The ocular safety of hydroxychloroquine

doi:10.1016/S0049-0172(10)80009-5

Seminars in Arthritis and Rheumatism

Volume 23, Issue 2, Supplement 1, October 1993, Pages 62-67

https://doi.org/10.1016/S0049-0172(10)80009-5 Get rights and content

The insert currently supplied with hydroxychloroquine states that patients should have an initial ophthalmological assessment and then regular assessments every 3 months. The rheumatologist should expect a report from the ophthalmologist, which includes a corneal assessment of tissue dose, a reference to visual field defects if present on the Amsler grid, and a comment concerning the status of the patient's color vision. Daily dose is more important than duration of dose, regarding maculopathy. The visual prognosis of retinopathy is excellent if the diagnosis is made at an early stage of the disease. This report suggests that ophthalmological review need only occur initially and on a yearly basis if the daily dose of hydroxychloroquine is less than 6.5 mg/kg/d and the duration of therapy is less than 9 years.

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Cited by (63)

Natural history of COVID-19 and current knowledge on treatment therapeutic options
2020, Biomedicine and Pharmacotherapy
Citation Excerpt :
Regarding the side effects of hydroxychloroquine and chloroquine, both have been in clinical use for several years, thus their safety profile is well established [126]. Gastrointestinal upset has been reported with hydroxychloroquine and retinal toxicity has been described with long term use of both drugs [127–129]. Retinal toxicity may also be related to over-dosage [130].
Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.
Antimalarial medications
2018, Dubois' Lupus Erythematosus and Related Syndromes
Antimalarials (AMs) are one of the oldest medications used to treat human disease and one of the first and safest disease-modifying antirheumatic drugs. Several factors have favored the wide use of AMs in systemic lupus erythematosus (SLE). First, there is convincing evidence that they are effective. Second, there are enough data showing that continuous use of AMs leads to better outcomes, prevents damage accrual, and improves survival. Third, effective retinal monitoring strategies to identify early and reversible retinal changes are currently available.
AMs should remain a first-line drug in the management of all SLE patients. Adherence to AM therapy in SLE remains a challenge. Although future therapeutic advances may promise better outcomes, for now AMs are inexpensive, safe, and effective and remain key agents in the management of SLE.
Evaluation of a follow-up protocol for patients on chloroquine and hydroxychloroquine treatment
2016, Archivos de la Sociedad Espanola de Oftalmologia
Evaluar el protocolo implantado en nuestro hospital para el cribado de toxicidad ocular por antipalúdicos (AP) revisando las características de los pacientes estudiados y los problemas encontrados tras su implantación.
Estudio retrospectivo de las historias clínicas, retinografías, fotos de autofluorescencia (FAF) y campos visuales (CV) centrales 10-2 de los pacientes que iban a iniciar tratamiento con AP, desde el momento de la implantación del protocolo en mayo de 2012 hasta enero de 2014.
Se han revisado 126 pacientes. El 94,4% procedían del servicio de reumatología y el 5,6%, del de dermatología. La edad media fue de 59,7 años, y el 73,8% fueron mujeres. Todos estaban en tratamiento con hidroxicloroquina, siendo la dosis más frecuente 300 mg diarios. La artritis reumatoide fue el diagnóstico más frecuente (40,5%), seguido del lupus eritematoso (15,9%). La agudeza visual media fue de 0,76; 26 pacientes presentaban opacidades de cristalino. En 97 pacientes los CV resultaron normales, 8 presentaron defectos leves o moderados sin patrón definido, y en 9 los resultados fueron poco fiables. De los 51 pacientes mayores de 65 años, 16 (31,4%) presentaron CV alterados o no valorables. La FAF resultó normal en 104 pacientes (82,5%) y anormal, aunque congruente con los hallazgos oftalmoscópicos, en 12 pacientes.
El rendimiento de los CV como test de referencia para el diagnóstico de toxicidad por AP es relativamente bajo en pacientes mayores de 65 años. Por ello creemos recomendable usar la FAF como test primordial y asociarlo quizás a otro test objetivo, como el SD-OCT, en detrimento de los CV.
To review the problems found after a new follow-up protocol for patients on chloroquine and hydroxychloroquine treatment.
Retrospective study was conducted between May 2012 and January 2013 on the clinical files, retinographies, fundus auto-fluorescence (FAF) images, and central-10 degree visual fields (VF) of patients who were referred to the Ophthalmology Department as they had started treatment with hydroxychloroquine.
One hundred twenty-six patients were included; 94.4% were referred from the Rheumatology Department and 5.6% from Dermatology. Mean age was 59.7 years, and 73.8% were women. All of them were on hydroxychloroquine treatment, and 300 mg was the most frequent daily dose. Rheumatoid arthritis was the most common diagnosis (40.5%), followed by systemic lupus erythematosus (15.9%). The mean Snellen visual acuity was 0.76, and 26 patients had lens opacities. The VF were normal in 97 patients, 8 had mild to moderate defects with no definite pattern, and in 9 the results were unreliable. Of the 51 patients older than 65 years, 16 (31.4%) had altered or unreliable VF. The FAF was normal in 104 patients (82.5%), and abnormal, but consistent with ophthalmoscopic features, in 12 patients (pathological myopia, age related changes, early, middle or late age-related macular degeneration).
Visual fields as a reference test for the diagnosis of AP toxicity are not quite reliable for patients over 65. Therefore, the FAF is recommended as primary test, perhaps combined with another objective test, such as SD-OCT instead of VF.
Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease
2015, Canadian Journal of Ophthalmology
To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD).
Cohort study.
Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010.
Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG.
Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull’s-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity.
High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity.
Évaluer la toxicité rétinienne de fortes doses d’hydroxychloroquine (HCQ) chez des patients traités pour la maladie du greffon contre l’hôte (GVHD) chronique.
Étude de cohorte.
Douze (12) patients atteints de GVHD chronique traités avec 800 mg/jour d’HCQ entre juin 2005 et décembre 2010.
Pendant l’étude, les participants ont subi un examen ophtalmologique annuel et des examens complémentaires : vision des couleurs, grilles d’Amsler, photographie du fond de l’œil, périmétrie automatisée (Humphrey 10-2), tomographie de cohérence optique en domaine spectral (TCO-DS) et électrorétinographie multifocale.
Toxicité de l’HCQ démontrée par la présence de scotomes (test d’Amsler et périmétrie automatisée) et confirmée par au moins un test objectif (TCO-DS ou électrorétinographie multifocale).
Des 12 patients, 7 étaient des hommes et 5 étaient des femmes. L’âge moyen était de 49 ans. La meilleure acuité visuelle corrigée moyenne de référence était de 20/25; elle était toujours de 20/25 au suivi final. La durée médiane du traitement à l’HCQ était de 22,8 mois. La dose ajustée médiane était de 11,5 mg/kg/jour. Sept patients ont développé une cornée verticillée. Aucun signe de rétinopathie pigmentaire ni de maculopathie en œil de bœuf n’a été relevé chez aucun des patients. Trois patients ont développé une toxicité rétinienne avec scotomes selon le test d’Amsler et la périmétrie automatisée, de même qu’une électrorétinographie multifocale anormale. La structure rétinienne mesurée par TCO-DS était anormale chez 2 des 3 patients présentant une toxicité rétinienne. La vision des couleurs mesurée par le test d’Ishihara et par le test de Farnsworth-Munsell 100 Hue était anormale chez 2 de ces 3 mêmes patients.
L’administration de fortes doses d’HCQ à des patients atteints de GVHD chronique était associée à une incidence accrue de toxicité rétinienne et à l’apparition précoce de la toxicité rétinienne.
Hydroxychloroquine screening practice patterns within a large multispecialty ophthalmic practice
2015, American Journal of Ophthalmology
To determine provider compliance with hydroxychloroquine screening following the revised recommendations published in 2011 by the American Academy of Ophthalmology.
Evaluation of adherence to a screening protocol.
Subjects were identified with hydroxychloroquine as a medication by electronic query at a large multispecialty ophthalmic practice. Patients were excluded if patients: (1) were screened by an outside physician; (2) lacked recorded height, weight, start date, or dosing; or (3) took hydroxychloroquine for malaria prophylaxis. Screening tests were stratified by ophthalmic subspecialty. Guidelines define proper screening as 1 subjective test—Humphrey visual field (HVF), and 1 objective test—spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), or multifocal electroretinography (mfERG). Adherence to guidelines was determined by categorizing practices as: (1) “appropriate”—consistent with guidelines; (2) “underscreened”—insufficient testing; or (3) “inappropriate”—no testing.
The study comprised 756 patients with a mean age of 56 years undergoing 1294 screening visits. Twenty-one patients received initial screenings outside the institution. Most common screening tests employed included SD OCT (56.6%), 10-2 HVF (55.0%), and Amsler grid (40.0%). Of the 735 initial screenings, 341 (46.4%) were appropriately screened, 204 (27.8%) underscreened, and 190 (25.9%) inappropriately screened. Of those who presented solely for screening (560), 307 (54.8%) were appropriately screened, 144 (25.7%) underscreened, and 109 (19.5%) inappropriately screened.
Of patients presenting for hydroxychloroquine screening, 54.8% of patients received appropriate evaluation, indicating lack of adherence to guidelines. Overall, SD OCT and 10-2 HVF were the preferred screening modalities, with FAF and mfERG less frequently ordered.
Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies
2014, Toxicology Reports
For many years chloroquine was used as a prophylactic agent against malaria, and more recently as a mild immunosuppressive. However, due to lengthy treatment periods, adverse effects have become apparent, which included retinopathy. The structurally related hydroxychloroquine is less toxic, thought to be owing to a lower tissue accumulation in melanin rich areas. This study primarily focused on quantifying melanin binding between chloroquine and hydroxychloroquine at physiological pH to investigate the potential link between binding and reported toxicity. In addition, for the first time this study quantified the actual extent of adsorption of chloroquine and hydroxychloroquine to melanin and examined the desorption profile of both drugs from melanin to demonstrate the affinity between the pigment and the solutes. The results suggest that there is a difference between the adsorption affinities of chloroquine and hydroxychloroquine, potentially explaining the differences in bioaccumulation in retinal tissue. In addition, both solutes displayed a strong physical attraction to the absorbent.

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The ocular safety of hydroxychloroquine

Lancet

Semin Arthritis Rheum

Am J Med

Am J Ophthalmol

Am J Med

Am J Ophthalmol

Ophthalmology

Unusual ocular lesions in a case of systemic lupus erythematosus

Arch Ophthalmol

Ocular complications of chloroquine therapy

Can Med Assoc J

Ocular lesions after treatment with chloroquine

Br J Ophthalmol

Is corneal deposition of antimalarial any indication of toxicity?

Can J Ophthalmol

Comparison of hydroxychloroquine and chloroquine in the development of retinal toxicity

J Rheumatol