title: Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration.
abstract: OBJECTIVE
  To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later.
  
  
  METHODS
  Prospective cohort.
  
  
  METHODS
  Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators.
  
  
  METHODS
  Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD.
  
  
  METHODS
  Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline.
  
  
  RESULTS
  Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline.
  
  
  CONCLUSIONS
  Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, 2 tissues with prominent age- and AMD-related pathology.
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: owsley@uab.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Owsley
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Clark
authors.affiliation: MacuLogix Inc., Hummelstown, Pennsylvania.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Jackson
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Callahan
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Lanning B
authors.initials: LB
authors.lastname: Kline
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: C Douglas
authors.initials: CD
authors.lastname: Witherspoon
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003623:Dark Adaptation / Q000502:physiology*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D014792:Visual Acuity / Q000502:physiology
chemical_list: D015415:Biomarkers