Central Retinal Vein Occlusion

Management of CRVO(continued)

A. MEDICAL TREATMENTS

• Anticoagulants and antiplatelet agents: The required treatment for many of the major systemic venous thromboembolic disorders (e.g., deep vein thrombosis) is anticoagulants or agents which reduce platelet aggregation. Because of that, unfortunately, there is a common impression among ophthalmologists and hematologists that these therapeutic agents should also help patients with CRVO. My studies of CRVO have shown anticoagulant therapy to be harmful because it increases the amount of retinal hemorrhages, with devastating results - often converting a benign form of CRVO into blinding CRVO¹¹. Not only that, but I also have many patients who developed CRVO while on anticoagulants for various systemic diseases, clearly indicating lack of therapeutic benefit by anticoagulants. I have found that patients on antiplatelet agent, such as aspirin, are also liable to develop excessive retinal hemorrhages which adversely affect the outcome.¹¹
  
  Conclusion: Available evidence and our experience of managing more than 700 cases of CRVO over more than three decades indicate that anticoagulants and antiplatelet agents are contraindicated in CRVO¹¹; they are not only of no therapeutic value but are definitely harmful. Therefore, they should never be used unless there are other more important life-threatening systemic indications.

• Hemodilution: A few studies have suggested the presence of abnormal blood viscosity in CRVO patients. Based on that assumption, some authors have advocated the use of hemodilution in CRVO. I recently reviewed⁶ all the available reports on hemodilution in the literature and found that there is little scientifically valid evidence of beneficial effects of this therapy.
  
  Conclusion: There is no convincing evidence that hemodilution benefits patients with CRVO. Therefore, I do not advocate this therapy.

• Systemic corticosteroids: In non-ischemic CRVO, as discussed above, the primary cause of visual disability is the presence of macular edema. Therefore, in these cases the most important management consideration is controlling macular edema. There is no definite therapy available to treat macular edema. In our prospective studies on the subject for about 30 years, I have found that there is a small group of patients with non-ischemic CRVO who respond to systemic corticosteroids when given in high doses (80 mg Prednisone daily), with resolution of macular edema and visual improvement while they are on therapy. Unfortunately, when the steroids therapy is lowered below a certain level (usually 40 mg Prednisone), the macular edema returns and the vision starts to deteriorate. It is not at all uncommon for those who respond to treatment to require a maintenance dose of about 40 mg Prednisone or so for many months. For example, in one young man with non-ischemic CRVO in his only eye and a visual acuity of 20/200 (6/60) initially, visual acuity immediately improved to 20/30-20/40 (6/9-6/12) with 80 mg prednisone. To maintain that visual acuity he required a maintenance dose of 30-40 mg Prednisone for almost 3 years, and every attempt to go any lower immediately produced worsening of macular edema and deterioration of visual acuity. He finally ended up with a visual acuity of 20/20 (6/6) and no visual or systemic disability. Of course, a maintenance therapy for a long period produces side-effects of corticosteroids and the patient needs a close follow-up by both the ophthalmologist and the internist.
  
  The most critical thing to remember in systemic corticosteroid therapy for macular edema is that it does not work in every patient. If a patient shows no improvement within two weeks, I stop the treatment. It is also important to stress to the patient that the treatment is simply helping to reduce or eliminate macular edema to prevent long term permanent macular changes, and that it is NOT a cure for the CRVO which has to take its own natural course.

• Intravitreal corticosteroids: Recently improvement of macular edema and visual acuity has been reported in a few eyes with non-ischemic CRVO and macular edema with intravitreal injection of triamcinolone acetonide. I have discussed this regimen of treatment in my recent review⁶. Intravitreal injection of triamcinolone acetonide temporarily improved visual acuity but on a long-term follow up there was no significant difference between the initial pre-injection visual acuity and the final visual acuity (personal communication from Professor Jost Jonas). Among the reported side-effects of intravitreal injection of triamcinolone acetonide (most of the studies are in diabetic macular edema) are development of ocular hypertension (requiring anti-glaucoma therapy) in about 33% to 50% of eyes after about one to two months, progression of cataract in some, and, rarely, endophthalmitis. Repeated intravitreal injections of triamcinolone acetonide can result in primary open angle glaucoma; this is particularly important in CRVO since in these patients there is already a significantly high incidence of glaucoma and ocular hypertension¹². In contrast to this, in my experience of treating these patients with systemic steroids (see above), the incidence of developing ocular hypertension is very low.
  
  Conclusion: Available evidence indicates that oral or intravitreal corticosteroids may help to reduce macular edema associated with non-ischemic CRVO and improve visual acuity in some patients, but only as long as they are on the treatment. I have found steroid therapy of no help in ischemic CRVO in spite of the presence of macular edema, most probably because of irreversible ischemic damage to the retinal ganglion cell in the macular region.

• Systemic acetazolamide (Diamox): I have found that some patients (but not all) with non-ischemic CRVO and macular edema respond to this therapy; but once again the macular edema is under control only so long as the patient is taking the drug. I usually give sustained release acetazolamide (Diamox Sequels) 500 mg twice daily. Unfortunately this drug can also produce severe systemic side-effects in some patients. If a patient does not respond within 2 weeks, there is high likelihood that he/she is not going to respond. I have not found this helpful in ischemic CRVO.
  
  Conclusion: Available evidence indicates that Diamox may help to reduce macular edema associated with non-ischemic CRVO and improve visual acuity for some patients, but only as long as they continue the treatment.

• Ocular hypotensive therapy: Ophthalmologists often start the eye with CRVO on ocular hypotensive therapy, e.g., topical beta blockers, etc. or even systemic carbonic anhydrase inhibitors, under the erroneous impression that lowering the intraocular pressure in the involved eye improves the retinal blood flow. With venous outflow obstruction, lowering the intraocular pressure does not influence the retinal blood flow. Moreover, our clinical and experimental studies have clearly shown that development of CRVO, by some unknown mechanism, actually lowers the intraocular pressure, usually more than any of the ocular hypotensive agents do. We have discussed the whole subject in detail elsewhere¹². I jokingly tell my residents and fellows that CRVO is the most effective treatment available to lower intraocular pressure! Thus, eyes with CRVO usually have normal intraocular pressure unless they develop neovascular glaucoma. In eyes with normal intraocular pressure, ocular hypotensive therapies seldom lower the pressure appreciably. Furthermore, lowering the IOP to very low levels could enhance macular edema.
  
  Since there is a high incidence of ocular hypertension or glaucoma in patients with CRVO, development of CRVO in one eye mandates treatment of ocular hypertension in the fellow uninvolved eye to reduce the risk of development of CRVO in that eye¹².
  
  Conclusion: There is no scientific rationale for the use of ocular hypotensive therapy in CRVO eyes with normal IOP. However, the fellow uninvolved eye MUST be treated to reduce the chances of its developing CRVO if it has ocular hypertension or glaucoma.