Therapeutic Algorithm for Recurrent Anterior Non-Granulomatous (e.g. HLA-B27-Associated) “Autoimmune” Uveitis
Dan Gordon of Cornell got it right as far back as 1952 when he realized that topical steroids represented a breakthrough in the medical therapy of patients with uveitis. Further, he even understood early on that one should be bold and “use enough soon enough” to get the job done, and then slowly taper and discontinue the medication before steroid-induced side effects were produced. We believe Gordon’s philosophy of the use of corticosteroids for the care of uveitis is perfect, and therefore, advocate their use just as he did forty years ago. We use topical preparations first (our favorite is Lotemax for mild to moderate uveitis because of the reduced propensity to raise intraocular pressure); the compliance of patients to vigorously shake a bottle of medication prior to instilling a drop every hour to every thirty minutes is quite poor, and therefore, solutions are probably preferable (despite the reputed increased penetration of prednisone acetate suspensions) simply because patients taking suspensions not shaken properly don’t really receive the reputed 1% drop each time they apply the medication. During an active uveitis episode, we apply steroid drops to our uveitis patients every thirty to sixty minutes while awake, mydriatic/cycloplegic therapy as well. If the patient’s uveitis is severe (3 to 4 plus or hypopyon), we supplement the aforementioned topical therapy with regional injection therapy (usually with triamcinolone acetonide, 40 milligrams) delivered through the inferior preorbital septum (transseptal injection). We do not believe there are significant advantages to delivering the drug into the supratemporal sub-Tenon space. Available data suggest that the incidence of intraocular pressure elevation may be higher with this route, and patient acceptance of repeated injections is likely lower. Depo preparations are not used unless the patient has been demonstrated not to be a “steroid responder” as regard to pressure rises, and the patient has derived substantial benefits from shorter acting steroid injections, but has relapsed within two weeks of such injections. Systemic steroids are also employed in cases of severe uveitis, typically beginning with a dose of one milligram per kilogram body weight per day, with tapering beginning seven days after initiation of therapy, and usually discontinuing within 3-4 weeks of initiation.
Our tolerance for long-term steroid use is extremely limited. Patients with non-severe uveitis who experience recurrence during corticosteroid tapering or after discontinuation may be treated with oral nonsteroidal anti-inflammatory drugs (NSAIDs), such as Naproxen 500 mg, twice daily, with the usual warnings of the GI tract, the need for periodic monitoring and complete blood count (CBC) and renal function tests [blood urea nitrogen (BUN) and creatinine (Cr)] , etc. Our experience has strongly suggested that such therapy often (perhaps as much as 60% of the time) enables one to withdraw steroids being used for the current recurrence without yet another recurrence after the corticosteroids are tapered and discontinued. If this is the case, then we maintain our patients on long-term oral NSAIDs for approximately two years before an attempt to taper and stop that medication.
For patients who continue to have recurrent inflammation despite the constant and faithful use of an NSAID, we apprise them of the potential risks and benefits of immunomodulatory therapy. Although low-dose weekly methotrexate is typically our first-line agent, the choice of therapy is ultimately guided by factors such as patient age, plans for conception (in both men and women), medical history, and social considerations. For example, we would not choose methotrexate therapy for a person who is a frequent and chronic user of alcohol; nor would we choose methotrexate for a patient who had previously had an episode of hepatitis or who was known to be hepatitis B or C positive. Clearly, most ophthalmologists are not interested in taking on the responsibility for such decision making, much less the longitudinal and monitoring of patients placed on immunomodulatory therapy; however, a collaboration between the ophthalmologist and a rheumatologist or hematologist typically can work beautifully, with the ophthalmologist apprising the chemotherapist of the state of the ocular inflammation (the goal being complete abolition of all active inflammation) and the chemotherapist then monitoring the patient and telling the ophthalmologist whether or not more drug can be safely used, a switch in medication should be made to achieve the goal, etc.
Other conventional immunomodulatory agents, including azathioprine and mycophenolate mofetil, as well as T-cell inhibitors such as cyclosporine and tacrolimus, may be used to treat recurrent autoimmune uveitis. However, T-cell inhibitors are avoided in patients with a solitary kidney, uncontrolled hypertension, or known renal disease. Additionally, monitoring of liver enzymes is essential when using azathioprine.
During the past two decades, the advent of biologic response modifiers and targeted immunomodulatory therapies has revolutionized the management of patients with recurrent uveitis. Currently, adalimumab, an FDA-approved biologic response modifier, as well as multiple other agents, can be used to treat patients who do not respond to conventional immunotherapy.
Uveitis is a significant cause of vision loss in the United States, accounting for an estimated 10–15 % of blindness and affecting individuals primarily in young and working‑age adults, resulting in considerable socioeconomic impact given its tendency to strike earlier in life. We believe that until increasing numbers of ophthalmologists adopt a philosophy of complete intolerance to even low-grade inflammation chronically, no additional progress will be made in this area. The vast majority of patients are cared for, after all by ophthalmologists in general practice, not by the referral center uveitis specialists. We hope that providing information such as this on this Web Site will stimulate increasing numbers of ophthalmologists in practice to seriously consider taking this last step on the stepladder algorithm of therapy for uveitis and collaborate with chemotherapists in the care of patients whose uveitis continues to be a significant problem despite the more traditional therapeutic approaches.
 |
|
|
|
