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.

Validity and Repeatability of a Novel Dynamic Visual Acuity System.

PURPOSE: In many sports, athletes rely on visual information from the environment to perform. Some literature suggests athletes have superior visual abilities to non-athletes, particularly on tasks representative of the visual demands of their sport, such as dynamic acuity, eye movement accuracy and speed, and peripheral vision. Other literature suggests there is no difference between athletes and non-athletes, at least when standard clinical assessments are employed. A limitation of the literature is that almost none of the research has been conducted with standardized, validated tools. This is partly caused by a lack of readily available tools to measure tasks representative of the visual demands of sport, and available tests have typically not been validated against current clinical standards. The purpose of this study is to examine the validity and repeatability of a novel visual acuity system (moV&; V&MP Vision Suite) recently developed in the Vision & Motor Performance Lab (V&MP). moV& permits the measurement of many visual function parameters including dynamic visual acuity with predictable, random, and jittering target motion. METHODS: Twenty-five participants attended two study visits, separated by a minimum of 2 weeks. At each visit, static and dynamic visual acuity was measured using Snellen, ETDRS, and moV& charts. Static visual acuities were compared to determine the validity of moV&, and both static and dynamic visual acuities were compared between visits to determine the test-retest repeatability. RESULTS: moV& static visual acuities are clinically similar to visual acuities measured with the ETDRS chart (moV&, -0.09 ± 0.13; ETDRS, -0.03 ± 0.11, concordance correlation coefficient 0.726). Additionally, all static, dynamic, and jitter visual acuities demonstrate good test-retest repeatability (Lin's concordance correlation coefficient range 0.451-0.953). CONCLUSIONS: moV& provides good clinical measures of static visual acuity that are comparable to both Snellen and ETDRS measures. Dynamic visual acuity measures demonstrate good test-retest repeatability.

Hypersensitivity to Cold Stimuli in Symptomatic Contact Lens Wearers.

PURPOSE: To examine the cooling thresholds and the estimated sensation magnitude at stimulus detection in controls and symptomatic and asymptomatic contact lens (CL) wearers, to determine whether detection thresholds depend on the presence of symptoms of dryness and discomfort. METHODS: Forty-nine adapted CL wearers and 15 non-lens wearing controls had room temperature pneumatic thresholds measured using a custom Belmonte esthesiometer, during Visits 1 and 2 (Baseline CL), Visit 3 (2 weeks no CL wear), and Visit 4 (2 weeks after resuming CL wear). CL wearers were subdivided into symptomatic and asymptomatic groups based on comfortable wearing time (CWT) and CLDEQ-8 score (<8 hours CWT and ≥14 CLDEQ-8 stratified the symptom groups). Detection thresholds were estimated using an ascending method of limits and each threshold was the average of the three first-reported flow rates. The magnitude of intensity, coolness, irritation, and pain at detection of the stimulus were estimated using a 1-100 scale (1 very mild, 100 very strong). RESULTS: In all measurement conditions, the symptomatic CL wearers were the most sensitive, the asymptomatic CL wearers were the least sensitive, and the control group was between the two CL wearing groups (group factor p < 0.001, post hoc asymptomatic vs. symptomatic group, all p's < 0.015). Similar patterns were found for the estimated magnitude of intensity and irritation (group effect p = 0.027 and 0.006 for intensity and irritation, respectively) but not for cooling (p > 0.05) at detection threshold. CONCLUSIONS: Symptomatic CL wearers have higher cold detection sensitivity and report greater intensity and irritation sensation at stimulus detection than the asymptomatic wearers. Room temperature pneumatic esthesiometry may help to better understand the process of sensory adaptation to CL wear.

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.

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.

The roles of neural adaptation and sensitization in contact lens discomfort.

PURPOSE: To investigate the roles of neural adaptation and sensitization in contact lens discomfort (CLD). METHODS: Cooling stimuli (20 °C) were applied to the cornea in a group comprising 24 symptomatic and 25 asymptomatic contact lens (CL) wearers as well as 15 non-CL wearing controls, using a computerized Belmonte esthesiometer. The adaptation paradigm consisted of 20 repetitive stimuli at threshold, sub- and supra-threshold levels. The sensitization paradigm involved five levels of suprathreshold stimuli ranging between 1x to 2x threshold. Following each stimulus, participants rated the sensation magnitude regarding intensity, coolness and irritation. Measurements were taken with habitual CL (BL_CL), after 2 weeks of no-CL (No_CL) and after restarting habitual CL wear (ReSt_CL). RESULTS: The symptomatic subjects exhibited a lower threshold but reported enhanced sensations during the adaptation and sensitization paradigm, compared to the asymptomatic and control groups (all p ≤ 0.021). At the BL_CL and ReSt_CL visits, they showed increased ratings to repeated subthreshold stimuli (p = 0.025) and greater irritation during the sensitization paradigm (p ≤ 0.032). Ratings in asymptomatic and control groups were relatively unchanged over time (p ≥ 0.181). Logistic regression revealed a link between the augmented sensory responses and increased likelihood with CLD. CONCLUSION: The maladaptive sensory responses seen in CLD subjects, with reduced adaptation and heightened sensitization to ocular surface stimulation, suggest an imbalance between sensitization and adaptation in CLD. As CLD may represent a reversible subcategory of dry eye, it can serve as a human dry eye model for studying the neurosensory effect of ocular surface stimulation.

Association between reading speed, cycloplegic refractive error, and oculomotor function in reading disabled children versus controls.

BACKGROUND: Approximately one in ten students aged 6 to 16 in Ontario (Canada) school boards have an individual education plan (IEP) in place due to various learning disabilities, many of which are specific to reading difficulties. The relationship between reading (specifically objectively determined reading speed and eye movement data), refractive error, and binocular vision related clinical measurements remain elusive. METHODS: One hundred patients were examined in this study (50 IEP and 50 controls, age range 6 to 16 years). IEP patients were referred by three local school boards, with controls being recruited from the routine clinic population (non-IEP patients in the same age group). A comprehensive eye examination was performed on all subjects, in addition to a full binocular vision work-up and cycloplegic refraction. In addition to the cycloplegic refractive error, the following binocular vision related data was also acquired: vergence facility, vergence amplitudes, accommodative facility, accommodative amplitudes, near point of convergence, stereopsis, and a standardized symptom scoring scale. Both the IEP and control groups were also examined using the Visagraph III system, which permits recording of the following reading parameters objectively: (i) reading speed, both raw values and values compared to grade normative data, and (ii) the number of eye movements made per 100 words read. Comprehension was assessed via a questionnaire administered at the end of the reading task, with each subject requiring 80% or greater comprehension. RESULTS: The IEP group had significantly greater hyperopia compared to the control group on cycloplegic examination. Vergence facility was significantly correlated to (i) reading speed, (ii) number of eye movements made when reading, and (iii) a standardized symptom scoring system. Vergence facility was also significantly reduced in the IEP group versus controls. Significant differences in several other binocular vision related scores were also found. CONCLUSION: This research indicates there are significant associations between reading speed, refractive error, and in particular vergence facility. It appears sensible that students being considered for reading specific IEP status should have a full eye examination (including cycloplegia), in addition to a comprehensive binocular vision evaluation.

Impact of silicone hydrogel lenses and solutions on corneal epithelial permeability.

PURPOSE: The primary purpose of this pilot study was to compare epithelial barrier function (EBF) and staining in a small group of participants using a silicone hydrogel (SH) lens worn on a daily basis with two different care regimens. Secondarily, the aim was to see if there was any correlation between corneal staining and EBF. METHODS: The corneal EBF of 10 non-lens wearers (control) and 15 age-matched asymptomatic SH contact lens wearers (test) were assessed using fluorophotometry. Biomicroscopy was performed to assess corneal staining after the EBF was measured. The lens wearers wore PureVision (FDA group V) SH lenses for two consecutive 1-month periods while using either Alcon Opti-Free Express or Renu Fresh using a randomized, investigator-masked, crossover design. Control subjects were assessed on one occasion, and lens wearers were examined before fitting with lenses and after 7, 14, and 28 days of lens wear, with each combination. RESULTS: Compared with the control group, both study groups had an increase in epithelial permeability at baseline (p ≤ 0.04). There were no changes in EBF during the treatment period for either solution (p = 0.87). A significant difference in EBF was found between the test groups during the treatment period (p = 0.02), with greater permeability in the Renu Fresh-disinfected lenses. There was poor correlation between corneal staining and EBF (r = 0.35, p > 0.05) because of large individual variations. CONCLUSIONS: Daily wear of highly oxygen-permeable SH lenses increases corneal epithelial permeability to fluorescein probably because of increased mechanical effects. In addition, certain lens-solution interactions can add to this effect, as seen in this study. Despite having a low amount of central corneal staining in the Renu Fresh group, staining and EBF did not prove to be well correlated. The presence of central corneal staining is a confounding factor when measuring EBF.

Estimating tear film spread and stability through tear hydrodynamics.

PURPOSE: The stability and ease of spread of the tear-film over the contact lens surface may be an indicator of contact lens surface dewetting. The present in vivo methods of determining lens dewetting are complex. This study introduces a novel and objective way of determining the upward spread and stability of the tear-film through measurement of tear-film particle dynamics. METHODS: Ten adapted contact lens wearers wore the same type of contact lens. Using a video camera mounted to a slit-lamp, the tear-film spread over the lens surface was recorded after a blink, at 8× magnification and capture rate of 30 frames per second, at morning after lens insertion, and after 8 h of lens wear. Images from 20 videos, without blinks and without an observable change in fixation were analyzed without any further postprocessing of the images. Using a customized calibrated ImageJ macro for particle tracking, the velocity of naturally occurring reflective particles was determined. The results were analyzed using the R program and ProFit. RESULTS: The results established that the upward particle velocity was highest immediately after a blink and declined with time. The spread of the tear film measured through upward particle velocity was different on lens insertion than after 8 h of lens wear (p = 0.001). The exponential time constants ± SE were 346.02 ± 29.0 for lens insertion at morning and 1413.13 ± 419.6 after 8 h of lens wear. CONCLUSIONS: A novel and non-invasive way to measure in vivo spread and stability of the prelens tear-film has been developed. Additional studies are needed to understand whether this simple measure is able to differentiate the performance of different soft contact lenses and how this method may help in the understanding other aspects of lens performance such as non-invasive tear breakup time, surface deposition, and lens comfort.

Multiple Criterion and Multiple Stimulus Signal Detection Theory Analysis of Corneal Painful and Cool Pneumatic Stimuli.

Purpose: To evaluate the detectability of pneumatic corneal stimuli and response bias using multi-stimuli multi-criterion signal detection theory (MSDT). Methods: Thirty-six participants were recruited using convenience sampling. A Waterloo Belmonte esthesiometer was used to deliver cold, mechanical, and chemical stimuli to the center of the cornea at three separate study visits. The stimulus type was assigned randomly to each visit at the start of the study. The threshold (baseline for detection theory experiment) for the assigned stimulus type was obtained using the ascending method of limits. In the cold and mechanical MSDT experiments, 100 trials (80 signal (20 each for 4 intensities) and 20 catch trials) were presented in randomized order, and participants responded with a 5-point confidence rating to each trial. In the chemical MSDT experiments, 50 trials (20 signal trials each for two intensities and 10 catch trials) were presented, and responses were provided using 4-point confidence ratings. Detection theory indices were calculated individually and as groups, which were then analyzed using mixed models and paired t-tests. Results: Detectability (da) and the area under the curve (Az) were significantly different between stimulus intensities within each stimulus type (all p < 0.001) but were not different between the stimulus types. Receiver operating characteristics (ROC) curves were separable between the scaled intensities for all stimulus types, and no overlaps were observed in the z-ROC space. The log-likelihood ratio (lnß) depended on stimulus intensity and psychophysical criterion for all stimulus types. Conclusion: It is feasible to use MSDT for analyzing ocular surface sensory processing and the theory provides insight into the possible bias associated with the use of pneumatic stimuli. With noxious and non-noxious pneumatic stimulation, detectability and criteria vary systematically with stimulus intensity, a result that cannot be derived using classical psychophysics and this highlights the importance of signal detection theory and its approaches in studying ocular surface pain and thermal processing.

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.

Canonical Grading Scales of Corneal and Conjunctival Staining Based on Psychophysical and Physical Attributes.

Purpose: In this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions. Methods: Subjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes. The same procedure was followed for conjunctival staining after instillation of 2 µl of 1% lissamine green. A subset of the best corneal and bulbar conjunctival staining images were anonymized and a spectroradiometer measured photometric attributes (luminance and chromaticity). The images were scaled psychophysically by study investigators, who participated in constructing grading scales based on physical and psychophysical analyses. The final grading scales were refined following consultation with outside DE experts. Results: Photographs were collected from 142 subjects (81% women), with an average age of 58 ± 17 years; 89% were diagnosed with DE. There was a monotonic relationship between between physical measurements and psychophysically scaled staining of both corneal (fluorescein) and bulbar (lissamine green) staining. Michelson contrast and u' (chromaticity) accounted for 66% and 64% of the variability in the psychophysically scaled images of fluorescein corneal and lissamine green conjunctival staining, respectively. Translational Relevance: This paper provides examples of the first ever clinically usable ocular surface staining scales validated using psychophysical scaling and the physical attributes (luminance and chromaticity) of the staining itself. In addition, it provides a generalizable method for the development of other clinical scales of ocular appearance.

The conversion of bulbar redness grades using psychophysical scaling.

PURPOSE: To use psychophysical scaling to investigate if the inclusion of reference anchors affected the perceived redness of the reference images of four bulbar redness grading scales and to convert grades between scales. METHODS: Ten participants were asked to arrange printed copies of the McMonnies/Chapman-Davies (6), IER (4), and Efron (5) grading scale images relative to each other, using the stationary but unlabeled 10, 30, 50, 70, and 90 reference images of the validated bulbar redness scale as additional anchors within a given 0 (minimum) to 100 (maximum) redness range (anchored scaling). The position of each image was averaged across observers to represent its perceived redness within this range. Anchored scaling data were then compared with data from a previous study, where the images of all four grading scales had been scaled for the same experimental setup, but with no reference anchors provided (non-anchored scaling). Averaged perceived redness as determined with anchored scaling was used to cross-calibrate grades between scales. RESULTS: Overall, perceived redness of the reference images was significantly different within each scale (repeated measures analysis of variance, all scales p < 0.001). There were differences in perceived redness range and when comparing reference levels between scales. Anchored scaling resulted in an apparent shift to lower perceived redness for all but one reference image compared with non-anchored scaling, with the rank order of the 20 images for both procedures remaining fairly constant (Spearman's ρ = 0.99). CONCLUSIONS: The re-scaling of the reference images in the anchored scaling experiment suggests that redness was assessed based on within-scale characteristics and not using absolute redness scores, a mechanism that can be referred to as clinical scale constancy. The perceived redness data allow practitioners to modify the grades of the scale they commonly use for comparison of their grading estimates with grades obtained with another calibrated scale.

Repeatability of pachymetry and thinnest point localization using a fourier-domain optical coherence tomographer.

PURPOSE: To evaluate the repeatability of pachymetry measures at six distinct locations using a Fourier-domain optical coherence tomographer. The location of the thinnest point was also described using vector analysis, and repeatability of the localization of the thinnest point was calculated. METHODS: The right eye of 25 healthy subjects had 3 images of their right cornea captured using the pachymetry protocol and anterior segment lens of a commercially available Fourier-domain optical coherence tomographer (RTVue-100, Optovue, Fremont, CA). The first two images were used to quantify repeatability in the central (2 mm) and paracentral (2-5 mm) cornea. Cartesian coordinates representing the location of the thinnest point were used to determine the mean location in relation to the central cornea. RESULTS: Mean central thickness was 536.8 ± 31.1 µm, and the mean minimum thickness was 526.4 ± 33.1 µm. The thickest paracentral zone was the superior cornea and the thinnest was the temporal cornea. Intraclass correlation values ranged between 0.969 and 0.996, and the mean coefficient of repeatability was 1.74% across all locations evaluated. The thinnest point was located in the inferior temporal region in 80% of eyes and was an average distance of 1.01 mm from the corneal apex, subtending an angle of 26.7° from the horizontal. CONCLUSIONS: The RTVue-100 provides a highly repeatable measure of corneal thickness at various locations. The instrument is capable of describing and consistently duplicating the location of the thinnest point of the cornea; however, further comparative work with other clinical imaging modalities is required.

Factor analysis of the clinical characteristics of primary Sjogren syndrome.

PURPOSE: The purpose of this study was to use factor analysis to analyze 90 clinical characteristics of a cohort of 231 patients with primary Sjogren syndrome (pSS). METHODS: The records of all patients seen at the University Health Network Sjogren Syndrome Clinic from October 1992 to July 2006 were reviewed and documented. Those diagnosed as pSS by the American European Consensus Criteria of 2002 were included. The 90 clinical variables, including health history, blood analysis, symptoms of dry eye and dry mouth, salivary flow and biopsy, tear flow and staining, were analyzed by factor analysis. RESULTS: Two hundred thirty-one patients with pSS charts were reviewed, and 90 variables were recorded. Factor analysis resulted in three factors: factor 1: ocular surface staining, factor 2: antimicrosomal antibodies and antithyroid antibodies, and factor 3: serum anti-Ro and anti-La. CONCLUSIONS: Ocular surface staining accounted for the greatest variance in this population of patients with pSS.

Tear lipocalin and lysozyme concentrations in postmenopausal women.

PURPOSE: To investigate the potential relationship between subjective symptomatology, tear volume, and tear break up time with tear film lipocalin and lysozyme concentrations in a group of symptomatic dry-eyed postmenopausal (PM) women compared to age-matched controls. METHODS: Eighty-five healthy PM females (>50 years of age) were categorized as mild or moderate dry eye (DE), or asymptomatic [non-dry eye (NDE)] based on their responses to the Ocular Surface Disease Index (OSDI) questionnaire. Non invasive tear breakup time (NITBUT) and tear secretion were measured. Tears were collected via capillary tube and an eye wash method. Tear lysozyme and lipocalin concentrations were determined via Western blotting. RESULTS: Ocular Surface Disease Index responses revealed 16 mild DE, 30 moderate DE, and 39 NDE. The OSDI total score and sub scores for the DE groups were significantly greater than for the NDE group (p < 0.001). The mild and moderate DE groups exhibited significantly shorter NITBUTs compared to NDE (p < 0.004). Tear secretion using the Phenol Red Thread (PRT) test was found to be significantly lower in the moderate DE group compared to NDE (p < 0.001). No difference in tear lysozyme or lipocalin concentration was found between DE and NDE groups, irrespective of tear collection method, although method of collection significantly influenced absolute concentrations (p < 0.008). Significant correlations were not found between symptoms or signs of DE compared to either lipocalin or lysozyme concentration. CONCLUSION: Within a PM population, lipocalin and lysozyme are invariant, irrespective of the presence and severity of DE symptoms. This is the first comprehensive study of lipocalin and lysozyme in dry-eyed PM women and our results suggest that neither protein would offer utility as a biomarker of DE.

Influence of the blink interval on tear meniscus height in soft contact lens and nonlens wearers.

PURPOSE: Tear meniscus height (TMH) is an indirect measurement of tear film volume. This study investigated the temporal changes in the TMH during the blink interval in the morning (8-9 am) and at the end of the day (5-6 pm) in both soft contact lens (CL) and nonlens wearers (NLW). METHODS: Fifty participants (25 CL; 25 NLW) were evaluated for their subjective symptoms, TMH, noninvasive break up time, and bulbar hyperemia at the am and pm visits on the same day. The TMH was measured at set intervals between 2 and 15 sec during the blink interval, using an optical coherence tomographer. RESULTS: The NLW group revealed no changes in a variety of symptoms during the day, whereas the CL group reported an increase in dryness (P=0.03) and grittiness (P=0.02) over the day. For both groups, the TMH and calculated tear meniscus volume revealed lower values immediately after the blink and increased progressively afterwards, mainly due to reflex tearing. The am tear meniscus volume values tended to be higher than the pm values for both groups, but this was not significant (NLW P=0.13; CL P=0.82). Noninvasive break up time deteriorated during the day for both groups but was only significant for the CL group (P=0.002), whereas bulbar hyperemia revealed no statistically significant change for either group. CONCLUSIONS: Reflex tearing may play a substantial role in the TMH differences observed over the blink interval. Standardization of the time when a TMH measurement is performed will be valuable in comparing tear film clinical studies.

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.

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.