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Background Venous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs. Objectives To evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment. Methods A prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0 = 0.25, P1 = 0.45, alpha = 0.1, beta = 0.2) was planned. Patients with VLUs present for ≥ 24 weeks and with ≥ 50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm2 VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥ 40% reduction in ulcer area at week 12 (W12). Results Forty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35–93] years). At W12, ≥ 40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls. Conclusions These results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.

Jianming Wu,&ast; Fangyan Zhou,&ast; Yu Gao Department of Dermatological, Yuying Children’s Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Gao Email 570875734@qq.comPurpose: Assessment of the clinical effectiveness and safety of 755-nm long-pulse alexandrite laser combined with 0.5% timolol maleate eye drops in treating thicker infantile hemangioma (IH).Materials and Methods: Retrospective analysis of IH treated with 755-nm long-pulse alexandrite laser and topical timolol in the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to October 2020. Seventy-eight cases were included, with a five-week laser treatment interval. Treatment status was documented during the 35 weeks before each treatment, the effect was assessed at the visual analog scale (VAS), and side effects were recorded. During the 6-month follow-up period, the recurrence and residual skin lesions were monitored. The relationship between IH thickness, treatment duration and VAS was analyzed.Results: Among the 78 children with hemangioma, 4 children were treated with a combination of propranolol, fractional laser and cinnamyl alcohol injection due to poor curative effect. Finally, the lesions were effectively alleviated. At the 5th, 15th, 25th, and 35th weeks of treatment, the average VAS of 74 children were 3.56 ± 1.20, 4.61 ± 1.43, 5.63 ± 1.60, and 6.63 ± 1.72, respectively. We analyzed VAS in different thickness groups with Repeated Measures Analysis of Variance(RMANOVA). The results show that the VAS of the thickness 2– 3 mm and 3– 5mm groups were higher than the 5– 7mm and 7– 8mm groups (F group = 440.54, P < 0.05, F time = 448.31, P < 0.05). During the 6-month follow-up period, none of the 74 children relapsed and the residual skin lesions gradually vanished.Conclusion: Combined treatment of IHs with a 755-nm long-pulse alexandrite laser and 0.5% timolol maleate eye drops which has apparent clinical efficacy and safety reduce residual skin lesions and decrease the IH recurrence rate.Keywords: infantile hemangioma, 755-nm long-pulse alexandrite laser, timolol maleate eye drops, thick

Weikang Shi,&ast; Huiyi He,&ast; Jicong Jiang, Yu Gao, Hehe Quan Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hehe Quan Email 13587748556@qq.comPurpose: Infantile hemangioma (IH) is the most common benign tumor in infancy, and superficial IH is the most common type. IH can reportedly resolve spontaneously, but this is associated with complications, such as scars, atrophy, hypopigmentation, telangiectasia, and skin sagging, in 70% of cases. This study explores the safety and feasibility of therapeutic intervention with the 595-nm pulsed-dye laser (PDL) combined with 0.5% timolol maleate solution in superficial IH and compares the difference in efficacy between the early group and the late group.Patients and Methods: This retrospective study examined 167 patients with superficial IH who underwent combination therapy at the Dermatology Clinic of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University between July 2019 and July 2020. The early and late groups were composed of children aged ≤ 2 and > 2 months, respectively. Treatment was administered for 6 months, and patients were followed up for another 6 months. Two independent, double-blinded physicians reviewed photographs of the skin lesions before and after treatment to evaluate efficacy.Results: The early group demonstrated higher treatment efficacy than the late group. The early (n = 45) and late (n = 122) groups had treatment efficacy rates of 95.5% and 86.1%, respectively; the difference was statistically significant (P< 0.05). The early and late groups underwent 3.51 ± 0.50 and 4.73 ± 0.68 months of treatment, respectively; the difference was statistically significant (P< 0.05). Seventeen (44.4%) patients in the early group had immediate adverse reactions but no permanent sequelae, whereas 25 (20.49%) and 13 (10.7%) patients in the late group had immediate and permanent sequelae, respectively. The difference was statistically significant (P< 0.05).Conclusion: This retrospective study demonstrated that 595-nm PDL combined with 0.5% timolol maleate solution was a safe and effective local treatment for superficial IH. Early treatment required fewer treatments, had better curative effects, and a lower probability of permanent sequelae.Keywords: infantile hemangiomas, pulsed-dye laser, timolol maleate solution, timing and efficacy

Infantile hemangiomas are common benign vascular tumors but are rarely found in an intracranial location. Our literature review identified 41 reported cases. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids or interferon. Although beta-blockers have been widely prescribed in the treatment of cutaneous infantile hemangiomas since 2008, their use in the treatment of intracranial infantile hemangiomas has been minimal. We present a case of infantile hemangioma affecting the right orbit, associated with intracranial extension, causing intermittent right facial nerve palsy. The patient achieved an excellent outcome following combined treatment with oral propranolol and topical timolol maleate 0.5%, with complete regression of the lesion by 4 months. We conclude that beta-blockers are a safe and effective treatment of intracranial infantile hemangiomas and can be employed as first-line management of these lesions.

Selective laser trabeculoplasty and brimonidine tartrate 0.2%/timolol maleate 0.5% were shown to be equivalent in lowering intraocular pressure in uncontrolled primary open angle glaucoma patients when used as adjunct therapy for patients on a prostaglandin analog. Additionally, this is the first prospective study of optometrists performing selective laser trabeculoplasty. Although this study had a small sample size, the results appeared to show that efficacy and complication rates were comparable to previously published data; however, these results need to be confirmed with a larger multi-centered trial

Purpose The aim of this study was to analyze the effect of timolol maleate (0.5%) eye drops in the treatment of myopic regression after laser-assisted in-situ keratomileusis (LASIK). Methods The study was conducted at a tertiary care eye hospital in north India between April 2017 & March 2018 as a prospective interventional study. Patients who underwent uneventful myopic LASIK with hansatome mechanical keratome and presented with regression were included in the study. Baseline demographic characteristics, time to presentation with regression best-corrected visual acuity (BCVA), refraction, intraocular pressure, central corneal thickness and keratometry were recorded at baseline and at each follow-up visit. The enrolled patients were prescribed timolol maleate (0.5%) eyedrops twice daily. They were followed up every month till 3 months on timolol maleate (0.5%) eyedrops and at 6 months post stopping the treatment. Results Twenty-nine eyes of 15 patients were enrolled in the study. Mean pre LASIK spherical equivalent (SE) was - 7.48 ± 2.9 Diopters (Range-3.125 to -11.75 Diopters) and mean regression spherical equivalent was -1.02 ± 1.1 Diopters. There was a decrease in mean SE from presentation (intervention start point) up to 6 months follow-up (-1.34 ± 0.89 to -0.30 ± 0.29 Diopters). While posterior corneal curvature (K1 and K2 Back) changed significantly over treatment period (P = 0.0029, P = 0.0024 respectively), changes in anterior corneal curvature (K1 and K2 Front) were not significant (P = 0.05, P = 0.06 respectively). Central corneal thickness (CCT) and intraocular pressure (IOP) did not change significantly over treatment course. Conclusion Timolol maleate (0.5%) eyedrop is an effective modality for the treatment of refractive regression post LASIK circumventing the need for laser re-treatment in such patients. The most probable mechanism is reversal of the anterior bowing of the cornea in response to intraocular pressure changes.

The aim of this study was to evaluate the effects of 0.0015% preservative-free (PF) tafluprost alone and in combination with 0.5% timolol maleate or 0.5% betaxolol HCl on Schirmer tear test (STT), intraocular pressure (IOP), and pupil diameter (PD) in clinically normal dogs. Twenty-one healthy adult castrated male cross-bred dogs were used in this study. Dogs were randomly divided into three groups. The first group received one drop of (PF) tafluprost (Taf), in a randomly selected eye. The second group received one drop of (PF) tafluprost plus one drop of timolol maleate (Taf-Tim), and the last group received one drop of (PF) tafluprost plus one drop of betaxolol HCl, (Taf-Bet). In all groups, the fellow eyes were served as control and received one drop of saline as a placebo. IOP, STT, and PD measurements were performed at the baseline and every 30 min for the first 2 h, every 2 h for the next 10 h, and at 24 h and 36 h post-instillation (PI). In all groups, significant differences in IOP values were observed between treated and untreated eyes (Taf: p

Infantile haemangiomas (IHs) are the most common benign tumours of the eyelid and orbits in infancy. Beta-blockers, in the form of oral propranolol, have become first-line treatment in severe cases with functionally significant or disfiguring IH. However, adverse drug reactions of oral propranolol in infants are reported in 1 in 11 and serious or potentially life-threatening systemic side effects in 1 in 38, including dyspnoea, hypotension, hyperkalaemia, hypoglycaemia, and cyanosis, therefore requiring careful and close monitoring during the course of systemic treatment. More recently, two large meta-analyses have shown topical beta-blockers, such as timolol maleate 0.5%, to be as effective as oral propranolol in superficial IH, but with no or significantly fewer adverse effects, and have advocated that topical beta-blockers replace oral propranolol as the first-line treatment of superficial IH. We have previously reported the therapeutic response of deep periocular IH to primary topical timolol maleate 0.5% monotherapy. Here we also describe the first successful treatments of large orbital IHs with primary topical timolol maleate 0.5% monotherapy in four infants, resulting in immediate cessation of progression and rapid clinical improvement or resolution in all cases. No adverse effects and no recurrence during long-term follow-up of up to 2.5 years after cessation were seen in any of the patients treated with topical timolol maleate 0.5%.Infantile Hämangiome (IH) sind die häufigsten gutartigen Tumoren des Augenlids und der Augenhöhlen im Säuglingsalter. Betablocker in Form von oralem Propranolol sind in schweren Fällen mit funktionell signifikantem oder entstellendem IH zur Erstlinienbehandlung geworden. Unerwünschte Arzneimittelnebenwirkungen von oralem Propranolol werden jedoch in 1 von 11 Säuglingen und schwerwiegende oder potenziell lebensbedrohliche Nebenwirkungen in 1 von 38 Säuglingen berichtet, einschließlich Dyspnoe, Hypotonie, Hyperkaliämie, Hypoglykämie und Zyanose, die daher eine sorgfältige und genaue Überwachung während der oralen Behandlung erfordern. In jüngerer Zeit haben 2 große Metaanalysen gezeigt, dass topische Betablocker wie Timololmaleat 0,5% bei oberflächlichem IH genauso wirksam sind wie orales Propranolol, jedoch ohne oder mit signifikant weniger Nebenwirkungen, und befürworten die Ersetzung von oralem Propranolol durch topische Betablocker als Erstlinienbehandlung von oberflächlichem IH. Wir haben bereits über das therapeutische Ansprechen von tiefen periokulären IH auf eine primäre topische Timololmaleat-0,5%-Monotherapie berichtet. Hier beschreiben wir die ersten erfolgreichen Behandlungen von großen orbitalen IH mit topischem Timololmaleat 0,5% bei 4 Säuglingen, was in allen Fällen zu einem sofortigen Ende des klinischen Fortschreitens und einer schnellen klinischen Verbesserung oder vollständigen Heilung führte. Bei keinem der Patienten, die mit topischem Timololmaleat 0,5% behandelt worden waren, wurden während der Behandlung Nebenwirkungen oder nach Beendigung der Behandlung während der Langzeitnachbeobachtung von bis zu 2,5 Jahren ein Wiederauftreten beobachtet.

Aim: To analyze the percentage cost variations among different brands of the commonly prescribed anti–glaucoma drugs. Material and Methods: The maximum and minimum price of each brand of the drug in INR was noted by using CIMS January to April 2018 edition Drug Today April to June 2018 Vol-1. The cost ratio and the percentage cost variation for individual drug brands was calculated. The cost of each eye drop was calculated. At last the cost ratio and percentage cost variation of various brands was compared. Results:Percentage variation in cost for anti-glaucoma eye preparations marketed in India was found to be Eye drop Timolol maleate (0.5%) of 5ml:263.63, Eye drop Dorzolamide (2%) of 5ml:9.77, Eye drop Pilocarpine (2%) of 5ml:160.40, Eye drop Betaxolol (0.5%) of 5ml:56.54, Eye drop Latanoprost(50mcg/ml) of 2.5ml:135.88, Eye drop Brimonidine tartarate (0.15%) of 5ml:183.9, Eye drop Levobunolol (5mg/ml) of 5ml:32.38, Conclusion:Glaucoma is the most common ocular disease and eye drops are to be prescribed for prolonged period. If a costly brand is prescribed, the patients have to pay more money unnecessarily for their treatment. The clinicians prescribing these drugs should be aware of these variations in cost to reduce the cost of drug therapy. Keywords: Glaucoma, Percentage cost variation, Cost ratio.

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is

Objective: To evaluate in an in vivo rabbit model, the effect of topical timolol maleate therapy on the central corneal thickness response to acute intraocular pressure increases. Method: In this prospective and interventional controlled study, the central corneal thickness and intraocular pressure were measured in vivo in 12 rabbit eyes treated with topical timolol maleate for 1 month and in 12 controls at baseline, and after the intraocular pressure (measured by direct cannulation of the anterior chamber) was increased to 15 and 30 mmHg using a forced saline infusion into the anterior chamber. Results: There were no significant differences in the basal central corneal thickness values (control group, 373.2±12.9 µm; study group, 377.5±19.2 µm, p=0.5) or the central corneal thickness values when the intraocular pressure was increased to 15 mmHg (control group, 335.2±14.3 µm; study group, 330.0±32.1 µm, p=0.6) and to 30 mmHg (study group, 318.8±25.3 µm; control group, 329.8±21.0 µm, p=0.3). Conclusion: Rabbit corneas treated with topical timolol maleate for 1 month did not show a strain response to acute intraocular pressure increases that differed from control eyes. This is in contrast to a previous finding in which rabbit eyes treated with prostaglandin analogues had a greater decrease in central corneal thickness in response to a sudden intraocular pressure increase compared with untreated corneas.

Infantile haemangiomas (IHs) are relatively common benign vascular tumours found in the paediatric population. They have varying sizes and involve different depths in the skin leading to various colours, shapes and textures. Although considered harmless in most cases, they may lead to life-threatening complications or cause permanent disfigurations and organ dysfunction. For problematic IHs, the treatment options include oral and topical beta-blockers, systemic corticosteroids, laser treatment, and surgery. In this narrative review, the treatment options for problematic IH are compared and delivered concisely to facilitate the clinical decisions from practitioners, including those in primary care settings. Oral propranolol is currently considered the first-line intervention for problematic IHs. For superficial lesions, there is robust evidence for the use of topical timolol maleate. Systemic corticosteroids are sometimes used in specific situations such as resistance or contraindications to beta-blockers. Surgical excision can be considered in cases requiring urgent intervention such as airway obstruction; this can be done alongside laser therapies for the removal of residual tissue or when reconstructing areas of deformity. The combination of multiple treatment modalities may lead to a more rapid clinical response.

Objective: To observe efficacy of Timolol maleate 0.5% by topical and surface application in infantile superficial capillary hemangioma of eyelid. Methods: This multi-centered clinical case series was carried out at Ophthalmology Department of Bilawal Medical College and Institute of Ophthalmology, LUMHS, Jamshoro from November 2019 to May 2020. We included 14 subjects. All the patients were subjected to detailed clinical examination. Before starting the topical beta blockers, the enrolled subjects had obtained the expert opinion by pediatrician to rule out any preexisting developmental cardio vascular disease. Topical beta blockers 0.5% drops were thus started with, against the ongoing finding of superficial capillary hemangioma of eyelid. Results: There was significant regression in size of infantile hemangioma after treating with topical timolol maleate 0.5%. We included 14 subjects in this study. Mean±SD age of patients was 4.94. Complete regression was seen in 08 subjects at the end of 12 weeks (64%) while 03 were completely cured at 08 weeks (21%) and 01 patient lost follow up with us. No significant ocular and systemic side effects were noted. Conclusion: Topical timolol maleate 0.5% can be the first-line treatment modality for superficial capillary hemangiomas due to its better safety and efficacy. doi: https://doi.org/10.12669/pjms.37.7.4317 How to cite this:Junejo MS, Rebecca, Memon MN, Shaikh SP. Role of topical beta blockers in regression of infantile capillary hemangioma. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4317 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Chronic wounds remain a challenge for the clinician and healthcare system. It is therefore vital for additional therapies that target steps involved in wound recalcitrance. Recently, topical timolol has shown promising results for use in wound healing. Objective: The goal of this study was to assess timolol’s effectiveness in healing wounds of varying etiologies. Methods: This multi-center series took place from 2016¬–2019 at the wound healing centers at the University of Miami Health System and the Veterans Affairs Northern California Healthcare. We identified all wound patients who received treatment with topical timolol maleate 0.5% for at least 4 weeks after failing previous treatments. Timolol drops at a dose of 1 drop per cm2 of wound area were instilled with dressing changes twice a day, once a day, every other day, or continuous application. Once they began the study, they stopped all concurrent therapies aside from standard of care. Healing outcomes were classified into 3 categories: healed, defined as complete re-epithelialization of the wound and closure, improved, defined as decreasing wound size area (WSA), and worsening, defined as increasing WSA. Results: We identified 39 patients, 32 males and 7 females that had a total of 55 chronic wounds of varying etiologies. Thirty-four of the wounds had completely healed, 15 wounds improved in WSA, 4 wounds were unchanged in WSA, and 2 wounds worsened in WSA. Conclusions: In line with our previous experience, we found topical timolol to be a safe, cost-effective, and efficacious treatment for recalcitrant wounds of varying etiologies.

Background A minority of infantile hemangiomas showing minimal or arrested growth (IH-MAGs) have been recognized in the literature. Nevertheless, the clinical features and treatment outcomes of IH-MAGs have not been well investigated. Objective This study aimed to understand the clinical characteristics of IH-MAGs better and their response to treatment with topical timolol maleate. Methods We retrospectively reviewed medical records and clinical images of patients with IH-MAGs. Treatment response with topical timolol was assessed in both IH-MAGs and classic infantile hemangiomas (IHs) groups. Results Of the 1,038 patients with IHs, only 31 (3.0%) were diagnosed with IH-MAGs. Lesions with non-proliferative components were more frequently distributed in the lower half of the body (61.5%) than those with proliferative components (16.7%). In 14 patients treated with topical timolol, the global assessment scale showed more significant and rapid improvement than in those with classic IHs. Conclusion Although the prevalence of IH-MAGs may be relatively low, understanding their clinical features will help in differential diagnosis. Furthermore, these type of lesions might be more responsive to topical timolol than classic IHs.

Objective: To study the efficacy and safety of fractional 2940 nm laser-assisted drug delivery of timolol maleate 0.5% solution for the treatment of deep IHs.Methods: In this study, 30 deep IHs were included, and a fractional 2940 nm laser was applied with 2-weeks intervals. Topical timolol maleate 0.5% was applied under occlusion for 30 min four times/day for 24 weeks. The plasma concentration of timolol maleate was monitored for 0.5 h after the first treatment. The HAS scores and the depth, lateral diameter, vertical diameter of hemangiomas were evaluated before treatment, at 8 weeks and 24 weeks of treatment, and at 4 weeks after treatment.Results: Twenty-three patients (76.7%) demonstrated excellent regression, 4(13.3%) showed good response, and 3(10%) experienced moderate regression. The HAS score was declined from 3.6 ± 0.7 to 2.3 ± 0.6 at 8 weeks, and from 1.3 ± 0.5 to 0.8 ± 0.5 at 24 weeks (p < .05). Plasma timolol concentration was not detected in 11 infants, and the rest ranged from 1.580 pg/mL to 14.718 pg/mL, which were

BACKGROUND The aim of the study is to evaluate the effectiveness of topical 0.5% timolol maleate solution for superficial infantile haemangioma (IH). MATERIALS AND METHODS This prospective study was carried out over a period of 4-years and included patients of IH. All patients were managed on outpatient basis. Parents were asked to apply 2 drops of 0.5% solution of timolol maleate eye drops over the entire haemangioma two times in a day. The total duration of treatment was 8 months. They were called for review on 15th day, then every two months for a total period of one year. Any side effect or recurrence were noted. The response was categorized into five groups: no response, controlled growth, partial response, good response and excellent response. RESULTS 78 patients who satisfied inclusion and exclusion criteria were included in this study. All patients showed response to topical timolol application. Timolol application resulted in controlled growth in six patients (7.7%); partial response in seven (8.9%) patients; good response in 21 (26.9%) patients and excellent response in 44 (56.4%) patients. Complete regression was observed in 35 patients after completing the treatment. No patient showed any relapse in 6 months follow up after completion of treatment. Significant difference in the degree of response was noted between patients less than 6 months and more than 6 months. Also, the response rate in patients less than 2 months was significantly higher than that in older patients. None of the parents reported any adverse effects of the drug during treatment. CONCLUSION 0.5% timolol maleate solution is an effective therapy option for infantile haemangioma without any major side effects and should be considered as a regular treatment.

Purpose: Primary open angle glaucoma (POAG) is one such field in Ophthalmology where ophthalmologists have failed to stop blindness due to it. All the available treatment modalities are directed towards the reduction of intraocular pressure (IOP) but without interfering the basic aetiopathogenesis. In this study we propose to study efficacy, potency and adverse effects of topical Timolol and Betaxalol in primary open angle glaucoma. Methodology: A comparative study of topical Betaxalol 0.5% and Timolol 0.5% in the management of POAG was conducted at Tertiary care hospital. Fifty patients of newly diagnosed POAG of different age, sex, religion from both urban and rural population attending eye OPD were included in this study. 25 patients were treated with topical Timolol maleate 0.5% ophthalmic solution BD and 25 patients were treated with topical 0.5% Betaxalol hydrochloride phthalmic solution BD. At 20 weeks follow up IOP levels n both the groups measured by applanation tonometer were compare to each other. Results: In this study a total of 50 patients with POAG were studied. 25 patients were treated with Timolol maleate 0.5% ophthalmic solution and 25 patients were treated with 0.5% Betaxalol hydrochloride ophthalmic solution. Out of 50 patients, 29 (58%) were male and 21(42%) were female patients. POAG was most common in the age group of 51-60 years with average age 51.50 (S.D. 9.8) years. Average age in males was 54.50 years, while in female it was 49.31 years. Conclusion: both Timolol and Betaxalol are effective in decreasing IOP in POAG patients. The magnitude of Timolol in decreasing IOP is more as compared to Betaxalol. The selective beta 1 adrenergic inhibition of Betaxalol provides an added benefit for those patients in whom beta 2 blockade could be harmful.

BACKGROUND Glaucoma is an ischaemic optic neuropathy comprising of three entities; one is raised intraocular pressure, second one is optic disc changes and third one is visual field defects. Intraocular pressure remains the major modifiable risk factor. The aim of the treatment is to lower the IOP and thereby prevent the significant functional visual defect and preserve the visual function. MATERIALS AND METHODS The current study is a prospective hospital-based observational study conducted over a period of two years in a sample of 50 patients attending the Outpatient Department, Department of Ophthalmology, Rangaraya Medical College, Government General Hospital, Kakinada, Andhra Pradesh. RESULTS A study of efficacy of prostaglandin analogues in comparison with timolol maleate as first drug of choice in the treatment of primary open- angle glaucoma. CONCLUSION According to the study, prostaglandin analogues showed higher efficacy in reducing the intraocular pressure as compared to that of the timolol maleate.

To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma. This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared. Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P

Infantile haemangioma is a relatively common benign tumour which often does not require treatment. We present a case of a segmental infantile haemangioma with periocular involvement impacting on early visual development which was successfully treated with topical timolol maleate 0.5% drops in the developing world.

Background To discuss the safety and efficacy of desonide combined with timolol for the treatment of superficial infantile hemangiomas. Methods From June 2017 to December 2017, 56 infants with superficial hemangiomas were treated by topical application of desonide cream and timolol maleate eyedrops. Patients’ clinical data including gender, age, hemangioma position and their changes before and after treatment were retrospectively analyzed. The therapeutic effects were evaluated by two dermatologists at 2 weeks and 3 months after desonide and timolol treatment. The therapeutic effects were rated as: ineffective, the lesion continued growing; partly effective, lesion remission rate ≥50% but no complete remission in size, color and texture; effective, the lesion was in complete remission. Results A total of 56 patients received desonide and timolol treatment, and 20 patients were observed as controls. Two weeks after treatment the hemangioma became softer and smaller. At 3 months, the overall response was ineffective in 3 patients (5.36%), partly effective in 15 (26.79%), and effective in 38 (67.86%), of which 5 patients’ hemangiomas had completely disappeared but had a small amount of angiotelectasis. In the control group, the overall response was ineffective in 16 patients (80%), partly effective in 3 (15%), and effective in 1 (5%). The effectiveness and regression rate of the desonide and timolol treated group (94.64%, 67.86%) were significantly better than the control group (20%, 5%) (p Conclusion It is safe and effective to use desonide and timolol to treat superficial infantile hemangiomas.

The aim of the present study was to assess the efficacy and safety of topical timolol maleate combined with oral propranolol for parotid infantile hemangiomas. Between October 2012 and April 2014, propranolol was administered orally at a dose of 1.0–1.5 mg/kg/day to 22 infants with proliferating hemangiomas in the Department of Oral and Maxillofacial Surgery (Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China). A small amount of 0.5% timolol maleate eye drop solution was topically applied with medical cotton swabs to the area of the lesion twice a day, every 12 h. The study group consisted of 9 males and 13 females, aged 2–9 months, with a median age of 4.7 months. The lesions were all located in the parotid region, and measured between 3.5×4×0.5 and 7×8×3 cm in volume. The planned duration of therapy was 6–8 months, or the two drugs were stopped when complete regression of the lesions was obtained. The therapeutic outcomes and safety were assessed by the change in the size and color of the tumor, and the presence of adverse effects throughout the course of treatment. The mean duration of therapy was 21.1 weeks and ranged from 3 to 8 months. Of the 22 patients, 16 demonstrated an excellent response, 6 showed a good response and 2 displayed a moderate response. No major collateral effects were observed. Overall, oral propranolol combined with topical timolol maleate may be used as the first-line therapeutic choice in the treatment of infantile parotid mixed hemangioma.

Made available in DSpace on 2018-12-11T17:28:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01. Added 1 bitstream(s) on 2019-10-09T18:32:34Z : No. of bitstreams: 1 S0102-09352016000300641.pdf: 797547 bytes, checksum: c412fbdef61a59ebda38cdb6347631f4 (MD5) The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.). The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P

Eye is a vital organ of our body and any complication not only poses the risk of serious medical condition but also economic burden on the individual. Timolol maleate is one of the preferable therapeutic agents for the management of glaucoma. Globally, eye drops are among the most common and popular conventional formulations, but they are also associated with some limitations in terms of therapeutic response, bioavailability, dosing frequency and poor patient compliance. Present paper gives an overview of the drug delivery systems developed for management of glaucoma, advances and novel approaches with special emphasis on timolol drug delivery.

Background: The DBA/2J mouse strain is known to develop glaucomatous changes. Intraocular pressure (IOP) fluctuations affected by age or antiglaucoma drug administration were compared among three mouse strains, DBA/2J, C57BL/6, and BALB/c. Methods: IOP was measured using the TonoLab tonometer under systemic anesthesia. For each mouse strain, the effects of age and topical administration of antiglaucoma medications (timolol maleate, dorzolamide, brimonidine tartrate, and travoprost) were assessed, and results were compared among the three strains. Results: IOP started to rise in DBA/2J mice at 21 weeks of age. The highest values of IOP were distributed from 18 to 51 mm Hg. Eighty percent of DBA/2J mice showed maximum IOP at either 35 or 46 weeks. IOP of C57BL/6 ranged from 9 to 14 mm Hg as the mice aged. Treatment with any of the antiglaucoma medications resulted in IOP-lowering effects in all three strains. The difference in levels before and after administration ranged from 6 to 10 mm Hg on average in DBA/2J. Conclusion: DBA/2J mice are a useful animal model to study the effects of antiglaucoma therapy.

Background: Infantile hemangioma (IH) may have implications on parental distress and cosmetic disfigurement. To date, ultrapotent corticosteroids are used as a treatment of choice for superficial IH. However, due to their side effects and sometimes lack of IH regression, it is necessary to find alternative topical therapies. Timolol maleate 0.5% solution and gel are nonselective β-blockers that could inhibit proliferation and trigger regression of IH. Objective: To evaluate the efficacy of topical ultrapotent corticosteroids and timolol maleate 0.5% solution and gel for superficial IH. Patients and Methods: The study design was prospective. Two hundred and seventy-eight patients diagnosed as having superficial IH were enrolled from the outpatient clinic of the Department of Dermatology and Venereology, Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2009 to December 2014. Patients were divided into three groups: A = treated with topical ultrapotent corticosteroid, B = timolol maleate 0.5% solution and C = timolol maleate 0.5% gel. Patients were followed for 6 months to evaluate the lesion. Lesion size was measured from scaled photodocumentation with the software program ImageJ®. Results: There were significant differences in IH size after treatment with timolol maleate 0.5% solution compared with ultrapotent corticosteroids (p < 0.001) and timolol maleate 0.5% gel compared with ultrapotent corticosteroids (p < 0.001). There was no significant difference in IH lesions after treatment with timolol maleate 0.5% solution versus gel (p = 0.744). Conclusion: Timolol maleate 0.5% solution and gel were significantly superior to topical ultrapotent corticosteroids in size reduction of superficial IH.

The concept of in-vitro and in-vivo correlation studies was used in pharmaceutical research because a simple in-vitro release study on a drug product will be insufficient to predict its therapeutic efficiency. Therefore, correlation between in-vitro release behavior of a drug and its in-vivo absorption in rabbits must be demonstrated experimentally to reproduce therapeutic response. Aim of the study was to study the in vitro and in vivo evaluation and correlation of timolol maleate ocular insert. Timolol maleate ocular inserts were prepared by solvent casting method using guar gum in different proportions (0.25% w/v, 0.50% w/v, 0.75 % w/v, and 1.0% w/v). In vitro transcorneal permeation study was performed on goat cornea using modified Franz diffusion cell. The in vivo study was done using New Zeland albino rabbits and the in vitro invivo correlation (IVIVC) was determined by plotting a graph of in vivo drug release was plotted against in vitro release to determine the correlation. The cumulative % drug releases from the formulation ranged from 50.22±1.41 to 97.72±0.67over a period of 24 h. In vivo release of the timolol maleate from the optimized ocular inserts F2, through conjunctival cul-de-sac of rabbits was 76.03±1.43 at the end of 24 h. A high value of correlation coefficient (r2=0.9965) suggested good correlation between the in vitro-in vivo data of the timolol maleate ocular insert. Keywords: Guar gum, IVIVC, in vitro transcorneal permeation study, ocular insert, timolol maleate Formulasi dan Korelasi In vitro-In vivo pada Timolol Maleat dengan Penyisipan Okular Konsep studi korelasi in-vitro dan in-vivo telah digunakan dalam penelitian farmasi karena studi invitro yang sederhana pada produk obat tidak cukup untuk memprediksi efisiensi terapi. Oleh karena itu, korelasi antara pelepasan in vitro obat dan penyerapan secara in vivo pada kelinci harus dapat didemonstrasikan secara eksperimental untuk menghasilkan respons terapi. Tujuan penelitian ini adalah mengevaluasi formulasi dan korelasi in vitro dan invivo pada timolol maleat dengan penyisipan okular. Penyisipan okular timolol maleat disiapkan dengan metode pemilihan pelarut menggunakan guar gum pada proporsi berbeda (0,25% w/v, 0,50% w/v, 0,75 % w/v, dan 1,0% w/v). Permeasi transkorneal in vitro dilakukan pada kornea kambing menggunakan modifikasi difusi sel Franz. Studi in vivo dilakukan pada kelinci albino New Zeland dan korelasi invitro invivo (IVIVC) ditentukan dengan pelepasan in vivo obat yang diplot pada grafik yang dihubungkan dengan pelepasan in vitro untuk menentukan korelasi. Pelepasan kumulatif obat (%) dari formulasi memiliki rentang antara 50,22±1,41 sampai 97,72±0,67 pada lebih dari periode 24 jam. Pelepasan in vivo timolol maleat dari penyisipan okular teroptimasi F2, melalui konjungsi kul-de-sak pada kelinci yaitu 76,03±1,43 pada akhir periode 24 jam. Nilai yang tinggi dari koefisien korelasi (r2=0,9965) menunjukkan korelasi yang baik antara invitro dan invivo data penyisipan okular pada timolol maleat. Kata kunci: Guar gum, IVIVC, penyisipan okular, studi permeasi transkorneal in vitro, timolol maleat

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.

The present study involved formulation of an in situ gelling system of brimonidine tartrate and timolol maleate for the treatment of glaucoma. Carbopol® 980 NF, xanthum gum and hydroxypropyl methylcellulose K4 M were used as polymers. The prepared in situ gelling systems were evaluated for clarity, appearance, texture analysis, pH, viscosity, rheological properties, in vitro gelation, isotonicity, drug content uniformity, in vitro release studies, microbiological evaluation, ex vivo release studies and stability testing. The results of the attenuated total reflectance spectroscopy and differential scanning calorimetry studies confirmed that there is no incompatibility between the drugs and the excipients. The formulations exhibited pseudoplastic rheology and formulation 3 showed the highest release of both the drugs from the formulation. The stability studies showed that the formulation was stable over the given period of time. Thus, it is evident that the in situ gelling system is a promising drug delivery system for the treatment of glaucoma.

Superior oblique myokymia is a rare condition, characterized by spontaneous rhythmic contractions of the superior oblique muscle and was first described by Duane in 1906. However, the pathophysiology of this condition remains poorly understood even today. A number of medical and surgical treatment modalities have been tried, with variable results. We report a case of superior oblique myokymia in a pregnant female, which could be triggered with flashlight stimulation, and the result of treatment with timolol maleate 0.5% ophthalmic solution.

Purpose: To investigate the effect of a single dose of topical timolol maleate 0.5% on anterior segment structure, pupil dynamics, and retinal and choroidal thickness in healthy subjects. Materials and Methods: Thirty subjects were included in this prospective and observational study.One eye of the participants received a single dose of topical benzalkonium chloride (BAC) preserved Timolol maleate 0.5% (Timosol 0.5%, Bilim Ilac, Istanbul, Turkey) (treated eye). Contralateral eye received a single dose of sodium hyaluronate ophthalmic solution without preservative (control eye). Main outcome measures were central corneal thickness (CCT), aqueous depth, anterior chamber volume, iridocorneal angle, horizontal anterior chamber diameter, static and dynamic pupil functions, central macular thickness, and choroidal thickness. Results: Mean CCT was signifi cantly higher after timolol instillation in treated eyes (p=0.001). Timolol did not affect aqueous depth, anterior chamber volume, iridocorneal angle and horizontal anterior chamber diameter in treated eyes (p>0.05 for each). Mean pupil diameters were similar under scotopic, mesopic and photopic conditions before and after timolol instillation (p>0.05 for each); however, pupil dilation speed was signifi cantly lower after timolol instillation in the treated eyes (p0.05). Pre- and post-instillation outcomes were similar in control eyes for all parameters (p>0.05 for each). Conclusion: Topical BAC-preserved timolol maleate reduces pupil dilation speed without any effect on static pupil functions and increases the CCT and central macular thickness.

The aim of the present study wasto investigate the potential inhibitory effect of timolol on topical glucocorticoid-induced skin telangiectasia. In rabbits, flumethasone ointment was used to induce skin telangiectasia in the inner ear. Subsequently, timolol maleate (0.5%) eye drops (TMEDs) were administered twice daily for 4 weeks. Expression of the antibacterial peptides 37-amino acid peptide (LL-37) and kallikrein-5 (KLK5) was detected using quantitative polymerase chain reaction (PCR) and semi-quantitative reverse transcription-PCR. In patients with facial skin telangiectasia, one cheek of each patient was assigned to a treatment group and the other to a control group. For the treatment group cheeks, topical application of TMEDs was combined with 0.1% tacrolimus ointment once or twice daily for 8 weeks. The control group cheeks were administered with 0.1% tacrolimus ointment alone. Alterations in lesions were recorded by dermoscopy, and the L, a and b values of lesions were measured, based on the Commission Internationale de l'Éclairage system, with a chromameter prior to and at 1, 2, 4 and 8 weeks following treatment. The results indicated that erythema, papules and telangiectasia were significantly diminished following 4 weeks of treatment with TMEDs in rabbits. Notably, the expression of LL-37 and KLK5 mRNA was increased in the negative control group; however, it was decreased in the trial and blank groups. Clinical and dermoscopy images demonstrated that erythema was reduced in the 2 groups for 1 week, and that telangiectasia in the treatment group was markedly reduced compared with the control group at 4 weeks. The difference of the L and a values of lesions between the treatment and control group was significant (P

The recent International Society for the Study of Vascular Anomalies (ISSVA) classification of vascular anomalies can be applied to orbital lesions, dividing them into vascular tumors and vascular malformations. Orbital cavernous hemangiomas are probably best considered cavernous venous malformations under this classification. Management of symptomatic lesions can be with surgical excision or stereotactic fractionated radiotherapy in selected cases. Beta-blockers including propranolol and topical timolol maleate represent first-line therapy for infantile hemangiomas, although surgery has a role in selected cases. Orbital venous-lymphatic malformations are problematic but with improved imaging, neuroradiological intervention, and a multidisciplinary approach to management, outcomes are improving.