One-year experience with latanoprostene bunod ophthalmic solution 0.024% in clinical practice: A retrospective observational study.

PURPOSE: We evaluated the IOP-lowering efficacy and safety of latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta®), the first topical nitric oxide-donating prostaglandin analog (PGA), in clinical practice. MATERIALS AND METHODS: A retrospective medical chart review from July 2021 to July 2023 of patients with open-angle glaucoma receiving LBN with at least 1 year follow-up was conducted. All included patients received LBN 0.024% as a replacement for a PGA, with examinations at 1-, 3-, 6-and 12-months follow-up. Main outcome measures were IOP, retinal nerve fiber layer thickness, visual fields before/after LBN use and adverse effects. Subgroup analysis with glaucoma types and PGA use were performed for additional IOP reduction after LBN use. RESULTS: Among 78 included patients, 47 patients (81 eyes), 60% with open-angle glaucoma (OAG) remained on LBN throughout 12-month follow-up. Baseline IOP was 18.2±4.2 mm Hg, and Prostaglandin analog (PGA)-IOP was 14.4 ± 3.0 mm Hg (21% mean IOP reduction). After switched to LBN, mean additional IOP reduction was 1.0 mm Hg at month 1, and the greatest reduction was 1.6 mm Hg (8.8% additional mean IOP reduction) at month 12 (P<0.0001). Subgroup analysis (NTG, 73%) showed that mean additional IOP reduction at month 12 was 1.3±2.0 mm Hg in NTG group and 2.1±3.2 mm Hg in POAG group (7.7% vs. 8.7% additional IOP reduction rates, P = 0.23). Subgroup analysis of PGA use at month 12 was 1.8±2.3 mm Hg in tafluoprost group and 0.5±1.7 mm Hg in travoprost group (9.5% vs.2.6% additional IOP reduction rates, P = 0.02). Tolerable ocular adverse effects included irritation (n = 16, 19.8%), mild conjunctival hyperemia (n = 11, 13.6%), dark circles (n = 4, 4.9%) and blurred vision (n = 2, 2.5%). There were no significant visual field and retinal nerve fiber layer thickness changes after 12 months of treatment with LBN 0.024%. CONCLUSIONS: Although high intolerable adverse effects including conjunctival hyperemia and eye irritation happened in the first month, remaining sixty percent of patients exhibited statistically significant additional IOP reductions in the replacement of other PGAs during 12 months of clinical use of LBN 0.024%.

GSK3ß Inhibitors Inhibit TGFß Signaling in the Human Trabecular Meshwork.

Purpose: Primary open-angle glaucoma (POAG) is a leading cause of blindness, and its primary risk factor is elevated intraocular pressure (IOP) due to pathologic changes in the trabecular meshwork (TM). We previously showed that there is a cross-inhibition between TGFß and Wnt signaling pathways in the TM. In this study, we determined if activation of the Wnt signaling pathway using small-molecule Wnt activators can inhibit TGFß2-induced TM changes and ocular hypertension (OHT). Methods: Primary human TM (pHTM) cells and transduced SBE-GTM3 cells were treated with or without Wnt and/or TGFß signaling activators and used for luciferase assays; for the extraction of whole-cell lysate, conditioned medium, cytosolic proteins, and nuclear proteins for Western immunoblotting (WB); or for immunofluorescent staining. Human donor eyes were perfusion cultured to study the effect of Wnt activators on IOP. Results: We found that the small-molecule Wnt activators (GSK3ß inhibitors) (BIO, SB216763, and CHIR99021) activated canonical Wnt signaling in pHTM cells without toxicity at tested concentrations. This activation inhibited TGFß signaling as well as TGFß2-induced extracellular matrix deposition and formation of cross-linked actin networks in pHTM cells or SBE-GTM3 cells. We also observed nuclear translocation of both Smad4 and ß-catenin in pHTM cells, which suggested that the cross-inhibition between the TGFß and Wnt signaling pathways may occur in the nucleus. Using our ex vivo model, we found that CHIR99021 inhibited TGFß2-induced OHT in perfusion-cultured human eyes. Conclusions: Our results showed that small-molecule Wnt activators have the potential for treating TGFß signaling-induced OHT in patients with POAG.

Effect of ripasudil after trabeculectomy with mitomycin C: a multicentre, randomised, prospective clinical study.

BACKGROUND: To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors. METHODS: This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil-ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups. RESULTS: A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success. CONCLUSION: Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

Evaluation of the lamina cribrosa after topical latanoprost therapy in primary open-angle glaucoma or ocular hypertension.

PURPOSE: To investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. METHODS: In this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy. RESULTS: The mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048). CONCLUSION: POAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes.

Corneal thickness and endothelial change after use of ocular hypotensive agents.

Corneal transplantation can restore visual function when visual impairment is caused by a corneal disease. However, this treatment is associated with the scarcity of cornea donors. The suitability of corneal donation from patients with glaucoma using ocular hypotensive agents (OHAs) is controversial. This study aimed to elucidate changes in corneal thickness, corneal endothelial cell density, and corneal endothelial cell hexagonality after OHA use in patients with primary open-angle glaucoma. We retrospectively reviewed the data of 53 glaucoma suspect eyes without OHA use and 106 primary open-angle glaucoma eyes under OHA use. All participants underwent corneal parameter assessment using SP-3000P (Topcon Corp., Tokyo, Japan) at the time of diagnosis and the final visit. The OHA dose and timing of use were recorded. The ocular hypotensive agents score (OHAS) was determined based on the number, formula, frequency, and duration of OHA use. Baseline data showed no significant differences between the two groups with and without OHA use. At the final visit, the OHA-treated group showed significantly lower corneal thickness and corneal endothelial cell density than those of the control group. A weak positive correlation between the OHAS and changes in corneal endothelial cell hexagonality was noted. However, no correlation was observed between the OHAS and changes in corneal thickness or endothelial cell density. In conclusion, patients with glaucoma and using OHAs should undergo the corneal structural properties examinations before donation to ensure the quality of donor cornea.

Silibinin attenuates TGF-ß2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways.

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.

Understanding the treatment paradigm and the sequencing of antiglaucoma fixed-dose combinations in a tertiary center in South India.

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. RESULTS: Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta-blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with ß-blockers being the most consistent one. CONCLUSION: This study is a fairly large study with a minimum of a 5-year follow-up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time.

Preservative-Free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% for Treatment-Naive Patients with Open-Angle Glaucoma.

PURPOSE: To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in treatments-naive patients with primary open-angle glaucoma (POAG). METHODS: This was a retrospective, real-world clinical practice setting study that included 107 eyes of 107 subjects with POAG who had never been treated for glaucoma. All subjects were received PF tafluprost/timolol FC once daily. Intraocular pressure (IOP) levels were documented for each eye at the untreated baseline and up to 6 months after the initiation of medical treatment. All adverse events, including ocular and systemic adverse reactions, were recorded. Additionally, the reasons for medication discontinuations were thoroughly documented. RESULTS: A total of 32 POAG patients with high-baseline IOP (>21 mmHg) and 75 with normal-baseline IOP were included in the study. The subjects' baseline mean age was 62.4 ± 8.7 years (range, 26.0-85.0 years); among them, 42 were female (39.3%). Mean IOP at baseline for all patients was 18.6 ± 4.3 mmHg. The mean IOP at 6 months was 12.6 ± 4.7 mmHg, representing a significant decrease compared to the baseline (-32%, p < 0.001). In POAG patients with high-baseline IOP, mean IOP was significantly lowered from 28.0 ± 5.7 mmHg at baseline to 18.0 ± 5.5 mmHg (-35%, p < 0.001); in patients with normal-baseline IOP, from 14.6 ± 3.4 mmHg at baseline to 10.3 ± 4.1 mmHg (-29%, p < 0.001). PF tafluprost/timolol FC was well-tolerated and safe. After 6 months, 97.2% of all patients remained on therapy. CONCLUSIONS: In this real-world observational study, once-daily treatment with PF tafluprost/timolol FC demonstrated clinically relevant and statistically significant efficacy, as well as safety and good tolerability, in treatment-naive patients diagnosed with POAG.

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.

Predictors and long-term patterns of medication adherence to glaucoma treatment in Denmark-an observational registry study of 30 100 Danish patients with glaucoma.

BACKGROUND: Self-treatment with glaucoma medication (eye drops) has been associated with adherence challenges. Poor adherence results in worse outcomes in terms of visual field loss. OBJECTIVE: To investigate patterns in medication adherence among Danish patients with glaucoma in relation to selected predictors of adherence, long-term adherence patterns, and long-term societal economic consequences of poor adherence. METHODS AND ANALYSIS: This register-based study included 30 100 glaucoma patients followed for 10 years between 2000 and 2018. Glaucoma was identified from the Danish national registers by diagnosis of Open Angle Glaucoma and/or by redeemed prescriptions of glaucoma medication. Logistic regression models were applied to estimate patient characteristics related to medical adherence. Diagnosis-related group fees were applied to estimate healthcare costs. RESULTS: High adherence in the first year(s) of treatment was less likely among men (ORfirst year: 0.78, 95% CI: 0.75 to 0.82), younger individuals and among those with a positive Charlson Comorbidity Index (CCI) score (ORfirst year/CCI≥3: 0.71, 95% CI: 0.63 to 0.80). Adherence in the first year and in the first two years was associated with adherence in the fifth (ORfirst year: 4.55, 95% CI: 4.30 to 4.82/ORfirst two years: 6.47, 95% CI: 6.10 to 6.86) as with adherence in the 10th year with slightly lower estimates. Being medical adherent was related to higher costs related to glaucoma medication after 5 and 10 years comparing with poor adherence, whereas poor adherence was associated with a marked increase in long-term costs for hospital contacts. CONCLUSION: Increasing age, female sex and low comorbidity score are correlated with better adherence to glaucoma treatment. Adherence in the first years of treatment may be a good predictor for future adherence. In the long term, patients with poor adherence are overall more expensive to society in terms of hospital contacts.

Cystoid macular edema occurring after intracameral bimatoprost implantation.

PURPOSE: This case report aims to report the development of cystoid macular edema (CME) unilaterally following the administration of bimatoprost implant (Durysta) injections in both eyes for the treatment of primary open-angle glaucoma (POAG). OBSERVATIONS: An 84-year-old female patient, previously diagnosed with POAG, underwent bimatoprost implant (Durysta) injections in both eyes, spaced one month apart. Subsequently, the patient experienced a gradual decline in visual acuity in her left eye attributed to the development of CME. The condition resolved following a treatment regimen involving topical dexamethasone and nepafenac. CONCLUSION: The use of bimatoprost implant may lead to the occurrence of CME. Ophthalmologists must vigilantly monitor patients post-implantation, especially if they exhibit visual symptoms or have risk factors for a CME.

Minimally invasive micro sclerostomy (MIMS) procedure in the treatment of open-angle glaucoma.

BACKGROUND: To evaluate the safety and efficacy of the Minimally Invasive Micro Sclerotomy (MIMS) procedure in the management of uncontrolled open-angle glaucoma. METHODS: A prospective, open-label, single-arm clinical evaluation with intra-subject comparisons performed at the Ophthalmologic Center after S.V. Malayan, Yerevan, Armenia. Included were adults with primary open-angle glaucoma (OAG) (N = 114) or exfoliative glaucoma (N = 6) who were uncontrolled (IOP > 21) on tolerated topical medication. Mild (N = 7), moderate (N = 66) and severe (n = 47) cases were prospectively included without preselection. Following subconjunctival Mitomycin C, an ab-interno MIMS procedure was performed alone (N = 100) or combined with phacoemulsification (N = 20). Patients were followed for 52 weeks. Procedure-related complications and adverse events were recorded. Success criteria were defined as -5 < IOP ≤ 21mmHg OR a reduction in IOP of ≥ 20% from baseline with (qualified success) or without (complete success) hypotensive medications. RESULTS: Mean patient age was 69 ± 10.1 years. The mean duration of the procedure was 2:01 ± 0:41 min:sec. Scleral drainage channels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Iris plugging of the sclerostomy site and early spikes in IOP were the most common adverse events. The only reason for failure was final IOP > 21 mmHg on tolerated medication. At 52 weeks (n = 93), mean IOP decreased by 38% from baseline (P < 0.001), from 27.9 ± 3.7 to 17.5 ± 5.3 mmHg, a difference of 10.5 mmHg (95% CI: -11.7, -9.3). One-year qualified success was documented in 82.1% (95% CI: 72.9%,89.2%) of the patients and complete success, in 70.5% (60.3-79.4%). 60% (95 CI:49.4%,69.9%) of the patients achieved maximum IOP level of 14 mmHg or at least 30% reduction in IOP. CONCLUSIONS: MIMS procedure is a relatively simple, short and safe minimally invasive bleb-forming procedure. Its efficacy, as found in this short-term evaluation, lends it suitable for mild and moderate uncontrolled open-angle glaucoma patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04503590 2019-05-29.

Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial.

PRCIS: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12 mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44 mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.

Differential Effects of Benzalkonium Chloride on Human Trabecular Meshwork Cells Not Treated or Treated with Transforming Growth Factor-ß2 or Dexamethasone.

Purpose: The objective of the present study was to evaluate the effects of low concentrations of benzalkonium chloride (BAC) (10-7%, 10-6%, or 10-5%) on healthy and glaucomatous human trabecular meshwork (HTM) cells. For this purpose, we used in vitro models replicating a healthy HTM and HTM with primary open-angle glaucoma (POAG) or steroid-induced glaucoma (SG) using two-dimensional (2D) cultures of HTM cells not treated or treated with a 5 ng/mL solution of transforming growth factor-ß2 or 250 nM dexamethasone (DEX). Methods: Analyses were carried out for (1) the intercellular affinity function of 2D HTM monolayers, as determined by transepithelial electrical resistance (TEER) measurements; (2) cell viability; (3) cellular metabolism by using a Seahorse bioanalyzer; and (4) expression of extracellular matrix (ECM) molecules, an ECM modulator, and cell junction-related molecules. Results: In the absence and presence of BAC (10-7% or 10-5%), intercellular affinity function determined by TEER and cellular metabolic activities were significantly and dose dependently affected in both healthy and glaucomatous HTM cells despite the fact that there was no significant decrease in cell viabilities. However, the effects based on TEER values were significantly greater in the healthy HTM. The mRNA expression of several molecules that were tested was not substantially modulated by these concentrations of BAC. Conclusions: The findings reported herein suggest that low concentrations of BAC may have unfavorable adverse effects on cellular metabolic capacity by inducing increases in the intercellular affinity properties of the HTM, but those effects of BAC were different in healthy and glaucomatous HTM cells.

An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper.

PURPOSE: To examine if 12.5 µl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 µl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. PARTICIPANTS: Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. METHODS: Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. MAIN OUTCOME MEASURES: The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). RESULTS: Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. CONCLUSIONS: Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study.

PURPOSE: To compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. METHODS: 691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. RESULTS: 661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia. CONCLUSION: The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.

Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study.

PURPOSE: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT). METHODS: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (ß-blocker) (Cohort 2); PG analogue, ß-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout. RESULTS: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity. CONCLUSION: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT. TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCT2080225063. DATE OF REGISTRATION: 17 February 2020.

How glaucoma patients balance between the advantages and disadvantages of acceptance to the recommended treatment regimen in real-life: Perspectives from a middle-income country.

PURPOSE: Patients with primary open-angle glaucoma (POAG) are required to take long-term treatments with topical medications to halt disease progression. This cross-sectional survey aimed to describe the level of acceptance of Brazilian patients toward the long-term treatment with eyedrops and to find possible correlates of high acceptance. METHODS: POAG patients were recruited from the Glaucoma Service-Santa Casa of Sao Paulo, Sao Paulo, Brazil. Clinical and demographic data were retrieved from participants' electronic records. All patients answered the ACCEPT© questionnaire. This is a generic patient-reported outcome questionnaire specifically developed to assess patients' acceptance of long-term medications and not adherence. Summed scores and those for each domain were calculated to range from 0 to 100 with a higher score indicating greater acceptance. RESULTS: The sample comprised 96 patients with POAG. The mean age was 63.2 ± 8.9 years; 48 were male and 48 female; 55 (57.3%) were white, 36 (37.5%) African-Brazilian, and 5 (5.2%) were of mixed color; most patients (97.9%) had less than high school degree and all had a family income