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ABSTRACT We report five cases of spider angiomas in children treated topically with timolol 0.5% (ophthalmic solution or gel‐forming solution), for 6 months. Parents and patients were advised to apply one drop twice daily. Four of them showed either partial (2) or complete response (2) and only one patient had no clinical change. No adverse effects were reported. This pilot case series shows that topical timolol may prove useful as a noninvasive, available and well‐tolerated treatment option for spider angiomas in children who seek a treatment alternative to pulsed dye laser. [ABSTRACT FROM AUTHOR]

Two cases of pyogenic granulomas in burned skin were presented, a 17‐month‐old boy and a 7‐year‐old girl, being given oral propranolol and topical timolol. Both cases showed lesions improvement with no adverse effects, suggesting that beta‐blocker therapy may have a positive impact on the treatment of pyogenic granuloma after burns. [ABSTRACT FROM AUTHOR]

Herein, a portable and cost‐effective electrochemical sbased on Silver/tannic acid/titanium dioxide/glassy carbon electrode (Ag/TA@ TiO2/GCE) was fabricated to determine timolol(TM) assay. The Ag/TA@TiO2/GCE offered an irreversible oxidation peak at +0.99 V, and exhibited an extraordinary electrochemical performance with a wide linear working ranges from 0.01–0.84 and 0.84–49.0 μM and a low detection limit of 5.2 nM. The detection of TM in the presence of interfering agents and real samples was also analyzed. The sensor's selectivity was studied by comparing the binding of TM, propranolol, nebivolol, and metoprolol. The developed electrochemical sensing platform could have promising potential for the determination of TM in clinical samples. [ABSTRACT FROM AUTHOR]

Background: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. Objective: The objective was to analyze the inter‐ and intra‐observer agreement among pediatric dermatologists in the choice of treatment for IH. Methods: We performed a cross‐sectional inter‐rater and intra‐rater agreement study within the Spanish infantile hemangioma registry. Twenty‐seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra‐rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). Results: Twenty‐four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter‐rater agreement on the treatment decision was fair (AC1 = 0.39, 95% confidence interval [CI]: 0.30–0.47). When stratified by risk category, good agreement was reached for high‐risk hemangiomas (AC1 = 0.77, 95% CI: 0.51–1.00), whereas for intermediate‐ and low‐risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16–0.46 and AC1 = 0.38, 95% CI: 0.27–0.48, respectively). Propranolol was the main option for high‐risk hemangiomas (86.4%), timolol for intermediate‐risk (36.8%), and observation for low‐risk ones (55.9%). The intra‐rater agreement was good. The inter‐rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate‐ and low‐risk hemangiomas. [ABSTRACT FROM AUTHOR]

A combination product of human mesenchymal stem/stromal cells (MSCs) embedded in an extracellular matrix scaffold and preconditioned with hypoxia and the beta‐adrenergic receptor antagonist, timolol, combined with sustained timolol application post implantation, has shown promising results for improving wound healing in a diabetic mouse model. In the present study, we extend those findings to the more translatable large animal porcine wound model and show that the combined treatment promotes wound reepithelialization in these excisional wounds by 40.2% and increases the CD31 immunostaining marker of angiogenesis compared with the matrix control, while maintaining an accumulated timolol plasma concentration below the clinically safe level of 0.3 ng/mL after the 15‐day course of topical application. Human GAPDH was not elevated in the day 15 wounds treated with MSC‐containing device relative to wounds treated with matrix alone, indicating that the xenografted human MSCs in the treatment do not persist in these immune‐competent animals after 15 days. The work demonstrates the efficacy and safety of the combined treatment for improving healing in the clinically relevant porcine wound model. [ABSTRACT FROM AUTHOR]

Aim: Cessation of smoking induces nicotine withdrawal symptoms such as anxiety, depression, and dysphoria, which could lead to smoking relapse. In the present study, we examined the role of noradrenergic transmission within the ventral bed nucleus of the stria terminalis (vBNST) on nicotine withdrawal‐induced aversive behavior. Methods: Nicotine dependence in rats was established by subcutaneous implantation with a nicotine‐filled osmotic minipump on day 1. Nicotine withdrawal was precipitated by administration of the nicotine receptor antagonist, mecamylamine (3.0 mg/kg, s.c.), on day 15. Nicotine withdrawal‐induced intra‐vBNST noradrenaline release and aversive behavior were examined by in vivo microdialysis and a conditioned place aversion (CPA) test, respectively. Results: Intra‐vBNST noradrenaline release was significantly increased during nicotine withdrawal. Nicotine withdrawal induced aversive behavior, which was attenuated by intra‐vBNST injection of the β‐adrenoceptor antagonist, timolol. Conclusions: These results suggest that enhanced noradrenergic transmission via β‐adrenoceptors in the vBNST plays a crucial role in nicotine withdrawal‐induced aversive behavior. [ABSTRACT FROM AUTHOR]

Polyzwitterions are biocompatible and protein‐adsorption‐resistant polymers which makes them very attractive for pharmaceutical applications, especially as drug and gene delivery systems. Two different poly(sulfobetaine methacrylate) (PSB) based vehicles were synthesised in the present study using reversible addition‐fragmentation chain transfer polymerization, namely linear macromolecules and a crosslinked network as microgels, in order to be tested as ocular drug delivery systems for timolol maleate (TM). The differences in their structure were expected to result in different physicochemical properties as well as in different performances as potential ocular drug delivery systems. The PSB vehicles' structure and properties were investigated using dynamic light scattering, zeta potential measurements and SEM. The drug entrapment efficiency of TM in both PSB carriers was determined and the TM release profiles were monitored. In this way, the relationship between the PSB vehicles' structure and the TM release profiles was outlined. © 2022 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Background/objective: The association between antiglaucoma medications and the development of ocular pseudopemphigoid (OPP) has been described; however, the independent risk of each medication has not been quantified. Methods: Case/non‐case analyses were performed in the FDA Adverse Events Reporting System (FAERS) using data from 2010–2020 to examine the reporting odds ratio (ROR) signal for OPP for all classes of antiglaucoma medications under multiple conditions: (i) comparison to all other drugs in FAERs, (ii) comparison to other antiglaucoma medications, (iii) comparison to vehicle/hydrating eye drops with cases of OPP and (iv) comparison to vehicle/hydrating eyedrops with and without cases of OPP to control for topical irritant and preservative effects. Results: A statistically significant ROR for OPP was found for aggregate antiglaucoma medications under the first condition but not the third or fourth (i.96.97 (95% CI 52.54–178.98). The largest signal for OPP when compared to other glaucoma drugs and eye drops was seen with unoprostone (ii.68.96 (95% CI 8.35–569.50, iii.39.85 (95% CI 4.14–383.33), iv.581.67 (95% CI 49.38–6851.57) followed by carteolol (ii.32.51(95% CI 9.02–117.67), iii.10.67 (95% CI 1.77–64.13), iv.77.84 (95% CI 12.95–467.78) and betaxolol (ii.23.38 (95% CI 7.28–74.46), iii.6.94 (95% CI 1.27–38.01), iv.50.67 (95% CI 9.26–277.25). A statistically significant ROR was noted only for the beta‐blockers class aggregate under conditions ii and iv. Conclusions: Our findings support an association between OPP and antiglaucoma medications; under the most stringent control for topical irritant/preservative effect by of comparison to topical eye drops, unoprostone, carteolol, betaxolol and timolol all had a significant ROR for OPP. [ABSTRACT FROM AUTHOR]

Background: Centrofacial erythema associated with telangiectasis is the most common presentation of rosacea, known as erythematotelangiectatic rosacea (ETR). However, successful management of these symptoms remains challenging. Aim: The purpose of this study was to evaluate the efficacy and safety of topical timolol maleate eye drops 0.5% for ETR. Methods: In this randomized, single‐center, single‐blind, placebo‐controlled split‐face study, 16 patients with mild‐to‐moderate ETR who presented at West China Hospital between January 2019 to September 2020 were randomized to receive either topical timolol maleate eye drops 0.5% to one side of their face daily for 28 days and normal saline to the other side of the face. Patients were assessed with both the Clinician Erythema Assessment (CEA) and Patient Self‐Assessment (PSA) at the 28‐day follow‐up appointment. Subjective assessment was performed by asking participants to grade their sensation of warmth and burning. Results: The sides treated with timolol demonstrated a significant improvement in both the CEA and PSA at the 28‐day assessment. Patients reported a significant difference in warmth and burning sensations. The only adverse reaction was worsened redness on both sides of the face at Day 1 in one patient. Conclusions: In this small study, the application of topical timolol maleate was safe and effective for the treatment of ETR. [ABSTRACT FROM AUTHOR]

Background: Topical β‐blockers, propranolol, and timolol were used for pyogenic granuloma (PG) treatment; however, their efficacies and safety profiles were not compared. Aims: The aim was to evaluate the safety and efficacy of propranolol 1% and timolol 0.5% creams in the treatment of pyogenic granulomas. Patients: The study included 30 PG patients. They were divided into three groups (10 patients each). Group I patients received propranolol 1% cream. Group II patients used timolol 0.5% l cream. Group III patients used placebo cream. Creams were applied twice daily for 2 months. Patients were followed up for 3 months to detect any recurrence. Results: Complete resolution was reported in 6 patients of groups I and II, while none of the control patients reported complete resolution. Despite the absent change in lesions' size in 40% of β‐blockers treated groups, they all reported decreased bleeding tendency. There was insignificant difference between the clinical responses between β‐blockers groups. No recurrence was reported in any of the patients who achieved complete resolution after 3 months of follow‐up. Younger patients respond better to β‐blockers. Three patients were deteriorated on beta‐blockers treatment. Conclusion: β‐blockers are a promising PG treatment option in cases where invasive modalities are not desirable especially in younger patients. [ABSTRACT FROM AUTHOR]

A 34‐day‐old, male, white‐bellied caique (Pionites leucogaster) was presented for a complaint of bilateral buphthalmos. Clinical examination was unremarkable apart from the ophthalmic findings. The ophthalmologic examination was negative for direct, consensual, and dazzle reflexes in both eyes. The intraocular pressure exceeded 40 mm Hg OU. Fluorescein stain demonstrated corneal surface lesions suggestive of exposure keratopathy subsequent to bilateral buphthalmos. Diagnostic imaging tests were conducted to perform ocular biometric measurements and investigate the intraocular structures, including the iridocorneal angle and lens, by means of high‐resolution ultrasonography (HRUS). The presence of congenital glaucoma in this young parrot was strongly suspected after clinical and ophthalmological examination and the results of diagnostic imaging. Pharmacological treatment to reduce intraocular pressure was initiated using dorzolamide hydrochloride 2% and timolol maleate 0.5%. A month later, the parrot's eyes did not show any visual improvement, but the intraocular pressure had returned to normal. The parrot was unable to feed itself and died during a feeding procedure. Postmortem examination revealed ab ingestis pneumonia. Both eyes were submitted for histopathology, with severe anterior segment dysplasia and goniodysgenesis found OU. Histological findings added to the clinical presentation, the ophthalmologic examination and the imaging findings, confirmed the presence of congenital glaucoma. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness and safety of topical β‐receptor blocker in treating superficial infantile haemangiomas (SIH) and compare the effectiveness and safety of topical β‐receptor blocker against other therapies. Methods: A search of the literature using PubMed, Embase, Cochrane Review database, China National Knowledge Infrastructure and Wanfang were performed to identify the studies that estimated the effectiveness and safety of topical β‐receptor blocker in treating SIH, the fixed‐effect or random‐effects meta‐analytical techniques were applied to assess the outcomes. Results: Twenty studies, involving 2098 patients, were included to conduct this analysis. Topical propranolol and topical timolol were discovered to be as effective as oral propranolol in treating SIH (propranolol, odds ratio [OR] = 0.486, 95% confidence interval [CI] 0.165, 1.426, P =.189; timolol, OR = 0.955; 95%CI 0.700, 1.302; P =.769), and topical timolol was more effective than topical imiquimod (OR = 2.561; 95%CI 1.182, 5.550; P =.017), observation (OR = 18.458; 95%CI 5.660, 60.191; P <.001) and topical saline solutions (OR = 19.193; 95%CI 8.837, 41.683; P <.001) in treating SIH. The comparison between topical propranolol and oral propranolol led to no discovery of significant difference in the incidence of adverse effects (OR = 1.258; 95%CI 0.471, 3.358; P =.647). Compared with oral propranolol, topical timolol was associated with fewer incidences of adverse effects (OR = 0.191; 95%CI 0.043, 0.858; P =.031). No significant difference in the incidence of adverse effects was found when topical timolol and topical imiquimod were compared (OR = 0.077; 95%CI 0.005, 1.206; P =.068). Conclusion: This meta‐analysis provided evidence that topical β‐receptor blockers (propranolol and timolol), especially timolol, may replace oral propranolol as a first‐line treatment for SIH. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of early and prolonged administration of aqueous suppressants in reduction of hyperencapsulation and intraocular pressure (IOP) control after paediatric Ahmed glaucoma valve (AGV) implantation. Methods: A prospective randomized interventional study recruited children who had AGV implantation for paediatric glaucoma. All patients received postoperative Timolol 0.5% for either 12 months (Group A) or 3 months (Group B). Additional IOP‐reducing medications were added if IOP exceeded 21 mmHg or hyperencapsulation developed in either group. Primary outcome measures were rate of hyperencapsulation and reduction of IOP. Results: Eighty sex children completed the 12‐month follow‐up visits. Baseline IOP was significantly reduced from 31.95 ± 9.1 to 16.94 ± 3.4 mmHg at 12 months in Group A and from 32.7 ± 7.4 to 19.85 ± 6.9 mmHg at 12 months in Group B. IOP was significantly lower in Group A than B at 6‐, 9‐ and 12‐month follow‐up visits. In the first 4 months, the hyperencapsulation rate was similar in both Group A (six eyes, 13.3%) and Group B (seven eyes, 17.1%). However, the hyperencapsulation rate was significantly lower in Group A than B at both 6 months (22.5% versus 36.6%) and 12 months (31.1% versus 46.3%). Anti‐glaucoma medications were significantly lower in Group A than B at both 6 months (1.3 versus 3.2 drugs) and 12 months (1.5 versus 3.6 drugs). Conclusion: Early and prolonged use of aqueous suppressants significantly reduced the rate of hyperencapsulation and provided better IOP control after paediatric AGV implantation. [ABSTRACT FROM AUTHOR]

Thus, off-label use of IH with ophthalmic timolol maleate was initially reported in 2010,[4] and since that time reports of ACD are still scarse.[[6]] Thus, although generally well tolerated, ACD by topical ophthalmic timolol in dermatology is just underestimated or misdiagnosed. Systemic propanolol is, indeed, indicated for IH which might be life-threatening and with a functional or aesthetic risk.[5] Moreover, as systemic propanolol and topical timolol are used in different types of IH, it remains an open question if it is possible to use systemic propanolol in skin-sensitized patients to timolol. [Extracted from the article]

Background/Objectives: First‐line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta‐blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off‐label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. Methods: A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. Results: Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2 months duration (P = 0.006) and were a median of 1.7 months younger (P = 0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P = 0.036). Conclusions: Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta‐blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures. [ABSTRACT FROM AUTHOR]

For partial responder patients (timolol group and one patient of propranolol group), we decided to start therapy with elastic stocking. Patients were randomly divided into two treatment groups; six patients were treated with timolol maleate 0.5% gel (available for ophthalmic use), while the remaining patients were treated with 2% propranolol cream (galenic preparation). [Extracted from the article]

Overall, 19 patients completed the treatment and follow-up, as one patient in the PDL group lost to follow-up after the first treatment (Table 1). Infantile haemangioma (IH) is the most common benign vascular tumour of infancy, and approximately 10-15% of patients with IH develop complications, among which ulceration is the most frequent.1 To date, oral propranolol has been most widely used in ulcerated IHs.2 Nevertheless, for relatively small ulcers, the topical application of timolol was proposed as an alternative method.3 Meanwhile, pulsed dye laser (PDL) may also promote the resolution of ulcerated IHs.4 However, there are no clinical studies comparing the efficacy of these two localized therapies in promoting ulcer healing in IHs. [Extracted from the article]

Topical timolol has been shown to be effective on treatment of Kaposi sarcoma. We present the case of a 72‐year‐old man with classic Kaposi sarcoma on upper limbs, treated with topical timolol 0.5% twice a day with a pruritic eruption on areas of application. [ABSTRACT FROM AUTHOR]

Propranolol and topical timolol treatment length varied from 30 days to 10 months and follow-up time ranged from 30 days to 22 months. One trial of oral propranolol ( I n i = 460) reported clinician-assessed clearance in 60.3% of children receiving 3 mg/kg/day of oral propranolol, 49% of children receiving 1 mg/kg/day of oral propranolol, and 3.6% of children receiving placebo after 6 months of treatment. They reported patients who had an improvement of at least 50% in the size of their haemangiomas as having effective treatment and found no difference between the groups (69.2% receiving propranolol vs. 61.5% receiving topical timolol). Although this review indicates that both oral propranolol and topical timolol maleate are options for treatment of infantile haemangiomas, the evidence was not assessed as high quality. [Extracted from the article]

Abstract: We present three patients with agminated pyogenic granulomas who experienced significant decrease in size and bleeding with treatment with topical timolol solution with minimal side effects. One patient had complete clinical resolution. For patients with agminated pyogenic granuloma who may otherwise have limited treatment options, timolol is an effective potential solution. [ABSTRACT FROM AUTHOR]

Abstract: Background/Objective: To report our observations from a trial of the short‐term effectiveness and safety of topical carteolol hydrochloride drops to treat infantile hemangiomas (IHs). Methods: From October 2012 to September 2015, the study recruited 349 children with superficial IHs. Participants were randomized to two groups: treatment (n = 224 who received 2% carteolol hydrochloride drops administered to the lesion surface twice daily) and observation (n = 125 who did not receive treatment). Therapy duration was 6 months. Results: The mean age at the beginning of treatment was 3.2 months. Treatment responses were categorized as class 1 (total regression), class 2 (partial regression or controlled growth), or class 3 (no response). Of infants receiving carteolol treatment, 10.7% (24 patients) were categorized as class 1, 72.3% (162 patients) as class 2, and 17.0% (38 patients) as class 3. Of infants in the observation group, 5.6% (7 patients) were categorized as class 1, 25.6% (32 patients) as class 2, and 68.8% (86 patients) as class 3. No adverse effects were noted during treatment. Conclusion: Carteolol is an effective, safe topical treatment for superficial IHs. Carteolol may be used to treat proliferative superficial IHs, particularly in infants younger than 6 months. [ABSTRACT FROM AUTHOR]

Purpose To compare the additive effects and safety of 1% brinzolamide/0.5% timolol fixed combination ( BTFC) versus the low-dose regimen of 1% dorzolamide/0.5% timolol fixed combination ( DTFC) in patients with open-angle glaucoma and ocular hypertension ( OAG/ OH) following treatment with prostaglandin analogues ( PGAs). Methods A prospective, randomized, double-masked, multicentre, parallel-group and active-controlled study included 201 Japanese OAG/ OH patients who had been treated with PGA. Efficacy was assessed as the change in intra-ocular pressure ( IOP) from baseline after weeks 4 and 8. Safety was assessed with adverse event rates, ocular discomfort score, blur scale, blood pressure and heart rates, best-corrected visual acuity (BCVA) and slit lamp examinations. Results Intra-ocular pressure (IOP) change from baseline at 9 AM/11 AM pooled over the 8 weeks was −3.3/−3.3 mmHg in the BTFC group and −2.9/−3.4 mmHg in the DTFC group, demonstrating non-inferiority of BTFC to DTFC. Ocular irritation was frequently seen in DTFC group. Although blurred vision was frequently seen in BTFC group, it was transient and blurring became the equivalent 3 min after instillation between two groups. No noteworthy issue was observed in other safety outcome. Conclusion Non-inferiority of BTFC to DTFC in IOP reduction was demonstrated after adding onto PGA therapy in Japanese OAG/ OH patients. Although the score of blurred vision was transiently higher in BTFC than DTFC, treatment difference decreased and disappeared with time. Thus, BTFC can be considered as a safe and effective agent for glaucoma treatment. [ABSTRACT FROM AUTHOR]

Finally, timolol has been suggested to be beneficial in the treatment of erythematotelangectatic rosacea following a split-face, randomized trial of 8 patients over 16 weeks, in which 0.5% gel-forming solution was used twice daily.[5] REFERENCES 1 Kalantari Y, Dadkhahfar S, Etesami I. Post-acne erythema treatment: a systematic review of the literature. Moreover, Al Mokadem et al.[4] suggested adding topical timolol to the standard treatment protocol of acne after they observed improvement in acne comedones and resistant inflammatory erythema. Topical timolol 0.5% gel-forming solution for erythema in rosacea: a quantitative, split-face, randomized, and rater-masked pilot clinical trial. [Extracted from the article]

Background/Objectives Infantile hemangiomas ( IHs) are vascular tumors with the potential for significant morbidity. There is a lack of validated objective tools to assess IH severity and response to treatment. Diffuse optical spectroscopy ( DOS), a noninvasive, nonionizing imaging modality, can measure total hemoglobin concentration and hemoglobin oxygen saturation in tissue to assess IH vascularity and response to treatment. Our objective was to evaluate the utility of a wireless, handheld DOS system to assess IH characteristics at selected points during their clinical course. Methods Thirteen subjects (initial age 5.8 ± 2.0 mos) with 15 IHs were enrolled. IHs were classified as proliferative, plateau phase, or involuting. Nine patients with 11 IHs were untreated; four patients with 4 IHs were treated with timolol or propranolol. Each IH was evaluated by placing the DOS system directly on the lesion as well a normal contralateral skin site. IH vascularity and oxygenation were scored using a newly defined normalized hypoxia fraction ( NHF) coefficient. Measurements were recorded at various intervals from the initial visit to 1 to 2 years of age. Results For the nine untreated IHs, the NHF was highest at 6 months of age, during proliferation. Differences in NHFs between the proliferation and the plateau (p = 0.02) and involuting (p < 0.001) stages were statistically significant. In treated patients, the NHF normalized to 60% after 2 months. One treated IH came within 5% of the NHF for normal skin after 12 months. Conclusions DOS can be used to assess the vascularity and tissue oxygenation of IHs and monitor their progression and response to treatment. [ABSTRACT FROM AUTHOR]

This work was aimed to synthesize and characterize poly(2-hydroxyethyl methacrylate) [poly (HEMA)]-based molecularly imprinted polymer nanoparticles (MIP NPs) containing timolol maleate (TM) via precipitation polymerization. The molecular structures of the MIP and non-imprinted polymer (NIP) NPs were compared by means of Fourier transform infrared spectroscopy. The morphological observations by using scanning electron microscopy and transmission electron microscopy confirmed the formation of MIP NPs as small as 128 nm in average diameter with appropriate synthesis conditions. Thermal behaviors of the samples were also studied by the use of thermogravimetric analysis and differential scanning calorimetry. By considering a series of key factors such as monomer : template ratio, cross-linker type, pH, and temperature, the sample with promising characteristics was found to be that of HEMA : TM ratio of 10:1, 40 mmol of ethylene glycol dimethacrylate as cross-linker, and polymerization temperature of 60°C in acetonitrile as porogenic solvent. Furthermore, the ultraviolet-visible (UV-vis) spectrophotometry results proved a controlled release of TM from the MIP NP samples compared with NIP ones at extended periods. Moreover, the cytotoxicity of the MIP and NIP NPs samples was evaluated on mesenchymal stem cells, and the obtained observations showed that they had no adverse side effect on the living cells; especially the surface of the MIP NPs sample depicted highly cell's biocompatibility. Finally, the outcomes from designed different experiments conducted us that the HEMA-based MIP NPs have great potential as an ocular nanocarrier for TM delivery. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a case study of 84-year-old male diagnosed with exfoliation glaucoma in age of 69 years. Topics discussed include undergone with bilateral cataract surgery with intraocular lens implantation; intraocular pressure measurement with Goldmann applanation tonometry; and mention about prescription of bimatoprost and timolol as treatment.

Purpose: To compare the efficacy and safety of rho kinase inhibitor (ROKi) with placebo or other glaucoma medication in people diagnosed with open‐angle glaucoma (OAG), primary open‐angle glaucoma (POAG) or ocular hypertension (OHT). Methods: We searched CENTRAL, MEDLINE, Embase, PubMed, LILACS, ClinicalTrials and ICTRP for randomized clinical trials and controlled clinical trials with no restrictions of type, year, and publication status. Two review authors independently screened, extracted data, and evaluated risk of bias. Results: We included 17 trials (4953 participants) evaluating the efficacy and safety of marketed ROKI‐based drugs; netarsudil and ripasudil. Trial duration varied from 24 h to 12 months. The intraocular pressure (IOP) lowering effect of netarsudil may be superior to placebo (mean difference (MD) 3.11 mmHg 95% CI 2.59–3.62; low‐certainty evidence), but inferior to latanoprost (MD 0.97 mmHg 95% CI 0.67–1.27; moderate‐certainty) and timolol (MD 0.66 95% CI 0.41–0.91; low‐certainty). Combining netarsudil and latanoprost probably further reduces IOP compared with either netarsudil (MD 2.66 mmHg 95% CI 2.35–2.98; moderate‐certainty) or latanoprost (MD 1.64 mmHg 95% CI 1.11–2.16; moderate‐certainty). Combining ripasudil and timolol may probably reduce IOP compared with timolol monotherapy (MD 0.75 mmHg 95% CI 0.21–1.29; moderate‐certainty). The certainty of evidence reporting ocular adverse events (AEs) was very low or low. However, compared to timolol, netarsudil (21 additional ocular AEs per 100‐person‐months 95% CI 14–27; moderate‐certainty) and combination therapy with ripasudil/timolol (35 additional ocular AEs per 100 person‐months 95% CI 25–45; moderate‐certainty) probably lead to more ocular AEs. ROKi was not associated with any particular serious AEs. Conclusions: The current evidence suggests that in people diagnosed with OHT or (P)OAG, the hypotensive effect of netarsudil may be inferior to latanoprost and slightly inferior to timolol. Combining netarsudil and latanoprost probably further reduces IOP compared with monotherapy. However, differences are small and may not be clinically significant. Netarsudil as mono‐ or combination therapy may result in more ocular AEs, but the evidence on AEs is limited. [ABSTRACT FROM AUTHOR]

Objective To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution ( GFS) on intraocular pressure ( IOP), pupil diameter ( PD), and heart rate ( HR) in normal cats and cats with feline primary congenital glaucoma ( FCG). Animals studied and procedures A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes ( OU) every 2 h ( PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. Results Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. Conclusion Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma. [ABSTRACT FROM AUTHOR]

Background The success of oral propranolol for treatment of infantile hemangiomas (IHs) has led practitioners to use topical β-blockers. In preterm infants, clinicians frequently turn to topical timolol, with the presumption that topical application will result in less systemic absorption. We used Holter monitoring to assess for drug-induced bradycardia in high-risk infants. Methods We retrospectively reviewed the charts of 22 at-risk infants who received a Holter monitor to assess for association between timolol administration and development of significant bradycardia. Results Four infants had episodic bradycardia detected by Holter monitoring. Two of these infants were full term; weighed more than 3,000 g; and had rare, brief, asymptomatic episodes unrelated to the timing of the timolol application. The other two infants had symptomatic bradycardia while on timolol and were the only two babies that weighed less than 2,500 g at initiation of therapy. Both were young (postmenstrual age [PMA] 34 and 37 wks) at initiation and had a timolol dose above the average exposure for the cohort. Conclusion In this cohort of at-risk infants, topical timolol appeared to provide safe treatment for IHs in full-term infants receiving a dose of less than 0.2 mg/kg/day, but infants with a PMA of less than 44 weeks and weight at treatment initiation of less than 2,500 g may be at risk of adverse events, including bradycardia, hypotension, apnea, and hypothermia. We recommend close monitoring of temperature, blood pressure, and heart rate in premature and low-birthweight infants with IHs at initiation of and during therapy with topical timolol. [ABSTRACT FROM AUTHOR]

Background Echocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta-blocker used in glaucoma is safe and transiently decreases HR in clinical trials. Hypothesis Administration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects. Animals Twenty-five apparently healthy cats. Methods Electrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR. Results Acclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed ( P < .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20, P = .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first-degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats. Conclusions and clinical importance Ocular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function. [ABSTRACT FROM AUTHOR]

Background Pyogenic granuloma ( PG) is a benign vascular tumor that can be treated by cautery (chemical or thermal), laser, excision, curettage, sclerotherapy, and cryotherapy. Topical timolol is emerging as a non-invasive modality for the treatment of PGs. Methods We recruited a series of 10 patients with PG, who received treatment with 0.5% timolol maleate ophthalmic solution applied 4 times a day, 2 drops per dose. No other medication, topical or systemic, was given. Pulse rate, blood pressure, and blood glucose were monitored at baseline and weekly thereafter for the duration of treatment. ECG was done at baseline. The efficacy of the treatment was evaluated by considering a complete response, a partial response, and no response. Results Of 10 patients, four showed complete response within 3-24 days, with no recurrence at 3-month follow-up. Three patients each showed partial or no response. No local or systemic side effects were reported in any of the patients. Conclusions The response of PGs to β blockers seems to be variable. Although topical timolol has the advantage of minimal adverse events, ease of administration, and better cosmetic outcomes, it's efficacy in PG may not be universal unlike in infantile hemangiomas. Topical timolol may be a treatment option in young children, incapacitated elderly, and over delicate areas like face, nails, and gums where invasive modalities are not desirable. [ABSTRACT FROM AUTHOR]

Background Topical use of timolol for infantile hemangiomas has recently emerged with promising results. It is unknown whether topical β-blockers act locally or if their effect is partly due to systemic absorption. This study investigates whether topically applied timolol is absorbed and reports on the efficacy of this treatment. Methods We treated 40 infants with small proliferating hemangiomas with topical timolol gel 0.5% twice daily and assessed urinary excretion and serum levels in a proportion of patients. Clinical response was evaluated on a visual analog scale of standardized photographs after 1, 2, 3, and 5 months. Results Forty infants with a median age of 18 weeks (range 2-35 wks) were included; 23 (58%) had superficial and 17 (42%) mixed-type hemangiomas. The median size was 3 cm2 (range 0.1-15 cm2) and nine hemangiomas were ulcerated. The hemangiomas improved significantly during treatment, with a median increase in visual analog scale of 7 points after 5 months (p < 0.001). Urinalysis for timolol was performed in 24 patients and was positive in 20 patients (83%). In three infants, serum levels of timolol were also measured and were all positive (median 0.16 ng/mL [range 0.1-0.18 ng/mL]). No significant side effects were recorded. Conclusion Topical therapy with timolol is effective for infantile hemangiomas, but systemic absorption occurs. Serum levels in our patients were low, suggesting that using timolol for small hemangiomas is safe, but caution is advised when treating ulcerated or large hemangiomas, very young infants, or concomitantly using systemic propranolol. [ABSTRACT FROM AUTHOR]

Objective To compare the effect of commercially available solution and compounded ointment formulations of dorzolamide(2%)-timolol(0.5%) on intraocular pressure ( IOP) of normal horses. Animals Eighteen clinically normal horses. Procedures A randomized, masked prospective design was used with horses divided into two equal groups. One eye of each horse was selected for topical ophthalmic treatment with either 0.2 mL of dorzolamide(2%)-timolol(0.5%) solution or 0.2 g of dorzolamide(2%)-timolol(0.5%) ointment every 12 h for 5 days. The contralateral eye of horses in both groups was untreated. Rebound tonometry was performed every 6 h starting 2 days prior to and ending 2 days after the treatment period. Results The mean IOP reduction in eyes treated with the solution or ointment formulations was 13%. Untreated eyes in both groups experienced a lesser but still statistically significant reduction in IOP. The IOP values did not return to baseline within 48 h of the last treatment. Conclusions and Clinical Relevance The commercially available solution and compounded ointment formulations of ophthalmic dorzolamide(2%)-timolol(0.5%) had similar effects on IOP in normal horses. Persistent IOP reduction following cessation of treatment may indicate prolonged drug effect or acclimation of horses to tonometry. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Rapid Complete Regression of an Early Infantile Hemangioma With Topical Timolol Gel" by K. Semkova and J. Kazandjieva published in the journal in 2014.

Lasers, 595-nm pulsed dye and 1,064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG), have been used successfully for the treatment of infantile hemangiomas ( IHs). Recently the use of a topical β-blocker, specifically timolol maleate, has been promising in the treatment of IHs. The objective of this study was to compare the effectiveness of topical timolol 5 mg/mL solution with that of combined sequential dual-wavelength laser in the treatment of IHs. Sixty children with IHs were divided randomly into two equal groups. Group 1 was treated with applications of timolol drops (5 mg/mL) twice daily. Group 2 was treated with sequential pulsed dye and Nd:Yag laser. Treatments were performed every month for a maximum of six sessions. Efficacy was evaluated clinically and by measuring the average hemoglobin level. A significant decrease in the average hemoglobin level was determined in both groups and a dramatic response was observed in superficial hemangiomas in the timolol group. The timolol group received treatment for an average of 4.0 ± 1.1 months and the laser group for 5.5 ± 0.9 months. The degree of improvement of mixed hemangiomas to laser treatment was greater than that of the timolol group. During 3 months of follow-up, no further improvement or relapse was reported in either group. Timolol solution is a safe and effective alternative to laser treatment in superficial hemangiomas. In mixed hemangiomas, the combined sequential 595-nm and 1,064-nm dual-wavelength laser provided better results than timolol solution because it penetrated deeply so that deep dermal blood vessels were reached. [ABSTRACT FROM AUTHOR]

Purpose Glaucoma is a chronic ocular disease, which is usually managed with long-term daily medical therapy, in the form of eye drops. Patients who are intolerant to preservatives in topical medicines require preservative-free versions. From early 2011 patients attending Moorfields Eye Hospital, London, UK, started to report recurring problems with the supply of the following preservative-free glaucoma medications: Timolol 0.25% (Timoptol 0.25%, MSD UK); Dorzolamide (Trusopt, MSD UK); Dorzolamide and Timolol 0.5% (Cosopt, MSD UK). This study investigates the impact of the supply problems of these medications at Moorfields Eye Hospital from a patient, administrative and clinical perspective. Methods Information was sought by interviewing both patients and hospital staff, and by a retrospective case note review between April 2010 and May 2013. Results Many hospital roles, both administrative and clinical, were involved in attempting to resolve the impact of the supply problems. All staff reported a considerable increase in their workload. At the peak of the problem, the glaucoma secretaries received about 150 enquiries per week. A review of 83 sets of patient notes, retrieved from a random sample of 125 patients, showed that 22% encountered a supply problem. Of these, more than one-third attended Moorfields Eye Hospital Accident & Emergency (A&E) for repeat supplies and 89% eventually had their medication changed. In telephone interviews with 39 of a random sample of 50 patients (a subset of the 83 notes retrieved), 59% of the interviewees reported a supply problem. Of these, one-third attended Moorfields Eye Hospital A&E for repeat supplies and half eventually required an alternative medication. Some patients reported going to considerable lengths to obtain ongoing supplies in the community. Conclusions This study shows that medication supply problems can have a major impact on patients and hospital services. Supply problems occur across many fields of medicine and with increasing frequency. The findings of this study highlight the importance of early communication of impending shortages between manufacturers and the Department of Health, as recommended in the best practice guidelines. In order to minimise the impact of medicine shortages on patients, clinicians and administrative staff, hospitals need immediate notification of potential supply problems and clear updates on supply resolution. In addition, hospitals should consider nominating an individual as a contact point for patient enquiries regarding medicine supply problems. [ABSTRACT FROM AUTHOR]

Oral and topical β-blockers are used to treat infantile hemangiomas ( IHs). Although a recent consensus report provided guidelines for the treatment of IH with propranolol, there are no standard guidelines for the use of topical timolol. The objectives of this study were to determine the current use of oral propranolol and topical timolol by pediatric dermatologists in an outpatient setting and to compare current propranolol use with published propranolol consensus guidelines. An electronic survey was sent to pediatric dermatologists in May and June 2013. One hundred forty-nine pediatric dermatologists responded to the survey, a 79% response rate. Of the respondents, 96% prescribed oral propranolol, but 75% did not follow consensus guidelines exactly; recommended history, physical examination, initial dose, and frequency varied. The dose of propranolol was usually titrated up to goal dose as recommended (89%). Fifty-six percent monitored vital signs in patients after the initial dose and 49% continued to monitor vital signs in their clinic after each dose escalation, which did not meet consensus guideline recommendations. Ninety-one percent reported using topical timolol for the treatment of IH and 66% responded they had used topical timolol in conjunction with oral propranolol to treat IH. The most common indication was superficial hemangiomas (97%). Most practitioners (74%) did not routinely monitor heart rate or blood pressure in infants treated with topical timolol. This study highlights the variability in prescribing and monitoring practices of physicians using propranolol for the treatment of IHs and demonstrates that topical timolol is commonly used alone and in conjunction with oral propranolol to treat IHs. [ABSTRACT FROM AUTHOR]

Background/Objectives Topical timolol maleate solution or gel-forming solution is used alone or in conjunction with oral propranolol for the treatment of infantile hemangiomas. The consistency of the amount of timolol dispensed has never been evaluated. We evaluated the variability of drug delivery between different brands and formulations of timolol solution and gel-forming solution. Methods Five blinded volunteers sequentially dispensed five drops from each of the eight bottles containing timolol 0.5% solution or gel-forming solution. This was repeated three times per user for each bottle. The average amount of timolol dispensed was analyzed according to brand, formulation, and user for variability. The intra- and interuser variability of dispensing both formulations of timolol was also measured. Results Our study demonstrates statistically significant differences in the amount of timolol dispensed between timolol solution and gel-forming solution, with the latter closer to manufacturer estimates. Significant differences in the amount of timolol dispensed were noted between users regardless of the formulation or brand. Variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution. Inter- and intrauser variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution. Conclusion Statistically significant differences were noted in the amount of timolol dispensed according to formulation, brand, and user. Whether this is clinically significant is unknown given the lack of pharmacokinetic data available for timolol. [ABSTRACT FROM AUTHOR]

Objective To evaluate for drugs with superior neuroprotective efficacy and investigate their underlying mechanisms related to antioxidation. Procedures Brinzolamide (1%), timolol (0.5%), minocycline (22 mg/kg), lidocaine (1.5 mg/kg), and methylprednisolone (30 mg/kg) were administered to Sprague-Dawley ( SD) rats. The retina was evaluated by electroretinography and histological analysis. The antioxidative capacity of drugs was evaluated to clarify the underlying mechanism. The oxidant/antioxidant profiles of plasma, red blood cells, and retina were analyzed by lipid peroxidation (malondialdehyde) and by measuring the activities of antioxidants. Proteomic analysis was used to investigate the possible protective mechanisms of the drug against ischemia-reperfusion injury. Results The results suggested that timolol, methylprednisolone, and minocycline protected retinal function. Methylprednisolone and minocycline possessed good antioxidative activity. Brinzolamide and lidocaine preserved the structural integrity of the retina, but not retinal function. Conclusion Methylprednisolone, minocycline, and timolol have potential acute or delayed benefit in retinal ischemia-reperfusion injury. Their neuroprotective actions depend at least partially on the ability to alleviate oxidative stress. [ABSTRACT FROM AUTHOR]

Infantile hemangiomas ( IHs) are benign vascular tumors of infancy. Topical timolol has recently been reported to be an effective treatment for superficial IHs, although it failed to have an effect on deep IHs. This prospective study was aimed at evaluating the feasibility of ablative fractional laser-assisted drug delivery for enhancing topical timolol permeation into deep IHs. Nine patients ages 1 to 6 months with deep IHs were enrolled. A fractional carbon dioxide ( CO2) laser system was applied to the skin surface of deep IHs using the Deep Fx mode (25-30 mJ/pulse, 5% density, single pulse) at 1-week intervals. Topical timolol maleate 0.5% ophthalmic solution was applied under occlusion for 30 minutes four to five times per day for an average treatment duration of 14.2 weeks. Clinical improvement was evaluated according to a global score and the Hemangioma Activity Score ( HAS). Four patients (44.4%) demonstrated excellent regression, four (44.4%) showed good response, and one (11.1%) experienced moderate regression. The HAS declined from 4.1 ± 0.7 at baseline to 1.7 ± 0.7 at 1 week (p < 0.001) and 1.4 ± 0.7 at 3 months (p = 0.03) after the last treatment procedure. Plasma timolol concentration was not detected in any of the patients after the first administration of topical timolol. No systemic complication or skin side effects were observed in any of the patients. Ablative fractional laser-assisted transdermal delivery of topical timolol is a safe and effective method for the treatment of deep IHs. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters. Methods Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests ( IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy ( IVCM) were performed in all patients at baseline and after 12 months. IVCM ( HRT II Rostock Cornea Module; Heidelberg Engineering Gmb H, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity. Results IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 ± 7.70) than in the preservative-free beta-blocker group (86.83 ± 22.17, p < 0.001) and controls (88.9 ± 18.33, p < 0.001). The epithelial layer was significantly more regular in the preserved beta-blocker medication group than in the preservative-free beta-blocker group (p < 0.001) and the control group (p < 0.001). A significant reduction in both Schirmer I and BUT was found in the group of preserved timolol (respectively, 11.3 ± 2.97 and 8.12 ± 0.99) compared with preservative-free timolol (16.8 ± 1.83 and 11.27 ± 1.27, p < 0.001) and controls (17.8 ± 1.87 and 12.10 ± 1.28, p < 0.001). Conclusions Based on our IVCM data, preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma. [ABSTRACT FROM AUTHOR]

Propranolol and timolol are nonselective ß-adrenergic antagonists that induce peripheral vasoconstriction and affect angiogenic cytokines. Oral and topical ß-blocker therapy has become the de facto first-line treatment for complicated infantile hemangiomas because of its superior efficacy and tolerability. Pyogenic granulomas or lobular capillary hemangiomas are common acquired vascular tumors accounting for 0.5% of all skin nodules in children. Although they are benign vascular proliferations, treatment is often sought because of recurrent episodes of bleeding and for cosmetic considerations. Numerous treatment options are available, but recurrence rates are high. Noninvasive methods of treatment are being sought, particularly for young children. Herein we report a series of seven cases of cutaneous and mucosal pyogenic granulomas treated successfully using oral or topical ß-blockers. [ABSTRACT FROM AUTHOR]

Propranolol has become the treatment of choice of large and complicated infantile hemangiomas. There is a controversy concerning the safety of systemic propranolol. Here we show that topical use of the beta-blocker timolol can also inhibit the growth and promote regression of infantile hemangiomas. In this case series we treated 11 infantile hemangiomas in nine children including six preterm babies with the nonselective betablocker timolol. A timolol containing gel was manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel was applied using a standardized occlusive dressing (Finn-Chambers) containing approximately 0.25 mg of timolol. In all infants topical timolol was associated with growth arrest, a reduction in redness and thickness within the first 2 weeks. Seven hemangiomas showed almost complete resolution, and four became much paler and thinner. No data are available on the transdermal absorption of timolol. Even supposing complete absorption of timolol from the occlusive dressing, a maximum dose of 0.25 mg of timolol would result per day and hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in this case series occurred earlier than spontaneous regression which is generally not observed before the age of 9-12 months. The promising results need to be verified in prospective randomized trials on topical beta blocker administration for infantile hemangiomas which should address dose, duration, and mode of application. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the circadian and blood pressure (BP) reduction obtained with timolol maleate 0.5% solution administered twice daily versus timolol 0.1% in gel-forming carbomer administered in the morning in patients with primary open-angle glaucoma (POAG). Methods: This investigator-masked, crossover study prospectively enrolled naive POAG patients not receiving systemic cardiovascular medications. Following a baseline evaluation, they were randomized to receive a timolol 0.5% solution or timolol 0.1% hydrogel for 2 months and then switched to the alternative medication for a further 2 months. Intraocular pressure (IOP) phasing (sitting Goldmann tonometry at 10 am, 2 pm, 6 pm, and 10 pm and supine Perkins tonometry at 2 am and 6 am) and ambulatory home BP monitoring were measured at baseline and after each treatment period. Results: On the basis of a prospective sample size estimate, 28 patients were analyzed. Mean 24-hour IOP decreased from 23.1 ± 0.7 mm Hg at baseline to 18.9 ± 0.6 mm Hg after timolol 0.5% and 18.9 ± 0.8 mm Hg after timolol 0.1% hydrogel (P < .001); both formulations also significantly decreased diurnal, nocturnal, and individual time point IOP in a statistically similar manner. Systolic and diastolic BP remained generally unaffected. The calculated diastolic ocular perfusion pressure was either unaffected or tended to increase with either medication. Conclusion: Both timolol formulations show similar and significant circadian efficacy and have minimal effects on BP and calculated diastolic ocular perfusion pressure. [ABSTRACT FROM PUBLISHER]

Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta-blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel-forming solution and had photographic documentation of the IH and at least one follow-up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel-forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH. [ABSTRACT FROM AUTHOR]

The authors discuss the known and unknown potential side effects of topical timolol for treating infantile hemangiomas (IH) that will help physicians in deciding which patients are the right candidates for this therapy. They mention the potential and adverse effect of timolol which include bronchial asthma, severe chronic obstructive pulmonary disease, and sinus bradycardia. Furthermore, they note that topical therapy in IH can delay the use of systemic therapy.

Isothermal titration calorimetry (ITC) was used to identify the optimal timolol:functional monomer ratio for preparing soft contact lenses (SCLs) able to sustain drug release. ITC profiles revealed that each timolol molecule required six to eight acrylic acid (AAc) monomers to saturate the binding and that these ratios could be the most suitable for creating imprinted cavities. Various poly(hydroxyethyl methacrylate- co-AAc) hydrogels 0.2 and 0.9 mm thick were prepared with timolol:AAc molar ratios ranging from 1 : 6 to 1 : 32 and also in the absence of timolol. The hydrogels were reloaded with timolol by immersion in 0.04, 0.06, 0.08, and 0.10 m M drug solutions. Both imprinted and nonimprinted hydrogels showed a high affinity for the drug because of the presence of AAc. Nevertheless, the 1 : 6 and 1 : 8 imprinted hydrogels loaded less timolol but sustained the release better than the other hydrogels. These differences were explained in terms of the different arrangement of the functional monomers along the network. The imprinting effect was more noticeable in the case of the thinnest hydrogels, where the contribution of the diffusion path to the release rate was smaller. The results obtained prove the interest of ITC for the rational design of drug-imprinted networks to be used as medicated SCLs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. Methods: Aqueous eyedrops with hydroxypropyl-β-cyclodextrin containing 0.01–2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg). Results: Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf-life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10–22 hours after administration and duration of up to 32 hours. Conclusions: Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low-viscosity aqueous eyedrop formulations. [ABSTRACT FROM AUTHOR]

Timolol has been widely used in the treatment of glaucoma. Topically applied, timolol may cause adverse cardiovascular effects due to systemic absorption through the nasolacrimal duct. Timolol is mainly metabolized by cytochrome P450 2D6 (CYP2D6) in the liver. The aim of the present study was to characterize further the metabolism of timolol in vitro. Especially the effect of several drugs such as selective serotonin reuptake inhibitors on the metabolism of timolol was evaluated. In human liver microsomes, four timolol metabolites were identified, in cryo-preserved hepatocytes nine. In both in vitro experiments, the hydroxy metabolite M1 was the main metabolite. The in vivo half-life predicted for timolol was 3.7 hr. in cryo-preserved hepatocytes, corresponding to the half-life of timolol in humans in vivo. Fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine inhibited the formation of M1 in microsomes with IC50 values of 1.4, 2.0, 3.5, 21 and 20 μM, respectively. In human cryo-preserved hepatocytes, the IC50 values for fluoxetine, paroxetine and fluvoxamine were 0.7, 0.5 and 5.9 μM, respectively. In conclusion, compounds known to be potent CYP2D6 inhibitors inhibited timolol metabolism in in vitro experiments. The present results strongly suggest that fluoxetine and paroxetine may significantly affect the metabolism of timolol also in vivo and may thus potentiate the adverse cardiovascular effects of topically administered timolol. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effects of adding dorzolamide to timolol monotherapy on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (POAG). Methods: Twenty-four patients (12 healthy, 12 with POAG) were treated with dorzolamide/timolol combination (DT) versus timolol maleate 0.5% twice daily in a randomized, crossover, double-blind study conducted over a period of 18 months. Patients received each treatment for 8 months then crossed over to the other treatment after a 1-month washout and second baseline. Goldmann applanation tonometry, Heidelberg retinal flowmetry (HRF), colour Doppler imaging (CDI) and retinal photographic oximetry were performed at each visit. Results: DT significantly reduced intraocular pressure (IOP) in both glaucomatous [right eye (OD) −13.15%, left eye (OS) −14.43%; p < 0.036] and non-glaucomatous (OD −12.4%, OS −13.88%; p < 0.039) patients compared to timolol after 8 months of treatment. DT significantly reduced the number of zero blood flow pixels in the superior (−39.72%; p < 0.014) and inferior (−51.44%; p < 0.008) retina in the non-glaucomatous group and inferior retina in the glaucomatous group (−55.38%, p < 0.006). The continuation of timolol monotherapy from baseline did not change (p < 0.05) any measured parameter and neither treatment had a significant effect (p < 0.05) on retinal oximetry or CDI parameters. Conclusion: The addition of dorzolamide to timolol monotherapy decreases IOP and increases retinal blood flow in the superficial retinal vasculature in both glaucomatous and healthy patients following 8 months of treatment. The combination of increased retinal blood flow with consistent oxygen saturation may potentially increase oxygen delivery to the retina. [ABSTRACT FROM AUTHOR]