Corneal nerve damage reflects renal dysfunction in type 2 diabetes
Aims: To investigate the association between corneal nerves, ocular surface health, and renal function in a large cohort of patients with type 2 diabetes (T2DM) with and without diabetic kidney disease (DKD).
Methods: A total of 538 patients with T2DM underwent corneal confocal microscopy (CCM) to quantify corneal nerve metrics, epithelial cell and immune cell parameters. Ocular surface assessment included tear-break up time (TBUT), Schirmer test, corneal staining scores, ocular surface disease index (OSDI) and corneal sensitivity. Renal function was assessed using eGFR, serum creatinine, urine albumin, urine albumin-creatinine ratio (UACR) and urine protein-creatinine ratio. DKD was defined by eGFR < 60 ml/min/1.73 m2.
Results: Patients with DKD showed significantly lower corneal nerve fibre density (CNFD), length (CNFL), area and fractal dimension, and higher corneal nerve fibre width (CNFW). They also demonstrated poorer ocular surface integrity (lower TBUT and Schirmer values, higher staining scores and OSDI) and reduced epithelial cell count and density with larger cells. After adjustment for confounders, lower CNFD was associated with higher urine albumin, while higher CNFW was associated with both higher urine albumin and UACR. In logistic models, CNFL and CNFW were independently associated with DKD.
Conclusions: In T2DM, corneal nerve impairment is associated with renal dysfunction, and patients with poorer corneal nerve metrics might be at higher risk of DKD. Equally, patients with DKD may benefit from corneal nerve and ocular surface assessment.
Comments: This is one of the largest studies linking corneal nerve morphology and ocular surface integrity to renal function in T2DM. A key strength is the comprehensive phenotyping combined with multivariable modelling, showing that albuminuria measures (urine albumin/UACR) correlate with CNFD and CNFW. This is expected, as diabetic microvascular injury affects both small nerve fibres and the kidney, suggesting that CCM may reflect overall disease burden.
However, due to the cross-sectional design, it remains unclear whether corneal nerve damage precedes renal dysfunction, develops in parallel, or reflects more advanced disease. Therefore, the findings demonstrate association rather than prediction or causation. Longitudinal studies would be needed, although this is challenging due to the long natural history of DKD and delayed onset of microalbuminuria. Furthermore, CCM availability remains limited to specialist centres.
Overall, this study suggests that CCM holds promise as a surrogate marker for diabetic nephropathy, but prospective longitudinal studies are needed to determine if it adds predictive value beyond standard renal markers.
Alise Kalteniece
Reference. Liu C, Tan HC, Yu M, Lee IXY, Cheng CY, Liu YC. The Association among Corneal Nerve Metrics, Ocular Surface Integrity, and Renal Function in Type 2 Diabetes. Ophthalmol Sci. 2025 Dec 8;6(2):101031. doi: 10.1016/j.xops.2025.101031. PMID: 41584095; PMCID: PMC12830328.
