Purpose: To identify quantifiable markers of disease progression in patients with foveal-sparing atrophic late-onset retinal degeneration using fundus autofluorescence and spectral-domain optical coherence tomography imaging. Methods: Natural history study evaluating patients within a 3-year interval. Disease progression was assessed based on the area of retinal atrophy, macular topographic distribution of lesions, retinal and choroidal thickness and volume, and choroidal vascularity index. Results: Twenty-four eyes (12 individuals) were included for fundus autofluorescence, and 31 eyes (16 individuals) for spectral-domain optical coherence tomography studies. Measurements were symmetrical between eyes of the same patient. The area of atrophy significantly enlarged (P = 0.002), with a growth rate of 2.67 mm2/year (SD: 2.13; square rooted: 0.57 mm/year, SD = 0.34). Baseline area of atrophy and progression both correlated with age. Most atrophic lesions were found in the temporal macula and progressed nasally at follow-up. Central choroidal and retinal thicknesses and volume in late-onset retinal degeneration cases were significantly reduced compared with controls, but only central retinal thickness decreased significantly at follow-up. Conclusion: This study identifies the area of atrophy and central retinal thickness, but not chorioretinal volume or choroidal thickness, as markers of short-term progression in late-onset retinal degeneration. These findings may be useful for disease monitoring and late-onset retinal degeneration interventional studies.