(454h) Tear Film Stability and Electrolytic Composition: Implications for Dry Eye Treatment

Dry Eye Syndrome (DES) is a prevalent condition that affects approximately 10% of the global population. It results from inadequate tear production or poor tear quality, leading to increased friction between the cornea and the conjunctiva. Although hyperosmolarity of the tear film is a common marker of DES, the role of electrolytic composition in tear film stability remains unclear. This study investigates the effects of sodium chloride (NaCl) and hydrogen phosphate-based salts on the dewetting of electrolytic aqueous films on a curved glass dome.

Experiments were carried out by elevating a glass dome across an air-water interface and tracking the film drainage using interferometry. The film thinning process is governed by two mechanisms – capillary-driven film drainage and evaporative film thinning. By scaling analysis, it can be shown that for sufficiently large films in the lateral direction, the film thinning is evaporation-dominated. The subphase, such as water or model aqueous tear liquid, was maintained at either room temperature (about 22°C) or physiological temperature (35°C). Tests were also conducted on both smooth and rough glass domes. The rough glass domes were produced by sonicating the domes in DI water for 12-24 hours. The cavitation and subsequent collapse of bubbles during sonication process can create shockwaves, leading to a local erosion of the glass dome surface. The roughness was quantified using Atomic Force Microscopy.

When pure de-ionized (DI) water was used as the subphase, the film thinning was rapid. However, when NaCl was present in the water at an osmolality of 300 mOsm (physiologically-relevant concentration), the film thinning process was significantly slowed down. This was due to the rise in surface tension with increased salt concentration driving a solutal Marangoni influx from the bulk to the film region. Additionally, the presence of salts can lower the vapor pressure to an extent. A surprising observation was that an increased concentration of NaCl leads to the formation of crystals during the evaporative thinning of tear films. These crystals act as points for heterogeneous nucleation-based dewetting of the thin films (see figure below; left). The appearance of crystals was markedly significant when the glass dome had nanoscale roughness, produced by prior sonication of the glass domes in DI water. This is because for a smooth surface, a thin film containing NaCl above the saturation concentration can still resist a phase change to form crystals. On the other hand, the presence of roughness factors can lead to crystal formation even when the thin film is undersaturated in NaCl due to a significant reduction in the energy barrier to crystal formation.

In contrast, the addition of trace amounts of hydrogen phosphate-based salts, such as sodium phosphate dibasic (Na₂HPO₄) and potassium phosphate monobasic (KH₂PO₄), significantly delays dewetting of the aqueous films. This delay is attributed to several factors, including increased viscosity due to hydrogen bonding, suppression of NaCl crystal growth, and solutal Marangoni-driven influx into the film. Furthermore, the increased film viscosity caused by hydrogen phosphate-based salts leads to a Taylor-Saffman instability (viscous fingering) during the observed fluid influx from the bulk reservoir into the film (see figure; right). The instability is more pronounced at 35°C, as the evaporation leaves a more concentrated film region, causing much higher viscosities and stronger solutal Marangoni fluxes. But, unlike NaCl, the nucleation of hydrogen phosphate leads to a uniform layer of hydrated crystals. When the dome is smooth, heterogeneous nucleation of crystals is significantly reduced. Strong Marangoni flows then prevent a significant increase in salt concentration in the film region, leading to a hyperstable film without the observation of a fingering instability.

Overall, this study highlights the significant impact of electrolytic composition on tear film stability and demonstrates the potential of hydrogen phosphate-based salts as a treatment for DES.