Electrocardiographic evaluation of healthy dogs treated with ophthalmic solution of timolol maleate 0.5%: preliminary study / Avaliação eletrocardiográfica de cães clinicamente hígidos sob tratamento com solução oftálmica de maleato de timolol 0.5%: estudo preliminar

Timolol maleate 0.5% is a drug recommended for glaucoma treatment in dogs. After administration, it is absorbed to systemic circulation and being an antagonist of beta adrenergic receptors it has important systemic side effects on cardiac electrical conduction. The present study evaluated the modification caused by ophthalmic timolol 0.5% in the electrocardiogram. Six clinically normal dogs were selected to participate in two different ophthalmic treatments: in the first one, a placebo (hypromellose 0.5%) was used and in the second one, timolol 0.5% was administered. Each solution was applied twice a day, for 14 days. The electrocardiographic parameters were measured in times: zero, 10, 60, 120, 240, 360 and 720 min after ocular solution instillation in first, seventh and 14th days of each treatment. The differences found in electrocardiogram were more evident between 120 and 240 min after instillation of timolol 0.5% when compared with placebo treatment. The rhythm was irregular, with sinus arrhythmia and sinus bradycardia moments. The RR and PR intervals lengthen notoriously (p 0.05) from the first day of timolol administration, and are more expressive in the 14th day of treatment. The QT interval demonstrated a few changes, just lengthening noticeably (p 0.05) in the 14th day of timolol application. The QTc interval did not show expressive change. Despite the changes in the electrocardiogram, no clinical manifestation related to beta-adrenoceptor antagonists were observed. One must consider, however, that the animals studied were healthy and thus, clinical signs could result from the changes implied by the use of timolol in animals with pre-existing heart disease. Therefore, cardiac assessment of patients prior to prescription of ophthalmic timolol is recommended.

O maleato de timolol 0,5% é um fármaco recomendado para tratamento de glaucoma em cães. Após instilação, e absorvido para a circulação sistêmica e por ser um antagonista beta-adrenérgico pode promover efeitos colaterais sistêmicos importantes sobre a condução elétrica cardíaca. No presente estudo, foi avaliada a alteração causada pelo timolol 0,5% oftálmico no eletrocardiograma. Foram selecionados seis cães hígidos para participar de dois tratamentos oftálmicos diferentes: no primeiro foi instilado placebo (hipromelose 0,5%) e no segundo utilizou-se timolol 0,5%. O colírio foi instilado a cada 12 horas por 14 dias. Os parâmetros eletrocardiográficos foram mensurados nos tempos: zero, 10, 60, 120, 240, 360 e 720 minutos após instilação da solução ocular nos dias primeiro, sétimo e décimo quarto de cada tratamento. As alterações eletrocardiográficas foram mais evidentes entre 120 e 240 minutos pós-instilação de timolol 0,5% quando comparado com o tratamento placebo. O ritmo foi irregular, com momentos de arritmia sinusal e bradicardia sinusal. Os intervalos RR e PR prolongaram significativamente (p 0,05) desde o primeiro dia de instilação de timolol, sendo o prolongamento mais expressivo no décimo quarto dia de tratamento. O intervalo QT demonstrou pouca variação, apenas prolongando significativamente (p 0,05) no décimo quarto dia de aplicação de timolol. O intervalo QTc não demonstrou alteração significativa (p > 0,05). Apesar das alterações encontradas, não foram observadas manifestações clínicas relacionadas ao timolol nos animais estudados. Deve-se considerar, porém, que os animais em questão eram hígidos e, portanto, as alterações decorrentes do uso do timolol em animais com cardiopatias preexistentes poderiam promover sinais clínicos, sendo recomendada a avaliação cardíaca de pacientes previamente à prescrição do timolol oftálmico.

Comparison of Cytotoxic Effects on Rabbit Corneal Endothelium between Preservative-free and Preservative-containing Dorzolamide/timolol

PURPOSE: To evaluate and compare the toxic effects of eyedrops containing a fixed combination of 2.0% dorzolamide and 0.5% maleate timolol with or without preservatives on rabbit corneal endothelium. METHODS: This study was performed with 22 eyes of New Zealand white rabbits. Dorzolamide/timolol eyedrops with preservative (Cosopt group) or without preservative (Cosopt-S group) were diluted with a balanced salt solution at a 1 : 1 ratio. We injected 0.1 mL of diluted Cosopt into the anterior chamber of left eyes and an equal volume of diluted Cosopt-S into the anterior chamber of right eyes. Corneal thickness, corneal haze, and conjunctival injection were measured before and 24 hours after treatment. Endothelial damage was compared between both eyes by vital staining (alizarin red/trypan blue staining), live/dead cell assay, TUNEL assay, and scanning electron microscopy. RESULTS: Corneal endothelial damage was severe in the Cosopt group. Cosopt-treated eyes exhibited remarkable corneal edema and prominent apoptosis of endothelial cells. In addition, the live/dead cell assay revealed many dead cells in the endothelium, and scanning electron microscopy analysis showed that corneal endothelial cells exhibited a partial loss of microvilli on the surface as well as extensive destruction of intercellular junctions. However, in the Cosopt-S group, corneal edema was mild and the damage to the corneal endothelium was minimal. CONCLUSIONS: The main cause of corneal endothelial toxicity was due to the preservative in the dorzolamide/timolol fixed combination eyedrops, and not the active ingredient. Thus, it appears to be safer to use preservative-free eyedrops during the early postoperative period.

Diurnal Intraocular Pressure with Bimatoprost/Timolol Fixed Combination versus Latanoprost/Timolol Fixed Combination in Healthy Subjects

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.

Diurnal Intraocular Pressure with Bimatoprost/Timolol Fixed Combination versus Latanoprost/Timolol Fixed Combination in Healthy Subjects

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.

Efectividad y seguridad de la combinación de brimonidina con timolol para el tratamiento de glaucoma de ángulo abierto y cerrado y de la hipertensión ocular / Effectiveness and safety of the combination of brimonidine and timolol for the treatment of open and closed angle glaucoma and ocular hypertension

Antecedentes: Descripción de la condición de salud de interés: El glaucoma se define como una neuropatía óptica con daño estructural del nervio óptico acompañado de una disfunción visual secundaria. Un daño leve del nervio óptico puede ser asintomático; 50% de los pacientes en países desarrollados con glaucoma pueden no saber que padecen de dicha enfermedad. Sin embargo, conforme la enfermedad avanza los síntomas se instauran y empeoran reduciendo la visión periférica, la sensibilidad al contraste, entre otras funciones propias de la visión, comprometiendo la realización de las actividades diarias y en última instancia, el desarrollo de ceguera. Descripción de la tecnología: El tratamiento farmacológico para el glaucoma busca disminuir la presión intraocular a un nivel que sea seguro para el paciente, disminuyendo la producción de humor acuoso o aumentando la salida del mismo del ojo, con el fin de evitar la aparición de ceguera por glaucoma. Evaluación de efectividad y seguridad: Pregunta de investigación: En pacientes con Glaucoma de Ángulo Abierto (GAA) o Cerrado (GAC) o con Presión Intraocular (PIO) elevada, ¿es más efectiva y segura la combinación de brimonidina con timolol, en comparación con brimonidina, timolol, latanoprost, acetazolamida, pilocarpina, betaxolol, tafluprost o Bimatorprost para reducir la presión intraocular? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, reportes de evaluación de tecnologías, revisiones sistemáticas y narrativasd la iteratura, estudios de prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. Población: Adultos con diagnóstico de hipertensión intraocular, glaucoma de ángulo abierto o de ángulo cerrado. Métodos de síntesis de la evidencia: Para cada comparación y sus respectivos desenlaces (de seguridad y efectividad) se seleccionó el estudio que cumplió con los siguientes criterios: a) disponibilidad de evidencia directa (estudios cabeza a cabeza, con análisis pragmáticos "Intención a Tratar"), b) evidencia de alta calidad, c) no importante heterogeneidad clínica, estadística y metodológica y d) precisión del tamaño del efecto. Conclusiones: Efectividad: La combinación de \r\nbrimonidina con timolol es igual de efectiva a timolol como monoterapia. No se encontraron comparaciones contra brimonidina, latanoprost, acetazolamida, pilocarpina, betaxolol, tafluprost y bimatoprost. Seguridad: Seguridad: No se encontraron desenlaces de seguridad en el estudio incluido.

Efectividad y seguridad de timolol combinaciones y dorzolamida combinaciones en pacientes con glaucoma de ángulo abierto, glaucoma de ángulo cerrado o presión intraocular elevada / Effectiveness and safety of timolol combinations and dorzolamide combinations in patients with open-angle glaucoma, angle-closure glaucoma or elevated intraocular pressure

Introducción: Antecedentes: Descripción de la condición de salud de interés: El glaucoma se define como una neuropatía óptica con daño estructural del nervio óptico acompañado de una disfunción visual secundaria (1). Un daño leve del nervio óptico puede ser asintomático; 50% de los pacientes en países desarrollados con glaucoma pueden no saber que padecen de dicha enfermedad (2-3) . Sin embargo, conforme la enfermedad avanza los síntomas se instauran y empeoran reduciendo la visión periférica, la sensibilidad al contraste, entre otras funciones propias de la visión, comprometiendo la realización de las actividades diarias y en última instancia, el desarrollo de ceguera. Descripción de la tecnología: El tratamiento farmacológico para el glaucoma busca disminuir la presión intraocular a un nivel que sea seguro para el paciente, disminuyendo la producción de humor acuoso o aumentando la salida del mismo del ojo, con el fin de evitar la aparición de ceguera por glaucoma. Evaluación de efectividad y seguridad: Pregunta de investigación: En pacientes con Glaucoma de Ángulo Abierto o Cerrado o con Presión Intraocular elevada, ¿es más efectivo y seguro el timolol y dorzolamida en combinaciones en comparación con brimonidina, timolol, latanoprost, acetazolamida, pilocarpina, betaxolol, tafluprost o bimatoprost para reducir la presión intraocular? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, reportes de evaluación de tecnologías, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. Población: Adultos con diagnóstico de hipertensión intraocular, glaucoma de ángulo abierto o de ángulo cerrado. Tecnología de interés: \tTimolol y dorzolamida en combinaciones (Timolol con: dorzolamida, latanoprost, travoprost, bimatoprost. Dorzolamida combinado con Timolol). Conclusiones: Efectividad: en pacientes con presión intraocular o glaucoma de ángulo abierto, timolol en sus combinaciones (travoprost o latanoprost) es más efectivo que los análogos de prostaglandinas solos (latanoprost y travoprost) para la reducción de la presión intra ocular. Asimismo, la combinación de timolol con travoprost, latanoprost y dorzolamida comparado con timolol solo, es más efectiva para la reducción de la presión intraocular. Seguridad: las combinaciones de medicamentos producen más hiperemia conjuntival que el tratamiento con un solo medicamento. No hay evidencia de comparaciones directas entre los medicamentos de interés para definir diferencias respecto a seguridad. La combinación de timolol con bimatoprost fue la que más eventos adversos produjo, comparado con la monoterapia de travoprost, seguido de latanoprost. dorzolamida con timolol es más seguro en comparación con bimatoprost como monoterapia. No se encontró evidencia para otras combinaciones de timolol o dorzolamida.(AU)

Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES: To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate METHODS: A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer's test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872 RESULTS: All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer's test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression. CONCLUSIONS: All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in ...

Timolol tópico en el tratamiento de rosácea eritematotelangiectásica: ensayo clínico randomizado doble ciego / Topical timolol in the treatment of erythematotelangiectatic rosacea: double blind randomized clinical trial

Introducción: La rosácea es un síndrome inflamatorio crónico frecuente que afecta principalmente la zona centrofacial. El subtipo más común, la rosácea eritematotelangiectásica (RET), no cuenta con un tratamiento efectivo demostrado. Estudios in vitro han propuesto que el factor de crecimiento endotelial (VEGF) podría tener un rol clave en la génesis de la rosácea al inducir angiogénesis. El uso exitoso de betabloqueadores orales (propanolol) y tópicos (timolol) en el hemangioma de la infancia abrió las puertas al estudio de la inhibición de la angiogénesis como principal objetivo terapéutico de las patologías vasculares benignas. Debido a que este subtipo de rosácea y los hemangiomas podrían presentar una etiopatogenia similar, se propone el estudio del efecto del timolol en este subtipo de rosácea. Metodología: Ensayo clínico randomizado doble ciego. Se reclutaron 67 pacientes con RET desde septiembre a diciembre de 2011. Se asignó un grupo con timolol tópico al 1 por ciento en base oil free y otro sólo con base oil free. Todos los pacientes recibieron instrucción y tratamiento estándar consistente en un limpiador, hidratante y protector solar. Nuestro outcome primario fue la diferencia de reducción del grado de eritema a las 12 semanas con colorímetro CR 200 de Minolta, y fue analizado según intención de tratar. Se evaluaron además las diferencias en las características clínicas, demográficas, el tamaño de las telangiectasias, la calidad de vida, evaluación subjetiva del tratamiento por el paciente, la adherencia a tratamiento y las reacciones adversas. Resultados: No hubo diferencia significativa en el grado de eritema a las 12 semanas de tratamiento entre los grupos, lo que permite rechazar la hipótesis diagnóstica. Tampoco se encontró diferencia alguna en los otros parámetros estudiados.

Introduction: Rosacea is a common chronic inflammatory syndrome that mainly affects the midface area. The most common subtype, Erythematotelangiectatic rosacea (ETR) has no proven effective treatment. Studies in vitro have suggested that vascular endothelial growth factor (VEGF) may have a key role in the pathogenesis of rosacea inducing angiogenesis. The successful use of oral (propanolol) and topical (timolol) betablockers in the childhood hemangioma conducted to the study of inhibition of angiogenesis as a main therapeutic target of benign vascular pathologies. Because this subtype of rosacea and hemangiomas share a similar pathogenesis, we proposed to study the effect of timolol in this subtype of rosacea. Methodology: Double blind randomized clinical trial. We recruited 67 patients with ETR from September to December of 2011. Two groups were assigned one with 1percent topical timolol oil free based and the other group used only the vehicle. All patients also received education and standard treatment consisting of a cleanser, moisturizer and sunscreen. The primary outcome was the difference in reducing the degree of erythema at week 12, and was evaluated through the Minolta CR 200 colorimeter and analyzed by intention to treat. Secondary outcomes were differences in clinical and demographic characteristics of the patients, the size of telangiectasias, quality of life, subjective evaluation from the patient, adherence to treatment and adverse reactions. Results: No significant difference was seen in the reduction of erythema degree at week 12 allowing us to reject the hypothesis. There were also no difference in all the other parameters. Conclusion: The present study shows that the use of topical timolol its not superior to placebo in reducing the degree of erythema or any of the variables analyzed. This study shows that topical timolol not constitute a possible treatment in ETR.

An Indian perspective on primary angle closure and glaucoma.

Aim: To provide a synopsis of primary angle closure disease in India, and Indian studies on the same. Results: Primary angle closure glaucoma forms almost half of all adult primary glaucomas seen in a hospital setting in India. Anatomically, corneal diameters and anterior chamber depths were least in acute and chronic PACG eyes as compared to subacute eyes and controls. Besides relative pupillary block, a Valsalva maneuver during activities of daily living may be responsible for intermittent angle closure and raised IOP in predisposed eyes. Iridotomy alone, controlled the intraocular pressure in 66.7% of subacute eyes and 12.9% of the acute. Medical therapy was additionally required for 35.5% of the acute eyes, 12.1% of the subacute and 30.0% of the chronic cases. There was a greater mean and peak IOP reduction, achieved with 0.005% latanoprost once daily, 8.2 ± 2.0 mm Hg, compared with 0.5% timolol twice daily, 6.1 ± 1.7 mm Hg2. A progression of PACS to PAC was seen in 22%, PAC to PAC OHT in 38.7% and PAC OHT to PACG in 30.7% over 5 years. Conclusions: Primary angle closure disease is common in India, and can be managed well with iridotomy, followed by an appropriate control of IOP.

Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system.

Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

Avaliação econômica das associações fixas de prostaglandina/prostamida e timolol no tratamento do glaucoma e da hipertensão ocular / Economic evaluation of prostaglandin/prostamide and timolol fixed combinations in the treatment of glaucoma and ocular hypertension

OBJETIVO: Avaliar o custo ao final de 5 anos, a efetividade e a relação custo-efetividade das associações fixas de prostaglandina ou prostamida com timolol 0,5 por cento para o tratamento do glaucoma e da hipertensão ocular no Estado de Minas Gerais, Brasil. MÉTODOS: Este estudo transversal avaliou as seguintes associações fixas: bimatoprosta/timolol 0,5 por cento (BT), latanoprosta/timolol 0,5 por cento (LT) e travoprosta/timolol 0,5 por cento (TT). O custo foi calculado a partir do número médio de gotas de 5 frascos de cada associação, da duração (dias) e do preço máximo ao consumidor (PMC). A efetividade na redução da pressão intraocular (PIO) foi obtida na literatura. Para cada uma das associações, calculou-se o custo diário, mensal, anual e em 5 anos. A relação custo-efetividade foi definida como o custo em 5 anos de cada percentual de redução da PIO. RESULTADOS: O PMC, número médio de gotas por frasco e a duração média (dias) foram, respectivamente: R$ 83,07; 109,4 e 54,7 para BT; R$ 126,03; 97,0 e 48,5 para LT e R$ 97,47; 96 e 48,0 para TT. A capacidade de redução percentual da PIO encontrada na literatura foi 35,10 por cento para BT, 35,00 por cento para LT e 34,70 por cento para TT. O custo em 5 anos para cada percentual de redução da PIO foi de R$ 61,02 para BT, R$ 104,71 para LT e R$ 82,53 para TT. A associação BT é dominante sobre as demais. CONCLUSÕES: BT apresentou em 5 anos menor custo e maior efetividade que LT e TT.

PURPOSE:To assess the 5-year cost, effectiveness and costeffectiveness of fixed combinations of prostaglandin or prostamide and timolol 0. 5 percent on glaucoma and/or ocular hypertension in the state of Minas Gerais, Brazil. METHODS: This cross-sectional study evaluated the following fixed combinations: bimatoprost/timolol 0. 5 percent (BT), latanoprost/timolol 0. 5 percent (LT) and travoprost/ timolol 0. 5 percent (TT). Cost was obtained through mean number of drops in a sample of 5 containers of each medication, duration (days) and the average wholesale price (AWP). Effectiveness in reducing intraocular pressure IOP was derived from the literature. Daily, monthly, annually and 5-year cost was calculated. Costeffectiveness was defined as cost by each percentage of IOP reduction over 5 years. RESULTS: AWP, mean number of drops and mean duration (days) were: R$ 83. 07; 109. 4 and 54. 7 for BT; R$ 126. 03; 97. 0 and 48. 5 for LT and R$ 97. 47; 96. 0 and 48. 0 for TT. Mean percentage of IOP reduction, obtained from literature, was: 35. 10 percent for BT, 35. 00 percent for LT and 34. 70 percent for TT. Cost-effetiveness ratio (R$/ percent) was: 61. 02 for BT, 104. 71 for LT and 82. 53 for TT. BT was dominant over LT and TT. CONCLUSION: BT presented lower costs and better effectiveness when compared to LT and TT. The most cost-effective fixed combination was BT.

Skin eruption and thrombocytopaenia in a woman with glaucoma: a case report / Erupción cutánea y trombocitopenia en una mujer con glaucoma: reporte de un caso

Antibiotic and non-antibiotic sulphonamides are often prescribed. Although chemical differences make cross-reactivity rare, reactions may be severe in patients allergic to sulphur. Adverse reactions are common with sulphonamides but low platelets and skin changes are rarely associated with eye-drops for glaucoma. A woman treated with dorzolamide and timolol presented with disseminated eruption. On admission, her physical examination was unremarkable except for the skin changes and severe thrombocytopaenia was detected. Skin biopsy showed hyperkeratosis, acanthosis, perivascular and periadnexal infiltrates with no vasculitis. After discontinuation of eye-drops, the eruption improved but low platelets persisted. Skin changes reappeared with use of dapsone which suggested sulphonamide cross-reactivity.

A menudo se prescriben sulfonamidas antibióticas y no-antibióticas. Aunque las diferencias químicas hacen que la reactividad cruzada sea algo raro, las reacciones pueden ser severas en los pacientes alérgicos al azufre. Las reacciones adversas son comunes con las sulfonamidas pero las plaquetas bajas y los cambios en la piel raramente se asocian con las gotas oculares para el glaucoma. A una mujer a quien se le hizo un tratamiento con dorzolamida y timolol, se le presentó una erupción diseminada. En el momento del ingreso, su examen físico fue común y corriente excepto por los cambios en la piel. Además se le detectó una trombocitopenia severa. La biopsia de la piel reveló hiperqueratosis, acanthosis, infiltrados perivasculares y periadnexales sin vasculitis. Tras descontinuar las gotas oculares, la erupción mejoró pero las plaquetas bajas persistieron. Los cambios de la piel reaparecieron con el uso de dapsona, lo que hizo pensar en una reactividad cruzada de la sulfonamida.

Evaluation of the role of timolol 0.1% gel in myopic regression after laser in situ keratomileusis

To evaluate the efficacy of the concomitant administration of antiglaucoma medications namely timolol 0.1% gel in cases with myopic regression after myopic laser in situ keratomileusis [LASIK]. Prospective observational clinical trial. Ninty five eyes of 75 patients were included in this study prospectively. The mean myopic regression was-1.29 +/- 0.83 diopters [range-0.5 to-4.62] after myopic LASIK. The eyes were divided into two groups: 50 eyes administrated timolol 0.1% gel once daily for 12 months [treated group], and 45 eyes were age matched [control group]. We assessed the amounts of myopic regression in terms of changes in the refraction [spherical equivalent and astigmatism], intraocular pressure [IOP], pachymetry and the refractive power of the cornea measurements for all participants. The refractive error and visual acuity were similar between the two groups at baseline. The treated group had an improvement in spherical equivalent significantly from-1.29 +/- 0.83 to-0.94 +/- 1.07 diopters [P=0.012]. Astigmatism was changed from-0.94 +/- 0.53 to-0.86 +/- 0.60 diopters but this change was not statistically significant [P=0.20]. The IOP was decreased significantly from 12.6 +/- 1.9 to 9.0 +/- 1.1 mm Hg [P<0.001]. Central corneal thickness was changed from 425.6 +/- 19.86 to 429 +/- 18.1 micro m but not statistically significant [P=0.56]. The central corneal power decreased significantly from 37.2 +/- 1.8 to 36.4 +/- 1.3 diopters [P<0.05]. Timolol 0.1% gel was effective for reduction and improvement of myopic regression especially the spherical errors after myopic LASIK

Eficácia do latanoprosta x travoprosta avaliada pela curva diária de pressão intraocular / Efficacy of latanoprost versus travoprost assessed by daily intraocular pressure curve

OBJETIVO: Avaliar, através da curva diária de pressão intraocular (CDPo), a eficácia do latanoprosta (L) e do travoprosta (T) como monoterapia e do L e T associados ao maleato de timolol 0,5 por cento (LTim 0,5 por cento e TTim 0,5 por cento) em pacientes glaucomatosos. MÉTODOS: Análise retrospectiva da curva diária de pressão intraocular de pacientes glaucomatosos em uso de L ou T ou das associações LTim 0,5 por cento e TTim 0,5 por cento. Foram excluídos os pacientes que não usaram a(s) medicação(ões) de maneira correta na curva diária de pressão intraocular e aqueles que estavam em uso de L ou T associado a outro hipotensor qão o timolol 0,5 por cento ou em uso de mais de dois colírios antiglaucomatosos. Foram analisados, em cada grupo, a pressão média (Pm) e a variabilidade (V) e seus respectivos desvios padrões. Utilizou-se o programa SPSS 11.0 na análise estatística. Raça, idade, sexo e tipo de glaucoma não foram critérios para a inclusão ou a exão dos pacientes. RESULTADOS: Foram incluídos 75 pacientes (142 olhos) com idade média de 61,7 anos, sendo 33 (44,0 por cento) do sexo masculino e 42 (56,0 por cento) do feminino. Treze pacientes (26 olhos - 18,3 por cento) usavam L; 18 pacientes (33 olhos - 23,2 por cento) usavam T; 18 pacientes (32 olhos - 22,5 por cento) estavam em tratamento com LTim 0,5 por cento e 26 pacientes (51 olhos - 35,9 por cento) usavam a associação TTim 0,5 por cento. Sessenta e nove pacientes (92,0 por cento) eram portadores de glaucoma crônico simples; 5 (6,7 por cento) de glaucoma congênito e 1 (1,3 por cento) de glaucoma pós-pseudofacia. Nos grupos L e T, os valores da Pm foram 15,2 (± 4,2) mmHg e 14,8 (±3,2) mmHg e os da V foram 2,0 (± 1,2) e 3,2 (± 1,9), respectivamente. Nos grupos LTim 0,5 por cento e TTim 0,5 por cento, os valores da Pm foram 14,9 (± 2,2) mmHg e 15,0 (±3,2) mmHg e os da V foram 2,4 (± 1,2) e 2,8 (± 1,6), respectivamente. Não houve diferença estatisticamente significativa na Pm entre ...

PURPOSE: To assess the efficacy of latanoprost (L) and travoprost (T) as monotherapy as well as both drugs associated with 0.5 percent timolol maleate twice a day regarding the daily curve of intraocular pressure (DCPo) with the measurement of intraocular pressure (IOP) at 6 am in bed. METHODS: Retrospective study analyzing the daily curve of intraocular pressure of patients treated with L or T with or without 0.5 percent Tim. Patients who did not correctly follow the treatment were excluded. We also excluded the patients who used the prostaglandin analog associated with any other antiglaucomatous drug different from 0.5 percent Tim and those who were treated with more than two antiglaucomatous drugs. Statistical analysis was made through the SPSS 11.0 program calculating mean intraocular pressure (Pm), variability (V), p value and standard deviation. Ethnic aspects or type of glaucoma were no criteria of inclusion or exclusion in this study. RESULTS: Seventy-five patients (142 eyes) were included. The average age was 61.7 years. Thirty-three (44.0 percent) patients were male and 42 (56.0 percent) were female. Thirteen patients (26 eyes 18.3 percent) used L, 18 patients (33 eyes - 23.2 percent) were treated with T, 18 patients (32 eyes - 22.5 percent) used latanoprost and 0.5 percent timolol (L 0.5 percentTim) and 26 patients (51 eyes - 35.9 percent) used travoprost and 0.5 percent timolol (T 0.5 percentTim). Chronic simple glaucoma was the most common type (92.0 percent), followed by congenital glaucoma (6.7 percent) and glaucoma secondary to cataract surgery (1.3 percent). Pm was 15.2 (± 4.2) mmHg among those treated with L and 14.8 (± 3.2) mmHg among the T users. Those patients showed a V of 2.0 (± 1.2) and 3.2 (± 1.9). In the group of L 0.5 percentTim and T 0.5 percentTim the Pm and V were 14.9 (± 2.2) mmHg, 15.0 (± 3.2) mmHg, 2.4 (± 1.2) and 2.8 (± 1.6) respectively. No statistical significant difference was found in the Pm neither ...

Conjunctival changes induced by prostaglandin analogues and timolol maleate: a histomorphometric study

PURPOSE: To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva. METHODS: Fifty New Zealand rabbits were divided in 5 groups of 10 animals. The left eyes were treated daily with one drop of bimatoprost 0.03 percent, travoprost 0.004 percent, latanoprost 0.005 percent, timolol maleate 0.5 percent or artificial tears containing benzalkonium chloride (BAK) for 30 days. The right eyes served as controls. Superior limbic conjunctival biopsies were performed at the 8th and 30th day in 5 rabbits of each group. The conjunctiva was fixed with 10 percent formaldehyde, followed by HE and PAS staining. Morphohistometric quantitative analyses were performed to evaluate the following parameters: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. RESULTS: At the 8th and 30th posttreatment days, all groups, except one that received artificial tears, exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin (PG) analogues groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (p=0.0035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (p=0.0006), and at the 30th day in those treated with bimatoprost (p=0.0021) and latanoprost (p=0.009). CONCLUSIONS: Although a moderate, diffuse inflammatory infiltrate was observed in PG-treated eyes, no changes in conjunctival epithelial thickness or subconjunctival collagen density were observed with these medications, suggesting that these drugs induce fewer changes than timolol maleate in the rabbit conjunctiva.

OBJETIVOS: Comparar alterações histológicas induzidas por medicação anti-glaucomatosa na conjuntiva de coelhos. MÉTODOS: Cinqüenta coelhos da raça Nova Zelândia foram divididos em 5 grupos de 10 animais. Os olhos esquerdos foram tratados com uma gota diária de bimatoprosta 0,03 por cento, travoprosta 0,004 por cento, latanoprosta 0,005 por cento, maleato de timolol 0,5 por cento ou lágrimas artificiais contendo cloreto de benzalcônio (BAK) por 30 dias. Os olhos direitos serviram como controles. Foram realizadas biópsias conjuntivais límbicas superiores no 8º e 30º dias em 5 coelhos de cada grupo. A conjuntiva foi fixada com formaldeído 10 por cento, seguido por coloração de HE e PAS. Foi realizada análise quantitativa morfohistométrica para avaliar os seguintes parâmetros: infiltrado inflamatório, espessura epitelial, número de células caliciformes, diâmetro e número de vasos sanguíneos. RESULTADOS: No 8º e 30º dias de tratamento, todos os grupos, exceto aquele que recebeu lágrimas artificiais, exibiram infiltrado inflamatório difuso, composto por linfócitos e neutrófilos, sendo mais denso no grupo timolol do que nos grupos dos análogos de prostaglandinas. No 30º dia, o grupo timolol apresentou um aumento na densidade de colágeno subepitelial e um aumento significativo da espessura epitelial (p=0,0035). A densidade de células caliciformes aumentou significativamente no 8º dia no grupo tratado com travoprosta (p=0,0006), e no 30º dia nos grupos tratados com bimatoprosta (p=0,0021) e latanoprosta (p=0,009). CONCLUSÕES: Embora tenha sido observado um infiltrado inflamatório difuso e moderado nos olhos tratados com análogos de prostaglandinas, não houve alterações na espessura epitelial conjuntival ou densidade colágena subepitelial com essas medicações, sugerindo que essas drogas induzem menores alterações que o maleato de timolol na conjuntiva de coelhos.

Concentração de proteínas no humor aquoso de pacientes com glaucoma primário de ângulo aberto em tratamento clínico / Aqueous humor protein concentration in patients with primary open-angle glaucoma under clinical treatment

OBJETIVOS: Comparar a concentração total de proteínas no humor aquoso entre pacientes com glaucoma primário de ângulo aberto e sem glaucoma. MÉTODOS: Foram coletadas amostras de humor aquoso de 22 pacientes com glaucoma primário de ângulo aberto (grupo GPAA) no momento da trabeculectomia. Na coleta, 0,1 mL de humor aquoso foi aspirado da câmara anterior através de uma agulha de calibre 26, no início do procedimento cirúrgico. Coleta semelhante foi realizada em 22 pacientes sem glaucoma no início da cirurgia de catarata (grupo controle). A amostra de humor aquoso foi armazenada a -20°C após a coleta. A concentração total de proteínas no humor aquoso foi determinada por meio de um teste colorimétrico. RESULTADOS: A média geométrica da concentração total de proteínas no humor aquoso foi de 32 mg/dL (amplitude: 8-137 mg/dL) no grupo glaucoma primário de ângulo aberto e de 16 mg/dL (amplitude: 2-85 mg/dL) no grupo controle. A razão da concentração total de proteínas no humor aquoso entre estes dois grupos foi de 2,0 (intervalo de confiança de 95 por cento: 1,3 a 3,2; p=0,003). CONCLUSÕES: A concentração total de proteínas no humor aquoso de pacientes com glaucoma primário de ângulo aberto foi aproximadamente duas vezes maior quando comparada aos pacientes sem glaucoma.

PURPOSE: To compare total protein concentration in the aqueous humor of primary open-angle glaucoma and non-glaucomatous patients. METHODS: Aqueous humor samples were obtained from 22 patients just before trabeculectomy for clinically uncontrolled primary open angle glaucoma (POAG group). Aqueous humor (0.1 mL) was aspirated by inserting a 26-gauge needle into the anterior chamber. The same procedure was performed in 22 non-glaucomatous patients just before cataract surgery (control group). Immediately after collection, the aqueous humor was stored at -20°C. Aqueous humor total protein concentration was determined using a colorimetric assay. RESULTS: The geometric mean of total protein concentration of the aqueous humor samples was 32 mg/dL (range: 8-137 mg/dL) in the primary open angle glaucoma group and 16 mg/dL (range: 2-85 mg/dL) in the control group. The ratio of the protein concentration between the two groups was 2.0 (95 percent confidence interval: 1.3 to 3.2; p=0.003). CONCLUSIONS: The total protein concentration in primary open-angle glaucoma aqueous humor was approximately two times higher than that in non-glaucomatous subjects.

Mieux prescrire le timolol dans hypertension intraoculaire et dans le glaucome chronique a angle ouvert

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Análise dos efeitos da injeção subtenoniana posterior de triancinolona: série de casos / Effects of analysis of posterior subtenon injection of triamcinolone: a case series

OBJETIVO: Avaliar os efeitos da injeção subtenoniana posterior de acetato de triancinolona em pacientes com inflamação intra-ocular. MÉTODOS: Série de casos em que foram avaliados 24 pacientes (26 olhos) submetidos a injeção subtenoniana posterior de acetato de triancinolona para o tratamento de inflamação intra-ocular. Em todos os pacientes foi associado o maleato de timolol 0,5 por cento por 30 dias. RESULTADOS: Foi observado melhora da acuidade visual em 81 por cento dos pacientes após injeção única de acetato de triancinolona. Não foi observado aumento significativo da pressão intra-ocular em nenhum dos olhos tratados. CONCLUSÃO: O acetato de triancinolona sob a forma de injeção subtenoniana posterior mostrou ser uma forma eficaz e segura de tratamento para as inflamações intra-oculares.

PURPOSE: To evaluate the effects of posterior subtenon injection of triamcinolone acetonide in patients with intraocular inflammation. METHODS: Case series enrolling 24 patients (26 eyes) submitted to posterior subtenon injection of triamcinolone acetonide for intraocular inflammation treatment. Maleate timolol at 0.5 percent was prescribed for all patients for 30 days. RESULTS: Improvement of visual acuity was observed in 81 percent of the patients after a single injection of triamcinolone acetonide. Increase in the intraocular pression was not observed in the treated eyes. CONCLUSION: Posterior subtenon injection of triamcinolone acetonide proved to be a safe and effective way of treating intraocular inflammations.

Serum lipid profile and timolol gel.

Topical use of timolol eye drops in the management of glaucoma is associated with various systemic side effects including alteration of lipid profile with increase in cardiovascular risk factors. Change over to timolol gel altered results in normalisation of altered lipid profile with decrease in cardiovascular risk factors. The decrease seen is attributable to lack of systemic absorption of timolol gel.