Age-related macular degeneration (AMD) is traditionally viewed through an ocular lens, shaped by local pathology and well-established risk factors such as age, smoking, and genetics. However, a new study published in Ophthalmology Science challenges this eye-centric view, presenting compelling evidence that chronic kidney disease (CKD) is not merely associated with AMD, but may play a causal role in its development.
Using a dual approach that combined prospective cohort analysis with Mendelian randomization, the multi-institutional researchers provide some of the strongest evidence to date linking systemic renal dysfunction with advanced AMD.
The study analyzed data from more than 430,000 participants in the UK Biobank, followed for over a decade. Individuals with CKD at baseline were found to have a significantly higher risk of developing incident AMD, even after adjustment for major cardiovascular and metabolic confounders.
To address the perennial question of causality, the team then turned to Mendelian randomization, leveraging genetic variants associated with kidney function in over one million individuals. Lower genetically determined eGFR was causally linked to a more than twofold increase in the risk of advanced AMD. Importantly, multiple sensitivity analyses supported the robustness of this finding, reducing the likelihood that it reflects confounding or pleiotropy.
Perhaps the most intriguing insight comes from the colocalization analysis, which identified a shared genetic signal at the apolipoprotein E (APOE) locus. APOE is already familiar to ophthalmologists for its role in lipid metabolism and AMD susceptibility, but it is also implicated in renal disease progression. The identification of a shared causal variant suggests that common biological pathways — potentially involving lipid transport, endothelial dysfunction, or chronic inflammation — may underpin both kidney and retinal degeneration.
This finding reinforces the concept of AMD as a systemic disease manifestation rather than simply an isolated ocular disorder.
For ophthalmologists, the implications are clear. Patients with CKD represent a higher-risk group for AMD, and this risk appears to be biologically driven rather than purely coincidental. The authors argue that targeted AMD screening in patients with impaired kidney function may be warranted — particularly given the asymptomatic nature of early disease and the benefits of timely intervention in advanced AMD.
The study also highlights the importance of interdisciplinary care. As ophthalmology increasingly intersects with nephrology, cardiology, and genetics, clinicians must remain alert to systemic signals that influence ocular outcomes.
Using a dual approach that combined prospective cohort analysis with Mendelian randomization, the multi-institutional researchers provide some of the strongest evidence to date linking systemic renal dysfunction with advanced AMD.
The study analyzed data from more than 430,000 participants in the UK Biobank, followed for over a decade. Individuals with CKD at baseline were found to have a significantly higher risk of developing incident AMD, even after adjustment for major cardiovascular and metabolic confounders.
To address the perennial question of causality, the team then turned to Mendelian randomization, leveraging genetic variants associated with kidney function in over one million individuals. Lower genetically determined eGFR was causally linked to a more than twofold increase in the risk of advanced AMD. Importantly, multiple sensitivity analyses supported the robustness of this finding, reducing the likelihood that it reflects confounding or pleiotropy.
Perhaps the most intriguing insight comes from the colocalization analysis, which identified a shared genetic signal at the apolipoprotein E (APOE) locus. APOE is already familiar to ophthalmologists for its role in lipid metabolism and AMD susceptibility, but it is also implicated in renal disease progression. The identification of a shared causal variant suggests that common biological pathways — potentially involving lipid transport, endothelial dysfunction, or chronic inflammation — may underpin both kidney and retinal degeneration.
This finding reinforces the concept of AMD as a systemic disease manifestation rather than simply an isolated ocular disorder.
For ophthalmologists, the implications are clear. Patients with CKD represent a higher-risk group for AMD, and this risk appears to be biologically driven rather than purely coincidental. The authors argue that targeted AMD screening in patients with impaired kidney function may be warranted — particularly given the asymptomatic nature of early disease and the benefits of timely intervention in advanced AMD.
The study also highlights the importance of interdisciplinary care. As ophthalmology increasingly intersects with nephrology, cardiology, and genetics, clinicians must remain alert to systemic signals that influence ocular outcomes.
