Steroid reliance too common in treating uveitis
Steroid reliance too common in treating uveitis
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Although steroids are useful in treating uveitis (pictured here), long-term use results in side effects, such as cataracts Source: Manolette Roque, M.D.
More training with uveitis experts is needed; disease is curable with immunosuppressive therapy
Despite major inroads in the treatment of many ocular diseases, uveitis rates have remained nearly the same for the past 35 years.
The disease has an estimated prevalence of 38 in 100,000. Of that, 10% of patients will become blind.
"The reason that there has been no significant progress in driving down the prevalence in developed countries around the world is because of the exclusive reliance on steroid therapy by the bulk of ophthalmologists who care for patients with uveitis," said C. Stephen Foster, M.D., clinical professor of ophthalmology, Harvard Medical School, Boston. "They do so because that's all they've ever been taught."
Dr. Foster is founder and president of the Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution, Cambridge. He offered some valuable advice to general ophthalmologists faced with treating the non-infectious autoimmune intraocular inflammation.
Training is key
First, ophthalmic training programs need to include faculty who are trained in ocular immunology, specifically in uveitis and the use of drugs other than steroids for treating patients with uveitis, Dr. Foster said. Of the 130 ophthalmology residencies in the U.S., there are about 20 with a fellowship-trained uveitis specialist on the faculty.
"Every June 30, another class of graduating residents finishes their training having only seen steroids used in the care of patients with uveitis," he said. "When they go out to their own practice, what do you think they're going to do? They're going to use steroids and only steroids, whether it's injecting or using them as drops. I am convinced, and many of us on the executive committee of the American Uveitis Society are convinced, that no measurable change in practice patterns is going to happen until more training programs are developed or more chairmen of the departments actively recruit a properly trained ocular immunologist or uveitis specialist onto their faculties."
Dr. Foster said uveitis specialists are often seen as a drain on a department's budget because they will eat up space, salary, and support staff resources and not result in sufficient reimbursement to the department to cover the cost.
"That's categorically wrong," Dr. Foster said. "If the uveitis specialist is correctly trained, he or she will actually be a money maker for the department."
Steroids are valuable, but …
Since the first steroid was administered in a human eye in 1949 by Dan Gordon, M.D., professor at Cornell Medical Center, New York, nothing has come close to its effectiveness for snuffing out inflammation quickly.
However, Dr. Gordon, and doctors at the Mayo Clinic who were the first to use systemic steroids to treat patients, soon realized the disturbing side effects of the drug.
"Within a year, they realized that the chronic use of steroids comes at a fairly high price in terms of side effects that are not desirable," Dr. Foster said. "Most drugs have potential side effects. With corticosteroids, they are 100% guaranteed."
When steroids are used locally in the eye long enough, cataracts would be 100% guaranteed.
"Thirty percent of the patients who have chronic steroid use end up with elevated IOP and some damage to the retinal ganglion cells that is evidenced by classic glaucoma," Dr. Foster said.
Steroids and then what?
Like most practitioners, Dr. Foster begins therapy with a course of steroids and then tapers them off.
"For example, if I am dealing with a child who has juvenile idiopathic or juvenile rheumatoid arthritis associated uveitis, I always use steroids first and then taper them," he said. "If the problem recurs, I use steroids again and then taper them, and if the problem occurs again, I have a conversation with the parents about steroid-sparing therapy, but I will go ahead and use steroids again."
If the patient—pediatric or adult—has been using steroid therapy for 6 months, whether it is chronic use, steady use, or intermittent use, Dr. Foster said that's when it's time to move on.
"That's the point that a tremendous number of comprehensive ophthalmologists simply have not incorporated into their bone marrow yet," he said. "The easiest and the knee-jerk reflex thing to do is what the doctor was taught to do in residency, and that is to simply do what worked before. That is to start dousing with steroids again and not invest the time, intellect, and energy in the more difficult matter of conversations about referrals and steroid-sparing therapy."
The type of uveitis dictates how Dr. Foster will approach treatment.
"That governs when I will suggest getting invasive by doing an intraocular injection, intraocular implant, or doing surgery, which involves cleaning out the vitreous and all the inflammatory cells in it, or pulling the trigger on so-called steroid-sparing immunosuppressive therapy," he said.
Immunosuppressive therapy
Uveitis doesn't have to involve a lifelong treatment course.
"There are a few diseases that require long-term care, but the bulk of the diseases we deal with are, frankly, curable," Dr. Foster said. "The immune system, if manipulated correctly, has the capacity to relearn how to behave itself properly and not begin attacking the patient's tissues yet again when medications are taken away."
After a patient is entirely off steroids, it takes a minimum of 2 years on immunomodulatory drugs to see a cure.
"Patients have to be off the steroids for you to know that the immunomodulators are in the right dose, are the right type, and that they are, in fact, setting the stage for the re-education of the immune system," Dr. Foster said. "We have a tremendous number of various types of uveitis that are outright cured—in remission, off steroids, on immunosuppressants for a finite period. The immunosuppressants are then tapered and withdrawn, and 5-10 years later, the patients are still without any evidence of recurrence of uveitis. It's like in cancer: You get to 5 years, and you have to call that a cure."
A whole panoply of immunomodulators is available, according to Dr. Foster.
Those include antimetabolites such as methotrexate, mycophenolate mofetil, and azathioprine; calcineurin inhibitors such as cyclosporine, tacrolimus, and sirolimus; and alkylating drugs such as cyclophosphamide and chlorambucil. Another category of immunomodulatory drugs is a class called biologic response modifiers, or biologics, including anakinra, eculizumab, rituximab, infliximab, and adalimumab. There are drugs in the pipeline, such as Interleukin-17, that inhibit the other molecules important in inflammation, Dr. Foster said. "In general, if you pluck an arrow out of your quiver to shoot at the inflammatory problem, no matter what arrow you pick or what drug you choose, there's about a 70% chance that the drug is going to be the salvation of that particular patient," Dr. Foster said. "It's going to fix the problem—no muss, no fuss, no need for anything more. Keep patients on it for 2 years and you're home free."
It's OK to move along if one of these drugs isn't working, he added.
Co-management
Comprehensive ophthalmologists shouldn't feel pressured to know every immunosuppressive drug available to patients. Instead, they should work on developing and maintaining co-management relationships with doctors who do.
Partner with a hematologist or rheumatologist, Dr. Foster advised.
"They're very collaborative and collegial," he said. "It's important to feel comfortable in the co-management of the patient."
Editors' note: Dr. Foster has no financial interests related to his comments.
Contact information
Foster: 617-621-6377, sfoster@mersi.us
by Jena Passut EyeWorld Staff Writer
--------------------------------------------------------------------------------
Although steroids are useful in treating uveitis (pictured here), long-term use results in side effects, such as cataracts Source: Manolette Roque, M.D.
More training with uveitis experts is needed; disease is curable with immunosuppressive therapy
Despite major inroads in the treatment of many ocular diseases, uveitis rates have remained nearly the same for the past 35 years.
The disease has an estimated prevalence of 38 in 100,000. Of that, 10% of patients will become blind.
"The reason that there has been no significant progress in driving down the prevalence in developed countries around the world is because of the exclusive reliance on steroid therapy by the bulk of ophthalmologists who care for patients with uveitis," said C. Stephen Foster, M.D., clinical professor of ophthalmology, Harvard Medical School, Boston. "They do so because that's all they've ever been taught."
Dr. Foster is founder and president of the Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution, Cambridge. He offered some valuable advice to general ophthalmologists faced with treating the non-infectious autoimmune intraocular inflammation.
Training is key
First, ophthalmic training programs need to include faculty who are trained in ocular immunology, specifically in uveitis and the use of drugs other than steroids for treating patients with uveitis, Dr. Foster said. Of the 130 ophthalmology residencies in the U.S., there are about 20 with a fellowship-trained uveitis specialist on the faculty.
"Every June 30, another class of graduating residents finishes their training having only seen steroids used in the care of patients with uveitis," he said. "When they go out to their own practice, what do you think they're going to do? They're going to use steroids and only steroids, whether it's injecting or using them as drops. I am convinced, and many of us on the executive committee of the American Uveitis Society are convinced, that no measurable change in practice patterns is going to happen until more training programs are developed or more chairmen of the departments actively recruit a properly trained ocular immunologist or uveitis specialist onto their faculties."
Dr. Foster said uveitis specialists are often seen as a drain on a department's budget because they will eat up space, salary, and support staff resources and not result in sufficient reimbursement to the department to cover the cost.
"That's categorically wrong," Dr. Foster said. "If the uveitis specialist is correctly trained, he or she will actually be a money maker for the department."
Steroids are valuable, but …
Since the first steroid was administered in a human eye in 1949 by Dan Gordon, M.D., professor at Cornell Medical Center, New York, nothing has come close to its effectiveness for snuffing out inflammation quickly.
However, Dr. Gordon, and doctors at the Mayo Clinic who were the first to use systemic steroids to treat patients, soon realized the disturbing side effects of the drug.
"Within a year, they realized that the chronic use of steroids comes at a fairly high price in terms of side effects that are not desirable," Dr. Foster said. "Most drugs have potential side effects. With corticosteroids, they are 100% guaranteed."
When steroids are used locally in the eye long enough, cataracts would be 100% guaranteed.
"Thirty percent of the patients who have chronic steroid use end up with elevated IOP and some damage to the retinal ganglion cells that is evidenced by classic glaucoma," Dr. Foster said.
Steroids and then what?
Like most practitioners, Dr. Foster begins therapy with a course of steroids and then tapers them off.
"For example, if I am dealing with a child who has juvenile idiopathic or juvenile rheumatoid arthritis associated uveitis, I always use steroids first and then taper them," he said. "If the problem recurs, I use steroids again and then taper them, and if the problem occurs again, I have a conversation with the parents about steroid-sparing therapy, but I will go ahead and use steroids again."
If the patient—pediatric or adult—has been using steroid therapy for 6 months, whether it is chronic use, steady use, or intermittent use, Dr. Foster said that's when it's time to move on.
"That's the point that a tremendous number of comprehensive ophthalmologists simply have not incorporated into their bone marrow yet," he said. "The easiest and the knee-jerk reflex thing to do is what the doctor was taught to do in residency, and that is to simply do what worked before. That is to start dousing with steroids again and not invest the time, intellect, and energy in the more difficult matter of conversations about referrals and steroid-sparing therapy."
The type of uveitis dictates how Dr. Foster will approach treatment.
"That governs when I will suggest getting invasive by doing an intraocular injection, intraocular implant, or doing surgery, which involves cleaning out the vitreous and all the inflammatory cells in it, or pulling the trigger on so-called steroid-sparing immunosuppressive therapy," he said.
Immunosuppressive therapy
Uveitis doesn't have to involve a lifelong treatment course.
"There are a few diseases that require long-term care, but the bulk of the diseases we deal with are, frankly, curable," Dr. Foster said. "The immune system, if manipulated correctly, has the capacity to relearn how to behave itself properly and not begin attacking the patient's tissues yet again when medications are taken away."
After a patient is entirely off steroids, it takes a minimum of 2 years on immunomodulatory drugs to see a cure.
"Patients have to be off the steroids for you to know that the immunomodulators are in the right dose, are the right type, and that they are, in fact, setting the stage for the re-education of the immune system," Dr. Foster said. "We have a tremendous number of various types of uveitis that are outright cured—in remission, off steroids, on immunosuppressants for a finite period. The immunosuppressants are then tapered and withdrawn, and 5-10 years later, the patients are still without any evidence of recurrence of uveitis. It's like in cancer: You get to 5 years, and you have to call that a cure."
A whole panoply of immunomodulators is available, according to Dr. Foster.
Those include antimetabolites such as methotrexate, mycophenolate mofetil, and azathioprine; calcineurin inhibitors such as cyclosporine, tacrolimus, and sirolimus; and alkylating drugs such as cyclophosphamide and chlorambucil. Another category of immunomodulatory drugs is a class called biologic response modifiers, or biologics, including anakinra, eculizumab, rituximab, infliximab, and adalimumab. There are drugs in the pipeline, such as Interleukin-17, that inhibit the other molecules important in inflammation, Dr. Foster said. "In general, if you pluck an arrow out of your quiver to shoot at the inflammatory problem, no matter what arrow you pick or what drug you choose, there's about a 70% chance that the drug is going to be the salvation of that particular patient," Dr. Foster said. "It's going to fix the problem—no muss, no fuss, no need for anything more. Keep patients on it for 2 years and you're home free."
It's OK to move along if one of these drugs isn't working, he added.
Co-management
Comprehensive ophthalmologists shouldn't feel pressured to know every immunosuppressive drug available to patients. Instead, they should work on developing and maintaining co-management relationships with doctors who do.
Partner with a hematologist or rheumatologist, Dr. Foster advised.
"They're very collaborative and collegial," he said. "It's important to feel comfortable in the co-management of the patient."
Editors' note: Dr. Foster has no financial interests related to his comments.
Contact information
Foster: 617-621-6377, sfoster@mersi.us
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