Understanding uveitis: The impact of research on visual outcomes

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Abstract

The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age.

Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects.

The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved.

Section snippets

The clinical importance of uveitis

Uveitis is an umbrella term used to describe a wide variety of inflammatory conditions occurring inside the eye. The term literally means inflammation of the uvea (Latin for grape), i.e. the iris, ciliary body and choroid, but adjacent structures such as the retina, optic nerve and sclera may also be involved. Uveitis accounts for 5–20% of legal blindness in both the United States and Europe, and perhaps as much as 25% of blindness in the developing world (Bodaghi et al., 2001, Rothova et al.,

Animal models in uveitis

Taking repeated ocular biopsies from patients is not ethically possible. Hence our understanding of the mechanisms of ocular damage in uveitis have come from using animal models (de Smet and Chan, 2001). Furthermore, histopathologic data derived from ocular samples provides data at only one timepoint, usually late in the course of the disease, whereas experimental models allow analysis during the entire disease process. Several animal species can be used to understand different aspects of the

Clinical, diagnostic and evaluation challenges in uveitis

Although uveitis encompasses a multitude of etiologies and disease phenotypes, its management relies on a set of pivotal factors: correct anatomical classification and etiologic diagnosis, identification of complications, assessment of disease activity, and the presence of any systemic disease associations (Guly and Forrester, 2010). Challenges remain in all of these areas, particularly as traditional biomedical thinking in uveitis care has led to an overemphasis on diagnostic testing. An

Challenges in disease management

Uveitis is a disease of varying phenotypes and visual prognosis: inflammation may be mild, moderate or severe; sight-affecting or sight-threatening complications may already be present at presentation; patients may be very symptomatic, particularly if there is severe anterior chamber involvement, macular edema with visual loss or vitritis with numerous floaters. These factors often drive clinical decision-making, but not all patients with uveitis require treatment. Patients with chronic

Predictors of disease activity

It would be ideal to identify patients who are in a high risk group for visual loss early in their disease process. This would enable a more aggressive approach to therapy to be taken, possibly preventing this loss of vision. It would also be useful to predict which patients are likely to be refractory to commonly used medication, to have more a severe inflammatory process, or to develop complications of uveitis such as glaucoma. Cytokine levels in blood and ocular fluids, intracellular

How can disease management be improved

Classical clinical trials rest on binary outcomes. This approach has endured the test of time and is favored by regulators, but it carries with it important ethical, economic and timing issues. For example, eyes in a control arm are at risk of permanent vision loss unless protocols are set up to include eyes with less severe disease even in the presence of rescue therapy. We group under the term uveitis a number of very different clinical entities whose only common denominator is the presence

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