Evaluating Viscosity and Tear Breakup Time of Contemporary Commercial Ocular Lubricants on an In Vitro Eye Model.

Purpose: To evaluate the link between the viscosity of ophthalmic formulation and tear film stability using a novel in vitro eye model. Methods: The viscosities and noninvasive tear breakup time (NIKBUT) of 13 commercial ocular lubricants were measured to evaluate the correlation between viscosity and NIKBUT. The complex viscosity of each lubricant was measured three times for each angular frequency (ranging from 0.1 to 100 rad/s) using the Discovery HR-2 hybrid rheometer. The NIKBUT measurements were performed eight times for each lubricant using an advanced eye model mounted on the OCULUS Keratograph 5M. A contact lens (CL; ACUVUE OASYS [etafilcon A]) or a collagen shield (CS) was used as the simulated corneal surface. Phosphate-buffered saline was used as a simulated fluid. Results: The results showed a positive correlation between viscosity and NIKBUT at high shear rates (at 10 rad/s, r = 0.67) but not at low shear. This correlation was even better for viscosities between 0 and 100 mPa*s (r = 0.85). Most of the lubricants tested in this study also had shear-thinning properties. OPTASE INTENSE, I-DROP PUR GEL, I DROP MGD, OASIS TEARS PLUS, and I-DROP PUR had higher viscosity in comparison to other lubricants (P < 0.05). All of the formulations had a higher NIKBUT than the control (2.7 ± 1.2 seconds for CS and 5.4 ± 0.9 seconds for CL) without any lubricant (P < 0.05). I-DROP PUR GEL, OASIS TEARS PLUS, I-DROP MGD, REFRESH OPTIVE ADVANCED, and OPTASE INTENSE had the highest NIKBUT using this eye model. Conclusions: The results show that the viscosity is correlated with NIKBUT, but further work is necessary to determine the underlying mechanisms. Translational Relevance: The viscosity of ocular lubricants can affect NIKBUT and tear film stability, so it is an important property to consider when formulating ocular lubricants.

Rheological behavior of commercial artificial tear solutions.

PURPOSE: To measure the rheological behavior of artificial tears to gain insight into the potential role of rheology in predicting the efficacy of artificial tear solutions for the treatment of dry-eye disease (DED). SETTING: Research laboratories of I-MED Pharma, Canada, Rohn and Associates, Inc., New Jersey, and Hydan Technologies, New Jersey. DESIGN: Laboratory investigation. METHODS: Twenty commercially available artificial tear drops were purchased in Canada and the United Kingdom. Rheological measurements of viscosity and normal stress as a function of shear rate were performed at 25°C. RESULTS: For comparison of the rheological behavior, the various artificial tears were sorted into 3 groups: group A, which exhibit significant non-Newtonian shear-thinning behavior; group B, which exhibit moderate non-Newtonian shear-thinning behavior; and group C, which exhibit Newtonian behavior throughout the shear rate range. Results of normal stress difference, N1, as a function of shear rate were concordant with the rheological testing, indicated the viscoelastic nature of the samples in groups A and B, whereas members of group C did not exhibit any elasticity. CONCLUSIONS: The various artificial tear solutions were sorted into groups based on their Newtonian or non-Newtonian behaviors. The results suggest that non-Newtonian solutions should provide better comfort and longer-lasting symptomatic relief for DED. It remains to be confirmed clinically if there is a direct correlation between the rheological behavior of artificial tears and their ability to provide prolonged relief in DED, or if other factors are more important.

Role of rheology in tears and artificial tears.

The study of viscoelastic fluids as artificial tears dates back to the late 1970s. Healon, the first ophthalmic viscosurgical device, was approved in 1980, but studied extensively before then, exhibits very interesting shear-thinning properties that were found to be beneficial in both ophthalmic surgery and somewhat later as a tear replacement solution. Unlike the previous tear film replacements, which were mainly viscous in nature, viscoelastic solutions, particularly those based on hyaluronan, exhibited very interesting, potentially beneficial, rheological properties, especially when slightly altered to become elastoviscous. This review examines the rheological properties that are significant in artificial tear solutions. We define herein the necessary parameters that need to be further studied to design and formulate rheologically better artificial tears, which should provide enhanced efficacy compared with their predecessors.

Validity and Reliability of a Novel Handheld Osmolarity System for Measurement of a National Institute of Standards Traceable Solution.

PURPOSE: To evaluate the validity and reliability of a novel handheld osmolarity system (I-PEN Osmolarity System; I-MED Pharma Inc, Dollard-des-Ormeaux, Quebec, Canada) for measurement of the osmolarity of a National Institute of Standards and Technology (NIST) traceable solution at a variety of ambient temperatures. METHODS: A total of 65 measurements of an NIST solution with a verified osmolarity of 290 ± 2 mOsmol/L were taken using 3 separate handheld osmolarity systems, 65 unique single-use sensors (SUSs) from 3 different lots, and 2 adaptors. Mean values were calculated using the device, SUS, and adaptor. Measurements were taken using a handheld osmolarity system, an adaptor, and 56 individual SUSs at 6 different ambient temperatures ranging from 17.7 to 26.5°C. RESULTS: Overall, the mean osmolarity measured was 294.06 mOsmol/L (SD ±2.29; percent coefficient of variation 0.78), ranging from 286.60 to 298.18 mOsmol/L. This fell within a prespecified acceptable variability of ±4 mOsmol/L (SD ±7). Mean values did not vary across devices, adaptors, or single-use sensors used. Mean osmolarity measurements increased with rising ambient temperatures, with an R = 0.88. The temperature correction factor was calculated to be 2.01 mOsmol/L per °C. CONCLUSIONS: The osmolarity system reliably and accurately measured the osmolarity of an NIST solution in a laboratory setting, using an adaptor to correct for differences in resistance between a laboratory NIST solution measurement and direct measurements on the palpebral conjunctiva of the eyelid. The handheld osmolarity system represents a rapid and accurate instrument for measurement of tear osmolarity in a simulated testing setting.