Proposal, Derivation, and External Validation of a Novel Geographic Atrophy Outcome Measure

Area of Science:

• Ophthalmology
• Medical Imaging
• Biostatistics

Background:

• Existing geographic atrophy (GA) outcome measures have limitations.
• Best-corrected visual acuity (BCVA) is functional but subjective; GA area is objective but assumes uniform macular importance.

Purpose of the Study:

• To derive and validate the Geographic Atrophy Weighted-by-Acuity Index (GAWAIN) as a novel outcome measure.
• To align a structural GA measure with the functional BCVA measure.

Main Methods:

• Developed GAWAIN using in silico analyses and data from AREDS2 and GA Minocycline Trial.
• Empirically weighted macular pixels in concentric annuli based on BCVA deficit and age.
• Validated GAWAIN against BCVA and GA area using Pearson correlation and ROC analysis.

Main Results:

• GAWAIN showed stronger correlation with BCVA deficit than GA area on internal (r=0.58 vs 0.32) and external (r=0.69-0.70 vs 0.56-0.58) validation.
• GAWAIN more accurately predicted BCVA thresholds than GA area.
• Changes in GAWAIN correlated more strongly with BCVA decline than changes in GA area.

Conclusions:

• GAWAIN, a novel outcome measure, aligns structural GA assessment with functional BCVA.
• This provides a more objective and meaningful surrogate for tracking predicted functional decline in GA.