title: Safety and efficacy of subretinal visual implants in humans: methodological aspects.
abstract: BACKGROUND
  Replacing the function of visual pathway neurons by electronic implants is a novel approach presently explored by various groups in basic research and clinical trials. The novelty raises unexplored methodological aspects of clinical trial design that may require adaptation and validation.
  
  
  METHODS
  We present procedures of efficacy and safety testing for subretinal visual implants in humans, as developed during our pilot trial 2005 to 2009 and multi-centre clinical trial since 2010.
  
  
  RESULTS
  Planning such a trial requires appropriate inclusion and exclusion criteria. For subretinal electronic visual implants, patients with photoreceptor degeneration are the target patient group, whereas presence of additional diseases affecting clear optic media or the visual pathway must be excluded. Because sham surgery is not possible, a masked study design with implant power ON versus OFF is necessary. Prior to the efficacy testing by psychophysical tests, the implant's technical characteristics have to be controlled via electroretinography (ERG). Moreover the testing methods require adaptation to the particular technology. We recommend standardised tasks first to determine the light perception thresholds, light localisation and movement detection, followed by grating acuity and vision acuity test via Landolt C rings. A laboratory setup for assessing essential activities of daily living is presented. Subjective visual experiences with the implant in a natural environment, as well as questionnaires and psychological counselling are further important aspects.
  
  
  CONCLUSIONS
  A clinical trial protocol for artificial vision in humans, which leads a patient from blindness to the state of very low vision is a challenge and cannot be defined completely prior to the study. Available tests of visual function may not be sufficiently suited for efficacy testing of artificial vision devices. A protocol based on experience with subretinal visual implants in 22 patients is presented that has been found adequate to monitor safety and efficacy.
authors.affiliation: Center for Ophthalmology, University of Tübingen, Tübingen, Germany. katarina.stingl@med.uni-tuebingen.de
authors.forename: Katarina
authors.initials: K
authors.lastname: Stingl
authors.forename: Michael
authors.initials: M
authors.lastname: Bach
authors.forename: Karl-Ulrich
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Angelika
authors.initials: A
authors.lastname: Braun
authors.forename: Anna
authors.initials: A
authors.lastname: Bruckmann
authors.forename: Florian
authors.initials: F
authors.lastname: Gekeler
authors.forename: Udo
authors.initials: U
authors.lastname: Greppmaier
authors.forename: Gernot
authors.initials: G
authors.lastname: Hörtdörfer
authors.forename: Akos
authors.initials: A
authors.lastname: Kusnyerik
authors.forename: Tobias
authors.initials: T
authors.lastname: Peters
authors.forename: Barbara
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Robert
authors.initials: R
authors.lastname: Wilke
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
mesh_terms: D000203:Activities of Daily Living; D001766:Blindness / Q000503:physiopathology / Q000534:rehabilitation*; D006801:Humans; D011474:Prosthesis Design; D012160:Retina / Q000503:physiopathology*; D011795:Surveys and Questionnaires; D014792:Visual Acuity; D057488:Visual Prosthesis