Corneal Nerve Morphological Changes May Reveal Dry Eye Disease

Proteomic analysis may identify individuals who can benefit from dry eye treatments.

Corneal nerve morphological changes may indicate dry eye disease (DED), according to research published in Experimental Eye Research. These alterations are associated with 6 tear film biomarkers, which show a positive correlation with corneal nerve branch density and corneal nerve branch total density, the report shows.  

Researchers included individuals with DED (n=43; mean age, 42.1 years; 62.8% women) and age-matched control group participants (n=16; mean age, 38.9 years; 56.3% women) in the prospective, cross-sectional investigation between October and November 2017. In the course of 4 visits, participants underwent proteomic analysis, ophthalmic examination, tear breakup time (TBUT) and Schirmer 1 assessments, and completed subjective DED questionnaires, which included the Ocular Surface Disease Index (OSDI) and the 5-Item Dry Eye Questionnaire (DEQ-5). The team performed retinal tomography to determine corneal nerve fiber length, density, branch density, and total branch density. 

Participants with DED had lower TBUT scores (4.57 vs 8.40 seconds; P <.001) and demonstrated worse pain tolerance capacity, evidenced by higher aesthesiometer readings (44.1 vs 35.9 mm; P =.034), compared with control group participants, the report shows. Corneal nerve morphological changes, including corneal nerve branch density and corneal nerve total branch density values, were significantly higher among the cohort with DED compared with the control group (21.3 vs 14.6/ mm2; P =.022 and 45.0 vs 28.6/ mm2; P =.007, respectively), and these values negatively correlated with TBUT scores. 

These findings suggest that DED is associated with corneal nerve morphological changes, and proteomic analysis confirmed that these alterations correlated with 6 biomarkers, which include cystatin-S, immunoglobulin kappa constant, neutrophil gelatinase-associated lipocalin, profilin-1, protein S100-A8, and protein S100-A9, according to the report. 

Assessment of these proteins as biomarkers will enable identification of subjects who could benefit from targeted therapy. 

“Our tear proteomics helped identify some molecules that correlated with nerve branch density,” according to the researchers. “Assessment of these proteins as biomarkers will enable identification of subjects who could benefit from targeted therapy.”

Study limitations include a small sample size and single center design.

Disclosure: This research was supported by Senju Pharmaceutical Co., Ltd. Please see the original reference for a full list of disclosures.


Uchino Y, Uchino M, Mizuno M, Shigeno Y, Furihata K, Shimazaki J. Morphological alterations in corneal nerves of patients with dry eye and associated biomarkers. Exp Eye Res. Published online March 16, 2023. doi:10.1016/j.exer.2023.109438