Diabetes mellitus has been identified as a risk factor for dry eye syndrome (DES). The prevalence of DES in diabetes has been reported to be up to 54.3% (1). DES compromises quality of life because it induces ocular discomfort and visual disturbance and may be complicated by corneal epithelial defects, erosions, or ulcers. Therefore, it is recognized as a growing public health problem that should be diagnosed and treated (1).

Among the various forms of diabetic neuropathies, chronic sensorimotor distal symmetric polyneuropathy (PN) is the most common form and may manifest with symptoms while sensory and motor deficits are detected (2). The cornea is one of the most densely innervated parts of the human body containing myelinated A-δ and unmyelinated C fibers, deriving its innervation from the ophthalmic division of the trigeminal nerve. Recent data suggested that patients with PN have corneal nerve fiber damage and reduced corneal sensitivity (3). According to the International Dry Eye WorkShop (DEWS), the reduced corneal sensitivity favors the occurrence of DES in two ways: first by decreasing the reflex-induced lacrimal secretion and second by reducing the blink rate and increasing evaporative tear loss (4). Although PN and DES are common in diabetes, the relationship between them is not known. The research hypothesis we tested herein was that subjects with PN may more often have DES as a result of reduced corneal sensitivity and impaired balance of tear production/evaporation.

A total of 61 subjects with type 2 diabetes and 38 control subjects were recruited in this cross-sectional study. PN was assessed by using the neuropathy disability and neuropathy symptom scores (5). We used the DEWS recommendation to assess DES (4). Moreover, the Schirmer I test, tear film breakup time (TBUT) and corneal sensitivity were evaluated (3). Subjects who wore contact lenses, had ocular/glaucoma drops, were on antihistamine or antidepressant medications, or underwent ocular surgery were excluded.

PN was diagnosed in 34 patients (55.7%). DES was diagnosed more often in subjects with PN than in those without PN and control subjects (76.5, 44.4, and 28.9%, respectively; P < 0.001). The values of the Schirmer I test, TBUT, and corneal sensitivity were worse in patients with PN than in those without PN and control subjects (P < 0.001). There were significant correlations (P < 0.05) between neuropathy disability, Schirmer I test, TBUT, and corneal sensitivity (Table 1).

Table 1

Ocular findings in control subjects and in subjects with diabetes according to the presence (PN+) or absence (PN−) of diabetic PN

Control subjects (n = 38)PN− (n = 27)PN+ (n = 34)P
Ocular surface dryness (DEWS criteria) 11 (28.9) 12 (44.4) 26 (76.5) <0.001 
Schirmer I test, mm     
 Right eyes 15.10 ± 6.78 12.15 ± 4.93 10.05 ± 6.75 0.004 
 Left eyes 15.73 ± 7.68 13.61 ± 6.31 10.48 ± 7.07 0.01 
TBUT, s     
 Right eyes 11.36 ± 2.92 9.69 ± 3.68 7.08 ± 2.56 <0.001 
 Left eyes 12.02 ± 3.20 10.09 ± 3.29 7.51 ± 2.76 <0.001 
Cochet-Bonnet score, cm     
 Right eyes 4.71 ± 0.34 4.46 ± 0.42 3.50 ± 0.81 <0.001 
 Left eyes 4.69 ± 0.35 4.48 ± 0.45 3.51 ± 0.84 <0.001 
Cochet-Bonnet score     
 ≥4.5 (normal) 20 (52.6) 8 (29.6) 3 (8.8)  
 4–4.49 (borderline) 18 (47.4) 18 (66.7) 10 (29.4)  
 <4.0 (abnormal) 0 (0) 1 (3.7) 21 (61.8) <0.001 
Control subjects (n = 38)PN− (n = 27)PN+ (n = 34)P
Ocular surface dryness (DEWS criteria) 11 (28.9) 12 (44.4) 26 (76.5) <0.001 
Schirmer I test, mm     
 Right eyes 15.10 ± 6.78 12.15 ± 4.93 10.05 ± 6.75 0.004 
 Left eyes 15.73 ± 7.68 13.61 ± 6.31 10.48 ± 7.07 0.01 
TBUT, s     
 Right eyes 11.36 ± 2.92 9.69 ± 3.68 7.08 ± 2.56 <0.001 
 Left eyes 12.02 ± 3.20 10.09 ± 3.29 7.51 ± 2.76 <0.001 
Cochet-Bonnet score, cm     
 Right eyes 4.71 ± 0.34 4.46 ± 0.42 3.50 ± 0.81 <0.001 
 Left eyes 4.69 ± 0.35 4.48 ± 0.45 3.51 ± 0.84 <0.001 
Cochet-Bonnet score     
 ≥4.5 (normal) 20 (52.6) 8 (29.6) 3 (8.8)  
 4–4.49 (borderline) 18 (47.4) 18 (66.7) 10 (29.4)  
 <4.0 (abnormal) 0 (0) 1 (3.7) 21 (61.8) <0.001 

Data are mean ± SD or n (%). PN−, absence of diabetic PN; PN+, presence of diabetic PN.

Limitations of the study are 1) the small number of participants; 2) its cross-sectional design; 3) only patients with type 2 diabetes were included; and 4) the function of the corneal nerve plexus but not the anatomical corneal innervation and the blink rate was evaluated.

In conclusion, we have shown that DES is particularly common in patients with type 2 diabetes who have PN, and it is associated with reduced corneal sensitivity. Corneal hypoesthesia reduces patient’s symptoms, and DES might be asymptomatic and insidious. We suggest that patients with PN be screened for DES and probably treated long-term for the prevention of ocular surface damage.

Acknowledgments. This work was approved by the University of Athens Medical School Clinical Research Ethics Committee.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Author Contributions. V.A. executed the conception and design, collected and researched data, and wrote and reviewed the manuscript. I.E. collected data and researched data and edited the manuscript. E.K. reviewed/edited the manuscript and researched data. K.I.V. and E.S. reviewed/edited the manuscript. P.G.T. researched data and reviewed/edited the manuscript. N.T. executed the conception and design, analyzed and researched data, and wrote and reviewed the manuscript. V.A. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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