Approach to Therapy

Corticosteroids

The fourth general rule is that acute episodes of inflammation should be treated with corticosteroids, whereas chronic inflammation is better treated with corticosteroid-sparing therapy. Corticosteroids have a plethora of effects on the immune response, a full discussion of which is beyond the scope of this book. For acute, systemic treatment, the authors will typically use prednisone 0.75 to 1 mg/kg up to 80 mg PO daily. There are exceptions to this dosing. Vogt–Koyanagi–Harada syndrome and sympathetic ophthalmia may require very large doses of systemic corticosteroids (e.g., prednisone 100 mg PO daily) to gain adequate initial control. Intravenous (IV) methylprednisolone can also be used if particularly large doses are required to control intraocular inflammation. Once quiescence has been established, the prednisone is tapered. The author uses the following tapering schedule: 70 mg PO daily×1 week, then 60 mg PO daily×1 week, 50 mg PO daily×1 week, 40 mg PO daily×1 week, 30 mg PO daily×1 week, 20 mg PO daily×2 weeks, 15 mg PO daily×2 weeks, 10 mg PO daily × 2 weeks, then hold at 5 to 7.5 mg PO daily×3 months before resuming the taper ( Box 3.1 ).

Other uveitis specialists endorse other tapering regimens, but the authors feel this program strikes a good balance between the competing goals of efficacious therapy tapered slowly and the many adverse effects of systemic corticosteroid therapy, which usually become much more tolerable at a dose of approximately 10 mg PO daily. Holding prednisone at a low dose before resuming the taper is helpful to prevent recurrences, but there is no high-level evidence for this recommendation.

Systemic Immunomodulatory Therapy: When to Start

The decision to start IMT is driven by an understanding of the severity, laterality, and chronicity of the patient’s intraocular inflammation; the status of the patient’s fellow eye in cases of unilateral uveitis; the adverse effects incurred by local and/or systemic treatment with corticosteroids; and the patient’s ability to adhere to the frequent laboratory and clinical follow-up necessary for all patients on IMT. If this sounds complex, it can be. However, a few straightforward guidelines can help to make the decision ( Box 3.2 ).

First, any patient with active, bilateral, chronic uveitis despite prednisone 10 mg or greater should typically be on IMT. Chronic doses of 10 mg or more have been shown to significantly increase the risk of osteoporosis and cardiac disease with long-term treatment. Chronic unilateral uveitis requiring ≥10 mg is a different situation, as local therapies, detailed later, may allow for disease quiescence with an acceptable level of local adverse effects and for tapering of prednisone to <10 mg PO daily.

Second, and in a similar vein, some patients with either chronic unilateral or bilateral uveitis may achieve quiescence with a combination of low doses of systemic prednisone (<10 mg PO daily) and local therapies (e.g., intravitreal or periocular triamcinolone, fluocinolone implants, etc.) but incur unacceptable adverse effects. Whereas a cataract is easily managed with a safe and effective surgical procedure, glaucoma can be more difficult to control in certain patients. Patients with severe and prolonged increases in IOP with local corticosteroid therapy are also candidates for IMT.

In a monocular patient, one has a heightened sensitivity both to ocular adverse effects and the damaging impact of uveitis flares that may arise as the effects of local therapy wane. Thus in monocular patients with chronic unilateral uveitis, the authors have a lower threshold (though not absolute indication) to start IMT.

Finally, an understanding of the severity of a patient’s disease and the potential for irreversible damage with any flare is critical, not simply in monocular patients but in all patients. Certain uveitic syndromes are highly vision-threatening and present strong indications for nearly immediate initiation of IMT ( Box 3.3 ), almost simultaneous with high-dose corticosteroid therapy. Other cases are less clear-cut and highly specific to the individual patient. These can present a challenging and somewhat subjective assessment for the clinician. For instance, some patients with recurrent HLA-B27–associated anterior uveitis experience severe flares, albeit in one eye, causing profound inflammation and hypotony from which it can take many months to recover. Every flare is a prolonged physical and psychological ordeal for these patients. Moreover, one worries about the potential for cyclitic membranes to develop with multiple severe flares, a condition that portends a poor prognosis. Thus even if the patient only flares once a year, for instance, IMT may be a reasonable management plan based on the history of extremely severe flares.