TOPLINE:

Worsening of cardiovascular-kidney-metabolic syndrome was associated with an increased risk for developing age-related macular degeneration (AMD), with stage 4 disease linked to a 48% higher risk for the retina disorder than stage 0 disease; genetic risk for AMD did not appear to substantially modify the association.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to examine the association between cardiovascular-kidney-metabolic syndrome and the risk for AMD and whether genetic risk for AMD modified this association.
• They analyzed data of 319,638 participants (mean age, 56.3 years; 51.7% women) from the UK Biobank who did not have AMD at baseline, recruited across the UK between 2006 and 2010.
• Participants were classified as having stage 0-4 cardiovascular-kidney-metabolic syndrome using adapted American Heart Association criteria based on metabolic risk factors, chronic kidney disease, cardiovascular risk, and established cardiovascular disease. Classification into stage 0 required a BMI between 18.5 and 24.9 and a waist circumference smaller than 88 cm for women or under 102 cm for men, with no other risk factors.
• Researchers used a polygenic risk score for AMD to categorize participants as having a low or high genetic predisposition to AMD.
• Participants were followed up for a median of 12.5 years to identify the diagnosis of AMD from hospital records, data on death registration, and self-reports.

TAKEAWAY:

• During follow-up, 4982 participants (1.56%) developed AMD.
• Advanced stages of cardiovascular-kidney-metabolic syndrome were associated with higher risks for AMD than stage 0, with the adjusted hazard ratios (aHRs) of 1.15 (95% CI, 1.02-1.30) for stage 1, 1.25 (95% CI, 1.13-1.38) for stage 2, 1.22 (95% CI, 1.08-1.38) for stage 3, and 1.48 (95% CI, 1.30-1.68) for stage 4. Each one-stage increase corresponded to a 9% increased risk for AMD.
• A higher polygenic risk score for AMD was associated with a 70% increased risk for AMD. However, researchers observed no significant interaction between genetic predisposition and stages of cardiovascular-kidney-metabolic syndrome.
• Participants with stage 4 cardiovascular-kidney-metabolic syndrome and high genetic predisposition had the highest risk for AMD compared with those with stage 0 disease and low genetic predisposition.

IN PRACTICE:

“Although we did not observe a significant interaction between CKM [cardiovascular-kidney-metabolic] syndrome and genetic predisposition on incident AMD, joint analyses revealed that participants with CKM stage 4 and high genetic predisposition showed the highest risk of AMD,” the researchers reported. “Taken together, the current study highlights the importance of routine screening and management of CKM syndrome, regardless of genetic predisposition.”

SOURCE:

The study was led by Fengyue Wu and Kun Xu of Shengjing Hospital of China Medical University in Shenyang, China. It was published online on January 22, 2026, in the American Journal of Ophthalmology.

LIMITATIONS:

The observational design could not establish that cardiovascular-kidney-metabolic syndrome caused AMD. Participants were mostly White and from healthier and more affluent community settings, which may have limited the generalizability of findings. Diagnoses of AMD relied on records, registries, and self-reports, which may have missed some cases and introduced recall bias.

DISCLOSURES:

The study received support from the Liaoning Provincial Science and Technology Plan Joint Program. The authors reported having no financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.