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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

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

  • Norihiro Nagai1
  • Hajime Shinoda1
  • Shu Meguro2
  • Shozo Sonoda3
  • Taiji Sakamoto3
  • Kazuno Negishi1
  • Yoko Ozawa1,4
4 affiliations
  1. 1Department of Ophthalmology, Keio University School of Medicine
  2. 2Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine
  3. 3Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences
  4. 4Department of Clinical Regenerative Medicine, Fujita Medical Innovation Center Tokyo & Eye Center, Fujita Health University Haneda Clinic
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Abstract

Background: Recent progress in medical science allows patients with diabetes to expect preservation of good central vision. However, the influence of diabetes-related systemic factors on the macula is not fully understood. We therefore investigated associations among central vision, macular neural and vascular parameters, and systemic biomarkers to explore the pathogenesis of early diabetic retinal disease (DRD).

Methods: In this retrospective observational study, we evaluated best-corrected visual acuity (BCVA), size parameters of components of the neural retina, and blood flow in the retina and choroid in patients with diabetes and no obvious macular lesions. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used for the ocular assessments. Serum biomarker levels were determined from routine blood tests. Associations among ocular parameters and between ocular parameters and serum biomarkers were analyzed using Spearman’s rank correlation coefficient analyses and multiple regression analyses adjusted for age, sex and duration of diabetes.

Results: The study included 121 eyes of 121 patients (mean age, 61.7 years), of whom 80 (66.1%) were male. In analyses adjusted for age, sex and duration of diabetes, worse BCVA was associated with shorter photoreceptor outer segment (PROS) length (β = −0.278, P = 0.005) and lower retinal vessel density (β = −0.328, P = 0.002). PROS length was positively associated with retinal pigment epithelium (RPE) volume (β = 0.318, P < 0.001). RPE volume was positively associated with serum high-density lipoprotein cholesterol (HDL) levels and negatively associated with oxidized low-density lipoprotein cholesterol (LDL), uric acid and hemoglobin A1c (HbA1c) levels (β = 0.289, -0.216 −0.210, and −0.215, respectively; all P ≤ 0.05). Lower retinal and/or choroidal vascular values were associated with higher HbA1c and high-sensitivity C-reactive protein (hsCRP) levels (β = −0.256 to −0.384; all P ≤ 0.05).

Conclusion: This study links subtle macular neural and vascular changes with systemic biomarkers in diabetic patients without visible macular lesions. Impaired central vision was associated with shorter PROS, lower RPE volume, and reduced vascular parameters. These findings improve understanding of early DRD and suggest that monitoring HbA1c, HDL, oxidized LDL, uric acid, and hsCRP may help estimate the risk of visual impairment.

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Cite

BibTeXRIS
BibTeX
@article{nagai2026early,
  title = {{Early changes in the central vision and the macula in diabetic retinal disease: associations with serum biomarkers}},
  author = {Norihiro Nagai and Hajime Shinoda and Shu Meguro and Shozo Sonoda and Taiji Sakamoto and Kazuno Negishi and Yoko Ozawa},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1972307},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1972307/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Early changes in the central vision and the macula in diabetic retinal disease: associations with serum biomarkers
AU  - Norihiro Nagai
AU  - Hajime Shinoda
AU  - Shu Meguro
AU  - Shozo Sonoda
AU  - Taiji Sakamoto
AU  - Kazuno Negishi
AU  - Yoko Ozawa
PY  - 2026
DA  - 2026/10/06
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1972307
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1972307/full
AB  - Background: Recent progress in medical science allows patients with diabetes to expect preservation of good central vision. However, the influence of diabetes-related systemic factors on the macula is not fully understood. We therefore investigated associations among central vision, macular neural and vascular parameters, and systemic biomarkers to explore the pathogenesis of early diabetic retinal disease (DRD).  Methods: In this retrospective observational study, we evaluated best-corrected visual acuity (BCVA), size parameters of components of the neural retina, and blood flow in the retina and choroid in patients with diabetes and no obvious macular lesions. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used for the ocular assessments. Serum biomarker levels were determined from routine blood tests. Associations among ocular parameters and between ocular parameters and serum biomarkers were analyzed using Spearman’s rank correlation coefficient analyses and multiple regression analyses adjusted for age, sex and duration of diabetes.  Results: The study included 121 eyes of 121 patients (mean age, 61.7 years), of whom 80 (66.1%) were male. In analyses adjusted for age, sex and duration of diabetes, worse BCVA was associated with shorter photoreceptor outer segment (PROS) length (β = −0.278, P = 0.005) and lower retinal vessel density (β = −0.328, P = 0.002). PROS length was positively associated with retinal pigment epithelium (RPE) volume (β = 0.318, P < 0.001). RPE volume was positively associated with serum high-density lipoprotein cholesterol (HDL) levels and negatively associated with oxidized low-density lipoprotein cholesterol (LDL), uric acid and hemoglobin A1c (HbA1c) levels (β = 0.289, -0.216 −0.210, and −0.215, respectively; all P ≤ 0.05). Lower retinal and/or choroidal vascular values were associated with higher HbA1c and high-sensitivity C-reactive protein (hsCRP) levels (β = −0.256 to −0.384; all P ≤ 0.05).  Conclusion: This study links subtle macular neural and vascular changes with systemic biomarkers in diabetic patients without visible macular lesions. Impaired central vision was associated with shorter PROS, lower RPE volume, and reduced vascular parameters. These findings improve understanding of early DRD and suggest that monitoring HbA1c, HDL, oxidized LDL, uric acid, and hsCRP may help estimate the risk of visual impairment.
SN  - 1664-2392
ER  -