Study finds artificial tear viscosity and shear-thinning behavior vary by formulation

A large international study¹ that evaluated the properties of dry eye drops showed that the commercially available formulations exhibited varying degrees of shear-thinning behavior, which affects the impact on the ocular surface. Ulrich Graf, PhD, the first author from the Department of Clinical Pharmacology, Medical University of Vienna, Vienna, reported.

The authors explained, “Natural tears exhibit complex rheologic properties, including non-Newtonian, shear-thinning behavior, where viscosity decreases as shear rate increases.² This property is crucial for tear function—higher viscosity when the eye is open helps maintain tear-film stability, while lower viscosity during blinking reduces friction between the lid and ocular surface.³ Thus, artificial tears should mimic the non-Newtonian properties of natural tears, providing adequate lubrication while maintaining optical clarity.”

Hyaluronic acid (HA) is characterized by properties that make it critical to the effectiveness of dry eye tears. Its viscoelasticity is characterized by higher viscosity at low shear rates and reduced viscosity under dynamic conditions, which Graf and colleagues explained “closely resembles the non-Newtonian properties of natural tears and is essential for stabilizing the tear film during eye opening while minimizing mechanical friction during blinking.^2,3”

They also discussed the inclusion of other components in the commercial tear products, such as trehalose, carboxymethyl cellulose, or lipids added to improve biocompatibility and surface adhesion, the ratios of which can vary considerably with HA. Some formulations, they noted, rely mostly on higher concentrations of HA and others use lower concentrations in the presence of the complementary polymers to achieve target rheologic properties.⁴ This indicates that the overall rheological performance results from an interaction of the molecular characteristics of HA and those of other components of the formulation.^5-7 “The rheological behavior of artificial tear formulations,” the investigators stated, “cannot be reliably predicted based solely on the molecular weight or concentration of hyaluronic acid, underscoring the need for empirical evaluation under physiologically relevant conditions.^7,8”

The investigators evaluated the shear-stress-dependent viscous properties of seven commercially available tear formulations. They also studied the viscosity of natural tears. They carried out the viscosity measurements using an automated optical rheometer that combines microfluidic and imaging technologies. The study was set up to mimic the eye conditions during blinking; the temperature was maintained at 34°C and at shear rates ranging from 3,000 to 30,000 shear rate (s⁻¹).

The products that were analyzed in the study included the artificial tear formulations Thealoz Duo (Laboratories Théa), Ivizia (Théa Pharma Inc.), Hylo Comod and Hylo Parin (Ursapharm Arzneimittel GmbH), Xailin HA (VISUfarma BV), Vismed (Horus Pharma), and Systane Hydration (Alcon, Inc.).

Hylo Comod and Hylo Parin contain high-molecular-weight HA (>1,000 kDa); Xailin HA and Vismed contain medium-molecular-weight HA (500–1,000 kDA); and Systane Hydration, Thealoz Duo, and Ivizia contain low-molecular-weight HA (<500 kDa).

Viscosity findings

Graf and colleagues reported, “Among the artificial tear formulations, ThealozDuo had the lowest viscosity (2.62 ± 0.01 mPa·s at 3000 s⁻¹), followed by Ivizia(2.42 ± 0.02 mPa·s), Hylo Comod (3.69 ± 0.01 mPa·s), Hylo Parin (3.87 ± 0.01 mPa·s), Xailin HA(4.73 ± 0.02 mPa·s), Vismed (5.42 ± 0.02 mPa·s), and Systane Hydration(7.76 ± 0.1 mPa·s).”

The analysis of the natural tears showed a minimal change in viscosity in response to changes in shear stress, with viscosity values of 0.91 megapascal (mPa)·s at 3,000 s⁻¹ and 0.80 mPa·s at 30,000 s⁻¹.

The products containing low-molecular-weight HA had viscosity levels that most closely resembled that of natural tears at the shear rates measured in this study.

The authors summarized, “Our rheological analysis revealed distinct shear-thinning behaviors across all seven commercial artificial tear formulations and natural tears, with Ivizia and Thealoz Duo exhibiting profiles most similar to the profile of natural tears. Medium- and high-molecular-weight formulations demonstrated steeper viscosity gradients, while our findings confirmed that rheological behavior depends not solely on the HA concentration or molecular weight but on the complex interplay with co-polymers and additional excipients.”

References

1. Graf U, Schmidl D, Garhöfer G, Schmetterer L. Shear-stress-dependent viscous properties of hyaluronic-based lubricants. J Clin Med. 2025;14:8753; https://doi.org/10.3390/jcm14248753

2. Tiffany JM. The viscosity of human tears. Int Ophthalmol. 1991;15:371–6.

3. Arshinoff S, Hofmann I, Nae H. Rheological behavior of commercial artificial tear solutions. J Cataract Refract Surg. 2021;47:649–54.

4. Kathuria A, Shamloo K, Jhanji V, Sharma, A. categorization of marketed artificial tear formulations based on their ingredients: a rational approach for their use. J Clin Med. 2021;10:1289.

5. Jones L, Downie LE, Korb D, et al. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017,;15:575–628.

6. Snetkov P, Zakharova K, Morozkina S, Olekhnovich R, Uspenskaya M. Hyaluronic acid: the influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymer. Polymers. 2020;12:1800.

7. Aragona P, Simmons PA, Wang H, Wang T. Physicochemical properties of hyaluronic acid-based lubricant eye drops. Transl Vis Sci Technol. 2019;8:2.

8. Kapadia W, Qin N, Zhao P, et al. Shear-thinning and temperature-dependent viscosity relationships of contemporary ocular lubricants. Transl Vis Sci Technol. 2022;11:1.