Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?

doi:10.1016/S0002-9394(01)00838-8

American Journal of Ophthalmology

Volume 131, Issue 6, June 2001, Pages 761-766

https://doi.org/10.1016/S0002-9394(01)00838-8 Get rights and content

Abstract

PURPOSE: To determine if mutations in ABCR (ABCA4) are associated with chloroquine/hydroxychloroquine retinopathy.

METHODS: DNA from eight patients with chloroquine or hydroxychloroquine retinopathy was studied. Controls were 80 individuals over age 65 years with normal retinal examinations. Ophthalmoscopy, color vision testing, visual fields, retinal photography, and fluorescein angiography were performed on the eight patients. Direct DNA sequencing of the exons and flanking intronic regions of the ABCR gene was completed for all patients.

RESULTS: Clinical evaluation confirmed the diagnosis of chloroquine/hydroxychloroquine retinopathy and excluded Stargardt disease in each patient. Two patients had heterozygous ABCR missense mutations previously associated with Stargardt disease. None of the controls had these missense mutations. Three other patients had other missense polymorphisms.

CONCLUSIONS: Some individuals who have ABCR mutations may be predisposed to develop retinal toxicity when exposed to chloroquine/hydroxychloroquine. We urge further study of a larger cohort of patients with chloroquine/hydroxychloroquine retinopathy.

Section snippets

Methods

Patients with documented exposure to either chloroquine or hydroxychloroquine were recruited from regional and national ophthalmologists specifically because of established retinal toxicity with the characteristic appearance and pattern associated with drug exposure. As part of investigations of Stargardt disease and other rare retinal disorders, this protocol was approved by the Institutional Review Board for Human Subject Research at Baylor College of Medicine. Local subjects received a

Results

Patients were referred for ophthalmic evaluation of suspected chloroquine or hydroxychloroquine retinopathy. Ophthalmoscopic examination, retinal photography, fluorescein angiography, and color vision and visual field testing were performed for all patients when appropriate. The diagnosis of chloroquine/hydroxychloroquine retinopathy was confirmed by an independent observer (R.A.L.) after review of all available records. Subject 2 started treatment during the first years of life for an

Discussion

We evaluated eight subjects with documented chloroquine/hydroxychloroquine retinopathy for alterations in ABCR by direct sequence analysis. These patients received chloroquine/hydroxychloroquine for treatment of systemic lupus erythematosus, rheumatoid arthritis, congenital pulmonary fibrosis, and for malaria prophylaxis (Table 1). Patients presented with complaints of visual impairment and were documented to have maculopathy by ophthalmoscopy, visual field and color vision testing, and retinal

Acknowledgements

We thank the patients and the referring physicians (George Bresnick, MD, Lawrence A. Gans, MD, R. E. Hardberger, MD, Burton J. Kushner, MD, Martin D. Lidsky, MD, Linda Margulies, MD, H. Stanley Thompson, MD, and J. Patrick H. Wyse, MD, PhD) for their generous and continued cooperation in this study.

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^☆: Mr Shroyer is supported by a National Eye Institute, National Institutes of Health, Bethesda, Maryland, predoctoral training grant (T32 EY07102). Dr Lewis is a Senior Scientific Investigator of Research to Prevent Blindness, New York, New York. This work was supported in part by grants from the National Institutes of Health (R01 EY1780), the Milton and Ruth Steinbach Fund, New York, New York; the Foundation Fighting Blindness, Hunt Valley, Maryland; and unrestricted funds from Research to Prevent Blindness to the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.

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Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?☆

Abstract

Section snippets

Methods

Results

Discussion

Acknowledgements

Am J Ophthalmol

Am J Ophthalmol

Am J Hum Genet

Am J Hum Genet

Anal Biochem

Am J Hum Genet

Am J Ophthalmol

Am J Hum Genet

Am J Hum Genet

Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice

Arthritis Rheum

Retinal toxicity in long term hydroxychloroquine treatment

Ann Rheum Dis

Comparison of hydroxychloroquine and chloroquine use and the development of retinal toxicity

J Rheumatol

Incidence of chloroquine retinopathy

Acta Ophthalmol (Copenh)

Ophthalmological monitoring for hydroxychloroquine toxicitya scientific review of available data

Br J Rheumatol

Ocular damage in chloroquine therapy

Acta Ophthalmol (Copenh)