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Background: Dry eye is a condition related to long-term topical eye therapy. We wish to evaluate the effectiveness and tolerability of preservative free prostaglandin drops versus benzalkonium chloride containing prostaglandin drops in the treatment of glaucoma., Methods: Patients undergoing prostaglandin monotherapy underwent a washout period of at least 1 month after which baseline measurements of dry eye severity were taken. Patients were randomised to receive either 0.0015% tafluprost drops or 0.005% latanoprost preserved with 0.02% benzalkonium chloride. Repeat measurements were taken after a 2-month interval., Results: Thirty-five patients completed randomised treatment. No significant difference between groups was found in objective and subjective measurements of dry eye severity. No significant difference was found in measurement of treatment effectiveness., Conclusion: Preservative-free and benzalkonium chloride-containing drops were found to be equally effective in lowering IOP with no significant difference in either subjective or objective measurements of dry eye severity., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Purpose: To investigate the long-term effects of topical latanoprost 0.005% treatment on pupillary functions in early-stage primary open-angle glaucoma (POAG) eyes using automated pupillometry., Methods: This prospective study involved 20 eyes of 20 treatment-naive subjects with early-stage POAG. After comprehensive ophthalmic examination, static and dynamic pupillometry measurements were performedbefore treatment, at the 1st follow-up visit (1.10 ± 0.30 months) and the 2nd follow-up visit (25.85 ± 10.26 months) after treatment initiation. Dynamic parameters included resting diameter (mm), amplitude (mm), latency (ms), duration (ms), and velocity (mm/s) of pupil contraction and dilation. Static pupillometry parameters were pupil diameter (PD, mm) in high-photopic, low-photopic, mesopic and scotopic conditions., Results: The velocity of pupil dilation significantly decreased during the 1st visit ( p  = 0.008) and the 2nd visit ( p  = 0.0003) of treatment compared to the pre-treatment visit. The resting PD was also significantly higher after the 1st visit ( p  = 0.003) and the 2nd visit ( p  = 0.001) compared to the pre-treatment visit. However, the difference in resting PD measured between the 1st and 2nd visits did not reach statistical significance ( p  = 0.065). There were no significant changes in other dynamic parameters ( p  > 0.05 for all). Additionally, a mild, but not significant, mydriatic effect was observed in PD measurements under scotopic, mesopic and low photopic lighting conditions after follow-up. None of the static and dynamic parameters correlate with age, changes in intraocular pressure (IOP) or mean deviation (MD) values of visual field tests., Conclusion: The long-term topical latanoprost 0.005% treatment in early-stage POAG has a slight mydriatic effect on the pupil. Further longitudinal clinical studies with larger patient cohorts are necessary to better understand the effects of latanoprost on pupillary functions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: We evaluated the IOP-lowering efficacy and safety of latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta®), the first topical nitric oxide-donating prostaglandin analog (PGA), in clinical practice., Materials and Methods: A retrospective medical chart review from July 2021 to July 2023 of patients with open-angle glaucoma receiving LBN with at least 1 year follow-up was conducted. All included patients received LBN 0.024% as a replacement for a PGA, with examinations at 1-, 3-, 6-and 12-months follow-up. Main outcome measures were IOP, retinal nerve fiber layer thickness, visual fields before/after LBN use and adverse effects. Subgroup analysis with glaucoma types and PGA use were performed for additional IOP reduction after LBN use., Results: Among 78 included patients, 47 patients (81 eyes), 60% with open-angle glaucoma (OAG) remained on LBN throughout 12-month follow-up. Baseline IOP was 18.2±4.2 mm Hg, and Prostaglandin analog (PGA)-IOP was 14.4 ± 3.0 mm Hg (21% mean IOP reduction). After switched to LBN, mean additional IOP reduction was 1.0 mm Hg at month 1, and the greatest reduction was 1.6 mm Hg (8.8% additional mean IOP reduction) at month 12 (P<0.0001). Subgroup analysis (NTG, 73%) showed that mean additional IOP reduction at month 12 was 1.3±2.0 mm Hg in NTG group and 2.1±3.2 mm Hg in POAG group (7.7% vs. 8.7% additional IOP reduction rates, P = 0.23). Subgroup analysis of PGA use at month 12 was 1.8±2.3 mm Hg in tafluoprost group and 0.5±1.7 mm Hg in travoprost group (9.5% vs.2.6% additional IOP reduction rates, P = 0.02). Tolerable ocular adverse effects included irritation (n = 16, 19.8%), mild conjunctival hyperemia (n = 11, 13.6%), dark circles (n = 4, 4.9%) and blurred vision (n = 2, 2.5%). There were no significant visual field and retinal nerve fiber layer thickness changes after 12 months of treatment with LBN 0.024%., Conclusions: Although high intolerable adverse effects including conjunctival hyperemia and eye irritation happened in the first month, remaining sixty percent of patients exhibited statistically significant additional IOP reductions in the replacement of other PGAs during 12 months of clinical use of LBN 0.024%., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hsueh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients., Methods: In this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy., Results: The mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048)., Conclusion: POAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024. Published by Elsevier B.V.)

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P 4 ) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P 4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To assess the ocular hypotensive effect of 15-keto fluprostenol, the oxidized metabolite of travoprost, on glaucoma patients, through a randomized double-masked placebo-controlled study., Methods: Twelve patients with ocular normal tension glaucoma (NTG) (intraocular pressure [IOP] < 22 mmHg) were enrolled. In order to ensure patient compliance to treatment, all study subjects were hospitalized. In each patient, the eye to be submitted to the treatments was randomly chosen. After hospital admission (day 1), those patients received for 5 days at 8 P.M. either one drop of 15-keto fluprostenol (35 μg/ml) or one drop of placebo. IOP evaluation was performed within 8 A.M. and 8 P.M. for 6 days. Furthermore, we performed a determination of cardiovascular parameters before and after the treatments., Results: Starting with the first IOP measurement after the first treatment (8 A.M. on day 2), IOP was reduced of about 14% in the eyes treated 15-keto fluprostenol, in comparison with baseline IOP values of 15-keto fluprostenol-treated patients. The IOP reduction in the 15-keto fluprostenol-treated group was significantly compared to placebo group (p < 0.05) starting from day 3 till day 6 of the study. Except for mild hyperemia in one 15-keto fluprostenol-treated eye, no other side effects were observed or reported by the enrolled patients., Conclusions: The travoprost metabolite 15-keto fluprostenol was effective in decrease IOP and maintained IOP reduction along 5 days of treatment. The 15-keto fluprostenol can be developed as a good candidate for once-a-day NTG patients' treatment.

Background: Eyelashes have both a protective and an aesthetic function. Hypotrichosis of the eyelashes may negatively influence an individual's self-perception., Objective: To evaluate efficacy and safety of topical administration of a new cosmetic preparation containing 15 keto fluprostenol isopropyl ester (80 µgr/mL) for the treatment of idiopathic hypotrichosis of the eyelashes., Methods: This is a monocentric, double-blind, vehicle-controlled study. Forty patients (18 years) with idiopathic hypotrichosis (GEA 1 or 2), who also exhibit feelings of low confidence, based on the ESQ score, were divided into two groups. Group 1: twenty women treated with once-daily 15 keto fluprostenol isopropyl ester gel and Group 2: twenty women treated only with the vehicle gel., Results: Group 1: The average difference in eyelash length measured at the midpoint of palpebral margins between T0 and T2 for Group 1 was 1633 mm and for Group B was 0.25 (P < 0.0001). Comparing the ESQ questionnaires of Groups 1 and 2 from T0 to T2, only the 80% of the patients of Group 1 declared to dedicate less time to the application of cosmetic mascara, having longer and darker lashes at T2 vs patients of Group 2, of which only 20% reported longer and darker eyelashes at T2. About safety, only one patient of Group 1 experienced sensation of ocular sensation heaviness and headache. No other side effects were referred., Conclusions: 15 keto fluprostenol isopropyl ester gel was effective in enhancing eyelash growth, with an excellent safety profile., (© 2019 Wiley Periodicals, Inc.)

Importance: Glaucoma treatment has often been associated with adverse side-effects from preservatives that are included in the used eye drops., Background: To evaluate changes in the ocular surface and the presence of prostaglandin-induced corneal disorders after being switched from latanoprost 0.005% to low preservative tafluprost 0.0015% ophthalmic solution., Design: Single centre, prospective study., Participants: Patients with primary open-angle glaucoma or ocular hypertension that had received treatment with once daily latanoprost 0.005% ophthalmic solution for control of intraocular pressure (IOP) for 3 months, with a score of above 1 on the National Eye Institute (NEI) ocular surface staining scale., Methods: Following the ≥3 month latanoprost treatment period, patients were switched to once daily low preservative tafluprost 0.0015% ophthalmic solution. Patients were followed for a minimum of 3 months., Main Outcome Measures: Ocular surface changes were assessed by fluorescein staining score (NEI scale). Additional evaluations included tear break-up time, hyperaemia score, subjective symptoms, changes in intraocular pressure and presence of adverse reactions., Results: Out of 59 patients enrolled, 51 were included in the final analysis. Fluorescein staining scores at baseline, prior to treatment switch, were 6.9 ± 3.1 and 3.3 ± 2.7 at the end of the study period (change in scores was -3.6 ± 2.2 [P < 0.001]). At last follow-up, significant improvements were observed in tear break-up time, hyperaemia score and subjective symptoms (all P < 0.05)., Conclusions and Relevance: The clinical signs of ocular surface disease and subjective symptoms of dry eyes improved following the switch to low preservative tafluprost and demonstrated comparable IOP lowering effectiveness., (© 2018 The Authors Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

OBJECTIVE To compare morphology of the ciliary cleft (CC) region in dogs after topical administration of latanoprost, pilocarpine, or a combination of latanoprost and pilocarpine. ANIMALS 6 Beagles. PROCEDURES A prospective 4-phase crossover study with washout periods was performed. Latanoprost (phase L), pilocarpine (phase P), pilocarpine followed by latanoprost (phase PL), and latanoprost followed by pilocarpine (phase LP) were administered to the right eye. Artificial tears were administered to the left eye (control eye). For each phase, pupil diameter and intraocular pressure (IOP) were measured and ultrasonographic biomicroscopy was performed 2 hours after topical treatment. Angle opening distance (AOD), ciliary cleft width (CCW), ciliary cleft length (CCL), and ciliary cleft area (CCA) were evaluated. RESULTS All treated eyes had marked miosis without significant differences in pupil diameter among phases. Significant IOP reductions were detected for all phases, except phase P. The AOD and CCA were significantly increased in all phases for treated eyes, compared with results for control eyes. The CCW was significantly increased in phases P, PL, and LP; CCL was significantly increased in phases PL and LP. Comparison of treated eyes among phases revealed that CCW differed significantly between phases L and P and between phases L and PL. CONCLUSIONS AND CLINICAL RELEVANCE Prostaglandin-mediated and cholinergic-mediated miosis caused variations in CC configurations. When latanoprost and pilocarpine were used in combination, the first drug administered determined the cleft morphology, which was not fully reversed by the second drug. The CC morphology did not fully explain IOP reductions.

Purpose: To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma., Methods: This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared., Results: Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P < 0.05)., Conclusion: All three fixed combinations effectively controlled IOP for 24-h and had a similar effect on diurnal and nocturnal IOP variations.

Purpose: To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy., Study Design: An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined., Results: The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group., Conclusion: Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

Purpose: To evaluate the efficacy and safety between two generic prostaglandins Lataz-Xalaprost (Greece) and the corresponding original drops (Xalatan ® )., Material and Methods: In this prospective randomized study, 60 patients diagnosed with open-angle glaucoma or ocular hypertension were enrolled, who had never received antiglaucoma treatment. Subjects were divided randomly into three groups (Xalatan, Lataz, and Xalaprost groups) and they were studied over 16 weeks. At each visit, the mean applanation tonometry values and tear break-up time were measured. The Ocular Surface Disease Index questionnaire was used to evaluate patient's symptoms., Results: There was a statistically significant difference (p < 0.001) in the mean values of the intraocular pressure between the baseline and the last visit (Xalatan group: from 23.11 ± 1.61 mmHg to 15.81 ± 1.22 mmHg, Lataz group: from 23.26 ± 1.33 mmHg to 15.80 ± 1.47 mmHg, and Xalaprost group: from 23.08 ± 1.45 mmHg to 16.08 ± 1.38 mmHg). Both generic eye drops showed mean percentage intraocular pressure reduction comparable to the standards of prostaglandin analogues (Xalatan: 31.57%, Lataz: 32.06%, and Xalaprost: 30.34%). Xalatan reduced the tear break-up time less, followed by Lataz and then by Xalaprost (Xalatan: from 8.5 to 8 s, Lataz: from 8.2 to 7.4 s, and Xalaprost: from 8.7 to 7.7 s). Xalatan presented the best safety profile, followed by Lataz and least was Xalaprost, according to Ocular Surface Disease Index questionnaire's results., Conclusion: No significant difference was recorded in the effectiveness of each generic prostaglandin compared to the original. Furthermore, no patient had to change medication. The differences that arose in the safety profile of the three eye drops suggest a prompt closer initial monitoring of patients who are administered generic eye drops.

The combined effect of six consecutive timed artificial inseminations (TAIs) on pregnancy rates, following two different synchronization protocols on buffalo heifers, over a period of seven months typically characterized by low breeding performances, were investigated in this study. A total of 2189 TAIs were performed on 1463 buffalo heifers within a large buffalo farm in the south of Italy. Individual animals were allowed to undergo synchronization protocol (either a slightly modified Ovsynch or Progesterone treatment) and TAI until establishment of pregnancy or else for not more than six consecutive times. Semen of seven proven bulls was used throughout the study, which was carried out from March to September of the same year. Therefore, other than the effect given by consecutive TAIs over time, a monthly and a seasonal effect could also be tested, once the entire period was split into a Low Breeding Season (LBS) from March to June, and a Transition to Breeding Season (TBS) from July to September. From the data recorded in this study and the statistical analysis performed, it can be stated that the two protocols for the synchronization of ovulation were similar in efficiency in determining pregnancies with an overall fertility rate of 89.4% when the comparison was run both on a monthly basis or when months were grouped into two different seasons. In addition, an average of 1.83 AI/pregnancy was reported, slightly higher for the Ovsynch when compared to the Progesterone protocol: 1.91 vs 1.70, respectively. Finally, when considering the number of progressive synchronization treatments implemented over time as covariate, neither Ovsynch nor Progesterone treatment significantly affected pregnancy rates following the first of the six synchronization sessions. However, repeating the synchronization procedure, the progesterone based protocol resulted in significantly higher probability of success in terms of established pregnancies during the second and third re-synchronization sessions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs)., Materials and Methods: In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD., Results: PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05)., Conclusions: PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

Latanoprostene bunod (LBN) is a topical ophthalmic therapeutic for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (OHT). LBN is composed of latanoprost acid (LA) linked to a nitric oxide (NO)-donating moiety and is the first NO-releasing prostaglandin analog to be submitted for marketing authorization in the United States. The role of latanoprost in increasing uveoscleral outflow of aqueous humor (AqH) is well established. Herein, we review findings from nonclinical studies, which evaluated the role of NO in the IOP-lowering efficacy of LBN. Pharmacokinetic studies in rabbits and corneal homogenates indicate that LBN is rapidly metabolized to LA and butanediol mononitrate (BDMN). NO is subsequently released by BDMN as shown by increased cyclic guanosine monophosphate (cGMP) levels in (1) the AqH and iris-ciliary body after administration of LBN in rabbits and in (2) human trabecular meshwork (TM) cells after incubation with LBN. LBN reduced myosin light chain phosphorylation, induced cytoskeletal rearrangement, and decreased resistance to current flow to a greater extent than latanoprost in TM cells, indicating that NO released from LBN elicited TM cell relaxation. LBN also lowered IOP to a greater extent than latanoprost in FP receptor knockout mice, rabbits with transient OHT, glaucomatous dogs, and primates with OHT. Along with results from a Phase 2 clinical study in which treatment with LBN 0.024% resulted in greater IOP-lowering efficacy than latanoprost 0.005%, these data indicate that LBN has a dual mechanism of action, increasing AqH outflow through both the uveoscleral (using LA) and TM/Schlemm's canal (using NO) pathways.

Objective: To determine whether topical hypotensive medications prevent postoperative ocular hypertension (POH) after phacoemulsification., Animals Studied: 52 client-owned dogs (88 eyes)., Procedures: Diabetic and nondiabetic dogs having undergone phacoemulsification were included in this retrospective study. The control group received no ocular hypotensive medications. The treatment groups received latanoprost, dorzolamide, or dorzolamide/timolol, beginning immediately after surgery, for 2-week duration. IOPs were obtained at initial examination followed by 4 h, 24 h, 7 days, and 14 days postoperatively. POH was defined as an IOP above 20 mmHg (POH20) or 25 mmHg (POH25)., Results: POH20 occurred in 33 of 87 eyes (37.93%), including 11 of 21 eyes (52.38%) in the control group, three of 23 eyes (13.04%) in the latanoprost group, eight of 15 eyes (53.33%) in the dorzolamide group, and 11 of 28 eyes (39.29%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.11). POH25 occurred in 22 of 86 eyes (25.58%), including seven of 21 eyes (33.33%) in the control group, two of 23 eyes (8.70%) in the latanoprost group, five of 15 eyes (33.33%) in the dorzolamide group, and eight of 27 eyes (29.63%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.31). Intraoperative use of intracameral tissue plasminogen activator significantly decreased the chances of POH25 (P = 0.0063)., Conclusions and Clinical Relevance: The latanoprost group had a substantially lower percentage of POH 20 and POH25 compared to the control and other active treatment groups, although statistical significance was not achieved. Intraoperative intracameral tissue plasminogen activator decreased the incidence of POH25., (© 2017 American College of Veterinary Ophthalmologists.)

Objective: To evaluate the effect of topical ophthalmic 0.005% latanoprost alone and in combination with 0.1% diclofenac on healthy horses., Animals Studied: Twelve healthy adult horses., Procedures: A randomized, masked crossover design was used with horses divided into three groups for once daily treatment in one randomly selected eye. For arm 1 of the study, Group D (n = 3) received 0.1% diclofenac, Group L (n = 3) received 0.005% latanoprost, and Group DL (n = 6) received 0.005% latanoprost and 0.2 ml of 0.1% diclofenac. For arm 2 of the study, horses from Group D and L were placed into Group DL and horses from Group DL were placed into either Group D or L. Evaluations of intraocular pressure (IOP), vertical pupil diameter, aqueous flare, conjunctival hyperemia, epiphora, blepharospasm, and blepharoedema were performed 4 times daily on days 1 and 2 (baseline), days 3 to 7 (arm 1 treatment), days 8 to 11 (washout), days 12 to 16 (arm 2 treatment), and days 17 and 18 (return to baseline)., Results: During the treatment period, significant reduction in IOP and vertical pupil diameter occurred in treated eyes of Groups L and DL, but not Group D. These variables did not differ significantly between Groups L and DL. Blepharospasm, blepharoedema, epiphora, and conjunctival hyperemia scores were significantly higher in Group L than in Groups D and DL., Conclusions: Latanoprost reduced IOP in healthy horses and signs of drug-induced discomfort were mitigated by concurrent use of diclofenac., (© 2016 American College of Veterinary Ophthalmologists.)

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, β-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

Background: Prostaglandin analogs (PGAs) are commonly used to treat glaucoma because of their powerful intraocular pressure lowering effect. However, various periorbital changes associated with the use of PGAs have been reported. We investigated the incidence of periorbital changes in Korean patients who were treated with PGAs, and analyzed clinical factors associated with superior sulcus deepening., Methods: This study included 58 glaucoma patients who were treated with latanoprost, travoprost, or bimatoprost unilaterally. Face photographs were collected, and periorbital changes such as superior sulcus deepening, eyelid pigmentation, ptosis, lid retraction, dermatochalasis, and redness were evaluated by two oculoplastic specialists. For each patient, the contralateral eye served as a control. The frequency of ptosis, dermatochalasis, pigmentation, erythema, and superior sulcus deepening were analyzed. Demographic and ocular factors were compared between patients who showed superior sulcus deepening and those who did not., Results: Thirty-one patients (53.4%) showed one or more periorbital changes associated with PGAs. The most common change was superior sulcus deepening (24.1%), followed by eyelid pigmentation (19.0%), eyelid erythema (19.0%), dermatochalasis (10.3%), eyelid retraction (5.2%), and ptosis (3.4%). The age of the patient and the duration of PGA administration was significantly correlated with superior sulcus deepening (p = 0.007, p = 0.002, respectively)., Conclusions: Periorbital changes are frequently seen in patients who use PGAs, and superior sulcus deepening is the most common change in Korean patients. Long-term use of PGAs and old age were associated with superior sulcus deepening.

Purpose: To compare various characteristics of Xalatan ® and five generic latanoprost ophthalmic solutions., Methods: Drop size, volume, pH values, buffer capacity, viscosity, hardness of bottles and costs were determined. Drop sizes were measured in triplicates by micropipettes, and the number of drops counted in three separate bottles of each generic product was determined. pH values were measured in triplicates by a calibrated pH meter. Buffer capacity was exploited by titrating known quantities of strong base into 2.5 ml of each brand and interpolated to neutral pH. Kinematic viscosity was determined by linear regression of timed gravity flow from a vertical syringe through a 21-G cannula. The hardness of the bottles was evaluated by gradually increasing tension on a hook placed around each bottle until a drop was expelled reading the tension on an attached spring scale., Results: Drop sizes and the number of drops in the bottles varied significantly between the generic drugs. The control value of pH in the brand version (Xalatan ® ) was markedly lower compared to the generic latanoprost products. Titration of Xalatan ® to neutrality required substantially more NaOH compared to the generic latanoprost products. Finally, the viscosity revealed a significant variability between brands. Remarkable differences were found in bottle shapes, bottle hardness and costs of the latanoprost generics., Conclusion: Generic latanoprost eye drops should not be considered identical to the original brand version as regards to drop size, volumes, pH values, buffer capacity, viscosity, hardness of bottles and costs. It is likely that these issues affect compliance and intraocular pressure (IOP)-lowering effect. Therefore, re-evaluation of the requirements for introducing generic eye drops seems reasonable., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The purpose of the study is to assess the changes in the long-term effects of prostaglandin analogues (PGAs) on intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG). Data of POAG patients treated with latanoprost (0.005 %), travoprost (0.004 %), or bimatoprost (0.03 %) as the first line treatment for 5 years or more were retrospectively evaluated. Baseline ophthalmic assessment values were recorded together with the IOP at the 6th month, 1st year, and then annually. The 79 patients included 33 (41.8 %) men and 46 (58.2 %) women. There were 34 (43.0 %) patients using latanoprost (0.005 %), 23 (29.1 %) patients using bimatoprost (0.03 %), and 22 (27.8 %) patients using travoprost (0.004 %). There was no difference between the groups in terms of age, gender, or baseline IOP levels. IOP levels at the 6th month were significantly lower than baseline IOP levels in all groups (p < 0.01, Friedman test). The IOP decrease was maintained after the 6th month in all three group with no statistically significant difference compared to the 6th month IOP value (p > 0.05, Friedman test) and no statistically significant difference between the groups during follow-up (Kruskal-Wallis test, p > 0.05). IOP reductions with PGAs were adequate and stable in the 5-year follow-up period with no decrease in effectiveness over time.

Background/aims: ONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan., Methods: Adults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days., Results: Day 29 mean diurnal IOP was -7.2 mm Hg for ONO-9054 vs -6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤-25%, ≤-30% and ≤-35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p<0.05, post hoc analyses). The percentage of subjects achieving target IOPs on day 29 (≤17, ≤16 and ≤15 mm Hg) was greater for ONO-9054 than for Xalatan; the odds of achieving an IOP ≤15 mm Hg for ONO-9054 were 2.4 times more than the odds for Xalatan (p<0.01, post hoc analysis)., Conclusions: Subjects randomised to receive ONO-9054 were more likely to achieve a greater per cent reduction in IOP and were more likely to achieve target IOPs than those receiving Xalatan. The effects of ONO-9054 in reducing IOP appear to persist longer than those of Xalatan., Trial Registration Number: NCT02083289, Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

To compare the reproductive performance after TAI in ewes synchronized with mid (12 or 13) or long (14-16 d) interval prostaglandin (PG) or progesterone plus eCG (P4-eCG) based protocols, 440 multiparous Corriedale ewes were synchronized with two PG injections administered 12-16 d apart (PG12, PG13, PG14, PG15 and PG16 respectively), or P4-eCG (MAP sponges 14 d and eCG). Cervical TAI (Day 0) was performed with fresh semen. It was evaluated the ovulated ewes (OE, %) and the ovulation rate (OR) on Day 8 by trans-rectal ultrasonography, the rate of non-return to service between Days 13 and 21 by painted rams, and the pregnancy rate, prolificacy and fecundity on Day 60 by trans-abdominal ultrasonography. No significant differences were found in OE among groups (P>0.05), but P4-eCG achieved higher OR (P<0.05) compared to PG protocols, without differences among them (P>0.05). Similar NRR-21, pregnancy and fecundity were observed among PG15 (64.3, 62.9 and 84.3), PG16 (59.7, 59.7 and 77.8) and P4-eCG (70.3, 66.2 and 95.9), but higher compared to PG12 (42.5, 39.7 and 52.1) and PG13 group (44.0, 40.0 and 48.0, respectively; P<0.05). PG14 achieved intermediate results compared to other groups. No differences were found in prolificacy among groups (P>0.05), except PG13 that was lower compared to P4-eCG (P<0.05). In conclusion, long interval between PG injections (15 or 16 d) determined better reproductive outcome that mid interval (12 or 13 d), equating the P4-eCG based protocol after cervical TAI with fresh semen during the breeding season in sheep., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To determine the changes in the anterior chamber flare and central macular thickness (CMT) under topical antiglaucomatous therapy., Methods: This study included 121 eyes of 73 patients and 36 eyes of 18 controls. Glaucoma patients were divided into 3 groups (timolol maleate, latanoprost, and bimatoprost). Control eyes did not receive any medications. Flare and CMT measurements were performed at baseline and follow-up visits (15th day, and 1st, 3rd, 6th, and 12th month)., Results: Statistically significant increases were detected in the flare values in the bimatoprost and latanoprost groups (P < 0.001, P = 0.011, respectively). Significant increases were also found in CMT values measured in these 2 groups (P < 0.001, P = 0.002, respectively). However, increased flare and CMT values were not clinically manifested as uveitis and macular edema. Flare and CMT values did not change statistically in the timolol maleate and control groups., Conclusions: Although the use of prostaglandin (PG) analogs was found to be associated with increased flare and CMT, these increases were not clinically significant. PG analog monotherapy may be safely and effectively used in the treatment of glaucoma.

The purpose of this study was to comparatively evaluate the pharmaceutical characteristics of various marketed generic formulations of prostaglandin analogue latanoprost in the Indian market. Three generics of latanoprost and one branded (Xalatan) formulation (five vials each) were obtained from authorized agents from the respective commercial sourcing having the same batch number. These formulations were coded, and the labels were removed. At a standardized room temperature of 25 °C, the concentration, osmolarity, drop size, pH, and total drops per vial were determined for Xalatan and all the generics of latanoprost. The concentration of various brands varied between 50.49 ± 0.36 and 58.90 ± 0.52 µg/ml as compared to the standard labeled concentration of 50 µg/ml on the latanoprost vials. The concentration of drugs in individual drop varied from 1.30 ± 0.05 to 1.78 ± 0.04 µg/drop. The volume of drug formulation per bottle varied from 2.4 ± 0.12 to 2.6 ± 0.09 ml/bottle. The number of drops per bottle varied from minimum of 88.60 ± 0.10 drops to maximum of 102.0 ± 4.3 drops across all the formulations, while the drop size varied from 25.72 ± 2.70 to 29.97 ± 1.38 µl. The osmolarity of 2/4 drugs was within 300 mOs M (±10 %). The specific gravity varied between 0.98 ± 0.01 and 1.007 ± 0.01, while pH was between 7.05 ± 0.004 and 7.13 ± 0.005. Two of the generic brands were outside the United States pharmacopoeia limits (±10%) for ophthalmic formulation, with concentration exceeding the limits by 3 % (p = 0.151) and 8 % (p = 0.008), respectively. This pilot study highlights that there are significant variations in the drug concentrations and physical properties of generic latanoprost formulations. Although none of the brands had concentrations below the recommended level, two of the brands had concentrations exceeding the limits by 3 and 8 %, respectively.

The objective of the present study was to determine the ovarian response induced with the prostaglandin-based protocol Synchrovine (two doses of PGF 2α given 7 d apart), as well as the fertility after FTAI. In Experiment 1, 15 females received the Synchrovine protocol using two different PGF 2α analogues (Delprostenate vs. D-Cloprostenol). No differences in estrus response, time of ovulation and follicular dynamics were found between both groups (P < 0.05). The ovulation after Synchrovine was synchronized in a similar mean interval (68.8 ± 7.1 h) than when the females received a single dose of PGF 2α (70.2 ± 20.7 h; P=NS), but the dispersion between the first and the last ovulation was reduced with this protocol (range 60-84 h vs. 24-96 h, respectively; P < 0.05). In experiment 2, 318 ewes were treated with the Synchrovine protocol and cervical FTAI was performed using different sperm cell concentrations. Pregnancy rate was higher using 200 × 10 6 and 100 × 10 6 sperm cells (38.2%, 39/102; and 34.9%, 38/109, respectively) than using 50 × 10 6 (23.4%, 25/107, P < 0.05). In Experiment 3, 444 ewes received the Synchrovine protocol and were assigned to receive 300 IU of eCG or not at the moment of the second dose of PGF 2α , and cervical FTAI was performed 42 h or 48 h after the second dose of PGF 2α . No effect was found related to the eCG administration nor the time of insemination. In Experiment 4, 342 received cervical or intrauterine insemination after treatment with the Synchrovine protocol, resulting in greater pregnancy rate for intrauterine insemination than cervical insemination (52.5%, 90/171 vs. 31%, 53/171, P < 0.05). These experiments demonstrate that the Synchrovine protocol effectively induces luteolysis, estrus and ovulation in most of the treated females, and ovulation is synchronized into a narrow window of 24 h. Pregnancy rate obtained with cervical FTAI is around 30-45%, with similar results using 100 × 10 6 or 200 × 10 6 sperm cells, the eCG administration seems not to be necessary, the type of PGF2α analogue does not appear relevant, and fertility is improved with intrauterine semen deposition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops., Objectives: To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials., Selection Criteria: We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication., Data Collection and Analysis: Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane., Main Results: We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months., Authors' Conclusions: Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.

Purpose: To assess the impact of latanoprost on central corneal thickness (CCT) after ceasing medication in patients with normal tension glaucoma (NTG)., Methods: A total of 46 eyes from 46 NTG patients, and 44 eyes from 44 individuals with glaucoma suspect (controls), were included in this retrospective study. Newly diagnosed early NTG patients (visual field mean deviation >-6.00) were administered latanoprost 0.005% monotherapy once a day. CCTs were measured by ultrasound pachymetry before treatment, for 5 years during treatment, and for 2 years after ceasing treatment., Results: Mean CCT was reduced significantly in the NTG group during treatment [544.4 ± 35.8 μm vs. 531.4 ± 32.5 μm (n = 46), P < 0.001]. After ceasing latanoprost treatment, mean CCT increased [531.4 ± 32.5 μm vs. 544.6 ± 37.1 μm (n = 46), P < 0.01] over the course of 2 years. In the control group, however, mean CCT was not significantly different [553.5 ± 27.5 μm vs. 561.8 ± 24.7 μm (n = 44), P = 0.06] at the 7-year follow-up., Conclusions: Latanoprost significantly reduced CCT in NTG patients after 5 years of treatment; however, the reduction was reversed 2 years after discontinuation of treatment.

Aim: The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels., Methods: Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase)., Results: The IC50 values for Lumigan UD ® (bimatoprost 0.3 mg/mL), Monoprost ® (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively., Discussion: All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost., Competing Interests: The authors report no conflicts of interest in this work.

The aim of this study was to evaluate the relationship between the ovarian follicular response at the start of the OVsynch-fixed-time artificial insemination (TAI) program and pregnancy outcome in the Mediterranean river buffalo. The study involved 116 pluriparous buffaloes at 118 ± 65 days in milk maintained under commercial conditions on a buffalo dairy enterprise in southern Italy. Synchronization of the stage of the estrous cycle in the Ovsynch-TAI program involves an injection of GnRH on Day 0 (GnRH1), PGF 2α on Day 7, and GnRH on Day 9 (GnRH2). Timed artificial insemination is carried out on Day 10. Ovarian ultrasound examinations were undertaken on days 0, 2, 7, 9, 10, and 11 to record total follicles, the dimensions of follicles greater than 0.75 cm, dimensions of the corpus luteum (CL), and the occurrence of ovulation. Blood concentrations of P4 were measured on days 0 and 10 and 10 days after TAI. Pregnancy status was determined on days 27 and 45 after TAI to calculate late embryonic mortality. The data were analyzed by ANOVA and multiple logistic regression. A total of 70 of 116 (60.4%) buffaloes showed ovulation after GnRH1. Buffaloes that ovulated after GnRH1 had a smaller (P < 0.05) area of the ovulatory follicle on Day 0 compared with buffaloes that did not ovulate (1.08 ± 0.1 and 1.29 ± 0.1 cm 2 , respectively). The former buffaloes also had a larger (P < 0.05) CL area (1.81 ± 0.1 and 1.51 ± 0.1 cm 2 , respectively) and greater (P < 0.05) blood concentrations of P4 (1.84 ± 0.2 and 1.34 ± 0.2 ng/mL, respectively) on Day 0. A larger (P < 0.05) proportion of buffaloes that ovulated after GnRH1 showed regression of the CL after the injection of PGF 2α on Day 7 compared with buffaloes that did not ovulate (68 of 69 [98.6%] and 27 of 32 [84.4%], respectively). Buffaloes that ovulated after GnRH1 also had a greater (P < 0.05) ovulation rate after GnRH2 than buffaloes that did not ovulate (65 of 70 [92.8%] and 37 of 46 [80.4%], respectively). Buffaloes that ovulated after GnRH1 had a higher (P < 0.01) pregnancy rate than buffaloes that did not ovulate, both at Day 27 (53 of 70 [75.7%] and 14 of 46 [30.4%], respectively) and Day 45 (46 of 70 [65.7%] and 10 of 46 [21.7%], respectively). The incidence of late embryonic mortality tended to be less for buffaloes that ovulated after GnRH1 than buffaloes that did not ovulate (7 of 53 [13.2%] and 4 of 14 [28.6%], respectively). The present findings have demonstrated a strong direct relationship between the ovarian follicular response at the start of an OVsynch-TAI program and pregnancy outcome in the Mediterranean river buffalo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To assess the intraocular pressure (IOP)-lowering effects and safety of a carteolol/latanoprost fixed combination drug (OPC-1085EL) vs latanoprost (Study 1) and carteolol (Study 2) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH)., Design: Multicenter, randomized, evaluator-masked (Study 1)/double-masked (Study 2), parallel-group studies., Methods: Setting: Twenty-eight clinical sites (Study 1) and 19 clinical sites (Study 2) in Japan., Study Population: Outpatients with bilateral POAG or OH whose predose IOP was 18 to <35 mm Hg in the study eye after 4 weeks' treatment with latanoprost (Study 1) or carteolol (Study 2) (defined as baseline)., Intervention: In Study 1, 237 patients applied OPC-1085EL (n = 118) or latanoprost (n = 119) for 8 weeks. In Study 2, 193 patients applied OPC-1085EL (n = 78), carteolol (n = 78), or carteolol/latanoprost concomitant therapy (n = 37) for 8 weeks., Main Outcome Measure: Adjusted mean IOP reduction at predose from baseline to week 8., Results: In Study 1, the adjusted mean IOP reductions (95% confidence interval [CI]) were 2.9 (2.5-3.3) mm Hg and 1.6 (1.2-2.0) mm Hg in the OPC-1085EL and latanoprost groups, respectively (P < .0001). In Study 2, the adjusted mean IOP reductions (95% CI) were 3.5 (3.1-3.9) mm Hg and 1.6 (1.2-2.0) mm Hg in the OPC-1085EL and carteolol groups, respectively (P < .0001). All adverse drug reactions of OPC-1085EL observed in both studies were mild in severity and only 1 patient in each study discontinued because of an adverse drug reaction., Conclusions: OPC-1085EL is superior to latanoprost or carteolol alone in terms of lowering IOP, and was well tolerated., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management., (© 2016 Wiley Periodicals, Inc.)

Purpose: To compare the diurnal and nocturnal effects of latanoprostene bunod 0.024% solution with timolol maleate 0.5% solution on intraocular pressure (IOP) and ocular perfusion pressure., Design: Prospective, open-label randomized crossover trial., Methods: Twenty-five patients (aged 43-82 years) with ocular hypertension or early primary open-angle glaucoma were enrolled. Baseline IOP and blood pressure were measured in a sleep laboratory every 2 hours in the sitting and supine positions during the 16-hour diurnal/wake period and in the supine position during the 8-hour nocturnal/sleep period. Subjects were randomly assigned to bilateral treatments of latanoprostene bunod at 8 PM or timolol at 8 AM and 8 PM. The second laboratory recording occurred after the 4-week treatment. Subjects were crossed over to the comparator treatment for 4 weeks before the third laboratory recording. Mean IOP and calculated ocular perfusion pressure were compared for the diurnal and nocturnal periods., Results: Twenty-one subjects completed the study. Both treatments reduced diurnal sitting and supine IOP compared to baseline by 2.3-3.9 mm Hg (all P < .001) with no statistically significant difference between the 2 treatments. Nocturnal IOP under latanoprostene bunod treatment was 2.5 ± 3.1 mm Hg (mean ± SD) less than baseline (P = .002) and 2.3 ± 3.0 mm Hg less than timolol treatment (P = .004). Latanoprostene bunod treatment resulted in greater diurnal sitting and supine ocular perfusion pressures compared with baseline (P ≤ .006) and greater nocturnal ocular perfusion pressure compared with timolol treatment (P = .010)., Conclusions: During the nocturnal period, latanoprostene bunod caused more IOP reduction and more increase of ocular perfusion pressure than timolol., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent., Methods: 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients)., Results: The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important., Conclusion: This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

Objectives: To evaluate the safety and efficacy of unpreserved latanoprost eye drops (UNL) in comparison with preserved latanoprost eye drops (LBAK) in patients with glaucoma or ocular hypertension stabilized with preserved latanoprost eye drops as monotherapy., Methods: Multicenter, randomized, open, two-parallel group study. The intraocular pressure (IOP), ocular signs and symptoms, adverse events and a quality of life questionnaire were evaluated at inclusion (D0) and after 3 months of treatment (D84)., Results: One hundred and eighty-three patients were evaluated (38.7 % with an ocular hypertension and 61.3 % with open-angle glaucoma): 130 in the UNL group and 53 in the LBAK group). In the UNL group, mean IOP remained unchanged after 3 months of treatment and the mean difference with LBAK was 0.503mmHg with a confidence interval between -0.202 and 1.208, establishing non-inferiority of UN-L versus BAK-L. Overall, the total score of conjunctival hyperemia improved to a greater extent in the UNL group (-0.5±0.8) compared to the LBAK group (-0.1±0.6, P=0.0004), as well as the total score of symptoms on instillation (-2.0±2.7 versus -0.9±2.2, P=0.0035), and between instillations (-1.8±2.8 vs. -0.3±1.3, P=0.0003)., Conclusion: The results of this study showed that preserved latanoprost eye drops may be substituted with unpreserved latanoprost eye drops with better tolerability in glaucoma patients with stable IOP., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Latanoprostene bunod (LBN) is a novel nitric oxide (NO)-donating prostaglandin F2α analog. We evaluated the long-term safety and intraocular pressure (IOP)-lowering efficacy of LBN ophthalmic solution 0.024% over 1 year in Japanese subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Methods: This was a single-arm, multicenter, open-label, clinical study. Subjects aged 20 years and older with a diagnosis of OAG or OHT instilled 1 drop of LBN ophthalmic solution 0.024% in the affected eye(s) once daily in the evening for 52 weeks and were evaluated every 4 weeks. Safety assessments included vital signs, comprehensive ophthalmic exams, and treatment-emergent adverse events (AEs). Absolute and percent reductions from baseline in IOP were also determined., Results: Of 130 subjects enrolled, 121 (93.1%) completed the study. Mean age was 62.5 years, and mean (standard deviation) baseline IOP was 19.6 (2.9) and 18.7 (2.6) mmHg in study eyes and treated fellow eyes, respectively. Overall, 76/130 (58.5%) and 78/126 (61.9%) subjects experienced ≥1 AEs in study eyes and treated fellow eyes, respectively. In both study eyes and treated fellow eyes, the most common AEs were conjunctival hyperemia, growth of eyelashes, eye irritation, and eye pain. At 52 weeks, 9% of treated eyes had an increase in iris pigmentation compared with baseline based on iris photographs. No safety concerns emerged based on vital signs or other ocular assessments. Mean reductions from baseline in IOP of 22.0% and 19.5% were achieved by week 4 in study and treated fellow eyes, respectively. These reductions were maintained through week 52 (P < 0.001 vs. baseline at all visits)., Conclusion: Once daily LBN ophthalmic solution 0.024% was safe and well-tolerated in Japanese subjects with OAG or OHT when used for up to 1 year. Long-term treatment with LBN ophthalmic solution 0.024% provided significant and sustained IOP reduction., Trial Registration: ClinicalTrials.gov identifier, NCT01895972., Funding: Bausch & Lomb, Inc. a division of Valeant Pharmaceuticals International Inc.

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification., (© 2016 Wiley Periodicals, Inc.)

Objective: This study compared the efficacy, safety, and pharmacokinetics of a preservative-free latanoprost formulation to an established, benzalkonium chloride (BAK) containing formulation for the treatment of open-angle glaucoma or ocular hypertension., Methods: This was a phase II, randomized, cross-over, investigator-masked, multi-center, pilot study (NCT01494753). A total of 30 untreated adult patients (aged ≥18 years) with primary open angle glaucoma, pseudo-exfoliative glaucoma, pigmentary glaucoma, or ocular hypertension received either preservative-free or preserved latanoprost once daily in both eyes for 6 weeks, before crossing over to receive the other treatment. Efficacy (intraocular pressure [IOP] at 8 am, midday, 4 pm and 8 pm, and global efficacy assessment by investigator), safety (adverse events, ocular symptoms and global tolerance, slit lamp examination, funduscopy, visual field examination, visual acuity, and heart rate), and pharmacokinetics were assessed at Days 0, 42, and 84., Results: Both treatments resulted in a reduction in IOP that was similar for the preservative-free and the preserved formulation at all time points. Similarly, the overall diurnal reduction was similar in both groups (6.3 mmHg [27.9% reduction] and 6.4 mmHg [28.1% reduction] for preserved and preservative-free latanoprost, respectively). There were no differences in global efficacy assessment or in the safety and tolerance of each treatment. Systemic concentrations of latanoprost were very low; AUC0-30 and Cmax were lower and tmax was longer for preservative-free latanoprost., Conclusions: Preservative-free latanoprost showed similar efficacy at all time points compared to BAK preservative containing formulation, with no difference in tolerance, allowing progression to phase III clinical development.

Introduction: To investigate the efficacy of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery., Methods: Single arm, prospective, interventional multicenter study. Primary pediatric glaucoma patients younger than 13 years after a single surgical procedure with IOP between 22 and 26 mmHg were considered eligible. At baseline, patients were allocated to latanoprost monotherapy once daily. Depending on intraocular pressure (IOP) reduction at first visit, the patients were allocated to one of three groups: continuation of latanoprost monotherapy, addition of dorzolamide twice daily, or switch to dorzolamide three times daily. The same approach for allocation in medication groups was used in all subsequent visits. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered non-responders and withdrawn. Study treatment and patient follow-up will continue for 3 years or until treatment failure. The primary endpoint is the percentage of responders. Secondary endpoints are time to treatment failure and frequency of adverse events., Results: A total of 37 patients (69 eyes) were enrolled. The mean age was 4.0 ± 3.8 years, the female/male ratio was 1/1.7, and the majority of patients were Caucasian. Eighty percent of patients had bilateral glaucoma. Goniotomy was the most frequently performed surgery (38.6%), followed by trabeculotomy (22.8%), trabeculectomy (21.1%), and trabeculectomy plus trabeculotomy (17.5%). The baseline IOP was 23.6 ± 1.5 mmHg., Conclusion: The study population is representative of patients frequently encountered after the first surgery for primary pediatric glaucoma. The study will produce evidence on the medium-term efficacy of a defined pharmacological approach.

Purpose: In this study, we investigated the effect of a slow-releasing hydrogen sulfide (H2S) donor, GYY 4137, on intraocular pressure (IOP) in normotensive rabbits. Furthermore, we compared the IOP-lowering action of GYY 4137 with those elicited by other H2S-producing compounds, l-cysteine and ACS67 (a hybrid compound of latanoprost with an H2S-releasing moiety)., Methods: IOP was measured in New Zealand normotensive male albino rabbits using a pneumatonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY). At 0 h, 50 μL of test compounds were applied topically to 1 eye of each animal, while the contralateral eye received the same quantity of vehicle (saline). IOP was measured hourly until baseline IOP readings were attained and animal eyes monitored for potential side effects (i.e., tearing, hyperemia)., Results: GYY 4137 (0.1%-2%) produced a dose-dependent decrease in IOP reaching a maximum of 27.8% ± 3.14% (n = 5) after 6 h. Interestingly, a significant contralateral effect was observed in vehicle-treated controls eyes at all doses tested. l-cysteine (5%) and ACS67 (0.005%) also elicited a significant (P < 0.01) decrease in IOP that achieved a maximum of 28.84% ± 1.53% (n = 5) and 23.27% ± 0.51% (n = 5), respectively, after 3 h. All 3 H2S-producing compounds also caused a significant contralateral effect in vehicle-treated control eyes., Conclusion: We conclude that GYY 4137 and other H2S-producing donors can reduce IOP in normotensive rabbits. However, the profile of IOP-lowering action of GYY 4137 was different from the other H2S donors affirming its ability to act as a slow-releasing gas donor.

Aim: to evaluate the effectiveness of prolatan (latanoprost 0.005%) in the treatment of primary open-angle glaucoma (POAG)., Material and Methods: The study included 35 POAG patients (41 eyes) aged 55-72 years, of them 20 men and 15 women. The patients were randomized into two groups followed up for 3 months. Group 1 consisted of 17 patients (19 eyes) who received prolatan once daily in the evening. Group 2 consisted of 18 patients (22 eyes) under Xalatan 0.005% once daily in the evening., Results: The true intraocular pressure (IOP) decreased by the average of 28.6%. Analysis of perimetry results showed a statistically reliable increase in the MD - by 17.4% in the study group and by 20% in the control group, and PSD indices - by 10.7% and 11.9%, respectively. Optical coherence tomography revealed an improvement of optic disc parameters in both groups. In particular, the cup volume decreased reliably by 8.4% and 6.3% and cup area - by 24.4% and 28.5%, respectively, while the rim area increased by 20.8% and 17.9%, respectively. The patients complained of neither burning, nor discomfort, nor foreign body sensation after prolatan instillations. We also report the absence of side effects., Conclusion: The study has proved high antihypertensive effectiveness of prolatan. Improved morphometric parameters of the optic disc (decreased cup volume and area, increased rim area) indirectly indicate the neuroprotective potential of the drug. Being well-tolerated by the patients, prolatan can be recommended as the first choice treatment of glaucoma.

Ocular hypertension is a major risk factor for the development and progression of glaucoma. Frequent and long-term application of latanoprost often causes undesirable local side effects, which are a major cause of therapeutic failure due to loss of persistence in using this glaucoma medical therapy. In the present study, we developed a thermosensitive chitosan-based hydrogel as a topical eye drop formulation for the sustained release of latanoprost to control ocular hypertension. The developed formulation without preservatives may improve compliance and possibly even efficacy. The results of this study support its biocompatibility and sustained-release profile both in vitro and in vivo. After topical application of latanoprost-loaded hydrogel, triamcinolone acetonide-induced elevated intraocular pressure was significantly decreased within 7 days and remained at a normal level for the following 21 days in rabbit eyes. This newly developed chitosan-based hydrogel may provide a non-invasive alternative to traditional anti-glaucoma eye drops for glaucoma treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To assess the effect of switching 1 eye to topical travoprost 0.004% preserved with SofZia (TRAVATAN Z solution) in patients who had chronic superficial punctate keratitis (SPK) in both eyes treated with benzalkonium chloride-preserved latanoprost 0.005% (XALATAN)., Methods: This was a prospective, randomized, controlled, multicenter, open-label, comparative 3-month follow-up study. Patients with open-angle glaucoma or ocular hypertension who received XALATAN monotherapy for at least 3 months and had SPK in both eyes were enrolled at 9 facilities. For each patient, 1 eye was randomly selected and switched to TRAVATAN Z solution (T-group); the contralateral control eye was treated with XALATAN (X-group). SPK in 5 corneal regions, conjunctival hyperemia, tear breakup time (TBUT), and intraocular pressure (IOP) were examined in a masked manner at baseline, 1 month, and 3 months. Changes in SPK, hyperemia, TBUT, and IOP were compared within treatment groups and between treatment groups., Results: Fifty-six patients completed the study. The frequency of SPK significantly decreased from baseline in the T-group and the X-group at 1 and 3 months (T-group, P<0.001; X-group, P<0.05). In the T-group, SPK scores were significantly improved in 4 corneal regions, excluding the superior region, at 1 and 3 months (all P<0.05), whereas in the X-group, SPK scores were significantly improved only in the temporal region at 1 month and in the inferior region at 3 months (P<0.05 for both). The total SPK score at 1 and 3 months in the T-group was significantly lower compared with the score in the X-group (P=0.0023 and 0.0102, respectively). The SPK score for the superior and central corneal region at 3 months in the T-group was significantly lower compared with the score in the X-group (P=0.0212 and 0.022, respectively). There were no substantial intergroup or intragroup differences in changes from baseline for hyperemia scores, TBUT, or IOP reduction., Conclusions: Switching therapy from benzalkonium chloride-preserved latanoprost to travoprost preserved with SofZia ameliorated chronic SPK. There were no clinically relevant changes in hyperemia, TBUT, or IOP.

Therapeutic soft contact lenses (TSCLs) are frequently used to support or protect the cornea during healing. Our aim was to quantitatively evaluate the efficacy of topical medications in TSCL-fitted dogs and determine whether it is affected by the presence of TSCLs. In Phase I, pupil diameter was measured in eyes treated with tropicamide and in eyes covered with TSCLs and then treated with tropicamide, with 1-week intervals between sessions. In Phase II, intraocular pressure (IOP) was measured in uncovered and TSCL-covered eyes treated with latanoprost, with 1-week intervals between sessions. Tropicamide caused significant mydriasis in both uncovered and TSCL-covered eyes (P = 0.005). On the other hand, latanoprost caused a significant decrease in IOP when applied to uncovered eyes (P = 0.002), but had no significant effect on IOP when applied to TSCL-covered eyes (P = 0.7). As we used the same dogs and identical TSCLs throughout the study, we conclude that the different outcomes of the two drugs are due to properties of the drugs themselves, or their formulations, affecting their interaction with the TSCLs. The clinical efficacy of topical drugs applied to TSCL-covered eyes may have to be determined for each drug and/or formulation., (© 2015 John Wiley & Sons Ltd.)

Purpose: To evaluate discrepancies in doses per bottle, bottle fill volume, and cost among branded and generic formulations of latanoprost., Design: Comparative economic analysis., Methods: This study was conducted at the Ruiz Department of Ophthalmology and Visual Science at The University of Texas Health Science Center at Houston (UTHealth). Four regionally available latanoprost formulations were measured. Number of drops per bottle and actual bottle fill volume were measured for a calculated sample size (10 bottles). Annual cost (using average wholesale price), days use per bottle, drops per milliliter, and number of bottles used per year were calculated. Data were summarized using mean and standard deviation; 1-way analysis of variance and post hoc Tukey's studentized range test were used for comparing means among manufacturers., Results: Pfizer's branded lantanoprost, Xalatan (New York, New York, USA), had the largest fill volume (P < .001). Pfizer had the highest yearly cost at $1198 (P < .001), whereas Akorn (Lake Forest, Illinois, USA) and Bausch & Lomb (Rochester, New York, USA) had the lowest ($184 and $201, respectively). Pfizer and Bausch & Lomb had the most drops per bottle (87.3 and 88.7, respectively), which was statistically more (P < .001) than either Akorn or Sandoz (Princeton, New Jersey, USA) (77.6 and 76.6, respectively), but there was no statistical difference among the standard deviation of drops per bottle (Levene 0.14)., Conclusions: Annual cost and number of doses per bottle, factors important to patients, vary significantly depending on the manufacturer of latanoprost. Practitioners can better advise patients by being aware of these differences., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with β-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls., Patients and Methods: This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up., Results: Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (-3.1 μm/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers (-5.8 and -3.8 μm/y for right and left eye, respectively)., Conclusions: We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

The combination of timolol and latanoprost, which are ocular hypotensive agents, has a greater ocular hypotensive effect than each as monotherapy. However, the protective effect of the combination is not well understood. In the present study, we investigated whether latanoprost/timolol in combination has an additive or synergistic cytoprotective effect on neuro retinal cells (RGC-5). To investigate the protective effects of timolol/latanoprost in combination, cultured RGC-5 were treated with various concentrations of these two agents, singly or together, after which the cells were exposed to oxidative stress, serum deprivation, or endoplasmic reticulum (ER) stress in vitro. Cells were also treated with an Akt inhibitor, LY294002, to examine the mechanism of the protective effect. Latanoprost, timolol, and the two in combination reduced cell death induced by oxidative stress, serum deprivation, or ER stress. The latanoprost/timolol combination reduced cell death to a greater extent than monotherapy with latanoprost or timolol on serum deprivation only, and LY294002 inhibited the protective effect of their combination. These findings suggest that timolol/latanoprost in combination have a protective effect against serum deprivation only by activation of Akt signaling. Furthermore, this combination has not only an ocular hypotensive effect but also a neuroprotective effect.

The aim of this study was to evaluate whether changing the interval from CIDR removal to timed artificial insemination (TAI) according to the diameter of the preovulatory follicle (POF) would improve pregnancy per AI in cows. In Study 1, a retrospective analysis of TAI experiments (n=96 cows) was performed to characterize the time of ovulation according to the diameter of the dominant follicle. It was observed that cows with a larger POF had ovulations earlier than cows with smaller POF, according to the equation: y=0.72x(2)-26.74x+264.54 (R(2)=0.63; P<0.001). In Study 2, lactating Nelore cows (n=412) were subjected to an EB-CIDR based TAI protocol. On the morning of Day 10 (time of TAI), cows were randomized into Control (n=209) and Block (n=203) groups; (1) Cows in the Control Group were TAI 48 h after CIDR removal (08:00 am on Day 10), and; (2) Cows in the block group were inseminated once at one of the following time points, according to the diameter of the POF on Day 10: B0 (POF≥15mm, TAI 0 h after convetional TAI), B1 (POF 13-14.9 mm, TAI 6h later), B2 (POF 10.1-12.9 mm, TAI 24h later) and B3 (POF≤10mm, TAI 30 h later). The cows of the Block Group had greater pregnancy rates per AI than the Control Group (129/203, 63.5% when compared with 102/209, 48.8%, respectively; P<0.01). In conclusion, results of the present study demonstrate that adjusting the timing of TAI according to the diameter of the POF can be an effective practice for improving fertility of cows in TAI protocols., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: A prospective study was performed to compare the ocular pulse amplitude (OPA)-lowering effects of tafluprost and latanoprost, used in the treatment of glaucoma, using dynamic contour tonometry., Methods: The study population consisted of patients with normal-tension glaucoma (NTG) (n = 27) or primary open-angle glaucoma (POAG) (n = 14) treated with tafluprost and latanoprost. All patients were newly diagnosed with NTG and POAG and had undergone no previous treatment. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry (GAT), OPA was measured by dynamic contour tonometry, and corrected OPA (cOPA) was calculated before and after 1 week, 1-3 months of treatment., Results: Initial IOP and OPA were 17.12 ± 3.75, 2.30 ± 0.56 mmHg and 17.53 ± 2.87, 2.65 ± 0.94 mmHg in the tafluprost and latanoprost groups, respectively. After 3 months of treatment, IOP and OPA were 13.00 ± 2.04 mmHg (24.1%) and 1.51 ± 0.30 mmHg (34.3%), respectively, in the tafluprost group. These values were 15.40 ± 2.32 mmHg (12.2%) and 2.08 ± 0.83 mmHg (21.5%), respectively, in the latanoprost group. Therefore, tafluprost significantly reduced IOP (P = 0.01), but OPA-lowering effects did not differ significantly between the 2 groups (P = 0.17). However, the cOPA-lowering effect of tafluprost (1.27 mmHg, 55.2%) was significantly greater than that of latanoprost (0.84 mmHg, 31.7%) after 3 months of treatment (P < 0.001)., Conclusions: Tafluprost and latanoprost, used to treat glaucoma, have marked OPA-lowering effects as well as IOP-lowering effects. Moreover, tafluprost has a greater effect than latanoprost. Therefore, it can be used for patients in need of IOP reduction and at risk of glaucoma progression.