Accommodative response to ocular surface pain.

CLINICAL RELEVANCE: The discovery of an accommodative response to ocular surface stimulation could inform clinicians and patients that optical effects may occur due to ocular discomfort and perhaps an assessment of the accommodative system after carrying out interventions impacting the ocular surface, may be warranted. BACKGROUND: There have been no previous reports evaluating the effect of noxious stimulation on accommodation. Here, the accommodative response of healthy participants after the application of noxious corneal stimulation is characterised. METHODS: A computerised Belmonte pneumatic esthesiometer was used to determine detection thresholds (using ascending method of limits), and to randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps, to the central cornea of 15 healthy subjects. For each suprathreshold stimulus, accommodative and pupil responses were measured with a validated eccentric infrared photorefractor. Quantitative differences in accommodative/pupil response, stimulus modality/intensity and left/right eye were analysed using repeated measures ANOVA. Tukey HSD tests were used for all post hoc analyses. RESULTS: Accommodation increased from baseline as the corneal apical stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA, p < 0.05). At 200% threshold, accommodative response was greater than all stimulus intensities (Tukey HSD, all p < 0.05). There was no difference in pupil response between the stimulation intensities (100%, 150% and 200% threshold). There was no difference in accommodative response between the left and right eye for mechanical (ANOVA, p > 0.05) and chemical stimulation (ANOVA, p > 0.05). CONCLUSION: Noxious stimulation of the cornea seems to produce a dose-dependent increase in the accommodative response in the eyes but not a dose-dependent pupil response.

Determining the spectral transmittance of photochromic contact lenses.

PURPOSE: This study evaluates the spectral transmission of photochromic contact lenses. METHOD: A custom built photochromic filter transmission testing device (ICS photochromic bench) was developed to measure the spectral transmission of light adaptive filters. The spectral properties of seven contact lenses were measured using the ICS photochromic bench at 23°C and 35°C in their exposed (darkening) state at time points 0 s, 45 s, 90 s, and 15 min. and their unexposed (fading) state at 45 s, 15 min. and 20 min.. Mixed between and within repeated measures ANOVA (MRM-ANOVAs) and generalized additive modeling (GAMs) were used to compare the effects of temperature and solar exposure time on spectral transmittance of photochromic contact lenses. RESULTS: The mean (±SD) transmission of photochromic contact lenses in the exposed state were 94.7 ± 0.2, 39.1 ± 1.4, 27.0 ± 0.7 and 14.7 ± 1.0, and 93.7 ± 0.9, 38.8 ± 2.4, 30.2 ± 1.8, and 26.1 ± 1.0 at times 0 s, 45 s, 90 s, and 15 min. at 23°C and 35°C respectively. The mean (±SD) transmission of photochromic contact lenses in the unexposed state were 18.3 ± 1.5, 71.3 ± 2.4, and 80.2 ± 2.4, and 39.1 ± 1.0, 90.6 ± 1.0 and 91.1 ± 0.9 at times 45 s, 15 min. and 20 min. at 23°C and 35°C respectively. There was a significant decrease in light transmission as solar exposure time increased (GAM, MRM-ANOVA, p < 0.05). There was a significant effect of temperature and solar exposure time on the photochromic contact lenses (GAM, MRM-ANOVA, p < 0.05). The differences in the light transmitted by the photochromic contact lenses occurred at time 90 s and 15 min (Tukey HSD, at 90 s and 15 min, p < 0.05), where contact lenses at a temperature of 35°C showed greater light transmission than that at 23°C. There were differences in spectral transmittance based on the temperature of the contact lens. Contact lenses at 35°C transmitted more light than at 23°C at all unexposed times (MRM-ANOVA, p < 0.05). CONCLUSION: Spectral transmission of photochromic contact lenses were successfully measured with the ICS photochromic bench. Temperature appears to influence both the activation and deactivation of photochromic contact lenses such that the higher the temperature, the greater the light transmission.

Detectability and Bias Indices of Pneumatic Corneal Stimuli Using Signal Detection Theory.

Purpose: To evaluate the feasibility of using signal detection theory (SDT) in estimating criterion and detectability indices for corneal pneumatic stimuli and test corneal psychophysical data against linking hypotheses from nonprimate physiology using Bayesian analysis. Methods: Corneal pneumatic stimuli were delivered using the Waterloo Belmonte esthesiometer. Corneal thresholds were estimated in 30 asymptomatic participants and 1.5× threshold stimuli were used as signals (with 0.4 probability). There were 100-trial mechanical and cold stimulus experiments and 50-trial chemical experiments. Trials were demarcated auditorily and "yes" or "no" recorded after each trial. Cold stimulus experiments were conducted with 0.6 signal probability. Criterion (c), likelihood ratio (lnß), and d' were calculated from the yes-no responses. Results: Average d' was 0.59 ± 0.1, 1.65 ± 0.37, and 1.14 ± 0.3 units for cold, mechanical, and chemical stimuli, respectively. Bayes factors obtained using Bayesian analysis of variance mildly favored (BF10 = 1.55) differences between d's of the stimulus types, with no support for differences in criteria between stimulus types. Multiple comparisons of d' supported linking hypotheses based on nociception and nerve conductance theories. Conclusions: Our experiments are the first to demonstrate the feasibility of estimating SDT indices and test different hypotheses. The conservative strategy (reporting "no" more often) chosen by participants was anticipated due to relatively large proportion of catch trials. Translational Relevance: SDT when using pneumatic esthesiometry is vital to evaluate bias in responses of participants. Considering the varied forms of inherent noise in the corneal sensory system, SDT is critical to understand the sensory and decisional characteristics.

Role of diurnal variation of corneal sensory processing in contact lens discomfort.

PURPOSE: To examine the diurnal variation of corneal threshold and suprathreshold sensory processing, symptoms, and tear secretion in symptomatic and asymptomatic contact lens (CL) wearers and controls. METHODS: 26 symptomatic and 25 asymptomatic CL wearers and 15 asymptomatic non-CL wearing controls participated. Cooling thresholds, symptoms and tear meniscus height (TMH) were measured on each of 3 measurement days (random order) on the following schedules; Day-1 within 1 h of awakening (Baseline) and 3, 6 and 9 h later, Day-2 baseline and 9 h later (CLs worn in CL group) and Day-3 baseline and 9 h later. Magnitudes estimates for threshold-scaled suprathreshold stimuli were also estimated on Day-3. Data were analyzed using mixed models and repeated measures ANOVA. RESULTS: Cooling thresholds for the symptomatic group were lower and decreased over Day-1 (p < 0.008) and after 8 h of CL wear on Day-2 (p < 0.001) and were paralleled by increased symptoms (all p < 0.001), whereas minimal variations were found in the asymptomatic and control groups. Magnitude estimates for suprathreshold stimuli were higher (p ≤ 0.002) in the symptomatic group but did not differ significantly over the day. TMH varied little over time and was lower in the symptomatic group, but the difference was not statistically significant. CONCLUSION: Corneal sensitivity and symptoms, but not TMH, increased diurnally irrespective of CL wear in symptomatic CL wearers. These results reveal the essential role of neurosensory abnormalities in CL discomfort and suggest involvement of a central mechanism in the diurnally increased symptoms of these patients.

Pupil response to noxious corneal stimulation.

PURPOSE: Ocular somatosensory-autonomic reflexes play critical roles in maintaining homeostasis of the eye. The purpose of this study was to investigate the pupil response to nociceptive corneal stimuli. METHODS: A Waterloo-Belmonte pneumatic esthesiometer was used to determine detection thresholds and randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each stimulus, imaging of the stimulated/unstimulated eye was performed using two modified/calibrated Logitech c920 digital cameras for 4 seconds each, pre/post stimulus capture. The data were processed with a custom segmentation algorithm to help identify the pupils and pupil diameter was measured using ImageJ software. Pupil dilation response differences between the ipsi- and contralateral eye was analyzed using dependent t-tests. The effect of stimulus intensity, modality and sex of subjects were analyzed using repeated measures. RESULTS: In mechanical and chemical stimulation experiments, there was no difference in pupil responses between the stimulated eye and the unstimulated eye, (all dependent T-test p > 0.05). On average, pupil diameter increased from baseline as the corneal stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA p < 0.05). At 200% threshold, pupil diameter was greater than at all stimulus intensities (Tukey HSD, all p < 0.05). Based on stimulus intensity, females had greater pupil diameters than males at levels of 150% threshold and 200% threshold (ANOVA p < 0.05, all Tukey HSD p < 0.05). CONCLUSION: This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive stimuli to autonomic responses and in combination with our work on completely separate autonomic circuits of bulbar conjunctival vessel dilation and reflex tearing suggests that the monotonic measurements of redness, tearing and pupils provide accurate, separable responses that reflect painful stimulus intensity.

A Method to Calibrate the Carbon Dioxide (Chemical) Stimuli of Pneumatic Esthesiometer Externally.

PURPOSE: To determine the feasibility of using a portable carbon dioxide (CO2) sensor to calibrate a pneumatic esthesiometer and then to calibrate the chemical stimuli. METHODS: The chemical stimuli in ocular surface experiments are combinations of medical air and added CO2 (%CO2). These stimuli were calibrated using a portable CO2 sensor (COZIR CM-0041) and data logger, delivered for 100 seconds by using the Waterloo Belmonte esthesiometer. The distances between the sensor and esthesiometer tip were 0 (to measure feasibility), 3, 5, and 10 mm. In experiment I, 100% CO2 was tested using four different flow rates (50, 100, 150, and 200 mL/min) at three working distances. In experiment II, flow rates of 20 to 100 mL/min and concentrations of 20% to 100% CO2 were tested in 20 steps at 3 working distances. RESULTS: The CO2 sensor correctly reported the esthesiometer extremes of 0% and 100% CO2 when placed at the esthesiometer tip. There were progressive, systematic increases in concentrations reaching/reported by the sensor with increasing flow rates and nominal concentrations and progressive decreases in measurements with increases in working distance. CONCLUSIONS: CO2 concentrations in pneumatic esthesiometers can be calibrated and, as expected, vary with flow rate and distance, highlighting the importance of calibration and standardization of CO2 stimuli in these instruments. TRANSLATIONAL RELEVANCE: Calibrated CO2, a chemical sensory stimulus in humans, may be used in testing the surface of the eye as well as other membranes within which the CO2 can be dissolved (e.g., mucous) to produce an acidic stimulus.

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.

Effects of Tear Film Instability on Sensory Responses to Corneal Cold, Mechanical, and Chemical Stimuli.

Purpose: To investigate the effects of tear film instability (TFI) induced by sustained tear exposure (STARE) on sensory responses to corneal cold, mechanical, and chemical stimuli. Methods: Fifteen normal subjects were enrolled. TFI was induced during 10 repeated trials of STARE. Pneumatic cold, mechanical, and chemical stimuli were delivered using a computer-controlled Belmonte esthesiometer on three separate visits. The magnitude of the sensory responses to threshold and suprathreshold (1.25 and 1.50 times threshold levels) stimuli were assessed for intensity, coolness or warmness, irritation and pain, using a 0 (none) to 100 (very strong) scale, before and after STARE trials. Symptoms of ocular discomfort were evaluated using the Current Symptom Questionnaire (CSQ). Repeated measures ANOVA was used for data analysis. Results: Following STARE trials, the intensity and coolness ratings to cooling stimuli decreased (P = 0.043 and 0.044 for intensity and coolness, respectively), while rated irritation to mechanical stimuli was increased (P = 0.024). The CSQ scores also increased regardless of visits (all P < 0.001). Intensity ratings, coolness to room temperature stimuli and irritation to mechanical and chemical stimuli increased for all suprathreshold stimuli with increasing stimulus levels (P ≤ 0.005). Conclusions: Repeated TFI induced by STARE affects neurosensory function of the ocular surface. The decrease in reports of cooling and increase in irritation after repeated TFI suggest a complex interaction of neural mechanisms (particularly nonnociceptive cold and nociceptive mechanical) giving rise to ocular surface sensation in humans.

Conjunctival Redness Response to Corneal Stimulation.

SIGNIFICANCE: The conjunctiva is an integral component of the ocular surface, and its vasculature forms a terminal vascular bed of the human internal carotid artery. No research on the response of conjunctival vasculature to ocular surface stimulation exists; however, it is essential to understand the local physiological and pathological responses to such a stimulus. PURPOSE: The purpose of this study was to characterize the ocular redness levels in healthy participants after the application of noxious corneal stimulation. METHODS: A computerized Belmonte pneumatic esthesiometer was used to determine detection thresholds (using ascending method of limits) and to randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each suprathreshold stimulus, a spectrophotometer was used to measure ipsilateral and contralateral conjunctival redness before and after delivery of the corneal stimulus. Redness between the stimulated and unstimulated eyes was analyzed using dependent t tests. The effects of stimulus intensity and modality on conjunctival redness were analyzed using repeated-measures analysis of variance (ANOVA). Tukey honestly significant difference tests were used for all post hoc analyses. P ≤ .05 was considered statistically significant. RESULTS: In mechanical and chemical stimulation experiments, the stimulated eye became redder than the unstimulated eye (all t tests, P > .05). On average, redness increased from baseline as the corneal stimulus intensity increased with corneal stimulation (ANOVA, P < .05). Chemical stimulation produced greater conjunctival redness than did mechanical stimulation at all stimulation levels (ANOVA, P < .05; all Tukey honestly significant difference tests, P < .05). CONCLUSIONS: Stimulation of the central cornea by noxious mechanical and chemical stimuli evokes a dose-dependent autonomic conjunctival redness response. Chemical stimulation of the cornea seems to evoke a greater response compared with mechanical stimulation. This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive ocular surface stimuli to autonomic responses.

Mixed Model Analysis of Between-Subject Variability in Overnight Corneal Swelling and Deswelling With Silicone Hydrogel Lenses.

Purpose: To model between subject variability of corneal swelling (CS) and deswelling after overnight wear of silicone hydrogel (SiHy) contact lenses. Methods: A total of 29 neophyte subjects wore 12 SiHy lenses with central transmissibility range of 31 to 211 Dk/t units on separate nights, in random order, and on one eye only. The contralateral eye served as the control. Central corneal thickness was measured using digital optical pachymetry before lens insertion, immediately after lens removal on waking, then 20, 40 minutes, 1, 2, and 3 hours later. Mixed modelling was conducted for simultaneous analysis of group and between-subject effects of CS and deswelling. Results: The best model for overnight CS versus Dk/t was linear with a random intercept showing constant between-subject differences in CS for different Dk/t values. The best fit for corneal deswelling versus time was a curvilinear random intercept and random slope model. About 90% of the total between-subject deswelling variance in either lens or control eyes was due to the intercept variability with much less (∼10%) being due to the variability of the individual deswelling rate (slope). Subject age, sex, and ametropia were not predictors of individual corneal swelling in the swelling versus Dk/t analysis. Age, however, was a significant (inverse) predictor of the rate of corneal deswelling, only in lens-wearing eyes. Conclusions: A large proportion of variability in corneal swelling is because of subject-specific differences in corneal response to hypoxia. This shows that "low swellers" and "high swellers" actually do exist.

Influence of Vision on Ocular Comfort Ratings.

PURPOSE: To evaluate the influence of blur on ocular comfort while systematically manipulating vision using habitual refractive correction, induced spatial blur, dioptric defocus, and under the absence of visual structure. METHODS: Twenty emmetropic subjects rated vision, ocular comfort, and other sensations (burning, itching, and warmth) under clear viewing condition, spatial blur, and dioptric defocus, each lasting for 5 min. During each condition, subjects viewed digital targets projected from a distance of 3 m, and vision and ocular sensations were rated using magnitude estimation. Dioptric defocus was induced using +6.00DS contact lens, and equivalent spatial blur was produced by spatially filtering the targets. In a separate study, 15 participants rated vision and comfort while viewing a ganzfeld and behind an occluding patch (each of which provided an absence of visual structure) in addition to the above experimental conditions. Repeated-measures analysis of variance was used to compare the ratings of vision and comfort under the different experimental conditions. RESULTS: Vision under blurred conditions (both spatial blur and dioptric defocus) was rated significantly different (p < 0.001) from clear viewing condition. Vision was significantly different when targets were dioptrically defocused than when they were spatially blurred (p < 0.001). Ratings of comfort showed significant differences between clear and blurred conditions (p < 0.001). However, there was no significant difference in comfort ratings between dioptric defocus and spatial blur (p value at least 0.28). There were also no differences in comfort (p value at least 0.99) between clear vision, ganzfeld viewing, and occlusion despite the lack of visual structure in the latter two conditions. CONCLUSIONS: There does seem to be an association between clarity of vision and ocular comfort. Although the pathways for ocular surface pain and vision are perhaps exclusive, complex psychological influences such as nocebo or Hawthorne effects can subtly influence the participants to anticipate a change in comfort when vision is blurred.

Overnight corneal swelling with high and low powered silicone hydrogel lenses.

PURPOSE: To compare central corneal swelling after eight hours of sleep in eyes wearing four different silicone hydrogel lenses with three different powers. METHODS: Twenty-nine neophyte subjects wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60) and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00 and +6.00 D on separate nights, in random order, and on one eye only. The contra-lateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. RESULTS: For the +6.00 D and -10.00 D, lotrafilcon A induced the least swelling and galyfilcon A the most. The +6.00 D power, averaged across lens materials, induced significantly greater central swelling than the -10.00 and -3.00 D (Re-ANOVA, p<0.001), (7.7±2.9% vs. 6.8±2.8% and 6.5±2.5% respectively) but there was no difference between -10.00 and -3.00 D. Averaged for power, lotrafilcon A induced the least (6.2±2.8%) and galyfilcon A the most (7.6±3.0%) swelling at the center (Re-ANOVA, p<0.001). Central corneal swelling with +6.00 D was significantly greater than -10.00 D lens power despite similar levels of average lens transmissibility of these two lens powers. CONCLUSIONS: The differences in corneal swelling of the lens wearing eyes are consistent with the differences in oxygen transmission of the silicone hydrogel lenses. In silicone hydrogel lenses central corneal swelling is mainly driven by central lens oxygen transmissibility.

Impact of Blur on Suprathreshold Scaling of Ocular Discomfort.

PURPOSE: To examine the suprathreshold scaling of pneumatic stimuli, and the ratings of discomfort and intensity under clear and defocused visual conditions. METHODS: Twenty-one participants rated sensory intensity and discomfort of a series of mechanical stimuli from a pneumatic esthesiometer, using a 0 to 100 numerical scale under clear and defocused visual conditions. Esthesiometry was performed on one eye while the fellow eye viewed a 3-m distant 6/60 target through a trial lens. For the clear visual condition, a +0.25DS lens was used over the subject's refractive correction, and for defocus, an additional +4.00DS was used. Central corneal mechanical thresholds were first estimated using ascending methods of limits. Then, stimuli that were 25%, 50%, 75%, and 100% above threshold were presented in random order in three sessions of clear and defocused vision, and subjective ratings were recorded. Power exponents that define the slope of the sensory transducer functions were derived for discomfort and intensity estimates. RESULTS: No significant differences (P = 0.66) in mechanical thresholds, ratings of discomfort (P = 0.54), and intensity (P = 0.30) were observed between the visual conditions. Power exponents for discomfort showed significant differences (P = 0.05) between clear and defocus conditions, but not intensity (P = 0.22). Comparison between discomfort and intensity showed differences in exponents when vision was clear (P = 0.02) and defocused (P < 0.001). CONCLUSIONS: Scaling of suprathreshold pneumatic stimuli varies with viewing conditions. When vision was not clear, the exponent of the average transducer function for discomfort was steeper and this finding is the first demonstration of an association between ocular surface sensation and quality of vision.

Optical edge effects create conjunctival indentation thickness artefacts.

PURPOSE: Conjunctival compression observed in ultrahigh resolution optical coherence tomography (UHR-OCT) images of contact lens edges could be actual tissue alteration, may be an optical artefact arising from the difference between the refractive indexes of the lens material and the conjunctival tissue, or could be a combination of the two. The purpose of this study is to image the artefact with contact lenses on a non-biological (non-indentable) medium and to determine the origins of the observed conjunctival compression. METHODS: Two-dimensional cross-sectional images of the edges of a selection of marketed silicone hydrogel and hydrogel lenses (refractive index ranging from 1.40 to 1.43) were acquired with a research grade UHR-OCT system. The lenses were placed on three continuous surfaces, a glass sphere (refractive index n = 1.52), a rigid contact lens (n = 1.376) and the cornea of a healthy human subject (average n = 1.376). The displacement observed was analysed using ImageJ. RESULTS: The observed optical displacement ranged between 5.39(0.06) µm with Acuvue Advance and 11.99(0.18) µm with Air Optix Night & Day when the lens was imaged on the glass reference sphere. Similarly, on a rigid contact lens displacement ranged between 5.51(0.03) and 9.72(0.12) µm. Displacement was also observed when the lenses were imaged on the human conjunctiva and ranged from 6.49(0.80) µm for the 1-day Acuvue Moist to 17.4(0.22) µm for the Pure Vision contact lens. CONCLUSIONS: An optical displacement artefact was observed when imaging a contact lens on two rigid continuous surfaces with UHR-OCT where compression or indentation of the surface could not have been a factor. Contact lenses imaged in situ also exhibited displacement at the intersection of the contact lens edge and the conjunctiva, likely a manifestation of both the artefact and compression of the conjunctiva.

Measurement of difference thresholds on the ocular surface.

PURPOSE: To establish difference thresholds of the central cornea and compare thresholds between contact lens wearers and noncontact lens wearers. METHODS: Mechanical sensitivity of the central cornea was determined in 12 lens wearers and 12 nonlens wearers using a modified Belmonte pneumatic esthesiometer and method of limits. Then, a series of systematically increasing stimuli were presented, with the first stimulus being 25% less than threshold. Subjects compared intensity of each stimulus with the preceding one and reported if any difference in intensity was detectable. Intensities at which an increase was perceived from the prior stimulus were recorded and the difference between the intensities was the difference threshold (DL). Five DLs were measured for each subject. Weber's constants that relate the size of difference threshold to stimulus intensity were derived for each DL level. Repeated-measures ANOVA was used to compare Weber's constants between lens wearers and nonlens wearers. RESULTS: A significant main effect of DL level on Weber's constant (P < 0.001) was observed, with the first DL being higher than following DLs. Lens wearers had higher Weber's constants than nonlens wearers (P = 0.02) However, no interaction was found between DL level and group type on Weber's constants (P = 0.38). CONCLUSIONS: Differential sensitivity of the ocular surface can be successfully measured with a pneumatic esthesiometer and it appears that Weber's law holds for corneal nociceptive sensory processing. There are subtle differences in mechanical difference thresholds between lens wearers and nonlens wearers, suggesting the possibility of different neural activity levels in the two groups.

Grading bulbar redness using cross-calibrated clinical grading scales.

PURPOSE: To determine the between-scale agreement of grading estimates obtained with cross-calibrated McMonnies/Chapman-Davies (MC-D), Institute for Eye Research (IER), Efron, and Validated Bulbar Redness (VBR) grading scales. METHODS: Modified reference images of each grading scale were positioned on a desk according to their perceived redness (within a 0 to 100 range) as determined in a previous psychophysical scaling experiment. Ten observers were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Only 0 and 100 were marked on the scale, but not the numerical position of the reference images. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. RESULTS: Overall, perceived redness depended on the sample image and the reference scale used (repeated measures ANOVA; P = 0.0008); six sample images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability ranged from five units (IER vs. VBR) to eight units (IER vs. Efron) of the 0 to 100 range. CONCLUSIONS: The use of cross-calibrated reference grades for bulbar redness grading scales allows comparison of grading estimates obtained with different scales. Perceived redness is dependent on the dynamic range of the reference images of the scale, with redness estimates generally being found to be higher for scales with a shorter dynamic range.

A role of corneal mechanical adaptation in contact lens-related dry eye symptoms.

PURPOSE: To compare corneal mechanical adaptation measured psychophysically in contact lens wearers with or without dry eye symptoms. METHODS: Two groups of contact lens wearers were recruited. One group (symptomatic) consisted of subjects with dry eye symptoms (according to the subjective evaluation of symptom of dryness [SeSoD] questionnaire). The second control group (asymptomatic) consisted of subjects reporting no symptoms. There were 32 (aged 20 to 42 years, 6 males and 26 females) and 29 subjects (aged 21 to 36 years, 9 males and 20 females) in the symptomatic and asymptomatic groups, respectively. Mechanical stimulus thresholds of the cornea were determined using a Belmonte pneumatic esthesiometer and the ascending method of limits. Then three stimulus intensity groups (subthreshold, threshold, and suprathreshold) were applied to the eye in random order, each 20 times. Subjects rated the intensity of the stimuli using a scale of zero to four. The rating data from the two groups were compared by Friedman nonparametric ANOVA. Adaptation was defined as the reduction in subsequent ratings compared with earlier ones. RESULTS: No significant difference was seen in subjects' thresholds in both groups (P = 0.22). The symptomatic group rated their sensations to suprathreshold stimuli higher than the asymptomatic group. More importantly, there was significant adaptation with suprathreshold mechanical stimulation in the asymptomatic group (P = 0.006) but not in the symptomatic group (P = 0.08). There was no adaptation during threshold and subthreshold stimulus sessions in either group. CONCLUSIONS: Adaptation was found to suprathreshold mechanical stimuli in the asymptomatic group but not in the symptomatic group.

Effects of silicone hydrogel contact lens wear on ocular surface sensitivity to tactile, pneumatic mechanical, and chemical stimulation.

PURPOSE: To determine the effects of silicone hydrogel lens wear and lens-solution interactions on ocular surface sensitivity. METHODS: Forty-eight adapted lens wearers completed the study, which comprised two phases. Phase 1 included habitual lens wear, no lens wear (7 ± 3 days), and balafilcon A lenses (PV; PureVision; Bausch & Lomb, Rochester, NY) with a hydrogen peroxide-based regimen for 2 weeks; phase 2 included wear of PV with the use of a multipurpose solution containing either polyhexamethylene-biguanide (PHMB) or Polyquad/Aldox (Alcon Laboratories, Fort Worth, TX) preservative, each for 1 week, with a 2-week washout period between solutions. Tactile and pneumatic (mechanical and chemical) stimuli were delivered, and thresholds were determined by Cochet-Bonnet (Luneau Ophthalmologie, Chartres, France) and Belmonte (Cooperative Research Centre for Eye Research and Technology, Sydney, NSW, Australia) pneumatic esthesiometers, respectively. Corneal and conjunctival thresholds and staining scores were assessed at baseline, after 2 and 8 hours of lens wear on day 1 and at the end of each wearing cycle (2 hours). RESULTS: In phase 1, compared to the no-lens baseline, corneal tactile thresholds increased at the 1-day, 8-hour and the 2-week visits (P < 0.05), whereas conjunctival mechanical thresholds decreased at the 1-day, 2-hour and the 2-week visits (P < 0.05). In phase 2, the chemical thresholds were lower with PHMB-preserved solution compared with the Polyquad/Aldox system at the 1-day, 2-hour and the 1-week visits (P < 0.05). Staining scores correlated inversely with conjunctival chemical thresholds (all P < 0.05). CONCLUSIONS: Ocular surface sensitivity changed in adapted lens wearers, when lenses were refit after a no-lens interval and during lens wear with different care regimens. The corneal staining that was observed with certain lens-solution combinations was accompanied by sensory alteration of the ocular surface-that is, higher levels of staining correlated with increased conjunctival chemical sensitivity. (ClinicalTrials.gov number, NCT00455455.).

Interaction of corneal nociceptive stimulation and lacrimal secretion.

PURPOSE: To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. METHODS: Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. RESULTS: TMH increased with increasing stimulus intensity (P < 0.05), and the overall increase was higher with central stimulation than with peripheral stimulation (P < 0.05). The changes in TMH with threshold-scaled stimulus intensity depended on test location (P < 0.05) and stimulus modality (P < 0.05). The maximum intensity of mechanical stimulation of the central cornea induced the greatest TMH (all P < 0.05). For chemical stimulation, the stimulus intensity required to induce detectable tearing was higher than that required to detect a stimulus and higher in the periphery than at the center (all P < 0.05). CONCLUSIONS: Noxious mechanical and chemical stimuli evoked measurable tear secretion, with central corneal mechanical stimulation evoking the strongest lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.