The Effect Of Diquafosol On Tear Film Inflammatory Markers Of Dry Eye Patients: A Non-Comparative, Open-Label, Proof-Of-Concept Study

This study analyzed the change in the levels of tear film pro-inflammatory cytokines, dry eye symptoms, and tear film stability before and after treatment with diquafosol sodium 3% (Diquas, Santen Pharmaceutical Co., Ltd., Japan) ophthalmic solution among patients with dry eye disease.

Forty consecutive patients were recruited from the Ophthalmology Out Patient Department of St. Luke’s Medical Center-Quezon City (SLMC).

In an open-label, non-comparative, one group, pre and post treatment, proof-of-concept design, dry eye patients given diquafosol sodium 3% eyedrops one drop six times a day for 4 weeks. Tear samples were collected prior to initiation and at the conclusion of treatment. Levels of interferon gamma (IFN-γ), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured simultaneously in tear film samples using a MILLIPLEX MAP human cytokine/chemokine magnetic bead panel (HCYTOMAG-60K, Merck Millipore, Germany) and analyzed. Ocular surface disease index (OSDI) scores and fluorescein tear break-up time (TBUT) were determined before and after treatment.

IL-6 and TNF-α were detected in all samples while IFN-γ and IL-1β were detected in 96% and 8% at baseline. All inflammatory markers except IL-1β showed reductions in concentration compared to pretreatment. A ≥25% reduction in cytokine concentration  was seen in 4%, 64.10%, 56.41%, and 46.15% of eyes for IL-1β , IL-6, TNF-α, and IFN-γ, respectively. TNF-α showed a significant decrease (p= 0.020). Improvement in TBUT (6.79 to 7.95 seconds; p= 0.0022) and OSDI (23.73  to 15.74;p= 0.0074) were seen.  Reduction of the individual cytokines did not appear to be correlated with pre- and post- OSDI scores and TBUT. None of the clinical parameters increased the likelihood of individual cytokine response except female sex with IL-6 (OR 5.56, p= 0.03).