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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: 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 compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Design: Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial., Methods: 691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months., Results: 661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia., Conclusion: The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma., Competing Interests: FINANCIAL DISCLOSURES The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background and Objective: All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in in vitro and in vivo drug permeability studies., Methods: Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined in vitro using a reconstructed human corneal epithelium tissue. Then, in vivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB)., Results: In vitro, the cumulative transport of LAT was linear between 1 h and 4 h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2 h and 12 h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8 h (p < 0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1 h in ICB (p = 0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p < 0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3 h., Conclusion: BAK did not influence the corneal penetration of latanoprost in in vitro and in vivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations., (© 2023. The Author(s).)

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional β-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs., Competing Interests: None

Glaucoma is the leading cause of irreversible blindness, and its treatment is attracting widespread attention. Drug-loaded lacrimal suppositories can effectively treat xerophthalmia, but there is little research on the treatment of glaucoma with drug-loaded lacrimal suppositories. This article explored and expanded the non-pharmacological model of lacrimal suppository therapy for glaucoma by using a combination of lacrimal suppository and medication. The drug-loaded lacrimal suppository was rationally designed through the conjugation of gelatin with polyamide (PAM) via the formation of amide linkages, followed by Schiff base reaction grafting with latanoprost. In vitro drug release studies showed that latanoprost released from drug-loaded lacrimal embolus had sustained-release properties with a release time of 33 days and a drug release volume of 82.6%. The biological evaluation of drug-loaded lacrimal thrombus was carried out by IOP test, retinal potential test, and retinal H&E staining. The results showed that the IOP decreased to 27.125 ± 1.1254 mmHg, and the a and b waves of retinal potential increased to 4.39 ± 0.16 μV and 67.9 ± 2.17 μV, respectively. It indicated that latanoprost lacrimal suppository has a good therapeutic effect on glaucoma.

Glaucoma is a chronic disease that requires lifelong treatment, whereas, discomfort caused by frequent medication may affect the quality of life. Moreover, the therapeutic efficacy of traditional local administration was unsatisfactory due to the rapid ocular clearance mechanism and the ocular barrier. Herein, a triple crosslinked micelle-hydrogel lacrimal implant with low polymer content was fabricated for localized and prolonged therapy of glaucoma. Latanoprost and timolol were simultaneously entrapped in the PEG-PLA micelles with high encapsulation efficiency and further loaded into the triple crosslinked hydrogel, facilitating a double sustained release of drugs. Subsequently, the implant was constructed by a unique molecular orientation fixation technology, which enables the implant to be fixed in the lacrimal duct. The triple crosslinked micelle-hydrogel lacrimal implant manifested a distinguished physicochemical characterization to sustain the release of latanoprost and timolol. In vitro release experiment demonstrated the duration of two drugs was extended for up to 28 days. The in vivo test of elevated intraocular pressure (IOP) in a rabbit model revealed that the IOP-lowering effects were sustained longer than 28 days as expected. The relative pharmacological availability (PA) of lacrimal implants was 5.7 times greater than that of the eye drops. The results of the studies on ocular irritation and histological examination demonstrated the good safety of the lacrimal implant. In conclusion, the triple crosslinked micelle-hydrogel lacrimal implant could effectively lower the IOP with splendid compatibility, demonstrating the promising prospect in the long-term noninvasive treatment of glaucoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center., Methods: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use., Results: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from - 1.6 ± 3.5 to - 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of - 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan-Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4)., Conclusion: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: It is difficult to follow changes in the intraocular pressure (IOP) in glaucomatous eyes comprehensively because of the limited number of outpatient examinations. We report our findings in a case of normal tension glaucoma (NTG) in which frequent self-measurements of the IOP were used to evaluate the IOP-lowering effect of different medications., Patient Concerns: A 50-year-old man with NTG had a nasal step visual field defect in his right eye and was being treated with 0.005% latanoprost (LAT) ophthalmic solution (XALATAN®)., Diagnosis: The patient was diagnosed with NTG., Interventions: The patient had a mean IOP in the right eye of 10.9 ± 1.5 mm Hg (68 measurements in 1 month, Period A) during treatment with 0.005% LAT ophthalmic solution. During the second month (Period B), the mean IOP in the same eye was 9.8 ± 1.7 mm Hg (59 measurements) with treatment with a LAT and carteolol fixed combination (LCFC). And during the third month (Period C), the mean IOP was 7.4 ± 1.1 mm Hg (57 measurements) on the same right eye after the addition of brimonidine and brinzolamide fixed combination ophthalmic solution to the LCFC ophthalmic solution., Outcomes: Comparisons of the IOPs between Periods A and B and between B and C showed that the reductions in the IOP were significant., Conclusion: We conclude that frequent self-measurements of the IOP can determine that small changes of the IOPs are significant., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma., Methods: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy., Results: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each., Conclusions: Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.

Purpose: Only a few trials have compared the intraocular pressure-lowering effects of prostaglandin analogs to carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy in patients with pseudoexfoliative glaucoma. Furthermore, the influence of the glaucoma stage on the intraocular pressure-lowering effects of these drug types has not been studied. The purpose of this study was to compare the IOP-lowering efficacy of latanoprost, a prostaglandin analog versus dorzolamide/timolol fixed combination, a carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy, in patients with pseudoexfoliative glaucoma based on glaucoma stage., Methods: The data of 32 eyes (32 patients) diagnosed with uniocular pseudoexfoliative glaucoma and treated with topical latanoprost (Group 1) or dorzolamide/timolol fixed combination (Group 2) were retrospectively assessed. The groups were subdivided into early and moderate-advanced stages. Patients' demographics, baseline intraocular pressure, final intraocular pressure, and intraocular pressure difference (the difference between the baseline and final intraocular pressure) were determined from medical records and compared between groups and according to glaucoma stage., Results: The mean drug use duration was 17.7 ± 13.5 months. No significant differences in mean baseline intraocular pressure, mean final intraocular pressure and mean intraocular pressure difference between Groups 1 and 2. In Group 2, the mean intraocular pressure difference was significantly greater in patients with early versus moderate-advanced stage glaucoma (p=0.015). The difference, however, was not detected in Group 1. The mean intraocular pressure difference in early-stage glaucoma was significantly greater in Group 2 versus 1 (p=0.033)., Conclusions: Latanoprost and dorzolamide/timolol fixed combination are effective treatments for newly diagnosed pseudoexfoliative glaucoma. In early-stage pseudoexfoliative glaucoma, greater intraocular pressure reduction was noted with dorzolamide/timolol fixed combination than with latanoprost; thus, dorzolamide/timolol fixed combination should be considered when a significant decrease in intraocular pressure is desired in early-stage glaucoma.

Objective: To compare effects of latanoprost, a topical prostaglandin analogue (PGA) commonly used to treat glaucoma and lens instability in dogs, and latanoprostene bunod, a novel PGA with a nitric oxide-donating moiety, on intraocular pressure (IOP) and pupil diameter (PD)., Animals Studied: Ten ophthalmologically normal Beagle dogs., Procedures: Dogs were treated twice a day for 5 days in a randomly selected eye with either latanoprost or latanoprostene bunod. After a 6-week washout period, dogs were treated with the opposite drug. IOP and PD were measured at treatment times, at midday on days 1 and 5, and for 6 days post-treatment., Results: Both drugs significantly decreased IOP and PD. At midday on day 5 of treatment, mean IOP in eyes treated with latanoprost was 4.5 mmHg lower than the fellow eye and 3.0 mmHg lower than the same eye at baseline, while mean IOP in eyes treated with latanoprostene bunod was 5.5 mmHg lower than the fellow eye and 3.6 mmHg lower than baseline. Mean PD was 0.94 mm in eyes treated with latanoprost and 0.76 mmHg in eyes treated with latanoprostene bunod. There was no significant difference between the two drugs for either parameter at that time point (p = .372 and .619, respectively, for IOP relative to control and to baseline; p = .076 for PD) or when analyzed longitudinally. Significant diurnal variation in PD was noted and may have implications for treatment of lens' instability., Conclusions: Latanoprost and latanoprostene bunod produce similar IOP reduction and miosis in normal canine eyes., (© 2022 American College of Veterinary Ophthalmologists.)

Objective: To measure the magnitude and duration of the hypotensive effect of two prostaglandin analogues in glaucoma patients using the water drinking test (WDT)., Methods: Patients received latanoprost or travoprost every 24 h and then every 48 h. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44 h after the last dose; intraocular pressure (IOP) peak, fluctuation and the difference between peak and isolated IOP measurements at consultation times were calculated., Results: Forty-one eyes of 21 patients with primary open-angle glaucoma were included; 22 eyes received latanoprost, and 19 received travoprost. Mean untreated isolated IOP was 17.20 standard deviation (S.D.) 3.73 and 16.95 S.D. 2.61 mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79 mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12 h, 18.44% and 14.64% at 36 h and 16.17% and 14.46% at 44 h, respectively. The fluctuation without treatment was 4.36 and 5.11 mmHg, and with treatment at 12 h was reduced to 2.77 and 2.89 mmHg, increasing again at 36 and 44 h., Conclusions: A hypotensive effect was evident up to 44 h after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12 h., (Copyright © 2021 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To evaluate the ocular hypotensive efficacy and safety of razuprotafib, a novel Tie2 activator, when used as an adjunct to latanoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Methods: Subjects with OAG or OHT and an unmedicated IOP from ≥22 mm Hg to <36 mm Hg were randomized to one of three treatment arms: razuprotafib every day (QD) + latanoprost; razuprotafib twice daily (BID) + latanoprost; or latanoprost monotherapy. The primary endpoint was change in mean diurnal IOP from baseline at day 28., Results: A total of 194 subjects were randomized, and 193 (99.5%) completed the study. Razuprotafib BID + latanoprost resulted in a significantly larger reduction in diurnal IOP than latanoprost alone (7.95 ± 0.26 mmHg vs. 7.04 ± 0.26 mm Hg, P < 0.05). A smaller improvement was observed after 14 days of treatment (7.62 ± 0.26 mm Hg vs. 7.03 ± 0.26 mm Hg, P = 0.11). Razuprotafib QD dosing did not demonstrate additional IOP lowering compared to latanoprost alone. Conjunctival hyperemia on Day 28 increased by 1.1 units on the four-point Efron scale two hours post dose from a baseline value of 0.6 units, and decreased thereafter., Conclusions: Topical ocular razuprotafib as an adjunct to latanoprost therapy was well tolerated and significantly reduced IOP in patients with OAG/OHT., Translational Relevance: These data support the IOP lowering efficacy of targeting Tie2 activation in Schlemm's canal in the relevant patient population.

Purpose: To compare the efficacies of latanoprost 0.005%, travoprost 0.004%, and tafluprost 0.0015% in reducing diurnal intraocular pressure (IOP) fluctuations in patients with newly diagnosed primary open-angle glaucoma (POAG)., Methods: In this prospective randomized clinical trial, 60 patients who were newly diagnosed with POAG were divided into three equal groups. Patients were examined at presentation and at second and sixth weeks. Diurnal phasing of IOP was conducted using a calibrated Goldmann applanation tonometer. IOP measurements were recorded from 8:00 am to 9:00 am, from 3:00 pm to 4:00 pm, and from 7:00 pm to 8:00 pm., Results: The study groups were distributed similarly in terms of age and gender ( p -values: 0.76) and the participants had a mean age of 52.98 ± 13.43 years. The IOP at the day of inclusion was not statistically significant among the three groups ( p -values 0.27, 0.51, and 0.64 at 8 am, 2 pm, and 8 pm, respectively). Similar nonsignificant differences were noticed on the follow-up visits. However, the tafluprost group showed a significant reduction in IOP on the follow-up visit at the second week at 8 pm (30.5% reduction, p -value: 0.03). All three drugs showed a comparable and significant reduction in IOP and IOP fluctuations. The pattern of side effects was similar in all the groups., Conclusion: Latanoprost, travoprost, and tafluprost show a similar effectiveness in reducing the mean IOP and the diurnal IOP fluctuation in POAG. Importantly, the three drugs have comparable tolerability with insignificant differences regarding the pattern of their side effects.

Introduction: To compare the tolerability and efficacy of a preservative-containing latanoprost (PCL) to a preservative-free formulation of latanoprost (PFL) in patients with open-angle glaucoma or ocular hypertension., Methods: A pooled analysis was performed of data from five published studies. The primary outcome was tolerability as evaluated by the severity of hyperemia. The secondary objectives were patient tolerance based on a composite ocular surface disease (OSD) score arising from ocular signs and symptoms, patient and investigator satisfaction, and a comparison of IOP-lowering efficacy., Results: There were three randomized controlled trials and two observational studies included in the analysis. Conjunctival hyperemia improved significantly in 25.6% (388) of patients switched to the PFL group versus 11.7% (117) of patients switched to the PCL group (p < 0.001). PFL was two times superior to PCL in reducing ocular hyperemia (odds ratio = 1.96; p < 0.001). The mean OSD composite score decreased by 32.2% in patients switched to the PFL group and 14.1% in the PCL group (p < 0.001). At 3 months, the mean IOP was similar between groups (p = 0.312)., Conclusion: This post hoc pooled analysis confirmed the findings of the individual studies that PFL is as efficacious at reducing IOP as PCL but better tolerated. After switching to PFL, there was twice the improvement in the OSD composite score. PFL was twice as effective at reducing ocular hyperemia and other ocular signs. These findings suggest that PFL has features that may improve patient compliance, thereby potentially improving the IOP-lowering efficacy on a long-term basis.

Purpose of Review: To discuss a new class of medication that has recently become available for the treatment of glaucoma; as well as share insights into developments in glaucoma medicine administration which has the potential to revolutionize medical therapy for glaucoma., Recent Findings: Newly available eye drops, netarsudil 0.02% and latanoprostene bunod 0.024%, are improving aqueous outflow through the conventional outflow tract. Other new developments in medical glaucoma are focused on alternative methods for sustained glaucoma medication delivery., Summary: Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need of glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl., Patients and Methods: From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation., Results: The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost., Conclusions: Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.

Introduction: To describe the changes in endothelial cell density (ECD), the coefficient of variation (CV), the percentage of hexagonal cells (%HEX), and central corneal thickness (CCT) following 3 months of therapy with netarsudil 0.02%/latanoprost 0.005% fixed combination, and to compare these changes with those seen with netarsudil 0.02% or latanoprost 0.005% in eyes with ocular hypertension or open-angle glaucoma., Methods: A subset of subjects enrolled in a Phase 3 evaluation of the intraocular pressure-lowering efficacy and safety of netarsudil 0.02%/latanoprost 0.005% fixed combination once daily (QD) versus each of its individual components underwent corneal endothelial cell imaging by specular microscopy and ultrasound pachymetry at baseline and following 3 months of therapy. Images were evaluated in masked fashion at an independent reading center. Changes from baseline to 3 months in ECD, CV, %HEX, and CCT were compared between treatment groups., Results: Data from 415 subjects obtained at both baseline and Month 3 were included in this post hoc analysis. Changes from baseline to Month 3 in ECD, CV, and %HEX were clinically insignificant in all three groups, and the changes in the netarsudil/latanoprost fixed combination group demonstrated no statistical difference from those seen in the netarsudil and latanoprost groups. Mean CCT decreased more in the fixed combination group (- 6.4 µm) than in either the netarsudil group (- 3.3 µm, p = 0.0248) or the latanoprost group (- 1.2 µm, p < 0.0001)., Conclusions: Netarsudil 0.2%/latanoprost 0.005% fixed combination QD for 3 months in eyes with ocular hypertension or open-angle glaucoma had no clinically significant effects on endothelial cell density or morphology. The significant decrease in CCT in the fixed combination group compared to the two individual component groups may indicate that the potential effects of each drug on CCT are additive, although the magnitude of the observed effects is likely of negligible clinical significance. CLINICALTRIALS., Gov Identifier: NCT02674854.

Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. The IOP-lowering actions of LBN are mediated by dual mechanisms of the molecule for increasing aqueous humour outflow. The prostaglandin analogue moiety (latanoprost acid) increases uveoscleral outflow, whereas nitric oxide, released by the nitric oxide-donating moiety (butanediol mononitrate), increases outflow through the trabecular meshwork and the Schlemm's canal. The clinical efficacy and safety of LBN 0.024% in patients with open-angle glaucoma or ocular hypertension were established in two similarly designed, double-masked, pivotal phase 3 studies, APOLLO and LUNAR, the pooled three-month efficacy phase of which demonstrated significantly greater IOP-lowering of once-daily LBN 0.024% over twice-daily timolol 0.5% at all time points. Additional support for the IOP-lowering effects of LBN 0.024% was provided by two phase 2 studies in patients with open-angle glaucoma or ocular hypertension (a dose ranging study versus latanoprost and a 24-hour IOP crossover study versus timolol) and a phase 1 study of healthy volunteers with IOP in the normal range. In addition, long-term efficacy and safety were demonstrated in the open-label safety-extension phases of the phase 3 pivotal studies and a phase 3 52-week open-label study of patients with open-angle glaucoma (including normal-tension glaucoma) or ocular hypertension. In conclusion, LBN 0.024% has demonstrated both short-term and long-term IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension, including in healthy volunteers and patients with IOP in the normal range, without apparent clinically-limiting safety or tolerability concerns., (© 2019 The Authors. Clinical and Experimental Optometry published by John Wiley & Sons Australia, Ltd on behalf of Optometry Australia.)

Purpose: The purpose of this study was to assess the intraocular pressure (IOP) - reducing effect of latanoprost in treatment-naïve patients with newly detected open-angle glaucoma with no restriction of the level of untreated IOP., Methods: Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after initiation of treatment was recorded., Results: Mean untreated IOP for all eyes was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9 mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in IOP ranged from -2.3 to 25.3 mm Hg after 1 month, and from -1.3 to 33.3 mm Hg after 3 months. The pressure-lowering effect was considerably more pronounced in eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg higher untreated IOP. Four eyes, with untreated IOP within statistically normal limits, had no or negative IOP-reduction. A regression model predicted that IOP reduction ended at untreated IOP≤16 mm Hg. Multiple regression analysis showed that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with pseudoexfoliation glaucoma., Conclusions: To the best of our knowledge, this paper is the first to report the IOP-reducing effect of latanoprost treatment at all untreated IOP levels in newly detected glaucoma patients. The effect was proportional to the untreated IOP at all levels above 16 mm Hg and better at higher untreated IOP levels, also in relative terms. Our results further confirm the indication of latanoprost as a first-line therapy for glaucoma.

This article discusses eight drugs recently approved by the FDA, including their indications and contraindications, precautions, dosage, and nursing considerations. The article also includes summary charts on 14 recently approved antineoplastic drugs and four drugs approved for rare disorders.

Introduction: An elevated intraocular pressure (IOP) remains the main risk factor for progression of glaucoma upon which we can efficiently act. Pharmacological strategies to reduce IOP are directed towards the reduction of aqueous humour (AH) production and/or the increase in AH drainage through the uveoscleral pathway. However, there are no drugs currently available as first-line treatment to increase AH outflow primarily via the conventional route. Ocular nitric oxide (NO) production takes place in AH outflow pathways and in the ciliary muscle, modulating the cellular response to elevated IOP., Methods: This review describes the mechanism of action of endogenous NO and NO-donating compounds that are under research. It includes information regarding pre-clinical and clinical studies previously conducted with these compounds, discussing their role and therapeutic potential in the pharmacological treatment of ocular hypertension in glaucoma., Results: The topical ocular administration of NO-donating compounds significantly lowered IOP and maintained it in animal models of glaucoma and subjects with ocular hypertension., Conclusions: The mechanism of action of these compounds is novel and scientific evidence that shows promising results. However, there is a need for more comprehensive studies to assess long-term safety and tolerability in order to properly evaluate their use in chronic therapies., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM)., Methods: This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire., Results: In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group., Conclusion: TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores., Trial Registration: UMIN Clinical Trials Registry Identifier, UMIN000023862., Funding: Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Latanoprostene bunod ophthalmic solution 0.024% (hereafter referred to as latanoprostene bunod 0.024%) [Vyzulta™] is a nitric oxide (NO)-donating prostaglandin F 2α analogue approved in the USA for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension. It is thought to lower IOP by increasing aqueous humour outflow through the uveoscleral pathway (mediated by latanoprost acid) and increasing the facility of aqueous humour outflow through the trabecular meshwork pathway (mediated by NO). Results from two multinational, phase III studies (APOLLO and LUNAR) and a pooled analysis of these studies demonstrated the noninferiority of latanoprostene bunod 0.024% to timolol ophthalmic solution 0.5% (hereafter referred to as timolol 0.5%) in terms of IOP-lowering efficacy over 3 months in patients with OAG or ocular hypertension, with the superiority of latanoprostene bunod 0.024% over timolol 0.5% subsequently demonstrated in APOLLO and the pooled analysis. Moreover, there was no apparent loss of IOP-lowering effect in subsequent safety extension periods of up to 9 months. The IOP-lowering efficacy seen in APOLLO and LUNAR was confirmed in a phase III study (JUPITER) in Japanese patients, with IOP reductions observed early (week 4) and maintained over the longer-term (12 months). Latanoprostene bunod 0.024% was well tolerated over up to 12 months in these studies, with most ocular treatment-emergent adverse events (TEAEs) being mild to moderate in severity. Thus, current evidence indicates once-daily latanoprostene bunod 0.024% is an effective and well tolerated treatment option for the reduction of IOP in adults with OAG or ocular hypertension.

Background: Alopecia areata (AA) is one of the most common causes of localized hair loss. There is no universally proven therapy that induces and sustains remission of hair growth in AA., Objective: To compare the efficacy and safety of topical latanoprost, minoxidil and betamethasone valerate on hair growth in patients with AA., Patients and Methods: Hundred patients with AA classified into five groups of 20 treated with: Group I, latanoprost 0.1% lotion; Group II, minoxidil 5% lotion; Group III, betamethasone valerate 0.1% solution; Group IV, combination of latanoprost lotion and betamethasone valerate solution and Group V, a vehicle lotion control group., Results: There was a statistically significant improvement in all therapeutic groups when compared with control group and reduction of severity of alopecia tool score of scalp and beard before and after treatment for all therapeutic groups., Conclusion: Latanoprost, minoxidil and betamethasone valerate are effective and safe in the treatment of patchy AA. The use of latanoprost added to the therapeutic efficacy of topical betamethasone valerate in the treatment of AA and could be an effective adjunctive topical therapy for AA.

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.

Purpose: To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) 0.024% with timolol maleate 0.5% in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Patients and Methods: Pooled analysis of two phase 3, randomized, multicenter, double-masked, parallel-group, noninferiority trials (APOLLO and LUNAR), each with open-label safety extension phases. Adults with OAG or OHT were randomized 2:1 to double-masked treatment with LBN once daily (qd) or timolol twice daily (bid) for 3 months followed by open-label LBN treatment for 3 (LUNAR) or 9 (APOLLO) months. IOP was measured at 8 AM, 12 PM, and 4 PM at week 2, week 6, and months 3, 6, 9, and 12., Results: Of the 840 subjects randomized, 774 (LBN, n=523; timolol crossover to LBN, n=251) completed the efficacy phase, and 738 completed the safety extension phase. Mean IOP was significantly lower with LBN versus timolol at all 9 evaluation timepoints during the efficacy phase (P<0.001). A significantly greater proportion of LBN-treated subjects attained a mean IOP ≤18 mm Hg and IOP reduction ≥25% from baseline versus timolol-treated subjects (P<0.001). The IOP reduction with LBN was sustained through the safety phase; subjects crossed over from timolol to LBN experienced additional significant IOP lowering (P≤0.009). Both treatments were well tolerated, and there were no safety concerns with long-term LBN treatment., Conclusions: In this pooled analysis of subjects with OAG and OHT, LBN 0.024% qd provided greater IOP-lowering compared with timolol 0.5% bid and maintained lowered IOP through 12 months. LBN demonstrated a safety profile comparable to that of prostaglandin analogs.

Purpose: Cromakalim prodrug 1 (CKLP1) is a water-soluble ATP-sensitive potassium channel opener that has shown ocular hypotensive properties in ex vivo and in vivo experimental models. To determine its mechanism of action, we assessed the effect of CKLP1 on aqueous humor dynamics and in combination therapy with existing ocular hypotensive agents., Methods: Outflow facility was assessed in C57BL/6 mice by ex vivo eye perfusions and by in vivo constant flow infusion following CKLP1 treatment. Human anterior segments with no trabecular meshwork were evaluated for effect on pressure following CKLP1 treatment. CKLP1 alone and in combination with latanoprost, timolol, and Rho kinase inhibitor Y27632 were evaluated for effect on intraocular pressure in C57BL/6 mice and Dutch-belted pigmented rabbits., Results: CKLP1 lowered episcleral venous pressure (control: 8.9 ± 0.1 mm Hg versus treated: 6.2 ± 0.1 mm Hg, P < 0.0001) but had no detectable effect on outflow facility, aqueous humor flow rate, or uveoscleral outflow. Treatment with CKLP1 in human anterior segments without the trabecular meshwork resulted in a 50% ± 9% decrease in pressure, suggesting an effect on the distal portion of the conventional outflow pathway. CKLP1 worked additively with latanoprost, timolol, and Y27632 to lower IOP, presumably owing to combined effects on different aspects of aqueous humor dynamics., Conclusions: CKLP1 lowered intraocular pressure by reducing episcleral venous pressure and lowering distal outflow resistance in the conventional outflow pathway. Owing to this unique mechanism of action, CKLP1 works in an additive manner to lower intraocular pressure with latanoprost, timolol, and Rho kinase inhibitor Y27632.

Purpose: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery., Patients and Methods: Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results., Results: A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events., Conclusion: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.

Objective: Supplementation with Mirtogenol® improves the retinal microcirculation and reduces intraocular pressure (IOP) in ocular hypertension, when administrated either alone or in association with an ophthalmic solution (latanoprost). In this study, microcirculatory parameters (perfusion of the circle of Zinn-Haller and retinal circulation) and oxidative stress were tested to assess the effects of Mirtogenol® plus traditional antihypertensive drugs in patients with elevated IOP., Patients and Methods: 88 otherwise healthy patients with increased IOP were followed-up in a supplement registry for 12 weeks. Three groups received; (a) dorzolamide-timolol plus Mirtogenol®; (b) latanoprost drops plus Mirtogenol® or (c) latanoprost only. Oral supplementation consisted of two tablets/day of Mirtogenol® (80 mg of bilberry extract, Mirtoselect® plus 40 mg of Pycnogenol®). IOP, retinal blood flow, perfusion of the circle of Zinn-Haller, and oxidative stress were measured during the registry period., Results: The three study groups were comparable; IOP and ocular blood flow velocity at inclusion were also comparable. Over the study period the decrease in IOP and the improvements in retinal microcirculation were statistically significant for all management groups, with a marginally more evident benefit in Mirtogenol®+latanosprost-treated patients. At 12 weeks, the altered perfusion at the circle of Zinn-Haller was improved in all groups; patients using Mirtogenol® showed a better perfusional pattern compared with subjects using only latanoprost. A reduction in oxidative stress was observed in supplemented subjects at the end of the study period; no significant change was seen in non-supplemented patients. All managements were well-tolerated without side effects., Conclusions: Supplementation with Mirtogenol®, in addition to local ophthalmic treatments, is safe and may contribute as a supplementary management to reach a normal IOP and ocular microcirculatory parameters.

Primary open angle glaucoma (POAG) is the most common type of glaucoma, and is responsible for approximately 90% of glaucoma cases in North America. POAG is characterized by an asymptomatic onset, where patients do not present with symptoms until significant visual loss occurs in late stages of the disease. Importantly, while glaucoma is associated with several risk factors that contribute to damage and disease progression, intraocular pressure (IOP) is the only proven modifiable risk factor at this time. Treatments for POAG include use of pharmacologic and surgical interventions. As of this writing, available pharmacologic options reduce IOP through reduction of aqueous humor production or by facilitating aqueous humor drainage through the uveoscleral outflow pathway (the unconventional pathway). Although cholinergic agonists (eg, pilocarpine) indirectly targets aqueous humor draining through the trabecular meshwork/Schlemm's canal (the conventional outflow pathway), cholinergic agonists are not frequently used, and as of this writing, no agents are currently available that target both the conventional and unconventional outflow pathways. Therapies in late-stage development include trabodenoson, netardsudil, and latanoprostene bunod.

Purpose: To investigate the effects of the long-term use of prostaglandin analogs for glaucoma treatment on the indigenous flora of the conjunctiva., Methods: Bacterial isolates were collected from the conjunctival sacs of 68 patients at Miyata Eye Hospital from February to September 2014, who had been receiving continuous monotherapy with prostaglandin analogs for glaucoma for at least 1 year. Minimum inhibitory concentrations of levofloxacin, gatifloxacin, moxifloxacin, cefmenoxime, tobramycin, chloramphenicol, and erythromycin against the isolates were measured to determine susceptibility., Results: The positive culture rate in all cases was 90.5% (57/63 eyes), and a total of 79 bacterial strains were isolated. The isolated bacteria included aerobic gram-positive cocci (8% Staphylococcus aureus and 41% Staphylococcus epidermidis), coagulase-negative staphylococci (5%), Streptococcus spp. (1%), Corynebacterium spp. (4%), gram-negative bacteria (4%), and the facultative anaerobe Propionibacterium acnes (33%). The positive culture rates for patients using 0.005% latanoprost (Xa group) and 0.004% travoprost (Tz group) were 88.9% and 92.6%, respectively, with no statistically significant difference in the composition of isolated bacteria between groups. Methicillin-resistant S. epidermidis (MRSE) was significantly more frequently isolated in the Xa group. The antimicrobial susceptibility rates of S. epidermidis were significantly lower in the Xa group for levofloxacin, gatifloxacin, moxifloxacin, and tobramycin., Conclusions: The indigenous flora may be affected by the long-term use of prostaglandin analogs. The higher incidence of MRSE in the Xa group should be considered during the long-term, continuous administration of eye drops, such as in glaucoma treatment.

Purpose: To determine factors related to prostaglandin-associated periorbitopathy (PAP) and its prevalence in glaucoma or ocular hypertension (OHT) patients using prostaglandins analogs (PGAs)., Design: A cross-sectional study., Methods: A study of glaucoma or OHT patients, using topical PGAs for at least 3 months, was performed. Eyes treated with PGAs were photoraphed and independently evaluated for PAP by 2 glaucoma specialists using at least 4 out of 7 clinical appearances. The factors of interest were sex, age, body mass index (BMI), types of glaucoma, types of PGAs, duration of PGA use, and concurrent 0.5% timolol. Univariate (χ2 test) and multivariate (multiple logistic regression) analyses assessing risk factors for PAP were performed to estimate the odds ratios (OR) with 95% conidence intervals (CIs)., Results: One hundred thirty-four eyes from 134 patients were included. Seventy (52.2%), 21 (15.7%), and 43 (32%) eyes received components of latanoprost, travoprost, and bimatoprost, respectively. Prevalence of PAP was 44.8% (95% CI, 36.3 to 53.3). Older age >60 years (OR, 3.0; 95% CI, 1.2 to 7.8), bimatoprost (OR, 4.0; 95% CI, 1.6 to 9.5), travoprost (OR, 3.3; 95% CI, 1.1 to 10.1), and timolol (OR, 2.9; 95% CI, 1.3 to 6.8) were at risk of PAP development. In addition, BMI ≥23 kg/㎡ (OR, 0.3; 95% CI, 0.1 to 0.7) was reversely associated with PAP., Conclusions: Older age, bimatoprost, or travoprost were associated with PAP, whereas high BMI was found as a protective factor. Interestingly, timolol possibly precipitated periorbital change when in use with prostaglandins., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma.

Purpose of Review: To discuss recent advances in the medical management of glaucoma and to highlight future medical therapies currently in development., Recent Findings: In 1996, latanoprost (Xalatan) was approved in the United States as a new chemical entity and new class (prostaglandin analogs) for the topical treatment of ocular hypertension and glaucoma. In the period from the late 1990s-2010s, while there were additional new chemical entities, fixed dose combinations, and formulation improvements, there were no new classes of ocular hypotensive medications approved worldwide. We summarize new pharmacological treatments that are currently in clinical trials - new classes, new molecules and new delivery systems., Summary: Although challenges in medical treatment of glaucoma exist, particularly in patient adherence, medical therapy remains the first line treatment for almost all glaucoma patients. Few new medications for glaucoma therapy are currently available for our patients, but multiple drugs with novel mechanisms of action, new formulations, and new delivery mechanisms are currently in development.

Introduction: Intraocular pressure (IOP)-lowering has been demonstrated to slow the progression or onset of visual field loss in open-angle glaucoma (OAG) or ocular hypertension (OHT). Pharmacological lowering of IOP is the most common initial intervention in patients with OAG or OHT, however, many patients will require more than one therapy to achieve target IOP. Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α analog for the reduction of IOP. Areas covered: Current knowledge concerning the mechanism of action of latanoprostene bunod is presented. Additionally, clinical safety and efficacy data from published Phase 1 (KRONUS), Phase 2 (VOYAGER, CONSTELLATION) and Phase 3 (APOLLO, LUNAR, JUPITER) studies are reviewed. Expert opinion: Latanoprostene bunod is a dual mechanism, dual pathway molecule, consisting of latanoprost acid, which is known to enhance uveoscleral (unconventional) outflow by upregulating matrix metalloproteinase expression and remodeling of the ciliary muscle's extracellular matrix, linked to an NO-donating moiety, which enhances trabecular meshwork/Schlemm's canal (conventional) outflow by inducing cytoskeletal relaxation via the soluble guanylyl cyclase-cyclic guanosine monophosphate (sGC-cGMP) signaling pathway. Latanoprostene bunod 0.024% solution applied topically once daily appears more effective in reducing IOP in OHT and OAG subjects than either latanoprost or timolol, with a side effect profile similar to that of latanoprost.

What Is Known and Objective: Genomewide association studies have identified a number of genetic variants that are associated with the development of primary open-angle glaucoma (POAG). This study aimed to explore possible correlations of common single nucleotide polymorphisms (SNPs) in AFAP1, GMDS and PTGFR genes with intra-ocular pressure (IOP) response to latanoprost in POAG patients., Methods: From January 2012 to December 2014, 135 patients with POAG were enrolled into our study. Direct sequencing of polymerase chain reaction (PCR) products was used to analyse the distribution of allelic and genotypic frequencies of AFAP1 rs11723068 G>A and rs757253 T>C, GMDS rs9503012 C>T and rs17134549 T>A, and PTGFR rs3753380 C>T and rs3766355 A>C., Results and Discussion: After 1, 2 and 4 weeks of latanoprost treatment, the IOP of POAG patients decreased significantly (all P < 0·05). The genotype frequencies of six SNPs in AFAP1, GMDS and PTGFR genes were conformed to Hardy-Weinberg equilibrium (HWE). Before latanoprost treatment, the baseline IOP levels of POAG patients carrying CC+AC genotypes of PTGFR rs3766355 A>C were higher than those carrying AA genotype (P < 0·05). After 1, 2 and 4 weeks of latanoprost treatment, POAG patients carrying TT genotype of GMDS rs9503012 C>T showed better response to latanoprost than those carrying CC+CT genotype (P < 0·05). Similarly, POAG patients carrying AA genotype of PTGFR rs3766355 A>C showed better response to latanoprost than those carrying CC+AC genotypes (P < 0·05). Logistic regression analysis showed that age, CC+CT genotypes of GMDS rs9503012 C>T and CC+AC genotypes of PTGFR rs3766355 A>C were independent risk factors for poor response to latanoprost in POAG patients., What Is New and Conclusions: GMDS rs9503012 C>T and PTGFR rs3766355 A>C may be associated with IOP response to latanoprost in POAG patients., (© 2016 John Wiley & Sons Ltd.)

Churg-Strauss syndrome is a rare, systemic vasculitis of unknown cause. Ocular involvement is a rare but established complication and can lead to vision damage or blindness if not treated promptly. Treatment of ocular manifestations corresponds with systemic treatment of the disease and consists primarily of corticosteroids.

Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well-known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of aging phenotype: the defect of klotho gene in mice results aging phenotype such as hypokinesis, arteriosclerosis, and short lifespan. After that, the function of klotho was also reported to maintain calcium homeostasis and to exert a neuroprotective effect in various models of neurodegenerative disease. However, the function of klotho in eyes including retina is still poorly understood. Here, we show that klotho is a key factor underlying the neuroprotective effect of latanoprost during post-axotomy retinal ganglion cell (RGC) degeneration. Importantly, a quantitative RT-PCR gene expression analysis of klotho in sorted rat retinal cells revealed that the highest expression level of klotho in the retina was in the RGCs. Latanoprost acid, the biologically active form of latanoprost, inhibits post-traumatic calpain activation and concomitantly facilitates the expression and shedding of klotho in axotomized RGCs. This expression profile is a good match with the localization, not of the FP receptor, but of organic anion transporting polypeptide 2B1, known as a prostaglandin transporter, in the ocular tissue. Furthermore, an organic anion transporting polypeptide 2B1 inhibitor suppressed latanoprost acid-mediated klotho shedding ex vivo, whereas an FP receptor antagonist did not. The klotho fragments shed from the RGCs reduced the intracellular level of reactive oxygen species, and a specific klotho inhibitor accelerated and increased RGC death after axotomy. We conclude that the shed klotho fragments might contribute to the attenuation of axonal injury-induced calpain activation and oxidative stress, thereby protecting RGCs from post-traumatic neuronal degeneration., (© 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Purpose: To compare latanoprost/timolol (LT) versus travoprost/timolol (TT) fixed combinations for ocular hypertension (OHT) associated with uveitis., Methods: Thirty-six patients (55 eyes) who were treated with LT (28 eyes) or TT (27 eyes) for OHT associated with uveitis were reviewed retrospectively. Intraocular pressure (IOP) and inflammation scores at the initiation of treatment and at the last visit during therapy were analyzed., Results: Although IOP was reduced significantly in both LT and TT groups, the reduction rate was significantly greater with TT group than with LT. The differences in the reduction of IOP between the groups remained significant when the cases were classified into inflammation-induced OHT and steroid-induced OHT. Inflammation score was not exacerbated by LT or TT treatment., Conclusions: Both LT and TT are safe and effective for the treatment of OHT associated with uveitis and greater IOP reduction may be achieved by TT than by LT treatment.

Purpose: To evaluate whether defects in cervical lymphatic drainage influence the intraocular pressure (IOP)-lowering effect of latanoprost in patients with primary open-angle glaucoma (POAG) who have undergone unilateral radical neck dissection (uRND)., Methods: We enrolled (1) bilateral POAG patients who had started (bilateral) latanoprost (0.005%) monotherapy prior to their uRND and (2) treatment-naïve, bilateral glaucoma suspects (GSs) who had undergone the same surgery. We compared the eyes ipsilateral to the uRND with their fellow eyes in terms of the changes in IOP between the baseline (prior to the uRND) and the follow-up visits (1, 3, and 6 months after the uRND)., Results: The study involved 22 eyes of 11 POAG patients and 14 eyes of 7 GSs. In the POAG patients, IOP had increased significantly after surgery in the eyes ipsilateral to the uRND (from 14.7±1.4mmHg to 17.1±2.2mmHg; P = 0.007). Interestingly, in the eyes contralateral to the uRND, IOP had not changed significantly after surgery (from 14.2±1.8mmHg to 14.4±2.0mmHg; P = 0.826). In GSs, the eyes ipsilateral to the uRND did not differ significantly from their fellow eyes in terms of post-operative IOP change (ipsilateral value: 0.3±0.5mmHg, fellow eyes: -0.1±0.7mmHg; P = 0.242)., Conclusion: In the POAG patients, IOP had increased significantly in the eyes ipsilateral to the uRND. However, it had not changed significantly in the eyes contralateral to the surgery or in the eyes of the GSs. These findings suggest that, latanoprost works, at least in part, by enhancing outflow from the aqueous humor via the uveolymphatic pathway., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD)., Methods: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period., Results: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001)., Conclusions: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy., Trial Registration: ClinicalTrials.gov (NCT02802137)., Funding: Santen.

Purpose: To determine the relationship between the polymorphisms of the prostaglandin F2α receptor (PTGFR) and solute carrier organic anion transporter family 2A1 (SLCO2A1) genes and response to latanoprost treatment in Han Chinese patients with glaucoma., Materials and Methods: 89 patients with POAG or OH received latanoprost treatment and intraocular pressure (IOP) data was collected on day 7 and day 30. The rs12093097, rs35586449, rs3753380, and rs3766355 single-nucleotide polymorphisms (SNPs) in the PTGFR gene and rs2370512, rs34550074, and rs4241366 SNPs in the SLCO2A1 gene were analyzed using direct DNA sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: The IOP in patients with GG allele of rs4241366 was lower than in patients with GC+CC on day 7 (p = 0.007). The IOP in patients with CC allele of rs3766355 was lower than in patients with CA+AA on day 30 (p = 0.024). Multiple regression analysis demonstrated that even after adjusting for baseline IOP, the rs4241366 in SLCO2A1 gene and the rs3766355 in PTGFR gene correlated with response to latanoprost on day 7 (rs4241366, p = 0.014) and day 30 (rs3766355, p = 0.035), respectively, in Han Chinese patients with glaucoma., Conclusions: An association was found between single nucleotide polymorphisms of the PTGFR and SLCO2A1 genes and the response to latanoprost in Han Chinese patients with glaucoma. These SNPs may be important determinants of differential response to latanoprost.