Medications and retinal toxicity Stephen G. Schwartz, MD a , William F. Mieler, MD b, * a Department of Ophthalmology, Medical College of Virginia, Commonwealth University, 8th Floor, MCV Box 980262, 1101 E. Marshall Street, Richmond, VA, 23298-0262, USA b Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, NC-205, 6565 Fannin, Houston, TX 77030, USA Introduction Several pharmaceuticals are associated with tox- icity in the retina, the retinal pigment epithelium (RPE), and their blood supplies. It is important to be aware of these associations because prompt recog- nition and discontinuation of the agent may amelio- rate its effect. Alternatively, some medications only cause problems when they are overdosed. In these patients, the ophthalmologist may make a vision- sparing or life-saving diagnosis. Drugs causing pigmentary degeneration Quinolines The quinoline antimalarial chloroquine (Aralen) and its safer derivative hydroxychloroquine (HCQ; Plaquenil, Sanofi Winthrop Pharmaceuticals, New York, NY) cause a well-documented retinopathy— bull’s-eye maculopathy. Signs of visual dysfunction typically precede symptoms. Loss of the foveal light reflex (Fig. 1) may progress to macular pigment stippling and then to a bull’s-eye lesion (Fig. 2). Pigment mottling in the retinal periphery may ad- vance to a tapetoretinal-like degeneration with vas- cular attenuation and optic disc atrophy (Fig. 3). An asymptomatic, verticillata-like change of the corneal epithelium may also occasionally be seen [1 – 4]. Perimetry often demonstrates a paracentral sco- toma, which may be the first evidence of disease, particularly with the use of a red test object [5]. Similarly, a red Amsler grid may indicate abnor- mal results early [6], and color vision defects are frequent [7]. Chloroquine toxicity is more dependent on daily rather than cumulative dosage. Most cases occur in patients ingesting more than 250 mg/d for at least 1 year [8]. With prompt recognition of toxicity and discon- tinuation of chloroquine therapy, early maculopathy may resolve. In contrast, more advanced cases may progress even after the medication has been discon- tinued [9,10]. Retinopathy may not develop until years after the medication is discontinued [11,12], perhaps because of the exceptionally long clearance time of the drug [13]. Hydroxychloroquine toxicity is clinically iden- tical to toxicity caused by chloroquine (Fig. 4), though it occurs less frequently. The reason for the relative safety of hydroxychloroquine is unknown. Retinopathy rarely occurs at or below the theoret- ically safe dosage of 6.5 mg/kg per day [14,15] and generally is not seen before 7 years of usage of the medication. Because of the rarity of hydroxychloroquine toxicity, several authors have questioned the neces- sity of screening these patients [16 –18]. Recently, a Task Force from the American Academy of Oph- thalmology established new monitoring guidelines, and these guidelines were recently published [19]. It should be noted that obese patients and possibly those with renal and hepatic disease may be at increased risk for toxicity. Quinolines are stored in 0896-1549/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII:S0896-1549(02)00051-2 Partially supported by an unrestricted grant from Research to Prevent Blindness, New York, NY. * Corresponding author. E-mail address: wmieler@bcm.tmc.edu (W.F. Mieler). Ophthalmol Clin N Am 15 (2002) 517 – 528