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1.
BMJ Case Rep ; 17(5)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806396

RESUMO

Pityriasis rubra pilaris (PRP) is a rare dermatological condition which may present with ocular manifestations. We report a case of recurrent cicatricial ectropion (CE) with topical beta-blocker use in the rare dermatological condition PRP. The patient underwent release of scar tissue, lateral tarsal strip and full-thickness supraclavicular skin graft for CE following immunosuppression with methotrexate for 3 months. Postoperatively, CE recurred, with skin graft shrinkage and resumption of periocular disease activity, 8 weeks following the introduction of topical timolol. The patient was referred for further immunosuppression and substitution of timolol before consideration for further surgery. PRP has a variety of potential ocular complications. Surgery has a high risk of recurrence and should be performed when the overall disease is quiescent and drugs, which could trigger reactivation, have been discontinued and/or substituted. Skin grafts should be oversized to off-set shrinkage.


Assuntos
Ectrópio , Pitiríase Rubra Pilar , Humanos , Pessoa de Meia-Idade , Antagonistas Adrenérgicos beta/uso terapêutico , Cicatriz/complicações , Cicatriz/etiologia , Ectrópio/etiologia , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Recidiva , Transplante de Pele , Timolol/uso terapêutico , Timolol/administração & dosagem
3.
J Ocul Pharmacol Ther ; 40(4): 240-245, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38598266

RESUMO

Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.


Assuntos
Anti-Hipertensivos , Tartarato de Brimonidina , Glaucoma de Ângulo Aberto , Pressão Intraocular , Latanoprosta , Hipertensão Ocular , Sulfonamidas , Timolol , Humanos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pessoa de Meia-Idade , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Latanoprosta/administração & dosagem , Latanoprosta/uso terapêutico , Latanoprosta/farmacologia , Tartarato de Brimonidina/administração & dosagem , Tartarato de Brimonidina/uso terapêutico , Tartarato de Brimonidina/farmacologia , Tartarato de Brimonidina/efeitos adversos , Masculino , Feminino , Estudos Prospectivos , Timolol/administração & dosagem , Timolol/uso terapêutico , Timolol/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Adulto , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia , Tiazinas/administração & dosagem , Tiazinas/uso terapêutico , Tiazinas/efeitos adversos , Combinação de Medicamentos , Resultado do Tratamento , Soluções Oftálmicas/administração & dosagem
4.
Mo Med ; 121(1): 33-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404426

RESUMO

This is the first reported case series of nasally delivered beta blocker (timolol 0.5%) for the treatment of acute migraine. In a retrospective chart review, 16 patients were found who had received intranasal timolol for sub-optimally treated acute migraines. Of these, 10 (62.5%) reported to their provider that the medication was helpful. Encouragingly, the treatment was beneficial even for patients previously refractory to other medications. Intranasal timolol was well tolerated, with only one patient reporting mild nasal congestion and no other side effects reported. These findings suggest the need for a prospective pilot study followed by a larger double-blind randomized placebo-controlled trial to determine the overall efficacy and safety of nasally delivered beta blockers for acute migraine treatment.


Assuntos
Transtornos de Enxaqueca , Timolol , Humanos , Antagonistas Adrenérgicos beta/uso terapêutico , Cefaleia , Transtornos de Enxaqueca/tratamento farmacológico , Projetos Piloto , Estudos Retrospectivos , Timolol/uso terapêutico , Resultado do Tratamento
5.
Am J Ophthalmol ; 263: 23-34, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38395329

RESUMO

PURPOSE: The SPECTRUM 4 and 3 studies assessed the intraocular pressure (IOP)-lowering efficacy and safety of omidenepag isopropyl (OMDI) 0.002% vs timolol 0.5% in patients with glaucoma or ocular hypertension (OHT). DESIGN: Phase 3, randomized, controlled, double-masked, noninferiority studies. METHODS: Multicenter studies in the US. Inclusion criteria for adults ≥ 18 years (SPECTRUM 4 [N = 409] and 3 [N = 413]) were open-angle glaucoma or OHT, and IOP ≥ 22 mm Hg and ≤ 34 mm Hg; and for pediatric patients < 18 years (N = 13, SPECTRUM 3) were pediatric glaucoma or OHT. The primary objective in both studies was OMDI noninferiority to timolol in reducing IOP (3 months). SPECTRUM 3 included an additional 9 months of OMDI treatment. Safety evaluations were of ocular/non-ocular adverse events (AEs). RESULTS: The IOP-lowering range of OMDI remained consistent in SPECTRUM 4 and 3 (-5.6 to -5.9 vs -5.3 to -5.7 mm Hg, respectively); however, timolol efficacy varied (-5.4 to -6.1 vs -6.4 to -7.0 mm Hg, respectively). OMDI noninferiority was achieved in SPECTRUM 4. Efficacy was maintained with 12-month treatment in SPECTRUM 3. Both studies reported more ocular AEs with OMDI, but lower rates of appearance-altering AEs vs timolol. No new safety concerns were identified. Rates of macular edema in pseudophakic patients increased with prolonged OMDI exposure. CONCLUSIONS: SPECTRUM 4 and 3 demonstrated consistent 3-month IOP-lowering efficacy and safety of OMDI vs timolol in patients with glaucoma or OHT. The 12-month data from SPECTRUM 3 suggest OMDI may have long-term benefits in patients with glaucoma or OHT.


Assuntos
Anti-Hipertensivos , Glaucoma de Ângulo Aberto , Pressão Intraocular , Hipertensão Ocular , Soluções Oftálmicas , Timolol , Tonometria Ocular , Humanos , Timolol/uso terapêutico , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Método Duplo-Cego , Feminino , Masculino , Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Adolescente , Adulto Jovem , Criança , Glicina/análogos & derivados , Pirazóis , Piridinas
6.
Pharm Res ; 41(3): 531-546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38366235

RESUMO

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


Assuntos
Lentes de Contato , Glaucoma , Poliésteres , Polietilenoglicóis , Sulfonamidas , Tiazinas , Humanos , Timolol/farmacocinética , Timolol/uso terapêutico , Micelas , Anti-Hipertensivos/farmacocinética , Glaucoma/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Soluções Oftálmicas/uso terapêutico
7.
Transl Vis Sci Technol ; 13(1): 21, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38285464

RESUMO

Purpose: To compare the efficacy of morning and evening latanoprost/timolol fixed-combination (LTFC) dosing in patients with primary open-angle glaucoma (POAG) and ocular hypertension. Methods: In this double-blind, randomized clinical trial, 63 untreated Chinese patients with POAG and ocular hypertension were enrolled. All patients received LTFC and were randomized (1:1) to group 1, morning (8 AM) dosing, or group 2, evening (8 PM) dosing. Vehicle drops were used in the morning or evening, accordingly, to preserve masking. Patients were treated for 4 weeks. Outcomes included mean reduction of the 24-hour intraocular pressure (IOP) and IOP fluctuation from baseline after a 4-week treatment. Results: Fifty-six patients were included in the final analysis. In both groups, the posttreatment IOP values were significantly lower than those at baseline at each 24-hour measuring time point. A significant difference between the groups in IOP reduction from baseline was observed at the 9:30 AM time point (4.01 ± 2.62 vs. 2.42 ± 3.23 mm Hg, evening dosing versus morning dosing group; P = 0.048). Both groups showed decreased IOP fluctuation after treatment. However, the morning dosing group had a significantly greater decrease in diurnal IOP fluctuation than that of the evening dosing group (2.04 ± 2.32 mm Hg vs. 0.50 ± 1.70 mm Hg, respectively; P = 0.012). Conclusions: Both morning and evening LTFC dosing can effectively reduce 24-hour IOP and IOP fluctuation. Morning dosing is more likely to effectively control diurnal IOP fluctuations. Translational Relevance: This multicenter, double-blind, randomized clinical trial generates robust evidence on the optimal LTFC dosing regimen to help clinical decision-making in the treatment of raised IOP.


Assuntos
Glaucoma de Ângulo Aberto , Hipertensão Ocular , Humanos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular , Latanoprosta , Hipertensão Ocular/tratamento farmacológico , Timolol/uso terapêutico , Método Duplo-Cego
8.
Curr Opin Pharmacol ; 74: 102426, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168596

RESUMO

More than 75 million people worldwide suffer from ocular hypertension (OHT)-associated retinal and optic nerve degenerative diseases that cause visual impairment and can lead to blindness. In an effort to find novel pharmaceutical therapeutics to combat OHT with reduced side-effect potential, several emerging drug candidates have advanced to human proof-of-concept in recent years. One such compound is a nonprostaglandin (non-PG) EP2-receptor-selective agonist (omidenepag isopropyl ester). Omidenepag (OMD; free acid form) is a novel non-PG that selectively binds to and activates the human EP2-prostglandin receptor (EP2R) with a high affinity (Ki = 3.6 nM) and which potently generates intracellular cAMP in living cells (EC50 = 3.9-8.3 nM). OMD significantly downregulated COL12A1 and COL13A1 mRNAs in human trabecular meshwork (TM) cells, a tissue involved in the pathogenesis of OHT. Omidenepag isopropyl (OMDI) potently and efficaciously lowered intraocular pressure (IOP) in ocular normotensive rabbits, dogs, and monkeys, and also in ocular hypertension (OHT) Cynomolgus monkeys, after a single topical ocular (t.o.) instillation at doses of 0.0001-0.01%. No reduction in IOP-lowering response to OMDI was observed after repeated t.o. dosing with OMDI in dogs and monkeys. Additive IOP reduction to OMDI was noted with brinzolamide, timolol, and brimonidine in rabbits and monkeys. OMDI 0.002% t.o. decreased IOP by stimulating the conventional (TM) and uveoscleral (UVSC) outflow of aqueous humor (AQH) in OHT monkeys. In a Phase-III clinical investigation, 0.002% OMDI (once daily t.o.) reduced IOP by 5-6 mmHg in OHT/primary open-angle glaucoma (POAG) patients (22-34 mmHg baseline IOPs) that was maintained over 12-months. In an additional month-long clinical study, 0.002% OMDI induced IOP-lowering equivalent to that of latanoprost (0.005%), a prostanoid FP-receptor agonist, thus OMDI was noninferior to latanoprost. Additive IOPreduction was also noted in OHT/OAG patients when OMDI (0.002%, once daily t.o.) and timolol (0.05%, twice daily t.o.) were administered. Patients with OHT/POAG who were low responders or nonresponders to latanoprost (0.005%, q.d.; t.o.) experienced significant IOP-lowering (additional approximately 3 mmHg) when they were switched over to OMDI 0.002% (q.d.; t.o.). No systemic or ocular adverse reactions (e.g. iris color changes/deepening of the upper eyelid sulcus/abnormal eyelash growth) were noted after a year-long, once-daily t.o. dosing with 0.002 % OMDI in OHT/POAG patients. However, OMDI caused transient conjunctival hyperemia. These characteristics of OMDI render it a suitable new medication for treating OHT and various types of glaucoma, especially where elevated IOP is implicated.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Glicina/análogos & derivados , Hipertensão Ocular , Pirazóis , Piridinas , Humanos , Coelhos , Animais , Cães , Latanoprosta/uso terapêutico , Glaucoma de Ângulo Aberto/induzido quimicamente , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular , Timolol/uso terapêutico , Glaucoma/tratamento farmacológico , Glaucoma/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Macaca fascicularis , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico
10.
Telemed J E Health ; 30(3): 881-884, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37651201

RESUMO

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


Assuntos
Hemangioma , Neoplasias Cutâneas , Telemedicina , Humanos , Lactente , Pandemias , Antagonistas Adrenérgicos beta/uso terapêutico , Timolol/uso terapêutico , Hemangioma/tratamento farmacológico , Hemangioma/complicações , Neoplasias Cutâneas/complicações , Resultado do Tratamento
11.
Lasers Surg Med ; 56(1): 39-44, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37431532

RESUMO

OBJECTIVES: The current gold standard treatment for port-wine stains (PWS) is pulsed dye laser (PDL). However, multiple treatment sessions may be necessary and complete resolution is often not achieved. Neoangiogenesis can occur soon after treatment and is thought to be a major factor contributing to treatment failure. Adjuvant antiangiogenic topical therapies may therefore improve the efficacy of pulsed dye laser treatment of port-wine stains. MATERIAL AND METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and clinicaltrials.gov using "port-wine stain," "nevus flammeus," "capillary malformation," "sturge weber," and "pulsed dye laser" as keywords and medical subject heading (MeSH) terms. Articles were included if they (1) were a randomized controlled trial (RCT); (2) studied patients with PWS; and (3) investigated topical adjuvant therapies with PDL. Bias was assessed using the Critical Appraisal Skills Programme (CASP) Randomized Controlled Trial Standard Checklist. RESULTS: 1835 studies were identified, with six studies meeting inclusion criteria. The total number of patients studied was 103 (range: 9-23), with 8-36 week follow-up. The average age ranged from 11 to 33.5 years old. Three studies examined adjuvant topical sirolimus (n = 52), two examined timolol (n = 29), and one studied imiquimod (n = 22). Two of three RCTs reported no improvement through colorimetric analysis with topical sirolimus; however, one of these studies did show a significant improvement through Investigator Global Assessment (IGA) score. The last sirolimus study showed significant improvement through digital photographic image scoring (DPIA). Studies examining topical timolol reported no change in PWS appearance compared to placebo. The addition of 5% adjuvant imiquimod cream did lead to significant improvement. A variety of outcome measures were used. Imiquimod and sirolimus led to mild cutaneous adverse events, while timolol caused no side effects. None of the adverse events led to treatment discontinuation. Study quality was moderate in three, high in two, and low in one. CONCLUSION: The efficacy of adjuvant topical therapy was unclear. Limitations included variation in concentration and duration of adjuvant therapies, differences in follow-up time, and inconsistent outcome measure reporting. Given their potential clinical promise, larger prospective studies examining topical adjuvant therapies should be considered.


Assuntos
Lasers de Corante , Mancha Vinho do Porto , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Mancha Vinho do Porto/tratamento farmacológico , Imiquimode/uso terapêutico , Timolol/uso terapêutico , Lasers de Corante/uso terapêutico , Sirolimo/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Calcif Tissue Int ; 114(3): 295-309, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38102510

RESUMO

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.


Assuntos
Hipertensão , Pentoxifilina , Humanos , Ratos , Feminino , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Densidade Óssea , Timolol/farmacologia , Timolol/uso terapêutico , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Pentoxifilina/farmacologia , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Pressão Sanguínea
13.
Nano Lett ; 23(23): 11193-11202, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38039401

RESUMO

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.


Assuntos
Glaucoma , Lipossomos , Ratos , Animais , Lipossomos/uso terapêutico , Agentes Antiglaucoma , Glaucoma/tratamento farmacológico , Timolol/farmacologia , Timolol/uso terapêutico , Administração Tópica , Sistemas de Liberação de Medicamentos
14.
Cell Mol Biol (Noisy-le-grand) ; 69(10): 115-120, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37953576

RESUMO

To investigate the efficacy of timolol in the treatment of facial hemangioma and the effect on the proliferation and apoptosis of hemangioma stem cells, 60 cases of children with IHs admitted to our hospital between 2020 and 2021 were selected and divided into two groups. The grouping was according to the lottery method, with 30 cases in each group. In the observation group, 0.5% timolol maleate eye drops were applied topically, and in the control group, propranolol hydrochloride tablets were administered orally to observe the efficacy of hemangioma, changes in hemangioma stem cells and the incidence of adverse reactions in both groups. Results showed that combined with the four-level score and ultrasound results, the number of effective treatment cases in the observation group was 28, which was higher than that in the control group, (P<0.05). The total number of adverse reactions in the observation group was 2, with an incidence rate. Under the intervention conditions of timolol, the proliferation level of hemangioma stem cells was inhibited, and the apoptosis rate of hemangioma stem cells increased with the increase of culture time (P<0.05). Among them, the apoptosis rate of the timolol group was higher than that of the blank control group at the same time point (P<0.05), and the difference was most significant at 48h (P<0.001). In conclusion, Timolol can effectively treat facial hemangioma in children, inhibit the proliferation of hemangioma stem cells and promote their apoptosis, with good curative effect, short treatment time and no obvious adverse reactions and it is economical and easy to accept.


Assuntos
Hemangioma , Neoplasias Cutâneas , Criança , Humanos , Lactente , Timolol/farmacologia , Timolol/uso terapêutico , Hemangioma/tratamento farmacológico , Resultado do Tratamento , Proliferação de Células
15.
Curr Allergy Asthma Rep ; 23(12): 689-701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37995018

RESUMO

PURPOSE OF REVIEW: To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. RECENT FINDINGS: Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.


Assuntos
Telangiectasia Hemorrágica Hereditária , Ácido Tranexâmico , Humanos , Epistaxe/terapia , Epistaxe/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Timolol/uso terapêutico , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Propranolol/uso terapêutico , Metanálise em Rede , Tacrolimo/uso terapêutico , Estriol/uso terapêutico , Estradiol/uso terapêutico , Tamoxifeno/uso terapêutico
16.
Biol Direct ; 18(1): 66, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833756

RESUMO

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.


Assuntos
Glaucoma de Ângulo Aberto , Humanos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/induzido quimicamente , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Estudo de Associação Genômica Ampla , Timolol/uso terapêutico , Genótipo
18.
Photodiagnosis Photodyn Ther ; 43: 103728, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37517427

RESUMO

BACKGROUND: In this study, we aimed to assess the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) thinning relationships with dry eye development monitoring and underestimated measurement of intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with timolol, dorzolamide, and brimonidine. METHODS: This longitudinal cohort study included 106 patients with POAG. All patients underwent a detailed ophthalmic examination. In addition, CET, CST, and CCT were measured using anterior segment optical coherence tomography (AS-OCT). Subsequently, the cohort was divided into three groups based on the therapy administered. The Tomec group received monotherapy with benzalkonium chloride (BAK)-preserved timolol + dorzolamide fixed combination. The Alphagan group received monotherapy with purite-preserved brimonidine, and the Combigan group received monotherapy with BAK-preserved timolol + brimonidine fixed combination. RESULTS: CET, CST, and CCT did not show a statistically significant decrease in the Alphagan group (p>0.05). However, the Tomec and Combigan groups showed significantly reduced measurements, except for stromal thickness (p<0.05). Finally, a significant positive correlation was found between changes in tear break-up time (TBUT) and CET during the follow-up period (r = 0.637, p = 0.001). CONCLUSIONS: CET and CCT thinning were higher in the Tomec and Combigan groups than in the Alphagan group. Furthermore, although CCT reduction was significant in the Tomec and Combigan groups, its effect on IOP underestimation was approximately 1%. Furthermore, the positive correlation between CET and TBUT suggests that CET measurement with AS-OCT may also be useful in dry eye monitoring.


Assuntos
Síndromes do Olho Seco , Glaucoma de Ângulo Aberto , Glaucoma , Fotoquimioterapia , Humanos , Timolol/uso terapêutico , Timolol/efeitos adversos , Tomografia de Coerência Óptica/métodos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/diagnóstico , Combinação Tartarato de Brimonidina e Maleato de Timolol , Estudos Longitudinais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Glaucoma/induzido quimicamente , Tartarato de Brimonidina/uso terapêutico , Síndromes do Olho Seco/diagnóstico por imagem , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/induzido quimicamente
19.
J Cataract Refract Surg ; 49(7): 764, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37390324

RESUMO

A 62-year-old woman with mild myopia presented to her local optometrist for a routine examination and was found to have intraocular pressure (IOP) of 30 mm Hg in both eyes and cupped nerves. She had a family history of glaucoma in her father. She was started on latanoprost in both eyes and was referred for a glaucoma evaluation. On initial evaluation, her IOP was 25 mm Hg in the right eye and 26 mm Hg in the left eye. Central corneal thickness measured 592 µm in the right eye and 581 µm in the left eye. Her angles were open to gonioscopy without any peripheral anterior synechia. She had 1+ nuclear sclerosis with a corrected distance visual acuity (CDVA) of 20/25 in the right eye and 20/30- in the left eye and uncorrected near visual acuity of J1+ in each eye. Her nerves were 0.85 mm in the right eye and 0.75 mm in the left eye. Optical coherence tomography (OCT) showed retinal nerve fiber layer thinning and a dense superior arcuate scotoma into fixation in her right eye, and superior and inferior arcuate scotomas in her left eye (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202307000-00019/figure1/v/2023-06-26T195222Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202307000-00019/figure2/v/2023-06-26T195222Z/r/image-tiff, Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A882 and http://links.lww.com/JRS/A883). She was successively trialed on fixed combination brimonidine-timolol, dorzolamide, and netarsudil, in addition to her latanoprost, but her IOP remained in the mid- to upper 20s in both eyes. The addition of acetazolamide lowered the pressure to 19 mm Hg in both eyes, but she tolerated it poorly. Methazolamide was also attempted with similar side effects. We elected to perform left eye cataract surgery combined with 360-degree viscocanaloplasty and insertion of a Hydrus microstent (Alcon Laboratories, Inc.). Surgery was uncomplicated with IOP of 16 mm Hg on postoperative day 1 with no glaucoma medications. However, by postoperative week 3, IOP returned to 27 mm Hg, and despite restarting latanoprost-netarsudil and finishing her steroid taper, IOP remained at 27 mm Hg by postoperative week 6. Brimonidine-timolol was added back to her left eye regimen and at postoperative week 8, IOP had elevated to 45 mm Hg. Maximizing her therapy with the addition of topical dorzolamide and oral methazolamide brought her IOP back down to 30 mm Hg. At that point, the decision was made to proceed with trabeculectomy of the left eye. The trabeculectomy was uneventful. However, postoperative attempts to augment filtration were rendered less successful by extremely thick Tenon layer. At her most recent follow-up the pressure in the left eye was mid-teens with brimonidine-timolol and dorzolamide. Her right eye IOP is in the upper 20s on maximum topical therapy. Knowing her postoperative course in the left eye, how would you manage the right eye? In addition to currently available options, would you consider a supraciliary shunt such as the MINIject (iSTAR) if such a device were U.S. Food and Drug Administration (FDA)-approved?


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Estados Unidos , Feminino , Adolescente , Pessoa de Meia-Idade , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/cirurgia , Latanoprosta/uso terapêutico , Metazolamida , Timolol/uso terapêutico , Resultado do Tratamento
20.
J Drugs Dermatol ; 22(6): 594-598, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37276157

RESUMO

BACKGROUND: Oral propranolol is considered the first line therapy in the treatment of infantile hemangiomas (IHs). However, there are considerable side effects due to its ability to penetrate the blood brain barrier. Alternatively, topical timolol, a non-selective beta blocker, has resulted in fewer side effects and is 4–10 times more potent in comparison to oral propranolol. This study evaluates the efficacy of 0.5% timolol maleate hydrogel for the treatment of IH. METHODS: This study was conducted via a quasi-experimental design from October 30, 2020 – April 29, 2021, at the Department of Dermatology Benazir Bhutto Hospital, Rawalpindi. 145 infants between 1–12 months in age diagnosed with superficial cutaneous hemangiomas were included in the study with a male to female ratio of 2.4:1. A thin layer of timolol maleate 0.5% hydrogel was applied to the entire surface of the patient’s IH three times daily. Digital photographs and measurements of the hemangiomas were taken at one-month intervals for a maximum of 6 months. RESULTS: The age range in this study was from 1–12 months with a mean age of 6.10 ± 2.52 months. The majority of the patients 89 (61.4%) were between 1–6 months of age. Of the 145 patients, 89 (61.4%) showed an excellent response, 44 (30.3%) showed a good response, and 12 (8.3%) showed no response to the topical 0.5% timolol maleate hydrogel treatment. CONCLUSION: The use of topical 0.5% timolol maleate hydrogel is a promising therapeutic option for the treatment of superficial IHs. Anwar F, Mahmood E, Sharif S, et al. Topical application of 0.5% timolol maleate hydrogel for the treatment of superficial infantile hemangiomas. J Drugs Dermatol. 2023;22(6):594-598. doi:10.36849/JDD.7054.


Assuntos
Hemangioma , Hidrogéis , Timolol , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Administração Tópica , Hidrogéis/uso terapêutico , Timolol/uso terapêutico , Resultado do Tratamento
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