How latanoprost changed glaucoma management.

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.

Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations.

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.

Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

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.

Prostaglandin analogs in ophthalmology.

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 ß-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.

A triple crosslinked micelle-hydrogel lacrimal implant for localized and prolonged therapy of 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.

Preparation and performance of latanoprost-loaded hydrogels as a lacrimal suppository for the treatment of glaucoma.

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.

The effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% at a tertiary glaucoma center.

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.

Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis.

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.

Comparative effects of latanoprost and latanoprostene bunod on intraocular pressure and pupil size in ophthalmologically normal Beagle dogs.

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.

Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients.

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.

Duración del efecto hipotensor de los análogos de prostaglandinas medido con la prueba de sobrecarga hídrica en pacientes con glaucoma / Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients

Objetivo Medir con la prueba de sobrecarga hídrica (PSH) la magnitud y duración del efecto hipotensor de dos análogos de prostaglandinas en pacientes con glaucoma. Métodos Los pacientes recibieron latanoprost o travoprost cada 24 horas y luego cada 48 horas. Se practicaron PSH sin tratamiento a las 7 am y con tratamiento 12, 36 y 44 horas después de la última dosis; se calcularon el pico de presión intraocular (PIO), la fluctuación y la diferencia entre el pico y las medidas aisladas de PIO en horas de consulta. Resultados Se incluyeron 41 ojos de 21 pacientes con glaucoma primario de ángulo abierto, 22 ojos recibieron latanoprost y 19, travoprost. La PIO aislada promedio sin tratamiento fue 17,20 desviación estándar (D.S.) 3,73 y 16,95 D.S. 2,61mmHg y el pico de presión 22,45 D.S. 2,91 y 21,58 D.S. 3,79mmHg, para los grupos de latanoprost y travoprost, respectivamente. Con tratamiento, la presión pico se redujo en 22,64% y 20,29% a las 12 horas, 18,44% y 14,64% a las 36 horas y 16,17% y 14,46% a las 44 horas, respectivamente. La fluctuación sin tratamiento fue 4,36 y 5,11mmHg, y con tratamiento a las 12 horas se redujo a 2,77 y 2,89mmHg, aumentando nuevamente a 36 y 44 horas. Conclusiones Se evidenció un efecto hipotensor hasta 44 horas después de la última dosis de latanoprost y travoprost, similar para los dos medicamentos y decreciente en el tiempo. La fluctuación de la PIO sólo se redujo a las 12 horas (AU)

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 24hours and then every 48hours. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44hours 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. 2.61mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12hours, 18.44% and 14.64% at 36hours and 16.17% and 14.46% at 44hours, respectively. The fluctuation without treatment was 4.36 and 5.11mmHg, and with treatment at 12hours was reduced to 2.77 and 2.89mmHg, increasing again at 36 and 44hours. Conclusions A hypotensive effect was evident up to 44hours after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12hours (AU)

Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension.

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.

Frequent self-monitoring of intraocular pressure can determine effectiveness of medications in eyes with normal tension glaucoma: A case report.

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 ±â€…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 ±â€…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 ±â€…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.

Preserved Versus Preservative-Free Latanoprost for the Treatment of Glaucoma and Ocular Hypertension: A Post Hoc Pooled Analysis.

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.

Preservatives in eye drops for glaucoma can cause side effects such as stinging and eye redness. These side effects can cause some patients to reduce the frequency of the drops as prescribed or stop using the drops. One of the most common drops for glaucoma is latanoprost. This study evaluated whether a preservative-free latanoprost (PFL) is as effective as preservative-containing latanoprost (PCL) for reducing eye pressure and whether PFL is better tolerated in patients with glaucoma. The results of the study indicated that PFL was as effective as PCL for reducing eye pressure. The results also indicated PFL was much better at reducing the side effects related to PCL. For example PFL reduces eye redness up to twofold compared to PCL. By reducing the side effects associated with PCL patients may continue to take their glaucoma drops as directed and thereby reduce the risk of vision loss from glaucoma.

Comparison between Latanoprost, Travoprost, and Tafluprost in reducing intraocular pressure fluctuations in patients with glaucoma.

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.

Advances in medical therapy for glaucoma.

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.

Effects of Netarsudil and Latanoprost Alone and in Fixed Combination on Corneal Endothelium and Corneal Thickness: Post-Hoc Analysis of MERCURY-2.

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.

Changes in Prostaglandin-associated Periorbital Syndrome After Switch from Conventional Prostaglandin F2α Treatment to Omidenepag Isopropyl in 11 Consecutive Patients.

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.

Latanoprostene bunod ophthalmic solution 0.024%: a new treatment option for open-angle glaucoma and ocular hypertension.

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.

New Drugs 2018, part 3.

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.