Trefford Simpson

A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada

Objective. To collect questionnaire data from patients in a large clinical population that would allow for an estimate of the prevalence of self-reported symptoms of dry eyes. Methods. A 13-point questionnaire (The Canada Dry Eye Epidemiology Study, CANDEES) was mailed to all optometric practices in Canada in October 1994, with the request that it be completed by 30 successive nonselected patients. Results. Four hundred fifty sets of questionnaires (total, 13,517) were analyzed (a 15.7% return rate) from patients aged from <10 years to >80 years; 55% were in the 21- to 50-year age group; 60.7% were female; and 24.3% were contact lens wearers. A total of 28.7% reported dry eye symptoms, of whom 24.2% reported concurrent dry mouth, 24.5% had worse symptoms in the morning, 30.3% reported concurrent lid problems, and 35.7% reported a history of allergies. Of the 3716 patients reporting symptoms, 62 (1.6%) were in the “severe” category and 290 (7.8%) were in the “constant but moderate” category. Contact lens wear, concurrent allergies, dry mouth, lid problems, or use of medications increased the chance of a patient reporting dry eye symptoms. Conclusions. The prevalence of patients reporting any level of symptoms of dry eyes was approximately 1 in 4; severe symptoms were reported by 1 in 225 patients.

Characterization of ocular surface symptoms from optometric practices in North America.

Purpose. This study characterized ocular symptoms typical of dry eye in an unselected optometric clinical population in the United States and Canada. Methods. Self-administered dry eye questionnaires, one for non–contact lens wearers (dry eye questionnaire) and one for contact lens wearers (contact lens dry eye questionnaire), were completed at six clinical sites in North America. Both questionnaires included categoric scales to measure the prevalence, frequency, diurnal severity, and intrusiveness of nine ocular surface symptoms. The questionnaires also asked how much these ocular symptoms affected daily activities and contained questions about computer use, medications, and allergies. The examining doctors, who were masked to questionnaire responses, recorded a nondirected dry eye diagnosis for each patient, based on their own diagnostic criteria. Results. The dry eye questionnaires were completed by 1,054 patients. The most common ocular symptom was discomfort, with 64% of non–contact lens wearers and 79% of contact lens wearers reporting the symptom at least infrequently. There was a diurnal increase in the intensity of many symptoms, with symptoms such as discomfort, dryness, and visual changes reported to be more intense in the evening. The 22% percent of non–contact lens wearers and 15% of contact lens wearers diagnosed with dry eye (most in the mild to moderate categories) reported symptoms at a greater frequency than those not diagnosed with dry eye. Conclusions. Our results show that symptoms of ocular irritation and visual disturbances were relatively common in this unselected clinical population. The intensity of many ocular symptoms increased late in the day, which suggested that environmental factors played a role in the etiology of the symptoms.

A link between tear instability and hyperosmolarity in dry eye.

PURPOSE Tear film instability and tear hyperosmolarity are considered core mechanisms in the development of dry eye. The authors hypothesize that evaporation and instability produce transient shifts in tear hyperosmolarity that lead to chronic epithelial stress, inflammation, and symptoms of ocular irritation. The purpose of this study was to provide indirect evidence of short-term hyperosmolar conditions during tear instability and to test whether the corneal epithelium responds to transient hyperosmolar stress. METHODS Five subjects kept one eye open as long as possible, and overall discomfort and sensations associated with tear break-up were scaled. Later, the same subjects used the same scales to report discomfort sensations after instillation of NaCl and sucrose hyperosmolar drops (300-1000 mOsM/kg). A two-alternative, forced-choice experiment was used to obtain osmolarity thresholds. In the second experiment, primary cultured bovine corneal epithelial cells were transiently stressed with the same range of hyperosmolar culture medium, and proinflammatory mitogen-activated protein kinase (MAPKs) were measured by Western blot analysis. RESULTS Tear instability led to an average discomfort rating of 6.13 and sensations of burning and stinging. These sensations also occurred with hyperosmolar solutions (thresholds, 450-460 mOsM/kg) that required 800 to 900 mOsM/kg to generate the same discomfort levels reported during tear break-up. MAPK was activated at 600 mOsM/kg of transient hyperosmolar stress. CONCLUSIONS These experiments provide a link between hyperosmolarity and tear instability, suggesting that hyperosmolar levels in the tear film may transiently spike during tear instability, resulting in corneal inflammation and triggering sensory neurons.

Hydrogel lens dehydration and subjective comfort and dryness ratings in symptomatic and asymptomatic contact lens wearers.

PURPOSE To determine whether lens dehydration correlates with discomfort, dryness, and noninvasive tear break-up time in symptomatic and asymptomatic contact lens wearers and whether dehydration of the two lens types varies. METHOD Twenty hydrogel contact lens wearers with dryness-related symptoms and 20 asymptomatic wearers wore an Etafilcon A lens (Acuvue; Vistakon, Inc., Jacksonville, Florida) in one eye and an Omafilcon A lens (Proclear; Biocompatibles, Norfolk, Virginia) in the contralateral eye for 7 h in a randomized, double-masked study. Lens water content was measured before and after 7 h of lens wear and prelens noninvasive tear film break-up time (NIBUT) was measured immediately after insertion and after 5 h of lens wear. Subjective comfort and dryness were rated at 0, 1, 3, 5, and 7 h of lens wear. RESULTS The symptomatic group had significantly reduced prelens NIBUT, decreased comfort, and increased dryness, but there was no difference between lenses for these variables. The Omafilcon A lenses dehydrated significantly less than the Etafilcon A lenses, but there was no significant difference in lens dehydration between two subject groups. CONCLUSION No correlation was found between lens dehydration and subjective dryness and comfort. Symptomatic hydrogel contact lens wearers with decreased wearing time had measurably decreased comfort, increased dryness ratings, and reduced NIBUT.

Diurnal variation of corneal and corneal epithelial thickness measured using optical coherence tomography.

Purpose. To determine the feasibility of optical coherence tomography (OCT) measurement of overnight corneal swelling and de-swelling and, specifically, to examine overnight changes in the corneal epithelium and recovery during the day. Methods. Ten healthy volunteers were recruited. Corneal OCT imaging was performed at 10:00 PM (baseline), 8:30 AM, and every 2 hours thereafter until 4:30 PM. Either the right or left eye was taped shut (using a gauze pad and surgical tape) until the 8:30 AM session of the next day. Measurements were made along a 1-mm strip centered on the visual axis. Results. At baseline, there were no differences in corneal or epithelial thickness between control and experimental eyes (all p > 0.05). Immediately after patch removal, corneal and epithelial thicknesses of patched eyes were higher than the baseline (all p < 0.05). In patched eyes, the cornea and epithelium swelled 5.5% and 8.1% overnight, respectively (p > 0.05). Two hours later, the epithelial thickness of the experimental eyes recovered to baseline level (p > 0.05), but corneal thickness did not reach to baseline level until 4 hours after patch removal. For control eyes, there were no differences compared with baseline (all p > 0.05). Conclusion. Both cornea and corneal epithelium experience proportionately similar amounts of overnight swelling. Recovery of overnight swelling may be slower for the cornea than for the epithelium. OCT provides valuable information about anterior segment morphometry.

Diurnal variation of corneal sensitivity and thickness.

Purpose. To measure the diurnal variation of central corneal sensitivity and thickness over 24 hours. Methods. A noncontact pneumatic esthesiometer to measure central corneal sensitivity and an optical pachymeter to measure central corneal thickness were used on 20 noncontact lens wearers. These measurements were performed at 22:00 before 8 hours of sleep and on the following day on eye opening and at hourly intervals between 7:00 and 22:00. Results. Central corneal sensitivity varied by 35% over the 24 hours. Sensitivity was significantly lower by 17.1 ± 2.1% on eye opening and recovered to the level of the previous night after 4 hours. Corneal sensitivity continued to increase throughout the day but was not significantly higher. Central corneal thickness varied by 3.9% over the 24 hours. The mean overnight corneal swelling was 2.9 ± 0.31%, and 2 hours after eye opening, the cornea had deswelled to the same thickness as the previous night. The cornea thinned further throughout the day, but there were no statistically significant differences between the values after 14:00. There was a high correlation between corneal sensitivity and thickness over time (r = 0.8;p < 0.05). Discussion. Corneal sensitivity correlated with corneal thickness: both were higher on awakening and then decreased and remained below the levels measured the previous night. This may be due to physiological and/or environmental factors. The lack of significant differences between the values after 14:00 suggests that baseline may be measured at any time from 7 hours after eye opening.

The measurement of corneal epithelial thickness in response to hypoxia using optical coherence tomography

PURPOSE To determine if corneal epithelial thickness increases in association with corneal edema induced by wearing soft contact lenses during eye closure. DESIGN Experimental study. METHODS One eye (randomly selected) of twenty noncontact lens wearers (10 males and 10 females, age 35.6 +/- 9.6 years) was patched during 3 hours of soft contact lens (SCL) wear and the contralateral eye acted as a control. Corneal and epithelial thickness of both eyes was measured before and after SCL wear using optical coherence tomography (OCT). RESULTS Immediately after contact lens removal, total corneal thickness was increased significantly by 13.8 +/- 2.3% (mean +/- SD) compared with baseline (P <.0001, paired t test) and after 100 minutes was still 4.5 +/- 2.3% thicker than baseline (P <.0001, paired t test). The control eyes showed no change in total corneal thickness (P >.05, paired t test). Immediately after contact lens removal, corneal epithelial thickness was increased by 1.7 +/- 4.8%, but this change was not statistically significant (P >.05, paired t test). Following contact lens removal, epithelial thickness changed significantly (Repeated measure analysis of variance [Re-ANOVA]: F((7,133)) = 4.91, p(H-F) < 0.001) over the next 100 minutes with thinning recorded at 60, 80, and 100 minutes (P <.05, paired t test). There was no significant change over time in epithelial thickness of the control eyes (Re-ANOVA: F(4, 76) = 0.91, p(H-F) = 0.464). CONCLUSION OCT demonstrated that corneal epithelial thickness does not increase in response to hypoxia from SCL wear and eye closure, in contrast to a significant increase in total corneal thickness.

CORNEAL AND EPITHELIAL THICKNESS IN KERATOCONUS: A COMPARISON OF ULTRASONIC PACHYMETRY, ORBSCAN II, AND OPTICAL COHERENCE TOMOGRAPHY

PURPOSE To compare corneal thickness measurements in individuals with keratoconus using optical coherence tomography (OCT), Orbscan II, and ultrasonic pachymetry and to measure epithelial and stromal thickness in these individuals using OCT. METHODS Twenty individuals with keratoconus and 20 controls (without keratoconus) were enrolled. The Orbscan II was used to locate the steepest area of the cornea, which was taken to represent the cone apex. Each instrument was used to obtain four total corneal thickness measurements-from the cone apex, corneal center, mid-nasal, and mid-temporal cornea. Optical coherence tomography scans were analyzed to provide epithelial and stromal thickness readings. RESULTS In individuals with keratoconus, mean central corneal thickness (CCT) measured by ultrasonic pachymetry, Orbscan, and OCT was 494.2 +/- 50.0 microm, 438.6 +/- 47.7 microm, and 433.5 +/- 39.7 microm, respectively. The central keratoconic cornea was 57.7 microm thinner than the normal cornea (post-hoc P<.001). The cone apex was thinner than the central cornea (P<.001). Keratoconic epithelium was 48.2 +/- 5.5 microm centrally and 42.1 +/- 4.5 microm at the apex. Central keratoconic epithelium was 4.7 microm thinner and central keratoconic stroma was 57.8 microm thinner than the normal cornea (P<.001, respectively). Comparing instruments, Orbscan and OCT correlated in CCT measurement (r=0.890) and apical thickness (r=0.846). All instruments produced similar readings for mid-nasal and mid-temporal corneal thickness in participants with keratoconus (P>.05). CONCLUSIONS Ultrasonic pachymetry produced the highest corneal thickness readings in the center and apex, compared to Orbscan II and OCT. Centrally, the total cornea, epithelium, and stroma were thinner in individuals with keratoconus than in normal individuals.

The repeatability of corneal and corneal epithelial thickness measurements using optical coherence tomography.

Purpose. The purpose of this study is to examine within and between session repeatability of clinical optical coherence tomography (OCT) imaging for anterior segment morphometry. Methods. Images of the corneal apex of each eye in 18 subjects were obtained using a Humphrey Zeiss OCT imager. Subjects viewed a target positioned to ensure that scans were orthogonal to the ocular surface and each image, consisting of 100 adjacent sagittal scans, analyzed using custom software. Repeatability data were analyzed using intraclass correlation coefficients (ICCs), correlation coefficient of concordance (CCC, perfect test–retest agreement ICC or CCC = 1.0), and coefficients of repeatability (COR, 95% confidence interval of test–retest differences). To account for each eye, the multivariate repeatability statistic Iota was estimated. Results. Mean central corneal and epithelial thickness of 32 eyes (OD and OS combined) is 536 ± 26 &mgr;m (standard deviation [SD]) and 52 ± 3 &mgr;m (SD) with 5th and 95th percentile thicknesses of 507 and 591 &mgr;m for central cornea and 48 and 57 &mgr;m for central epithelial. Worst case within session repeatability was defined as repeatability between images with greatest differences in mean thickness within a session. Corneal thickness worst case ICC was 0.95 and COR was ± 9.98 &mgr;m. Epithelium worst case ICC was 0.36, CCC was 0.12, and COR was ± 11.11 &mgr;m. First image between session corneal thickness had an ICC = 0.98 and a COR = 10.83 &mgr;m, whereas epithelium ICC = 0.38, CCC = 0.37, and COR was ± 12.84 &mgr;m. When we compared the average of the first three tests with the first three retest images, corneal ICC was 0.98 and COR was ± 10.64 &mgr;m and epithelium ICC = 0.73, CCC = 0.72, and COR was ± 6.53 &mgr;m. Iota (multivariate repeatability, using eye as a factor) for the cornea was at least 0.96 (worst case) and increased to at least 0.98 when within-session image data were averaged. Iota for epithelium measures ranged from 0.29 when first images were compared with 0.57 when within-session image data were averaged. Conclusions. There is very good repeatability of corneal thickness measurement using OCT; even the worst case measurements are similar between sessions. On the other hand, this is not the case for epithelium measurements, and if multiple images within a session are acquired, the worst case results demonstrate how important it is to optimize each OCT scan and also average multiple scans to maximize intersession repeatability.

Optical coherence tomography: an introduction to the technique and its use.

This report describes the new optical imaging technique of optical coherence tomography (OCT). OCT is capable of high-resolution, micrometer-scale, cross-sectional imaging of biological tissue. The OCT for ophthalmic application uses 843-nm, near-infrared light, which produces a longitudinal resolution of 10 to 20 microm and a penetration depth of a few millimeters. The scans are displayed in a false color representation scale on which warm colors represent areas of high optical reflectivity and cool colors represent areas of minimal or no reflectivity. A cross-sectional view similar to a histology section is obtained. The cornea, iris, and lens may be visualized as well as the retina and optic nerve. OCT has been used to investigate several ocular diseases. These include macular disease, genetic retinal disease, retinal detachment and retinoschisis, choroidal tumors, optic nerve disorders, and glaucoma.