Anticoagulants and Retinal Vein Occlusion
"Doc, will taking an aspirin help me see better?"
GAURAV GUPTA, MD & PAUL B.
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).
On examination, the patient's vision was 20/200 with a funduscopic exam consistent
with a CRVO.
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
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
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
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.
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.
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.
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
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 email@example.com.
Retinal Physician, Issue: May 2006