- Email: [email protected]
Discussion by Ronald M. Burde, MD
Ophthalmology Volume 106, Number 9, September 1999 Discussion by Ronald M. Burde, MD Chloroquine is known to produce ocular damage in what appears to be an accumulative dosage-related fashion. Chloroquine is a melanotropic drug that has an affinity for the retinal pigment epithelium. Its storage and release over several years of its discontinuance in some individuals, may lead to bilateral irreversible retinopathy. The affinity of retinal pigment epithelial cell melanin for chloroquine and its congers is presumably variable. This variability is demonstrated by the fact that absorption probably is subject dependent and cell dependent as witnessed by the range of chloroquine exposure capable of producing retinopathy. Apparently, exposure is dependent on concentration. The old adage that once pigment epithelial changes are seen, the damage is irreversible is now suspect. It is evident in certain cohorts that an early cessation of the use of chloroquine can lead to reversibility of functional loss, and in others, the functional loss continues despite the cessation of therapy. Numerous protocols for the routine monitoring of patients taking chloroquine or its derivative have been framed including various types of color vision testing, visual acuity determination, and visual field testing including the Amsler grid. The Amsler grid is a super threshold static field par excellence. Color testing in the mesopic range has been shown to be efficacious for detecting retinopathy. This article attempts to make sense of the subjective responses to color stimuli in patients exposed to chloroquine. Chloroquine retinopathy is defined by using the combined tests of static perimetry and Amsler grid presentation. The diagnosis of chloroquine retinopathy requires the presence of bilateral irreversible scotomas on static perimetry (Humphrey perimeter 10-2 white). Because color vision is often not a standard mode of routine screening, patients are at risk of developing chloroquine retinopathy because of the conflicting reports in the literature. This report attempts to make sense of the varied responses to color vision testing. In essence, the authors report the results of six different color vision tests on two cohorts of patients: the first group included patients with chloroquine retinopathy and the second group in-
From the Department of Ophthalmology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467. E-mail: [email protected].
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cluded patients exposed for a substantial length of time to chloroquine but without developing retinopathy. Of the tests administered, the standard Pseudoisochromatic Plates Part 2 and the AO HRR tests provided the most predictive data. The predominant color vision defect identified in the retinopathy group was a mixed BY–RG defect. Eyes with scotomas had a higher proportion of BY defects and eyes with deeper scotomas had a shift toward mixed or RG defects. Thus, clinical tests that are designed to detect both BY and RG defects are best suited to alerting the treating physician of possible ocular toxicity. However, color vision testing alone should neither be considered as a substitute for regular ophthalmic examinations nor as a reliable clue in isolation to suggest the presence of retinal dysfunction. The question facing the clinician remains as to the best method of monitoring patients taking chloroquine or its congers for prolonged periods of time. It is known that subjective visual function tests have been found to be the most sensitive detectors of the earlier stages of retinal damage. More objective techniques such as ERG showed changes only in the late stages of damage to the retina. It seems clear that the testing protocol developed by Carr et al1 using retinal threshold testing with red and blue lights at scotopic levels of illumination are very sensitive for early detection of retinal damage due to chloroquine. Unfortunately, it is not readily available or done regularly. The authors have demonstrated that threshold static perimetry performed at a mesopic level of illumination is capable of demonstrating characteristic central visual field defects at a stage of retinal toxicity when there may be little or no ophthalmoscopic changes in the macula and a complete, normal fluorescein angiogram. It is clear to me that patients using chloroquine or hydroxychloroquine for prolonged periods of time should be followed with macular static fields. Static threshold visual field testing using a Humphrey perimeter provides the “gold standard,” vis-a`-vis, the presence or absence of retinal toxicity. Reference 1. Carr RE, Gouras P, Gunkel, RD. Chloroquine retinopathy. Early detection by retinal threshold test. Arch Ophthalmol 1966;75:171– 8.
From the Department of Ophthalmology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467. E-mail: [email protected].
1804
cluded patients exposed for a substantial length of time to chloroquine but without developing retinopathy. Of the tests administered, the standard Pseudoisochromatic Plates Part 2 and the AO HRR tests provided the most predictive data. The predominant color vision defect identified in the retinopathy group was a mixed BY–RG defect. Eyes with scotomas had a higher proportion of BY defects and eyes with deeper scotomas had a shift toward mixed or RG defects. Thus, clinical tests that are designed to detect both BY and RG defects are best suited to alerting the treating physician of possible ocular toxicity. However, color vision testing alone should neither be considered as a substitute for regular ophthalmic examinations nor as a reliable clue in isolation to suggest the presence of retinal dysfunction. The question facing the clinician remains as to the best method of monitoring patients taking chloroquine or its congers for prolonged periods of time. It is known that subjective visual function tests have been found to be the most sensitive detectors of the earlier stages of retinal damage. More objective techniques such as ERG showed changes only in the late stages of damage to the retina. It seems clear that the testing protocol developed by Carr et al1 using retinal threshold testing with red and blue lights at scotopic levels of illumination are very sensitive for early detection of retinal damage due to chloroquine. Unfortunately, it is not readily available or done regularly. The authors have demonstrated that threshold static perimetry performed at a mesopic level of illumination is capable of demonstrating characteristic central visual field defects at a stage of retinal toxicity when there may be little or no ophthalmoscopic changes in the macula and a complete, normal fluorescein angiogram. It is clear to me that patients using chloroquine or hydroxychloroquine for prolonged periods of time should be followed with macular static fields. Static threshold visual field testing using a Humphrey perimeter provides the “gold standard,” vis-a`-vis, the presence or absence of retinal toxicity. Reference 1. Carr RE, Gouras P, Gunkel, RD. Chloroquine retinopathy. Early detection by retinal threshold test. Arch Ophthalmol 1966;75:171– 8.