Elsevier

Ophthalmology

Volume 123, Issue 2, February 2016, Pages 344-351
Ophthalmology

Original article
Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration

https://doi.org/10.1016/j.ophtha.2015.09.041Get rights and content

Purpose

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.

Design

Prospective cohort.

Participants

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.

Main Outcome Measures

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.

Section snippets

Methods

The Institutional Review Board at the University of Alabama at Birmingham (UAB) approved the study. Participants were recruited from 2 primary eye care practices at the Callahan Eye Hospital at UAB, Birmingham, Alabama. Eligibility criteria at baseline were as follows: (1) Age ≥60 years. (2) Normal macular health in both eyes as determined by 3-field digital stereo-fundus photos (450 Plus camera, Carl Zeiss Meditec, Dublin, CA) graded by an experienced grader masked to study variables. The

Results

At baseline, 390 persons participated in both fundus photography and DA testing. Of the baseline enrollees, 61 persons were lost at follow-up (15.6% of sample); the reasons were illness (22), no longer interested (19), unable to contact (7), deceased (6), worked full-time (4), moved away (3), and incomplete data at follow-up (4). Thus, the final analysis sample was 325 persons who completed both baseline and follow-up visits. Those lost at follow-up were on average 2 years older (P = 0.021) and

Discussion

Older adults with normal macular health were approximately twice as likely to develop early AMD 3 years later if they had abnormal rod-mediated DA at baseline. To our knowledge, this is the first study to demonstrate this relationship. Currently, there are no useful functional end point measures available for trials evaluating strategies for AMD prevention or interventions to arrest its progression at early stages. Visual acuity is the accepted standard end point for preventing or slowing

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  • Cited by (0)

    Financial Disclosure(s): The author(s) have made the following disclosure(s): C.O.: Patent for a method and apparatus for the detection of impaired DA, #20090153802, #20110007276, and #20110141437, with royalties paid.

    G.R.J.: Employee and stockholder of MacuLogix, Inc.

    Funded by the National Institute on Aging (R01AG04212) and National Eye Institute (R01EY06109), National Institutes of Health (Bethesda, MD); EyeSight Foundation of Alabama (Birmingham, AL); International Retinal Research Foundation (Birmingham, AL); Ludwig von Sallmann Prize (New York, NY); Research to Prevent Blindness Inc (New York, NY); and Alfreda J. Schueler Trust (Chicago, IL).

    Author Contributions:

    Conception and design: Owsley, McGwin, Jackson, Callahan, Kline

    Data collection: Owsley, Clark, Witherspoon

    Analysis and interpretation: Owsley, McGwin, Clark, Jackson, Curcio

    Obtained funding: Owsley, Curcio

    Overall responsibility: Owsley, McGwin, Clark, Jackson, Callahan, Kline, Witherspoon, Curcio

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