Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing

Abstract

Purpose: To describe the directional kinetics of the spread of geographic atrophy (GA) spread in eyes with age-related macular degeneration and foveal sparing.

Design: Prospective, noninterventional natural history study: Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM; clinicaltrials.gov identifier, NCT00393692).

Subjects: Participants of the FAM study exhibiting foveal sparing of GA.

Methods: Eyes were examined longitudinally with fundus autofluorescence (FAF; excitation wavelength, 488 nm; emission wavelength, >500 nm) and near infrared (NIR) reflectance imaging (Spectralis HRA+OCT or HRA2; Heidelberg Engineering, Heidelberg, Germany). Areas of foveal sparing and GA were measured by 2 independent readers using a semiautomated software tool that allows for combined NIR reflectance and FAF image grading (RegionFinder; Heidelberg Engineering). A linear mixed effect model was used to model GA kinetics over time.

Main outcome measure: Change of GA lesion size over time (central vs. peripheral progression).

Results: A total of 47 eyes of 36 patients (mean age, 73.8±7.5 years) met the inclusion criteria. Mean follow-up time was 25.2±16.9 months (range, 5.9-74.6 months). Interreader agreement for measurements of GA and foveal-sparing size were 0.995 and 0.946, respectively. Mean area progression of GA toward the periphery was 2.27±0.22 mm(2)/year and 0.25±0.03 mm(2)/year toward the center. Analysis of square root-transformed data revealed a 2.8-fold faster atrophy progression toward the periphery than toward the fovea. Faster atrophy progression toward the fovea correlated with faster progression toward the periphery in presence of marked interindividual differences.

Conclusions: The results demonstrate a significantly faster centrifugal than centripetal GA spread in eyes with GA and foveal sparing. Although the underlying pathomechanisms for differential GA progression remain unknown, local factors may be operative that protect the foveal retina-retinal pigment epithelial complex. Quantification of directional spread characteristics and modeling may be useful in the design of interventional clinical trials aiming to prolong foveal survival in eyes with GA.