July 29, 2006

Abortion Drug Offers Hope for People with Central Serous Chorioretinopathy

Posted in: Research and Developments, Therapies, Treatments, and Procedures

An abortion drug known as ru486 is showing potential as a treatment for central serous chorioretinopathy (CSC), a condition which can lead to loss of central vision. The drug, also called mifepristone, blocks the action of progesterone, a hormone necessary to sustain pregnancy. It is also a potent antiglucocorticoid agent.

Glucocorticoids are drugs and hormones which have anti-inflammatory characteristics and increase blood glucose levels. They may be synthetically-produced or they may occur normally as a product of the adrenal cortex, providing for stress response. Glucocorticoids (aka corticosteroids) have also been show to be a contributing factor in the development of CSC.

This was discussed in a guest editorial published in November 2002 (“Involvement of corticosteroids and catecholamines in the pathogenesis of central serous chorioretinopathy: a rationale for new treatment strategies.” Lee M. Jampol, M.D., Robert Weinreb, M.D., and Lawrence Yannuzzi, M.D. Ophthalmology (2002) 109: 1765-1766). According to the authors, “CSC has been reported in association with Cushing’s disease from pituitary adenomas or steroid producing adrenal tumors, administration of adrenocorticotrophic hormone therapy (ACTH), [and] exogenous administration of corticosteroids including use systemically, by inhaler or nasal spray, and depot injection.” Commonly used glucocorticoids include hydrocortisone, prednisone, methylprednisolone, and long-acting dexamethasone.

CSC also develops in patients who have not been administered corticosteroids. This, the authors speculate, could be due to any of several conditions:

1. The patients have elevated levels of endogenous corticosteroids

2. The binding affinity of corticosteroid receptors in those patients might be greater than in patients without CSC

3. There may be a difference in the bioavailability of corticosteroids in the choroid or RPE because of differences in absorption, penetration, or metabolism

4. There may be a difference in posttranslational corticosteroid effects.

Lee M. Jampol, M.D. has been working on the problem. In November 2002 he said, “I am certain steroids are playing a role in many or all cases of this disease,” and that “the steroid antagonists [i.e. ru486] are a very promising possibility” as treatment. FDA approval of the drug in September 2000 for use in abortions in the United States helped to pave the way for trials. Prior to that approval, it had been made available in this country only under compassionate use protocols for a small number of people with Cushing’s syndrome, meningioma, and breast cancer. Since that time, it has been shown to be safe and effective in humans, not only for abortion (in combination with misoprostol, a prostaglandin), but as a treatment for conditions and diseases that are caused by elevated levels of cortisol.

CSC most commonly affects middle-aged males who exhibit Type A personality behavior. It also affects women during pregnancy. In most cases, the condition resolves itself, but there can be permanent loss of vision with repeated episodes, persistent macular detachment, or diffuse disease. Simply put, ru486 blocks the glucocorticoid receptors in the body. This, in turn, prevents elevated levels of glucocorticoids, which can lead to episodes of CSC.

Dr. Jampol described his study as a 90-day randomized controlled trial of ru486 versus placebo. Ru486 has been approved for off-label use in the study by the Institutional Review Board, the purpose being to determine the drug’s value for patients with chronic CSC who are not treatable by other means. Patients were referred by their ophthalmologist, and multiple visits to the Chicago study center were necessary. There was no charge for the drug or placebo, and insurance covered most of the other costs.

In July 2006, Dr. Jampol reported results from the study. In a letter to the participants, he wrote that it “consisted of 8 patients, 4 taking mifepristone and 4 taking a placebo. Two patients taking the mifepristone demonstrated some improvement of their disease, with one patient having a particularly favorable response. One patient taking the placebo had some improvement of the disease on retinal imaging. No side effects were experienced by any patients taking the medication.”

For more information, doctors may contact Lee Jampol, M.D. at:

Northwestern Medical Faculty Foundation, Inc.
Department of Opththalmology Retinal Study Center
675 North St. Clair Street, Suite15-150
Chicago, IL 60611
Tel: (312) 695-8150
E-mail: l-jampol@northwestern.edu.

For more about central serous chorioretinopathy (CSC), also known as central serous retinopathy (CSR), see the web site of the Vitreous Retina Macula Consultants of New York.

To read a theoretical paper on the vicious circle of secondary stress caused by CSC, read “Glucocorticoids and Secondary Stress as Combined Causes of Chronic Central Serous Chorioretinopathy in Type A People” on this site.

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