Low Plasma Levels of Lipid Biomarker Indicate Early Retinopathic Changes

Absence of a link between total plasma sphingomyelin and retinal thickness supports the idea that functional impairments may happen earlier than structural changes, reinforcing the idea that functional metrics are more sensitive markers of early neurodegeneration occurring in the retina. Photo: Julie Torbit, OD. Click image to enlarge. When counseling a diabetes patient about risks of ocular complications like diabetic retinopathy (DR), doctors know that early diagnosis is vital to prevent serious deleterious effects by allowing for earlier intervention; however, early progression and manifestation of the disease can be challenging to detect.One potential biomarker that may indicate early involvement with DR is a cell membrane lipid called sphingomyelin (SM). Researchers observed this in a recent study in relation with key indicators of DR, including retinal neurodegeneration subgroups of corneal nerve measures, retinal layer thickness and mean retinal sensitivity.The investigation aggregated data from the Maastricht Study, with 3,598 total individuals included. Three groups were established of those with normal glucose metabolism, those with prediabetes and those with type 2 diabetes. Upon analysis, average plasma levels of total SM were found to be lower in those with type 2 diabetes than those with either prediabetes or the control group—even after accounting for lipid-modifying medications use. It was also found that lower SM levels were associated with reduced mean retinal sensitivity in both left and right eyes. Taken together, this represents a novel link between plasma SM and worse retinal function, as observed via the reduced mean retinal sensitivity.Interestingly, the current study did not find a statistically significant correlation between SM levels and corneal nerve measures, which the researchers explain may be due to the distinctive impact of SM levels on tissue and systemic levels. There was also no observed relationship of SM level and retinal layer thickness, even after adjusting for confounding variables. However, the one positive association of the plasma level with mean retinal sensitivity suggests a potentially supportive role of SM in maintenance of neuroretinal function.Aligned with this are the findings of a prior longitudinal investigation which found a specific plasma SM species was related to a reduced risk of DR. The current findings demonstrated systemic reduction in circulating SM levels in those with diabetes, with such reductions in retinal sensitivity indicative of neuronal dysfunction, and this could reflect neuronal apoptosis preceding this occurring in a diabetic retina.They also note that overall, SM levels locally in the eye may be distinct from levels circulating in the body and could be relevant to the pathophysiology of DR. With results from previous studies, the authors point toward evidence suggesting alterations in ocular SM metabolism occurring with type 2 diabetes.Due to these findings, the authors believe “this supports the utility of sphingomyelin as a biomarker of functional retinal health rather than structural loss, potentially enabling earlier detection of retinal neurodegeneration before irreversible thinning occurs.”Click here for the journal source. Jadhav SA, Benedikter BJ, Mokhtar SBA, et al. Plasma sphingomyelin as biomarkers for diabetic retinal neurodegeneration – the Maastricht Study. Ophthalmol Sci. June 27, 2025. [Epub ahead of print].