Effects of Chloroquine and Hydroxychloroquine on the Cardiovascular System - Limitations for Use in the Treatment of COVID-19

Abstract Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs, with anti-inflammatory properties that justify their use in the treatment of systemic lupus erythematosus and rheumatic diseases. A pandemic caused by the new coronavirus led the entire world's scientific community to look for drugs already available on the market, capable of exercising beneficial actions in the fight against the disease. Preliminary studies in patients, as well as in vitro studies, suggested possible therapeutic effects associated with the use of HCQ and CQ in the treatment of COVID-19. Despite controversies over the effects of these drugs in combating the "cytokine storm" associated with COVID and the dismal of results in different clinical trials in Brazil, their use has been encouraged and several ongoing investigative studies are underway. In addition to the possible beneficial effects on the prognosis of patients with SARS-CoV-2, such drugs include varied effects on the cardiovascular system, ranging from positive developments related to their vasodilator properties to potential negative effects, such as cardiotoxicity. This work presents the main effects exerted by these drugs on the cardiovascular system, in order to contribute to a scientific discussion about the repurposing of these drugs in the context of COVID-19.

Cloroquina e hidroxicloroquina: medicamentos potencialmente inapropriados a idosos? / Chloroquine and hydroxychloroquine: potentially inappropriate medications for older adults?

INTRODUÇÃO: Medicamentos potencialmente inapropriados a idosos (MPII) provocam mais efeitos adversos do que benefícios. Os critérios de Beers (CB) da American Geriatrics Society 2019 (CB2019) consideraram cinco situações clínicas como MPII. A análise de medicamentos por essas situações pode auxiliar na prescrição a idosos? Procurando exemplo prático dessa questão, optou-se por análise de fármacos atualmente questionados quanto ao seu uso seguro em idosos. OBJETIVO: Verificar se cloroquina e hidroxicloroquina se enquadram como MPII e se essa análise é aplicável clinicamente. METODOLOGIA: Sistematizou-se o objetivo pelas cinco situações clínicas definidas como MPII pelos CB2019. RESULTADOS: Ambos os fármacos preenchem respectivamente quatro (cloroquina) e cinco (hidroxicloroquina) dessas situações clínicas. Esta análise permitiu a provável definição de MPII para esses medicamentos de forma simples, por intermédio de breve análise de literatura acessível. CONCLUSÃO: Cloroquina e hidroxicloroquina podem ser considerados MPII. Espera-se replicar essa análise para outros medicamentos e reduzir iatrogenias em idosos.

INTRODUCTION: Potentially inappropriate medications (PIMs) for older adults cause more adverse effects than benefits. The 2019 American Geriatrics Society Beers Criteria (2019BC) considered five clinical situations as PIM use in older adults. Can drug analysis, according to these situations, assist in the act of making prescriptions for older people? Seeking a practical example for this question, we assessed drugs currently questioned as to their safe use among older people. OBJECTIVE: To check if chloroquine and hydroxychloroquine fit the PIM criteria for older adults and whether this analysis is clinically applicable. METHODS: We systematized the objective based on the five clinical situations defined as PIM use in older adults by the 2019BC. RESULTS: Chloroquine and hydroxychloroquine fulfill, respectively, four and five of these clinical situations. This evaluation allowed the likely definition of these drugs as PIMs for older adults in a simple way, based on a brief analysis of the available literature. CONCLUSION: Chloroquine and hydroxychloroquine may be considered PIMs for older adults. We expect that this analysis can be replicated with other drugs and reduce iatrogenesis in older people.

Seguridad de la cloroquina y la hidroxicloroquina para el tratamiento de pacientes con COVID-19 / Safety of chloroquine and hydroxychloroquine for treating COVID-19 patients

Introducción: La cloroquina y su análogo hidroxicloroquina han mostrado presentar efectos antivirales y antiinflamatorios, por lo que podría ser una alternativa de tratamiento ante el nuevo coronavirus SARS-CoV-2. Objetivo: Describir seguridad de la cloroquina e hidroxicloroquina para el tratamiento de la COVID-19 según la evidencia científica actual. Método: Se empleó la estrategia de búsqueda coronavirus OR COVID-19 OR SARS-CoV2 AND Cloroquina AND Hidroxicloroquina y se utilizaron las bases de datos Pubmed, SciELO, Lilacs, Cochrane Library y Web of Science. Se obtuvo un total de 32 referencias bibliográficas, seleccionándose a partir de criterios de selección. Conclusiones: La eficacia de la cloroquina y la hidroxicloroquina no ha sido probada del todo, pues los resultados no han sido concluyentes y se ha encontrado diferencias entre ellos, además de que no se han estudiado muestras suficientemente representativas. Las reacciones adversas de este medicamento, siendo las cardiovasculares las más peligrosas, no se deben ignorar ya que se han presentado con cierta frecuencia y en relación con la dosis administrada. Por ello, es necesario la realización de más ensayos clínicos aleatorizados, con mayor control de sesgos y muestras representativas, que evalúen la eficacia y seguridad de este medicamento(AU)

Introduction: Chloroquine and its analogue hydroxychloroquine have shown antiviral and anti-inflammatory effects, so it could be an alternative treatment to the new SARS-CoV-2 coronavirus. Objective: To describe the safety of chloroquine and hydroxychloroquine for treating COVID-19 according to current scientific evidence. Method: We used the search strategy for coronavirus OR COVID-19 OR SARS-CoV2 AND Chloroquine AND Hydroxychloroquine, and Pubmed, SciELO, Lilacs, Cochrane Library and Web of Science databases were used. Thirty two bibliographic references were recovered, selection followed the selection criteria. Conclusions: The efficacy of chloroquine and hydroxychloroquine has not been fully proven, since the results have not been conclusive and differences have been found between them, In addition to the fact that sufficiently representative samples have not been studied. The adverse reactions of these drugs, and the cardiovascular ones are the most dangerous, should not be ignored since they have occurred with certain frequency and in relation to the administered dose. Therefore, it is necessary to carry out more randomized clinical trials, with greater control of biases and representative samples, to evaluate the efficacy and safety of these drugs(AU)

Hidroxicloroquina: Mensajes desde la cardiología en tiempos de pandemia por Coronavirus / Hydroxychloroquine. Cardiology's viewpoint in times of coronavirus pandemic

Ante la pandemia de COVID-19 (del inglés coronavirus disease 2019), uno de los fármacos propuesto para su tratamiento es la hidroxicloroquina. Se revisan aquí aspectos cardiológicos del uso de cloroquina e hidroxicloroquina. Se realizó una revisión no sistemática en la literatura médica orientada a la búsqueda de información acerca de su seguridad y eficacia como antimaláricos y antivirales, así como en el tratamiento prolongado de enfermedades reumatológicas. Se halló un efecto antiinflamatorio con reducción de eventos cardiovasculares a largo plazo, una cardiopatía muy infrecuente por un efecto lisosomal del fármaco, y a nivel hemodinámico hipotensión, taquicardia, y prolongación del intervalo QT, exacerbado si se combina con azitromicina. Sin embargo, la tasa de eventos adversos cardíacos de la hidroxicloroquina y la cloroquina fue baja.

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of long-term cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.

Efetividade e toxicidade da cloroquina e da hidroxicloroquina associada (ou não) à azitromicina para tratamento da COVID-19. O que sabemos até o momento? / Effectiveness and toxicity of chloroquine and hydroxychloroquine associated (or not) with azithromycin for the treatment of COVID-19. What do we know so far?

Objetivos: identificar as evidências científicas existentes até o presente momento sobre a efetividade do uso da cloroquina, da hidroxicloroquina associada (ou não) à azitromicina para tratamento da afecção pelo coronavírus e seus possíveis efeitos adversos e tóxicos aos seres humanos. Métodos: a revisão narrativa utilizou-se das bases de dados PubMed, LILACS, SciElo e Google Acadêmico. Nessas, buscaram-se estudos, utilizando-se dos descritores "covid", "coronavirus", "SARS-CoV-2", "chloroquine", "hydroxychloroquine", "azithromycin" e "adverse effects" junto com os operadores booleanos "AND" e "OR". Resultados: sete artigos, das trinta publicações encontradas, atenderam aos critérios de inclusão, sendo utilizados para compor a presente revisão. Dos sete ensaios clínicos analisados, cinco apresentaram resultados de cura e/ou remissão dos sintomas e/ou redução da carga viral dos pacientes, no entanto apresentaram muitas limitações. Conclusão: a literatura científica é escassa e divergente quanto à efetividade dos medicamentos cloroquina e hidroxicloroquina associada (ou não) à azitromicina no tratamento da COVID-19, pela rápida disseminação e instalação da pandemia na esfera global. É necessário a realização de ensaios clínicos pragmáticos, envolvendo um número maior de pacientes, para que seja possível analisar a efetividade no combate ao coronavírus, bem como a segurança do uso desses fármacos.(AU)

Objective: to identify the scientific evidence existing to date on the effectiveness of the use of chloroquine, hydroxychloroquine associated (or not) to azithromycin for the treatment of COVID-19 disease and its possible adverse drug events and toxicity to human health. Methods: the narrative review was performed using the PubMed, LILACS, SciElo and Google Academic databases. In these, studies were sought, using the descriptors "covid", "coronavirus", "SARS-CoV-2", "chloroquine", "hydroxychloroquine", "azithromycin", "adverse effects" and "toxicity", together with the Boolean operator "AND" and "OR". Results: seven studies of thirty publications met the inclusion criteria and were used in the present review. Of the seven clinical trials analyzed, five showed results of cure and/or remission of symptoms and/or reduction of patients' viral load, however these studies had many limitations. Conclusion: scientific literature is scarce and divergent as to the effectiveness of the drugs chloroquine and hydroxychloroquine associated (or not) with azithromycin in the treatment of COVID-19, due to the rapid spread and installation of the pandemic in the global sphere. It is necessary to carry out pragmatic clinical trials, involving a larger number of patients, so that it is possible to analyze the effectiveness in combating the coronavirus, as well as the safety of the use of these drugs.(AU)

El escándalo de la cloroquina / The chloroquine scandal

El autor aborda el caso de la cloroquina y la hidroxicloroquina en el contexto de la actual pandemia de COVID-19, a través de dos ejes centrales. Por un lado, el escándalo a nivel editorial y de comunicación de la evidencia, y por otro, el de la toma de decisiones en salud pública. Describe flagrantes debilidades en la cadena de generación, difusión y aplicación del nuevo conocimiento. Adicionalmente, explora iniciativas y propuestas que podrían contribuir a solucionar estos problemas. (AU)

The author addresses the case of chloroquine and hydroxychloroquine in the context of the current COVID-19 pandemic, through two central axes. On the one hand, the scandal at the editorial and communication level of the evidence, and on the other, that of decision-making in public health. He describes flagrant weaknesses in the chain of generation, diffusion,and application of new knowledge. Additionally, it explores initiatives and proposals that could contribute to solving these problems. (AU)

Primum non nocere - Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.

Potenciales efectos pro-arrítmicos de la farmacoterapia contra SARS-CoV-2 / Potential pro-arrhythmic effects of pharmacotherapy against SARS-CoV-2

Resumen La pandemia por el virus SARS-COV-2 causante de la enfermedad COVID-19 representa un reto mundial dada su alta tasa de transmisión y ausencia de una terapia efectiva o vacuna. Este escenario ha propiciado el uso de diversos fármacos que in vitro han demostrado un potencial efecto contra el virus. Sin embargo, el tiempo no ha sido suficiente para evaluar su efectividad clínica con el adecuado rigor científico que precede a la prescripción de medicamentos. El uso de cloroquina/hidroxicloroquina, azitromicina y esquemas antivirales ha sido propuesto por diversos grupos, apoyado por series de pacientes limitada en número. Si bien puede representar la única esperanza para muchos enfermos, es importante conocer los principales efectos adversos asociados al uso de estas drogas y seleccionar mejor a los pacientes que puedan beneficiarse de ellas. El riesgo de arritmias ventriculares incrementa tanto por el uso de fármacos como por la gravedad de la propia enfermedad viral.

Abstract The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.

Evaluation of toxic retinopathy caused by antimalarial medications with spectral domain optical coherence tomography / Avaliação da frequência de retinopatia por antimaláricos com o exame tomografia de coerência óptica de domínio espectral

ABSTRACT Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen's table, color vision test - Ishihara's table, fundoscopy, and retinography - red-free). Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.

RESUMO Objetivo: Investigar a frequência da retinopatia tóxica em pacientes com lúpus eritematoso e artrite reumatóide com uso crônico de difosfato de cloroquina ou hidroxicloroquina, através de tomografia de coerência óptica de domínio espectral e os resultados dos exames oftalmológicos (acuidade visual - tabela de Snellen, teste de visão de cor - tabela de Ishihara, fundoscopia e retinografia - red free). Métodos: Foi realizado um estudo transversal envolvendo a avaliação oftalmológica de pacientes em uso regular de difosfato de cloroquina ou hidroxicloroquina por um período de um ano ou mais. Os pacientes responderam a um questionário sobre a sua opinião e regularidade do tratamento. Os mesmos pacientes realizaram exame oftalmológico clínico e tomografia de coerência óptica de domínio espectral. Resultados: A prevalência de retinopatia tóxica por antimaláricos foi de 4,15% (9 dos 217 pacientes), 7,4% (4 de 54 pacientes) após uso de difosfato de cloroquina e 0,82% (1 de 121 pacientes) após uso de hidroxicloroquina. Apenas os pacientes com maculopatia em fase avançada apresentaram alterações durante os exames clínicos: teste de visão de cores alterado em 11,1%, e a acuidade visual e fundoscopia foram alteradas em 33,3%. A identificação de retinopatia tóxica precoce, detectada em seis pacientes, foi possível por meio da tomografia de coerência óptica de domínio espectral. A duração média do tempo de uso de drogas antimaláricas entre os pacientes com retinopatia tóxica foi de 10,4 anos. Apenas 31% dos pacientes relataram algum sintoma durante o tratamento e apesar de 24% terem medo de usar a medicação, eles o fizeram conforme prescrito. Conclusão: O uso da tomografia de coerência óptica de domínio espectral foi essencial para o diagnóstico de retinopatia tóxica antimalárica em estágio inicial em pacientes com as seguintes características: uso assintomático, antimalárico 7 dias por semana por um período maior que cinco anos e exame oftalmológico clínico normal.

Daño en el ADN de linfocitos humanos por efecto de cloroquina / Damage to human lymphocyte DNA from chloroquine effect

RESUMEN El objetivo del estudio fue evaluar el efecto de cloroquina (CQ) en linfocitos humanos a través del ensayo cometa. Los linfocitos fueron aislados de muestras de sangre periférica obtenidas de tres donantes sanos, no fumadores de 24 a 30 años. Los linfocitos aislados fueron expuestos durante una hora a diversos tratamientos: peróxido de hidrógeno 2,5 % (control positivo), buffer fosfato salino 1X (control negativo) y cloroquina a concentraciones de 0 µg/ml, 0,25 µg/ml; 5 µg/ml y 300 µg/ml. Se registró los promedios del porcentaje de ADN en la cola del cometa, momento de la cola y momento de la cola de Olive, encontrándose diferencias significativas entre las diversas concentraciones de CQ (p<0,01). Asimismo, la magnitud de daño del ADN se incrementó en función de la concentración de CQ. Se demostró el efecto genotóxico de CQ en linfocitos humanos expuestos in vitro.

ABSTRACT The objective of the study was to evaluate the effect of chloroquine (CQ) on human lymphocytes through the Comet Assay. Lymphocytes were isolated from peripheral blood samples obtained from three healthy, non-smoking donors aged 24 to 30 years. The isolated lymphocytes were exposed for one hour to various treatments: hydrogen peroxide 2.5% (positive control), saline buffer phosphate 1X (negative control) and chloroquine at concentrations of 0 µg/ml, 0.25 µg/ml; 5 µg/ml and 300 µg/ml. The averages of the percentage of DNA in the comet tail, moment of tail and moment of Olive's tail were recorded, with significant differences between the different concentrations of CQ (p<0.01). Also, the magnitude of DNA damage was increased as a function of the CQ concentration. The genotoxic effect of CQ was demonstrated in human lymphocytes exposed in vitro.

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity. .

Ultra-high resolution optical coherence tomography analysis of bull's eye maculopathy in chloroquine users / Análise da maculopatia em bull's eye pela tomografia de coerência óptica de alta resolução em usuários de cloroquina

Purpose: Register and compare anatomical changes, structural and quantitative found in optical coherence tomography Stratus and Topcon 3D in chronic users of chloroquine. Methods: Five patients were diagnosed with toxic "bull's eye" maculopathy was submitted to macular optical coherence tomography examination (Stratus and Topcon 3D). Results: Both tools demonstrated an increase reflectivity of choriocapillaris unit just foveal retinal pigment epithelium atrophy. However, Topcon 3D provided to all patients better description of the line corresponding to the transition between inner and outer segments of photoreceptors. Using the possibility of assembling threedimensional images and subtraction selective retinal layers, we found a lesion with a target that reflects the greater thickness of retinal pigment epithelium in central and parafoveal region that is matched to preserve macular photoreceptors. Conclusion: it was observed better resolution and faster image capture by Topcon 3D than Stratus OCT, that provided more detailed analysis of the line corresponding to transition between outer and inner segment of photoreceptors in macular region. With Topcon 3D, it was possible to evaluate soundly the thickness of retinal pigment epithelium in central and parafoveal region that caused an increase reflectivity of choriocapillaris creating a image with a target unpublished before. .

Objetivo: Comparar e registrar as alterações quantitativas e qualitavivas na tomografia de coerência óptica nos pacientes com uso prolongado de cloroquina. Métodos: Avaliaram-se cinco pacientes com diagnóstico de bull’s eye no exame de tomografia de coerência óptica macular com dois modelos de aparelhos: Stratus e Topcon 3D. Resultados: Ambos aparelhos registraram aumento da refletividade coriocapilar foveal provocada pela atrofia do epitélio pigmentar da retina. Somente o Topcon 3D permitiu melhor visibilização da linha de transição entre o segmento interno e externo dos fotorreceptores. Este aparelho também permitiu a formação de imagens tridimensionais e subtração das camadas retinianas, com registro da diminuição da espessura do epitélio pigmentado da retina na região central e parafoveal macular. Conclusão: Foi possível observar a captação mais rápida e com melhor resolução das imagens geradas pelo Topcon 3D. A diminuição da espessura do epitélio pigmentado da retina, provocando o aumento da refletividade coriocapilar, com a formação de uma imagem linear circular cincundando a fóvea, foi mais detalhado pelos cortes realizados no Topcon 3D. .

Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy

A 53-year-old Asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus. Within a few years, she noticed circle-shaped shadows in her central vision. Upon examination, the patient's visual acuity was 20 / 25 in both eyes. Humphrey visual field (HVF) testing revealed a central visual defect, and fundoscopy showed a ring-shaped area of parafoveal retinal pigment epithelium depigmentation. Fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull's eye retinopathy. Adaptive optics scanning laser ophthalmoscope (AO-SLO) revealed patch cone mosaic lesions, in which cones were missing or lost. In addition, the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness. Unlike previous studies employing deformable mirrors for wavefront aberration correction, our AO-SLO approach utilized dual liquid crystal on silicon spatial light modulators. Thus, by using AO-SLO, we were able to create a photographic montage consisting of high quality images. Disrupted cone AO-SLO images were matched with visual field test results and functional deficits were associated with a precise location on the montage, which allowed correlation of histological findings with functional changes determined by HVF. We also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral-domain optical coherence tomography.

Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy

A 53-year-old Asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus. Within a few years, she noticed circle-shaped shadows in her central vision. Upon examination, the patient's visual acuity was 20 / 25 in both eyes. Humphrey visual field (HVF) testing revealed a central visual defect, and fundoscopy showed a ring-shaped area of parafoveal retinal pigment epithelium depigmentation. Fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull's eye retinopathy. Adaptive optics scanning laser ophthalmoscope (AO-SLO) revealed patch cone mosaic lesions, in which cones were missing or lost. In addition, the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness. Unlike previous studies employing deformable mirrors for wavefront aberration correction, our AO-SLO approach utilized dual liquid crystal on silicon spatial light modulators. Thus, by using AO-SLO, we were able to create a photographic montage consisting of high quality images. Disrupted cone AO-SLO images were matched with visual field test results and functional deficits were associated with a precise location on the montage, which allowed correlation of histological findings with functional changes determined by HVF. We also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral-domain optical coherence tomography.

Maculopatía tóxica por cloroquina y rehabilitación visual mediante microperímetro MP1 / Phacoemulsification in the treament of iridocorneal endothelial syndrome

La cloroquina es un fármaco que puede producir disfunciones visuales, baja visión e incluso ceguera según la dosis. Una dosis acumulativa menor a 100 g de cloroquina, o una duración de tratamiento de menos de un año raramente se asocia con lesión retiniana. El riesgo de toxicidad aumenta cuando la dosis acumulativa excede los 300 g (250mg/día durante 3 años). Este medicamento es utilizado en el tratamiento de enfermedades autoinmunes. Se presenta una paciente de 44 años de edad, con antecedentes de artritis reumatoide hace 14 años para lo cual se indicó tratamiento con cloroquina (1 tableta 250 mg/diaria) desde el diagnóstico inicial, y presenta un diagnóstico de maculopatía por cloroquina hace 5 años, a consulta por presentar baja visión y solicitando una posibilidad de rehabilitación visual. Se realizó examen oftalmológico, estudios complementarios y se rehabilitó mediante el microperímetro MP1. Se concluye que la maculopatía por cloroquina es una de las causas de discapacidad visual y que la rehabilitación visual con microperimetría proporciona mejoría en varios parámetros visuales, mejorando la calidad visual del paciente

Chloroquine-induced toxic maculopathy and visual rehabilitation through the use of microperimeter MP1.Chrloroquine is a drug that may cause visual dysfunctions, low vision and even blindness depending on dose. An accumulative dose lower than 100 g of chloroquine or a length of treatment less than one year is rarely associated to retinal injure. The toxicity risk increases when the accumulative dose exceeds 300 g (250mg/day for 3 years). This drug is used in treating autoimmune diseases. Here is the case of a 44 years-old patient, with history of rheumatoid arthritis for 14 years. Chloroquine treatment was indicated (one 250 mg tablet daily) at the time of initial diagnosis. Five years ago, he was diagnosed with chloroquine-induced maculopathy when he went to the doctor's because of low vision and asked for possible visual rehabilitation. An ophthalmologic exam, some supplementary studies and rehabilitation through the microperimeter MP1 were all performed. It was concluded that chloroquine-maculopathy with microperimetry provides improvement of several visual parameters and better visual quality for the patient

Chloroquine diphosphate: a risk factor for herpes zoster in patients with dermatomyositis/polymyositis

OBJECTIVES: Herpes zoster has been widely described in the context of different systemic autoimmune diseases but not dermatomyositis/polymyositis. Therefore, we analyzed the prevalence, risk factors and herpes zoster outcomes in this population. METHOD: A retrospective cohort study of herpes zoster infections in dermatomyositis/polymyositis patients was performed. The patients were followed at a tertiary center from 1991 to 2012. For the control group, each patient with herpes zoster was paired with two patients without herpes zoster. Patients were matched by gender and the type of myositis, age at myositis onset and disease duration. RESULTS: Of 230 patients, 24 (10.4%) had a histories of herpes zoster (19 with dermatomyositis and five with polymyositis, two-thirds female). The mean age of the patients with herpes zoster was 44.6±16.8 years. No difference between the groups was found regarding cumulative clinical manifestations. Disease activity, autoantibody, muscle and leukogram parameters were also comparable between the groups. No differences in immunosuppressive (alone or in association with other immunosuppressive therapies) or glucocorticoid (current use, medium dose and cumulative dose in the last two months) therapies were found between patients with and without herpes zoster. However, a higher proportion of patients in the herpes zoster group received chloroquine diphosphate compared to the control group. All of the patients received acyclovir; 58.3% of patients had postherpetic neuralgia and no cases of recurrence were reported. Furthermore, individuals who were taking high prednisone doses at the time of the herpes zoster diagnosis had reduced levels of postherpetic neuralgia. CONCLUSIONS: These data suggest that chloroquine diphosphate could predispose patients with dermatomyositis/polymyositis to developing herpes zoster, particularly women and dermatomyositis patients. .

Relación estructura función en la detección de daño retinal por cloroquina / Relation of structure and function in detecting the retinal damage due to chloroquine

Objetivo: determinar la utilidad de la microperimetría y la tomografía óptica coherente en la detección de daño retinal subclínico por cloroquina. Métodos: estudio prospectivo, observacional y analítico en pacientes consumidores de cloroquina, atendidos en la consulta de Neuroftalmología del Instituto Cubano de Oftalmología Ramón Pando Ferrer, entre septiembre 2010 y octubre 2011. Fueron incluidos 44 ojos. Se realizaron exámenes para evaluar función (psicofísica visual y microperimetría) y estructura (biomicroscopia y tomografía óptica coherente). Resultados: la edad promedio fue de 43 años con una dosis acumulada de cloroquina de 182 g y un tiempo de consumo inferior a cinco años. Existió relación significativa entre la dosis acumulada y las variables siguientes: visión del color (-0,495; p= 0,001), grosor retinal peripapilar temporal (-0,353; p= 0,019) e inferior (-0,336; p= 0,026), macular central (-0,652; p= 0,000) y sensibilidad retinal por microperimetría (-0,436; p= 0,003) con alteraciones funcionales y estructurales en relación con el incremento de la dosis acumulada. Conclusiones: se demostró que es posible detectar daño retinal funcional temprano mediante microperimetría y tomografía óptica coherente en pacientes consumidores de cloroquina, en presencia de otros estudios funcionales y biomicroscopia normales. Unido a la tomografía óptica coherente el microperímetro puede constituir una útil herramienta para pesquisa de toxicidad retiniana

Objective: to determine the usefulness of microperimetry and of the optical coherence tomography in the detection of subclinical retinal damage due to chloroquine. Methods: prospective, observational and analytical study in patients taking chloroquine, who were seen at the Neuro-ophthalmology service of "Ramón Pando Ferrer" Institute of Ophthalmology from September 2010 through October 2011. Forty four eyes were included. Tests were performed to assess function (visual psychophysics and microperimetry) and structure (biomicroscopy and optical coherence tomography). Results: mean age was 43 years with a cumulative dose of 182 g and less than 5 years taking this drug. There was significant correlation between the cumulative dose of chloroquine and the following variables: color vision (-0.495, p = 0.001), temporal peripapillary retinal thickness (-0.353, p= 0.019) and lower (-0.336, p = 0.026), central macular (-0.652, p = 0.000) and retinal sensitivity by microperimetry (-0.436, p= 0.003) with functional and structural changes related to the increase in cumulative dose. Conclusions: it was demonstrated that it is possible to detect early functional retinal damage by using microperimetry and optical coherence tomography in patients taking chloroquine, despite normal results of other functional studies and of biomicroscopy. The combination of microperimetry and optical coherence tomography may be a useful screening tool for retinal toxicity