Complement inhibitors for age-related macular degeneration

Advanced age-related macular degeneration (AMD) is an eye condition which principally affects the over 65s. In this age group it is the most common cause of loss of vision in the developed world, and the third most common cause globally. AMD causes loss of central vision. Despite advances in the understanding of AMD and the recent introduction of new treatments for some forms of AMD, the visual loss it causes is irreversible in most cases. When it affects both eyes, the impact on day to day functioning is huge. As the proportion of older people increases, larger numbers of people are likely to be affected by AMD in the future.

The complement cascade is the name for a series of proteins which form part of the body's immune system, helping to fight infection. The complement system is constantly active at a low level, and is tightly regulated. However evidence suggests that complement cascade overactivity may play a role in AMD, and so it is logical that drugs which inhibit the cascade may have a role in the treatment of AMD. This review sought to identify trials investigating the potential benefits and safety of complement inhibitors for AMD. No relevant trials have been completed but we anticipate that updates of this review will in future have results to analyse. There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD.

Authors' conclusions: 

There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

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Background: 

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD.

Objectives: 

To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations.

Selection criteria: 

We planned to include randomised controlled trials (RCTs) with parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade.

Data collection and analysis: 

Two authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis.

Main results: 

We identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study.

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