Association of Antiretinal Antibodies with Hydroxychloroquine Toxicity in SLE
Abstract
Hydroxychloroquine (HCQ) is an important medication for lupus patients because it has been shown to be effective at controlling flares of disease activity as well as preventing long term damage. However, recent studies suggest that patients taking hydroxychloroquine long-term may have a higher risk of developing retinal (eye) toxicity than previously thought. Current guidelines from the American Academy of Ophthalmology recommend dose limitations for all patients, which may prevent some lupus patients from receiving effective doses of an important lupus therapy. Our group has preliminary data indicating that 20/22 subjects with a diagnosis of HCQ-induced retinal toxicity had anti-retinal antibodies (91%), compared to 2/6 with normal retinal testing. We also have preliminary data from a small cohort of lupus patients. Based on this preliminary data, we hypothesize that anti-retinal antibodies may be a biomarker to identify patients at risk for retinal toxicity in SLE patients who are taking HCQ. Although lupus patients make many antibodies, anti-retinal antibodies have not been previously studied in lupus patients, and we do not know how often they appear and whether they are associated with HCQ, other medication use, or other lupus features. The goal of this proposal is to develop a better understanding of the typical pattern of these anti-retinal antibodies in lupus patients. In order to investigate our hypothesis, we plan the following Specific Aims: Specific Aim 1: Determine the cross-sectional frequency of anti-retinal antibodies in a group of 285 patients with SLE and 100 healthy age-matched controls, and to determine the relationship with (a) the length of exposure to HCQ and (b) relationship with abnormalities on retinal screening tests. Specific Aim 2a: Determine whether exposure to HCQ results in an increase in anti-retinal antibodies by testing a cohort of 45 SLE patients prior to any HCQ exposure, 3 months, 6 months, and 9 months after exposure. Specific Aim 2b: Determine possible mechanisms underlying retinopathy in SLE patients taking HCQ by examining the ability of blood cells from patients treated before and after HCQ and patients with retinopathy to secrete anti-inflammatory and pro-inflammatory cytokines. If we are able to demonstrate that anti-retinal antibodies are found more commonly in HCQ-treated patients who go on to develop retinopathy, we may be able to use these antibodies in the future to identify which SLE patients should lower or discontinue HCQ and also which patients should get more frequent and more sensitive eye testing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010674
Entities
People
- Maureen Mcmahon
Organizations
- United States Army
- University of California, Los Angeles