Relationship between the number of glaucoma medications, ocular surface disorder, and treatment adherence / Relação entre o número de medicamentos para glaucoma, distúrbio da superfície ocular e adesão ao tratamento

ABSTRACT Purpose: To determine the relationship of ocular surface disease, the number of glaucoma medications prescribed and its influence on treatment adherence. Methods: In this cross-sectional study, demographic data of patients with glaucoma were collected, and patients completed the ocular surface disease index questionnaire and the glaucoma treatment compliance assessment tool. Ocular surface parameters were assessed by "Keratograph 5M." Patients were stratified into two groups according to the amount of prescribed ocular hypotensive eye drops (Group 1, one or two classes of medications; Group 2, three or four classes) Results: In total, 27 eyes of 27 patients with glaucoma were included: 17 using 1 or 2 topical medications (Group 1) and 10 eyes using 3 or 4 classes (Group 2). For the Keratograph assessment, patients using ≥3 medications had significantly smaller tear meniscus height (0.27 ± 0.10 vs. 0.43 ± 0.22; p=0.037). The analysis of Ocular Surface Disease Index questionnaire showed higher scores among the groups using more hypotensive eye drops (18.67 ± 13.53 vs. 38.82 ± 19.72; p=0.004). Regarding the glaucoma treatment compliance assessment tool, Group 2 had worse scores in components of forgetfulness (p=0.027) and barriers due to lack of drops (p=0.031). Conclusion: Patients with glaucoma using more hypotensive eye drops had worse tear meniscus height and ocular surface disease index scores than those using fewer topical medications. Patients using three or four drug classes had worse predictors of glaucoma adherence. Despite worse ocular surface disease results, no significant difference in self-reported side effects was found.

RESUMO Objetivo: Determinar a relação entre doença da superfície ocular (OSD), número de medicamentos prescritos para o glaucoma, e como isso influencia na adesão ao tratamento. Métodos: Neste estudo transversal, pacientes com glaucoma foram submetidos à coleta de dados demográficos, preenchimento do questionário Ocular Surface Disease Index e do Glaucoma Treatment Compliance Assessment Tool. Os parâmetros da superfície ocular foram avaliados pelo "Keratograph 5M". Indivíduos foram estratificados em 2 grupos de acordo com a quantidade de colírios hipotensores oculares prescritos (Grupo 1: uma ou duas classes de medicamentos; Grupo 2: três ou quatro classes). Resultados: No total, 27 olhos de 27 pacientes com glaucoma foram incluídos: 17 usando 1 ou 2 medicamentos tópicos (Grupo 1) e 10 olhos usando 3 ou 4 classes (Grupo 2). Na avaliação do Keratograph, os pacientes em uso de 3 ou mais medicamentos apresentaram altura do menisco lacrimal significativamente menor (0,27 ± 0,10 vs. 0,43 ± 0,22; p=0,037). Análise do questionário OSDI mostrou escores mais altos entre o grupo que usou mais colírios hipotensores (18,67 ± 13,53 vs. 38,82 ± 19,72; p=0,004). Em relação ao Glaucoma Treatment Compliance Assessment Tool, o Grupo 2 apresentou piores escores nos componentes de esquecimento (p=0,027) e barreiras por falta de colírios (p=0,031). Conclusão: O estudo demonstrou que pacientes com glaucoma usando mais colírios hipotensivos apresentaram piores escores de altura do menisco lacrimal e Ocular Surface Disease Index, em comparação com aqueles que usaram menos medicamentos tópicos. Pacientes em uso de 3 ou 4 classes de colírios tiveram piores preditores de adesão ao glaucoma. Apesar dos piores resultados de doença da superfície ocular, não houve diferença significativa nos efeitos colaterais relatados.

Ligneous conjunctivitis: Fresh-frozen plasma and heparin use intra-and postoperatively, a report of two cases

ABSTRACT Ligneous conjunctivitis is a rare chronic form of recurrent membranous inflammation and plasminogen deficiency. Ocular manifestations may be associated with sites other than mucous membranes, such as the oral cavity, internal ear, respiratory, genitals, and kidney. Treatment is extremely difficult because of the lack of topic plasminogen drops, and a high volume is required for systemic supplementation. This report aimed to present two patients with ligneous conjunctivitis treated with membrane excision, topical fresh-frozen plasma, and heparin intra-, and postoperatively. No recurrence was found in the ligneous membrane in the 12-month follow-up. The use of topical fresh-frozen plasma and heparin after membrane excision could be effective to avoid recurrence.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study / Colírio de soro autólogo diluído com metilcelulose 0,5% e solução salina 0,9%: um estudo clínico comparativo

ABSTRACT Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

RESUMO Objetivo: Este estudo comparou o colírio de soro au tólogo manipulado com metilcelulose a 0,5% com solução salina 0,9%. Critérios subjetivos de melhora dos sintomas e critérios clínicos objetivos para resposta à terapia foram avaliados. Métodos: Este estudo prospectivo longitudinal envolveu 23 pacientes (42 olhos) com defeitos epiteliais persistentes ou doença de olho seco grave refratária à terapia convencional que usavam colírio de soro autólogo 20% preparado com metilcelulose por mais de 6 meses e iniciaram soro autólogo diluído em solução salina 0,9%. Os grupos controle e intervenção consistiam dos mesmos pacientes sob tratamentos alternados. Os critérios subjetivos para o alívio dos sintomas foram avaliados usando o Salisbury Eye Evaluation Questionnaire. Os critérios objetivos foram avaliados por meio de exame em lâmpada de fenda incluindo: tempo de ruptura da lágrima, coloração da córnea com fluoresceína, teste de Schirmer, coloração com rosa bengala e altura do menisco lacrimal. Esses critérios foram avaliados antes da troca do diluente e após 30, 90 e 180 dias. Resultados: Um total de 42 olhos foram analisados antes e após 6 meses usando soro autólogo diluído com solução salina 0,9%. Nenhuma diferença significativa foi encontrada nos critérios subjetivos, tempo de ruptura da lágrima, menisco lacrimal, coloração com fluoresceína ou rosa bengala. Os resultados dos testes de Schirmer pioraram significativamente em 30 e 90 dias (p=0,008). Não foram observadas complicações ou efeitos adversos. Conclusões: Este estudo reforça o uso do colírio de soro autólogo 20% como um tratamento de sucesso para a doença do olho seco grave resistente à terapia convencional. O soro autólogo diluído em solução salina a 0,9% não foi inferior à formulação de metilcelulose.

In search of disambiguation: development of eye drop bottle sleeves to aid in identification and survey among possible users. A cross-sectional study

BACKGROUND: Considerable numbers of individuals present low vision, blindness, illiteracy and other conditions that could possibly impair their identification of medications, such as eye drops. Through helping these individuals to identify their eye drops, they can achieve greater autonomy. Misidentification can be avoided through use of multisensory sleeves that can be adapted to most eye drop bottles. Correct use of eye drops is important for preventing progression of diseases like glaucoma that could potentially lead to blindness. OBJECTIVE: To develop bottle sleeves to aid in identification of eye drops and then interview a group of possible users to evaluate the acceptance of the solution. DESIGN AND SETTING: Cross-sectional survey performed at an ophthalmological clinic in São Paulo (SP), Brazil. METHODS: We describe the development of multisensory sleeves to assist in identification of eye drops. To assess the acceptance of this solution, we interviewed 18 patients who were currently using three or more types of eye drops. RESULTS: We developed four prototypes for eye drop bottle sleeves and conducted an acceptance test on them. Most of the patients who answered the survey about the sleeves were elderly. Most (95%) reported believing that the sleeves would help reduce the risk of mixing up eye drops with other medications that also dispense drops. They also believed that these would increase their autonomy in using eye drops. CONCLUSION: The solution presented was well accepted and may help increase safety in using eye drops through preventing misidentification.

Focusing on antioxidant treatment of dry eye and novel drug study / 中华实验眼科杂志

Dry eye is becoming more common worldwide.Its pathophysiology is complicated, and its condition is chronic.Treatment options of dry eye are ineffective.As a multifactorial ocular surface disease, tear film instability, tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities resulted from various causes are main natural pathological processes of dry eye.This multifactorial process of the disease leads to poor efficacy of single anti-inflammatory therapy.Oxidative stress is closely related to the occurrence of dry eye.During the decrease of tear film stability, reactive oxygen species produced by oxidative stress system damage the myelin sheath of ocular nerve and the lipid layer of tear film, inducing or aggravating the ocular inflammatory response.Targeting the main causes of dry eye's pathogenesis, stopping the vicious cycle of inflammatory responses in each link, and relieving patients' conditions are the main goals of antioxidant therapy.The development of anti-inflammatory and antioxidant medications is currently the main focus of international research on novel anti-dry eye medications.Some progresses have been made in the area of targeting oxidative stress biomarkers, mitochondrial targeting medications, mucin secretion, antioxidant enzymes like glycoprotein selenium and lactoferritin, as well as multifunctional nanoagents, and the antioxidant eye drops using nanomaterials have more advantages.Antioxidant treatment may be one of the potential future avenues of dry eye clinical research.Ophthalmologists and researchers should be fully aware of, pay close attention to and actively participate in investigations that are relevant to dry eye antioxidant therapy and the development of new medications.

Mass variability in drops of multidose eyedrops: a quality and reliability study / Variabilidade da massa das gotas dos colírios: um estudo de qualidade e confiabilidade

ABSTRACT Purpose: This quality and reliability study aimed to identify the mass variability of multidose eyedrops and to verify the existence of a reference pattern for the drop volume of eyedrops using standard lubricant eyedrops available on the Brazilian market. Methods: Five brands of lubricant eyedrops were evaluated. An ideal standard 20 µL drop of eyedrops from each manufacturer was captured using an adjustable micropipette. The eyedrop bottles were randomly selected, and five measurements of the samples' masses were collected using calibrated precision scales. Results: The mass of the 20 µL samples varied significantly (p<0.001) among the different manufacturers. However, among eyedrops of the same brand, mass variation was not statistically different. The global mean mass of all weighed drops was 18.24 mg, and non-uniformity was identified across all eyedrop brands. Conclusion: Significant variations in the drop masses of common lubricant eyedrops were identified using standard laboratory equipment. Heterogeneity in the drop volume of standard eyedrop medications suggest that potential dosage discrepancies exist, possibly altering treatment efficacy. A pre-established reference measure may lead to the production of more appropriately sized eyedrops for use in human eyes.

RESUMO Objetivo: Este estudo de qualidade e confiabilidade teve como objetivo identificar a variabilidade da massa do volume da gota de colírios multidose e verificar a existência de um padrão de referência para o volume da gota dos colírios usando lágrimas artificiais do mercado brasileiro. Métodos: Cinco marcas de colírios lubrificantes foram avaliadas quanto ao volume da gota. Uma gota padrão ideal de 20 µL de cada fabricante foi coletada usando uma micropipeta ajustável. Os frascos dos colírios foram selecionados aleatoriamente e cinco medidas das massas das amostras foram coletadas usando escalas de precisão calibradas. Resultados: A massa das amostras de 20 µL variou significativamente (p<0,001) entre os diferentes fabricantes. No entanto, entre os colírios da mesma marca, a variação da massa não foi estatisticamente diferente. A massa média global de todas as gotas pesadas foi de 18,24 mg e foi observada uma não-uniformidade entre todas as marcas de colírios. Conclusão: Identificou-se uma variação significativa nas massas do volume das gotas dos colírios lubrificantes, usando equipamento padrão de laboratório. A heterogeneidade no volume da gota dos colírios testados sugere a existência de discrepâncias potenciais em suas posologias, possivelmente alterando a eficácia do tratamento. Uma medida de referência pré-estabelecida pode levar à produção de colírios com gotas de tamanho mais apropriado para uso em olhos humanos.

Presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino / Preoperative intraocular pressure for the control of primary angle closure treated with clear lens extraction

Introducción: la extracción del cristalino transparente en pacientes con cierre angular primario se plantea si existe presión intraocular mayor o igual que 30 mm Hg o daño por glaucoma. En ojos con elevación moderada de la presión intraocular se desconocen los resultados. Objetivo: evaluar la influencia de la presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino transparente. Material y Métodos: se realizó un estudio pre-experimental, entre enero de 2013 y enero de 2020, incluyó 78 ojos de 78 pacientes con cierre angular primario tratados con extracción del cristalino transparente; divididos en dos grupos según presión intraocular preoperatoria. Para el análisis estadístico se empleó chi cuadrado de independencia, probabilidad exacta de Fisher, prueba t para muestras independientes y análisis de varianza de medidas repetidas; con significación estadística del 95 por ciento. Resultados: hubo diferencias significativas entre ambos grupos para longitud axial (p=0,003), grosor del cristalino (p<0,001) y espesor corneal central (p=0,016). La presión intraocular y número de colirios, variaron de forma muy significativa (p<0,001) entre el pre y posoperatorio, y entre ambos grupos en los diferentes momentos analizados. En el grupo A el 94,4 por ciento de los ojos mostró control absoluto posoperatorio invariable en el tiempo, en el grupo B la mayoría de los ojos tuvo control relativo con diferencias muy significativas (p<0,001) entre ambos. Conclusiones: la presión intraocular preoperatoria influye en el control del cierre angular primario tratado con extracción del cristalino transparente; valores previos menores que 30 mm Hg, propician mejor control posoperatorio(AU)

Introduction: Clear lens extraction is considered in patients older than 50 years with primary angle closure and intraocular pressure greater than or equal to 30 mm Hg or damage due to glaucoma. The results are unknown in eyes with a moderate elevation of intraocular pressure. Objective: To evaluate the influence of preoperative intraocular pressure in the control of the primary angle closure treated with clear lens extraction. Material and Methods: A pre-experimental study was conducted between January 2013 and January 2020. It included a total of 78 eyes of 78 patients with primary angle closure treated with clear lens extraction. They were divided into two groups according to preoperative intraocular pressure. For statistical analysis, Chi-square test, Fisher's exact probability test, and t test were used for independent samples and analysis of variance with repeated measurements; with 95 percent statistical significance. Results: There were significant differences in axial length (p=0,003), lens thickness (p<0,001) and central corneal thickness (p=0,016) between both groups. Intraocular pressure and the number of eye drops varied very significantly (p<0,001) between the pre-and postoperative periods and between both groups at the different moments analyzed. In group A, 94,4 percent of the eyes showed absolute postoperative control, which remained unchanged over time. In group B, most eyes had relative control. There were very significant differences (p<0,001) between both groups. Conclusions: Preoperative intraocular pressure influences the control of primary angle closure treated with clear lens extraction; previous values less than 30 mm Hg favor better postoperative control(AU)

Effect of steroid eyedrops after trabeculectomy in glaucoma patients: a keratograph analysis / Efeito de colirios esteróides pré-operatório em pacientes com glaucoma: análise com keratograph

ABSTRACT Purpose: To investigate the use of preoperative steroid eyedrops in glaucoma patients undergoing trabeculectomy for ocular surface disease. Methods: A total of 31 eyes of 31 glaucoma patients were included. Only glaucoma patients who had been using at least three topical intraocular pressure-lowering medications for longer than 6 months were included. All patients were treated with loteprednol etabonate ophthalmic suspension 0.5% four times per day for 1 week before trabeculectomy. Data from baseline (day of surgery) and the follow-up visit (2 weeks after surgery) were included. All patients underwent a detailed ophthalmologic examination. Ocular surface disease was evaluated using the Ocular Surface Disease Index questionnaire and clinical measures, including tear breakup time, conjunctival hyperemia, and biomicroscopy to detect the presence or absence of keratitis. Ocular Surface Disease Index scores greater than 13 indicated a clinically relevant presence of ocular surface disease. In addition, all patients underwent keratograph analysis. The comparison of ocular surface disease before and after trabeculectomy was assessed using a paired test. Results: The mean age of the glaucoma patients was 69.90 ± 10.77 years. The average visual acuity was 0.40 ± 0.34 logMAR. The overall Ocular Surface Disease Index prevalence rate was 27.20 ± 17.56 units. Clinical assessment revealed no significant difference in bulbar redness, breakup time, or keratitis before and after surgery (p>0.05 for all comparisons). Keratograph analysis showed that the only two parameters that were significantly different before and after trabeculectomy ewere the bulbar redness by keratograph (BR-K) and the average noninvasive tear breakup time. Patients presented more conjunctival hyperemia and shorter noninvasive tear breakup time after trabeculectomy as compared with before surgery (p=0.013 and p=0.041, respectively). Conclusions: The present study not only confirms the high prevalence of clinical findings of ocular surface disease in glaucoma patients but also reveals new objective parameters measured by keratograph analysis. Apart from using loteprednol etabonate ophthalmic suspension 0.5% 1 week before the surgery, our sample presented a worsening of conjunctival hyperemia (bulbar redness by keratograph) and also a shorter noninvasive tear breakup time postoperatively.

RESUMO Objetivo: Investigar a ação de colírios esteróides na doença de superfície ocular em pacientes a serem submetidos a cirurgia de trabeculectomia. Métodos: Foram incluídos 31 olhos de 31 pacientes com glaucoma em uso de pelo menos 3 medicações tópicas anti- hipertensivas há mais de 6 meses. Todos os pacientes foram tratados com colírio de etabonato de loteprednol 0,5% (1 gota a cada 6 horas) durante os 7 dias precedentes à cirurgia de trabeculectomia. Além disso, foram submetidos a exame oftalmológico completo e responderam questionário validado que visa avaliar parâmetros subjetivos correlacionados a doenças da superfície ocular (Ocular Surface Disease Index). Os aspectos clínicos avaliados foram: tempo de ruptura lacrimal, coloração da córnea após colírio de fluoresceína (ceratite) e hiperemia conjuntival. Os pacientes foram, ainda, submetidos à análise da superfície ocular através de novo software tecnológico denominado "Keratographic", tecnologia não invasiva que permite avaliar a doença da superfície ocular. A comparação da doença de superfície ocular antes e após a trabeculectomia foi avaliada estatisticamente através do teste pareado. Resultados: A média de idade dos participantes foi de 69,90 ± 10,77 anos. A AV média foi de 0,40 ± 0,34 logMAR. A taxa de prevalência global da Ocular Surface Disease Index foi de 27,20 ± 17,56 unidades. Em relação à avaliação clínica, não houve diferença significativa em relação hiperemia, ruptura lacrimal e ceratite antes e após a cirurgia (p>0,05 para todas as comparações). Em relação à análise com o "keratograph (menisco lacrimal, hiperemia, tempo de ruptura do filme lacrimal, meibografia para a pálpebra superior e inferior), os dois únicos parâmetros que diferiram significativamente antes e após a trabeculectomia, foram hiperemia e a média do tempo de rupture do filme lacrimal. Após a cirurgia de trabeculectomia, os pacientes apresentaram aumento da hiperemia conjuntival e diminuição do tempo de ruptura do filme lacrimal (p=0,013 e p=0,041, respectivamente). Conclusões: O presente estudo, não somente confirma a elevada prevalência da doença de superfície ocular em pacientes com glaucoma, como também demonstra que a mesma pode ser mensurada objetivamente através de parâmetros mensurados pelo Keratograph. Apesar de ter utilizado etabonato de loteprednol 0,5% uma semana antes da cirurgia, nossa amostra apresentou piora da hiperemia conjuntival e diminuição no tempo de ruptura do filme lacrimal no pós-operatório.

Recurrent pterygium resection associated to fibrin membrane graft: report of two cases / Resseção do pterígio recorrente associada ao enxerto de membrana fibrina: relato de dois casos

ABSTRACT We propose a novel surgical technique in cases of aggressive recurrent pterygium non-subsidiary of treatment with conjunctival autografts or antimetabolites. Two presented cases were treated with surgical excision and a sutured plasma rich in growth factors membrane (mPRGF) followed by rich in growth factors (PRGF) eye drops treatment. After surgery, dexamethasone, tobramycin and PRGF eye drops were prescribed for 6 weeks. After a 12-month and 3-year post-surgical follow-up respectively, treated eyes with mPRGF did not present relapse, and visual acuity improved in both cases. No ocular complications, pain, eye discomfort nor other symptoms were observed. The combined use of PRGF eye drops and mPRGF seems an effective and safe therapy for recurrent pterygium.

RESUMO Nós propomos uma nova técnica cirúrgica em casos de pterígio agressivo recorrente não subsidiário de tratamento com autoenxertos conjuntivais ou antimetabólitos. Dois casos foram tratados com excisão cirúrgica e um plasma suturado rico em membrana de fatores de crescimento (mPRGF), seguido de tratamento com colírios ricos em fatores de crescimento (PRGF). Após a cirurgia, foram prescritos colírios de dexametasona, tobramicina e PRGF por 6 semanas. Após 12 meses e 3 anos de acompanhamento pós-cirúrgico respectivamente, os olhos tratados com mPRGF não apresentaram recidiva e a acuidade visual melhorou nos dois casos. Não foram observadas complicações oculares, dor, desconforto ocular ou outros sintomas. O uso combinado de colírios de PRGF e mPRGF parece uma terapia eficaz e segura para o pterígio recorrente.

Questionnaire Survey on the Satisfaction of Ophthalmic Solutions and the Handling of Eye Drops in Patients with Ophthalmic Diseases / 医薬品情報学

Clarifying the current state of ophthalmic solutions and the handling of eye drops is important for the proper use of ophthalmic solutions. In this study, a questionnaire survey was conducted from May 2018 to February 2019 on 200 ophthalmic inpatients who provided consent. In total, 36.5% of the patients were dissatisfied with the usability of ophthalmic containers due to their hard material andthe difficulty of releasing the ophthalmic solution. In addition, 43.0% of the patients repliedthat they hadlearnedfrom medical professionals, such as doctors and pharmacists, about the handling of eye drops, whereas 45.0% reported failing to apply ophthalmic solutions onto their eyes correctly. Only 2.0% of the respondents answeredthat they hadconsulteddoctors or pharmacists about the use of ophthalmic solutions. These findings underscore the current problems about patients’ satisfaction with ophthalmic solutions andhandling of eye drops. Therefore, pharmacists may needto be actively involvedin patients’ selection of ophthalmic solutions andinstruct them regarding usage.

Evaluation of Pharmaceutical Characteristics and Carer Usability of Antiglaucoma Ophthalmic Solutions / 医薬品情報学

Objective: Glaucoma is the most frequent cause of blindness in Japan and is primarily treated using IOP-lowering ophthalmic solutions. Although the patients themselves frequently instill ophthalmic solutions, instillation by caregivers may be necessary for various reasons. Therefore, we evaluated pharmaceutical characteristics of antiglaucoma ophthalmic solutions and their usability from the caregivers' viewpoint.Methods: Five dorzolamide hydrochloride-timolol maleate ophthalmic solutions and 2 travoprost-timolol maleate ophthalmic solutions were evaluated concerning the pharmaceutical characteristics and subjective squeezability rated by adults aged 20 years or above.Results: Among the dorzolamide hydrochloride-timolol maleate compounding ophthalmic solutions, the squeeze force was the lowest in COSOPT® ophthalmic solution (11.8 N), and DORMOLOL® combination ophthalmic solution NITTEN was rated highest, with 68.2% of the subjects placing it within the top 3 levels of a 7-level scale. Of the travoprost-timolol maleate ophthalmic solutions, the squeeze force was 9.8 N, lower than the pioneer drug, in TraTimo® combination ophthalmic solution NITTO, which was also rated in the top 3 levels by 90.3% of the subjects. A strong negative correlation was observed between the squeeze force and squeezability.Conclusion: In instillation by caregivers, the squeeze force was shown to be correlated with subjective squeezability as in instillation by patients themselves. This study provided information concerning the usability of ophthalmic solutions from the caregivers' viewpoint. For the future, it is necessary to select ophthalmic solutions from the caregivers' as well as the patients' viewpoints by utilizing information obtained in this study.

Comparative Evaluation of the Pharmaceutical Properties of Original and Generic Betamethasone Ophthalmic Solution / 医薬品情報学

Objective: In this study, pharmaceutical properties were compared between the original and generic ophthalmic solutions containing betamethasone.Methods: The squeeze force, drop weight, surface tension, pH, kinematic viscosity, and total number of drops were measured. The drop volume was calculated from the drop weight and specific gravity. Information on preservatives contained in each product was collected from package inserts.Results: There was a significant difference in the squeeze force between the original and generic drugs. The pH and kinematic viscosity did not differ between the drugs. The drop volume was in the range of 30.3 to 47.2 μL, and the surface tension ranged between 33.7 and 65.2 mN/N. The total number of drops was approximately 100 in the original drug, being the lowest.Conclusion: The results of this study showed that the squeeze forces of all generic products but RINBETA PF, which was contained in a specific container, were smaller than that of the original product. The drop volumes of 2 generic products were ≥ 15-μL smaller than that of the original product, but they were within the permissible range. The maximum difference in the surface tension was approximately 33 mN/N, suggesting that drug solution relatively frequently overflows from the eyes. The total number of drops for all generic products was greater than that for the original product, suggesting that the former can be used at a higher frequency. Based on these results, pharmacists must select products in accordance with individual patients.

Quando a cor ajuda / When color helps

RESUMO Objetivo: Reduzir a identificação errônea de colírios, por meio do uso de substâncias com cores diferentes. Métodos: Um grupo de 34 voluntários saudáveis foi apresentado a dois grupos de quatro colírios cada. Todos os colírios foram colocados em frascos idênticos sem rótulo. Em um grupo de quatro colírios, todos tinham conteúdos transparentes. No outro grupo, cada um dos quatro possuía uma substância de cor diferente. A cada um foi atribuído um número, e o voluntário foi solicitado a identificá-lo por meio da cor. Medimos o índice de acerto na identificação dos colírios dos dois grupos. Resultados: Os voluntários possuíam nível de formação desde Fundamental incompleto até Pós-Graduação completa, sendo 16 do sexo masculino (48%) e 18 do sexo feminino (52%), com idades variando de 21 até 87 anos. O índice de acerto no grupo de colírios coloridos foi de 88% e, no grupo de colírios transparentes, de 24%. Conclusão: O uso de colorações em colírios pode auxiliar na diferenciação entre os frascos e prevenir a identificação errônea.

ABSTRACT Objective: To reduce the inappropriate identification of eye drops, through the use of different colors. Methods: A group of 34 healthy volunteers was presented to two groups of four eye drops each. All eye drops were placed in identical, unlabelled vials. In one group, all four eye drops were transparent. In the other group, each had a different color. A number was assigned to each eye drop, and the volunteer was asked to identify it by color. We measured the correct index in the identification of the eye drops of the two groups. Results: The volunteers had a level of education from incomplete junior school to complete graduate course, with 16 males (48%) and 18 females (52%), age range of 21 to 87 years. The success rate in the group of colored eye drops was 88% and, in the group of transparent, 24%. Conclusion: The use of colorings in eye drops can help distinguishing the vials and preventing misidentification.

Contaminação microbiana em colírios de pacientes em tratamento de glaucoma / Microbial contamination in eye drops of patients in glaucoma treatment

Resumo Objetivos: Avaliar o grau de contaminação por fungos e bactérias e o modo de conservação destes colírios hipotensores por parte dos pacientes no ambulatório de Glaucoma da Santa Casa de Ribeirão Preto. Métodos: Foram selecionados aleatoriamente cinquenta e cinco pacientes, em seguimento no ambulatório, e após consentimento dos mesmos os colírios eram coletados e enviados via correio para análise por microbiologista e patologista em até 72 horas. Foi analisado 0,5ml aproximadamente das medicações e os pacientes respondiam a um questionário simples sobre o método de conservação e se consideravam estes adequados. Resultados: Dos 55 colírios analisados, cinco (9,01%) estavam com seu conteúdo líquido contaminado. Entre os microrganismos isolados haviam 4 bactérias Gram negativas, sendo 1 (1,8%) por Serratia marcescens, 1 (1,8%) Pseudomonas aeruginosa e 2 (3,6%) Stenotrophomas maltophilia. Um colírio estava contaminado pelo fungo Cândida ssp Todos pacientes do estudo julgam seus métodos de armazenamento e instilação adequados. Os pacientes que tiveram os colírios positivados eram convocados para exame clínico e passavam por novo questionário pelo investigador. Conclusão: O tempo de abertura dos frascos e os métodos de conservação influenciam na contaminação dos medicamentos, todos os colírios com crescimento de microrganismos no presente estudo estavam abertos entre 30 e 90 dias. O fato de que a maioria dos pacientes levam seus colírios em tarefas cotidianas, aumenta a exposição dos frascos e podem ser um fator relevante para determinar a contaminação destas medicações.

Abstract Objetives: To assess the degree of fungal and bacterial contamination of hypotensive eye drops and the way these are preserved by the patients at the Glaucoma outpatient clinic of Santa Casa Hospital in Ribeirão Preto. Methods: Fifty-five patients were randomly assigned to follow-up in the outpatient clinic and, after their consent, an eye drop was collected per patient and later sent by mail for analysis by microbiologist and pathologist in up to 72 hours. Approximately 0.5ml of the medications were analyzed and the patients were asked to answer a simple questionnaire on the method of drug conservation and whether they considered it adequate. Results: Of the 55 analysed eye drops, five (9.01%) had their liquid contents contaminated. Among the microorganisms isolated there were 4 Gram negative bacteria, 1 (1.8%) by Serratia marcenses, 1 (1.8%) Pseudomonas aeruginosa and 2 (3.6%) Stenotrophomas maltophilia. An eye drop was contaminated by the fungus Candida ssp. All the patients in the study judged their methods of storage and instillation appropriate. The patients who had the positive coliria were summoned for clinical examination and passed through a new questionnaire by the investigator. Conclusion: The time and methods of preservation influence the contamination of medicinal products. All the eye drops that presented growth of microorganisms in the present study were open between 30 and 90 days. The fact that most patients take their eye drops on daily tasks increases the exposure of the bottles and can be a relevant fact to determine the contamination of these medications.

Effect of the bioprotectant agent trehalose on corneal epithelial healing after corneal cross-linking for keratoconus / Efeito do agente bioprotetor trealose na cicatrização epitelial da córnea após reticulação corneana para ceratocone

ABSTRACT Purpose: This study aimed to compare the effectiveness of eye drops containing a combination of sodium hyaluronate and trehalose and sodium hyaluronate for the treatment of corneal cross-linking and epithelial healing. Methods: This study included 46 eyes of 23 keratoconus patients who underwent corneal cross-linking on both eyes. Unpreserved trehalose 30 mg/mL and sodium hyaluronate 1.5 mg/mL (Thealoz Duo®; Thea, France) were applied six times a day on one eye of each patient and unpreserved sodium hyaluronate 0.15% (Eye Still®; Teka, Inc., Istanbul) was applied on the other eye. Patients were examined daily until complete re-epithelialization. Postoperative examinations to assess the measured size of epithelial defect were performed using slit-lamp biomicroscopy. Results: The study included 23 patients (13 females and 10 males) with a mean age of 20.9 ± 10.3 years. Corneal epithelial healing time after cross-linking was 2.3 ± 1.2 days for the trehalose and sodium hyaluronate group and 3.8 ± 2.9 days for the sodium hyaluronate group (p=0.03). Conclusion: The application of eye drops containing the combination of trehalose and sodium hyaluronate resulted in faster corneal re-epithelialization following corneal cross-linking than that of eye drops containing sodium hyaluronate alone.

RESUMO Objetivo: Este estudo teve como objetivo comparar a eficácia de colírios contendo uma combinação de hialurônico de sódio e hialuronato de sódio e trealose para o tratamento da cicatrização epitelial em pacientes com cross-linking corneano. Métodos: Este estudo inclui 46 olhos de 23 pacientes com ceratocone, que foram operados com cross-linking corneano em ambos os olhos. Trealose não preservada 30 mg/mL e hialuronato de sódio 1,5 mg/mL (Thealoz Duo®; Thea, França) foram aplicados seis vezes por dia em um olho de cada paciente e hialuronato de sódio não conservado, 0,15% (Eye Still®; Teka, Inc., Istambul) foi aplicada no outro olho. Os pacientes foram examinados diariamente até a completa reepitelização. Exames pós-operatórios para avaliar o tamanho medido do defeito epitelial foram realizados usando biomicroscopia com lâmpada de fenda. Resultados: O estudo incluiu 23 pacientes (13 mulheres e 10 homens) com idade média de 20,9 ± 10,3. O tempo de cicatrização epitelial da córnea após o cross-linking foi de 2,3 ± 1,2 dias para o grupo trealose e hialuronato de sódio e 3,8 ± 2,9 dias para o grupo hialurônico de sódio (p=0,03). Conclusão: A aplicação de gotas para os olhos contendo combinação de trealose e hialuronato de sódio resultou em uma re-epitelização da córnea mais rápida após o cross-linking corneano do que a de gotas contendo hialurônico de sódio apenas.

The relationship between topical anti-glaucoma medications and the development of lacrimal drainage system obstruction / A relação entre medicamentos tópicos anti-glaucoma e o desenvolvimento de obstrução do sistema de drenagem lacrimal

ABSTRACT Purpose: To evaluate whether any topical anti-glaucoma medications increase the risk of lacrimal drainage system obstruction or whether the presence of preservatives alone is sufficient to generate obstruction. Methods: This nested case-control study compared a group of patients with lacrimal duct obstruction who received topical anti-glaucoma medications to a control group of patients without obstruction. Results: The medical records of 255 patients with glaucoma who consulted the Oculoplastic Section with complaints of watery eyes were reviewed. Among these patients, 59 exhibited lacrimal drainage obstruction. Ninety-four percent of patients with lacrimal drainage obstruction used beta-blockers, and 41% used prostaglandin analogs. A logistic regression model was used to adjust for age, sex, and the use of other medications. No significant differences were observed regarding the topical anti-glaucoma medications used between groups. Conclusion: No single topical anti-glaucoma medication demonstrated a stronger association with the development of lacrimal duct obstruction.

RESUMO Objetivo: Avaliar se algum medicamento tópico anti-glaucoma aumenta o risco de obstrução do sistema de drenagem lacrimal ou se a presença de conservantes é su fi cien te para gerar obstrução. Métodos: Este estudo de caso-controle aninhado comparou um grupo de pacientes com obstrução do ducto lacrimal que receberam medicações tópicas anti-glaucoma contra um grupo controle de pacientes sem obstrução. Resultados: Foram revistos os prontuários de 255 pacientes com glaucoma que consultaram a Seção de Oculoplástica com queixas de olhos lacrimejantes. Dentre esses pacientes, 59 apresentavam obstrução da via lacrimal de drenagem. Noventa e quatro por cento dos pacientes com obstrução usaram betabloqueadores e 41% usaram análogos de prostaglandinas. Um modelo de regressão logística foi utilizado para ajustar a idade, sexo e o uso de outros medicamentos. Não foram observadas diferenças significativas em relação às medicações tópicas anti-glaucoma usadas entre os grupos. Conclusão: Nenhum medicamento anti-glaucoma tópico único demonstrou uma associação mais forte com o desenvolvimento de obstrução do ducto lacrimal.

Comparison of the efficacy of 0. 03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs / Comparação do colírio tacrolimus 0, 03% em óleo de oliva e linhaça no tratamento da ceratoconjuntivite seca em cães

ABSTRACT Objective: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. Results: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. Conclusion: In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% colírio, diluído em óleo de linhaça e óleo de oliva, no tratamento de ceratoconjuntivite seca em cães. Métodos: Foram utilizados 60 cães; 20 cães saudáveis como grupo controle, e 40 cães com diagnóstico de ceratoconjuntivite seca bilateral, distribuídos aleatoriamente em dois grupos: Tacrolimus em óleo de oliva (TO) e Tacrolimus em óleo de semente de linhaça (TL). Os animais foram avaliados mensalmente com exames oftálmicos, Teste lacrimal de Schirmer-1 (TLS-1), Tempo de ruptura do filme lacrimal (TRFL) e Teste de Fluoresceína (TF), e mensalmente com citologia conjuntival e com exame histopatológico no início e final do estudo. Resultados: Nos dois grupos de tratamento os sinais clínicos, Teste lacrimal de Schirmer-1, óleo de semente de linhaça e Tempo de ruptura do filme lacrimal apresentaram melhora após um mês de tratamento. E no final do estudo, na análise citológica, ambos apresentaram diminuição de linfócitos, neutrófilos, células metaplásicas e células escamosas, e na análise histopatológica houve diminuição de linfócitos, neutrófilos e o aumento de células caliciformes. No grupo óleo de semente de linhaça, a diminuição de neutrófilos foi mais significativa (p<0,05) em ambas análises. Conclusão: Em suma, tacrolimus 0,03% colírio diluído em óleo de oliva e óleo de linhaça foram eficientes no tratamento de ceratoconjuntivite seca. Nenhum dos parâmetros avaliados diferiu significativamente entre os dois grupos, exceto a contagem de neutrófilos, que foi significativamente menor no grupo TL. Assim, o óleo de linhaça pode ser considerado como um diluente alternativo para o colírio tacrolimus.

Case series of children with steroid-Induced glaucoma

@#Steroid-induced glaucoma is the most serious complication of the injudicious use of steroids, particularly among children affected by allergic conjunctivitis. This condition is steroid-dependent, and children are commonly being prescribed topical anti-inflammatories, including topical steroids, by general practitioners. Furthermore, topical steroids are also available over the counter, and this availability contributes to overuse without proper monitoring by an ophthalmologist. We present a series of five cases illustrating the devastating effect of unmonitored, long-term use of steroids among children for vernal keratoconjunctivitis. The medications were prescribed initially by general ophthalmologists and were continually bought over the counter by parents. At the presentation to our center, these patients were already compromised visually, exhibiting glaucomatous optic disc changes and high intraocular pressure. The series highlights the optic nerve damage resulting in irreversible visual compromises among children on long-term, topical steroids and the importance of regular monitoring with a low threshold for ophthalmologist referral.

Aqueous humor concentrations of topical fluoroquinolones alone or in combination with a steroid / Concentração de fluorquinolonas no humor aquoso após instilação tópica das associações com corticosteroides

ABSTRACT Purpose: To compare the aqueous humor (AH) concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% solutions alone or when treatment was combined with steroids, and to correlate these concentrations with the minimum inhibitory concentrations (MIC) for the most common endophthalmitis-causing organisms. Methods: Patients undergoing phacoemulsification were enrolled to receive one drop of one of the following solutions: moxifloxacin (G1), moxifloxacin + dexamethasone (G2), gatifloxacin (G3), or gatifloxacin + c (G4), every 15 min, 1h before surgery. AH samples were collected before surgery and analyzed using HPLC-tandem mass spectrometry. Results: The mean antibiotic concentrations in the AH were: G1= 1280.8 ng/mL; G2= 1644.3 ng/mL; G3= 433.7 ng/mL; and G4= 308.1 ng/mL. The mean concentrations statistically differed between G1 and G2 (p=0.01), and G3 and G4 (p=0.008). All samples achieved the MIC for Staphylococcus epidermidis; 100% of the samples from G1 and G2, and 97% from G3 and G4 reached the MIC for fluoroquinolone-sensitive Staphylococcus aureus; 100% of the samples from G1 and G2, 88% from G3, and 72% from G4 reached the MIC for enterococci (p<0.001); and 100% of samples from G1 and G2, 59% from G3, and 36% from G4 reached the MIC for Streptococcus pneumoniae (p<0.001). For fluoroquinolone-resistant S. aureus, 23% from G1, 44% from G2, and no samples from G3 or G4 achieved the MIC (p<0.001). Conclusions: Moxifloxacin + dexamethasone demonstrated a higher concen­tration in the AH than the moxifloxacin alone. Gatifloxacin + steroids demonstrated less penetration into the anterior chamber than gatifloxacin alone. Moxifloxacin was superior to gatifloxacin considering the MIC for enterococci, S. pneumoniae, and fluoroquinolone-resistant S. aureus.

RESUMO Objetivos: Comparar a concentração no humor aquoso entre as soluções de moxifloxacina 0,5% e gatifloxacina 0,3% sozinhas ou combinadas com corticosteroides, e correlacionar a concentração com a concentração inibitória mínima (MIC) para os agentes microbianos mais comumente relacionados a endoftalmites. Métodos: Pacientes que seriam submetidos a cirurgia de catarata foram selecionados para receber 1 gota a cada 15 min, 1 hora antes do procedimento de uma das seguintes soluções: moxifloxacina (G1), moxifloxacina + dexametasona (G2), gatifloxacina (G3) ou gatifloxacina + prednisolona (G4). Amostras do humor aquoso foram coletadas antes do início da cirurgia. Espectrofotometria de massa por HPLC determinou a concentração do antibiótico nas amostras. Resultados: A concentração media de antibiótico nas amostras foram: G1= 1280,8 ng/mL; G2= 1644,3 ng/mL; G3= 433,7 ng/mL; G4= 308,1 ng/mL. Concentração média entre G1 e 2 (p=0,01), e G3 e 4 (p=0,008). Todas as amostras alcançaram MIC para S. epidermidis; 100% das amostras do G1 e 2, e 97% do G3 e 4 atingiram o MIC para S. aureus fluoroquinolona-sensível; 100% das amostras do G1 e 2, 88% do G3 e 72% do G4 atingiram o MIC para Enterococci (p<0,001); e 100% das amostras do G1 e 2, 59% do G3 e 36% do G4 atingiram o MIC para S. pneumoniae (p<0,001). Para o S. aureus resistente a fluoroquinolona, 23% do G1, 44% do G2, e nenhuma das amostras G3 e 4 atingiram o MIC (p<0,001). Conclusão: Moxifloxacina + dexamethasona demonstrou maior concentração no humor aquoso comparado com a moxifloxacina sozinha. Gatifloxacina + esteróide demonstrou menor penetração na câmara anterior comparado a solução de ga­ti­floxacin sem corticóide. A moxifloxacina foi superior a gatifloxacina considerando o MIC para Enterococci, S. pneumoniae e S. aureus fluorquinolona resistente.

Assessment of eye drop instillation technique in glaucoma patients / Técnica de instilação de colírio em pacientes com glaucoma

ABSTRACT Purpose: To study the technique of eye drop instillation in glaucoma patients and identify independent factors that may influence their performance. Methods: In this cross-sectional study, 71 consecutive patients with glaucoma or ocular hypertension, self-administering topical anti-glaucoma medications for ≥6 months were evaluated. All patients instilled a tear substitute into the eye with the worst eyesight using the technique normally used at home. The following parameters were evaluated: age, number of years receiving treatment with ocular hypotensive eye drops, time spent to instill the first drop, number of drops instilled, correct location of the eye drops, contact of the bottle with the eye, closing of the eyelids or occlusion of the tear punctum, and asepsis of the hands. Results: The mean age of the patients was 66 ± 10.8 years, and patients were on ocular hypotensive drugs for 11.3 ± 7.3 (range, 2-35) years. Only 28% of the patients were able to correctly instill the eye drops (squeeze out 1 drop and instill it into the conjunctival sac without bottle tip contact). Touching the tip of the bottle to the globe or periocular tissue occurred in 62% of the patients. In 49% of the patients, the eye drops fell on the eyelids or cheek. Two or more drops were squeezed by 27% of the patients. Conclusions: The majority of glaucoma patients were unable to correctly instill eye drops. Age was an independent factor associated with eye drop instillation performance.

RESUMO Objetivo: Avaliar a técnica de instilação de colírio em portadores de glaucoma e identificar fatores independentes que pode influenciar o desempenho. Métodos: Neste estudo transversal 71 pacientes consecutivos com glaucoma ou hipertensão ocular que auto instilam seus colírios há pelo menos 6 meses, foram avaliados. Todos os pacientes instilaram um colírio lubrificante no olho de pior visão utilizando a mesma técnica de instilação de colírio que utilizam rotineiramente em casa. Foram avaliados parâmetros como: idade, número de anos em tratamento com colírios hipotensores oculares, tempo gasto para instilação da primeira gota, número de gotas instiladas, localização correta do colírio, contato do frasco com o olho, fechamento de pálpebras ou oclusão do ponto lacrimal e assepsia das mãos. Resultados: A idade média dos pacientes foi de 66 ± 10,8 anos. Os pacientes esta vam em tratamento com colírios hipotensores oculares por, em média, 11,3 ± 7,3 anos (variando de 2 a 35 anos). Apenas 28% dos pacientes foram capazes de instilar corretamente o colírio (instilação de 1 gota em saco conjuntival sem contato com a ponta do frasco). Contato da ponta do frasco com o olho ou tecido periocular ocorreu em 62% dos pacientes. Em 49% dos casos, o colírio caiu nas pálpebras ou fora do saco lacrimal na primeira tentativa. Duas ou mais gotas foram instiladas por 27% dos pacientes. Conclusão: A maioria dos pacientes com glaucoma é incapaz de instilar o colírio corretamente. A idade é um fator independente que influencia o desempenho da instilação de colírio.