Bisphosphonates and ocular problems
Background of the problem. In a letter to the editor, see N Engl J Med 348;12, March 20, 2003, p. 1187-8, Fraunfelder FW and Fraunfelder FT mention that there have been several reports of adverse ocular effects from bisphosphonates to the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, OR), the Food and Drug Administration (Rockville, MD), and the World Health Organization (Uppsala, Sweden). Here is a list of the some of the types of problems that have been reported with a layman's definition (or as close to a layman's definition as I can find) of the problem so you will be aware of it should you develop one of the reported eye problems. For an excellent Website giving much more detailed information on these and other ocular problems, see the Handbook of Ocular Disease Management.
1. Conjunctivitis: Inflammation of the mucous membrane that lines the inner surface of the eyelids and is continued over the forepart of the eyeball.
2. Uveitis: Inflammation of the posterior pigmented layer of the iris. This is a serious, painful condition that needs immediate diagnosis and treatment.
3. Scleritis: Inflammation of the dense fibrous opaque white outer coat enclosing the eyeball except the part covered by the cornea. This can be a serious condition with pain in the eye and surrounding regions, extremely inflamed sclera, and it requires proper diagnosis and treatment to avoid damage to the eye.
4. Episcleritis: Redness and inflammation of the lateral segment of the sclera of one or both eyes. This tends to be much less serious than uveitis or scleritis and is generally painless.
A summary of reported ocular problems associated with bisphosphonates. Pamidronate disodium, one of the early bisphosphonates used to treat osteoporosis, can cause uveitis, nonspecific conjunctivitis, episcleritis, or scleritis. Additionally, the other bisphosphonates have also been reported to cause ocular problems. For example, alendronate (Fosamax) has had reports for 94 cases of abnormal or blurred vision, 33 cases of ocular pain, 30 cases of nonspecific conjunctivitis, 19 cases of uveitis, and 4 cases of scleritis. Of interest is that it has been verified that the bisphosphonates were truly causative of (at least) some of these problems. The authors point out, "A finding of particular importance to clinicians is that no case of unilateral or bilateral scleritis that developed in a person receiving bisphosphonates resolved, regardless of therapy, until the bisphosphonate was discontinued. In view of these reports, the authors have made several recommendations for guidelines for the care of patients receiving bisphosphonates.
Suggested guidelines.
1. Patients with vision loss or ocular pain should be referred to an ophthalmologist.
2. Nonspecific conjunctivitis seldom requires treatment, and usually decreases in intensity during subsequent exposure to bisphosphonate.
3. More than one ocular side effect can occur at the same time; for instance, episcleritis may occur in conjunction with uveitis. In some instances it may be necessary for the drug to be discontinued for the ocular inflammation to resolve.
4. For scleritis to resolve, even during full medical therapy, the bisphosphonate must be discontinued.
Editor's comments. This is a very interesting letter to the editor. I wonder if some of the conditions might not be very much under reported since few if any of us taking bisphosphonates would associate some eye problem with the medication. I know that I definitely have episcleritis and have just assumed it was normal for me. Now I'm wondering if it isn't related to the Fosamax. Since it appears to be such a benign and painless condition, would there be any reason to stop the Fosamax for any other reason than to show the direct causal relationship? I don't know the answer to that one. Uveitis or Scleritis are painful and cause serious inflammation, so it would be hard to overlook them. But, how often would the patient or the ophthalmologist relate the ocular problem to the bisphosphonate? Perhaps this letter to the editor will start to get the word out. If any of the men reading this segment have had any of these problems I'd love to get an email telling me about the problems, how they were diagnosed and treated, and if the osteoporosis medication was implicated in the problem by anyone.