MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

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.

[ROCK (RHO-KINASE INHIBITORS) FOR THE TREATMENT OF OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION].

INTRODUCTION: Netarsudil ophthalmic solution 0.02% is a new treatment for open-angle glaucoma and ocular hypertension, which was approved for treatment in the United States and in the European Commission. The drug is a rho- kinase inhibitor (ROCK) that lowers intraocular pressure by enhancing the outflow at the trabecular meshwork and decreasing both aqueous humor production and episcleral venous pressure. This literature review aims to present this new treatment, characterize its specific mechanism of action, and discuss its effect and adverse events profile. The efficacy and safety of the drug were studied in the ROCKET and MERCURY clinical trials, in which Netarsudil was compared to other common drugs, including Timolol (Beta-blocker), Latanoprost (Prostaglandin analog), and a combination drop containing Netarsudil and Latanoprost. These trials showed a reduction of 16%-21% in the intraocular pressure (IOP) when using Netarsudil. Moreover, it was found that when using a combination of Netarsudil and Latanoprost, 64.5% of these patients achieved ≥30% reduction in mean diurnal IOP versus 28.8% of patients treated only with Netarsudil and 37.2% of patients treated only with Latanoprost (P<0.0001). The most common adverse event reported was conjunctival hyperemia, which was more frequent in patients using Netarsudil. However, this did not significantly affect the drug tolerance.

[Comparison of the effectiveness and safety of glaucoma drugs in the therapy of primary open-angle glaucoma]. / Sravnenie effektivnosti i bezopasnosti primeneniya protivoglaukomnykh preparatov v terapii pervichnoi otkrytougol'noi glaukomy.

The rise in the number of glaucoma drugs complicates the choice that the ophthalmologists have to do. PURPOSE: The study compares the effectiveness, safety and usability of the Russian latanoprost drug Trilaktan and the drug Xalatan in monotherapy for patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). MATERIAL AND METHODS: This is a multicenter observational study of the effectiveness and safety of eye drops Trilaktan (Groteks, Russia) and Xalatan (Pfizer MFG. Belgium N.V., Belgium) in monotherapy for patients with POAG of early and moderate stages or OH. The maximum duration of the regimen for the studied drugs was 87 days. The study included 76 patients: 56 (74%) women and 20 (26%) men aged 50-84 years (mean age 66.3±1.3 years). The groups were homogeneous in demographic, anthropometric and vital indicators. Effectiveness was assessed by the trends in intraocular pressure (IOP) changes, safety - by analyzing the adverse events, usability and ease of use - by the questionnaires the study patients filled. RESULTS: Both drugs investigated in this study decrease IOP by a mean of 6-8 mm Hg depending on tonometry method, with difference not exceeding 0.55 mm Hg. The proportion of patients with IOP decreased by 30% and more from the baseline level was 89.5% in both groups. The differences between the indicators of drug usability (by McMonnies conjunctival hyperemia scale, tear break-up time (TBUT), punctate keratopathy, OSDI questionnaire results) were insignificant, and the observed changes did not decrease the tolerability of the studied drugs. The patients using Trilaktan also commended the usability of the included eye drops dispenser. CONCLUSIONS: The results of this study allow a conclusion that the effectiveness and safety of Trilaktan (Groteks, Russia) eye drops are equal to those of Xalatan (Pfizer MFG. Belgium N.V., Belgium) eye drops in patients with POAG of early and moderate stages or OH. Trilaktan is easy to use thanks to the included eye drops dispenser.

The effect of latanoprost 0.005% solution in the management of scalp alopecia areata, a randomized double-blind placebo-controlled trial.

Alopecia areata (AA) is a recurrent chronic disease that affects hair follicles and results in hair loss. Make an increase in the number, thickness, and length of eyelashes is an important side effect of latanoprost eye drop. This study aimed to evaluate the effect of hypertrichosis property of latanoprost in the treatment of scalp AA. In this randomized double-blind placebo-controlled trial, 30 participants with scalp AA assigned to receive either topical latanoprost 0.005% solution or placebo for 12 weeks. In both arms, patients also received clobetasol 0.05% cream in isopropyl alcohol (1:1). The hair loss area pictured at baseline and the end of the fourth, eighth, and twelfth weeks. According to the images, the dermatologist assessed the hair loss area, hair density, and the severity of alopecia. Latanoprost significantly increased hair density (37.2 ± 26.1 vs. 14.6 ± 18.6) and regrowth (58.3 ± 39.3 vs. 21.6 ± 24.1) based on the Severity of Alopecia Tool (SALT) system compared to the control group (p = 0.03 and 0.02, respectively). However, there were no significant differences between the two groups in reduction in the hair loss area and SALT, and the incidence of side effects (p = 0.718, 0.262, and ≥0.99, respectively). Results showed the acceptable safety and efficacy of latanoprost 0.005% solution to increase hair density and regrowth. So, it could be safely used for the management of scalp AA.

Comparison of efficacy, safety and satisfaction of latanoprost versus minoxidil, betamethasone and in combination in patients with alopecia areata: A blinded multiple group randomized controlled trial.

Alopecia areata (AA), a polygenic and chronic autoimmune disease and there is no definitive cure. We aimed to evaluate latanoprost effects in patients with AA. In this controlled randomized double-blind clinical trial, we enrolled patients with AA randomly assigned to six groups of 18; Group 1 received latanoprost eye drops; group 2 minoxidil 5% solution; group 3 latanoprost eye drops and minoxidil 5% solution; group 4 betamethasone and minoxidil 5% solution; group 5 betamethasone solution and latanoprost eye drops; group 6 (the control group) betamethasone solution. The alopecia severity in patients before and after treatment was assessed by severity of alopecia tool (SALT). One hundred and eight patients, 50% male (mean age: 32.6 ± 10.4) were studied. The overall SALT score decreased in all. After 2 weeks, patients receiving betamethason-minoxidil and betamethason-latanoprost showed more decline in their SALT than other groups. In final, there was statistically significant difference among betamethasone-latanoprost group with minoxidil, betamethasone-minoxidil and betamethasone groups. Regrowth was higher in latanoprost and betamethasone-latanoprost groups than minoxidil. Topical latanoprost added to therapeutic efficacy of topical betamethason and minoxidil in treating patchy AA, suggesting it being beneficial and safe adjuvant therapy and add to efficacy of topical treatments without any adverse effects.

[Fixed combination of latanoprost and timolol in the long-term treatment of patients with normal-tension glaucoma]. / Fiksirovannaya kombinatsiya latanoprost/timolol v dolgosrochnom lechenii patsientov s glaukomoi normal'nogo davleniya.

The most well-studied and widely prescribed fixed-combination drug for open-angle glaucoma is latanoprost/timolol. Its significant hypotensive effect is especially important in challenging cases, among which are patients with normal-tension glaucoma. With long life expectancy and the constant need for treatment, requirements are high for both the effectiveness of the drug and its tolerability. This paper presents a follow-up of 7 patients with normal-tension glaucoma who have been using the fixed combination of latanoprost/timolol for 10 years. All patients showed very good tolerability to the drug and their quality of life was preserved. A moderate rate of disease progression according to static perimetry was noted in one case. A mild degree of dry eye syndrome according to the OSDI questionnaire and an objective assessment of the state of the ocular surface was observed in one patient. The latanoprost/timolol fixed combination is a well-tolerated, highly effective and safe long-term treatment choice for normal-tension glaucoma.

Effects of topical prostaglandin drops on angiogenesis in an in ovo chick chorioallantoic membrane model.

BACKGROUND: To investigate the effects of bimatoprost, latanoprost and travoprost on angiogenesis in the chick chorioallantoic membrane (CAM) model in ovo. MATERIALS AND METHODS: Fifty fertilized specific-pathogen-free chick eggs were used in this preclinical, prospective, experimental embryo study. Eggs were randomly distributed into 5 groups of ten eggs. Eggs were placed in the incubator after disinfection of their shells with alcohol and monitored appropriate temperature and humidity. On the 3rd day of incubation, a small window was opened on the eggshell. Bimatoprost in group 1, latanoprost in group 2, travoprost in group 3, bevacizumab in group 4, phosphate-buffered-saline (PBS) used in group 5 was applied by injection to CAM. The sterile film was glued onto the broken part of the shell and the eggs were placed in the incubator again. On the 8th day of incubation, eggs were opened and vascular structures on CAMs were examined. Digital photographs were taken, analysed in the ImageJ open source image processing software and differences between groups were evaluated. Thereafter, VEGF (Vascular endothelial growth factor) levels were measured appropriately in the embryo samples. RESULTS: All embryos in the prostaglandin groups and the PBS control group were observed to have life signs confirmed by heart rate. In 8 embryos in the bevacizumab group, no life signs were confirmed, while 2 embryos with life signs showed severe hypoplasia. Vascular density, number of vessels and VEGF levels in the bimatoprost, latanoprost and travoprost groups, there were statistically significantly higher than the PBS control group. CONCLUSION: This study demonstrates that topical prostaglandin drops increase angiogenesis in the chick CAM model in ovo.

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y-27632, a Rho kinase inhibitor.

Scar formation is the most common cause for failure of glaucoma filtration surgery because of increased fibroblast proliferation and activation. We have now examined the effect of Y-27632, a Rho-associated protein kinase (ROCK) inhibitor, on postsurgical scarring formation in human Tenon fibroblasts (HTFs). Collagen gel contraction assay was used to compare contractility activity of Y-27632 with several antiglaucoma drugs. Immunofluorescence and western blotting were used to examine expression of scar formation-related factors. We found that Y-27632 inhibited collagen gel contraction, as well as α-smooth muscle actin and vimentin expression; these were promoted by treatment with latanoprost, timolol, or transforming growth factor (TGF)-ß. To investigate the effect of Y-27632 in postsurgical scarring, we mimicked TGF-ß secretion by stimulating HTFs with TGF-ß prior to Y-27632 treatment. HTFs cultured in the presence of TGF-ß significantly increased gel contraction. In contrast, when HTFs were treated with 10µM Y-27632, contraction was significantly inhibited. Furthermore, Y-27632 reduced TGF-ß-induced phosphorylation of mitogen-activated protein kinase signalling. These results suggest that ROCK inhibitors may inhibit fibrosis by inhibiting transdifferentiation of Tenon fibroblasts into myofibroblasts and by inhibiting TGF-ß signalling after surgery through mitogen-activated protein kinase pathway suppression. These results implicate that ROCK inhibitors may improve outcomes after filtering surgery with a potential antiscarring effect, while latanoprost and timolol may induce fibrosis. SIGNIFICANCE OF THE STUDY: Scar formation is the primary cause of failure after glaucoma filtration surgery. A ROCK inhibitor, Y-27632, has been introduced as a novel potential antiglaucoma treatment to reduce intraocular pressure. The aim of our study was to elucidate the effect of Y-27632 on scarring formation after glaucoma filtration surgery, in direct comparison with other antiglaucoma drugs. Our findings thus suggested that Y-27632 may inhibit fibrosis and improve outcome after glaucoma filtration surgery through inhibition of transdifferentiation of Tenon fibroblasts into myofibroblasts, and the TGF-ß and MAPK signalling after surgery, while latanoprost and timolol may induce fibrosis.

Direct and crossover effects of brinzolamide, betaxolol, and latanoprost on choroidal thickness.

PURPOSE: To investigate the acute effects of brinzolamide, betaxolol, and latanoprost (drugs commonly used in the medical management of glaucoma) on choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Ninety healthy volunteers were evaluated in this prospective study. Participants were randomly divided into 3 groups. Brinzolamide, betaxolol, and latanoprost were administered into the left eyes of the first group (n = 30), second group (n = 30), and third group (n = 30), respectively, and artificial tear (Sodium hyaluronate) was instilled into the right eyes of all participants. Subfoveal choroidal thickness (SFCT) was measured using EDI-OCT before and 45 minutes after administration of the antiglaucomatous drops. RESULTS: SFCT revealed a significant increase in the left eye (administered antiglaucomatous drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.049) and a significant increase also in the right eye (administered artificial drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.001). However, SFCT did not reveal a significant increase in the left eye (p = 0.213) or in the right eye (p = 0.062) in the latanoprost group. CONCLUSION: Brinzolamide and betaxolol caused an increase in SFCT, while latanoprost had no significant effect on SFCT.

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.

The Effects of Latanoprost With Benzalkonium Chloride Versus Travoprost With SofZia on the Ocular Surface.

PURPOSE: To assess ocular surface changes in participants using latanoprost with benzalkonium chloride (Xalatan) and travoprost with SofZia (Travatan Z). METHODS: In this prospective, open-label, nonrandomized cohort study, participants were classified into two groups: group 1 (n=28) naive to glaucoma therapy, group 2 (n=27) on previous Xalatan monotherapy in both eyes. Both groups started (or continued) Xalatan in the right eye and Travatan Z in the left eye. Baseline, 1-, and 2-month measurements of tear breakup time (TBUT), corneal staining score, conjunctival staining score, conjunctival hyperemia score, tear production, and intraocular pressure were obtained. The Ocular Surface Disease Index questionnaire measured participants' comfort and dryness symptoms. Medication preference was recorded. RESULTS: Data were collected from 55 participants. Tear breakup time at baseline and 1-month follow-up in group 1 was significantly longer than that of group 2 (P=0.005). At 2 months, there was no significant difference in TBUT between the two groups (P=0.779). Tear production in group 1 at all three time points was significantly higher than group 2 (P<0.05). Conjunctival staining score at 2 months in group 1 was significantly higher than group 2 (P=0.031). There was no significant difference in other parameters between the groups at any other time point. No significant difference in any parameter was found between Xalatan and Travatan Z (intragroup comparison). CONCLUSIONS: Significant differences in ocular surface characteristics were detected between groups, but no significant difference was detected between participants treated with Xalatan and Travatan Z.

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.

HL3501, a Novel Selective A3 Adenosine Receptor Antagonist, Lowers Intraocular Pressure (IOP) in Animal Glaucoma Models.

PURPOSE: The A3 adenosine receptor (A3AR) is a known therapeutic target for glaucoma treatment. In this study, we developed HL3501 and examined its selectivity profile and in vitro and in vivo effects. METHODS: For the rabbit model, intraocular pressure (IOP) was increased by laser photocoagulation of the trabecular meshwork (TM). The rabbits were then topically treated with HL3501, latanoprost, timolol, or vehicle for 3 weeks. For the mouse model, HL3501, latanoprost, or vehicle was administered following induced IOP elevation by dexamethasone (Dex). The IOP of all rabbits and mice was measured. Electroretinography was performed on both eyes of dark-adapted anesthetized mice on days 0 and 21. The mice's eyes were enucleated at the end of the treatment for immunofluorescence staining. RESULTS: HL3501 was highly specific to the A3AR and inhibitory of A3AR function. In the rabbit glaucoma model, HL3501 and latanoprost significantly decreased the IOP. In the Dex-treated mouse model, HL3501 and latanoprost significantly decreased the IOP and increased the b-wave amplitude as compared with the vehicle treatment. HL3501 and latanoprost also inhibited fibronectin and α-smooth muscle actin expression induced by Dex treatment. CONCLUSIONS: HL3501 had effects similar to those of latanoprost in reducing ocular hypertension in animal models. HL3501 could be used as a novel approach to treat glaucoma. TRANSLATIONAL RELEVANCE: HL3501 is a novel preclinical compound targeting the A3 adenosine receptor, which may also be a new treatment option to fill the unmet needs of many glaucoma patients.

Ocular Surface Disease in Glaucoma Patients Randomized to Benzalkonium Chloride-Containing Latanoprost and Preservative-Free Bimatoprost.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to receive BAK-containing latanoprost (Xalatan) or preservative-free bimatoprost (Lumigan PF). Intraocular pressure (IOP), basal Schirmer's test, noninvasive keratograph tear-breakup time (TBUT), conjunctival redness score (R score), OSD index (OSDI), and corneal Oxford staining were recorded and compared between the 2 groups at 1-month and 4-month visits. The influence of BAK was analyzed by a generalized estimating equation model. Results: We enrolled 74 and 76 eyes treated with latanoprost and bimatoprost, respectively. The IOP decreased in both groups, although greater reduction was observed for latanoprost (13.95 vs. 15.42 mmHg, P = 0.0264). There was a significantly negative association between tear flow and latanoprost use (ß = -0.763, P = 0.0243). The first and average TBUT did not show intergroup differences, but the area with unstable tear film increased with latanoprost use and showed marginal significance at 4-month visit (9.33% vs. 5.94% P = 0.055). In both groups, OSDI decreased, whereas Oxford stain increased over time, and R scores showed improvement after transient increase in the first month. The bimatoprost group had significantly worse conjunctival hyperemia, whereas a negative association with conjunctival hyperemia was revealed for latanoprost use (R score-bulbar nasal: ß = -0.045, P = 0.0423). Conclusions: BAK-containing latanoprost was associated with decreased tear secretion and may be associated with tear-film instability, whereas bimatoprost was associated with worse conjunctival hyperemia. Ocular surface side effects should be considered when prescribing BAK-containing medication to glaucoma patients.

Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy.

ABSTRACT: The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ±â€Šstandard deviation, 69.9 ±â€Š14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ±â€Š5.4 mm Hg) than grades 0 (15.0 ±â€Š5.1 mm Hg, P = .032) and 1 (14.5 ±â€Š4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ±â€Š3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ±â€Š0.8) and bimatoprost (2.0 ±â€Š0.7) than latanoprost (1.0 ±â€Š0.8, P < .001 for both comparisons) and tafluprost (1.0 ±â€Š0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ±â€Š0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard ß = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.

Corneal Ectasia Induced by Prostaglandin Analogues.

Our purpose is to document the first case of unilateral mild corneal ectasia developed in an apparently nonpredisposed cornea after topical latanoprost treatment, and its regression after treatment withdrawal. We describe a 44-year-old man with visual impairment in his left eye (OS) and a past medical history of myopic refraction and ocular hypertension with latanoprost treatment, the rest of ocular examination was normal. A decrease in visual acuity was observed with a refractive change. Corneal tomography showed features of mild corneal ectasia in his OS. Topical prostaglandin analogue therapy was removed and replaced by other antiglaucoma topical treatment. Corneal tomography returned to normal, an improvement in the quality of vision was observed and refractive astigmatism recovered to baseline values. This case illustrates that topical latanoprost does affect the matrix metalloproteinases balance in corneal extracellular matrix, and subsequently may produce a corneal weakening. Corneal biomechanical features and corneal stiffness do probably recover after topical prostaglandin analogues withdrawal.

Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma.

BACKGROUND: Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence. METHODS: Preferred Reporting Items for Systematic review and Meta-Analyses guidelines were followed. Studies evaluating topical PGAs in patients with ocular hypertension or open angle glaucoma were included. MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, LILACS and ClinicalTrials.gov were searched between 1946 and 2019. Experimental studies, animal studies and randomised studies with other intraocular pressure-lowering eye drops were excluded. RESULTS: 214 studies (28 232 patients) met the inclusion criteria. Using prospective data, the incidence of uveitis and CME among PGA users were 62/28 232 (0.22%) and 25/28 232 (0.09%), respectively. A higher frequency of both uveitis and CME were found among latanoprost users compared with bimatoprost. There were 21 case studies reporting CME including 48 eyes in 43 patients. 47 of 48 eyes (97.9%) had previous incisional ocular surgery. 8 eyes were re-challenged, of which 7 (87.5%) recurred. 7 case studies reported uveitis in 15 eyes of 10 patients. 7 of 15 eyes (46.7%) were either pseudophakic or aphakic. 6 eyes were re-challenged, and all 6 (100%) recurred. CONCLUSIONS: Cases of uveitis or CME revealed a confounding effect of ocular surgery, aphakia or subluxed intraocular lens. PGAs may be used in non-surgical patients without concern of causing CME or uveitis. The incidences of PGA-associated CME and uveitis are rare with limited prospective studies on the cause-effect relationship.

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.