Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development

ABSTRACT

Introduction: Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches.

Areas covered: Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research.

Expert opinion: Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

KEYWORDS:

• Uveitis
• treatment
• therapeutics
• drug carriers
• drug delivery systems
• drug-related side effects
• animal models
• clinical trials
• experimental therapy
• macular edema

Declaration of interest

M Cordero-Coma has received speaker honoraria from AbbVie, Merck Sharp and Dohme and Allergan. They are also on the scientific advisory boards for AbbVie and Allergan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Article highlights

• Untreated uveitis can lead to permanent vision loss and commonly affects patients during their most economically productive years.

• Experimental animal models have provided extraordinary information for deeper understanding of the underlying pathogenic mechanisms in human uveitis.

• In the past few years, several advances in preclinical research have resulted in the development of more targeted therapies.

• The major challenge for ophthalmic pharmacotherapy is to maximize therapeutic benefits and minimize side effects in the short term and long term.

• It is crucial to achieve therapeutic drug concentrations at target tissues with limited toxicity to healthy structures.

• There is immense potential to treat uveitis with local therapies as various delivery systems have already been developed and evaluated, such as ocular inserts and implants, trans-scleral iontophoresis, and nanocarriers.

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