Abstract: Introduction: Data on prevalence, association with vascular risk factors, clinical management and outcome of antiphospholipid syndrome (APS) in retinal vein occlusion (RVO) are scarce. Methods: Patients diagnosed with RVO at a tertiary-care hospital, and two additional groups; population-based controls and patients with APS (RVO-APS) were studied. Prevalence, association with vascular risk factors, antiphospholipid antibody profile, clinical management, genetic thrombophilia profile, carotid ultrasound and outcome of RVO-APS patients were assessed and compared with controls. Results: Some 331 consecutive patients with RVO and 281 controls were included. Overall, aPLs were more prevalent in RVO-patients than in controls (33, 10% vs. 12, 4.3%; adjusted OR 2.47; 95% CI 1.25-4.88; p = 0.009). Patients with RVO-APS showed a high-risk "aPL profile" (lupus anticoagulant or triple-positive). We did not find any difference regarding classic vascular risk factors, hyperhomocysteinemia, prior vascular events, and carotid plaque, in RVO-patients with or without APS. The phenotype of RVO-APS also differed from APS. Seven patients received anticoagulation and 24 were on low-dose aspirin. After a median follow-up of 62 months, 7 patients suffered a RVO relapse (4 of them had APLs) and no RVO-APS patient had a new thrombotic or vascular event outside the retina. Conclusions: aPLs were more prevalent in RVO-patients than in controls, and in all patients, APS was not associated with any connective-tissue disease. RVO in the setting of APS seems not only related to atherosclerosis, but also to the "aPL profile". In most of our RVO-patients with APS, low-dose aspirin was effective to prevent new or recurrent thrombotic events outside the retinal vessels. In these patients, we suggest that RVO could behave as an organ-specific manifestation of APS.

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