Thinner RNFL Associated with Advanced Cardiovascular-Kidney-Metabolic Syndrome

Retinal nerve fiber layer (RNFL) has emerged as a potential noninvasive biomarker of systemic vascular and metabolic health. Because of the severity of cardiovascular-kidney-metabolic (CKM) syndrome, researchers examined the association between RNFL thickness and CKM syndrome in a large community-based cohort of healthy United Kingdom Biobank participants to determine a possible role for RFNL measurements as well as its validity as an indicator of systemic damage. They found that advanced CKM syndrome was more frequently found in those with the thinnest RNFL thickness. The findings were reported in American Journal of Ophthalmology.A total of 17,082 participants were included; of these, 93% had CKM syndrome stage 1 or higher at baseline. Advanced CKM syndrome (stage 3 or higher) was observed more frequently among patients with the lowest RNFL thickness grade (14.8%) vs. the thickest group (9.1%), suggesting that RNFL thickness may serve as a valuable marker for monitoring CKM syndrome. Similar trends were observed with overall macular thickness, where each 1µm decrease corresponded to a 2.4 increased likelihood of having advanced CKM syndrome—indicating the onset of subclinical or clinical cardiovascular disease. These findings suggest that ocular parameters such as RNFL may be potential indicators for especially advanced CKM syndrome and may have a role in screening for those with a high cumulative systemic burden, requiring intensive medical management. Photo: American Heart Assn. Click image to enlarge. In addition, the authors explained that the differences in the proportion of patients having CKM syndrome at baseline between the thickest and the thinnest were significant for the overall macular thickness and RNFL, but not the total macular volume. “Mutually reinforcing harmful relationships among metabolic diseases chronic kidney disease and cardiovascular disease were well-established, but through the present study, we offer support that their detrimental impacts reach beyond the heart and kidneys to include the central nervous system,” the authors wrote in their paper. “Our findings are in line with the assertion that nearly every major organ system is known to be affected as a consequence of CKM syndrome.”They also note that their effects on other organ systems may be cumulative, as the increasing severity of the disease (i.e., increasing number of abnormalities) were associated with thinner RNFL and macular thickness.“Lastly, the effects of CKM syndrome in the eye—at least in the early stages—are limited to the RNFL layer with preserved structural integrity in the outer retinal layers, even in the absence of overt diabetic or hypertensive retinopathy,” the authors wrote in their paper.While the mechanism through which CKM syndrome is associated with ocular parameters such as RNFL remains elusive, there are a few possible mechanisms, the researchers suggested. The first is related to excess body fat and related insulin resistance, which are also thought to be the root cause of many other harms from the disease.“Another possible mechanism is through the elevated glucose concentrations, which on their own, are also believed to be toxic for retinal ganglion, glial and endothelial cells,” the authors noted in their paper. “Other possible mechanisms include decreased flow in the capillaries supplying the macula, resulting in ischemic damage for retinal ganglion cells that have a high energy demand.”In conclusion, the authors suggest that RNFL measurements—obtainable via non-invasive OCT—may serve as a valuable marker for monitoring the severity of CKM syndrome. However, they noted that further longitudinal research is required to validate RNFL as a prognostic marker and to confirm its clinical utility in individual patient management.Click here for the journal source. Lee JS, Heo S-J, Myung D, et al. Association between retinal nerve fiber layer thickness and cardiovascular-kidney-metabolic syndrome: A UK Biobank cohort study. Am J Ophthalmol. April 21, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.