Potential biomarkers for chronic ocular pain associated with dry eye disease

Resumen

OBJECTIVES 1) To evaluate the clinical and molecular characteristics of the Lacrimal Functional Unit (LFU) of patients with chronic ocular pain associated with Dry Eye Disease (DED) and compare them with those of patients with DED but no pain and healthy controls. 2) To assess the ocular surface of patients with DED after treatment of periorbital wrinkles with thermo-mechanical action-based fractional skin treatment (Tixel®). METHODOLOGY To address the objective 1, a case-control study was conducted at the Institute of Applied Ophthalmobiology (IOBA) of the University of Valladolid (Valladolid, Spain). Three groups were recruited: a) patients with chronic ocular pain associated with DED; b) patients with DED but no pain; and c) subjects without DED or ocular pain (healthy controls). All participants were evaluated after 30 minutes under a normal controlled environment. After that, a detailed examination of the ocular surface was performed, and tear and conjunctival epithelial cell samples were collected and analysed for cytokines and substance P, and genes and microRNAs, respectively. To address the objective 2, a retrospective study was conducted at Aston University (Birmingham, United Kingdom). Data were collected from patients with DED who had periorbital wrinkles treated with Tixel®. Data were collected from 4 visits to which patients attended every 2 weeks +/- 5 days and from a 5th follow-up visit that took place 18 weeks +/- 5 days after the first visit. The same clinical examination was performed at all visits (ocular symptomatology, visual acuity, refraction, tear osmolarity, tear stability and keratometry), but the Tixel® treatment was applied at the first 3 visits. RESULTS IOBA project. Ninety-three subjects were included: 28 patients with chronic ocular pain associated with DED, 35 patients with DED but no pain, and 30 healthy controls. Patients with chronic ocular pain reported higher ocular and depression-related symptoms. In addition, differences in ocular surface clinical tests and in the expression of genes and microRNAs were observed in the group of patients with chronic ocular pain associated with DED compared to patients with DED but no pain and controls. Regarding tear cytokine analysis, IL-8/CXCL8 levels were higher in both groups of DED patients. Aston University project. Thirty-seven DED patients were included. A decrease in DED-related symptoms and an increase in tear stability were shown after Tixel® treatment. In addition, 27.27% of DED patients had a change in their keratometry of at least 0.50 dioptres between pre-treatment visit and 3-month visit. Regarding refraction, sphere and cylinder changed by at least 0.50 dioptres in 21.43% and 35.72% of patients, respectively, and the refractive axis changed by at least 20 degrees in 50%. CONCLUSIONS Patients with chronic ocular pain associated with DED have differences at both the clinical and the molecular levels in the LFU compared to those patients with DED but no pain or to control subjects. The development of more effective drugs and selective therapies for each subject (personalised medicine) targeting these differential clinical characteristics and potential biomarkers could improve the LFU and symptoms of these patients and thus their quality of life. In addition, thermo-mechanical action-based fractional skin treatment applied on periorbital wrinkles improves symptoms and clinical signs of DED patients. However, anterior corneal curvature and refraction can change. This fact must be considered before calculating the pre-surgical parameters to obtain satisfactory visual results and avoid additional surgical procedures.