Diagnosis of uveitis can be a confusing and frustrating process even for experienced clinicians. Careful history-taking, comprehensive review of systems, ocular examination, and targeted laboratory workup are essential steps for diagnosis. In order to generate a differential diagnosis, the gathered data are classified according to descriptive categories, such as demographic data, location of uveitis, and clinicopathologic features. When applicable, specific laboratory tests are then obtained to aid in arriving at a final, sometimes, “best guess” diagnosis. A correct diagnosis can be crucial in timely selection and institution of potentially sight-saving pharmacotherapy. The diagnostic features of the common noninfectious posterior uveitis entities are summarized in Table 22.1.

Since their introduction in the 1950s, corticosteroids have remained a mainstay of treatment for all types of noninfectious uveitis and are typically used for initial control of inflammation. However, their longterm systemic use is limited by the development of side-effects such as cushingoid syndrome, hyperglycemia, hypertension, gastrointestinal ulceration, and osteoporosis (Figure 22.1). For posterior-segment involvement, high drug levels of corticosteroids may be achieved by using the periocular, intravitreal, and systemic routes of administration.11 New intraocular devices have been developed and, when implanted, provide a sustained and controlled dose of steroids inside the eye (Retisert, Bausch & Lomb, Rochester, NY and Ozurdex,Allergan, Irvine, CA). These nonsystemic routes of administration minimize systemic side-effects.

Nonsteroidal anti-inflammatory drugs such as diclofenac sodium, ketorolac, and nepafenac are utilized to reduce mild inflammation, resolve CME, and minimize the incidence of corticosteroid-related sideeffects. They can be administered systemically or topically and may be combined with corticosteroids as steroid-sparing agents.11

Immunosuppressive agents are used for the treatment of several posterior uveitis entities (Table 22.2). They can be used as steroidsparing agents or added to corticosteroid therapy when an inadequate response is obtained. The International Uveitis Study Group has recommended that Adamantiades–Behçet disease (ABD), chronic VKH syndrome, and serpiginous choroidopathy (SPC) be considered absolute indications for immunosuppressive therapy due to their unacceptable long-term prognosis.12,13 In 2000, Jabs and Rosenbaum and a panel of inflammation experts published guidelines for corticosteroids, immunosuppressive and biologic drugs for patients with ocular inflammation.11 The following sections summarize their recommendations and

Figure 22.1  Moon facies, buffalo hump, acne, and hirsutism in a patient maintained on oral corticosteroids.

incorporate newer information regarding pharmacotherapy of common posterior uveitis entities.

ADAMANTIADES–BEHÇET DISEASE

Diagnostic features

ABD is a major cause of posterior uveitis in the Mediterranean and Asian regions. ABD is classically diagnosed in the presence of oral ulcers (Figure 22.2), genital ulcers, and uveitis. The International Study Group for Behçet’s Disease diagnostic criteria include recurrent oral ulcers (at least 3 times per year) plus any two of the following: recurrent genital ulcers, ocular inflammation, skin involvement (erythema nodosum, superficial migratory thrombophlebitis), or a positive pathergy (skinprick) test.13 Other systemic manifestations of ABD include: arthritis, epididymitis, neuropsychiatric symptoms, gastro­ intestinal, and vascular lesions. ABD may manifest as anterior uveitis with or without hypopyon. Posterior-segment involvement may manifest as vitritis, retinal vasculitis, focal necrotizing retinitis, and posterior uveitis. Left untreated, the visual outcomes are uniformly poor, with approximately 3 of 4 patients developing blindness within 3.5 years of onset.14

While there is no universally accepted laboratory test for ABD, there is an association between ABD and HLA-B51.15 During acute inflammation, fluorescein angiography (FA) demonstrates leakage from inflamed retinal vessels and the optic disc (Figure 22.3). Areas of capillary nonperfusion, neovascularization, telangiectasia, and edema may also be identified. Indocyanine green angiography (ICGA) may demonstrate subclinical choroidal involvement.16 The differential diagnosis of different posterior-segment clinical findings is outlined in Table 22.3.

Treatment modalities

Corticosteroid treatment alone does not change the long-term visual outcome but only delays the onset of blindness. For this reason, the early use of immunosuppressive drugs has been advocated for posterior uveitis due to ABD.17 There is excellent, level I evidence to show that azathioprine and cyclosporine-A (CSA) are effective in reducing the frequency and severity of uveitis attacks resulting from ABD.2,11,18,19 Low-dose CSAhas been recommended as first-line immunomodulatory­ therapy with or without low-dose corticosteroids. Cyclophosphamide

Figure 22.2  Oral ulcers in a patient with Adamantiades–Behçet disease.

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Table 22.2  Pharmacotherapeutic agents for common posterior-segment uveitis entities