Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The...

Genetic testing for age-related macular degeneration (AMD) risk reliably offers insight into an individual's susceptibility for future visual loss; however, an American Academy of Ophthalmology expert panel in 2012 discouraged routine AMD genetic risk testing because there was no evidence that such knowledge would alter an individual's clinical course. To address this knowledge gap, we investigated whether disclosure of AMD genetic risk to presymptomatic individuals would encourage healthier lifestyle adoption that could reduce the incidence of AMD later in life.

The Moran AMD Genetic Testing Assessment (MAGENTA) trial is a single-site, prospective, controlled clinical study (NCT05265624) that randomized 80 presymptomatic subjects in a 3:1 ratio to immediate or 1-year deferred disclosure groups. We stratified participants into high-, intermediate-, and low-risk groups by Mendelian randomization.

We enrolled Whites aged 18 to 64 years with no clinical signs of AMD.

As a biomarker of healthy nutritional status, participants' skin, plasma, and macular carotenoid concentrations were measured using resonance Raman and reflectance spectroscopies, high-performance liquid chromatography, and autofluorescence imaging, respectively. Nutritional and emotional status were assessed with validated surveys.

We looked for changes in skin, plasma, and macular carotenoids as biomarkers of healthier lifestyle adoption and for the impact of AMD genetic risk disclosure on participants' psychological well-being.

Of the 80 participants, 94% had a family history of AMD, and the AMD genetic risk distribution was 36% high, 24% intermediate, and 40% low. We found no statistically significant difference in skin, plasma, and macular carotenoids between study groups at 12 months relative to baseline (P > 0.05 for all comparisons). Participants' interest and compliance were high, as shown by the 95% subject study completion rate, and there was no evidence of worsening stress following AMD genetic risk disclosure to the participants.

While AMD genetic risk disclosure did not significantly impact nutritional biomarker levels over 12 months, there were no adverse psychological effects, and the subjects generally felt knowledge of their AMD risk was valuable. Our findings could guide future presymptomatic AMD genetic testing trials with extended biomarker assessments in larger and more diverse populations.

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