Clinical application of the Swiss Liquid Jet Aesthesiometer for corneal sensitivity measurement.

CLINICAL RELEVANCE: Corneal sensitivity represents an important indicator for corneal health, its innervation and hence also for ocular disease. It is therefore of great interest from a clinical and research perspective to quantify ocular surface sensation. BACKGROUND: The aim of this prospective cross-sectional cohort study was to clinically test the within-day and day-to-day repeatability of the new Swiss Liquid Jet Aesthesiometer, employing small droplets of isotonic saline solution for repeatability, and correlate with the Cochet-Bonnet aesthesiometer in a cohort of participants of two different age groups, based on participant feedback (psychophysical method). METHODS: Participants were recruited from two equally, large age groups: group A (18-30 years) and group B (50-70 years). The inclusion criteria were healthy eyes, Ocular Surface Disease Index (OSDI) ≤ 13, and no contact lens wear. Mechanical corneal sensitivity threshold measurements with means of liquid jet and Cochet-Bonnet methods were carried out twice during two visits (a total of four measurements), with a stimulus temperature equal to or slightly above the ocular surface temperature. RESULTS: Ninety participants completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). The coefficient of repeatability for the liquid jet method was 2.56 dB within visits and 3.61 between visits. For the Cochet-Bonnet method, it was 2.27 dB within visits and 4.42 dB between visits (Bland Altman with bootstrap analysis). Moderate correlation was observed between the liquid jet and the Cochet-Bonnet method (r = 0.540, p < .001, robust linear regression). CONCLUSIONS: Swiss liquid jet aesthesiometry offers a new examiner independent method for corneal sensitivity measurement with acceptable repeatability and moderate correlation with the Cochet-Bonnet aesthesiometer. It offers a large stimulus pressure range of 100-1500 mbar and a precision of 1 mbar. Stimulus intensity can be tuned more precisely and much smaller sensitivity fluctuations may be potentially detected.

Corneal sensitivity in silicone hydrogel and rigid gas permeable contact lens wear.

PURPOSE: The aim of this prospective cross-sectional cohort study was to test the effect of silicone hydrogel (SH) and rigid gas permeable (RGP) contact lens (CL) wear on corneal sensitivity, applying the new Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) and the Cochet-Bonnet (CB) aesthesiometer, based on subject feedback (psychophysical method). METHODS: Participants were recruited for three equally large groups: Group A (SH CL), Group B (RGP CL) and Group C (non-CL wearers). Inclusion criteria were healthy eyes and OSDI ≤ 13. Corneal sensory thresholds were determined twice during two visits, with aid of SLACS and CB. RESULTS: 96 participants completed the study (n = 33 in groups A and C, n = 30 in group B); average age in group A: 27.42 ± 6.83 years, group B: 36.90 ± 9.68 years and group C: 26.06 ± 6.19 years. No statistically significant difference in corneal sensitivity was observed between the three groups for either method (p = 0.302 for SLACS, p = 0.266 for CB; Kruskal-Wallis rank sum test). Higher CSTs were obtained for males than for females in both CL groups with SLACS, and with CB only in the RGP CL group (p = 0.041 in Group A, p = 0.006 in Group B with SLACS; p = 0.041 in Group B with CB; bootstrap analysis with age correction and gender balancing). No correlation was observed between CL comfort and corneal sensitivity for neither method applied (for SLACS r = 0.097 and p = 0.51, for CB r = 0.17 and p = 0.15; robust linear mixed model). CONCLUSIONS: No difference in corneal sensitivity with CL compared to non-CL wear was noted in this study. However, lower levels of corneal sensitivity were observed in the male CL groups, warranting further investigation.

Age-Related Changes in Corneal Sensitivity.

PURPOSE: The aim of this prospective cross-sectional cohort study was to clinically test whether corneal sensation decreases with age, based on subject feedback (psychophysical method), and whether it correlates with general pain perception. METHODS: Subjects were recruited from 2 equally large age groups: group A (18-30 years) and group B (50-70 years; n = 45 per group). The inclusion criteria were healthy eyes, Ocular Surface Disease Index ≤13, and no contact lens wear. Corneal sensitivity threshold (CST) measurements were performed twice during each of the 2 visits, with the aid of the new Swiss liquid jet esthesiometer for corneal sensitivity (SLACS) and Cochet-Bonnet (CB) esthesiometer. A general pain sensitivity score was obtained from all participants. RESULTS: Ninety subjects completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). Statistically higher CSTs for age group B were only observed for SLACS (mean difference: 1.58 dB, P < 0.001). No correlation was observed between the pain score and the CSTs obtained with either esthesiometry method (r = 0.11, P = 0.25 for liquid jet and r=-0.076, P = 0.61 CB). CONCLUSIONS: A statistically significant decrease in corneal sensitivity was observed for the older age group with SLACS in this study, with CB however only a trend in the same direction was noted. General pain perception was not found to correlate with ocular surface sensation.

Working principle and relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) evaluation.

PURPOSE: To describe and evaluate relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) for ocular surface sensitivity measurement. METHODS: Characteristics of Liquid Jet (LJ) droplets (consisting of isotonic saline solution) were analysed: vertical and horizontal displacement and speed of LJ droplets were recorded with the aid of the High Speed Photron FASTCAM NOVA S6 camera (stimulus duration: 40 ms). Stimulus mass was assessed for 20 sets of 10 LJs with aid of a microbalance (pressure range of 100-1500 mbar). RESULTS: Because continuous flow LJ disintegrated into droplets in the lower pressure range (<700 mbar), pulsed stimuli were applied in order to obtain similar stimulus characteristics across the applied pressure range. For all measurements, very little variability was observed. Vertical and horizontal displacement did not exceed 0.13 mm in either direction. The mass per shot showed an unexpected cubic dependency on pressure. Up to approximately 700 mbar, LJ speed showed an almost linear relationship. For the pressure range of >700-1500 mbar, variability increased and speed decreased compared to the expected in a linear manner. However, this may be caused by the difficulty of identifying pattern changes of LJ droplets from one high speed image frame to the next with increasing stimulus speed, when determining LJ speed via pixel count. CONCLUSIONS: Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity was shown to deliver fine droplets with a pulsed stimulus mode, in a repeatable manner with precise localisation to the ocular surface. Very little variability was observed in LJ speed and mass for the typical pressure range required for clinical sensitivity measurements.

Prospective randomized study to evaluate the efficacy and tolerability of Ectoin® containing Eye Spray (EES09) and comparison to the liposomal Eye Spray Tears Again® (TA) in the treatment of dry eye disease.

PURPOSE: To subjectively and objectively evaluate the efficacy and tolerability of preservative-free Ectoin ® Eye Spray - Colloidal (EES09) and Tears Again ® Eye Spray (TA) in subjects with mild-moderate dry eye disease (DED), and to compare efficacy of these two eye sprays with each other. METHODS: Thirty-six volunteers (average age 32.3 ± 16.1 years; 26 females) were successfully recruited for this prospective double-blind study with between-subject design and randomly divided into two groups (gender and age balanced): Group A received EES09 and Group B received TA during the treatment phase. Inclusioncriteria were a minimum age of 18 years, a score of 18.0 or higher on the OSDI questionnaire, and a non-invasive tear break up time (NIKBUT, Oculus Keratograph M5, Oculus, Germany) of no more than 10s in at least one eye. The objective variables NIKBUT, conjunctival redness, lipid layer and osmolarity (TearLab Cooperation, USA) were assessed at baseline, 10 min. after spray application and after a treatment phase of 10±3 days (3x applications daily). Symptoms, tolerance and handling were evaluated with the OSDI and VAS questionnaires. RESULTS: A statistically significant increase in NIKBUT and improvement in DED symptoms were obtained for the overall group (mean NIKBUT 7.7 ± 1.7s vs. 11.6 ± 4.6s, p<0.001; mean OSDI score: 36.1 ± 12.7 vs. 20. 7± 12.7, p<0.001) during course of treatment. No statistically significant effect was established for the variables lipid layer (p = 0.406), conjunctival redness (p = 0.766) and osmolarity (p = 0.378). No statistically significant differences were observed between the groups, for any variable. The noninferioritycriterion for EES09 towards TA could be shown for the scores of the dry eye symptoms via VAS questionnaire and the variable NIKBUT. CONCLUSIONS: A beneficial treatment effect was confirmed for both, symptoms of DED and the objective variable NIKBUT. Both eye sprays were rated favourably in view of perceived tolerability and handling of the spray bottle.

Agreement and repeatability of four different devices to measure non-invasive tear breakup time (NIBUT).

PURPOSE: Since tear film stability can be affected by fluorescein, the Dry Eye Workshop (DEWSII) recommended non-invasive measurement of tear breakup time (NIBUT). The aim of this study was to investigate the agreement and repeatability of four different instruments in the measurement of NIBUT. METHODS: 72 participants (mean 24.2 ± 3.6 years) were recruited for this multi-centre, cross-sectional study. NIBUT was measured three times from one eye using each of the instruments in randomized order on two separate sessions during a day, separated by at least 2 h. NIBUT was performed at three sites (Switzerland, Germany and UK) using three subjective instruments, Tearscope Plus (Keeler, Windsor, UK) (TS), Polaris (bon Optic, Lübeck, Germany) (POL), EasyTear Viewplus (Easytear, Rovereto, Italy) (ET) and the objective Keratograph 5 M (Oculus Optikgeräte GmbH, Wetzlar, Germany) (KER). As the latter instrument only analyses for 24 s, all data was capped at this value. RESULTS: NIBUT measurements (average of both sessions) between the four instruments were not statistically significantly different: TS (median 10.4, range 2.0-24.0 s), POL (10.1, 1.0-24.0 s), ET (10.6, 1.0-24.0 s) and KER (11.1, 2.6-24.0 s) (p = 0.949). The objective KER measures were on average (1.2 s ± 9.6 s, 95 % confidence interval) greater than the subjective evaluations of NIBUT with the other instruments (mean difference 0.4 s ± 7.7 s, 95 % confidence interval), resulting in a higher limits of agreement. The slope was -0.08 to 0.11 indicating no bias in the difference between instruments with the magnitude of the NIBUT. Repeated measurements from the two sessions were not significantly different for TS (p = 0.584), POL (p = 0.549), ET (p = 0.701) or KER (p = 0.261). CONCLUSIONS: The four instruments evaluated for their measurement of tear stability were reasonably repeatable and give similar average results.

General pain perception sensitivity, lid margin sensitivity and gas permeable contact lens comfort.

BACKGROUND: The non-predictable variability in the capability of sensory adaptation to rigid gas permeable (RGP) contact lenses (CLs) represents a considerable challenge for CL practitioners and patients when choosing this CL type. This study explored if lid margin sensitivity and general pain sensitivity at baseline may help predict experienced subjective comfort of RGP CL wear. METHODS: For this prospective clinical cohort study, subjects filled in the Pain Sensitivity Questionnaire and lid margin sensitivity was measured at the lid wiper of the upper and lower lid at baseline, using the Cochet Bonnet aesthesiometer. RGP CL parameters were determined based on corneal topography, with additional use of fluorescein simulation. During the second visit, lid wiper sensitivity measurement was repeated and the RGP CLs were worn for 40 minutes. Upon removal of the CLs, lid wiper sensitivity measurement was repeated and spontaneous CL comfort was rated. RESULTS: Thirty-four subjects participated (mean age: 23.85 ± 5.39 years; 17 male). No correlation could be observed between the baseline lid margin sensitivity and spontaneous CL comfort (r = 0.013, p = 0.9417, upper lid; r = 0.016, p = 0.9277, lower lid). A decrease in lid margin sensitivity was obtained after CL wear (p = 0.0004, upper lid; p = 0.0001, lower lid). A good correlation was observed between Pain Sensitivity Questionnaire score and spontaneous CL comfort (r = 0.62, p = 0.0007). CONCLUSION: The results of this study suggest that lid margin sensitivity may not play an important role in spontaneous RGP CL comfort. The use of the Pain Sensitivity Questionnaire may well help select patients who are more likely to show good spontaneous tolerance of RGP CLs.

Relationship Between the Degree of Iris Pigmentation and Corneal Sensitivity to a Cooling Stimulus.

PURPOSE: To explore the relationship between the degree of iris pigmentation and corneal sensitivity threshold (CST) on a variety of different ethnicities, using the air-jet noncontact corneal aesthesiometer and by applying a consistent method of subject iris pigmentation classification. METHODS: A total of 200 subjects (mean age 23.7 ± 3.1 years, 127 women) participated in this clinical cross-sectional study: 100 whites, 40 Asians, 40 Chinese, and 20 Afro-Caribbeans. CST was assessed within the central cornea using a noncontact corneal aesthesiometer, and the degree of iris pigmentation of each subject was noted according to the Seddon method using a set of graded photographs of iris pigmentation (grades 1-5). Inclusion criteria were absence of ocular disease including dry eye, no contact lens wear, and no use of artificial tears. Statistical testing between ethnicities was made by the pairwise t test with Holm adjustment, and a linear model was set up to analyze the effects of ethnicity and iris grade. RESULTS: A moderate trend for increasing CST with increasing iris pigmentation grade for all ethnicities was observed (R = 0.46; P < 0.0001), with CST changing from 0.66 ± 0.16 mbars for grade 1, 0.74 ± 0.18 mbars for grade 2, 0.86 ± 0.31 mbars for grade 3, 0.85 ± 0.32 mbars for grade 4, and 1.08 ± 0.40 mbars for grade 5. This correlation was stronger within the white group, representing the only ethnicity with all iris pigmentation grades (R = 0.50; P < 0.0001). CONCLUSIONS: There is a moderate relationship between corneal sensitivity and the degree of iris pigmentation, with sensitivity increasing as iris pigmentation decreases. This relationship is stronger within whites.

Does air gas aesthesiometry generate a true mechanical stimulus for corneal sensitivity measurement?

BACKGROUND: Belmonte Ocular Pain Meter (OPM) air jet aesthesiometry overcomes some of the limitations of the Cochet-Bonnet aesthesiometer. However, for true mechanical corneal sensitivity measurement, the airflow stimulus temperature of the aesthesiometer must equal ocular surface temperature (OST), to avoid additional response from temperature-sensitive nerves. The aim of this study was to determine: (A) the stimulus temperature inducing no or least change in OST; and (B) to evaluate if OST remains unchanged with different stimulus durations and airflow rates. METHODS: A total of 14 subjects (mean age 25.14 ± 2.18 years; seven women) participated in this clinical cohort study: (A) OST was recorded using an infrared camera (FLIR A310) during the presentation of airflow stimuli, at five temperatures, ambient temperature (AT) +5°C, +10°C, +15°C, +20°C and +30°C, using the OPM aesthesiometer (duration three seconds; over a four millimetre distance; airflow rate 60 ml/min); and (B) OST measurements were repeated with two stimulus temperatures (AT +10°C and +15°C) while varying stimulus durations (three seconds and five seconds) and airflow rates (30, 60, 80 and 100 ml/min). Inclusion criteria were age <40 years, no contact lens wear, absence of ocular disease including dry eye, and no use of artificial tears. Repeated measures (analysis of variance) and appropriate post-hoc t-tests were applied. RESULTS: (A) Stimulus temperatures of AT +10°C and +15°C induced the least changes in OST (-0.20 ± 0.13°C and 0.08 ± 0.05°C). (B) OST changes were statistically significant with both stimulus temperatures and increased with increasing airflow rates (p < 0.001), and were more marked with stimulus temperature AT +10°C. CONCLUSION: A true mechanical threshold for corneal sensitivity cannot be established with the air stimulus of the Belmonte OPM because its air jet stimulus with mechanical setting is likely to have a thermal component. Appropriate stimulus selection for an air jet aesthesiometer must incorporate stimulus temperature control that can vary with stimulus duration and airflow rate.

Blink Animation Software to Improve Blinking and Dry Eye Symptoms.

PURPOSE: To evaluate if the animation "blink blink" increases blink rate and improves dry eye symptoms during prolonged computer use. METHODS: Study part A: Blink rate was recorded at baseline and during computer work of normal subjects without symptoms of dry eye. Half of the subjects used "blink blink," instructed to blink on animation appearance; the other half used a placebo version for 1 week during computer use. Thereafter, blink rate was recorded again with the use of "blink blink." Study part B: Blink rate was recorded during computer work with dry eye symptoms (modified Ocular Surface Disease Index > 15.0). Subjects used the test and placebo version of "blink blink" each for 1 week (1 week washout; crossover) and were instructed to blink twice on presentation of the animation. Blink rate and dry eye symptoms were assessed after each phase and compared with baseline. RESULTS: Study part A: Ten subjects participated (mean [± SD] age, 38.3 [± 16.0] years; 5 women). A greater increase in blink rate was observed in the test group (5.62 blinks/min for the test group and 0.96 blinks/min for the control group). Study part B: Twenty-four subjects participated (mean [± SD] age, 39.3 [± 19.1] years; 11 women). Dry eye symptoms improved during both phases (with test and placebo) to a statistically significant degree (each, p < 0.001). This difference was more marked with the test (-5.42 [± 2.86] points) compared with the placebo version (-1.79 [± 1.38] points). Blink rate increased with the program by 6.75 (± 3.80) blinks/min (p < 0.001), compared with 0.50 (± 2.83) blinks/min with placebo (p = 0.396). This difference between test and placebo was statistically significant (p < 0.001). Twenty of the 24 subjects could tolerate "blink blink" well during computer use. CONCLUSIONS: Blink rate and dry eye symptoms improved with "blink blink." The double blink prompted by the animation allowed a decrease in number of presentations and improved acceptance of "blink blink."

The accuracy of dynamic contour tonometry over soft contact lenses.

PURPOSE: Dynamic contour tonometry (DCT) has been shown to measure the intraocular pressure (IOP) independently of corneal thickness. This study aimed to investigate if DCT remains accurate when the IOP measurement is taken over soft contact lenses (CLs) of different thicknesses and material characteristics. METHODS: This was a prospective clinical study that included 42 patients. Subject age was 22 to 59 years (26.5 ± 6.3 years). Intraocular pressure and ocular pulse amplitude (OPA) measurements were taken under topical anesthesia without CLs and over various daily disposable CLs with -0.50, +5.00, and -5.00 diopters (D) in hydrogel (Nelfilcon A) and in silicone hydrogel (Narafilcon A) materials. RESULTS: No statistically significant differences were found when comparing the IOP measurements obtained using either of the different CL powers of -0.50 or -5.00 D, irrespective of which CL material was being used. However, the difference of 0.62 mm Hg observed when the Nelfilcon A with a power of +5.00 D was used turned out to be highly statistically significant (p = 0.0002), whereas the Narafilcon A with the same power of +5.00 D, with a small difference of -0.16 mm Hg, was not. Regarding OPA measurements, no significant differences were found between measurements with and without CL neither for different materials nor for change in dioptrical power (F = 0, p = 1.000). CONCLUSIONS: This study showed good reliability of IOP and OPA measurements over CLs with varying thickness profiles and different soft materials when using the DCT. Only a small but statistically significant difference of 0.62 mm Hg was found for the IOP measurement with the hydrogel CL of +5.00 D compared with "no CL."

The application of a computerised videokeratography (CVK) based contact lens fitting software programme on irregularly shaped corneal surfaces.

PURPOSE: To explore the success of the application of a computerised videokeratography (CVK) software system for the fitting of rigid gas permeable (RGP) contact lenses (CLs) on irregular corneal surfaces and compare it to the standard diagnostic fitting procedure. METHODS: This was a comparative prospective study, over a 1-year period (2004-2005). It included 41 RGP CL wearers (68 eyes) with irregular corneal surfaces. Of these, 51 (75%) had keratoconus, 7 (10%) corneal scarring (infectious or traumatic), 6 (6.82%) corneal transplants, 2 (2.9%) astigmatism, and 2 (2.9%) aphakia. Each eye was being re-fitted with a new RGP CL based on a topographical measurement in conjunction with a CL fitting software programme. The performance of the CLs was evaluated regarding visual outcome, fitting characteristics, and efficiency of the fitting procedure. RESULTS: Of the 68 eyes, 53 (77.94%) chose the CL fitted using the CVK software system, 9 (13.24%) chose the CL fitted using the standard procedure, and 6 (8.82%) showed no preference for either CL. There was a statistically significant improvement regarding visual outcome [contrast sensitivity at the spatial frequencies of 0.66 (p=0.029), 3.40 (p=0.008), and 17 (p=0.032), subjective vision (p=0.009)], fitting characteristics [grading scale (p=0.00), lens comfort (p=0.00) and daily wearing time (p=0.002)], and efficiency [number of trial lenses required (p=0.00)] with the CL fitted using the CVK software system. Correlating factors for the likely preference for the CL fitted using the CVK software system were subjective vision (p=0.004), lens comfort (p=0.009), and convenience of the fitting procedure (p=0.023). CONCLUSION: The application of a CVK software system for the fitting procedure of RGP CLs on irregular corneal surfaces was a safe procedure and shown to be more successful and efficient than the standard diagnostic fitting method.