Hydroxychloroquine Maculopathy

This case demonstrates the typical fundus, spectral domain optical coherence tomography, and visual field findings of advanced hydroxychloroquine maculopathy. The patient described in this case was treated with hydroxychloroquine for systemic lupus erythematosus for more than 20 years and presented with classic findings of hydroxychloroquine maculopathy.

Title: Hydroxychloroquine maculopathy Authors: Rohit Balaji1; Ryan D. Walsh, MD1,2 Affiliations: 1. Medical College of Wisconsin 2. Departments of Ophthalmology & Visual Sciences, and Neurology This case demonstrates the typical fundus, spectral domain optical coherence tomography (SD-OCT), and visual field findings of advanced hydroxychloroquine maculopathy. The patient is a 58-year-old female with a past medical history significant for systemic lupus erythematosus (SLE) for which she had been taking hydroxychloroquine (HCQ) for greater than 20 years. The medication had been stopped 15 years prior to this exam, after she developed signs of retinal toxicity. Color fundus photographs (Figure 1) demonstrate the classic parafoveal bull’s-eye shaped region of hypopigmentation in both eyes. Humphrey visual fields (HVF) 10-2 (Figure 2) show bilateral parafoveal defects. SD-OCT scans (Figure 3) reveal bilateral parafoveal atrophy of the retinal pigment epithelium (RPE) and the photoreceptor inner segment/outer segment junction (arrows) with preservation of the central macular outer retinal layers presenting as the classic “flying saucer” sign. OD Figure 1. OS Figure 2. OD OD OS Figure 3. HCQ is a widely used drug for the treatment of a variety of rheumatologic diseases, including SLE. Maculopathy secondary to hydroxychloroquine is a well-established complication of the drug. HCQ binds to melanin in the RPE ultimately preventing phagocytosis of shed photoreceptor outer segments causing irreversible photoreceptor loss and RPE atrophy1. The risk of toxicity is dependent on dosage and duration of use of the drug2. At recommended doses (<5.0 mg/kg/day), the risk of toxicity up to 5 years is <1%, but it rises to almost 20% after 20 years2. Early toxicity may be asymptomatic or result in subtle visual symptoms (such as color vision changes or paracentral scotomas)3. In more advanced toxicity, photoreceptor damage and RPE atrophy occur, classically in a “bull’s-eye” perifoveal pattern (as seen in our patient)3. This bull’s-eye pattern is less common in patients of Asian heritage where a more peripheral pattern of damage is typical2. Once RPE damage has occurred, vision loss is permanent, thus, prevention and early detection of toxicity are paramount2. There are a variety of tests that can help screen for retinal toxicity, but the primary screening tests are automated visual field tests (HVF 102 to assess for parafoveal vision loss; HVF 24-2 or 30-2 to assess for more peripheral vision loss in patients of Asian descent), and SD-OCT3. As HCQ-related damage develops, SDOCT will demonstrate localized thinning of the photoreceptor layers, which can sometimes be recognized in early stages as distinct focal interruption of the photoreceptor outer segment structural lines2. As the damage advances, SD-OCT will demonstrate areas of outer nuclear layer thinning and RPE atrophy in parafoveal regions, with preservation of the outer nuclear layer in the central foveal region. This produces a unique appearance on the OCT sometimes referred to as the “flying saucer sign”1. References 1. Stokkermans TJ, Goyal A, Bansal P, Trichonas G. Chloroquine And Hydroxychloroquine Toxicity. PubMed. Published 2020. https://www.ncbi.nlm.nih.gov/books/NBK537086/ 2. Marmor MF, Kellner U, Lai Timothy YY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94. 3. Pellerano F, Chahin G, Niurka Leonar M, Stern H. Hydroxychloroquine-induced bull’s eye maculopathy. Lancet Rheumatol. 2020 Feb; 2(2): e120