Latanoprost Research Articles

Treatment merits of Latanoprost/Thymoquinone – Encapsulated liposome for glaucomatus rabbits

Elevation of the intraocular pressure (IOP) is recognized as a risk factor for glaucoma development. Latanoprost (LAT) is a prostaglandin analog used to reduce the (IOP). Thymoquinone (TQ) is a major bioactive ingredient of Nigella sativa. The aim of this study was to develop novel liposomal drug carriers for ocular delivery of LAT, TQ and a mixture of them to investigate their IOP lowering efficacy upon subconjunctival injection in glaucoma-induced rabbit's eye. The aim of the present work extends also to study the effect of the different liposome formulations on the aqueous humor oxidative stress. Liposome samples were prepared using thin film hydration method. The physiochemical properties of the prepared drugs were characterized. The IOP was recorded for 70 rabbits using Schiotz-tonometer. Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) activities and total antioxidant activity of the aqueous humor were estimated. Fourier transform infrared and differential scanning calorimetric studies confirmed the interaction between the drug and the vesicles, which resulted in high drug encapsulation efficiency ≥88%. The size of the prepared liposomes was less than 10 μm which make them suitable in ophthalmic applications. The sustained effect was achieved by liposome samples of Lip (LAT) and Lip (LAT + TQ) which were able to reduce the IOP significantly up to 84 h. Morever, the treatment of glaucomatous rabbits with liposome formulations containing TQ in their preparation [Lip (TQ) and Lip (LAT + TQ)] greatly improved the ocular tissue-induced histopathological lesions. None of the prepared liposome formulations succeeded to improve the glaucoma-induced oxidative stress damage.

The prevention of latanoprost on osteoclastgenesis in vitro and lipopolysaccharide-induced murine calvaria osteolysis in vivo.

Identification of agents that inhibit osteoclast formation and function is important for the treatment of osteolytic diseases which feature excessive osteoclast formation and bone resorption. Latanoprost (LTP), an analog of prostaglandin F2α, is a medication which works to lower pressure inside the eyes. Prostaglandin F2α was reported to regulate bone metabolism, however, the effect of LTP in osteoclastogenesis is still unknown. Here, we found that LTP suppressed RANKL-induced osteoclastogenesis in a dose-dependent manner as illustrated by TRAP activity and TRAP staining. In addition, the osteoclast function was also reduced by LTP treatment, as indicated in less osteoclastic resorption pit areas. Furthermore, LTP inhibited the mRNA expressions of osteoclast marker genes such as TRAP and cathepsin K. In order to illustrate its molecular mechanism, we examined the changing of mRNA and protein levels of NFATc1 and c-fos by LTP treatment, as well as the phosphorylation of ERK, AKT, JNK, and p38. The results suggested that LTP inhibited RANKL-induced osteoclastgenesis and function by inhibiting ERK, AKT, JNK, and p38 cascade, following by the c-fos/NFATc1 pathway. In agreement with in vitro results, using an in vivo lipopolysaccharide-induced murine calvaria osteolysis mouse model, we found that administration of LTP was able to reverse the lipopolysaccharide-induced bone loss. Together, these data demonstrated that LTP attenuated the bone loss in lipopolysaccharide-induced murine calvaria osteolysis mice through inhibiting osteoclast formation and function. Our study thus provided the evidences that LTP was a potential treatment option against osteolytic bone diseases.

Efficacy and side effects of latanoprost monotherapy compared to adding dorzolamide to timolol in patients with glaucoma and ocular hypertension - A three-month randomised study.

To compare the efficacy and safety of latanoprost monotherapy or dorzolamide and timolol in glaucoma patients inadequately controlled on adrenergic beta-receptor antagonist therapy. A total of 164 patients with primary open-angle glaucoma, capsular glaucoma or ocular hypertension were included in a three-month, open-label, randomised multicentre study. Patients with open-angle glaucoma were required to have IOP at least 22 mmHg and patients with ocular hypertension were required to have IOP at least 27 mmHg, on treatment with one or two ocular hypotensive drugs of which at least one had to be a beta-blocker. All patients were treated with timolol, 5 mg/ml twice daily, for a 2-4 week run-in period. They were then randomised to latanoprost, 50 g/ml once daily, or timolol 5 mg/ml plus dorzolamide, 20 mg/ml twice daily. The difference in mean diurnal IOP change from baseline to month 3 was compared in the two groups. When patients were switched to latanoprost, mean diurnal IOP was reduced by 5.2 mmHg (23%) compared to 4.0 mmHg (17%) in the group in which dorzolamide was added to timolol. The difference of 1.2 mmHg was statistically significant (p= 0.005). The majority of adverse events during both treatments were judged as mild. The results suggest that a switch to latanoprost monotherapy is an alternative to combined treatment with timolol and dorzolamide in patients inadequately controlled on a topical adrenergic beta-receptor antagonist alone. (Eur J Ophthalmol 2000; 10: 198-204).

Synchronized Separation of Timolol from Some Prostaglandin Analogs (Bimatoprost, Latanoprost and Travoprost) for Determination in their Combined Pharmaceutical Formulations Using RP-HPLC

A rapid, precise and selective RP-LC method was developed for the simultaneous determination of the well-known beta blocker, Timolol (TIM), along with some of the most commonly prescribed prostaglandin analogues, namely; Bimatoprost (BIM), Latanoprost (LAT) and Travoprost (TRV), in laboratory prepared mixtures and in their combined pharmaceutical formulations. The chromatographic separation was carried out using gradient elution mode with a mobile phase consisting of 25 mM phosphate buffer (pH 3 ± 0.1), acetonitrile and methanol at a flow rate of 1 mL/min on a stationary phase composed of Thermo Hypersil BDS C18 (4.6×250 mm, 5 μm) column. UV detection was carried out at 295 nm and 210 nm wavelength gradient at 25°C. The method was validated according to ICH guidelines. Linearity, accuracy and precision results were satisfactory over the concentration ranges of 10.00-600.00 μg/ml for TIM and 1.00-60.00 μg/ml for BIM, LAT and TRV. The correlation coefficients (r2 values) were 0.9965 for TIM, 0.99995 for BIM, 0.99998 for LAT and 0.99996 for TRV. The method was successfully applied for the determination of TIM in its synthetic mixture and co-formulated eye drops with each of the three prostaglandin analogues BIM, LAT or TRV. The developed method is specific and accurate for the quality control and routine analysis of the cited drugs in their pharmaceutical preparations. This method is considered global and can be applied to all prostaglandin analog combinations with TIM.

Does preservative content affect drug permeability? The permeability analysis invitro of 3 ophthalmic Latanoprost formulations in a human epithelial cell culture model.

Comparative permeability analysis of the 3 following Latanoprost formulations intended for ophthalmic use: Xaloptic (Pol­pharma S.A.), Xalatan (Pfizer Europe MA EEIG) and Monoprost (Thea Pharma S.A.) across human corneal epithelium (HCE-T culture model) in vitro. Permeability analysis was performed under conditions suitable for latanoprost API (active pharmaceutical ingredient). Statistical analysis of permeability and drug quantity after passing across a cellular membrane was performed using ANOVA test and Tukey’s multiple comparison test (GraphPad Prism 6.00 for Windows, GraphPad Software, La Jolla California, USA The following differences in permeability were noted between the analyzed drugs: The permeability rates for Xaloptic and Xalatan were 5.49 ± 1.64 x 10-6 cm/s and 4.66 ± 1.13 x 10-6 cm/s, respectively. Xaloptic showed the highest permeability through human corneal epithelium (23.70 ± 1.71 x 10-6 cm/s) and the highest conversion rate (28.13 ± 5.85%). As compared to Xaloptic, Xalatan slight, yet statistically significant differences with the permeability rate of 21.21 ± 1.29 x 10-6 cm/s and a conversion rate of 18.41 ± 2.96%). Monoprost demonstrated the lowest permeability (0.39 ± 0.07 x 10-6 cm/s) and thelowest conversion rate (0.34 ± 0.16%). The differences in permeability and bioavailability between the 3 ophthalmic latanoprost formulations are attributable to the differences in their composition. They are also related to the content of preservative in each preparation.

Fast separation and quantification of three anti-glaucoma drugs by high-performance liquid chromatography UV detection

In this study, a simple and accurate high-performance liquid chromatography method was developed and validated for fast separation of three anti-glaucoma drugs: timolol maleate (TM), brimonidine tartrate (BM), and latanoprost (LP). Separation of the three drugs was achieved in < 6 minutes using a BDS Hypersil phenyl column and a mobile phase consisting of acetonitrile: 25mM phosphate buffer, pH 4.0 (50: 50, v/v) at 1.2 mL/min with UV detection at 210 nm. The method was linear over the concentration ranges of 5.0–200.0 μg/mL, 2.0–80.0 μg/mL and 1.0–25.0 μg/mL with lower detection limits of 0.21 μg/mL, 0.10 μg/mL and 0.11 μg/mL for TM, BM and LP, respectively. The method was applied for the determination of two fixed-dose combination eye drops for the treatment of glaucoma, containing TM together with either BM or LP. Commercial samples of single-ingredient ophthalmic solutions containing the studied drugs were also successfully analyzed. The results obtained by the proposed method were favorably compared with those obtained by the comparison methods using Student's t test and the variance ratio F test.

In vitro Effects of Prostaglandin Analogs on Cultured Astrocytes Obtained from the Lamina Cribrosa

Purpose: To evaluate the effects of prostaglandin analogs (PGAs) on cell viability and apoptosis in cultured astrocytes obtained from the lamina cribrosa (LC) of the human optic nerve head (ONH).Methods: Astrocytes were cultured from LC samples obtained from human donor ONH and treated with three kinds of acid form of PGAs: latanoprost (LAT-A), tafluprost (TAF-A), and bimatoprost (BIM-A) (0.1, 1, 10, 50 and 100 ug/mL). Cell viability was assessed using the WST-1 assay. Cell apoptosis was measured using the deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay. Apoptotic protein expression was evaluated using western blot analysis.Results: ONH astrocytes expressed FP receptor in western blot analysis. In the presence of 0.1 ug/mL of LAT-A, BIM-A, and TAF-A, the cell viability was 85%, 85% and 82%, respectively. WST-1 assay revealed about 50% of cell viability following treatment with 50 ug/mL of all PGAs. After exposing astrocytes to 10 ug/mL of each PGA for 24 hours, apoptotic cells were stained in TUNEL assay. Western blot analysis revealed that the PGAs up-regulated Bax (pro-apoptotic protein) and down-regulated Bcl-xL (anti-apoptotic protein) in the astrocytes.Conclusions: PGAs affected cell viability in cultured astrocytes obtained from human ONH LC. PGA treatment may induce apoptosis in ONH astrocytes.

DEVELOPMENT AND INVESTIGATION OF TIMOLOL MALEATE AND LATANOPROST COMBINATION LIPOSOMES FOR THE TREATMENT OF GLAUCOMA

In this study liposomes were developed and evaluated for timolol maleate (TM) and latanoprost (LP) by lipid film hydration technique for the treatment of glaucoma. A 3 2 factorial design was utilized to study the effect of the molar ratio of 1, 2 – Dipalmitoyl - sn - glycero - 3 - phosphocholine ( DPCC ) ( X 1 ) and cholesterol ( X 2 ) on vesicle size, drug entrapment efficiency and in - vitro release study. Fourier transform infrared spectroscopy ( FT - IR) studies were performed to investigate and predict an y physiological interactions between components in the formulation. The liposomal vesicles were found to be uniform in size and shape. The drug entrapment efficiency values for the seven batches showed a variation from a minimum of 56.65 ± 1.39 % to maximu m of 70.24 ± 1.14 %. This clearly indicates that the drug entrapment value is strongly dependent on the variables selected. The Zeta potential, av erage particle size and poly dispersibility index was found to be - 17.3 mV, 240 nm and 0.114 respectively. Mos t of the formulations were found to have a linear release and the formulations were found to provide approximately 72 % - 55 % of drug release for TM and LP respectively within a period of 6 h. Kinetic study reveals that release mechanism depends on swelli ng, diffusion and relaxation. Best formulation (F2) was found to be sterile and stable and free from microorganisms and passes the isotonicity test. Reduction in intra ocular pressure ( IOP ) was greater in liposomes as compared to the marketed product of al one and combination medication . A latanoprost - timolol maleate fixed combination, has the advantage of a more convenient delivery system as well as providing a simple summing effect of the two constituents .

Randomized parallel group study of 0.0015% tafluprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension (comparison with 0.005% latanoprost ophthalmic solution)

To confirm the non-inferiority of the IOP-lowering effect of the 0.0015% Tafluprost ophthalmic solution to the 0.005% Latanoprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.Safety was also compared between two groups. This study was conducted from August 2008 to December 2009, at five clinical trial sites in China. Patients of this study population was diagnosed with primary open-angle glaucoma or ocular hypertension in both eyes.Subjects were randomized into 0.0015% Tafluprost group or 0.005% Latanoprost group.Intraocular pressure (IOP) measurement by Goldmann applanation tonometer, slit-lamp microscopy, Gonioscopy, Fundascopy, Visual acuity test, Perimetry, Blood pressure and pulse rate, Subjective symptoms were compered between two groups at Week 0, Week 2 and Week 4.For main effectiveness evaluation index adopt the bad effect evaluation, safety evaluation index by Fisher's exact test probability method. The 246 subjects/246 eyes were randomized (Tafluprost group:122 subjects/122 eyes, Latanoprost group:124 subjects/ 124 eyes). Change in the IOP at 17:00 of Week 2 is (8.8 ± 3.8) mmHg and (8.9 ± 4.4) mmHg (1 mmHg = 0.133 kPa) in Tafluprost group and Latanoprost group. Percent change in the IOP at 17:00 of Week 2 is (33.2 ± 12.8)% and (34.4 ± 14.1)% in Tafluprost group and Latanoprost group. Change in the IOP at 17:00 at the end of treatment is (9.8 ± 4.0) mmHg and (9.2 ± 4.1) mmHg in Tafluprost group and Latanoprost group. Percent change in the IOP at 17:00 at the end of treatment is 37.2% ± 13.4% group and 35.7% ± 13.0% in Tafluprost and Latanoprost group.In addition, distribution of subjects with percentage decrease of IOP > 30% was 72.5% in Tafluprost group higher than 63.8% in Latanoprost group. The major adverse reactions were conjunctival hyperemia, eye irritation, eye pain and foreign body sensation. The incidence of adverse reactions is 31.7% in Tafluprost group and 20.8% in Latanoprost group. The inter-group difference had no statistical significance. Efficacy and safety of Tafluprost ophthalmic solution are no less than Latanoprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.

Multicenter trial of therapeutic efficacy and safety of domestic latanoprost on primary open angle glaucoma and ocular hypertension

Background Prostaglandin eye drops is front-line medicines of lowing intraocular pressure for primary open angle glaucoma (POAG),but its price is higher for long-term application.Domestic latanoprost drops has been applied in clinic.However,its trial of lowing intraocular pressure effect and safety from sizable sample and multi-center is lack.Objective This study was to observe the efficacy and safety of domestic latanoprost for POAG and ocular hypertension.Methods This prospective,multicenter trial was conducted at 25 hospitals in 5 territories of China,and 837 eyes of 576 patients with POAG and ocular hypertension were recruited in the hospitals based on the uniform criteria.Domestic latanoprost drops was topically used once per day at night for 3 months.Intraocular pressure (IOP) was measured 1 month and 2 months,3 months to assess the efficacy of drug,and vision acuity,blood pressure,pulse,ocular symptoms and signs were observed to evaluate the safety of the drug.This study approved by the Ethics Committee of Wuhan General Hospital of Guangzhou Military Command,and all patients were informed consent and signed informed consent.Results IOP was (28.36±7.86),(19.66±5.46),(19.59±7.86) and (19.35 ± 5.03) mmHg in pretreatment and posttreatment 1 month,2 months and 3 months,respectively,showing a significant difference among various time points (F =748.325,P =0.000),and the IOPs were markedly lower in posttreatment than those in pretreatment (all at P＜0.001).The falling range of IOP was (30.43 ±7.18)％,(30.19 ± 8.72)％,(30.71±9.90) ％ in posttreatment 1 month,2 months and 3 months,respectively.The efficiency was 95.70％,91.76％ and 88.05％ in 1 month,2 months and 3 months.Conjunctival hyperemia was observed in 13％ eyes at the end of following-up.No drug-related systemic and other ocular adverse reactions were found.Conclusions Domestic latanoprost drops can low IOP effectively without serious adverse reaction in POAG and ocular hypertensive patients. Key words: Prostaglandin drug; Latanoprost drops/domestic; Glaucoma/open angle, therapy; Intraocular pressure

Efficacy observation and safety evaluation of latanoprost and timolol maleate in treating open angle glaucoma

Objective To study the efficacy and safetv of latanoprost and timolol maleate in treating open angle glaucoma.Methods Open angle glaucoma patients were enrolled and randomly divided into observation group (given latanoprost and timolol maleate) and control group (given timolol maleate).Then RNFL thickness,visual field defect degree were detected and adverse reaction was observed.Results ① Field defect in above view field,lower visual field,visual field,nasal visual field of observation group were lower than those of control group; ② RNFL thickness in above view field,lower visual field,visual field,nasal visual field of observation group were higher than those of control group; ③There were no statistical significant difference found in incidence of adverse reaction cases between two groups.Conclusion Latanoprost and timolol maleate have positive clinical value for it can improve RNFL thickness,visual field defect and achieve equal safety. Key words: Open angle glaucoma; Latanoprost; Timolol maleate; Visual field defect

Neutralization of polyethylene glycol on ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost

Background Reducing ocular surface toxicity induced by topical antiglaucoma medications,and thus improving the therapeutic compliance of glaucomatous patients to treating drug become an urgent issue in the long-term antiglaucomatous therapies.Whether polyethylene glycol,a new type of artificial tear,can play a protective role from ocular surface toxicity induced by topical antiglaucoma medications remains further study.Objective The present study was to investigate the protective effect of polyethylene glycol on ocular surface toxicity induced by prolonged use of benzalkonium chloride-preserved latanoprost eye drops.Methods Thirty adult female New Zealand rabbits were randomly divided into normal control group,phosphate buffer solution (PBS) group and polyethylene glycol eye drops group.PBS with 0.005％ latanoprost was topically administered for consequent 60 days in the PBS group,and 0.005％ latanoprost with polyethylene glycol eye drops was used at the same way in the polyethylene glycol group.Schirmer Ⅰ test,fluorescein and rose bengal staining of cornea and conjunctiva,conjunctiva impression cytology specimens collecting were performed before experiment as well as 31 and 61 days after administration of drug.Histomorphological and ultrastructural changes of cornea and conjunctiva were observed under the light microscopy,scanning and transmission electron microscopy on day 61.Results The score of corneal fluorescine staining was significantly different among the control group,PBS group and polyethylene glycol group (H =25.265,P＜0.001 ;H=29.426,P＜0.001) on day 31 and day 61.Significant difference also was found in the score of rose bengal staining of cornea and conjunctiva (H=26.167,P＜0.001 ;H =29.212,P＜0.001),Schirmer Ⅰ test value (F=4.746,P＜0.05) and conjunctival goblet cell density (F=18.055,P＜0.001).Compared with the control group,corneal fluorescein scores [0(0,1.0) vs.3 (2.0,3.0)] and rose bengal scores [0(0,1) vs.2(2,3)] were significantly increased (both P＜0.001),and Schirmer Ⅰ test value scores and conjunctival goblet cell density were decreased ((5.18±0.46/)mm vs.(9.43±0.57)mm;(53.04±2.98)/HP vs.(87.73±2.34)/HP) (both P＜0.01)on day 61.Impaired microvilli and organelles of the corneal and conjunctival epithelial cells were observed.Compared with PBS-treated group,PEG-treated group showed decrease in fluorescein [3(2.0,3.0) vs.1 (0.5,1.0)] and rose bengal scores [2 (2,3) vs.1 (0,1)] (both P＜0.001),increase in Schirmer Ⅰ test value scores [(7.00±0.71)mm vs.(5.18±0.46) mm,P＜0.05],increase in goblet cell density ((63.88±3.32)/HP vs.(53.04±2.98)/HP,P＜0.05) and improvement of grading scores of conjunctival epithelium on day 61.In addition,complete mierovilli and cell organelles were found in the corneal and conjunctival epithelial cells in the polyethylene glycol group.Conclusions Topical application of polyethylene glycol can decrease the ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost. Key words: Polyethylene glycol; Latanoprost; Benzalkonium chloride; Ocular surface toxicity

Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost

Although useful for reducing intraocular pressure (IOP), bimatoprost (BIM) can cause deepening of the upper eyelid sulcus (DUES), one of the symptoms of prostaglandin-associated periorbitopathy (PAP). We investigated recovery from BIM-induced DUES after switching treatment to latanoprost (LAT). Prospective, observer-masked, open-label study. Twenty-five Japanese patients suffering from primary open-angle glaucoma treated with LAT in both eyes for longer than 6months and requiring further IOP reduction were prospectively enrolled in the study. During the first 6months after the switch to BIM, 15 of the 25 patients (60%) developed DUES. Among these patients, 13 were switched back to LAT and re-examined for DUES at 2-month intervals for an additional 6months. Two months after the switch back to LAT, for 11 of the 13 patients (85%) the DUES symptoms had either decreased or disappeared, and this was maintained for at least 6months. During this time, 6 of 8 patients (75%) subjectively positive for DUES self-reported a decrease in DUES. Although DUES is a frequent side effect of treatment with BIM, switching to LAT may reverse the condition for most patients.

Effects of concomitant administration of latanoprost and pilocarpine on the intraocular pressure of experimentally glaucomatous rabbits

Summary The purpose of this study was to evaluate the effects of a combination of latanoprost and pilocarpine on the intraocular pressure in experimentally glaucomatous rabbits. Ocular hypertension was induced in 11 conscious rabbits by the oral administration of tap water (70 mL/kg) via an orogastric tube. The study was conducted in three therapeutic groups to test the effects of latanoprost (group L), pilocarpine (group P) and a combination of the two drugs (group LP). After evaluating the first drug, a washout period of 1 week was allowed before the second drug was evaluated. The left eye of rabbits in group L received one drop of normal saline and one drop of 0.005% latanoprost, in group P one drop of normal saline and one drop of 2% pilocarpine and in group LP, one drop of 0.005% latanoprost and one drop of 2% pilocarpine. The right eyes of all rabbits received two drops of normal saline (as control eyes). The intraocular pressure (IOP) and pupil diameter (PD) were measured before and at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min post-water loading. The results showed that eyes, which received pilocarpine had a significantly lower increase in IOP at 15, 30, 45 and 60 min after drug administration compared to placebo eyes, whereas groups L and LP did not prevent an IOP increase. The PD decreased in groups P and LP throughout the study, whereas it did not change in group L. It was concluded that the topical administration of latanoprost alone or in combination with pilocarpine appeared to have no effect on IOP in acute ocular hypertensive rabbits.

Effects of switching to SofZia-preserved travoprost in patients who presented with superficial punctate keratopathy while under treatment with latanoprost

To investigate the effects of switching to SofZia-preserved travoprost (TRV) on superficial punctate keratopathy (SPK) observed in patients using benzalkonium chloride (BAC)-preserved latanoprost (LAT). Patients with either primary open-angle glaucoma or ocular hypertension treated with LAT for at least 1 month who presented with SPK participated in this prospective, multicenter, open-label uncontrolled study. After the switch from LAT to TRV, patients were monitored at 2 weeks and at 1, 2, and 3 months. The use of concomitantly employed ophthalmic solutions was continued during the observation period. The intensity of SPK in each of five areas defined on the cornea was scored on a standard scale. Repeated measurements were tested with a linear mixed model. Of the 48 patients enrolled, 45 patients completed the study. After the switch to TRV, the mean SPK score in the whole cornea decreased significantly at every observation point (P < 0.0001 at each point) while intraocular pressure did not change significantly. Throughout the observation period, the SPK score tended to be higher in patients using a larger number of concomitant medications that contained BAC. Switching to TRV improved SPK observed in a population using LAT, likely because of a decrease in exposure to BAC.

Effects of Switching from Topical β-Blockers to Latanoprost on Intraocular Pressure in Patients with Normal-Tension Glaucoma

The effects of switching from topical beta-blockers (beta) to latanoprost (LA) on intraocular pressure (IOP) and IOP-reduction rate (IOP-RR) in patients with normal-tension glaucoma (NTG) were investigated. Sixty (60) NTG patients (60 eyes) were divided into three equal groups receiving carteolol hydrochloride (group A), nipradilol (group B), and betaxolol hydrochloride (group C) twice-daily for 3 months. The drugs were changed to topical LA administered once-daily for the next 3 months. Baseline IOP was 14.4 +/- 0.9, 14.6 +/- 0.6, and 14.6 +/- 0.9 mmHg in groups A, B, and C, respectively. At 3 months, IOP was 12.4 +/- 0.6, 13.4 +/- 0.6, and 12.9 +/- 0.8 mmHg and 10.5 +/- 0.5, 11.1 +/- 0.8, and 11.7 +/- 0.8 mmHg at 6 months in groups A, B, and C, respectively. At 3 months, IOP-RR was 10.4 +/- 5.5, 9.5 +/- 2.6, and 10.8 +/- 4.7% and 24.1 +/- 4.3, 22.9 +/- 5.9, and 19.4 +/- 3.8% at 6 months in groups A, B, and C, respectively. The groups did not significantly differ in the first 3 months regarding IOP and IOP-RR. Switching to LA significantly decreased IOP and increased IOP-RR in all groups. In NTG patients, LA reduced IOP more effectively than the beta tested.

Profound sweating episodes and latanoprost

Profound sweating episodes and latanoprost

Effects of latanoprost eye drops on the proliferation of human Tenon's fibroblasts in tissue culture

To observe whether there is a direct effect of latanoprost eye drops on the proliferation of cultured human Tenon's capsule fibroblasts (HTCFs) in vitro. Human Tenon's capsule fibroblasts were cultured in vitro. Latanoprost eye drops was serially diluted in order to make nine concentrations ranging from 5.00 microg/ml, 0.50 microg/ml, 0.05 microg/ml to 5 x 10(-8) microg/ml. Fibroblasts growth was evaluated with MTT assay. Morphological changes were observed under phase contrast microscope. Majority of cultured human Tenon's capsule fibroblasts was dead at the concentration of Latanoprost (5 microg/ml), the A values were significantly decreased (P < 0.01). There were no significant changes of the A values (P > 0.05) in lower concentration (under 0.05 microg/ml) compared with control. there was no statistical difference in proliferation of HTCFs after latanoprost treatment for 24 hours, 48 hours, 72 hours. Latanoprost has the toxic effect on the fibroblast at higher concentrations, but there is no influence on the proliferation of HTCFs at the lower concentrations.

Naturalistic, prospective study of glaucoma and ocular hypertension treatment in France: Strategies, clinical outcomes, and costs at 2 years.

To prospectively observe second-line treatment strategies, their clinical outcomes, and treatment costs in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) in France. Second-line patients were recruited from September 14, 1998, to December 20, 2000, in 37 centers and were followed for up to 2 years. Outcomes were numbers of and reasons for treatment changes, changes in clinical parameters (intraocular pressure (IOP) levels, visual field defects, and optic nerve excavation), and direct medical costs associated with glaucoma management. This article reports results of the final analysis of 2-year follow-up data for patients with at least two contacts with a study ophthalmologist. Data were analyzed for 346 patients and 672 treated eyes. Monotherapy was used as first-line therapy in 92.0% of eyes. Second-line treatment was initiated an average of 2.8+/-0.2 years after diagnosis, primarily due to insufficient IOP control (60.3%) and adverse drug reactions (18.3%). Relative risk (RR) (95% CI) for adverse drug reactions (ADR) under monotherapy was 1.00 (1.00-1.00) under beta blockers (n=116) versus 0.40 (0.16-0.64) under latanoprost (n=21), 2.30 under carbonic anhydrase inhibitors (n=29), and 2.90 under adrenergics (n=38); RR for ADR under combination therapy was 1.00 (1.00-1.00) for unfixed combinations without latanoprost (n=66) versus 0.11 (0.00-0.22) for unfixed combinations of latanoprost + timolol (n=3). Cardiac or pulmonary problems have been reported in 26.9% of patients. Persistency on initial therapy was 62.5% (95% CI 53.0-72.0) for latanoprost monotherapy versus 41.1% (34.8-47.4) for beta-blocker monotherapy and 43.6% (26.6-60.6) for the latanoprost + timolol combination versus 29.8% (15.2-44.4) for combination therapies that did not include latanoprost. Average daily cost for latanoprost monotherapy was similar to that for patients who failed beta-blocker monotherapy: latanoprost + timolol did not cost more than therapeutic combinations without latanoprost. Insufficient IOP control and adverse drug reactions are the two main reasons for changing first-line treatment in patients with POAG or OH. After 2 years, second-line treatment with latanoprost, as monotherapy or combined with timolol, provides superior safety and persistency to treatment at an acceptable cost. (Eur J Ophthalmol 2005; 15: 562-80).

Cystoid macular edema associated with latanoprost after uncomplicated cataract surgery.

To report clinically symptomatic and angiographically documented cystoid macular edema (CME) associated with the use of latanoprost in two pseudophakic eyes after uncomplicated cataract surgery. Retrospective review of two patients who had history of latanoprost use and uncomplicated cataract surgery and described blurred vision in the first postoperative month. Ocular examination revealed CME, which was confirmed by fluorescein angiography. The visual acuities of patients improved and the CME was angiographically resolved after discontinuation of latanoprost and the initiation of nonsteroidal anti-inflammatory eyedrops and oral acetazolamide. Until a causal relationship between CME and latanoprost is proved or disproved, caution in its use in pseudophakic patients would be prudent. (Eur J Ophthalmol 2005; 15: 158-61).