Cardiovascular

Early changes in the central vision and the macula in diabetic retinal disease: associations with serum biomarkers.

Nagai N, Shinoda H, et al. • Frontiers in endocrinology • 2026

PubMed 42921263 DOI 10.3389/fendo.2026.1972307
TL;DR

In diabetic patients without visible macular lesions, worse central vision was associated with shorter photoreceptor outer segments, lower retinal vessel density, and lower RPE volume, which in turn were linked to serum HbA1c, HDL, oxidized LDL, uric acid, and hsCRP.

Key Findings

Results

Worse best-corrected visual acuity (BCVA) was independently associated with shorter photoreceptor outer segment (PROS) length in diabetic patients without obvious macular lesions.

  • Multiple regression adjusted for age, sex and duration of diabetes gave β = -0.278, P = 0.005.
  • The study was a retrospective observational analysis of 121 eyes of 121 patients (mean age 61.7 years; 80 male, 66.1%).
  • PROS length was measured with optical coherence tomography (OCT).
Results

Worse BCVA was also associated with lower retinal vessel density.

  • Adjusted analysis gave β = -0.328, P = 0.002.
  • Retinal vessel density was assessed with OCT angiography (OCTA).
  • Patients had no obvious macular lesions.
Results

PROS length was positively associated with retinal pigment epithelium (RPE) volume.

  • Adjusted for age, sex and diabetes duration: β = 0.318, P < 0.001.
  • This links the RPE with the photoreceptor outer segments, which are in turn related to central vision.
Results

RPE volume was associated with serum lipid, uric acid and glycemic markers.

  • RPE volume was positively associated with HDL cholesterol (β = 0.289).
  • RPE volume was negatively associated with oxidized LDL (β = -0.216), uric acid (β = -0.210) and HbA1c (β = -0.215); all P ≤ 0.05.
  • Models were adjusted for age, sex and duration of diabetes.
Results

Lower retinal and/or choroidal vascular values were associated with higher HbA1c and high-sensitivity C-reactive protein (hsCRP).

  • Standardized β coefficients ranged from -0.256 to -0.384; all P ≤ 0.05.
  • Vascular parameters were derived from OCTA of the retina and choroid.
Conclusions

Subtle macular neural and vascular changes were linked with systemic biomarkers in diabetic patients without visible macular lesions, and monitoring certain biomarkers may help estimate visual impairment risk.

  • Impaired central vision was associated with shorter PROS, lower RPE volume and reduced vascular parameters.
  • The authors suggest that monitoring HbA1c, HDL, oxidized LDL, uric acid and hsCRP may help estimate risk of visual impairment.
  • Analyses used Spearman's rank correlation and multiple regression; the design was retrospective and observational, so causality cannot be established.

What This Means

This study looked at people with diabetes whose eyes showed no obvious damage to the macula, the central part of the retina used for sharp vision. Using detailed eye scans (OCT and OCT angiography) and routine blood tests in 121 patients, the researchers examined how vision, the thickness and size of retinal layers, blood flow, and blood markers relate to each other. Even without visible damage, poorer central vision was linked to shorter light-sensing outer segments of photoreceptors and to lower blood vessel density in the retina. Shorter outer segments were in turn linked to a smaller volume of the retinal pigment epithelium, a supporting layer under the photoreceptors. A smaller volume of this layer was associated with lower HDL ('good') cholesterol and higher oxidized LDL, uric acid and HbA1c (a measure of long-term blood sugar). Lower blood flow in the retina and choroid was associated with higher HbA1c and a marker of inflammation (hsCRP). This research suggests that subtle changes in the macula may occur early in diabetes and be tied to blood sugar, cholesterol, uric acid, and inflammation. Because the study was retrospective and showed associations only, it cannot prove that these blood markers cause the eye changes. The findings may help guide future work on which routine blood tests could help flag the risk of vision problems.

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Citation

Nagai N, Shinoda H, Meguro S, Sonoda S, Sakamoto T, Negishi K, et al.. (2026). Early changes in the central vision and the macula in diabetic retinal disease: associations with serum biomarkers.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1972307