Pigment dropout found in middle-aged man’s first eye exam

Issue: September/October 2013

A 45-year-old Burmese man presented with a translator for his first eye examination. His chief complaint was blurry vision at night. His systemic health history was significant for HIV diagnosed 1 year ago, for which he was on Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate, Bristol-Myers Squibb and Gilead Sciences). He was not sure of his CD4 count or viral load. The patient was born and raised in Burma (now Myanmar), in Southeast Asia. He had moved to the U.S. about 1 year ago.

The patient’s best corrected visual acuities were 20/20 in each eye. Pupils were reactive with no afferent defect. Extraocular movement was full in each eye. Intraocular pressures were 18 mmHg in each eye by Goldmann applanation tonometry. On HRR color vision testing, the patient correctly identified 8/10 plates in the right and left eyes. Humphrey 10-2 visual fields showed nasal defects in each eye, in the left greater than the right.

Dilated fundus exam showed healthy optic nerves with small optic cups in each eye. There was a large, symmetrical area of pigment dropout and mottling across the maculae and into the posterior pole in each eye. Small crystalline deposits were noted in this area in both eyes.

Anna Bedwell

Spectral domain optical coherence tomography images revealed retinal pigment epithelium thinning and photoreceptor integrity line (PIL) thinning in each eye. The PIL was nonexistent temporally in each eye. The fovea was spared in each eye with normal retinal thickness of 256 microns in the right eye and 228 microns in the left eye. The OCT findings were consistent with the patient’s excellent visual acuities and nasal visual field defects.

Inquiring further into the patient’s history, he reported no family members with vision loss. The patient had only been aware of his HIV status for the past year, but reported no history of infections. The patient did note that he had malaria about 10 years prior. He said he was put on “especially high doses” of a medicine for several weeks to treat the malaria.

The patient’s malaria history as well as the characteristic SD-OCT findings raised suspicion for chloroquine maculopathy. Chloroquine is actively used in Southeast Asia and Africa for malaria treatment. In this case, the OCT demonstrates the characteristic loss of the PIL that spares the fovea, known as the flying saucer sign.

Dilated fundus exam showed a large, symmetrical area of pigment dropout and mottling across the maculae and into the posterior pole, with small, crystalline deposits in this area in both eyes.

Images: Bedwell A

Chloroquine is a 4-aminoquinolone drug used around the world for malaria treatment and prevention. Malaria is an infection caused by the Plasmodium parasite and contracted through mosquito bites. It is characterized in the early stages by fever, chills, sweats and body aches and can be fatal if left untreated.

This patient emigrated to the U.S. from Myanmar, a country where the World Health Organization shows high rates of malaria. There are five known species of Plasmodium that can infect humans. Chloroquine remains an effective drug for malaria treatment and prevention, although there are some areas of the world where chloroquine resistance has developed. It is rarely used in the U.S., where it has been replaced by Plaquenil (hydroxychloroquine, Sanofi-Aventis) to treat autoimmune and inflammatory diseases.

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Retinal toxicity has been a well-recognized side effect of chloroquine since its introduction. The mechanism by which retinal toxicity occurs is still poorly understood. The classic presentation of toxicity is a bilateral bull’s eye maculopathy with depigmentation of the retinal pigment epithelium encircling the fovea, corresponding to visual field loss. The fovea is initially spared, but eventually central vision loss can occur as the drug is continued. Cessation of the drug rarely provides reversal of functional vision loss. Vision loss can progress after chloroquine is stopped, as the drug takes months to clear from the body.

Screening guidelines

The goal of screening patients on chloroquine and hydroxychloroquine is to detect retinal toxicity prior to visible fundus changes. In 2011, the American Academy of Ophthalmology published its revised recommendations for screening patients on chloroquine and hydroxychloroquine, stressing the cumulative dose as an important risk factor. The baseline exam at the start of therapy should include either SD-OCT, fundus autofluorescence or multifocal ERG in addition to 10-2 automated visual fields. Amsler grid and color vision testing are no longer recommended. After 5 years of hydroxychloroquine therapy, annual screenings are suggested. Patients with kidney or liver dysfunction or retinal diseases and/or pre-existing maculopathy should be monitored more closely. The risk of toxicity increases to about 1% when the cumulative dose has reached 1,000 G of hydroxychloroquine or 460 G of chloroquine.

The characteristic sign of toxicity on spectral domain OCT is retinal thinning, in particular dropout of the PIL parafoveally, preserving the photoreceptors at the fovea. Chen and colleagues dubbed this the “flying saucer” sign, as an ovoid appearance is created. Time domain OCT does not have the resolution necessary to detect these subtle changes. Autofluorescence imaging shows the distribution of lipofuscin in the retina, which shows increased fluorescence in early toxicity and decreased fluorescence in the late stages. Toxicity is detected on multifocal electroretinogram by pericentral loss or loss of the central peak waveform. Abnormal findings should prompt communication with the patient’s internist or rheumatologist to consider cessation of treatment.

SD-OCT revealed RPE and PIL thinning, sparing the fovea, in each eye.

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Another important consideration during screening is calculating a patient’s daily dose. A daily dose over 6.5 mg/kg/day is a well-known risk factor for toxicity. Chloroquine is not retained in adipose tissue, so dosing should be based on the lesser of the ideal body weight based on height and actual body weight. Overdosing of hydroxychloroquine is quite common in short, obese patients, as ideal body weight is not properly used in calculations. Dosage reduction should be recommended to the prescriber if a daily dose is calculated at greater than 6.5 mg/kg/day, to reduce the risk of toxicity.

This patient’s management

For this patient, the characteristic SD-OCT findings gave the needed insight into the diagnosis, as the fundus lacked the typical bull’s eye appearance. This case demonstrates an example of minimal functional vision loss in the presence of advanced fundus changes due to chloroquine toxicity. We were unable to determine the patient’s cumulative chloroquine intake and further insight into his medical history because translation provided a barrier. As no treatment is warranted, yearly observation was recommended for this patient.

References:

Browning, D. Am J Ophthalmol. 2013;155:418-428.
Centers for Disease Control and Prevention. Malaria. Available at: http://www.cdc.gov/MALARIA/. Accessed July 10, 2013.
Chen E, et al. Clin Ophthalmol. 2010;4:1151-1158.
Marmor MF, et al. Ophthalmology. 2011;118:415–422.
Michaelides M, et al. Arch Ophthalmol. 2011;129(1):30–39.
Tehrani R, et al. Semin Ophthalmol. 2008;23(3):201–209.
World Health Organization. Malaria. Available at: http://www.who.int/malaria/en/. Accessed July 10, 2013.

For more information:

Anna Bedwell, OD, is a visiting clinical faculty member at Indiana University. She sees patients at the university’s satellite clinic, Indianapolis Eye Care Center. She can be reached at abedwell@indiana.edu.
Edited by Leo P. Semes, OD, a professor of optometry, University of Alabama at Birmingham and a member of the Primary Care Optometry News Editorial Board. He may be contacted at 1716 University Blvd., Birmingham, AL 35294-0010; (205) 934-6773; lsemes@uab.edu.
Disclosures: Bedwell has no relevant financial disclosures.