Studies on tear evaporation and ocular surface temperature

Abstract

Introduction Evaporative Dry Eye (EDE), the most prevalent subtype of Dry Eye Disease (DED), is primarily driven by excessive tear loss from the ocular surface due to deficiencies in the tear film’s lipid layer. Accurate and repeatable measurement of Tear Evaporation Rate (TER) and related ocular surface parameters, such as Ocular Surface Temperature (OST), Lipid Layer Thickness (LLT), and Non-Invasive Tear Break-Up Time (NITBUT) is essential for understanding tear film instability and guiding clinical decision-making. However, measurement variability, lack of standardized protocols, and limitations in existing instrumentation have hindered the adoption of TER and OST assessment in routine practice. This thesis addresses these challenges through a series of in vitro and in vivo experiments aimed at quantifying tear film dynamics and optimizing measurement methodologies. Overall Aims The primary aim of this research was to characterize tear evaporation and ocular surface thermal behavior under a range of physiological and controlled conditions. This thesis specifically sought to: 1. Quantify the evaporation rates of distilled water versus an aqueous artificial tear solution (TheraTears®) in vitro. 2. Assess how changes in exposed ocular surface area and LLT affect TER using model eyes. 3. Investigate the effect of lipid-based artificial tears on LLT, TER, and NITBUT in vivo (PHASE I). 4. Optimize OST measurement parameters using ResearchIR software to improve accuracy and reproducibility. 5. Examine regional variation in OST and blink-related cooling profiles in vivo (PHASE II). 6. Integrate in vitro and in vivo findings to build a comprehensive model of tear film dynamics with implications for EDE diagnosis. Methods and Materials The experiments were conducted using custom-built and commercially available devices. In vitro studies used aluminum model eyes with varied surface areas and lipid layer simulations (via CALMO® Eye Spray) to evaluate their effect on TER, measured using the Waterloo Evaporimeter. In vivo studies were performed on healthy participants using the LipiView® II interferometer, OCULUS Keratograph® 5M, and FLIR A655sc thermal camera integrated with ResearchIR software. Data collection included real-time measurements of TER, LLT, NITBUT, and OST, with particular focus on blink-related cooling and temperature gradient analysis. Each experiment followed standardized protocols for blink control, Region of Interest (ROI) selection, and repeatability validation. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In vitro results demonstrated no significant difference in TER between distilled water and TheraTears®, suggesting that aqueous-based artificial tears do not provide meaningful evaporative protection. These findings also confirm that both distilled water and TheraTears® may be used interchangeably in laboratory-based evaporation studies where lipid content is not a critical variable. In contrast, increasing LLT using CALMO® spray led to a marked reduction in TER, and model eyes with larger surface areas consistently exhibited higher evaporation rates. In vivo, lipid eye drop instillation produced a significant increase in LLT, a prolongation of NITBUT, and a decrease in TER. OST monitoring revealed distinct blink-related cooling patterns, particularly in eyes with thinner lipid layers. Optimized OST protocols using ResearchIR improved temporal resolution and reproducibility across participants. Phase II confirmed consistent regional temperature variability and strong correlations between LLT, TER, and post-blink cooling. Conclusions This research confirms that LLT and ocular surface area are critical determinants of TER. Non-lipid formulations, such as TheraTears®, are ineffective in limiting TER, while lipid-based interventions significantly improve tear film stability both thermally and structurally. OST can be used as a reliable, non-invasive surrogate for assessing tear film dynamics when measured with optimized protocols. The Waterloo Evaporimeter and ResearchIR-enabled thermography provide robust, reproducible platforms for studying tear evaporation and cooling responses. These findings support a multimodal diagnostic approach integrating TER, LLT, NITBUT, and OST for the evaluation and management of EDE.