Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis.

backgroundNon-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long-term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti-tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid-sparing immunomodulatory agents in a wide range of non-ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti-TNF therapy in UMO, thus developing the evidence-base on which to make future treatment decisions and develop clinical guidelines in this area.

objectivesTo assess the efficacy of anti-TNF therapy in treatment of UMO. SEARCH

methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index- Science (CPCI-S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018. SELECTION CRITERIA: We planned to include all relevant randomised controlled trials assessing the use of anti-TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti-TNF versus no treatment or placebo; anti-TNF versus another pharmacological agent; comparison of different anti-TNF drugs; comparison of different doses and routes of administration of the same anti-TNF drug. The primary outcome measure that we assessed for this review was best-corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health-related quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full-text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full-text report for eligibility. We resolved discrepancies through discussion. MAIN

resultsWe identified no completed or ongoing trial that was eligible for this Cochrane Review. AUTHORS'

conclusionsOur review did not identify any evidence from randomised controlled trials for or against the role of anti-TNF agents in the management of UMO. Although there are a number of high-quality randomised controlled trials that demonstrate the efficacy of anti-TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.