Systemic Therapies for Inflammatory Eye Disease

Past, Present and Future

Alastair K Denniston; Andrew D Dick


BMC Ophthalmol. 2013;13(18) 

In This Article

Abstract and Introduction


In this review we consider the current evidence base for treatments in inflammatory eye disease, and in particular uveitis, from a historical perspective. We consider the challenges that have traditionally hindered progress in inflammatory eye disease including small target populations, heterogeneous disease groups, poorly defined phenotypes, diagnostic inconsistency, subjective outcome measures, specific issues around visual acuity as an outcome measure and low commercial interest. Strategies to address these issues are considered de novo and with reference to recent advances outside of ophthalmology and highlight the promise for ocular inflammation. Progress in these specialties has included the development of thriving clinical-trial cultures, public-private partnerships, pathogenetic- and structure-led drug design, efficient drug development pipelines, and biomarker-defined treatment protocols enabling personalization of medicine. Although there are challenges, these are exciting opportunities as we seek to develop safe and effective treatments for patients with inflammatory eye disease.


Philosophically we recognize that the past informs our present but realize less that our present actions and thoughts dictate our future. To this end, as we consider the progress that has been made in the systemic treatment of inflammatory eye disease, there is a danger that we over-value recent successes due to their proximity rather than merit. Newer drugs, like most recent news stories, may attract more of the reviewer's attention: they are the recent arrivals, usually accompanied by a promise of delivering better outcomes for our patients and with the advantage of having had time to demonstrate their short-term efficacy but not their long-term consequences (whether good or ill). Objective assessment of the merits of these systemic therapies requires the high-quality evidence that comes from well-designed randomized clinical trials, with extended follow-up to ensure late effects are not missed. We are currently a long way from being in that position. In the clinic we are inured to this and, on the basis of the limited available evidence alongside experience and anecdote,[1] we make the best therapeutic choice we can. We are reassured because cohort studies infer that a majority of patients improve,[2–8] but we do not know whether to what extent a placebo or indeed no treatment would have had the same effect. This is clearly an unsatisfactory position and we need to move on.

In this review we have not sought to appraise the individual systemic therapies currently available to us; this is important but is covered in detail elsewhere.[9,10] Rather we seek to provide a critical assessment of the state of the field: where we started from, what progress has been made and a vision of how we can bridge the considerable gap to get to where we need to be – providing therapies which are proven to be effective and safe and targeted to the individual patient in front of us.