13.1Medical Treatment of Retinal Vein Occlusion

Treatments for RVO attempt to reverse the underlying thrombosis or manage the secondary consequences. The Þrst class of treatments applies to acute RVO. For example, these treatments are not relevant in a patient who presents with a picture of chronic BRVO or CRVO with collateral vessels. Moreover, application of medical treatment to reverse thrombosis depends on severity of the clinical picture. In a young patient without vascular risk factors and with mild symptoms, excellent VA, and mild signs of a nonischemic CRVO, it is often prudent to observe the patient because many CRVOs will resolve spontaneously.

For acute RVO of a severity warranting intervention, many medical treatments have been advanced to address the suspected underlying physiology, but evidence of efÞcacy is generally

either lacking or so small that it is clinically unimportant.253 However, not all evidence is

negative.162,185,231

13.1.1 Anticoagulation

The rationale for anticoagulation in the treatment of CRVO is to change the balance between the naturally opposing forces of thrombosis and thrombolysis.69 Studies from the 1950s and 1960s took this approach, but because of drawbacks such as nonrandomized treatment allocation, nonstandardized and nonprospective data collection, and absence of statistical analysis, only vague conclusions could be drawn.67,69,291 More recent studies of anticoagulation and thrombolysis are similarly intuitive that the approach should work and better designed, but have also not shown beneÞt. Treatment of CRVO with warfarin is not

effective.253 There are many cases of patients with CRVO who developed their condition while on therapeutic doses of warfarin.31,59,108,189 In some cases of thrombophilia, however, warfarin therapy is indicated to reduce the probability of future systemic thrombosis. Whether this reduces the risk of subsequent same-eye or fellow-eye RVO is unknown.

Some have gone further and suggested that anticoagulation harms patients with RVO.100,101,109 In a retrospective study of 567 patients with CRVO and 119 patients with nonischemic HCRVO, patients were stratiÞed by baseline use of aspirin and warfarin.104 Use of aspirin was associated with worse retinal hemorrhage at baseline in nonischemic and ischemic CRVOs and nonischemic HCRVOs.104 In the patients with nonischemic CRVO and BCVA of 20/60 or better, baseline use of aspirin was associated with a higher rate of visual deterioration (adjusted OR 2.24, 95% CI 1.14Ð4.41, P = 0.02).104 Aspirin use was not associated with worse visual acuity outcomes in ischemic CRVOs or nonischemic HCRVOs.104

In a meta-analysis of three randomized clinical trials comparing subcutaneous injections of low molecular weight heparin (LMWH) versus aspirin for acute RVOs that included 111 BRVOs, the group receiving LMWH had statistically signiÞcantly improved VA at 6 months and fewer adverse ocular outcomes.162 Results were roughly the same for BRVO and CRVO, which led the authors to pool their cases.162 A drawback is that no study has compared LMWH to placebo, thus part of the effect difference might be an adverse effect of aspirin.100,104,108,162

Antiplatelet drugs that have been used in RVO include aspirin, ticlopidine, and beraprost. Aspirin is an irreversible inhibitor of the cyclooxygenase pathway. Ticlopidine increases intracellular cyclic AMP, which inhibits platelet aggregation. Beraprost, a stable prostacyclin analog, also increases intracellular cAMP. In one study, aspirin therapy failed to inhibit the formation of any size platelet aggregates in patients with pooled RVOs. Ticlopidine inhibited formation of small but not medium or large aggregates. Beraprost inhibited formation of aggregates of all sizes.311 None of

these drugs has been shown to be effective in CRVO or BRVO.67,253,290 Aspirin with intravenous thrombolysis has not reversed CRVO either.98,231 Ticlopidine was studied in a randomized trial of 54 patients with BRVO seen within 3 weeks of symptom onset. Ticlopidine taken orally for 6 months was associated with an improvement in VA in 69% of patients compared to 52% in the control group.116 The effect was not impressive enough for the therapy to be adopted, especially as ticlopidine has an adverse proÞle of potential side effects including neutropenia and thrombotic thrombocytopenic purpura.180,231

Troxerutin, an ingested drug that improves red cell deformability and reduces platelet aggregation, was tested in a placebo-controlled randomized trial of 26 patients with pooled BRVO and CRVO and ME. At 4 months follow-up, more patients receiving troxerutin had VA of 20/40 or better than the placebo group.82,231 The effect was not dramatic enough to stimulate a large-scale clinical trial, and this treatment has not been adopted.

In the rare instance when the antiphospholipid syndrome is found in association with RVO, treatment does involve anticoagulation, because the problem is interference by the APLAs with the coagulation system. Systemic steroids are not Þrst-line therapy in these cases.54 Patients with APLAs need systemic anticoagulation with warfarin until the absence of antiphospholipids has been documented for at least 6 months. Treatment is nonstandardized and sometimes includes immunosuppression with corticosteroids and the addition of antiplatelet drugs such as aspirin. Treatment can last for years, or even for the remainder of life, and is a decision to be made by the patient and the internist.

This may consist of warfarin, subcutaneous injection of enoxaparin, or other low molecular weight heparin, of oral pentoxifylline. Some patients with APLAs but not meeting the complete deÞnition of antiphospholipid syndrome have been treated with aspirin. EfÞcacy of these anticoagulation regimens in preventing future RVO has not been shown, and the treatments are based on hypotheses of efÞcacy or systemic considerations.