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The beta-adrenoceptor blocker timolol maleate (TML) is a commonly used pharmaceutical agent for the management of glaucoma. Conventional eye drops have limitations due to biological or pharmaceutical factors. Therefore, TML-loaded ethosomes have been designed to mitigate these restrictions and give a viable solution for reducing elevated intraocular pressure (IOP). The ethosomes were prepared using the thin film hydration method. Integrating the Box-Behnken experimental strategy, the optimal formulation was identified. The physicochemical characterization studies were performed on the optimal formulation. Then, in vitro release and ex vivo permeation studies were conducted. The irritation assessment was also carried out with Hen's Egg Test-Chorioallantoic Membrane model (HET-CAM), and in vivo evaluation of the IOP lowering effect was also performed on rats. The physicochemical characterization studies demonstrated that the components of the formulation were compatible with each other. The particle size, zeta potential, and encapsulation efficiency (EE%) were found as 88.23 ± 1.25 nm, -28.7 ± 2.03 mV, and 89.73 ± 0.42 %, respectively. The in vitro drug release mechanism was found as Korsmeyer-Peppas kinetics (R 2  = 0.9923). The HET-CAM findings verified the formulation's eligibility for biological applications. The IOP measurements revealed no statistical difference (p > 0.05) between the once-a-day application of the optimal formulation and the three-times-a-day application of the conventional eye drop. A similar pharmacological response was observed at lowered application frequencies. Therefore, it was concluded that the novel TML-loaded ethosomes could be a safe and efficient alternative for glaucoma treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To report the unforeseen complication of total obstruction of a glaucoma drainage implant (GDI) tube lumen by white deposit material and to present a preliminary report identifying the composition of this material., Methods: Two subjects with a high IOP due to total obstruction of a GDI tube were reviewed. Both patients had a long history with brinzolamide and timolol maleate eye drops. The GDI tube was swept with a 5-0 polypropylene suture stent in order to open the tube. The intraluminal solid sample was successfully collected from the implant tube in one patient. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to determine the origin of the intraluminal sample., Results: Intraluminal deposits containing components of antiglaucoma drugs e.g., timolol and brinzolamide are a rare cause of total obstruction of GDI tubes., Conclusions: Our study describes a new cause of total obstruction GDI tubes. The long-term use of timolol maleate and brinzolamide and their presence in the intraluminal solid sample collected from the blocked GDI tube suggest that the glaucoma medication may have a role in the pathogenesis. However, the exact mechanism is unknown and requires further studies.

Aims: Glaucoma is a chronic ophthalmic disease, which has become one of the leading causes to progressive and irreversible blindness. Current ophthalmic drug delivery to treat glaucoma is mostly eyedrop, whose rapid elimination on corneal surface can lead to poor bioavailability. The present study was aimed to develop a timolol maleate loaded thermo-sensitive gel (TM-TSG) with improved bioavailability to treat glaucoma., Main Methods: TM-TSG was prepared by homogeneously dispersing 0.3% (w/v) timolol maleate, 24.25% (w/v) poloxamer 407 (P407) and 1.56% (w/v) poloxamer 188 (P188) into phosphate buffer solution (pH = 7.4) and the formulated TM-TSG was characterized., Key Findings: TM-TSG was stored in liquid form at room temperature (25 °C) and transited to semisolid gel at physiological temperature (32 °C). The rheological property of TM-TSG was in favor of uniform distribution of drug. TM-TSG showed good stability at different conditions including centrifugation, autoclaving and different temperature. In vivo pharmacokinetic studies indicated that TM-TSG could enhance absorption of TM in aqueous humor and improve the ocular bioavailability in comparison of commercial TM eyedrops. In vivo experiment result showed that TM-TSG had greater effect in treating glaucoma than TM eyedrops by sustainably lowering intraocular pressure (IOP) for a week. Moreover, slit lamp test and histopathological analysis demonstrated that TM-TSG had excellent biocompatibility., Significance: TM-TSG could be a promising ophthalmic delivery system for glaucoma therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the present investigation, the effect of timolol maleate loaded ocuserts was studied as an alternative for conventional anti-glaucoma formulation. Ocuserts were prepared using natural polymer sodium alginate and ethyl cellulose. Physico-chemical properties along with drug entrapment efficiency (94-98%), content uniformity (93.1% ± 0.264-98.00% ± 0.321), in vitro drug release (83.42% ± 0.35 at end of 12 h), ex vivo permeation all showed satisfactory results, which was found to follow zero order kinetics. Ex vivo permeation studies showed better results, revealed that the permeability coefficient was dependent on polymer type. The sterility test accelerated stability studies and in vivo studies such as eye irritancy test, in vivo drug release of the optimized ocusert was determined. The anti-glaucoma activity was measured using Schiotz tonometer at different time interval. Significant reduction in Intra ocular pressure (IOP) within 3 days was observed in case of rabbits treated with ocusert in comparison to the rabbit treated with marketed eye drop formulation. Hence timolol maleate loaded ocuserts proved to be a promising and viable alternative over conventional eye formulation for the sustained and controlled ophthalmic drug delivery, targeting the drug within the ocular globe thus improving patient compliance for the treatment of glaucoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The combination of timolol maleate (TM) and brinzolamide (BRZ) has potential therapeutic prospects for treating glaucoma. However, the conventional formulation of TM and BRZ exhibits sub optimal therapeutic effects attributable to the poor ocular bioavailability of these drugs., Objective: Therefore, the aim of the present study was to design and evaluate TM and BRZ loaded nanostructured lipid carrier (NLC) to enhance the bioavailabilities, permeation and precorneal residence time of these drugs that would result in efficacious treatment of glaucoma., Methods: In this study, combination of drugs with different characteristic properties was loaded in NLC. The dual drugs loaded NLC was prepared by melt emulsification technique and evaluated for characteristic properties such as particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL), in vitro drug release and ex vivo drug penetration studies., Results: The PS and PDI of optimized NLC formulation were found to be 110.36 ±0.47 nm and 0.24 ± 0.00 respectively. The EE and DL of optimized NLC formulation were found to be 77.12 ± 0.64 % and 0.360 ± 0.01 % for TM respectively; whereas, 70.73±0.64 % and 0.71 ± 0.02 %for BRZ respectively. In vitro drug release studies showed a comparable initial rapid release of around 34 ± 2.90 % for TM and 38 ± 3.10 % for BRZ in the first 5 h followed by sustained drug release around 72.29 ± 5.90 % for TM and 70.08 ± 6.40 % for BRZ until last 24 h. Ex vivo drug penetration studies showed about 33.47 ± 2.80 % of TM and 36.20 ± 2.80 % of BRZ permeated in the first 5 h followed by 72.30 ± 6.40% of TM and 67.69 ± 6.500 % of BRZ until 24 h. There was remarkable enhancement in the release pattern and permeation of both the drugs from NLC as compared to that from their suspension., Conclusion: With dextrous optimization of dose and excipients concentration, the dual drugs with different characteristic properties can be successfully loaded in NLC formulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug., Objectives: The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops., Material and Methods: The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies., Results: The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye., Conclusions: It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

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). Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. 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. The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). 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. Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Background: Globally, it is expected that 111 million people will have glaucoma by 2040. Intraocular pressure (IOP) is the most crucial clinical risk factor for glaucoma onset and/or progression. Aims and Objectives: The aim of the study is to compare 0.4% ripasudil, 0.02% netarsudil, and 0.5% timolol in combination with 0.005% latanoprost in the medical management of primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Materials and Methods: The prospective randomized clinical study was conducted on patients with mild-to-moderate POAG or OHT on a single prostaglandin analog (e.g., latanoprost) not achieving target IOP. Patients with narrow-angle glaucoma, any ocular surgery, and advanced glaucoma were excluded from the study. Patients were followed up at 15 days, 1 month, 2 months, and 3 months for a complete ophthalmic examination. Results: The maximum number of patients showed 41-60 years of age group. The male-female ratio was 1.8:1. A mild-to-moderate adverse event in the form of conjunctival hyperemia was seen in all groups. The mean reduction in IOP (mmHg) from baseline to 3 months in Groups A, B, and C is 5.7±0.923, 7.11±0.832, and 6.83±0.707 mmHg, respectively. Conclusion: When given in combination with 0.005% latanoprost and comparing IOP reduction in terms of efficacy, 0.4% ripasudil and 0.02% netarsudil are almost similar, but ripasudil was well tolerated and showed minimal ocular adverse effects; hence, ripasudil is better in comparison to netarsudil. [ABSTRACT FROM AUTHOR]

Purpose: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. Methods: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 μL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. Results: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. In conclusion: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. Methods: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1–2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. Results: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. Conclusion: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. Trial Registry: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Aim The aim of this study was to compare 2% dorzolamide/0.5% timolol fixed combination brand name drug (Cosopt) to its generic counterpart (Twinzol) regarding efficacy and side effects. Patients and methods The study included 92 eyes of 92 patients diagnosed with primary open-angle glaucoma and are indicated for antiglaucoma fixed combination of 20 mg/ml dorzolamide/5 mg/ml timolol). Patients were randomly divided into two groups: the first group received Cosopt, whereas the second received Twinzol. In visit, intraocular pressure (IOP) was measured and any local side effects by either eye drops was recorded. Monitoring and recording the percentage of IOP drop each month and all over the 3 months duration of follow up visits were done. Results The percentage of IOP drop for Cosopt and Twinzol after 1 month showed a significant P value of 0.032, with a mean percent reduction in IOP of 28.55%, median percent reduction of 26.92%, the minimum is 3.82% while the maximum is 62.96% for the Cosopt group, while that for Twinzol was 23.14, 21.29, 4.17, and 57.14%, respectively. On the other hand, the percentage of drop of IOP between the two groups after 3 months showed insignificant P value (0.646). IOP measurement was statistically insignificant between the two groups at 1 (0.462) and 3 months (0.639). As regards side effects; both eye drops were comparable with an insignificant P value of 0.49. Conclusion The study demonstrated a reliable efficacy and safety on using generic therapy Twinzol compared with band counterpart Cosopt. [ABSTRACT FROM AUTHOR]

Background: Conventional aqueous eye drop formulations have a shorter retention period and wash out of the precorneal region more easily. In this study, biodegradable microsphere-loaded hydrogels were developed to extend the time of residence and improve the drug bioavailability. The prepared microspheres were fabricated using PLGA as the biodegradable polymer and PVA as the surfactant. Hydrogels were prepared using Carbopol 940 and Gellan gum as gelling agents. Methods: The microspheres were created through a technique known as double emulsion solvent evaporation method. Evaluation included for its percentage yield, entrapment efficiency, particle size and surface morphology of the prepared microspheres. Timolol Maleate microsphere loaded hydrogel underwent assessments for pH, spreadability, rheological behaviour, sterility, antimicrobial efficacy, in vitro release studies, drug release kinetics and ocular irritation. Results: FTIR analysis confirmed compatibility between the drug and polymer. SEM observations indicated spherical microspheres with sizes ranging from 1 to 12 µm, suitable for ocular application. All formulations exhibited pH values between 4.2 and 5.0, with gelation occurring at 35°C to 38°C. Formulation F3 demonstrated optimal viscosity (1486 - 1850 cps) and good spreadability. Sterility tests were successful, and F3 displayed a drug release of 82.6% after 24 hours. Antimicrobial studies exhibited inhibition zones, and ocular tests on rabbits revealed no irritation. Stability analysis indicated no significant changes in pH or clarity. Conclusion: Based on physiological, rheological, and in vitro evaluations F3 was identified as the most suitable formulation for extended Timolol Maleate release via hydrogel, holding promise for effective glaucoma treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] In situ gelling systems (ISGS) can prolong retention time and bioavailability of ophthalmic solutions. The complexity and cost of ISGS avert their industrial scale-up and clinical implementation. In this study, we demonstrate novel application of hot-melt extrusion (HME) technology for continuous manufacturing of ISGS (MeltDrops Technology). Timolol maleate (TIM) and dorzolamide hydrochloride (DRZ) loaded MeltDrops were successfully developed using HME for glaucoma management, thereby resolving issues with batch manufacturing of ISGS, prolonging retention time thus improving bioavailability. The MeltDrops technology involves one-step, i.e., passing all the ingredients through an extruder at a screw speed between 20 and 50 rpm and barrel temperature of 80 °C. The comparative evaluation of MeltDrops and batch-processed ISGS demonstrated that MeltDrops exhibited better physical and chemical content uniformity. The extrusion temperature and screw speed were critical factors influencing content uniformity and properties of the MeltDrops. MeltDrops showed sustained drug release for > 12 h in vitro (TIM = 83.07%; DRZ = 60.43%, 12 h) versus marketed eyedrops. The developed MeltDrops followed Peppas-Sahlin model, combining Fickian diffusion and swelling processes. The in vivo study in New Zealand rabbits revealed superior effectiveness and safety of the MeltDrops as compared to the marketed eyedrops. Herein we conclude, MeltDrops would serve as a cutting-edge platform technology that can be used to manufacture various ISGS with one-step processability, cost-effectiveness, and improved product quality, which are otherwise processed by batch manufacturing that involves numerous complex processing steps. [ABSTRACT FROM AUTHOR]

Introduction: Primary open angle glaucoma (POAG) treatment is characterized by long-duration therapy, prescription variability, and non-adherence. Patient awareness toward drug treatment is crucial to ensure adherence. The present study was planned to evaluate drug treatment awareness, patient-perceived drug adherence, and prescription patterns in POAG patients. Methodology: This was a cross-sectional, single-center, questionnaire-based study conducted in the ophthalmology out patient department of a tertiary care hospital from April 2020 to November 2021. Patients of either gender, aged 40-70 years, with a confirmed diagnosis of POAG, who had records of POAG medications for at least last 3 months and who provided written informed consent, were included. Prescription details were recorded, and subsequently, patients were administered a pre-validated drug treatment awareness (14 items) questionnaire, a self-reported medication adherence (9-item) questionnaire, and then they performed eye drop instillation in a simulated setting. Results: The total number of patients enrolled was 180, which yielded 200 prescriptions. The mean drug treatment awareness score was 8.18 ± 3.30, and 135 (75%) patients scored more than 50% (≥7/14). Similarly, 159 patients (83.33%) had scored >50% (i.e. >5/9), with a mean score of 6.30 ± 1.70 in the medication treatment adherence questionnaire. The mean eye drop instillation performance score was 7.18 ± 1.20. The 200 POAG prescriptions containing 306 drugs were analyzed, with beta blockers (184/200, 92%) and timolol (168/200, 84% encounters) being the highest prescribed classes/drugs. Conclusion: POAG patients did have adequate treatment awareness with good self-reported medication adherence and performance of eye drop instillation technique. Around 25% patients lacked awareness; hence, reinforcement education programs on medication regimens need to be implemented. [ABSTRACT FROM AUTHOR]

Introduction: Glaucoma is an irreversible chronic eye disease in which intraocular pressure (IOP) control is important. This study aimed to assess the IOP-lowering effects and adherence scores between fixed combination dorzolamide/timolol maleate (FCDT) and non-fixed combination dorzolamide and timolol XE (NFDT) in open-angle glaucoma (OAG) patients. Methods: A randomised controlled trial in a parallel, single-blinded study involving 60 OAG patients was conducted. The patients were randomised into FCDT or NFDT based on a block randomisation technique. A pre-study run-in with Gutt timolol was administered for two weeks. IOP was assessed at baseline, month 1 and month 3, with a bottle weight measurement at month 3. Results: Only 55 OAG patients were analysed, with 8.4% dropping out. A statistically significant mean IOP reduction was observed in each group from baseline to month 1 (FCDT: mean difference [MD] = 4.93, 95% confidence interval [CI] = 4.00, 5.86); NFDT: MD = 4.92, 95% CI = 4.024, 5.82) and from baseline to month 3 (FCDT: MD 5.17, 95% CI = 4.19, 6.15; NFDT: MD = 4.85, 95% CI = 3.874, 5.82). The overall FCDT mean IOP was significantly lower by 1.02 mmHg (95% CI = -2.01, -0.02) than NFDT (F(1, 53) = 4.19; P = 0.046). A significant interaction was observed between time and treatment at month 3, with the mean IOP for FCDT being lower by 1.22 mg than for NFDT (P = 0.037). The mean adherence score was significantly higher in the FCDT group than in the NFDT group (t stat (df) = 3.88 (53); P < 0.001). The reduction in IOP between the groups became non-significant after adherence was adjusted (F(1, 52) = 2.45; P = 0.124). Conclusion: Both drugs showed a decrease in IOP but more so in FCDT. However, no difference was found in terms of medication adherence. An emphasis on treatment compliance is needed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of fixed combination versus concomitant unfixed topical glaucoma treatment on patients' adherence and ocular surface health. Patients and Methods: This is a 6-month, prospective, parallel-group, observational study in patients with ocular hypertension (OHT), primary open-angle glaucoma (POAG), or exfoliation glaucoma (XFG). A total of 142 patients with similar baseline characteristics were enrolled in this study. Seventy-one patients received a Latanoprost 0.005%/Timolol 0.5% fixed combination in the evening, whereas seventy-one patients received the unfixed treatment with Latanoprost 0.005% in the evening and Timolol 0.5% twice daily. The primary outcome was the adherence rate at baseline, and at the 3- and 6-month follow-up visits. The secondary outcomes included the signs of ocular surface disease (OSD) and intraocular pressure (IOP). Results: The adherence of patients treated with the fixed combination was higher than the unfixed treatment at the 3-month (78.0% vs. 63.0%, p < 0.001) and at the 6-month visits (73.0% vs. 58.5%, p < 0.01). The Break-up Time, Schirmer test, and Van Bijsterveld score were worse in the unfixed group at baseline and all subsequent examinations (p < 0.05 for all comparisons). There were no differences in the mean IOP between groups at baseline, 1-, and 3-month visits. IOP appears higher in the unfixed group at 6 months (16.7 vs. 15.0 mmHg, p < 0.01). Conclusion: The patients with ocular hypertension and primary open-angle glaucoma treated with a fixed combination are significantly more adherent and show a healthier ocular surface than those treated with an unfixed combination. The study provides significant evidence of the benefits of fixed combination treatment. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of two fixed combination, preservative-free eye drops (bimatoprost 0.01% in combination with either timolol 0.1% or 0.5%) in a gel formulation, with bimatoprost 0.03%/timolol 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Phase II, randomized, investigator-masked, multicenter, 3-arm parallel group (Eudract No. 2017-002823-46). Eighty-six patients aged ≥18 years with OAG or OHT, with intraocular pressure (IOP) initially controlled for at least 6 months by a combination therapy of a dual prostaglandin and timolol or insufficiently controlled by first-line monotherapy were included. Patients were randomized to receive T4030a (bimatoprost 0.01%/timolol 0.1%; N = 29), T4030c (bimatoprost 0.01%/timolol 0.5%; N = 29) or bimatoprost 0.03%/timolol 0.5% (N = 28), administered once daily in the evening for 12 weeks. Primary endpoint was defined as change in IOP from day 1 to week 12 measured at 08:00 (±1 h). Further efficacy, safety and pharmacokinetic endpoints were assessed as secondary outcomes. The mean change in IOP from baseline to week 12 was −9.8 ± 2.1 mmHg for T4030a, −10.1 ± 2.5 mmHg for T4030c and −10.0 ± 2.8 mmHg for bimatoprost 0.03%/timolol 0.5%. All treatments were well tolerated with no safety issues identified in any group. In patients treated with T4030a, the systemic concentration of timolol was significantly lower after 12 weeks than in patients treated with T4030c or bimatoprost 0.03%/timolol0.5%. These study results suggest that the preservative-free ophthalmic formulation of T4030a (bimatoprost 0.01%/timolol 0.1%) can be regarded as a useful tool in the therapeutic management of OAG and OHT. [ABSTRACT FROM AUTHOR]

Based on data on the role of the Na+/H+ exchanger (NHE) in the modulation of intraocular pressure (which is the main factor in the development of glaucoma) and on previous studies by different authors (proving the presence of NHE-1 inhibitory activity in quinazoline derivatives), nine new compounds of this class were synthesized. The effect of the quinazoline derivatives obtained on the inhibition of the Na+/H+ exchanger and intraocular pressure (IOP) in rats as compared with zoniporide (NHE inhibitor) and timolol (IOP-lowering drug used in clinical practice) was studied. Among the studied compounds in vitro, all quinazoline derivatives at a concentration of 1 nM inhibited the activity of NHE-1; quinazoline acetylguanidine derivative was the most active. However, not all compounds demonstrated an IOP-lowering activity in vivo in rats. Thus, 4-oxoquinazoline acetylguanidine, its derivative brominated at the C6 position, and quinazoline propionylguanidine are the most active of the quinazoline derivatives. The structure–activity analysis demonstrated that the presence of the Br atom at the C6 position of 4-oxoquinazoline acetylguanidine derivative leads to a maximal decrease in IOP during instillation of the studied compound solution. [ABSTRACT FROM AUTHOR]

Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5–10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr). [ABSTRACT FROM AUTHOR]

We herein report a case of glaucoma with an intraocular pressure (IOP) decrease following total gastrectomy (TG) and anticancer treatment for gastric cancer. A 62-year-old male underwent trabeculectomy of the left and right eyes in August 2011 and July 2012, respectively. During the follow-up, IOP of the right eye was 9-12 mmHg (with bimatoprost, dorzolamide, and timolol maleate), and that of the left eye ranged between 14 and 26 mmHg (with bimatoprost, dorzolamide, timolol maleate, and brimonidine tartrate). In December 2014, TG was performed due to gastric cancer. After surgery, the patient received S-1+CDDP, weekly PAC, and CPT-11 therapies. The patient died on March X, 2017. Before TG, the body mass index (BMI) was 29.5 but decreased to 24.8 before the start of the two courses of weekly PAC therapy. IOP of the right eye was 6 mmHg (with bimatoprost), and that of the left eye was 10 mmHg (with bimatoprost, dorzolamide, and brimonidine tartrate), showing decreases. After the initiation of weekly PAC therapy, BMI was approximately 19. IOP of the right eye ranged between 6 and 10 mmHg until the final ophthalmological examination (January 11, 2017), while that of the left eye ranged between 8 and 15 mmHg. In this patient with glaucoma, IOP was not controlled by eye drop treatment, and TG for gastric cancer and postoperative treatment with anticancer drugs resulted in weight loss and a decrease in IOP. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a triple fixed-combination of bimatoprost, brimonidine, and timolol (TFC) in patients with glaucoma or ocular hypertension (OHT) treated with fixed-combination or unfixed brimonidine and timolol therapy (dual-combination therapy). Methods: In this multicenter, open-label, phase 3 study, patients who received 4– 8 weeks of dual-combination therapy twice daily and had an IOP > 18 and < 34 mmHg in at least one eye were switched (at baseline) to treatment with TFC twice daily for 12 weeks. At Weeks 4, 8, and 12 on TFC, IOP was assessed at Hours 0, 2, and 8. Primary efficacy variable: mean diurnal IOP change from baseline in the study eye at Week 12 (modified intent-to-treat [mITT] population). Sensitivity (per-protocol [PP] population) and subgroup (≤ 65 vs > 65 years) analyses were performed. Safety, including adverse events (AEs), was assessed at each visit. Results: Of 126 patients enrolled, 121 and 103 formed the mITT/safety and PP populations, including 109 (90.1%) and 94 (91.3%) who completed the study, respectively. In the mITT/safety population, mean age was 58.6 years. Patients had open-angle glaucoma (51.2%), angle-closure glaucoma with patent iridotomy (36.4%), and/or OHT (13.2%). At Week 12, the mean diurnal change in IOP from dual combination-treated baseline was statistically significant (P< 0.001) with TFC in the mITT (– 3.98 mmHg) and PP (– 4.22 mmHg) populations. Results were similar at all visits, regardless of the age subgroup. The most frequent treatment-related AEs were conjunctival hyperemia (14.0%) and dry eye (4.1%); 5.8% of the patients discontinued treatment due to ocular AEs. Conclusion: TFC offers a beneficial therapeutic alternative for patients with glaucoma or OHT whose IOP is not sufficiently controlled with dual-combination therapy. Safety and efficacy findings support those of published studies of TFC in primary open-angle glaucoma and OHT, despite differences in study designs. [ABSTRACT FROM AUTHOR]

Background and purpose: Prolonging the drug release can be a suitable approach to overcome the challenges related to topical ophthalmic administration of drugs especially the ones prescribed for chronic ailments. The sustained delivery of the drug would reduce the required frequency of administration which could extremely improve patient compliance and feeling of well-being. This study aimed to develop nanofibrous inserts for sustained ophthalmic delivery of timolol maleate (TIM) for the treatment of glaucoma. Experimental approach: Polycaprolactone-based nanofibers containing TIM were prepared using pure polycaprolactone or a blend of it with cellulose acetate or Eudragit RL100 polymers by the electrospinning method. Following the preparation, polymeric inserts were evaluated for morphological and physicochemical properties. The in vitro drug release was assessed and the in vivo efficacy of a selected insert in decreasing the intraocular pressure (IOP) was also evaluated in the equine eyes. Findings / Results: Prepared nanofibers indicated diameter ranged between 122-174 nm. The formulations showed suitable physicochemical properties and stability for ophthalmic administration. In vitro release study showed prolonged release of drug during more than 3 days. In vivo evaluation revealed that the prepared insert is non-irritant and non-toxic to the equine eyes while having suitable efficacy in decreasing the IOP during 6 days. Conclusions and implication: Prepared TIM inserts indicated a higher efficacy than commercial TIM eye drop in lowering IOP during a prolonged period. Thus, these formulations can be considered suitable for enhancing patient compliance by reducing the frequency of administration in the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Objectives The aim of the work was to introduce 3D printing technology for the design and fabrication of drug-eluting contact lenses (DECL) for the treatment of glaucoma. The development of 3D printed lenses can effectively overcome drawbacks of existing approaches by using biocompatible medical grade polymers that provide sustained drug release of timolol maleate for extended periods. Methods Hot melt extrusion was coupled with fusion deposition modelling (FDM) to produce printable filaments of ethylene-vinyl acetate copolymer–polylactic acid blends at various ratios loaded with timolol maleate. Physicochemical and mechanical characterisation of the printed filaments was used to optimise the printing of the contact lenses Key findings 3D printed lenses with an aperture (opening) and specified dimensions could be printed using FDM technology. The lenses presented a smooth surface with good printing resolution while providing sustained release of timolol maleate over 3 days. The findings of this study can be used for the development of personalised DECL in the future. [ABSTRACT FROM AUTHOR]

Background and purpose: Prolonging the drug release can be a suitable approach to overcome the challenges related to topical ophthalmic administration of drugs especially the ones prescribed for chronic ailments. The sustained delivery of the drug would reduce the required frequency of administration which could extremely improve patient compliance and feeling of well-being. This study aimed to develop nanofibrous inserts for sustained ophthalmic delivery of timolol maleate (TIM) for the treatment of glaucoma. Experimental approach: Polycaprolactone-based nanofibers containing TIM were prepared using pure polycaprolactone or a blend of it with cellulose acetate or Eudragit RL100 polymers by the electrospinning method. Following the preparation, polymeric inserts were evaluated for morphological and physicochemical properties. The in vitro drug release was assessed and the in vivo efficacy of a selected insert in decreasing the intraocular pressure (IOP) was also evaluated in the equine eyes. Findings / Results: Prepared nanofibers indicated diameter ranged between 122-174 nm. The formulations showed suitable physicochemical properties and stability for ophthalmic administration. In vitro release study showed prolonged release of drug during more than 3 days. In vivo evaluation revealed that the prepared insert is non-irritant and non-toxic to the equine eyes while having suitable efficacy in decreasing the IOP during 6 days. Conclusions and implication: Prepared TIM inserts indicated a higher efficacy than commercial TIM eye drop in lowering IOP during a prolonged period. Thus, these formulations can be considered suitable for enhancing patient compliance by reducing the frequency of administration in the treatment of glaucoma.

Introduction: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension. Methods: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication. Results: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9–7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0–6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan–Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density. Conclusions: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration. Trial registration numbers: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364. [ABSTRACT FROM AUTHOR]

Purpose: Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. Methods: An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Results: Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P < 0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. Conclusion: In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204. [ABSTRACT FROM AUTHOR]

Context: Glaucoma is a disease of the eyes characterized by an increase in the intraocular pressure. Timolol maleate is commonly used as eye drops for chronic glaucoma treatment. Aims: To formulate an ocusert (novel ophthalmic drug delivery systems) in order to overcome disadvantages of eye drops such as patient’s noncompliance and drainage of the administered solution. Also, to improve treatment outcomes by keeping sustained release of constant amount of timolol maleate and to avoid repeated administration of conventional eye drops. Methods: Timolol maleate ocuserts were formulated using cross-linked gelatin polymer which was prepared using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysuccinamide (NHS). Different ocusert formulas were prepared (M1-M17) by varying concentrations of EDC, different temperatures and time for the cross linking as per central composite design. Physicochemical characteristics of drug loaded ocuserts were investigated. Results: Selected formula (M8) exhibited an excellent in vitro drug release results which was extensively evaluated. Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and the polymer used. M8 formula was evaluated in vivo by assessing the eye irritancy, drug release and therapeutic effect when placed in the cul-de-sac of rabbit’s eyes and was compared with conventional eye drops therapy. Conclusions: There was a correlation between in vivo and in vitro release of timolol maleate which is associated with a decrease of glaucoma induced by dexamethasone eye drops in experimental rabbits. The data established the potential of ocusert to improve the therapeutic delivery of timolol maleate and offers a promising option in glaucoma treatment.

Purpose: To evaluate the intraocular pressure (IOP)-reducing efficacy and safety of Rho-kinase inhibitor (RKI). Methods: Published studies in PubMed and EMBASE were searched on March 20, 2021. Study selection and data extraction were performed according to PRISMA. Meta-analysis of the IOP-lowering effect was performed with the bivariate random-effects model, with studies categorized into 2 classes: RKI versus placebo and RKI versus another medication. The main outcome was the difference in IOP reduction between RKI and non-RKI groups. Subgroup analysis of adjunctive RKI efficacy and additional review of its major ocular adverse events (AE) were also performed. Results: Ten (2.6%) out of 391 studies were retrieved. In the RKI versus placebo class, RKI showed greater IOP reduction after 4–8 weeks (mean difference = − 1.69 mmHg [− 2.22, − 1.16], P < 0.001). In the RKI versus another medication class, IOP reduction by RKI was noninferior to timolol 0.5% twice-daily after 4–8 weeks (mean difference = 0.39 mmHg [0.01, 0.76], P = 0.043) and 12 weeks (mean difference = 0.48 mmHg [0.11, 0.85]; P = 0.011). In the subgroup analysis, the mean difference in IOP reduction by adjunctive RKI and placebo was − 1.42 mmHg (P < 0.001). The most common ocular AE of RKI was conjunctival hyperemia (19–65%), followed by conjunctival hemorrhage (6–20%) and cornea verticillata (13–26%). Conclusions: With a treatment duration of 1–3 months, RKI showed effective IOP reduction noninferior to timolol as monotherapy and as adjunctive therapy. Our results suggested RKI be a reliable IOP control medication; however, its higher incidence of some ocular complications should be attended to. [ABSTRACT FROM AUTHOR]

Background: The Glaucomas are a group of progressive optic neuropathies associated with corresponding visual field defects where IOP is a major modifiable risk factor and is the leading cause of irreversible blindness worldwide. Aims: This study was conducted to compare the diurnal variation of Intraocular pressure (IOP) among patients with asymmetric primary open-angle glaucoma and without glaucoma and to determine the influence of age, sex, diabetes, hypertension, and anti-glaucoma drugs over diurnal variation of IOP. Settings and Design: This prospective randomized comparative study was done at the Glaucoma Clinic at the Regional Institute of Ophthalmology, Medical College and Hospital, Kolkata from January 2018 to August 2019. Methods and Material The patients were categorized by Cases (all asymmetric POAG patients, 80 eyes) and Control (all 80 non-glaucomatous eyes). After taking history and clinical examinations, Central Corneal Thickness (CCT) corrected IOP was measured from 7 am to 7 pm at 2 hourly intervals before starting therapy. Cases were treated with either Timolol 0.5% twice daily or Topical Travoprost 0.004%once daily (9 pm). Follow-up examinations were done at 1month and 3 months. Statistical Analysis: Statistical Analysis was performed with Epi Info (TM) 3.5.3 software, USA. Standard statistical tests were applied where applicable. t-test was used to compare the Mean. p ≤0.05 was considered statistically significant. Results The mean age were 56.27±12.51 years and 56.47±15.40 years for the cases andcontrols. The mean VCDR: Diurnal variation of IOP was higher in more glaucomatous eyes (p<0.05). No significant relation between sex and diurnal variation was found. Travoprost showed a better reduction of the mean IOP in more glaucomatous eyes (p<0.05). In less glaucomatous eyes,reduction in mean diurnal variation and mean IOP were significantly higher in the Travoprost group (p<0.05). Conclusions. In asymmetric POAG, the more glaucomatous eye had significantly more diurnal variation of IOP. No significant association with age, sex, diabetes mellitus, or hypertension were found. The travoprost 0.004% showed more control of the diurnal variation in the less glaucomatous eye and more reduction of mean IOP both in the more and less glaucomatous eyes than timolol 0.5%. [ABSTRACT FROM AUTHOR]

Macular ganglion cell complex (GCC) thickness map is a functional ancillary test to detect early structural changes in glaucomatous optic neuropathy (GON). The temporal raphe sign is present in almost all patients with narrow retinal nerve fiber layer (RNFL) defect, especially when there is a small angular distance between the fovea and the RNFL defect. A case series of patients with GCC thickness map and a positive temporal raphe sign is presented. [ABSTRACT FROM AUTHOR]

Purpose: To present the pharmacological evaluation process in a case of a polymedicated patient presenting with toxic epidermal necrolysis (TEN). Summary: A 75-year-old Caucasian polymedicated woman had been treated for hip pain with nonsteroidal anti-inflammatory drugs and pregabalin in the months preceding the apparition of an expanding papulo-erythematous rash. She had also started using new medicated eye drops for glaucoma. She presented to the emergency department of a regional hospital where all of her medications were stopped. The patient was transferred and admitted to a tertiary-care teaching hospital's specialized burn unit for significant cutaneous detachment. It was estimated that 70% to 80% of the body surface area was affected. Skin biopsy showed keratinocyte necrosis with a partial detachment of the epidermis leading to a diagnosis of TEN. The reaction ceased to progress 2 days after the discontinuation of her medications. A complete reepithelialization was objectified after 10 days. A series of steps were followed by the hospital pharmacist to determine which drugs were the most probable culprits. A complete pharmacological history was obtained and a timeline for medication use in the 3 months preceding rash apparition was established. A review of the literature was done to determine the drugs' relationships to Steven-Johnson syndrome or TEN. Using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, it was determined that naproxen, pregabalin, and brinzolamide–timolol drops were all possible culprits. Conclusion: A systematic method for pharmacological evaluation of a polymedicated patient with TEN is presented. Naproxen, pregabalin, and brinzolamide–timolol drops were all retained as possible culprits. [ABSTRACT FROM AUTHOR]

Background:Open-angle glaucoma may lead to permanent blindness.1 Elevated intraocular pressure (IOP) is responsible for glaucoma, and most treatments are designed to reduce IOP. The present study compared LatanoprosteneBunod, Timolol Maleate, and latanoprost ophthalmic solutions in lowering intraocular pressure in open-angle glaucoma. Materials & Methods: 120 patients of open-angle glaucoma of both genders were allocated to 3 groups of 40 each. In group I, patients were prescribed latanoprost, in group II, patients received latanoprostenebunod, and in group III, patients were prescribed timolol maleate. Measurements of IOP was performed using calibrated pneumatonometer. Results: Group I had 24 males and 16 females, group II had 22 males and 18 females and group III had 17 males and 23 females. The mean IOP was 24.2 mm Hg in group I, 23.7 mm Hg in group II and 24.6 mm Hg in group III. Heart rate was 77.6 bpm in group I, 76.2 bpm in group II and 77.9 bpm in group III. Adverse events in group I, group II and group III was dry eyes seen in 5, 5 and 4, eye irritation in 3, 3 and 1, conjunctivalhyperemia in 2, 1 and 1, eye pain in 2, 1 and foreign body sensation in eyes in 1 patient each respectively. Conclusion: Latanoprostenebunod was more effective in reducing IOP in patients with openangle glaucoma than latanoprost and timolol. [ABSTRACT FROM AUTHOR]

This study aimed to compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination(Cosopt) in newly diagnosed primary open-angle glaucoma (POAG) patients. In this prospective, interventional case series, newly POAG patients were included. Patients were started on Cosopt twice a day (BID) for one month and then switched to three times a day (TDS) for an additional month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP), and 24-h heart rate (HR) measurements at baseline, month 1(BID), and month 2(TDS). Throughout the study, all adverse events were monitored by the investigators. In 31 POAG patients that completed the study, the mean baseline IOP was 23.1 ± 3.15 mmHg. IOP was decreased significantly 16.5 ± 2.21 at one month (p <.0001) and 13.9 ± 2.23 mmHg at 1 and 2 months follow up (p <.0001). IOP was significantly lower in month 2 compared to month 1 (p =.0004). While Cosopt BID significantly reduced the mean 24-h systolic BP and mean 24-h HR from baseline (p <.0001), the mean 24-h systolic BP and HR remained unchanged with Cosopt TDS compared to BID (p =.62). Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profiles. [ABSTRACT FROM AUTHOR]

Purpose: To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). Study design: Open-label, multicenter, Phase 3 study (NCT02822729). Methods: Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16– < 22 mmHg (Group 1) or ≥ 22– ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients (N = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. Results: Significant reductions in mean diurnal IOP from baseline occurred at every visit (P < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was −3.7 ± 0.3 mmHg (Group 1), −5.6 ± 0.5 mmHg (Group 2), and −8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. Conclusions: In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia. [ABSTRACT FROM AUTHOR]

This study assessed the clinical risk factors for periorbital dermatitis (PD) after using dorzolamide/timolol eye drops in a total of 1282 glaucoma patients. Both the PD(+) group and the PD(−) group were evaluated using clinical data such as age, sex, dosing duration, presence of benzalkonium chloride (BAK) in the formulation, ocular surgery history (e.g. cataract or glaucoma operations), height, weight, personal history of systemic hypertension, smoking, alcohol consumption, intraocular pressure, best-corrected visual acuity (BCVA), central corneal thickness, axial length, and visual field index (VFI). Univariate analyses showed that shorter dosing duration, higher rate of BAK-included cases, worse BCVA, worse VFI, more systemic hypertension history, and more ocular surgery history were more associated with the PD(+) group than the PD(−) group. The BAK(−) group showed a lower PD rate than the BAK-included group, which was supported by the Kaplan–Meier analysis (log-rank test, p = 0.0014). Multivariate analyses revealed that the probability of PD increased by 8 times if they had a history of ocular surgery and increased by 2.3% when the VFI decreased by 1% (Cox's hazard regression test, p < 0.001). Therefore, a preservative-free dorzolamide/timolol can benefit the subjects for those who had ocular surgery or who have worse VFI. [ABSTRACT FROM AUTHOR]

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is <5%. Our previous study revealed that magnesium hydroxide nanoparticles (nMH) have potency in improving the bioavailability of fixedcombined TM in rodent models. This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of TM and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs. Five clinically healthy dogs were administered topical saline, commercial 0.5% TM, and a 0.01% or 0.1% nMH-0.5% TM fixed combination (0.01% or 0.1% nMH-TM) twice daily in one eye for 7 days with at least a 28-day interval. The changes from baseline were calculated and were statistically analyzed for each drug. IOP was significantly reduced in both 0.01% and 0.1% nMH-TM-treated-dogs compared with saline- and TM-treated dogs. Meanwhile, 0.01% and 0.1% nMH did not exacerbate the side effects of TM. From these results, nMH improved the ocular hypotensive effect of TM without enhancing side effects. Topical nMH-TM is potentially more effective for canine ocular hypotensive eye drops than TM. [ABSTRACT FROM AUTHOR]

Purpose: We previously investigated the efficacy and safety of adding 0.1% brimonidine (Brim) or 0.5% timolol (Tim) to prostaglandin analogue (PGA) monotherapy to treat patients with normal-tension glaucoma (NTG) with intraocular pressure (IOP) of ≤ 16 mmHg. Herein, we describe an additional post-hoc stratifying analysis of the possible differences in the effect of IOP-lowering and pulse rate (PR) after adjunctive Brim or Tim to PGA. Patients and Methods: This study included 128 subjects. Patients with NTG treated with PGA were stratified based on their baseline IOP. The changes in IOP from baseline and the effect of patient factors on IOP changes were investigated. Patients were stratified by age for investigation of their PR and blood pressure (BP). The change and the effect of patient factors on PR and BP were investigated. Results: After stratification analysis, in 52 eyes treated with Brim and 61 eyes with Tim with baseline IOP 12 ≤ IOP ≤ 16 mmHg, both eye drops lowered IOP significantly (P < 0.0001), and the IOP-lowering efficacy of Brim was non-inferior to that of Tim. However, in 9 Brim- and 6 Tim-treated eyes with baseline IOP of < 12 mmHg, no statistically significant decrease in IOP was evident with either eye drop. In the Tim group, PR decreased significantly (P < 0.05) after stratification by age. Conclusion: The IOP-lowering efficacy of Brim was non-inferior to that of Tim after stratification by baseline IOP (12 ≤ IOP ≤ 16 mmHg). The discrepancy in the IOP-lowering effects of Brim and Tim observed in the previous study was thought to be related to enrolled subjects with low baseline IOP. PR decreased significantly in the Tim group even after age stratification. PR should be considered when selecting β-blockers for glaucoma treatment. [ABSTRACT FROM AUTHOR]