Sight-threatening uveitis: Newer therapies

October 15, 2009

Non-infectious uveitis involving the posterior segment is a leading cause of vision loss and long-term disability in the developed world and accounts for 10% to 20% of cases of legal blindness, particularly in younger individuals.

Non-infectious uveitis is associated with myriad complications such as cataracts, glaucoma, macular edema, choroidal neovascularization, retinal detachment, hypotony, and photoreceptor loss. It is a disease of younger individuals with a median age group of 35 to 39 years affected3; the recovery of vision following exacerbations of uveitis may be prolonged, with increasing duration of visual morbidity associated with poorer visual acuity.

In one study, the mean duration of vision loss following an inflammatory episode was 21 months.2 The largest, recent epidemiologic study reported an incidence rate of 52 cases per 100,000 person-years, and a prevalence rate of 115 cases per 100,000 persons. The potential economic loss due to uveitis is considerable, given the longevity of patients affected by this condition. It has been reported that approximately 34% of individuals lose their jobs within 2 years of becoming visually impaired.4

Treatment agents

Although it has been estimated that 30,000 individuals become blind annually from uveitis in the United States alone, there has been little in the way of clinical development of agents for the treatment of this condition.5

Corticosteroids, whose potential anti-inflammatory properties were applied initially to the treatment of rheumatoid arthritis in 1950, represent the mainstay of therapy for noninfectious uveitis.6 Although effective in controlling inflammation associated with uveitis, significant morbidity is inevitable in long-term users even at doses as low as 7.5 mg/day prednisone or equivalent.7 It has, for example, been reported that steroid-induced bone loss occurs rapidly within the first 6 months of initiation of therapy with systemic corticosteroids and that pathologic fractures are observed after 5 years in 33% of women taking a mean dose of 8.6 mg of prednisone daily.8-11 Recent data suggest that chronic high doses of prednisone (>20 mg/day) are commonly used to control inflammation.12,13 The serious, though underappreciated, side effects of chronically elevated doses of systemic corticosteroid involve virtually every organ system and include: osteoporosis, hyperglycemia, hypercholesterolemia, hypertension, diabetes, cardiovascular events, mood disturbances, glaucoma, and cataract formation.

Treatment guidelines published in 2000 recommend the addition of immunomodulatory therapy (IMT; e.g. anti-metabolites, anti-proliferative drugs, alkylating agents, and, more recently, biologics) if control of uveitis cannot be achieved with ≤10 mg/day of prednisone (or equivalent).14 The efficacy of IMTs for the treatment of uveitis remains, however, largely unproven except for small, often non-randomized, controlled trials to date.