performed in 52 patients with glaucoma. Brinzolamide 1% (twice a day) or dorzolamide 1% (3 times a day) was randomly administered to the patients who had been treated with both latanoprost and a betablocker. RESULTS: Intraocular pressure (IOP) were both decreased significantly (P < 0.0001) from 18.6 +/- 2.3 mmHg to 16.7 +/- 2.3 mmHg and from 18.4 +/- 2.6 mmHg to 16.6 +/- 2.5 mmHg, respectively, 8 weeks after the addition of brinzolamide or dorzolamide. However, the difference between the groups was not significant (P = 0.86). The incidence of ocular irritation was significantly higher (P < 0.0001) in the dorzolamide group (74%) than the brinzolamide group (16%), but there was no significant difference in blurred vision between the groups (dorzolamide 37% versus brinzolamide 52%, P = 0.40). CONCLUSIONS: We concluded that the efficacy of brinzolamide 1% was equivalent to dorzolamide 1%; however, the safety of brinzolamide 1% was superior to dorzolamide 1% as adjunctive therapy to the combination with latanoprost and a beta-blocker.

Arch Ophthalmol. 2005 Feb;123(2):186-92.
Blood-aqueous barrier changes after the use of prostaglandin analogues in patients with pseudophakia and aphakia: a 6-month randomized trial.
Arcieri ES, Santana A, Rocha FN, Guapo GL, Costa VP.
Glaucoma Service, Department of Ophthalmology, University of Campinas, Campinas, Sao Paulo, Brazil. rsaran@triang.com.br

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Bimatoprost, latanoprost, and travoprost use may lead to disruption of the blood-aqueous barrier in patients with pseudophakia and aphakia.

J Ocul Pharmacol Ther. 2005 Feb;21(1):75-84.
Efficacy of latanoprost in patients with chronic angle-closure glaucoma and no visible ciliary-body face: a preliminary study.
Kook MS, Cho HS, Yang SJ, Kim S, Chung J.
Department of Ophthalmology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.

The aim of this study was to evaluate the efficacy of 0.005% latanoprost in lowering intraocular pressure (IOP) in patients with chronic angle-closure glaucoma (CACG) and no visible ciliary- body face. Fourteen eyes of 14 Korean patients with CACG with 360 degrees of peripheral anterior synechiae (PAS) and an IOP greater than 21 mmHg without medication were treated with 0.005% latanoprost once-daily. All patients completed 3 months of treatment with latanoprost. The IOP, which was 30.3 +/- 4.5 (mean +/- standard deviation) mmHg at baseline, decreased to 22.6 +/- 4.9 mmHg after 1 week, 19.6 +/- 5.5 mmHg after 1 month, 19.4 +/- 4.9 mmHg after 2 months, and 21.5 +/- 5.9 mmHg after 3 months of treatment with latanoprost (P < 0.01 for each). Ultrasound biomicroscopy of the anterior chamber angle showed anterior bowing of the iris with total occlusion of the angle by PAS, except for 5 eyes with focal microscopic openings to the ciliary-body face at various angles. Adverse ocular events were well-tolerated and transient. In this preliminary study, treatment with 0.005% latanoprost once-daily resulted in a significant reduction in IOP in CACG patients with 360 degrees of PAS on gonioscopy. Our results suggest that latanoprost may be considered as a therapy of choice in these rare cases.

Klin Oczna. 2004;106(1-2 Suppl):243-4.
[The effectiveness of latanoprost for the treatment of pediatric glaucoma]
[Article in Polish]
Urban B, Bakunowicz-Lazarczyk A, Mrugacz M, Ozieblo-Kupczyk M.
Kliniki Okulistyki Dzieciecej Akademii Medycznej w Bialymstoku.

Latanoprost is a prostaglandin F2alpha analog that reduces intraocular pressure by 20-40% in adults with open-angle glaucoma. The efficacy and safety of this drug in children has not been widely reported. In our study we evaluated the effect of latanoprost in 14 children aged 12-18 years (mean 15 years): 10 patients with glaucoma juvenile (I group); 2 patients with secondary glaucoma because of uveitis recidivans and 2 patients with aniridia and albinismus (II group). In the I group the average IOP decrement was 9 mmHg or 36.5% (range 29-44%). In the II group the average IOP decrement was 6.5 mmHg or 23.5% (range 11-33%). In one child with aniridia after one year of treatment IOL rose again to 26 mmHg and antiglaucomatous surgery was necessary. Ocular side effects in children of latanoprost are mild.

Eur J Ophthalmol. 2004 Sep-Oct;14(5):401-6.
Switching to latanoprost monotherapy for 24 weeks in glaucoma patients.
Takahashi I, Tanaka M.
Department of Ophthalmology, Juntendo University School of Medicine, Urayasu Hospital, Chiba--Japan. imk-tak@xb3.so-net.ne.jp

PURPOSE: To investigate the intraocular pressure lowering effect in glaucoma patients switched to latanoprost therapy from isopropyl unoprostone given as monotherapy or in combination with a beta-blocker. METHODS: Patients with primary open angle glaucoma or normal tension glaucoma treated with 0.12% isopropyl unoprostone as monotherapy or in combination with a beta-blocker were eligible for this single-center clinical study. Of the 51 patients (51 eyes) enrolled, 18 were men and 33 were women aged 62.1 +/- 12.3 years (mean +/- SD). Twenty-two patients had primary open angle glaucoma, and 29 patients had normal tension glaucoma. Intraocular pressure was measured twice within 3 months prior to the switch, and the mean value was taken as the baseline. The patients were then switched to latanoprost (0.005%) monotherapy (once-daily administration), and changes in intraocular pressure were monitored. One physician measured intraocular pressure after 4, 8, 16, and 24 weeks of administration in this 24-week study. RESULTS: The mean intraocular pressures were 16.0 +/- 2.4 mmHg at baseline, 13.7 +/- 2.3 mmHg after 4 weeks, 13.1 +/- 2.1 mmHg after 8 weeks, 13.6 +/- 2.0 mmHg after 16 weeks, and 13.3 +/- 2.4 mmHg after 24 weeks. A significant decrease in intraocular pressure was noted at all time points in both groups (paired t-test, p < 0.0001), and the intraocular pressure lowering effect persisted through week 24 of administration (analysis of variance, p < 0.0001). CONCLUSIONS: Switching to latanoprost monotherapy elicits further reduction in intraocular pressure in patients with primary open angle glaucoma or normal tension glaucoma.

Nippon Ganka Gakkai Zasshi. 2004 Aug;108(8):477-81.
[Short and long-term hypotensive effect of timolol-gel and latanoprost instillation in normal-tension glaucoma]
[Article in Japanese]
Hashimoto T, Hara T, Takahashi Y, Kubota S, Kubota M, Tsuru T.
Department of Ophthalmology, Jichi Medical School, Tochigi, Japan.

PURPOSE: To confirm the predictive value of the results of a 4-week trial of latanoprost alone, timolol-gel alone, or a combination of the two in normal-tension glaucoma (NTG) patients, when compared with the hypotensive response after a 6-month trial using the same combination of eye drops for the same patients. METHODS: One eye each of 45 NTG patients was used in a prospective 4-week trial of latanoprost alone, timolol-gel alone, or a combination of the two. Patients continued using the eye drops for 6 months, according to the results of the trial. The correlation of the results of the 6-moth use and the baseline data, and the baseline data and the results of the 4-week trial were evaluated by the paired-t test. RESULTS: The intraocular pressure(IOP)s of patients using timolol-gel alone were 13.9 mmHg at the base line, 9.7 mmHg after the trial, and 12.0 mmHg after 6-month use(baseline, trial: p < 0.05). IOPs when using latanoprost alone were 15.3 mmHg at baseline, 11.7 mmHg after the trial, and 11.5 mmHg after 6-month use(baseline: p < 0.05, trial: p = 0.33). IOPs using timolol-gel and latanoprost in combination were 14.8 mmHg at baseline, 11.4 mmHg after the trial, and 12.0 mmHg after 6-month use (baseline: p < 0:05, trial: p = 0.14). CONCLUSION: The result of the 4-weeks trial of latanoprost alone or in combination with timolol-gel can be indicative of the IOP after 6-month use.

Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3555-9.
Effect of latanoprost on intraocular pressure in mice lacking the prostaglandin FP receptor.
Crowston JG, Lindsey JD, Aihara M, Weinreb RN.
Hamilton Glaucoma Center, Department of Ophthalmology, University of California San Diego, La Jolla, California 92093-0946, USA.

PURPOSE: To determine whether latanoprost lowers IOP in prostaglandin FP receptor knockout mice. METHODS: Mean IOP difference between treated and untreated fellow eyes was measured on three separate occasions, 2 hours after a 200-ng dose of latanoprost to the right eye of homozygous (n = 9) and heterozygous (n = 15) FP knockout mice. C57BL/6 (n = 10) and NIH Swiss white mice (n = 17), which have normal FP receptor expression, provided the control population. The investigator was masked to the genotype of the FP knockout mice at the time of IOP measurement. RESULTS: Latanoprost had no effect on IOP in the homozygous FP knockout mice, with an average difference in IOP between treated and untreated fellow eyes of +0.25 mm Hg and a 95% confidence interval (CI) for the difference between means of -0.019 to +0.69. In contrast, latanoprost reduced IOP in the treated eye of the heterozygous FP knockout, C57BL/6, and Swiss white mice with mean differences and 95% CI of the difference in means of -0.52 (-0.91 to -0.14), -1.38 (-2.1 to -0.70), and -1.29 (-1.78 to -0.79) mm Hg, respectively. CONCLUSIONS: FP receptor signaling plays a crucial role in the early IOP response to latanoprost in the mouse eye.

Curr Med Res Opin. 2004 Sep;20(9):1341-5.
Ocular hypotensive efficacy of travoprost in patients unsuccessfully treated with latanoprost.
Kaback M, Geanon J, Katz G, Ripkin D, Przydryga J; START Study Group.
Glaucoma Consultants, Slingerlands, NY, USA.

OBJECTIVE: To evaluate the efficacy of travoprost 0.004% monotherapy in patients unsuccessfully treated with latanoprost monotherapy. RESEARCH DESIGN AND METHODS: Open-label, noncomparative study conducted at US academic and private practice clinics in adult patients with ocular hypertension or primary open-angle glaucoma who required a change in therapy (due to either inadequate efficacy or safety issues) as judged by the investigator. Intraocular pressure (IOP) was measured at entry and 30 days later. MAIN OUTCOME MEASURES: Mean change in intraocular pressure (mm Hg). RESULTS: Reported here are 488 per-protocol patients from 330 centers who were using latanoprost monotherapy prior to study entry, and who received travoprost monotherapy during the study. Patients had a mean age of 69 years, were approximately two-thirds Caucasian, 60% female, predominantly brown or blue eyes, and 91% were diagnosed as having primary open-angle glaucoma. The mean days in treatment were 31.9 +/- 6.4. Mean IOP at study entry was 21.2 mm Hg. Following travoprost monotherapy, this was reduced by a mean of 3.2 mm Hg to 18 mm Hg (p < 0.0001, paired t-test). There were 21 adverse events reported in the intent-to-treat (ITT) population for an incidence of 3.5%. There were some limitations to the current study including: no washout period, no control therapy, single IOP determinations at the beginning and the end of the study; patient compliance with the initial therapy was not measured, and the study was not masked. This study reflects a real-life situation of what a clinician can expect when he changes a patient from latanoprost monotherapy to travoprost monotherapy. CONCLUSION: This study showed that travoprost provided a statistically and clinically significant reduction (p < 0.0001) in IOP of 3.2 mm Hg for patients who had not been successfully treated with latanoprost monotherapy. The results of this trial demonstrate the potential benefit of using travoprost as a replacement therapy in order to ensure adequate IOP control.

Br J Ophthalmol. 2004 Oct;88(10):1295-8.
Short term efficacy and safety in glaucoma patients changed to the latanoprost 0.005%/timolol maleate 0.5% fixed combination from monotherapies and adjunctive therapies.
Hamacher T, Schinzel M, Scholzel-Klatt A, Neff HM, Maier H, Schlaffer G, Beausencourt E, Jutte M, Scholz R, Lorger C, Stewart WC.
Pharmaceutical Research Network, LLC, 1639 Tatum Street, Charleston, SC 29412-2464, USA.

AIMS: To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC). METHODS: A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months. RESULTS: In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p<0.001) compared to previous monotherapies including latanoprost, timolol, alpha agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a beta blocker added to either CAI, alpha agonist, or pilocarpine, or CAI added to an alpha agonist, or latanoprost added to either CAI, alpha agonist, or beta blocker (unfixed combination), and travoprost added to timolol (p<0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p = 0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%). CONCLUSION: In a clinical setting, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment.

Nippon Ganka Gakkai Zasshi. 2004 Jul;108(7):401-7.
[Comparison of the effects of latanoprost and timolol gel-forming solution on diurnal variation of intraocular pressure in normal-tension glaucoma]
[Article in Japanese]
Nakamoto K, Yasuda N, Nanno M, Fukuda T.
Department of Ophthalmology, Tokyo Metropolitan Police Hospital, Japan.

OBJECTIVE: To compare the effects of latanoprost (Lat) and timolol gel-forming solution (Tg) on the diurnal variation of intraocular pressure (IOP) in normal-tension glaucoma (NTG). SUBJECTS AND METHODS: A total of 47 NTG patients (47 eyes) were randomly assigned to receive Lat alone (25 eyes) or Tg alone (22 eyes). IOP was measured at fixed time points during 24 hours before and after treatment with each drug. In addition, blood pressure and pulse rate were measured before and after treatment. RESULTS: Lat reduced IOP significantly at all time points of measurement. Tg reduced IOP significantly at all time points of measurement except at 22:00 and 03:00. Percent reductions in the IOP at 03:00 and in the mean diurnal IOP were significantly greater in the Lat group than in the Tg group. In the Lat group there was no change in diastolic pressure or pulse rate after treatment, but in the Tg group these parameters decreased significantly. CONCLUSIONS: Comparison of diurnal variation of IOP before and after treatment shows that Lat is more effective than Tg in lowering IOP. In addition, Lat does not affect blood pressure or pulse rate.

Am J Ophthalmol. 2004 Aug;138(2):305-6.
Latanoprost exposure in pregnancy.
De Santis M, Lucchese A, Carducci B, Cavaliere AF, De Santis L, Merola A, Straface G, Caruso A.
Telefono Rosso Teratology Information Service, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. marcodesantis@rm.unicatt.it

PURPOSE: To observe pregnancies exposed to latanoprost, a prostaglandin analog administered in the treatment of glaucoma. Its prescription is limited in pregnancy, because reproduction studies in animals report a high incidence of abortion and human investigations are not adequate. As a consequence it is classified as category C drug according to the United States Food and Drug Administration's use-in-pregnancy ratings. DESIGN: Observational study. METHODS: We collected data, referred to our Teratology Information Service, relative to latanoprost exposure in pregnancy. We followed by phone interviews women treated with latanoprost during the first trimester, and we evaluated whether there had been any adverse effects on the fetus. RESULTS: Eleven cases of latanoprost exposure in pregnancy were referred to our Teratology Information Service. One case was lost to follow-up, and one case was complicated by miscarriage. Nine cases had a complete follow-up without congenital anomalies. CONCLUSIONS: Our series is too small to perform statistical significance; however, we found no evidence of adverse effects of latanoprost on pregnancy or neonatal outcomes.

Clin Experiment Ophthalmol. 2004 Aug;32(4):373-7.
Short-term effect of latanoprost on ocular circulation in ocular hypertension.
Akarsu C, Bilgili YK, Taner P, Unal B, Ergin A.
Department of Ophthalmology, University of Kirikkale, Turkey. cengizakarsu@hotmail.com

PURPOSE: To determine the short-term effects of latanoprost on retrobulbar circulation in ocular hypertension. METHODS: Forty-six eyes of 23 consecutive bilateral ocular hypertensive patients with an intraocular pressure (IOP) of greater than 22 mmHg were evaluated in a prospective controlled study. All subjects received a single drop of latanoprost 0.005% in one eye and placebo in the fellow control eye. Systemic circulatory parameters, intraocular pressure, blood flow velocities, and resistance indices of the ophthalmic, short posterior ciliary and central retinal arteries were measured using colour Doppler imaging at baseline and 2 h and 8 h after dosing. RESULTS: Latanoprost lowered IOP significantly after 2 h and 8 h (P < 0.01). The mean IOP reduction was 6.7 mmHg 8 h after dosing. At baseline, there were no statistically significant differences in any retrobulbar vessels of eyes that received a single drop of latanoprost when compared with the eyes that received placebo (P > 0.05). Comparisons with baseline and latanoprost conditions revealed that latanoprost did not alter the blood flow velocities and resistance indices in the ophthalmic (P > 0.05), posterior ciliary (P > 0.05) and central retinal (P > 0.05) arteries 2 h and 8 h after dosing. The systolic and diastolic blood pressures (p = 0.74, p = 0.29, respectively) and pulse rate (p = 0.68) remained unchanged over the 8-h period. CONCLUSIONS: This study found that a single drop of latanoprost significantly reduces intraocular pressure 8 h after dosing. However, it does not have any short-term effects on the retrobulbar haemodynamics in ocular hypertensive eyes.

Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):654-60.
The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: a double-masked placebo-controlled clinical study.
Dinslage S, Hueber A, Diestelhorst M, Krieglstein G.
Department of Ophthalmology, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany. sven.dinslage@uni-koeln.de

BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total outflow facility in human glaucomatous eyes. METHODS: In a randomized double-blind clinical study patients with POAG and OHT receive either Latanoprost 0.005% or placebo once in the evening. Fluorophotometry (Fluorotron Master II, Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10 patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out period all patients received a systemic antiglaucomatous therapy (Acetazolamide) up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg at baseline were excluded. Fluorophotometry, tonography and IOP were measured at baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's paired t test. RESULTS: All patients completed the protocol. The IOP significantly decreased (25%) after 1 and 2 weeks of treatment with Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow over time in both groups. Although tonographic mean C values in both groups did not show any difference over time, the estimated total outflow facility C (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2 weeks. A significant difference of outflow co-efficient correlated to normal pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05). CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow values in both groups showed no increase or decrease in aqueous humor dynamics as proved in many previous studies. The known effect of Latanoprost increase uveoscleral outflow by remodeling extracellular matrix and widening intermuscular spaces in the ciliary body may not detected by pneumotonography after 2 weeks of treatment. The significant increase in estimated total outflow facility (Goldmann formula) in latanoprost-treated eyes and the decrease of IOP took place at constant flow rates. The increase in conventional outflow facility may indicate trabecular meshwork changes, but it cannot explain the significant decrease in IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the major role as considered in many previous studies.

Clin Ther. 2004 May;26(5):755-68.
Comparison of latanoprost with fixed-combination dorzolamide and timolol in adult patients with elevated intraocular pressure: an eight-week, randomized, open-label, parallel-group, multicenter study in Latin America.
Sussana R Jr, Sheu WP; Latin American Glaucoma Society.
Glaucoma Service, University of Sao Paulo, Av. Sao Gualter 99, 05455-000 Sao Paulo, Brazil. rsusanna@terra.com.br

BACKGROUND: The newer ocular hypotensive agents available to treat glaucoma and ocular hypertension (OHT) include latanoprost, a prostaglandin F(2alpha) analogue, and the fixed combination of dorzolamide hydrochloride, a carbonic anhydrase inhibitor, and timolol maleate, a beta-blocker. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of latanoprost with that of the fixed combination of dorzolamide and timolol over 8 weeks. METHODS: This interventional, 8-week, randomized, open-label, parallel-group study was conducted at 18 centers in 6 Latin American countries. Patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT were randomized to receive latanoprost, 1 drop in the affected eye QD (evening), or fixed-combination dorzolamide/timolol, 1 drop in the affected eye BID (morning and evening). Medications were self-administered, 1 drop per affected eye. At baseline and week 8, intraocular pressure (IOP) was measured 3 times each at 8:30 am, 10:00 am, 2:00 pm, and 5:00 pm and after the water-drinking test, which estimates the IOP peak of diurnal tension curve, performed following the 5:00 pm IOP assessment. The primary efficacy outcome was change in diurnal IOP (the mean of IOP measurements) from baseline to week 8. Adverse effect (AE) data were recorded at each visit. RESULTS: A total of 229 patients were randomized (latanoprost, n = 112; dorzolamide/timolol, n = 117). Mean baseline diurnal IOP values were similar between the 2 groups. Mean (SD) diurnal IOP reductions at week 8 before the water-drinking test were 6.9 (3.0) mm Hg for the latanoprost group and 6.4 (3.2) mm Hg for the dorzolamide/timolol group. Mean IOP values were similar at all time points except at 5:00 pm, when levels were significantly lower in latanoprost-treated patients (P = 0.025). After the water-drinking test, the increase in IOP values was similar between groups at baseline but lower in latanoprost-treated patients at week 8 (adjusted difference, 1.08 mm Hg; P = 0.012). Fewer patients treated with latanoprost reported ocular or systemic AEs (P = 0.025 and P < 0.001, respectively). CONCLUSIONS: In this study of patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT IOP reductions generally were similar between treatment groups, except at 5:00 pm, when the mean IOP level was significantly lower in latanoprost-treated patients. Latanoprost was better tolerated than fixed-combination dorzolamide and timolol.

Eur J Ophthalmol. 2004 May-Jun;14(3):211-9.
Effects of betaxolol and latanoprost on ocular blood flow and visual fields in patients with primary open-angle glaucoma.
Erkin EF, Tarhan S, Kayikcioglu OR, Deveci H, Guler C, Goktan C.
Department of Ophthalmology, Celal Bayar University, Manisa, Turkey. esinerkin@hotmail.com

PURPOSE: To evaluate the effects of betaxolol and latanoprost on ocular blood flow and visual fields in patients with primary open-angle glaucoma (POAG) by means of an observer-masked, prospective clinical study. METHODS: Thirty-two patients with newly diagnosed POAG were included in the study. The patients were randomized into two groups. The first group was treated with betaxolol 0.50% twice daily and the second group with latanoprost 0.005% once daily. Baseline and posttreatment examinations on the first and third months of treatment included intraocular pressure (IOP) measurement, automated visual field testing, and ocular blood flow assessment. For evaluation of visual fields, mean defect and pattern standard deviation indices were used. Ocular blood flow was assessed by means of color Doppler imaging of the central retinal artery (CRA) and the temporal short posterior ciliary artery (PCA). For each vessel, peak systolic (PSV) and end-diastolic (EDV) blood flow velocities were measured and resistivity index (RI) calculated. RESULTS: After exclusion of one noncompliant patient, the study was completed with 31 eyes of 31 patients. Both drugs significantly reduced IOP (p<0.05). The mean IOP lowering effect of latanoprost was significantly higher than that of betaxolol (p=0.03). Visual field indices exhibited no significant changes in either group (p>0.05). There were no significant changes in PSV or EDV measurements of CRA or PCA in either group (p>0.05). RI decreased in both CRA and PCA with both drugs. The mean changes between baseline and 3 month blood flow measurements were not significantly different between betaxolol and latanoprost (p>0.05). CONCLUSIONS: Over a treatment period of 3 months, both betaxolol and latanoprost tended to improve ocular blood flow without one of them being superior to the other. The results suggest that the direct (non IOP-dependent) influence on ocular circulation is better for betaxolol than for latanoprost. In addition, neither drug caused significant generalized improvements in visual fields during this period.

Jpn J Ophthalmol. 2004 May-Jun;48(3):276-80.
Switch to latanoprost monotherapy from combined treatment with beta-antagonist and other antiglaucoma agents in patients with glaucoma or ocular hypertension.
Ito K, Goto R, Matsunaga K, Sugimoto K, Uji Y.
Department of Ophthalmology, Mie University School of Medicine, Tsu, Japan. itokunio@clin.medic.mie-u.ac.jp

PURPOSE: To investigate the effects on intraocular pressure (IOP) and the occurrence of adverse events upon switching directly to latanoprost monotherapy from multiple drug therapy, including a beta-antagonist, for glaucomatous eyes. METHODS: Patients with primary open-angle glaucoma or ocular hypertension and receiving long-term therapy with two or three topical ocular hypotensive drugs (including one topical beta-antagonist) were switched to latanoprost monotherapy for 12 weeks without any intervening washout period. Observations were performed before switching (baseline) and at weeks 4, 8, and 12 after switching to latanoprost monotherapy. RESULTS: Of the 29 enrolled patients, 26 (90%) completed this protocol. Three patients had excessive IOP elevation, and these patients were withdrawn. The switch to latanoprost monotherapy was followed by a significant ( P < 0.0001) mean reduction of 3.9 mmHg at week 12 in per-protocol cases ( n = 26) and a significant ( P = 0.0016) mean reduction of 2.8 mmHg at last postswitch visit in patients in the intent-to-treat analysis group ( n = 29). Adverse ocular events other than IOP elevation were mild. CONCLUSIONS: The switch to latanoprost monotherapy in glaucoma patients receiving multiple drug therapy resulted in an additional, significant IOP reduction.

Nippon Ganka Gakkai Zasshi. 2004 Apr;108(4):207-12.
[The effect of substituting latanoprost 0.005% for unoprostone 0.12%]
[Article in Japanese]
Otori Y, Tokugawa H, Morimura H, Okada M, Goto H, Miki A, Tano Y.
Department of Ophthalmology and Visual Science, Osaka University Medical School, 2-2 Yamadaoka, Suita 565-0871, Japan.

PURPOSE: To evaluate the effect of substituting latanoprost(LAT) 0.005% for unoprostone(UNO) 0.12% after a trial of unilateral treatment. METHODS: 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. RESULTS: 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. CONCLUSIONS: If LAT is substituted for UNO, it can be predicted that 63.3% of the patients will respond.