Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?

Mirian C. H. Janssen; Martin den Heijer; Johannes R. M. Cruysberg; Hub Wollersheim; Sebastian J. H. Bredie

doi:10.1160/TH04-11-0768

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(06): 1021-1026
DOI: 10.1160/TH04-11-0768

Review Article

Schattauer GmbH

Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?

A meta-analysis of thrombophilic factors

Mirian C. H. Janssen

¹Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

,

Martin den Heijer

²Department of Endocrinology and Epidemiology and Biostatistics, Radboud University Medical Centre, Nijmegen, The Netherlands

,

Johannes R. M. Cruysberg

³Department of Ophtalmology Radboud University Medical Centre, Nijmegen, The Netherlands

,

Hub Wollersheim

¹Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

⁴Centre for Quality of Care Research, Radboud University Medical Centre, Nijmegen, The Netherlands

,

Sebastian J. H. Bredie

¹Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

› Author Affiliations

Abstract

Summary

Previous studies have shown an increased risk of retinal vein occlusion (RVO) in patients with hypertension, hypercholesterolemia and diabetes mellitus. Literature on the association between thrombophilic factors and RVO consists of small studies and case reports. The objective was to determine the relationship between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein C and S deficiency, antithrombin deficiency, prothrombin gene mutation, anticardiolipin antibodies and lupus anticoagulant. For all currently known thrombophilic risk factors odds ratios for RVO were calculated as estimates of relative risk. The odds ratios were 8.9 (95% CI 5.7 –13.7) for hyperhomocysteinemia, 3.9 (95% CI 2.3 – 6.7) for anticardiolipin antibodies, 1.2 (95% CI 0.9 –1.6) for MTHFR, 1.5 (95% CI 1.0 – 2.2) for factor V Leiden mutation and 1.6 (95% CI 0.8 – 3.2) for prothrombin gene mutation. In conclusion, regarding thrombophilic risk factors and RVO there is only evidence for an association with hyperhomocysteinemia and anticardiolipin antibodies, factors that are known as risk factors for venous thrombosis as well as for arterial vascular disease. The minor effect of factor V Leiden mutation and the protrombin gene mutation (risk factors for venous thrombosis only) suggests that atherosclerosis might be an important factor in the development of CRVO.

Keywords

Retinal vein thrombosis - retinal vein occlusion - risk factors - hyperhomocysteinemia - anticardiolipin antibodies

Full Text

References

References
1 David R, Zangwill L, Badarna M. et al. Epidemiology of retinal vein occlusion and its association with glaucoma and increased intraocular pressure. Ophthalmologica 1988; 197: 69-74.
2 Beaumont PE, Kang HK. Clinical characteristics of retinal venous occlusions occurring at different sites. Br J Ophthalmol 2002; 86: 572-80.
3 Williamson TH. Central retinal vein occlusion: what's the story?. Br J Ophthalmol 1997; 81: 698-704.
4 Dryden RM. Central retinal vein occlusions and chronic simple glaucoma. Arch Ophthalmol 1965; 73: 659-63.
5 Vannas S, Tarkkanen A. Retinal vein occlusion and glaucoma: tonographic study of the incidence of glaucoma and of its prognosic significance. Br J Ophtalmol 1960; 44: 583-89.
6 Hayreh SS, Zimmerman B, McCarthy MJ. et al. Systemic diseases associated with various types of retinal vein occlusion. Am J Ophthalmol 2001; 131: 61-77.
7 Johnston RL, Brucker AJ, Steinmann W. et al. Risk factors of branch retinal vein occlusion. Arch Ophthalmol 1985; 103: 1831-32.
8 Prisco D, Marcucci R, Bertini L. et al. Cardiovascular and thrombophilic risk factors for central retinal vein occlusion. Eur J Intern Med 2002; 13: 163-9.
9 Prisco D, Marcucci R. Retinal vein thrombosis: risk factors, pathogenesis and therapeutic approach. Pathophysiol Haemost Thromb 2002; 32: 308-11.
10 Rath EZ, Frank RN, Shin DH. et al. Risk factors for retinal vein occlusions. A case-control study. Ophthalmology 1992; 99: 509-14.
11 Recchia FM, Brown GC. Systemic disorders associated with retinal vascular occlusion. Curr Opin Ophthalmol 2000; 11: 462-67.
12 Robinson MK, Halpern JI. Retinal vein occlusion. Am Fam Physician 1992; 45: 2661-6.
13 Sperduto RD, Hiller R, Chew E. et al. Risk factors for hemiretinal vein occlusion: comparison with risk factors for central and branch retinal vein occlusion: the eye disease case-control study. Ophthalmology 1998; 105: 765-71.
14 Swart J, Reichert-Thoen JW, Suttorp Schulten MS. et al. Diabetes mellitus: a risk factor affecting visual outcome in branch retinal vein occlusion. Eur J Ophthalmol 2003; 13: 648-52.
15 Wenzler EM, Rademakers AJ, Boers GH. et al. Hyperhomocysteinemia in retinal artery and retinal vein occlusion. Am J Ophthalmol 1993; 115: 162-7.
16 Sterne JAC, Bradburn MJ, Egger M. Meta-analysis in Stata. Systematic reviews 2001; 347: 69.
17 Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955; 19: 251-3.
18 Abu El-Asrar AM, Abdel Gader AG, Al Amro SA. et al. Hyperhomocysteinemia and retinal vascular occlusive disease. Eur J Ophthalmol 2002; 12: 495-500.
19 Adamczuk YP, Iglesias Varela ML, Martinuzzo ME. et al. Central retinal vein occlusion and thrombophilia risk factors. Blood Coagul Fibrinolysis 2002; 13: 623-6.
20 Brown BA, Marx JL, Ward TP. et al. Homocysteine: a risk factor for retinal venous occlusive disease. Ophthalmology 2002; 109: 287-90.
21 Cahill M, Karabatzaki M, Meleady R. et al. Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease. Br J Ophthalmol 2000; 84: 154-7.
22 Lahey JM, Tunc M, Kearney J. et al. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology 2002; 109: 126-31.
23 Marcucci R, Bertini L, Giusti B. et al. Thrombophilic risk factors in patients with central retinal vein occlusion. Thromb Haemost 2001; 86: 772-6.
24 Pianka P, Almog Y, Man O. et al. Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology 2000; 107: 1588-92.
25 Vine AK. Hyperhomocysteinemia: a risk factor for central retinal vein occlusion. Am J Ophthalmol 2000; 129: 640-4.
26 Weger M, Stanger O, Deutschmann H. et al. Hyperhomocysteinemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion. Ophthalmology 2002; 109: 1105-9.
27 Yildirim C, Yaylali V, Tatlipinar S. et al. Hyperhomocysteinemia: a risk factor for retinal vein occlusion. Ophthalmologica 2004; 218: 102-6.
28 Marcucci R, Giusti B, Betti I. et al. Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion. Thromb Res 2003; 110: 7-12.
29 Boyd S, Owens D, Gin T. et al. Plasma homocysteine, methylene tetrahydrofolate reductase C677T and factor II G20210A polymorphisms, factor VIII, and VWF in central retinal vein occlusion. Br J Ophthalmol 2001; 85: 1313-15.
30 Cahill M, Karabatzaki M, Donoghue C. et al. Thermolabile MTHFR genotype and retinal vascular occlusive disease. Br J Ophthalmol 2001; 85: 88-90.
31 Cruciani F, Moramarco A, Curto T. et al. MTHFR C677T mutation, factor II G20210A mutation and factor V Leiden as risks factor for youth retinal vein occlusion. Clin Ther 2003; 154: 299-303.
32 Glueck CJ, Bell H, Vadlamani L. et al. Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion. Arch Ophthalmol 1999; 117: 43-9.
33 Larsson J, Hultberg B, Hillarp A. Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand 2000; 78: 340-3.
34 Salomon O, Moisseiev J, Rosenberg N. et al. Analysis of genetic polymorphisms related to thrombosis and other risk factors in patients with retinal vein occlusion. Blood Coagul Fibrinolysis 1998; 9: 617-22.
35 Weger M, Stanger O, Deutschmann H. et al. Hyperhomocysteinemia and MTHFR C677T genotypes in patients with central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2002; 240: 286-90.
36 Aras S, Yilmaz G, Alpas I. et al. Retinal vein occlusion and factor V Leiden and prothrombin 20210 G:A mutations. Eur J Ophthalmol 2001; 11: 351-5.
37 Bombeli T, Basic A, Fehr J. Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems. Am J Hematol 2002; 70: 126-32.
38 Demirci FY, Kucukkaya R, Akarcay K. et al. Ocular involvement in primary antiphospholipid syndrome. Int Ophthalmol 1998; 22: 323-9.
39 Johnson TM, El Defrawy S, Hodge WG. et al. Prevalence of factor V Leiden and activated protein C resistance in central retinal vein occlusion. Retina 2001; 21: 161-6.
40 Kalayci D, Gurgey A, Guven D. et al. Factor V Leiden and prothrombin 20210 A mutations in patients with central and branch retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 622-24.
41 Marcucci R, Bertini L, Liotta AA. et al. Activated protein C resistance is a risk factor for central retinal vein occlusion. Ann Ital Med Int 2000; 15: 195-8.
42 Kadayifcilar S, Ozatli D, Ozcebe O. et al. Is activated factor VII associated with retinal vein occlusion?. Br J Ophthalmol 2001; 85: 1174-8.
43 Larsson J, Hillarp A, Olafsdottir E. et al. Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 634-7.
44 Tekeli O, Gursel E, Buyurgan H. Protein C, protein S and antithrombin III deficiencies in retinal vein occlusion. Acta Ophthalmol Scand 1999; 77: 628-30.
45 Abu El-Asrar AM, Abdel Gader AG, Al Amro S. et al. Hypercoagulable states in patients with retinal venous occlusion. Doc Ophthalmol 1998; 95: 133-43.
46 Carbone J, Sanchez-Ramon S, Cobo-Soriano R. et al. Antiphospholipid antibodies: a risk factor for occlusive retinal vascular disorders. Comparison with ocular inflammatory diseases. J Rheumatol 2001; 28: 2437-41.
47 Cobo-Soriano R, Sanchez-Ramon S, Aparicio MJ. et al. Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study. Am J Ophthalmol 1999; 128: 725-32.
48 den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a metaanalysis of published epidemiological studies. J Thromb Haemost 2005; 3: 292-9.
49 Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002; 325: 1202
50 den Heijer M. Hyperhomocysteinaemia as a risk factor for venous thrombosis: an update of the current evidence. Clin Chem Lab Med 2003; 41: 1404-7.
51 den Heijer M, Rosendaal FR, Blom HJ. et al. Hyperhomocysteinemia and venous thrombosis: a metaanalysis. Thromb Haemost 1998; 80: 874-77.
52 Greiner K, Hafner G, Dick B. et al. Retinal vascular occlusion and deficiencies in the protein C pathway. Am J Ophthalmol 1999; 128: 69-74.
53 Hodgkins PR, Perry DJ, Sawcer SJ. et al. Factor V and antithrombin gene mutations in patients with idiopathic central retinal vein occlusion. Eye 1995; 9: 760-2.
54 Linna T, Ylikorkala A, Kontula K. et al. Prevalence of factor V Leiden in young adults with retinal vein occlusion. Thromb Haemost 1997; 77: 214-6.
55 Harats D, George J, Levy Y. et al. Atheroma: links with antiphopholipid antibodies, Hughes syndrome and lupus. Q J Med 1999; 92: 57-9.
56 Vaarala O. Antiphospholipid antibodies and atherosclerosis. Lupus 1996; 5: 442-7.