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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]

Objectives: The aim of this study was to prepare a sustained-delivery mucoadhesive-thermosensitive formulation containing poloxamer 338 (P338), poloxamer 188 (P188), and mucoadhesive agents, such as chitosan (CHT) and carboxymethylcellulose (CMC), to increase the ophthalmic bioavailability of timolol maleate (TM). Materials and Methods: Gels were prepared by mixing different amounts of P338, P188, and a mucoadhesive agent in cold isotonic water using a magnetic stirrer. The sol-gel gelation time of the gels was determined using the test tube inversion method. Viscosity measurements and analysis of the mechanical properties of the gel formulations were performed. In vitro release using dialysis membranes and ex vivo permeation studies using fresh-warmed cow eyes were performed. Results: The gelation times of formulations containing 20:2.5 (P338:P188) and 0.1% CMC and formulations containing 20:2.5 (P338:P188) and 0.1% CHT were 35 s and 26.67 s, respectively. An optimally selected CHT mucoadhesive-thermosensitive in situ gelling system can successfully control the release of moderately hydrophilic drugs, such as TM. In the viscosity study, both formulations showed Newtonian fluid, and the CHT gel’s viscosity was found to be higher. The CHT gel showed better mechanical properties than the CMC gel. The amount of TM penetrating the cow cornea after 24 hours was 73.38%, 71.80%, 67.25%, and 60.55% from the CHT gel, CMC gel, TM solution, and commercial preparation, respectively. Conclusion: The improved mucoadhesive-thermosensitive in situ gelling system successfully controlled the release of TM. The significantly lower drainage of TM into the circulation compared with eye drops is an advantage in treating glaucoma, and the use of mucoadhesive agents increases drug penetration. [ABSTRACT FROM AUTHOR]

Background To study the ultra-trace simultaneous determination of drugs, the colorimetric method in combination with chemometrics can be used. Objective In this study, a simple, rapid, and sensitive UV-Vis spectrophotometric method using gold nanoparticles (AuNPs) was introduced for the simultaneous determination of ultra-trace amounts of pilocarpine (PIL) and timolol (TIM) in binary mixtures and biological samples. Methods AuNPs interacted with components and the aggregation mode of NPs occurred, and, finally, the color change of the solution (red to gray) was observed with the naked eye without the most modern and expensive instruments. The characterization of AuNPs was evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Results The validation of the colorimetric way was studied in the concentration range of 100–800 and 100–600 μg/L with good linearity equal to 0.9772 and 0.9891 for PIL and TIM, respectively. The limit of detection (LOD) was found to be 165.00 and 92.40 μg/L, where the limit of quantitation (LOQ) was 500.00 and 280.00 μg/L for PIL and TIM, respectively. The effect of some factors such as interaction time, the concentration of components, and the volume of buffer on absorbance was investigated. Partial least squares (PLS) as an efficient multivariate calibration method was combined with colorimetry for the simultaneous determination of PIL and TIM in binary mixtures. The optimum number of latent variables was selected by k-fold cross-validation based on minimum mean square error prediction (MSEP), and the number of components equal to 1 with MSEP of 1.085 and 0.763 was considered for PIL and TIM, respectively. The mean recovery was obtained at 100.20 and 101.55% for PIL and TIM, respectively. Conclusions The colorimetric method can be introduced as a proper option for the simultaneous determination of components in pharmaceutical formulations and other samples. Highlights A colorimetric method using AuNPs was proposed. The PLS method was coupled with a colorimetric method for the ultra-trace simultaneous estimation of PIL and TIM in binary mixtures. Ultra-trace amounts of PIL and TIM were also determined in biological samples. The proposed method is simple, fast, and less expensive than chromatography methods. [ABSTRACT FROM AUTHOR]

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 β‑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. [ABSTRACT FROM AUTHOR]

Objective The objective of the study was to compare the effective rate, cure rate, adverse reaction rate, and effective time of three methods in the treatment of infantile hemangioma, hoping to provide reference for improving the clinical therapeutic effect. Methods This is a retrospective study of 307 infantile hemangioma patients admitted to the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, from January 2014 to October 2021. The patients were divided into three groups. In group A, timolol maleate solution was introduced by the nano-microneedle technique (97 cases); in group B, timolol maleate drops dipped in medical swabs were applied (107 cases); and group C patients took propranolol orally (103 cases). The effective rate, cure rate, adverse reaction rate, and effective time of treatment were recorded and compared. Results The total effective rate, total cure rate, and total adverse reaction rate of the three groups were 87.6, 65.2, and 9.4%, respectively. The results showed that the effective and cure rates of group A were higher than those of group B (92.8 and 76.3%, respectively; p < 0.05), the adverse reaction rate of group C was higher than that of group B (17.5%, p < 0.05), and the effective time of group A was shorter than that of groups B and C. In most patients, symptoms significantly improved within 2 months (p < 0.05). Conclusion Timolol maleate introduced by nanometer microneedles is an effective and safe treatment for superficial hemangioma in infants with the highest effective and cure rates, lower incidence of adverse reactions, and the shortest effective treatment time. [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]

Objective: The aims of this study were to ascertain the effectiveness and safety of the off-label use of topical timolol as an adjunct treatment for hard-to-heal (chronic) wounds. Furthermore, to review and analyse the existing literature regarding the use of topical timolol on wounds of varying aetiologies. Method: A systematic review of literature in the English language published between May 1961–May 2021 on the application of topical timolol for hard-to-heal wounds in adults was performed. Each research study was evaluated by two reviewers independently. Studies eligible for inclusion in the review were randomised controlled trials (RCTs), clinical trials, observational studies of at least 4 weeks' duration, case series and case studies. Search strategies were performed according to PRISMA guidelines and included MeSH terms and keyword searches. Results: An initial 878 articles were identified from a search of PubMed, Ovid Medline, Embase, Cochrane, and SCOPUS. Of these, 699 were reviewed for eligibility, 19 were read in full-text, and 12 were selected for inclusion in the review. In total, two RCTs and 10 observational studies, including five case studies, were analysed. All studies demonstrated efficacy and safety of topical timolol; however, statistical analysis remained limited by lack of blinding and small sample sizes. Conclusion: This review concludes with all currently available evidence that topical timolol may be considered as an effective and safe adjunct treatment for refractory wounds, primarily venous leg ulcers and diabetic foot ulcers. Given the overall safety, low cost and ease of application of topical timolol, this review provides evidence in favour of off-label use and should prompt further, more rigorous studies. [ABSTRACT FROM AUTHOR]

Introduction: Infantile hemangiomas (IH) exacerbated by ulceration invariably necessitate hospitalization, although simple IHs are sometimes managed remotely. Furthermore, according to international regulations, β-blocker medication for such hemangiomas should be systemic and performed in a clinic, especially if there is infection and risk of bleeding. Case: War in Ukraine made it impossible to hospitalize and properly examine a patient with a complex ulcerated and infected IH, forcing us to administer β-blocker timolol therapy only through telemedicine. Conclusions: Our case demonstrates the possibility of successful distant treatment of IH with ulcer using only a topical β-blocker carried out remotely through telemedicine, which is critical in the context of the COVID-19 pandemic, war, hostilities, or natural disasters where inpatient treatment is not available. [ABSTRACT FROM AUTHOR]

A sustainable reversed-phase chromatographic method has been developed and validated for the simultaneous determination of three active pharmaceutical ingredients, dorzolamide, brinzolamide, and timolol, used to treat glaucoma. The eco-friendly solvent isopropanol has been used as an organic mobile phase constituent. According to the Hansen space green solvent selection tool, isopropanol has a G score of 6.5, comparable to ethanol, which has a G score of 6.6. The mobile phase consists of isopropanol: aqueous sodium acetate buffer (0.1 M, pH 4.25) in the ratio of 10:90 (v/v). The flow rate was maintained at 1 mL/min. Dorzolamide and brinzolamide were detected at 254 nm, and timolol was detected at 295 nm. A high-purity silica with a polymeric C18 modification column (150 × 4.6 mm, 5 µm particle size) was used for this separation. The three compounds were eluted within 8 min. The method was validated according to ICH guidelines. The calibration curves were linear in the range of 20–70 µg/mL, 40–140 µg/mL, and 20–70 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. The LODs were found to be 1.61 µg/mL, 1.60 µg/mL, and 3.16 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. Good accuracy and precision were obtained for the three compounds. The greenness and whiteness of the method were indicated using the AGREE, ChlorTox, and RGB12 tools. [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]

Objective: This study aimed to evaluate the efficacy and safety of 0.5% timolol maleate gel, reported as an efficacious option for management of infantile hemangiomas (IH) in children. Methods: A retrospective study was conducted among patients diagnosed with IH from January 2019 to December 2021. All patients were treated 0.5% timolol gel. Data parameters, including photographs, at baseline and the final or most recent follow-up visit, were reviewed. Outcomes based on photographic assessment were categorized as excellent, good, fair or poor. Results: Sixty-four children with 76 lesions were enrolled. Median age was eight months (two months to 36 months) with most lesions (75.0%) presenting during the first year of life. Female preponderance (84.4%) was seen and the cervicofacial region was most commonly involved (52.6%). The majority of lesions (54, 84.4%) were solitary and most were treatment naïve (n=61, 80.3%). Excellent, good, fair, and poor responses were seen in 24 (31.5%), 39 (51.3%), 6 (7.9%), and 7 (9.2%) lesions. No complications were seen and no statistically significant difference was observed with respect to gender, age group, region involved and treatment naïve versus previously treated patients. Conclusion: Timolol maleate 0.5% gel is an effective and safe treatment option for IH irrespective of location of lesion, age and history of prior treatment. [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]

Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1–13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL. [ABSTRACT FROM AUTHOR]

Pyogenic granuloma (PG) is a benign vascular tumor removed surgically or by physical modalities, such as electrocautery and cryotherapy. Other treatment options may be warranted, especially in children, using nonsurgical approach. The study aims to determine the effectiveness and safety of topical treatments on PG in children in the clearance of lesions. Systematic literature search were done in February 2023 in the following database: PubMed, HERDIN, Cochrane Library, Hindawi, Directory of Open Access Journals, ScienceDirect, and Google Scholar. The search included studies involving PG treated with topical medications in the pediatric age group. Twenty-five studies (9 cohort studies, 6 case series, and 10 case reports) were included and utilized the following medications: timolol, propranolol, corticosteroids, common table salt, imiquimod, and ingenol mebutate. Among the medications, timolol was the most reported drug to provide partial to complete resolution in 62 out of 149 patients. All the reviewed topical medications provided partial to complete resolution with minimal adverse effects. Among them, topical timolol, propranolol, and table salt have demonstrated high response rates. Topical therapy in children with PG may be considered as a nonsurgical option. However, further clinical trials are warranted to determine its effectiveness. [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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This article explores the potential of topical timolol solution in improving the cosmetic appearance of surgical scars after Mohs micrographic surgery (MMS) with primary linear closure. The study involved 19 adult patients with nonmelanoma skin cancer who underwent MMS, with one-half of the wound treated with timolol solution and the other half treated with standard wound care. The results showed no statistically significant differences in scar cosmesis between the two groups, suggesting a limited role for timolol in improving the appearance of surgical scars in healthy patients. However, further research is needed to determine if timolol can be beneficial in cases of impaired or delayed wound healing. [Extracted from the article]

Propranolol, timolol, and minoxidil have all shown benefits in treatment of burn injury and other skin wounds. The study evaluated their effects on full-thickness thermal skin burns in a Wistar rat model. Performed on 50 female rats; two dorsal skin burns were created on each animal. On the next day, the rats were divided into 5 groups (n = 10); each has received a specific treatment daily for 14 days: group I—topical vehicle (control), group II—topical silver sulfadiazine (SSD), group III—oral propranolol (5.5 mg) associated with topical vehicle, group IV—topical timolol 1% cream, and group V—topical minoxidil 5% cream. Wound contraction rates, malondialdehyde (MDA), glutathione (GSH, GSSG), and catalase activity in skin and/or serum were evaluated, and histopathological analyses were performed. Propranolol did not show advantages in necrosis prevention and wound contraction and healing, and did not reduce oxidative stress. It impaired keratinocyte migration, and promoted ulceration, chronic inflammation, and fibrosis, yet reducing the necrotic zone. Timolol prevented necrosis and promoted contraction and healing, increased antioxidant capacity and promoted keratinocyte migration and neo capillarization in comparison to the other treatments. Minoxidil reduced necrosis and enhanced contraction, resulting in positive outcomes after 1 week of treatment regarding local antioxidant defense, keratinocyte migration, neo capillarization, chronic inflammation, and fibrosis rates. However, after 2 weeks, it resulted in contrasting outcomes. In conclusion, topical timolol promoted wound contraction and healing, reducing local oxidative stress and improving keratinocyte migration, bringing arguments for potential benefits in skin epithelization. [ABSTRACT FROM AUTHOR]

Purpose: To describe a patient with high myopia who experienced slight myopic regression twice during follow-up after small incision lenticule extraction (SMILE), which can be eased by topical treatment of timolol. Methods: Case report. Results: Six months after a SMILE procedure for high myopia in both eyes, the patient's uncorrected distance visual acuity (UDVA) was 0.8 and both eyes lost one line compared to preoperative corrected distance visual acuity (CDVA) by myopic shift, which was accompanied by central corneal epithelial thickening. After 2 months of treatment with topical timolol eye drops, the UDVA improved two more lines with flattened corneal curvature and thinned epithelial thickness. After 5 months without timolol treatment, he lost two lines of UDVA again with thicker epithelial thickness. After another 2 months of treatment with timolol, the epithelial thickness could be seen to have thinned month by month, and the UDVA improved two or more lines. There was no notable myopic shift in both eyes for the next 3 months with medication withdrawal. During the whole follow-up period, the change in corneal and epithelial thickness remarkably fluctuated with the timolol treatment, but the posterior corneal curvature was stable. Conclusions: This case report describes refractive regression that can repeatedly occur in the middle and long term after a SMILE procedure for high myopia, which could be correlated with the thickening of the central corneal epithelium. Treatment with timolol eye drops can help to improve visual acuity by thinning the compensated epithelial thickness to flatten corneal curvature. [Journal of Refractive Surgery Case Reports. 2023;3(4):e47–e52.] [ABSTRACT FROM AUTHOR]

Pyogenic granuloma is a reactive proliferation of angiopoietic endothelial cells to usually unobvious stimuli; it is characterized by rapid growth leading to profuse bleeding. To avoid this worrying event, pyogenic granuloma is usually removed and for this reason we do not know its natural history, unlike other vascular proliferations. Since the efficacy of beta-blockers on infantile hemangioma was discovered, many dermatologists have used them in pyogenic granuloma especially for topical use after surgical removal to prevent frequent recurrences or even as substitutes for surgery. The current work reported the clinical observations on 21 cases of pyogenic granuloma observed between May and November 2018 in which, when possible, topical treatment with timolol was started; when removal was necessary, this was followed by topical therapy with timolol. The report showed that pyogenic granuloma can regress without any therapy, that surgery can be avoided in about a third of cases, and that timolol can favor the regression of pyogenic granuloma and prevent recurrences. [ABSTRACT FROM AUTHOR]

Pyogenic Granulomas (PGs) are benign vascular tumours primarily treated with surgical procedures. Recently, topical Timolol, a beta-adrenergic receptor antagonist, has been used for the treatment of PG due to its vasoconstrictive, anti-angiogenic, and wound healing properties. Herein, the authors presented a case series of 12 patients (10 males and two females) with red papules and nodules that spontaneously bleed. The age of the patients ranged from 7-51 years, and the duration of lesions ranged from one week to nine months. The lesions were located on the face, neck, hand, and mucosa. All patients were treated with topical Timolol maleate 0.5% drops twice daily for four weeks and followed-up weekly for four weeks. The treatment efficacy was evaluated based on complete response, partial response, or no response. Changes in colour, size, bleeding tendency, and adverse events were also assessed. Two patients showed complete resolution, while the bleeding tendency improved in the other patients. No side effects were encountered, except in one patient where the lesion increased in size and became secondarily infected. Thus, topical timolol appeared to provide symptomatic improvement by reducing bleeding and lesion size without any side effects. It can be considered as an alternative therapeutic option for small, uncomplicated classical PG. [ABSTRACT FROM AUTHOR]

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]

Multi-analyte determination techniques are favored over those that can only determine a single analyte at a time because they enable resource savings (cost, time, and solvents) and reduce generated waste and the number of samples required for analysis. This research presents a novel method for the simultaneous determination of brinzolamide (BRZ) and timolol maleate (TML) in pharmaceutical ophthalmic preparations using first-order derivative UV–Visible spectroscopy. The proposed approach is environmentally friendly and yet to be previously reported in the literature. In this approach, the peak amplitude of BRZ was quantified at the zero-crossing point of TML, i.e., 248.80 nm, whereas TML was determined by measuring absorbance at 297.60 nm. The developed method was validated according to the International Council for Harmonisation guidelines Q2(R1). The developed method was linear with excellent correlation coefficient values (R2 > 0.9998) in the range of 4 – 24 µg/ml for BRZ and 5 – 25 µg/ml for TML. The accuracy and precision results were within limits for both the analytes (%Relative standard deviation, RSD

Objective: Infantile hemangiomas (IH) are the most common benign vascular tumors of infancy. Propranolol (P), a nonselective beta-blocker, has been successfully used in managing IHs. Ongoing studies investigate the efficacy of the topical β-antagonist timolol maleate (TM) in IHs. The aim of this study is to assess the effects of interventions for managing infantile hemangiomas in children. Material and Methods: We retrospectively reviewed a total of 403 IH patients from March 2021 to March 2022. The patients were stratified into three groups. Patients in Group 1 were given TM at a dose of one drop topically twice a day, 0.5%. Patients in Group 2 were given P at a dose of 1 mg/kg twice a day. The patients in Group 3 did not receive any treatment, and observation was conducted solely by contacting the controls. Results: The median age of diagnosis was 5 months (range 0-60), with 57.1% of the cases being male. While TM treatment was applied to 32% of the children and P treatment was applied to 46.9% of the children, no treatment was administered in 21.1%. The most common location of hemangiomas was the face, accounting for 39.2%. Hemangiomas were observed in more than one location in 48 (12%) children. The median follow-up period for the patients was 4 months (range 0-28). Hemangiomas remained unchanged in 28.3% of all cases, shrank in 60.3%, and continued to grow in 11.4%. The primary indication for initiating TM was superficial hemangiomas and infants younger than 6 months. The leading reason for starting P significantly higher than in the other groups (p:0.001). No statistically significant differences were observed between the groups regarding bleeding and ulceration rates (p>0.05). Conclusion: The efficacy of propranolol in treating IH was higher than that of TM.

We present the case of a 63-year-old man with refractory Hailey–Hailey disease who successfully responded to topical timolol 0.5%. This is a novel therapeutic approach that provides an alternative management option in this challenging disease. [ABSTRACT FROM AUTHOR]

Background: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. Methods: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin ®) using the occlusion method to treat paronychia or PG. Results: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. Conclusion: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings [ABSTRACT FROM AUTHOR]

Hypertension is one of the leading causes of death globally and a major risk factor for different cardiovascular outcomes. This led to continuous discovery of new drugs and on-going update of drug combinations. In the present work, sustainable eco-friendly spectrophotometric methods were developed and validated for the estimation of amiloride hydrochloride (AML), hydrochlorothiazide (HCT) and timolol maleate (TIM) in their ternary pharmaceutical formulation. The proposed methods are inspired based on the unique spectral characteristics of this mixture including spectral extension of AML over both HCT and TIM spectra. AML exhibits UV maximum at 362.0 nm that permits its direct estimation by zero order spectrophotometric method without any interference in a linear range of 2.0–20 μg/mL. While for the estimation of HCT and TIM, two methods were applied. The first method is dual wavelength in ratio spectra, while the second one is ratio subtraction in conjunction with the first derivative of ratio spectra method. The two methods were found linear over the concentration range of 2.0–25 µg/mL for HCT and 5–80 µg/mL for TIM. The suggested methods were successfully adopted for the evaluation of the studied drugs in their marketed dosage form and further implemented for content uniformity evaluation. Additionally, method greenness profile was assessed using different assessment metrics. [ABSTRACT FROM AUTHOR]

The present study was conducted on timolol maleate (a non-selective beta-blocker) using in vitro assays and in vivo models of rats. It was tested for its anti-inflammatory activity at three dose levels (1.028 mg kg-1, 5.14 mg kg-1 and 10.28 mg kg-1). Furthermore, the investigation was supported by the estimation of tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1) and histopathological examination. It was observed that at 1.028 mg kg-1, 5.14 mg kg-1 and 10.28 mg kg-1 the drug showed anti-inflammatory activities. Moreover, plasma levels of TNF-a and IL-1 showed inhibition. Histopathological examination confirmed the highest anti-inflammatory activity at 5.14 mg kg-1. Thus, the conducted studies revealed that timolol maleate, when given orally does possesses an anti-inflammatory potential. [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]

Copyright of Ahi Evran Medical Journal is the property of Ahi Evran University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hard-to-heal or recurrent leg ulcers can have multiple aetiologies. One of these is incompetent veins. The main focus of this article is to discuss the common treatment for venous leg ulcers with the use of sclerotherapy. This simple surgical procedure obliterates smaller veins and telangiectasia. Veins with larger diameters (varicosities) can be treated with ablation therapy. The intent of sclerosis or ablation therapy is to destroy the incompetent veins and allow the collateral circulation to improve venous return, decreasing venous hypertension, which then enhances skin closure, wound healing and the resolution of the ulcer. [ABSTRACT FROM AUTHOR]

Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding β-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods. [ABSTRACT FROM AUTHOR]

The present study aimed to develop a validated RP-HPLC method for the simultaneous determination of timolol maleate (TM), moxifloxacin hydrochloride (MOXI), diclofenac sodium (DS) and dexamethasone (DEXA) in human plasma, bovine aqueous humor and pharmaceutical preparations. The chromatographic separation was studied using the C18 column. The chromatographic conditions, such as composition, pH, the flow rate of mobile phase, the temperature of column, wavelength of absorption and injection volume of the sample, were studied. The method was validated to confirm specificity, linearity and accuracy in accordance with an International Conference on Harmonization guidelines. The optimum conditions for separation included mobile phase 0.05 M monobasic phosphate buffer: acetonitrile (65:35 v/v), pH of buffer adjusted to 6.2 and the flow rate of 1 mL/minute. The optimum temperature of the column was found to be 35°C, absorption wavelength 265 nm and injection volume 50 μL. The baseline separation of all four drugs with good sensitivity, resolution, and a less than 15 min run time was achieved. The retention time of TM, MOXI, DS and DEXA were 4.3,5.7,9.9 and 13.5 minutes respectively. The limit of detection (LOD) values were 6.2, 4.8, 0.8 and 1.2 ng/mL for TM, MOXI, DS and DEXA, respectively, whereas their respective limit of quantification (LOQ) values was: were 42.6, 26.8, 5.6 and 6.2 ng/mL. The coefficient of variation for intra-day and inter-day were in the range of 0.32–1.57 and 1.29–3.07%, respectively. The method was found to be sensitive, precise and accurate in human plasma and bovine aqueous humor and can be applied for the quantification of these compounds in plasma, aqueous humor and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Infantile haemangioma (IH) is the most common benign tumour in childhood, with an incidence of 4% to 12%. Aim: to describe the characteristics of infantile haemangioma in a sample of Romanian children <2 years old at diagnosis, types of treatment applied, recorded complications and the response to the therapeutic approach. A two-year prospective case series study (August 2019 to August 2021) was carried out. Sample: 117 patients <24 months of age diagnosed with IH at the Emergency Hospital for Children "Marie Sklodowska Curie", in Bucharest, Romania. Five therapeutic approaches were used: oral treatment with propranolol, local treatment with timolol, surgical treatment, topical treatment with steroids and no treatment ("wait and see"). Recorded factors mentioned in the literature were also present in this study population: female patients—68.4%; phototype I—58%. In 53% of cases, IHs had a head and neck location and 10% developed local complications (traumatic bleeding). The majority of patients (86%) required one type of therapy: oral propranolol (51%). A low relapse rate was recorded (4%). We consider that any child with a vascular anomaly should be referred to a highly specialised medical service for therapeutic approach. [ABSTRACT FROM AUTHOR]

Purpose: Timolol maleate (timolol), a β-receptor blocker, reduces intraocular pressure by decreasing aqueous humor production. Timolol reportedly also protects ganglion cells, decreases aqueous humor outflow facility, and destroys the extracellular matrix in the trabecular meshwork. In this study, we investigated the effects of timolol on cultured human trabecular endothelial cells purchased from ScienCell using next-generation sequencing. Study design: Experimental investigation. Methods: Total ribonucleic acid (RNA) was extracted after 24 h. More than 100 million RNAs in control and timolol-treated group were sequenced using a next-generation sequencer. The expression of 55,778 RNAs was analyzed. Results: A total of 2,105 genes were significantly upregulated and 2,125 genes were downregulated, after the addition of timolol. VGF nerve growth factor inducible (VGF) (388-fold) had the maximum increase in expression, followed by amphiregulin (333-fold), a member of the epidermal growth factor family. Moreover, the expression of extracellular matrix-degrading enzymes, matrix metalloproteinases (MMPs) 1, 2, 3, 10, 12, and 14, increased. Conclusion: Timolol exerts various effects on human trabecular endothelial cells. The increase in MMP expression may contribute to the decrease in the aqueous humor outflow facility. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the therapeutic effects and safety of oral propranolol along with topical timolol maleate or oral propranolol alone for treatment. To study the increases in the success rate of propranolol when used along with timolol solution. Whether there is a decrease in the duration of therapy. To study the speed of improvement in haemangioma treatment with propranolol therapy when used along with timolol solution. Methods: From March 2019 to June 2020, 40 cases of Surface Infantile Patients were treated. The experimental group (20 patients with 7 males and 13 females) was treated using oral propranolol combined with topical timolol maleate, whereas the control group (20 patients with 5 males and 15 females) was treated with oral propranolol alone. Vas scale is used to grade the improvements. Results: In terms of the volume reduction of the lesion at the endof the study, the combination therapy (P+T) was found to be more efficacious than the monotherapy (only Propranolol), volume reduction percentage was(67.28 ± 17.11 %) for the combined therapy group (P + T) and (55.547 ± 16.39 %) for the single therapy group i.e only Propranolol, with P value (P=0.033), when the analysis was further carried on for the earlier age group, Reduction in terms on depth was found to be better in the Propranolol + Timolol group (Depth 0.765 ± 0.437 cm) thanthe propranolol alone, the combination therapy failed to show better results in terms of shortening of the duration of treatment and ameliorating the efficacy of propranolol However it was found that volumetric reduction was better in combination therapy than propranolol alone. Effects were seen better when the treatment was started in early age groups that is 0-6 months. Conclusions: In our study, we found out that the Propranolol 2-3mg per kg and Timolol solution of 0.5% applied thrice over the lesion were well tolerated by all the patients without any serious adverse events. The Propranolol and Timolol combination therapy fails to demonstrate a statistically approvable shorter period of treatment as well as efficacy when compared to Oral Propranolol alone. But clinically there is Volumetric reduction in terms of depth reduction and a decrease in duration of treatment. This was found to be better in the combination group than propranolol alone and was significant for early-age group patients. 0-12 months. [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]

Objective To record personal experience in treating infantile hemangioma using triple therapy on home basis. Methods This is a case series cross sectional clinical study and therapeutic trial of infantile hemangioma (IH) was carried out during the period from 2014-2022 where all cases with infantile hemangioma were evaluated. All types of hemangioma were included single or multiple superficial and deep. Oral propranolol was given at home in a dose of 1-2 mg/kg body weight a day in two divided doses. Oral prednisolone was started as 5mg syrup once a day for one month and then tapered gradually. Also timolol drop 0.5% was applied to hemangioma twice a day till the end of therapy. The duration of treatment ranged from 3-6 months with a median of 4 months. Objective scoring was used to assess the response to therapy. All side effects were carefully recorded by the mothers and dermatologist. Results A total of 182 infants, 129 (70.87%) females and 53 (29.12%) males with IHs were included and analyzed. The age of the patients ranged from 1-6 months with a mean of 4 months. The sites of lesions were mostly on heads including face and neck in 106 (58.24%) cases while in other parts of body in 76 (41.75%) cases, with size ranged from 2 cm2 to 23 cm2. The response to triple therapy was noticed week after starting treatment protocol but was obvious at 2 weeks. There was gradual reduction in color and size of lesions. In most of patients, there was about 25% reduction in the first two weeks that reached to 75-100% after 3-6 months. No adverse or side effects were seen in all infants even with normal growth development. Conclusion This triple therapy is the first study using oral propranolol and oral prednisolone plus topical timolol drops together on a home basis. It is safe effective therapy for infantile hemangioma and is more effective than single drug use. No need for hospital admission or cardiac assessment during treatment course and no laser therapy is recommended. [ABSTRACT FROM AUTHOR]

Abstract Designing new, verified methodologies with a focus on sustainability, analytical efficiency, simplicity, and the environment has become a major priority for pharmaceutical quality control units. In this way, sustainable and selective separation-based methodologies were designed and validated for the concurrent estimation of amiloride hydrochloride (AML), hydrochlorothiazide (HCT) and timolol maleate (TIM) in their fixed dose formulation (Moducren® Tablets) along with hydrochlorothiazide potential impurities, salamide (DSA) and chlorothiazide (CT). The first method is a high performance thin layer chromatographic method (HPTLC-densitometry). The first developed method employed silica gel HPTLC F254 plates as stationary phase using a chromatographic developing system composed of ethyl acetate–ethanol–water–ammonia (8.5:1:0.5:0.3, by volume). The separated drug bands were densito-metrically measured at 220.0 nm for AML, HCT, DSA and CT and at 295.0 nm for TIM. The linearity was assessed over a wide concentration range, 0.5–10 µg/band, 1.0–16.0 µg/band and 1.0–14 µg/band for AML, HCT and TIM, in order and 0.05–1.0 µg/band for each of DSA and CT. The second method is capillary zone electrophoresis (CZE). The electrophoretic separation was achieved using background electrolyte (BGE), borate buffer 40.0 mM with pH 9.0 ± 0.2, at applied voltage of + 15 kV with on-column diode array detection at 200.0 nm. The method linearity was reached over the concentration range of 20.0–160.0 µg/mL, 10.0–200.0 µg/mL, 10.0–120.0 µg/mL for AML, HCT and TIM, respectively and 10.0–100.0 µg/mL for DSA. The suggested methods were optimized to achieve best performance and validated agreeing with the ICH guidelines. Assessment of methods’ sustainability and greenness was performed using different greenness assessment tools. Graphical Abstract

Significance Statement: This case report demonstrates a novel approach to treating a rare indirect carotid cavernous fistula (CCF) and associated abducens palsy. Although endovascular treatment is the standard of care in the management of CCFs, it was contraindicated in this patient. Instead, she underwent an endoscopic endonasal approach (EEA) with decompression of the medial orbital apex, including the cavernous sinus and optic nerve, with complete resolution of headache, lateral gaze palsy, and diplopia within 2 months. [ABSTRACT FROM AUTHOR]