Comparison of Trehalose/Hyaluronic Acid (HA) vs. 0.001% Hydrocortisone/HA Eyedrops on Signs and Inflammatory Markers in a Desiccating Model of Dry Eye Disease (DED)

Abstract

Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo®, T/HA) with a tear substitute containing 0.001% hydrocortisone (I) and 0.2% HA (Idroflog®, I/HA), with respect to changes on signs and inflammatory markers in a mouse DED model. Methods: Thirty 12-week-old C57BL/6 mice were exposed in a controlled-environment chamber as a desiccating stress model of DED for 35 days. At day 14 (T1), administration of 5 µL T or I in the right eye (RE) or NaCl 0.9% in the left eye (LE) started, twice a day. Animals were sacrificed after 7 (T2), 14 (T3), 21 (T4, endpoint) days from the beginning of treatment. Corneal fluorescein staining ratio (Image J), histological and histochemical assessment of ocular surface tissues (goblet cell GC density and characterization —PAS, Alcian blue pH 2.5, pH 1.0, and MUC4 expression—in the superior and inferior conjunctiva), and levels of inflammatory markers HLA-DR, IL-1β and TNF-α in cornea and conjunctiva were measured. Results: No animal fully recovered from DED signs at the endpoint. Difference between arms was observed at T3 and T4, with T treated eyes showing a higher corneal damage reduction, PAS-positive GC recovery, lower inflammatory marker expression as compared to the I treated ones. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA.

Tear Film Stabilization and Symptom Improvement in Dry Eye Disease: The Role of Hyaluronic Acid and Trehalose Eyedrops versus Carmellose Sodium

“…At the baseline, group A's mean age was 22.00 ± 0.94 (21)(22)(23)(24)(25)(26) years old, while group B's mean age was 22.48 ± 2.29 (19)(20)(21)(22)(23)(24)(25)(26) years old, with no statistically significant differences observed (p = 0.33). In our study, the 60 participants were classified into three categories of DED severity based on their TBUT results, following the criteria established by the TFOS DEWS II [1,7]: mild (with a TBUT between 8 and 15 s), moderate (with a TBUT between 5 and 7 s), and severe (with a TBUT under 5 s).…”

“…The invasive tear quality test results of post-treatment group A revealed an average TBUT value of 12.95 ± 2.98 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) seconds, (t = 20.67, p < 0.01). This indicated a large effect of 3.30, with a TBUT increase of 8.41 ± 3.15 (7.60-9.23, 95% confidence interval) seconds.…”

“…Recently, a novel formulation combining hyaluronic acid and trehalose (HA/trehalose) in eyedrops was developed to leverage the bioprotective characteristics of trehalose [19][20][21][22][23][24]. This formulation, which is free of preservatives and available in a multi-dose preparation, facilitates prolonged use without inducing damage to the ocular surface.…”

Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer

“…It does not generate an immune response and has a viscoelastic capacity. When formulated in eye drops, it improves the stability of the tear film by better retaining water and helps keep the ocular surface lubricated, hydrated, and protected [10][11][12][13]. In addition, it has a high regenerative, antioxidant, and anti-inflammatory capacity [14,15].…”

Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model

“… 19 Loss of goblet cells, consistent decreases in MUC5AC and altered expression of transmembrane mucins, including MUC1, MUC4, and MUC16, with unstable tear film have been observed in both patients with Sjögren syndrome and non-Sjögren dry eye, 8 , 20 , 21 as well as in murine dry eye models. 22 – 24 Mucins are recognized as therapeutic targets for dry eye disease. 23 , 25 , 26 However, ocular mucins remain relatively under-studied and inadequately characterized.…”