Two-Year AMD Progression Predicts Late AMD and Long-Term Visual Loss
By Lynda Seminara
Selected and Reviewed By: Neil M. Bressler, MD, and Deputy Editors
Journal Highlights
JAMA Ophthalmology, June 2020
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Vitale et al. set out to determine whether patients with faster short-term worsening of age-related macular degeneration (AMD) would reach late AMD more quickly. They found that two-year progression along the 9-step Age-Related Eye Disease Study (AREDS) AMD severity scale correlated with poor clinical and visual outcomes by year 7.
This study focused on a cohort of 3,868 AREDS patients (7,736 eyes) who had at least one eye without late AMD or geographic atrophy (GA) at baseline. Two-year AMD progression was defined as an increase of ≥2 or ≥3 steps on the AMD scale. Year 7 outcomes were neovascular AMD, central GA, any GA, and best-corrected visual acuity (BCVA) loss of ≥2 or ≥3 lines.
Two-year progression of 2 steps or more occurred in 9% of eyes; progression of at least 3 steps occurred in 3.7%. By year 7, neovascular AMD was present in 6.7% of those eyes, 4.7% had central GA, 10% had any GA, and 37% and 20.9% had a loss in BCVA of ≥2 or ≥3 lines, respectively.
After adjusting for confounders and stratifying data by baseline AMD score, the authors noted that AMD progression of at least 2 steps in the first two years correlated with neovascular AMD by year 7; hazard ratios (HRs) ranged from 3.6 to 19.4. HRs for development of central GA or any GA ranged from 2.6 to 4.7 and from 1.6 to 16.9, respectively. HRs for decreased BCVA ranged from 1.3 to 2.8. The link to poor outcomes was stronger for two-year AMD progression of ≥3 steps than for ≥2 steps, and risk generally was higher for progressing eyes that had lower AMD scores at baseline. For external validation, the authors applied their analyses to a separate cohort of patients drawn from AREDS2; they noted similar predictor-outcome associations.
Clinical trials of AMD treatments, especially those targeting earlier disease stages, may be stymied by the need for large sample sizes and long follow-up times to account for slow infrequent progression to late AMD. Results of this study suggest that patients free of bilateral late AMD at baseline who have disease progression by year 2 are more likely than nonprogressing patients to have late AMD and visual loss by year 7. Further clinical studies in this at-risk subpopulation may help investigators detect meaningful treatment effects in smaller short-duration studies.
The original article can be found here.