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Review
. 2014 Jan;121(1):365-376.
doi: 10.1016/j.ophtha.2013.08.029. Epub 2013 Oct 26.

The future of uveitis treatment

Phoebe Lin  1 , Eric B Suhler  2 , James T Rosenbaum  3
Affiliations
Review

The future of uveitis treatment

Phoebe Lin et al. Ophthalmology. 2014 Jan.

Abstract

Uveitis is a heterogeneous collection of diseases with polygenic and environmental influences. This heterogeneity presents challenges in trial design and selection of end points. Despite the multitude of causes, therapeutics targeting common inflammatory pathways are effective in treating diverse forms of uveitis. These treatments, including corticosteroids and immunomodulatory agents, although often effective, can have untoward side effects, limiting their utility. The search for drugs with equal or improved efficacy that are safe is therefore paramount. A mechanism-based approach is most likely to yield the future breakthroughs in the treatment of uveitis. We review the literature and provide examples of the nuances of immune regulation and dysregulation that can be targeted for therapeutic benefit. As our understanding of the causes of uveitis grows we will learn how to better apply antibodies designed to block interaction between inflammatory cytokines and their receptors. T-lymphocyte activation can be targeted by blocking co-stimulatory pathways or inhibiting major histocompatibility complex protein interactions. Furthermore, intracellular downstream molecules from cytokine or other pathways can be inhibited using small molecule inhibitors, which have the benefit of being orally bioavailable. An emerging field is the lipid-mediated inflammatory and regulatory pathways. Alternatively, anti-inflammatory cytokines can be provided by administering recombinant protein, and intracellular "brakes" of inflammatory pathways can be introduced potentially by gene therapy. Novel approaches of delivering a therapeutic substance include, but are not limited to, the use of small interfering RNA, viral and nonviral gene therapy, and microparticle or viscous gel sustained-release drug-delivery platforms.

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Figures

Figure 1
Figure 1
The pathogenesis of uveitis. An imbalance between the regulatory mechanisms and inflammatory mechanisms contribute to uveitis. Only some examples of contributing role players such as regulatory T cells versus Th17 cells are shown. A combination of environmental risk factors and genetic risk factors tip the balance towards the development or chronicity of uveitis. RPE: retinal pigment epithelium; PMNs: polymorphonuclear cells
Figure 2
Figure 2
Sustained delivery formulations. A, Retisert®; B, I-vation™ implant; C, Suprachoroidal implant; D, E, Intravitreal implants (e.g. Ozurdex®, Illuvien); F, microparticles, nanoparticles, liposomes; G, Verisome system; H, Cortiject emulsion.
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