Examination of Contact Lenses and Dry Eye Using Evaporimetry

Abstract

Purpose: Evaporimetry is a non-invasive technique used to assess the stability of the tear film. The test measures the rate of tear evaporation, and has been used to investigate dry eye, contact lenses, and the efficacy of different treatments for dry eye and contact lens (CL) discomfort. There is currently only one modified dermatological instrument available for practitioners, and experts have stated a need to develop evaporimeters suitable for use in clinical practice. The purpose of this thesis was two-fold, namely to (i) evaluate the commercially available evaporimeter, and (ii) describe the design, development, and testing of a novel evaporimeter. The overall aims were (i) to assess the calibration of the only commercially available evaporimeter (Eye-VapoMeter), and to investigate its ability to detect in vitro differences between soft CLs, and (2) to describe the development, in vitro, and in vivo testing of a novel binocular evaporimeter. Methods and Materials: (i) In vitro differences between 7 silicone hydrogel and 9 hydrogel CLs were measured with the Eye-VapoMeter. The change in evaporation rate per minute was calculated from the slope of the evaporation rate over time. Four sequential 10-minute time periods were investigated from 0 to 40 minutes. (ii) Calibration of the Eye-VapoMeter was investigated by simulating evaporation from different ocular surface areas and by modifying the air volume inside the evaporimeter goggle using two types of model eyes. The absolute evaporation rate was determined from the slope of water loss over time. The unadjusted evaporation rate from the instrument was measured with different areas and volumes inside the evaporimeter. A linear regression was used to determine the correction factor for each goggle volume based on the unadjusted evaporation rate and absolute evaporation rate. (iii) A novel binocular evaporimeter was developed to measure the tear evaporation rate (TER) from the ocular surface. In vitro testing of the new evaporimeter was performed using four elliptical model eyes with different surface areas (1 to 2.5 cm² in 0.5 cm² steps) and air volumes within the evaporimeter. Measurements were recorded for each side of the goggle. (iv) In vivo pilot testing was performed by conducting a series of experiments on volunteers to determine the best way of performing evaporimetry with the new instrument. Measurements were taken with the eyes open and closed (n=5), with the effect of a liposomal spray (CALMO® Eye Spray), and with a single application of an artificial lubricant (Refresh Tears®) (n=5). Fixation was tested by comparing evaporation rates with the eyes open, and blinking normally in downgaze, primary gaze, and upgaze (n=1). Optimal blink rate was investigated using blink rates of three or five seconds in volunteers with self-reported dry eye (n=3). (v) The effect of a lipid nano-emulsion was assessed. Thirty-six non-CL wearers were enrolled and screened. Twenty-one participants were suitable and classified as dry eye or non-dry eye using the Ocular Surface Disease Index (OSDI) and non-invasive break-up time (dry eye: OSDI ≥13 and break-up time ≤5 seconds in the worst eye). At the test visit, two baseline TERs were taken, 20 minutes apart. A single dose of Systane® Complete was instilled, and TER assessed at 10, 30, and 60 minutes post-instillation. (vi) The effect of CL wear was assessed. Twenty CL wearers were screened and classified using the Contact Lens Dry Eye Questionnaire (CLDEQ-8) as asymptomatic (CLDEQ-8<12) or symptomatic (CLDEQ-8≥12). Two baseline TERs were recorded after a 15-minute interval. Participants were randomized to wear delefilcon A in one eye and nesofilcon A in the other eye. TER was assessed after 15 minutes and 6 hours of CL wear. Results: (i) In vitro measurements with the Eye-VapoMeter found a significant difference in evaporation rates reported for each 10-minute period for each CL. Evaporation rate varied with CL material, water content, and presence of an internal wetting agent. (ii) Calibration measurements showed that water loss occurred at a linear rate. Correction factors were calculated for the Eye-VapoMeter. All graphs of the correction factor and evaporimeter volume were fit with a second order polynomial non-linear regression. (iii) In vitro measurements with the novel evaporimeter measured a significantly lower evaporation rate with the smallest model eye compared to the larger ones, and a significantly lower evaporation rate for the 10 cm³ volume compared to the 13 and 18.63 cm³ volumes. (iv) Pilot testing demonstrated that the relative humidity (RH) significantly changed in each side of the goggle when the novel evaporimeter was placed over the open and closed eye. No significant differences in RH were detected between the goggles. The TER was significantly lower immediately after application of the liposomal spray compared to the second baseline measurement and 15 minutes after the spray was applied. Use of an artificial lubricant found significantly higher TER in both eyes after instillation compared to the first baseline measurement and 15 minutes post-instillation. Comparison of different positions of gaze revealed less change in RH over time in downgaze. Comparison of blink rate found that 2 out of 3 participants preferred a five second blink rate. (v) Twenty people (10 non-dry eye, 10 dry eye) completed the lipid nano-emulsion study. Changes in TER were observed during the study. Nano-emulsion instillation produced an initial increase in TER after 10 minutes, and a reduction in TER after 30 minutes. (vi) Twenty people (10 asymptomatic, 10 symptomatic) completed the CL study. The TER was significantly higher after 6 hours of CL wear. No significant difference in TER was detected between the two groups, or between CL type (delefilcon A and nesofilcon A) after 6 hours of wear. Conclusions: (1) Using a new in vitro technique, the Eye-VapoMeter was able to detect differences in evaporation rate from a range of CLs differentiated by material, water content, and presence of wetting agent. (2) Calibration of the Eye-VapoMeter found the relationship between correction factor and volume was best fit with a second order non-linear regression. (3) A novel closed-chamber binocular evaporimeter was designed, developed, and tested. (4) In vitro testing of the novel evaporimeter detected lower evaporation rates with a smaller surface area and volume. (5) In vivo testing demonstrated that the novel evaporimeter was able to: (a) measure higher TERs in dry eye participants compared to those without dry eye; (b) measure significant decreases in TER following the instillation of a lipid eye drop; (c) measure significantly higher TERs associated with CL wear.