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    This cross-sectional study describes the phenotypical characteristics of AMD patients carrying a rare variant in the complement factor H (CFH) gene.

    Study design

    Investigators analyzed color photographs of the fovea to characterize the fundus phenotype in 100 eyes of 51 CFH variant carriers. The cohort was compared with 204 eyes of 102 age-matched controls who have AMD but do not carry CFH variants.


    Rare pathogenic CFH variants in patients with AMD were associated with:

    • Larger drusen area (OR range 7.0 to 18.5; P=0.002)
    • Drusen nasal to the optic disc (OR range 4.0 to 7.4; P=0.003)
    • Drusen with crystalline or calcified appearance (OR 3.2; P=0.02)


    Peripheral retinal photographs of the fundus quadrants were not analyzed, limiting evaluation of extramacular drusen.

    Although patients with the phenotypes described above are likely to carry a rare variant in CFH, it is unlikely that carriers can be discriminated from noncarriers based solely on color fundus images.

    Clinical significance

    There is increasing interest in identifying risk factors for advanced AMD, especially with the rise of investigational complement-inhibiting therapies.

    High-risk eyes with the features described here should be referred for genetic testing, given the availability of commercially available, easy-to-use tests.