Venous thromboembolism does not share familial susceptibility with retinal vascular occlusion or glaucoma: a nationwide family study Bengt Zo ¨ller 1 • Xinjun Li 1 • Jan Sundquist 1,2 • Kristina Sundquist 1 Ó Springer Science+Business Media New York 2016 Abstract Inherited hypercoagulable states (i.e. throm- bophilia) have been suggested to be involved in retinal vascular occlusion but results are divergent. Vascular micronutrition and ischemia have been hypothesised to be involved in the pathogenesis of glaucoma. This nationwide study determines the importance of family history of venous thromboembolism (VTE) as a risk factor for retinal vein occlusion (RVO), retinal artery occlusion (RAO), primary open angle glaucoma (POAG) and primary angle- closure glaucoma (PACG). A total of 6,007,042 Swedish individuals were studied. Data from the Swedish Multi- generation Register for subjects aged 0–78 years old for the period 1997–2010 were linked to the Swedish Hospital Discharge Register and the Hospital Outpatient Register. Main exposure measure was family history of VTE in first- degree relatives (parents and/or siblings). Main outcomes were hazard ratios (HRs) for RVO, RAO, POAG, and PACG. During follow-up 9036 individuals developed RVO, 2137 individuals developed RAO, 29,176 individu- als developed POAG and 1498 individuals developed PACG. There was no association between family history of VTE and risk of RVO (HR = 1.04, 95 % CI 0.98–1.10), RAO (HR = 1.00, 95 % CI 0.89–1.13), POAG (HR = 0.96, 95 % CI 0.93–0.99), and PACG (HR = 0.92, 95 % CI 0.80–1.06) in the crude age and sex adjusted model. The results were similar in the fully adjusted model: RVO (HR = 1.04, 95 % CI 0.99–1.11), RAO (HR = 1.01, 95 % CI 0.89–1.13), POAG (HR = 0.97, 95 % CI 0.94–1.00), and PACG (HR = 0.91, 95 % CI 0.79–1.05). Family history of VTE is not a risk factor for RVO, RAO, POAG and PACG. Thus, it is unlikely that strong and common genetic variants associated with VTE are of importance for these disorders. Keywords Venous thromboembolism Á Epidemiology Á Family history Á Retinal occlusion Á Glaucoma Introduction Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) may lead to visual loss [1–4]. Inherited hyperco- agulability has attracted an increased interest as a cause of RAO and RVO [5, 6]. The five major inherited throm- bophilic factors involved in venous thromboembolism (VTE) are the rare deficiencies of the natural anticoagu- lants antithrombin, protein C, protein S and the two com- mon gene variants, factor V Leiden mutation and the prothrombin mutation [7]. Factor V Leiden and the pro- thrombin mutation are prevalent in the normal western population, 5–10 % and 1–2 % respectively [7]. These two mutations, or resistance to activated protein C (APC- resistance) which is due to the factor V Leiden mutation, have been studied among patients with RVO and RAO [5, 6, 8–43]. However, the published studies are divergent with both negative and positive studies [5, 6, 8–43]. Many of these association studies are hampered by their limited study size. Neovascular glaucoma (NVG) may occur in people with occlusions of major retinal vessels [44]. The pathogenesis of glaucoma involves alterations of the connective tissues & Bengt Zo ¨ller bengt.zoller@med.lu.se 1 Center for Primary Health Care Research, Ska ˚ne University Hospital, Lund University/Region Ska ˚ne, CRC Building 28, Floor 11, Entrance 72, SE-205 02 Malmo ¨, Sweden 2 Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA 123 J Thromb Thrombolysis DOI 10.1007/s11239-016-1387-7