Effects of benzalkonium chloride and cyclosporine applied topically to rabbit conjunctiva: a histomorphometric study / Efeitos do uso tópico do conservante cloreto de benzalcônio e ciclosporina na conjuntiva de coelhos: estudo histomorfométrico

ABSTRACT Purpose: Chronic instillation of benzalkonium chloride, a preservative, has inflammatory effects on the ocular surface. However, addition of the anti-inflammatory agent cyclosporine to a therapeutic protocol may mitigate these effects. This study compared the toxic effects of a 0.1% benzalkonium chloride solution and the possible protective effect of 0.05% cyclosporine when applied topically to the rabbit conjunctiva. Methods: Fifteen age- and weight-matched, female New Zealand white rabbits were categorized into three groups and treated for 30 consecutive days. Group 1, 2, and 3 - benzalkonium chloride received 0.1% every 24 h, 0.05% cyclosporine every 6 h, and both treatments, respectively. In each rabbit, the left eye was subjected to treatment and the right eye was a control. The rabbits were euthanized at after the experiment. Goblet cells and blood vessels were then enumerated in conjunctival tissues stained with periodic acid-Schiff and hematoxylin-eosin, respectively. Differences between treated and untreated eyes and between groups were compared using the t-test and analysis of variance. Results: Benzalkonium chloride treatment, with and without cyclosporine, significantly reduced (p≤0.05) in the number of goblet cells in treatment eyes compared with that in respective control eyes. Alternatively, adding cyclosporine to benzalkonium chloride did not prevent the loss of conjunctival goblet cells, and a significant reduction in the number of goblet cells was noted. Benzalkonium chloride-induced significant increase in the number of new blood vessels was mitigated significantly by the addition of cyclosporine. Conclusion: This study demonstrated the magnitude of conjunctival injury caused by chronic instillation of benzalkonium chloride. Although cyclosporine did not mitigate the effects on goblet cells, its addition minimized inflammatory angiogenesis induced by benzalkonium chloride.

RESUMO Objetivo: A instilação crônica de cloreto de benzal­cônio, um conservante, tem efeitos inflamatórios na superfície ocular. No entanto, a adição do agente anti-inflamatório ciclosporina a um protocolo terapêutico pode atenuar esses efeitos. Este estudo comparou os efeitos tóxicos de uma solução de cloreto de benzalcônio a 0,1% e o possível efeito protetor de ciclosporina a 0,05% quando aplicado topicamente à conjuntiva de coelho. Métodos: Quinze coelhos fêmeas brancos da raça Nova Zelândia, pareados por idade e peso, foram categorizados em três grupos e tratados por 30 dias consecutivos. Os grupos 1, 2 e 3 - receberam cloreto de benzalcônio 0,1% a cada 24h, ciclosporina a 0,005% a cada 6h e ambos os tratamentos, respectivamente. Em cada coelho, o olho esquerdo foi submetido a tratamento e o olho direito foi controle. Os coelhos foram submetidos à eutanásia após o experimento. Células caliciformes e vasos sanguíneos foram então enumerados em tecidos conjuntivais corados com ácido periódico-Schiff e hematoxilina-eosina, respectivamente. As diferenças entre os olhos tratados e não tratados e entre os grupos foram comparadas usando o teste t e análise de variância. Resultados: O tratamento com cloreto de benzalcônio, com e sem ciclosporina, reduziu significativamente (p£0,05) o número de células caliciformes nos olhos tratados em comparação com os olhos controle correspondentes. Alternativamente, a adição de ciclosporina ao cloreto de benzalcônio não impediu a perda de células caliciformes conjuntivais, e foi observada uma redução significativa no número de células caliciformes. O aumento significativo induzido pelo cloreto de benzalcônio no número de novos vasos sanguíneos foi significativamente mitigado pela adição da ciclosporina. Conclusão: Este estudo demonstrou a magnitude da lesão conjuntival resultante da instilação crônica de cloreto de benzalcônio. Embora a ciclosporina não tenha atenuado os efeitos nas células caliciformes, sua adição minimizou a angiogênese inflamatória induzida pelo cloreto de benzalcônio.

Effects of benzalkonium chloride and cyclosporine applied topically to rabbit conjunctiva: a histomorphometric study.

PURPOSE: Chronic instillation of benzalkonium chloride, a preservative, has inflammatory effects on the ocular surface. However, addition of the anti-inflammatory agent cyclosporine to a therapeutic protocol may mitigate these effects. This study compared the toxic effects of a 0.1% benzalkonium chloride solution and the possible protective effect of 0.05% cyclosporine when applied topically to the rabbit conjunctiva. METHODS: Fifteen age- and weight-matched, female New Zealand white rabbits were categorized into three groups and treated for 30 consecutive days. Group 1, 2, and 3 - benzalkonium chloride received 0.1% every 24 h, 0.05% cyclosporine every 6 h, and both treatments, respectively. In each rabbit, the left eye was subjected to treatment and the right eye was a control. The rabbits were euthanized at after the experiment. Goblet cells and blood vessels were then enumerated in conjunctival tissues stained with periodic acid-Schiff and hematoxylin-eosin, respectively. Differences between treated and untreated eyes and between groups were compared using the t-test and analysis of variance. RESULTS: Benzalkonium chloride treatment, with and without cyclosporine, significantly reduced (p≤0.05) in the number of goblet cells in treatment eyes compared with that in respective control eyes. Alternatively, adding cyclosporine to benzalkonium chloride did not prevent the loss of conjunctival goblet cells, and a significant reduction in the number of goblet cells was noted. Benzalkonium chloride-induced significant increase in the number of new blood vessels was mitigated significantly by the addition of cyclosporine. CONCLUSION: This study demonstrated the magnitude of conjunctival injury caused by chronic instillation of benzalkonium chloride. Although cyclosporine did not mitigate the effects on goblet cells, its addition minimized inflammatory angiogenesis induced by benzalkonium chloride.

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 the ocular surface after three months of glaucoma treatment.

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 ...

Level of agreement among Latin American glaucoma subspecialists on the diagnosis and treatment of glaucoma: results of an online survey.

PURPOSE: The aim of this research was to assess the level of agreement among glaucoma experts in Latin America on key practices related to treatment and diagnosis of glaucoma. METHODS: An online questionnaire was sent to a multinational panel of glaucoma experts. The questionnaire contained 107 statements on the medical treatment (Part 1) and diagnosis (Part 2) of glaucoma, and was developed in Spanish and translated into English. Agreement was defined as >70% of respondents. RESULTS: Fifty participants from 14 countries completed the questionnaire. For the medical treatment of glaucoma, nearly all respondents (98% or greater) confirmed that medical treatment as first-line therapy is preferred to surgery, prostaglandin analogs are the medication of first choice for primary open-angle glaucoma (POAG), longitudinal monitoring of efficacy should include intraocular pressure, structural and functional status, as well as if patients' quality of life is impaired by the high cost of medication. For the diagnosis of glaucoma section, all respondents confirmed that, after initial examination, gonioscopy should be repeated over time, standard automated perimetry is the most important functional examination for diagnosis and monitoring of primary open-angle glaucoma, central corneal thickness is important in assessment of glaucoma, and computerized imaging tests help in clinical evaluation of optic disc. CONCLUSIONS: This survey shows a high level of agreement on most aspects of glaucoma diagnosis and treatment among Latin American glaucoma experts. Areas of disagreement highlight the need for further evidence or education. These findings will be useful for guiding future efforts to optimize glaucoma practice by clinicians in Latin America.

Level of agreement among Latin American glaucoma subspecialists on the diagnosis and treatment of glaucoma: results of an online survey / Nível de concordância entre subespecialistas de glaucoma latino-americanos sobre o diagnóstico e tratamento do glaucoma: resultados de uma pesquisa digital

PURPOSE: The aim of this research was to assess the level of agreement among glaucoma experts in Latin America on key practices related to treatment and diagnosis of glaucoma. METHODS: An online questionnaire was sent to a multinational panel of glaucoma experts. The questionnaire contained 107 statements on the medical treatment (Part 1) and diagnosis (Part 2) of glaucoma, and was developed in Spanish and translated into English. Agreement was defined as >70% of respondents. RESULTS: Fifty participants from 14 countries completed the questionnaire. For the medical treatment of glaucoma, nearly all respondents (98% or greater) confirmed that medical treatment as first-line therapy is preferred to surgery, prostaglandin analogs are the medication of first choice for primary open-angle glaucoma (POAG), longitudinal monitoring of efficacy should include intraocular pressure, structural and functional status, as well as if patients' quality of life is impaired by the high cost of medication. For the diagnosis of glaucoma section, all respondents confirmed that, after initial examination, gonioscopy should be repeated over time, standard automated perimetry is the most important functional examination for diagnosis and monitoring of primary open-angle glaucoma, central corneal thickness is important in assessment of glaucoma, and computerized imaging tests help in clinical evaluation of optic disc. CONCLUSIONS: This survey shows a high level of agreement on most aspects of glaucoma diagnosis and treatment among Latin American glaucoma experts. Areas of disagreement highlight the need for further evidence or education. These findings will be useful for guiding future efforts to optimize glaucoma practice by clinicians in Latin America.

OBJETIVO: Avaliar o nível de concordância entre os especialistas de glaucoma na América Latina sobre as práticas mais importantes relacionadas ao tratamento e diagnóstico de glaucoma. MÉTODOS: Um questionário digital foi enviado a um painel multinacional de especialistas em glaucoma. O questionário continha 107 declarações sobre o tratamento médico (Parte 1) e diagnóstico (Parte 2) de glaucoma, e foi desenvolvido em espanhol e traduzido para o Inglês. Concordância foi definida como > 70% dos entrevistados. RESULTADOS: Cinquenta participantes de 14 países responderam ao questionário. Para o tratamento médico de glaucoma, quase todas as respostas (98% ou mais), confirmaram que o tratamento médico como terapia de primeira linha é preferido para a cirurgia, os análogos das prostaglandinas são os medicamentos de primeira escolha para o glaucoma primário de ângulo aberto (GPAA), a monitoração longitudinal eficácia deve incluir a pressão intraocular o estado estrutural e funcional além da qualidade de vida do paciente ser prejudicada pelo alto custo da medicação. Para a seção sobre o diagnóstico de glaucoma, todos os entrevistados confirmaram que, após análise inicial, a gonioscopia deve ser repetida ao longo do tempo, a perimetria automatizada padrão é o exame funcional mais importante para o diagnóstico e monitoramento do glaucoma primário de ângulo aberto, a espessura corneana central é importante na avaliação do glaucoma e exames de imagem computadorizados ajudam na avaliação clínica do disco óptico. CONCLUSÕES: Este estudo mostra um alto nível de concordância na maioria dos aspectos do diagnóstico e tratamento de glaucoma entre os especialistas em glaucoma latino-americanos. Áreas de desacordo destacam a necessidade de novas evidências ou educação. Estes resultados serão úteis para orientar futuros esforços na otimização de práticas em relação ao glaucoma por médicos da América Latina.