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Original Article
Influence of factor V Leiden on the development of neovascularisation secondary to central retinal vein occlusion
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  1. C Hvarfner1,
  2. A Hillarp2,
  3. J Larsson1
  1. 1Department of Ophthalmology, Lund University Hospital, Sweden
  2. 2Department of Clinical Chemistry, Malmö University Hospital, 211 85 Malmö, Sweden
  1. Correspondence to: Charlotte Hvarfner, Department of Ophthalmology, Lund University Hospital, 211 85 Lund, Sweden; charlotte.hvarfner{at}oft.lu.se

Abstract

Aims: To investigate if the presence of factor V Leiden has an influence on the prognosis in central retinal vein occlusion (CRVO).

Methods: 166 patients with CRVO were studied retrospectively. They were tested for factor V Leiden using DNA analysis. The presence of the mutation was studied in correlation with the development of neovascular complications 1 year after the thrombotic event.

Results: 56 of 166 patients (34%) developed neovascular complications after 1 year. In the patients who had the studied mutation 11 of 20 (55%) had developed neovascular complications after 1 year, compared to 45 of 146 patients (31%) in the group without factor V Leiden (p=0.04).

Conclusion: The presence of factor V Leiden seems to enhance the risk of developing neovascular complications in CRVO.

  • central retinal vein occlusion
  • factor V Leiden
  • neovascular complications

http://dx.doi.org/10.1136/bjo.87.3.305

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    Glaucoma, hypertension, arteriosclerosis, and diabetes are factors that are well known to be associated with central retinal vein occlusion (CRVO). These conditions affect vascular flow or cause vascular wall abnormalities, thereby contributing to the development of CRVO.1–5

    Hereditary alterations in the coagulation/anticoagulation pathways can result in thrombophilia, increasing the risk for thrombosis.6,7 It is, however, debatable whether hereditary alterations in the coagulation pathway are aetiological factors for CRVO.

    Activated protein C resistance is the most common genetic cause of venous thrombosis.6 A point mutation in factor V (factor V Leiden) renders it resistant to the normal inactivation by activated protein C. This “activated protein C resistance” produces a mild thrombophilic state. There are studies in the literature pointing towards an association between CRVO and factor V Leiden,8–12 though most of the evidence today indicates that factor V Leiden does not have a major aetiological role in CRVO.13–22

    After thrombus formation, independent of cause, a restoration of the venous lumen can occur spontaneously.23,24 We do not know the exact mechanism of this recanalisation, but it could be related to the balance of coagulation/anticoagulation.25 We stated the hypothesis that even though factor V Leiden has not been found to be an important risk factor for CRVO, it may have a more important role during the recanalisation phase after the thrombotic event. We wanted to investigate if the factor V Leiden influences the prognosis in CRVO, and so studied the prevalence of factor V Leiden in relation to the development of neovascular complications after CRVO.

    PATIENTS AND METHODS

    Patients

    A total of 190 consecutive patients with CRVO examined in the eye clinic of Lund University Hospital from 1994 to 2000 were invited to take part in the study; of these, 166 patients agreed to participate. Venous blood samples were collected after informed consent was obtained. Of the 166 patients, 86 were men and 80 were women. The patients were aged between 22 and 91 years (mean age 64 (SD 15) years).

    All patients were followed for at least 1 year. This time was chosen as we know that the majority of the patients who develop neovascular complications after CRVO have done so within this time period.26–29 The end point was the development of neovascular complications or not, 1 year after the thrombothic event. Neovascular complications were defined as any retinal, disc, iris, or chamber angle neovascularisations. Clinical information was derived from the patient records.

    DNA analysis

    Preparation of genomic DNA from EDTA blood and determination of the factor V Leiden mutation (G to A at nucleotide position 1691), which causes activated protein C resistance, was performed as described earlier.30

    RESULTS

    After a year 56 of 166 patients (34%) had developed neovascular complications. Factor V Leiden was present in 20 of 166 patients (12%). The patients with factor V Leiden did not significantly differ in age or sex compared to the patients without the studied mutation. The patients with factor V Leiden, 10 men and 10 women, ranged in age between 22 and 86 years (mean 58 years; median 64 years). The patients without factor V Leiden, 76 men and 70 women, ranged in age between 28 and 91 years (mean 65 years; median 68 years).

    In the patients with factor V Leiden, 11 of 20 (55%) developed neovascular complications. In the patients without the mutation 45 of 146 patients (31%) developed neovascular complications (p=0.04; Fischer’s exact test) (Fig 1). This gives an odds ratio of 2.7 (CI 95% 1.1 to 7.1).

    Figure 1
    Figure 1

    The presence of factor V Leiden correlated with the development of neovascular complication in CRVO. The result points towards an almost threefold risk of developing complications with the mutation present.

    DISCUSSION

    In this study we have shown that the presence of factor V Leiden seems to increase the risk for neovascularisation secondary to CRVO.

    The presence of factor V Leiden results in a mildly thrombophilic state. Although it has not been found to be an important risk factor for CRVO,13–22 it is possible that factor V Leiden may have a more important role in the recirculation phase after the thrombotic event. The mild predominance of coagulation over anticoagulation may contribute to a delayed recirculation, and thereby possibly a more severe ischaemia resulting in a higher risk for neovascular complications. Our study points towards an almost threefold risk of developing neovascular complications after CRVO with factor V Leiden present. We have not seen other studies in the literature regarding factor V Leiden and the prognosis for CRVO.

    As the presence of the studied mutation is independent of the time of the blood sample, this has enabled us to supplement the DNA tests independent of time for follow up. Since it is well established that the most important risk factor for the development of neovascular complications after CRVO is the extent of retinal ischaemia,2–29,31,32 it would have been of interest to see if the patients presenting with factor V Leiden mutation showed a more pronounced retinal ischaemia, as detected by fluorescein angiography, but a weakness of this study being retrospective is that this information is not complete. This would preferably be dealt with in another prospective study.

    The incidence of neovascular complications in our patients during the first year after the thrombotic event is in accordance with earlier reports.26–29,31,32 The prevalence of factor V Leiden is also at the level expected in the normal population in the studied area,6 which confirms that factor V Leiden probably does not have an important aetiological role in CRVO, as pointed out earlier.13–22

    In conclusion, the presence of factor V Leiden seems to enhance the risk of developing neovascular complications in CRVO.

    REFERENCES

    1. ↵
      McGrath MA, Wechsler F, Hunyor AB, et al. Systemic factors contributory to retinal vein occlusion. Arch Intern Med 1978;138:216–20.
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      Ring CP, Pearson TC, Sanders MD, et al. Viscosity and retinal vein thrombosis. Br J Ophthalmol 1976;60:397–410.
      OpenUrlAbstract/FREE Full Text
    3. Elman MJ. Systemic associations of retinal vein occlusion. Int Ophthalmol Clin 1991;31:15–22.
      OpenUrlCrossRefPubMedWeb of Science
    4. Hirota A, Mishima HK, Kiuchi Y. Incidence of retinal vein occlusion at the glaucoma clinic of Hiroshima University. Ophthalmologica 1997;211:288–91.
      OpenUrlPubMedWeb of Science
    5. ↵
      The Eye Disease Case-Control Study Group. Risk factors for central retinal vein occlusion. Arch Ophthalmol 1996;114:545–54.
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      Dahlback B. Blood coagulation. Lancet 2000;355:1627–32.
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      Spek CA, Reitsma PH. Genetic risk factors for venous thrombosis. Mol Genet Metab 2000;71:51–61.
      OpenUrlCrossRefPubMed
    8. ↵
      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.
      OpenUrlCrossRefPubMedWeb of Science
    9. Albisinni R, Coppola A, Loffredo M, et al. Retinal vein occlusion and inherited conditions predisposing to thrombophilia. Thromb Haemost 1998;80:702–3.
      OpenUrlPubMedWeb of Science
    10. Glueck CJ, Bell H, Vadlamani L, et al. Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion. Arch Ophthalmol 1999;117:43–9.
      OpenUrlPubMedWeb of Science
    11. Greiner K, Peetz D, Winkgen A, et al. Genetic thrombophilia in patients with retinal vascular occlusion. Int Ophthalmol 1999;23:155–60.
      OpenUrlCrossRefPubMed
    12. ↵
      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.
      OpenUrlPubMed
    13. ↵
      Ciardella AP, Yannuzzi LA, Freund KB, et al. Factor V Leiden, activated protein C resistance, and retinal vein occlusion. Retina 1998;18:308–15.
      OpenUrlPubMed
    14. Larsson J, Sellman A, Bauer B. Activated protein C resistance in patients with central retinal vein occlusion. Br J Ophthalmol 1997;81:832–4.
      OpenUrlAbstract/FREE Full Text
    15. Gottlieb JL, Blice JP, Mestichelli B, et al. Activated protein C resistance, factor V Leiden, and central retinal vein occlusion in young adults. Arch Ophthalmol 1998;116:577–9.
      OpenUrlCrossRefPubMedWeb of Science
    16. Graham SL, Goldberg I, Murray B, et al. Activated protein C resistance—low incidence in glaucomatous optic disc haemorrhage and central retinal vein occlusion. Aust NZ J Ophthalmol 1996;24:199–205.
      OpenUrlPubMedWeb of Science
    17. 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.
      OpenUrlPubMed
    18. 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.
      OpenUrlPubMedWeb of Science
    19. Raguenes O, Mercier B, Escoffre M, et al. [1691 G to A mutation of the factor V gene: no association with thrombosis of the central retinal vein] Presse Med 1996;25:460.
      OpenUrlPubMed
    20. 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.
      OpenUrlCrossRefPubMedWeb of Science
    21. 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.
      OpenUrlCrossRefPubMedWeb of Science
    22. ↵
      Scott JA, Arnold JJ, Currie JM, et al. No excess of factor V:Q506 genotype but high prevalence of anticardiolipin antibodies without antiendothelial cell antibodies in retinal vein occlusion in young patients. Ophthalmologica 2001;215:217–21.
      OpenUrlCrossRefPubMedWeb of Science
    23. ↵
      Chan CC, Green WR, Rice TA. Experimental occlusion of the retinal vein. Graefes Arch Clin Exp Ophthalmol 1986;224:507–12.
      OpenUrlCrossRefPubMed
    24. ↵
      Green WR, Chan CC, Hutchins GM, et al. Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Trans Am Ophthalmol Soc 1981;79:371–422.
      OpenUrlPubMed
    25. ↵
      Meissner MH, Zierler BK, Bergelin RO, et al. Coagulation, fibrinolysis, and recanalization after acute deep venous thrombosis. J Vasc Surg 2002;35:278–85.
      OpenUrlCrossRefPubMedWeb of Science
    26. ↵
      The Central Vein Occlusion Study Group N report. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. Ophthalmology 1995;102:1434–44.
      OpenUrlPubMedWeb of Science
    27. Magargal LE, Brown GC, Augsburger JJ, et al. Neovascular glaucoma following central retinal vein obstruction. Ophthalmology 1981;88:1095–101.
      OpenUrlPubMed
    28. Magargal LE, Donoso LA, Sanborn GE. Retinal ischemia and risk of neovascularization following central retinal vein obstruction. Ophthalmology 1982;89:1241–5.
      OpenUrlPubMedWeb of Science
    29. ↵
      Sinclair SH, Gragoudas ES. Prognosis for rubeosis iridis following central retinal vein occlusion. Br J Ophthalmol 1979;63:735–43.
      OpenUrlFREE Full Text
    30. ↵
      Zoller B, Svensson PJ, He X, Dahlback B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994;94:2521–4.
      OpenUrlCrossRefPubMedWeb of Science
    31. ↵
      Hayreh SS, Rojas P, Podhajsky P, et al. Ocular neovascularization with retinal vascular occlusion—III. Incidence of ocular neovascularization with retinal vein occlusion. Ophthalmology 1983;90:488–506.
      OpenUrlPubMedWeb of Science
    32. ↵
      Quinlan PM, Elman MJ, Bhatt AK, et al. The natural course of central retinal vein occlusion. Am J Ophthalmol 1990;110:118–23.
      OpenUrlPubMedWeb of Science