Multi-symptom Relief with Propylene Glycol-Hydroxypropyl-Guar Nanoemulsion Lubricant Eye Drops in Subjects with Dry Eye Disease: A Post-Marketing Prospective Study.

INTRODUCTION: The study aimed to evaluate multi-symptom relief of dry eye manifestations with the use of propylene glycol-hydroxypropyl-guar (PG-HPG) nanoemulsion lubricant eye drops, among subjects with dry eye disease (DED). METHODS: This was a post-marketing, prospective, single-arm study conducted in the USA. Subjects aged ≥ 18 years, with tear breakup time (TBUT) ≤ 10 s for both eyes, dry eye questionnaire-5 (DEQ-5) "watery eyes" symptom score 1-4, symptoms of burning/stinging, sore and tired eyes as determined by impact of dry eye on everyday living-symptom bother (IDEEL-SB) questionnaire, and IDEEL-SB score 16-65 were included. Subjects were required to complete IDEEL-SB and DEQ-5 at days 0, 14 ± 2, and 28 ± 2, and self-administer one drop of PG-HPG four times daily for 28 ± 2 days. Primary endpoints were change from baseline at day 28 in symptoms of sore, stinging/burning, and tired eyes on IDEEL-SB; and symptom of watery eyes on DEQ-5. Other endpoints evaluated were corneal staining and TBUT at baseline and day 28 ± 2; symptom relief (5-point Likert scale) at day 28 ± 2, and safety. RESULTS: Of 119 subjects enrolled, 95 completed the study (mean ± SD age 61.2 ± 13.0 years; female 69.5%). Mean IDEEL-SB scores reduced significantly from baseline at day 28 for symptoms of aching/sore eyes (change from baseline - 1.0 ± 1.1), burning/stinging eyes (change from baseline - 1.1 ± 0.9), and tired eyes (change from baseline - 1.1 ± 1.0) (all p < 0.0001). Mean DEQ-5 score for watery eye symptoms significantly reduced from baseline at day 28 (change from baseline - 0.9 ± 1.0, p < 0.0001). Corneal staining at day 28 was comparable to baseline. TBUT improved from baseline to day 28. On a Likert scale, more than 50% of subjects reported relief from symptoms of sore, stinging, and burning eyes. Three (3.1%) subjects reported treatment-emergent adverse events (non-ocular). CONCLUSIONS: PG-HPG nanoemulsion lubricant eye drops significantly improved multiple dry eye symptoms in subjects with DED over 28 days, with no new safety concerns. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT05056155.

Parameter Estimation for Mixed-Mechanism Tear Film Thinning.

Etiologies of tear breakup include evaporation-driven, divergent flow-driven, and a combination of these two. A mathematical model incorporating evaporation and lipid-driven tangential flow is fit to fluorescence imaging data. The lipid-driven motion is hypothesized to be caused by localized excess lipid, or "globs." Tear breakup quantities such as evaporation rates and tangential flow rates cannot currently be directly measured during breakup. We determine such variables by fitting mathematical models for tear breakup and the computed fluorescent intensity to experimental intensity data gathered in vivo. Parameter estimation is conducted via least squares minimization of the difference between experimental data and computed answers using either the trust-region-reflective or Levenberg-Marquardt algorithm. Best-fit determination of tear breakup parameters supports the notion that evaporation and divergent tangential flow can cooperate to drive breakup. The resulting tear breakup is typically faster than purely evaporative cases. Many instances of tear breakup may have similar causes, which suggests that interpretation of experimental results may benefit from considering multiple mechanisms.

Parameter Estimation for Evaporation-Driven Tear Film Thinning.

Many parameters affect tear film thickness and fluorescent intensity distributions over time; exact values or ranges for some are not well known. We conduct parameter estimation by fitting to fluorescent intensity data recorded from normal subjects' tear films. The fitting is done with thin film fluid dynamics models that are nonlinear partial differential equation models for the thickness, osmolarity and fluorescein concentration of the tear film for circular (spot) or linear (streak) tear film breakup. The corresponding fluorescent intensity is computed from the tear film thickness and fluorescein concentration. The least squares error between computed and experimental fluorescent intensity determines the parameters. The results vary across subjects and trials. The optimal values for variables that cannot be measured in vivo within tear film breakup often fall within accepted experimental ranges for related tear film dynamics; however, some instances suggest that a wider range of parameter values may be acceptable.

Changes in Corneal Detection Thresholds After Repeated Tear Film Instability.

Purpose: To use a human-based model to study the effects of repeated tear film instability on corneal detection thresholds to cold, mechanical, and chemical stimuli. Methods: Twenty-five subjects participated in three study visits. A computer-controlled Belmonte esthesiometer was used to estimate corneal detection thresholds to cold, mechanical, and chemical stimuli before, after, and 30 minutes following 10 consecutive sustained tear exposure (STARE) trials. Subjects turned a pain knob (0-10) to indicate discomfort during STARE trials. The area of tear breakup and thinning in each trial was analyzed. Symptoms were evaluated by the Current Symptom Questionnaire (CSQ). Results: There was a significant time effect on CSQ symptoms during both visits (Friedman test, P < 0.001), with immediately after repeated STARE and 30 minutes later significantly differing from before STARE (Wilcoxon, P < 0.017). Tear breakup occurred in every trial, ranging from 25% to 88% of the exposed corneal area and all subjects indicated discomfort during trials. There was a significant time effect on mechanical thresholds between before STARE mechanical thresholds and 30 minutes later (repeated measures analysis of variance [ANOVA] P < 0.001), but not cold (P = 0.057) or chemical (P = 0. 565) thresholds. Conclusions: In this study, tear breakup during STARE trials was associated with discomfort, which when repeated, resulted in increased symptoms of ocular discomfort and alterations of mechanical sensory thresholds after 30 minutes. These results suggest that tear film instability, which is thought to occur repeatedly during normal blinking among dry eye patients over the day, can produce neurosensory alterations.

A simple and cost effective method for preparing FL and LG solutions.

PURPOSE: The purpose of this study was to develop a clinically feasible method for obtaining dye concentrations of 2% fluorescein (FL) and 1% lissamine green (LG) by soaking commercially available dye impregnated strips in saline. METHODS: Calibration curves were established to related known concentrations of dye to prepared FL fluorescence and LG absorbance. To determine the optimum number of dye strips and soaking times (preliminary testing), 1, 2, 3 FL or LG strips were soaked in 200 µl commercially available saline for 0.5, 1, 2, 3, 4 and 5 min, using calibration curves to determine FL and LG concentrations. The best combination of number of dye strips and soaking time was soaking 3FL and 3LG strips for 5 min and these were finally tested in 2 ml centrifuge tubes, selected for ease of use in a clinical setting. RESULTS: Preliminary testing indicated that soaking 3 FL or 3 LG strips for 5 min in saline yielded an average (±standard deviation) of 2.0 ± 0.000% FL and 0.93 ± 0.010% LG. Final testing of FL in centrifuge tubes (strips soaked for 3-15 min) yielded an average of 1.99 ± 0.040% FL, with no significant difference among time periods or dye lots tested. However, LG showed more variable results with an average of 0.80 ± 0.160% LG (5-15 min), with significant differences among dye lots and times (2-way ANOVA, p < 0.05). CONCLUSIONS: This simple, reliable and relatively inexpensive method involves soaking 3 FL or LG strips in saline solution, yielding concentrations close to the 2%FL and 1%LG recommended for clinical trials, although LG showed more variability.