Histopathology of Chloroquine Retinal Toxicity

Wetterholm, Dennis H.; Winter, Frank C.

doi:10.1001/archopht.1964.00970010098016

Cited by 108 publications

(36 citation statements)

References 21 publications

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“…Chloroquine was found to act on the retina in a generalized toxic fashion, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers which accords with the previous reports by Bernstein & Ginsberg (1964), Monahen & Horns (1964) and Wetterholm & Winter (1964).…”

Section: Discussionsupporting

confidence: 90%

Profiles of serum proteins and free amino acids associated with chloroquine retinopathy

El-Sayed

Abdel‐Khalek

Gaafar

et al. 1998

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: The effects of chronic chloroquine administration on serum proteins and free amino acids of rabbits and the accompanying ultrastructural changes in the retina were investigated. Methods: Thirty pigmented rabbits were injected intramuscularly with chloroquine diphosphate (14 mg/Kg bw). Fifteen rabbits served as control. Blood samples drawn after 1, 2, 3, 4, 5, 6 and 12 months were assayed for serum proteins by Bio-analytic kits and horizontal electrophoretic technique. Free amino acids were determined by Beckman analyzer. Central retinal tissue was fixed in 4% glutaraldehyde, embedded in araldite CY 212 and sectioned for ultrastructural examination. Results: Histopathologic changes were apparent within three months, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers. Hypoproteinemia gradually developed mainly due to a sharp drop in albumin and alpha 1 and 2 globulin fractions, inspite of an increase in beta and gamma globulin fractions. The concentration of non-essential amino acids varied considerably from a depletion of taurine, aspartine, glutamine, tryptophan and arginine to an increase of serine, alanine, GABA and ornithine. The most outstanding effect was the disappearance of tyrosine and its return to normal value at the end of the experiment. Conclusion: The disturbances in protein pattern and free amino acid levels are an indication of chloroquine toxicity and may be implicated in the retinopathy.

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Section: Discussionsupporting

confidence: 90%

Profiles of serum proteins and free amino acids associated with chloroquine retinopathy

El-Sayed

Abdel‐Khalek

Gaafar

et al. 1998

Acta Ophthalmologica Scandinavica

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“…Le mécanisme de cet effet toxique n'est pas bien élucidé. En effet, il est difficile de décerner si c'est dû à la fixation de l'hydroxychloroquine par la mélanine de l'épithélium pigmenté ou bien s'il existe un autre mécanisme qui influence directement le métabolisme des photorécepteurs [44], [45]. …”

Section: Rétinotoxicitéunclassified

L’apport de l’électrorétinographie multifocale dans le suivi des patients traités par hydroxychloroquine

Aliferis

Mermoud

Safran

2011

Journal Français d'Ophtalmologie

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“…8,9 In their study on monkeys, Rosenthal et al 10 showed that CQ resulted in the degeneration of retinal ganglion cells. Pasadhika et al 11 showed that perifoveal retinal ganglion cell-inner plexiform layer (RGC-IPL) thickness decreased in patients who had been taking HCQ for a long time before any functional or structural impairment occurred in retinal pigment epithelium layer and photoreceptors.…”

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confidence: 99%

A New Objective Parameter in Hydroxychloroquine-Induced Retinal Toxicity Screening Test: Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness

Bulut¹

2018

Arch Rheumatol

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Objectives: This study aims to detect hydroxychloroquine (HCQ)-induced retinal toxicity at an earlier stage through the use of spectral-domain optical coherence tomography device, especially by measuring macular retinal ganglion cell-inner plexiform layer (RGC-IPL) thickness. Patients and methods: In this study, 92 eyes of 46 Caucasian female patients (mean age 53.6±8.1 years; range 32 to 69 years) who were taking HCQ were assigned to group 1, while 80 eyes of 40 age-matched Caucasian female control subjects (mean age 56.1±10.7 years; range 34 to 71 years) were assigned to group 2. RGC-IPL thickness and retinal nerve fiber layer thickness were measured in all subjects by Cirrus high-definition optical coherence tomography model 5000 device using macular cube 512¥128 and optic disc cube 200¥200 protocols. We performed an evaluation to see if there was any difference between the measured values of the groups. The correlation between average RGC-IPL thickness measures and cumulative dose of HCQ and duration of use was analyzed. Results: Retinal ganglion cell-inner plexiform layer of group 1 was found to be statistically thinner than that of group 2 both on average and in all segments (superior, superonasal, inferonasal, inferotemporal and superotemporal) except inferior segment when segmented (p<0.05). Additionally, a statistically significant negative correlation was found between the average RGC-IPL thickness and cumulative dose of HCQ (r= -0.371, p=0.001) as well as the duration of use (r= -0.308, p=0.006). Conclusion: Patients taking HCQ were found to have decreased RGC-IPL thickness at an early stage due to retinal toxicity induced by the drug. We think that measuring the RGC-IPL thickness may become an important objective in HCQ screening tests.

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Histopathology of Chloroquine Retinal Toxicity

Cited by 108 publications

References 21 publications

Profiles of serum proteins and free amino acids associated with chloroquine retinopathy

Profiles of serum proteins and free amino acids associated with chloroquine retinopathy

L’apport de l’électrorétinographie multifocale dans le suivi des patients traités par hydroxychloroquine

A New Objective Parameter in Hydroxychloroquine-Induced Retinal Toxicity Screening Test: Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness

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