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. 2014 Jan 15;2014(1):CD009300.
doi: 10.1002/14651858.CD009300.pub2.

Complement inhibitors for age-related macular degeneration

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Complement inhibitors for age-related macular degeneration

Michael A Williams et al. Cochrane Database Syst Rev. .

Update in

Abstract

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 methods: 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.

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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Conflict of interest statement

The authors have no conflicts of interest.

Figures

Figure 1
Figure 1
Results from searching for studies for inclusion in the review.

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References

References to ongoing studies

    1. NCT00935883. Eculizumab for the treatment of non‐exudative age‐related macular degeneration: an exploratory study to evaluate the effects of C5 inhibition on drusen and geographic atrophy. clinicaltrials.gov/show/NCT00935883 (accessed 28 May 2013).
    1. NCT00950638. A phase I study of ARC1905 (anti‐C5 aptamer) in subjects with dry age‐related macular degeneration. clinicaltrials.gov/show/Nct00950638 (accessed 28 May 2013).

Additional references

    1. Anonymous. Deal watch: Alcon licenses complement pathway inhibitor for macular degeneration. Nature Reviews Drug Discovery 2009;8:922. - PubMed
    1. Age‐Related Eye Disease Study Research Group. A randomized, placebo‐controlled, clinical trial of high‐dose supplementation with vitamins C and E, beta carotene, and zinc for age‐related macular degeneration and vision loss: AREDS report no. 8. Archives of Ophthalmology 2001;119(10):1417‐36. - PMC - PubMed
    1. Augood CA, Vingerling JR, Jong PT, Chakravarthy U, Seland J, Soubrane G, et al. Prevalence of age‐related maculopathy in older Europeans: the European Eye Study (EUREYE). Archives of Ophthalmology 2006;124(4):529‐35. - PubMed
    1. Bora PS, Sohn JH, Cruz JM, Jha P, Nishihori H, Wang Y, et al. Role of complement and complement membrane attack complex in laser‐induced choroidal neovascularization. Journal of Immunology 2005;174(1):491‐7. - PubMed
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References to other published versions of this review

    1. Williams MA, McKay GJ, Chakravarthy U. Complement inhibitors for age‐related macular degeneration. Cochrane Database of Systematic Reviews 2011, Issue 9. [DOI: 10.1002/14651858.CD009300] - DOI - PMC - PubMed

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