advertisement
Editors Selection IGR 18-3
Progression / Prognostic Factors: Could your biological age predict glaucoma progression speed?
Comment by Keva Li & Louis Pasquale on:
126605 Accelerated Epigenetic Aging Is Associated with Faster Glaucoma Progression: A DNA Methylation Study, Medeiros FA; Varma A; Jammal AA et al., Ophthalmology, 2025; 132: 550-560
Chronological aging is the dark matter that contributes to glaucomatous in mysterious ways. Biological aging, reflected by DNA methylation profile alterations, may offer deeper insight into why two patients of the same chronological age might have different disease courses. Medeiros et al. explore this possibility using blood-derived DNA methylation profiles from 200 patients with primary open-angle glaucoma - 100 were fast progressors, and 100 were slow progressors based on longitudinal optic nerve functional and structural data. The authors applied several established epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge) to estimate biological age acceleration.
Accelerated epigenetic age was strongly associated with the fast progression group, independent of IOP or baseline disease severity. By the Horvath clock, fast progressors had three years higher biological age, where each additional year increased the odds of fast progression by 15%. Associations were strongest in patients without elevated IOP, with an acceleration of 4.7 years. Application of the other epigenetic clocks provided results that were largely consistent with the Horvath clock.
The study is carefully designed with rigorous classification of progressors, multiple epigenetic clocks, and appropriate multivariable adjustments. The cross-sectional nature of the blood collection precluded assessment of whether any epigenetic changes have a causal role in disease progression. Moreover, more work is needed to determine if blood-based DNA methylation profiles mirror those exhibited in ocular tissues. Nonetheless, replication in a larger external replication set would spark more interest in whether delaying epigenetic aging is an actionable therapeutic strategy for glaucoma management.
These findings parallel reports in neurodegenerative diseases where accelerated biological aging has been associated with Alzheimer’s and Parkinson’s disease. This study provides the first evidence linking epigenetic aging with glaucoma progression. In this work, glaucoma is reframed as a neurodegeneration rooted in systemic biological aging, and not just as an IOP-driven process.
Comments
The comment section on the IGR website is restricted to WGA#One members only. Please log-in through your WGA#One account to continue.Log-in through WGA#One
