title: Drug discovery in ophthalmology: past success, present challenges, and future opportunities.
abstract: BACKGROUND
  Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines.
  
  
  CONCLUSIONS
  We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of 'translational research'. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from 'bench to bedside and back again') with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease.
authors.affiliation: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Nicholas J D
authors.initials: NJD
authors.lastname: Gower
authors.affiliation: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barry
authors.affiliation: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Edmunds
authors.affiliation: Birmingham and Midland Eye Centre, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK.
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Titcomb
authors.affiliation: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. a.denniston@bham.ac.uk.|Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK. a.denniston@bham.ac.uk.|Birmingham and Midland Eye Centre, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK. a.denniston@bham.ac.uk.
authors.forename: Alastair K
authors.initials: AK
authors.lastname: Denniston
mesh_terms: D015195:Drug Design; D055808:Drug Discovery / Q000639:trends*; D004345:Drug Industry; D006801:Humans; D009885:Ophthalmology / Q000639:trends*; D004364:Pharmaceutical Preparations
chemical_list: D004364:Pharmaceutical Preparations