Efficacy of topical latanoprost in the treatment of eyelid vitiligo: A randomized, double-blind clinical trial study.

Numerous studies have demonstrated that the pigmentation of iris and around the eyelid is a common side effect of latanoprost, a prostaglandin F2alpha analogue used in the treatment of glaucoma. Hence, the authors decided to study the effectiveness of topical latanoprost on vitiligo patches around the eyelid. In this randomized, double-blind, clinical trial study, 31 patients with vitiligo vulgaris and focal vitiligo involving the eyelids were evaluated. Patients were randomly divided into two groups. First group received topical latanoprost gel twice daily for 12 weeks, whereas the second group received placebo with the same protocol. To evaluate severity of the disease the VIDA rating system was used. Serial photos of the patches were taken to compare and evaluate the repigmentation percentage of the patches. The patients in both groups had almost similar VIDA score (p > .05). First group showed improved pigmentation, whereas participants in the second group did not show any improvement in the pigmentation. The group treated with latanoprost showed significant reduction in the symptoms of the disease, whereas those treated with placebo did not show any alteration (p > .05). No significant complications were observed in either groups. Latanoprost proved effective in treating vitiligo disease involving eyelids.

Latanoprost niosomes as a sustained release ocular delivery system for the management of glaucoma.

Objective: Glaucoma is a leading cause of irreversible blindness worldwide. Whereas latanoprost is one of the most effective drugs in glaucoma treatment, its eye drops need frequent application leading to lack of patient adherence. This study aimed to develop a patient-friendly niosome-in-gel system for the sustained ocular delivery of latanoprost.Methods: Niosomes were prepared by the reverse-phase evaporation technique and optimized for different formulation parameters, such as cholesterol/surfactant and drug/surfactant ratios. Selected niosomal formulations were incorporated into different gels and their viscosity and drug release kinetics were evaluated. Optimal niosomal gel was evaluated in vivo in rabbits' eyes for irritation potential and ability to reduce intraocular pressure.Results: FT-IR studies showed that there were nonspecific interactions between latanoprost and different niosomal components leading to drug encapsulation efficiency ≥88%. Latanoprost encapsulation efficiency increased with the drug/surfactant ratio and encapsulation efficiency ∼98% was obtained at a ratio of 50%. Pluronic® F127 had the best ability to sustain drug release from the niosomes. In rabbits' eyes, this gel was free of toxic and irritant effects and reduced intraocular pressure over a period of three days, which was significantly longer than that of commercial latanoprost eye drops.Conclusion: Latanoprost niosomal Pluronic® F127 gel may find applications in glaucoma management.

Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia.

Latanoprost has recently been used to treat alopecia as it causes an increase in the capillary density of patients. This work presents for the first time the development of polymeric nanocapsules containing latanoprost for the topical treatment of alopecia. Poly-ε-caprolactone nanocapsules loading latanoprost were developed by nanoprecipitation of the polymer on the surface of drug oily nanodroplets. The method encapsulated 93.9 ± 0.4% of the drug into nanocapsules of 197.8 (± 1.2) nm (PdI = 0.15 ± 0.01). The nanosystem presented a zeta potential equal to - 30.1 ± 1.8 mV and was stable for at least 90 days when stored at 6°C. The colloidal aqueous dispersion was non-irritating, according to the in vitro HET-CAM test. The nanocapsules improved latanoprost accumulation into the hair follicles when topically applied on porcine skin, delivering 30% more drug to these skin structures relative to the control solution (P < 0.05). Also, with a simple manual massage, latanoprost accumulation was increased by twofold (P < 0.05). In conclusion, in addition to being a stable and safe formulation, nanocapsules enhanced latanoprost accumulation into the hair follicles, being a nanosystem with high potential for use as a topical formulation for the treatment of androgenic alopecia.

Intractable Ocular Diseases and Treatment Progress.

In recent years, with the aging of the population and the frequent use of electronic devices, many eye diseases have shown a linear upward trend, such as dry eye disease, glaucoma, cataract, age-related macular degeneration, and diabetic retinopathy. These diseases are often chronic and difficult to cure. Based on the structure and barrier of the human eye, this review describes the pathogenesis and treatments of several intractable eye diseases and summarizes the advanced ocular drug delivery systems to provide new treatment ideas for these diseases. Finally, we also look forward to the prospect of RNAi therapy in the treatment of eye diseases.

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment Study.

PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. DESIGN: Multicenter, randomized, triple-masked, placebo-controlled trial. PARTICIPANTS: Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients from the treatment and placebo groups, respectively). METHODS: In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24 months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n = 272) and those with glaucomatous progression (n = 78), as determined by visual field change (primary outcome), were assessed. MAIN OUTCOME MEASURE: PROMs on health-related and vision-related quality of life. RESULTS: Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P = 0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P = 0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). CONCLUSIONS: Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to function as primary end points in clinical trials when participants have newly diagnosed early-stage glaucoma.

Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.

Treatment of canine postoperative ocular hypertension with combined latanoprost 0.005% and atropine 1% ophthalmic solutions.

OBJECTIVE: To compare the effects of topical 0.005% latanoprost (L) vs combined 0.005% latanoprost and 1% atropine (LA) on control of postoperative ocular hypertension (POH), development of posterior synechiae formation, pupil size, and blindness after phacoemulsification surgery in dogs. ANIMAL STUDIED: Dogs with postoperative ocular hypertension were included in the study: L-group, latanoprost (eight dogs, 14 eyes) and LA-group, latanoprost and atropine (nine dogs, 15 eyes). PROCEDURES: Complete ophthalmic examinations including tonometry were performed at 1, 7, and 21 days following phacoemulsification. RESULTS: No significant differences were found between the measured intraocular pressure (IOP) at days 1 and 7 postphacoemulsification surgery in the L-group and the LA-group (P = 0.26 [14.12 ± 1.76 mmHg vs 16.96 ± 1.68 mmHg] and P = 0.71 [15.45 ± 1.43 mmHg vs 16.20 ± 1.36 mmHg], respectively). No significant differences were found between pupil sizes at day 7 for the two groups (P = 0.25 [13.83% vs 24.77%]). No significant differences were found between odds of posterior synechiae formation at day 21 (P = 0.92) with a probability ± SE for L-group vs LA-group at 0.27 ± 0.14 vs 0.25 ± 0.13. No significant differences were found in odds of postoperative blindness between groups (P = 0.58) with a probability ± SE of 0.21 ± 0.11 vs 0.13 ± 0.09, respectively for L and LA. CONCLUSIONS: Combined topical latanoprost and atropine in dogs maintains normal postoperative IOPs but does not seem to cause increased mydriasis compared to latanoprost alone.

The effect of topical latanoprost on corneal clarity; 1-year prospective study†.

Purpose: Quantitatively investigate the effects of topical latanoprost on the corneal optical density parameters by using Scheimpflug system. Materials and methods: New cases of primary open-angle glaucoma treated with topical latanoprost as first-line treatment were enrolled in this prospective study. Corneal densitometry measurements obtained with the Scheimpflug system (Pentacam; Oculus, HR) at baseline and 1st, 3rd, 12th months after topical latanoprost treatment. For densitometry analysis, the 12-mm diameter area of the cornea was subdivided into 4 concentric radial zones and also into anterior, central, and posterior layers based on corneal depth. Pre and post-treatment values were compared statistically by a paired sample t-test. Results: The mean age of 18 female (66.7%) and 9 male (33.3%), totally 27 cases were 59.48 ± 10.1 years. There was no statistically significant difference between pretreatment and 1st-month post-treatment corneal densitometry values in all regions (p > 0.05 for all). Corneal densitometry values began to decline at 3rd month after treatment. The decrease continued until the 12th month of the beginning of the treatment and was significant in all zones except 2-6 mm of the anterior and central zones (p = 0.23, p = 0.08, respectively). Conclusion: Long-term administration of topical latanoprost may cause decrease in corneal densitometry measurements. Further prospective studies with a longer follow-up period are required to clarify the relationship between prostaglandin analogues and their effects on the cornea transparency.

Does using topical latanoprost affect subfoveal choroidal thickness?

Purpose: The aim of our prospective study was to investigate the effect of using latanoprost eye drops on subfoveal choroidal thickness in the macular area, as measured by using enhanced depth imaging optical coherence tomography (EDI-OCT). Materials and methods: A total of 39 eyes from 39 patients with bilateral glaucoma or ocular hypertension who had never received hypotensive therapy (study group) and 39 eyes from 39 age- and gender-matched healthy individuals (control group) were included in this study. The EDI-OCT measurements of subfoveal choroidal thickness were obtained during an initial visit before latanoprost therapy and at visits after 1 and 3 months of latanoprost therapy. Results: The mean subfoveal choroidal thickness was 309.5 ± 38.5 µm before latanoprost therapy in the study group and 307.3 ± 31.8 µm in the control group (p = .794). During latanorprost therapy in the study group, mean values of subfoveal choroidal thickness at the initial visit and at intervals of 1 and 3 months were 309.5 ± 38.5 µm, 314.2 ± 39.7 µm, and 318.3 ± 33.4 µm, respectively, which indicated a statistically significant difference between the initial and third visits only (p=.002). Conclusion: Subfoveal choroidal thickness increased after 3 months of topical latanoprost therapy.

Different medications for the treatment of Ménière's disease by intratympanic injection: A systematic review and network meta-analysis.

BACKGROUND: It is generally accepted that intratympanic injection provides an effective approach to manage severe vertigo in Ménière's disease. Although there are several medications available, that which is the most effective is still subject to debate. OBJECTIVE: To assess the effectiveness and safety of the different medications used in the treatment of Ménière's disease by intratympanic injection using a network meta-analysis. METHODS: PubMed, EMBASE, CINAHL and CENTRAL were searched. Only randomised controlled trials that compared the effectiveness of medications used for intratympanic injection to treat Ménière's disease with each other or a placebo were included. The primary outcome assessed was the effectiveness of medication in the management of vertigo symptoms. The effectiveness was expressed in terms of risk ratio (RR) with a 95% credible interval (CrI) for individual studies analysed. Network meta-analyses were performed by Stata version 15.0 using the network package. RESULTS: Nine studies involving 314 patients treated with five different medications were included in the present analysis. A number of injections given varied from 1 to 10 and the follow-up time from 3 to 28 months. When compared to each other or to a placebo, Gentamicin was found to be the most efficacious medication, followed by Methylprednisolone, Latanoprost, Dexamethasone and Ganciclovir in order of effectiveness. However, no significant difference in efficacy was found between Gentamicin and Methylprednisolone when outcomes from studies with a follow-up time equal to or more than 24 months were analysed. It was not possible to conduct subgroup and sensitivity analysis because of the limited number of studies that were included. CONCLUSION: All medications are more effective than a placebo in the treatment of Ménière's disease by intratympanic injection. According to the SUCRA, Gentamicin ranked the most effective, with Gentamicin and Methylprednisolone equally effective in the long-term effect. When the potential risk of hearing loss induced by Gentamicin is taken into consideration, Methylprednisolone may be the best choice for the treatment of Ménière's disease by intratympanic injection.

Switch from BAK-preserved to preservative-free latanoprost decreases anterior chamber flare in POAG patients.

PURPOSE: To validate the hypothesis that BAK induces low-grade inflammation in the anterior chamber, we designed a study to investigate whether switching from BAK-preserved to preservative-free latanoprost in patients with primary open-angle glaucoma (POAG) would reduce the flare levels. PATIENTS: Forty-one eyes of twenty-two patients with primary open-angle glaucoma treated with BAK-preserved latanoprost for at least 6 months as monotherapy were included. Exclusion criteria included any use of topical eye drops other than latanoprost, pseudoexfoliation and pigment dispersion glaucoma, wearing of contact lenses and intraocular surgery in the past year. METHODS: At the start of the study, we measured baseline flare values. We then switched all patients to preservative-free latanoprost. After 1, 2, and 3 months, a routine ophthalmological examination was performed and flare measurement repeated. RESULTS: Thirty-three eyes were followed up throughout the entire 3-month period. One month after the switch to preservative-free latanoprost, a statistically significant mean drop in flare of - 0.96 ph/ms (P = 0.025) was observed. Mean flare decreased further by - 1.31 ph/ms (P = 0.0027) after 2 months and by - 1.25 ph/ms (P = 0.0041) after 3 months. CONCLUSION: The switch from BAK-preserved to preservative-free latanoprost induced a statistically significant reduction in mean flare value. Whereas our previous study showed an increase in flare when initiating treatment with BAK-preserved eye drops, this study shows a decrease in flare upon cessation of BAK-preserved drugs. The combined evidence from the two studies strongly suggests that in humans BAK exerts its effects not only on the ocular surface, but also at the level of the anterior chamber.

Ocular surface status in glaucoma and ocular hypertension patients with existing corneal disorders switched from latanoprost 0.005% to tafluprost 0.0015%: comparison of two prostaglandin analogues with different concentrations of benzalkonium chloride.

IMPORTANCE: Glaucoma treatment has often been associated with adverse side-effects from preservatives that are included in the used eye drops. BACKGROUND: To evaluate changes in the ocular surface and the presence of prostaglandin-induced corneal disorders after being switched from latanoprost 0.005% to low preservative tafluprost 0.0015% ophthalmic solution. DESIGN: Single centre, prospective study. PARTICIPANTS: Patients with primary open-angle glaucoma or ocular hypertension that had received treatment with once daily latanoprost 0.005% ophthalmic solution for control of intraocular pressure (IOP) for 3 months, with a score of above 1 on the National Eye Institute (NEI) ocular surface staining scale. METHODS: Following the ≥3 month latanoprost treatment period, patients were switched to once daily low preservative tafluprost 0.0015% ophthalmic solution. Patients were followed for a minimum of 3 months. MAIN OUTCOME MEASURES: Ocular surface changes were assessed by fluorescein staining score (NEI scale). Additional evaluations included tear break-up time, hyperaemia score, subjective symptoms, changes in intraocular pressure and presence of adverse reactions. RESULTS: Out of 59 patients enrolled, 51 were included in the final analysis. Fluorescein staining scores at baseline, prior to treatment switch, were 6.9 ± 3.1 and 3.3 ± 2.7 at the end of the study period (change in scores was -3.6 ± 2.2 [P < 0.001]). At last follow-up, significant improvements were observed in tear break-up time, hyperaemia score and subjective symptoms (all P < 0.05). CONCLUSIONS AND RELEVANCE: The clinical signs of ocular surface disease and subjective symptoms of dry eyes improved following the switch to low preservative tafluprost and demonstrated comparable IOP lowering effectiveness.

Periorbital Changes associated with Topical Prostaglandins Analogues in a Hispanic Population.

OBJECTIVE: To describe the prevalent side effects of prostaglandin analogues (PA) in a Hispanic population and their effect on quality of life (QOL). PATIENTS AND METHODS: This is a cross-sectional study conducted in a tertiary medical facility in which patients were evaluated in a single visit. Total of 14 participants in the study, 10 women and 4 men. Ages ranged from 26-78 years old. Subjects underwent a single full Oculoplastic evaluation by two physicians; one was blinded on patient medical history and assessed for PA side effects. After evaluation, each study subject was asked to answer a self reported QOL questionnaire. RESULTS: Study participants had used or were currently using Bimatoprost (28.6%), Latanoprost (50%) or Travoprost (21.4%). After evaluate periorbital changes, 2 patients (14.3%) had ptosis, 2 (14.3%) had periorbital skin hyperpigmentation, 11 (78.6%) had periorbital fat show, 11 (78.6%) had eyelash elongation, 1 (7.1%) had injected conjunctiva, 5 (35.7%) had iris hyperpigmentation. 10 (71.4%) noted changes in the size/shape of their eyes. The questionnaire show that 10 (71.4%) disliked how their eyes looked. 9 (62.4%) reported dry eyes, 3 (21.4%) noted increased need to blink, 5 (35.7%) reported foreign body sensation, 7 (50%) reported burning sensation, 2 (14.2%) reported secretions and 3 (21.4%) reported sticky eyes. Mean QOL was 3.50, 2.14, and 2.00 in the Bimatroprost, Latanoprost, and Travoprost users respectively. CONCLUSION: QOL questionnaire showed that Bimatoprost side effects had the most negative impact in QOL, followed by the Latanoprost and Travoprost groups.

A Comparative Study on Efficacy of Intraocular Pressure Lowering of Two Fixed-Dose Antiglaucoma Drug Combination Brinzolamide-Brimonidine Versus Latanoprost-Timolol in Primary Open-Angle Glaucoma and Ocular Hypertension.

Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.

Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial.

Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

A Comparative Ocular Pharmacokinetics Study of Preservative-Free Latanoprost Unit-Dose Eye Drops and a Benzalkonium Chloride-Preserved Branded Product Following Topical Application to Rabbits.

Purpose: To evaluate the aqueous humor pharmacokinetics of a preservative-free 0.005% latanoprost unit-dose eye drop (test drug) compared with that of a benzalkonium chloride (BAK)-preserved 0.005% latanoprost branded product (control drug) following topical application to rabbits. Methods: A total of 120 healthy New Zealand albino rabbits were administrated test eye drops (T group) or control eye drops (C group) for a comparative pharmacokinetics study. The aqueous humor was collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after a single dose or multiple doses. Ultraperformance liquid chromatography-tandem quadrupole mass spectrometry was employed to detect latanoprost free acid (LTA, the active metabolite of latanoprost) in the aqueous humor. Results: For the single-dose study, there was no significant difference (t-test, P > 0.05) in the peak concentration (Cmax) of LTA in aqueous humor between the T group (69.0 ± 23.4 ng/mL) and C group (73.8 ± 28.7 ng/mL). The area under the curve values over 12 h (AUC0-12h) of LTA for the 2 groups were 254.4 (ng/mL) × h and 219.5 (ng/mL) × h, respectively. For the multidose study, there was also no significant difference (t-test, P > 0.05) in the Cmax of LTA in the aqueous humor between the T group (86.8 ± 21.2 ng/mL) and C group (70.5 ± 25.9 ng/mL). The AUC0-12h values of LTA for the 2 groups were 274.5 (ng/mL) × h and 256.3 (ng/mL) × h, respectively. Conclusions: The preservative-free 0.005% latanoprost unit-dose eye drops demonstrated similar pharmacokinetic properties to the BAK-preserved branded product following topical application to rabbits.

One Year of Netarsudil and Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Phase 3, Randomized MERCURY-1 Study.

PURPOSE: A phase 3 trial (MERCURY-1) investigated efficacy and safety of a once-daily, fixed-dose combination (FDC) of netarsudil and latanoprost, compared with each active component, in reducing elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). A planned 3-month analysis demonstrated the superiority of netarsudil/latanoprost FDC over its individual active components at every assessment. Herein, the 12-month efficacy and safety of netarsudil/latanoprost FDC are reported. DESIGN: Double-masked, randomized, active-controlled, parallel-group trial. PARTICIPANTS: Patients had unmedicated IOP >20 to <36 mmHg in both eyes at 8:00 am and met other standard criteria for OAG or OHT. METHODS: Randomization to once-daily netarsudil 0.02%/latanoprost 0.005% FDC (n = 238), netarsudil 0.02% only (n = 243), or latanoprost 0.005% only (n = 237). Patients instilled study drug into each eye between 8:00 pm and 10:00 pm. MAIN OUTCOME MEASURES: IOP was obtained at 8:00 am, 10:00 am, and 4:00 pm on day 1 (baseline); at weeks 2 and 6; and at months 3, 6, 9, and 12. Ocular and systemic safety were evaluated up to month 12. RESULTS: Netarsudil/latanoprost FDC maintained statistically superior IOP lowering compared to its components at every assessment for 12 months. Least squares mean diurnal IOP (± standard error) at month 12 was 16.2 ± 0.23 mmHg for netarsudil/latanoprost FDC, 17.9 ± 0.20 mmHg for netarsudil, and 17.6 ± 0.18 mmHg for latanoprost (P < 0.05 for netarsudil/latanoprost FDC versus each comparator). The safety profile of netarsudil/latanoprost FDC was consistent with its individual components. The proportion of patients who experienced at least 1 adverse event (AE) was 82.8% (197/238) in the netarsudil/latanoprost FDC group, 78.2% (190/243) in the netarsudil group, and 54.0% (128/237) in the latanoprost group. The most common AE was conjunctival hyperemia, mostly of mild severity, with an incidence of 63.0% in the netarsudil/latanoprost FDC treatment group compared with 51.4% in the netarsudil group and 21.9% in the latanoprost group. CONCLUSIONS: Results at 12 months revealed superior efficacy for netarsudil/latanoprost FDC compared with the individual components, netarsudil and latanoprost, at every time point assessed and an ocular tolerability profile similar to that of netarsudil alone.

The efficacy of the fixed combination of latanoprost and timolol versus other fixed combinations for primary open-angle glaucoma and ocular hypertension: A systematic review and meta-analysis.

BACKGROUND: Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system. RESULTS: We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group. CONCLUSIONS: LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.

Omidenepag Isopropyl Versus Latanoprost in Primary Open-Angle Glaucoma and Ocular Hypertension: The Phase 3 AYAME Study.

PURPOSE: To evaluate the efficacy and safety of omidenepag isopropyl (OMDI), a selective, non-prostaglandin, prostanoid EP2 receptor agonist, in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). DESIGN: Phase III, randomized, investigator-masked, active-controlled, parallel-group, noninferiority study (ClinicalTrials.govNCT02623738). METHODS: After a washout period of 1-4 weeks, eligible patients were randomized (1:1) to OMDI 0.002% or latanoprost 0.005% once daily for 4 weeks. Intraocular pressure (IOP) was measured at 9:00 AM, 1:00 PM, and 5:00 PM at weeks 1, 2, and 4. The primary endpoint was the change from baseline in mean diurnal IOP at week 4. The noninferiority margin for OMDI versus latanoprost was 1.5 mm Hg. Adverse events (AEs) were recorded. RESULTS: Of the 190 patients randomized, 189 had at least 1 post-baseline IOP measurement. At baseline, patients who received OMDI or latanoprost had a mean ± SD diurnal IOP of 23.78 ± 1.73 mm Hg and 23.40 ± 1.51 mm Hg, respectively. At week 4, least-squares mean ± SE reduction in IOP from baseline with OMDI (-5.93 ± 0.23 mm Hg) was noninferior to that of latanoprost (-6.56 ± 0.22 mm Hg; 95% confidence interval between groups: 0.01-1.26). The most frequently reported treatment-related ocular AEs (OMDI vs latanoprost) were conjunctival hyperemia (23/94 patients [24.5%] vs 10/96 patients [10.4%]), corneal thickening (11/94 patients [11.7%] vs 1/96 patients [1.0%]), and punctate keratitis (0/94 patients vs 5/96 patients [5.2%]). No serious AEs were observed in either group, and there were no discontinuations related to the study drug. CONCLUSIONS: OMDI 0.002% was noninferior to latanoprost 0.005% in reducing IOP in patients with OHT or POAG and was well tolerated.