Article Date: 5/1/2006

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Systemic Anticoagulants and Retinal Vein Occlusion
"Doc, will taking an aspirin help me see better?"
GAURAV GUPTA, MD & PAUL B. GREENBERG, MD

A 70-year-old engineer with history of hypertension and diabetes mellitus presented to his ophthalmologist with a complaint of progressive, monocular visual loss over
1 week. On examination, his vision was 20/200 with a funduscopic exam consistent with a central retinal vein occlusion (Figure). After a lengthy discussion about his condition with the ophthalmologist, the patient retorted, "If my vision loss is from a clot in my blood vessels, shouldn't taking a blood thinner like aspirin or Coumadin (like my neighbor does for his heart) prevent this from occurring in the other eye?"

To answer this astute patient's question, this article will explore the clinical evidence on the use of systemic anticoagulants in managing retinal vein occlusion (RVO).

Figure. On examination, the patient's vision was 20/200 with a funduscopic exam consistent with a CRVO.

ANTICOAGULATION AGENTS

Warfarin (Coumadin, Bristol-Myers Squibb, Co.) is an inhibitor of vitamin K-dependent cofactors produced by the liver: factors II, VII, IX, X. Inhibition of these factors leads to a blockade of the extrinsic pathway, reducing the risk of recurrent thromboembolic episodes in patients with a history of deep venous thrombosis, pulmonary embolus, and atrial fibrillation.

Despite warfarin's efficacy in preventing these thrombotic complications, it has not been demonstrated to be beneficial in preventing or treating patients with RVO. Limited retrospective studies have shown that patients who are currently being treated with warfarin still develop RVO despite therapeutic anticoagulation.1,2 Moreover, another observational study of 66 patients suggested that anticoagulation with warfarin may actually prolong the duration of hemorrhage, slowing potential visual recovery.3

ANTIPLATELET AGENTS

Antiplatelet agents are widely used to minimize complications associated with systemic occlusive vascular disease. They include aspirin, clopidogrel, and ticlopidine. These medications inhibit platelet aggregation and thus clot formation.

Aspirin is the traditional antiplatelet agent for the prevention and treatment of occlusive vascular disease, such as myocardial infarction and stroke. More recently, clopidrogel and ticlopidine have been shown to be superior to aspirin in the prevention of secondary cardiovascular, cerebrovascular, and peripheral vascular events. However, these new antiplatelet agents also carry risks of leukopenia, thrombocytopenia, rashes, and major hemorrhage (Table).4

The prevalence of RVO vs. multiple cardiovascular risk factors was examined in the Beaver Dam Study: after examination of the 4926 patients in this population-based study, neither the prevalence nor the 5-year incidence of RVO was significantly affected by aspirin use.5 These data suggest that aspirin use may not be protective against RVO.

Two recent studies have suggested a possible benefit of ticlopidine in RVO. One study used a light-scattering method of evaluating platelet aggregation in patients taking antiplatelet agents and found that ticlopidine may decrease the formation of small platelet aggregates; aspirin was not found to inhibit the formation of any size aggregate.
On the premise that small aggregates may predispose patients to RVO, the authors concluded that ticlopidine — not aspirin — may be beneficial in the treatment and prevention of RVO.6

Table. Risks Associated With Aspirin and Platelet Aggregation Inhibitors

Aspirin:

Minor:   dyspepsia, nausea / vomiting

Major:   hemorrhage, gastrointestinal ulcers, Reye's syndrome , angioedema, bronchospasm, tinnitus

Platelet Aggregation Inhibitors (ie, clopidrogel and ticlopidine):

Minor:   abdominal pain, constipation, diarrhea, gastritis, skin rash, purpura

Major:   major hemorrhage, thrombotic thrombocytopenic purpura (TTP), gastrointestinal ulcer, intracranial hemorrhage, anemia, agranulocytosis (rare), neutropenia (rare), abnormal liver function tests (rare), hepatitis (rare), anaphylaxis (rare)

Another study created experimental RVOs in rabbits with a rose bengal-mediated argon laser photothrombosis. The investigators treated the subjects with various antiplatelet agents and found that pretreatment with aspirin or ticlopidine would significantly increase the number of spots required to induce RVO, which suggests a possible benefit of these medications in the prevention of RVO.4

Larger controlled clinical studies will be needed to confirm these findings before making any definitive conclusions regarding the role of ticlopidine in the management of RVO.

CONCLUSION

Overall, there is a lack of firm clinical evidence supporting the use of antiplatelet or anticoagulant agents in the prevention or treatment of RVO. Some preliminary studies suggest a possible role for ticlodipine in decreasing the risk of RVO, but this potential benefit must be weighed against possible side effects of the medication. At this time, the authors only recommend the use of these agents in patients with RVO if indicated for management of their systemic vascular occlusive disease.

REFERENCES

1. Browning DJ, Fraser CM. Retinal vein occlusions in patients taking warfarin. Ophthalmology. 2004;111:1196-1200.

2. Furuta M, et al. Warfarin potassium for impending retinal vein occlusion. Journal of Japanese Ophthalmological Society. 1999;103:124-128.

3. Ota R, Okisaka S. Effects of anticoagulant therapy on retinal vein occlusion. Journal of Japanese Ophthalmological Society. 1995;99:955-958.

4. Arroyo JG, Dastgheib K, Hatchell DL. Antithrombotic effect of ticlopidine in an experimental model of retinal vein occlusion. Jpn J Ophthalmol. 2001;45:359-362.

5. Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: The Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2000;98:133-141.

6. Yamamoto T, et al. Comparative effect of antiplatelet therapy in retinal vein occlusion evaluated by the particle-counting method using light scattering. Am J Ophthalmol. 2004;138:809-817

Gaurav Gupta, MD, is an ophthalmology resident at the Division of Ophthalmology, Brown Medical School/Rhode Island Hospital. Paul B. Greenberg, MD, is a clinical assistant professor at the Division of Ophthalmology, Brown Medical School/Rhode Island Hospital and is in private practice at Retina Consultants, Inc. Neither author has any financial interest in the information presented in this article. Dr. Gupta can be reached by e-mail at gaurav.gupta@umassmed.edu.



Retinal Physician, Issue: May 2006