Rheumatology

Rheumatol Int DOI 10.1007/s00296-014-3129-5

INTERNATIONAL

ORIGINAL ARTICLE - OBSERVATIONAL RESEARCH

Risk factors for cataracts in systemic lupus erythematosus (SLE) Khaled Alderaan · Vuk Sekicki · Laurence S. Magder · Michelle Petri 

Received: 7 May 2014 / Accepted: 9 September 2014 © Springer-Verlag Berlin Heidelberg 2014

Abstract  Cataract is the most common ocular damage in systemic lupus erythematosus (SLE). We analyzed data from the Hopkins Lupus Cohort longitudinally to identify the factors that predict onset of cataract prior to 60 years of age. The Hopkins Lupus Cohort is a clinical cohort of patients with SLE seen quarterly. This analysis was based on the follow-up experience prior to age 60 of 2,109 SLE patients who had not had a cataract prior to cohort entry. Patients saw their ophthalmologist every 6 months. Cataract was defined by the SLICC/American College of Rheumatology Damage Index. The rate of incident cataract was calculated in subsets of the follow-up defined by patient characteristics and history. Multivariable logistic regression models were fit to identify predictors of cataract while controlling for potential confounding variables. The analysis was based on 11,887 persons-years of follow-up, with median follow-up time of 4.1 years per patient. The incidence of cataract was 13.2/1,000 persons-years. Adjusting for other predictors, a cumulative prednisone dose equivalent to 10 mg/day

K. Alderaan · M. Petri (*)  Division of Rheumatology, School of Medicine, Johns Hopkins University, 1830 East Monument Street Suite 7500, Baltimore, MD 21205, USA e-mail: [email protected] K. Alderaan  Rheumatology Section, King Fahad Specialist Hospital, Dammam, Saudi Arabia V. Sekicki  Department of Internal Medicine, Saint Agnes Hospital, Baltimore, MD 21229, USA L. S. Magder  University of Maryland, Baltimore, MD 21201, USA

for 10 years was a strong predictor of cataract (RR = 2.9, P  = 0.0010). Disease activity measured by SELENA– SLEDAI (P  = 0.0004) and higher systolic blood pressure (P  = 0.0003) were associated with cataract. Duration of SLE, diabetes mellitus, smoking, cholesterol, renal involvement, immunological profile and medication history other than prednisone were not associated with cataract. Cataract development in SLE patients is multifactorial with prednisone, systolic blood pressure and disease activity all playing a role. Keywords  Cataract · Predictor · Frequency · Systemic lupus erythematosus

Introduction Cataract is the leading cause of visual impairment worldwide, accounting for almost 50 % of blindness [1]. Age, female sex, non-Caucasian race, smoking, diabetes mellitus, hypertension, corticosteroid use, fewer years of education and ultraviolet B exposure are all known risk factors for cataract development in the general population [2–5]. A diet rich in vitamins and minerals may reduce the risk [2, 6]. The frequency of cataract in systemic lupus erythematosus (SLE) patients ranges from 5 to 32 % [7–16]. Cataract is the second most frequent item in the SLICC/American College of Rheumatology Damage Index, exceeded only by osteoporotic fractures [17]. The annual attributable cost for cataract in SLE is more than $2,000 per patient [18]. It is accepted that corticosteroid dose and/ or duration predispose to cataracts [7, 8, 12, 14]. Even doses of prednisone below 5 mg a day can induce cataracts [19]. However, individual susceptibility to develop

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corticosteroid-induced cataract is also a factor [20, 21]. Posterior subcapsular area of the lens is the most common location of corticosteroid-induced cataract [22]. Longterm exposure to corticosteroid activates the glucocorticoid receptors in the human lens epithelial cells and modulates mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K) regulators. These cell processes are implicated in steroid-induced cataract [23]. There is no preventive therapy for corticosteroidinduced cataract [24]. In a previous analysis, we showed that both the cumulative dose and the highest dose of prednisone prescribed were associated with cataract formation [7]. In one study, available only in abstract form, renal involvement and a higher SLICC/ACR Damage Index score were found to be associated with cataracts, while photosensitivity was protective [14]. However, there are virtually no reports on other risk factors for cataract in SLE. The objective of the present study was to determine predictive factors for cataracts in SLE that might be modifiable, above and beyond corticosteroid dose.

Patients and methods The Hopkins Lupus Cohort The Hopkins Lupus Cohort is a clinical cohort of patients diagnosed with SLE at Johns Hopkins University. The cohort was established in 1987 and has been approved by the Johns Hopkins University School of Medicine Institutional Review Board on a yearly basis. All patients gave written informed consent. Data were collected prospectively during participation in the Hopkins Lupus Cohort. At cohort entry, a detailed clinical history was obtained, including information on prior corticosteroid exposure. During cohort participation, patients were followed up by protocol quarterly, recently confirmed to be the ideal interval [25], or more often as clinically indicated. Ninety-five percent of patients met the ACR revised classification criteria for SLE [26, 27]. The remaining 5 % were diagnosed with SLE by Dr. Petri.

Rheumatol Int

Variables Cataract was defined per the SLICC/ACR Damage Index as lens opacity in either eye, ever, whether primary or secondary and documented by ophthalmoscopy [17]. Patients saw their ophthalmologist every 6 months. Disease activity was identified by the SELENA–SLEDAI index [28]. Skin and musculoskeletal activities were defined by the appropriate SLEDAI descriptors and Lupus Activity Index visual analog scales for these organs. Blood pressure was measured with the patient in the seated position, manually or by an electronic reading machine. Weight and body mass index were measured at every clinic visit. Renal failure was defined as chronic dialysis or kidney transplantation. Renal insufficiency was defined as a serum creatinine of 1.4 mg/dl or more. Diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association (ADA) [29]. Cumulative corticosteroid dose at any point in time was calculated based on the the actual past medical records and updated at each follow-up visit. Cumulative exposure to other medications (aspirin, hydroxychloroquine, NSAIDs and other immunosuppressants) was only based on exposure during cohort participation. The most frequently prescribed immunosuppressants medications included cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, rituximab and leflunomide. Cyclosporine usage was limit to a small number of pregnant patients. Occasionally, variables were not assessed at a quarterly visit. The proportion not assessed was generally

Risk factors for cataracts in systemic lupus erythematosus (SLE).

Cataract is the most common ocular damage in systemic lupus erythematosus (SLE). We analyzed data from the Hopkins Lupus Cohort longitudinally to iden...
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