OBJECTIVES : Geographic atrophy (GA) can cause irreversible blindness. Lesion growth is often used as an endpoint in GA trials. However, studies have not shown strong correlations between lesion size and vision or health-related quality of life (V/HRQOL).

METHODS : A targeted literature review was undertaken in January 2021 to identify studies on natural history or studies evaluating correlations between clinical outcome measures and HRQOL. Findings of this review were used to the develop a progression model for GA that considers clinical outcomes such as lesion size and functional outcomes like visual acuity, with the latter being more relevant to a person’s V/HRQOL

RESULTS : Twenty-four papers were identified using pre-defined exclusion criteria for full text review. There was a weak/moderate correlation between total atrophy and worsening visual acuity (VA) (r²>0.36). There was a smaller correlation between lesion growth and vision loss when growth was nonsubfoveal (r²=0.07); a stronger correlation emerged within the fovea (r²=0.49). Additional complexity results from the fact that the growth rate of nonsubfoveal lesions is faster, slowing upon entering the fovea. This combination of faster nonsubfoveal lesion growth, followed by slower subfoveal growth with higher impact on VA and vision-related QOL, produces challenges with developing a progression model throughout the lifecycle of GA. A multifactor progression model was developed combining GA location and impact on VA to better align clinical measures of progression with changing patient disease burden.

CONCLUSIONS : GA is a complex disease that combines faster lesion growth in the initial stages with slower, but more impactful, growth in later stages. A progression model incorporating both lesion growth and foveal involvement, and the resulting impact on VA and HRQOL, would be more reflective of the value to patients of future GA treatments.