Carolyn G. Begley

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.

Responses of contact lens wearers to a dry eye survey

The purpose of this study was to examine ocular symptoms that have been associated with dry eye among contact lens wearers. A dry eye questionnaire was administered at random to 83 contact lens wearers at a private practice in Toronto, Ontario. On average, the most frequent ocular symptom among those queried was dryness and the least frequent was soreness. There was a significant shift (p < 0.0001; paired t-test) toward increased symptoms in the evening compared with the morning. Blurry, changeable vision was also a frequent and noticeable symptom. However, most subjects reported that their ocular symptoms were not severe enough for them to stop work or hobbies or to remove their contact lenses. Our results show that the symptoms of ocular dryness and discomfort are relatively common among contact lens wearers, and that they worsen toward the end of the day. These findings suggest that lens care practitioners should examine their patients who wear contact lenses toward the end of the day to best identify symptomatic patients.

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.

Blinking and tear break-up during four visual tasks.

Purpose. This study investigates the relationship between blinking, tear film break-up, and ocular symptoms for normal and dry eye subjects performing four different visual tasks. Methods. Sixteen control and sixteen dry eye subjects performed four visual tasks (looking straight ahead, watching a movie, identifying rapidly changing letters, and playing a computer game) while blink patterns and fluorescein images of the tear film were videotaped. Pre and posttesting symptom questionnaires, querying the intensity of nine symptoms of ocular irritation, were completed by all subjects. Blink rate and blink amplitude were computed from digitized videos. The percentage of tear film break-up before the blink was calculated. Results. Dry eye subjects had a significantly higher blink rate (p = 0.017, t-test). Both groups blinked significantly less during the game and letter tasks (p < 0.04, t-test). Partial blinks were common as were clusters or “flurries” of rapid blinks, but there was no significant difference in blink amplitude for control and dry eye subjects. Tear film break-up in normal subjects was typically inferior; whereas dry eye subjects showed more tear break-up centrally and superiorly. Real-time video recording of tear break-up and blink behavior pointed to complex interaction between the two. Dry eye subjects shifted more toward intense ocular symptoms at posttesting (p < 0.05, Wilcoxon signed rank) than controls. Both groups showed a shift toward more corneal staining at posttesting (p < 0.05, Wilcoxon signed rank), which was typically inferior. Conclusions. Reduced and incomplete blinking along with increased tear film break-up during normal visual tasks may explain the increased level of ocular discomfort symptoms reported at the end of the day, particularly in dry eye patients.

Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): Discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses

PURPOSE To validate a subset of Dry Eye Questionnaire (DEQ) items that discriminate across self-assessed severity and various diagnoses of dry eye (DE). METHODS Subjects (n=260) in 2 studies received a clinical DE diagnosis, completed the 6-page DEQ and self-assessment of DE severity (SA-Sev). SA-Sev ratings were: 46 Severe, 107 Moderate, 77 Mild, and 46 None. Dry eye diagnoses were: 48 asymptomatic controls (C), 155 non-SS KCS, and 57 Sjögren Syndrome (SS). All DEQ items were correlated to SA-Sev by Spearman. Groups of highly correlated DEQ items were tested to discriminate SA-Sev; and the subset tested to distinguish across DE diagnosis. RESULTS The DEQ-5 comprises: frequency of watery eyes (r=0.48), discomfort (r=0.41), and dryness (r=0.35), and late day (PM) intensity of discomfort and dryness (r=0.42, 0.36) all significantly correlated to SA-Sev (p<0.01). Mean DEQ-5 scores by SA-Sev: Severe 14.9+/-2.3, Moderate 11.4+/-3.3, Mild 8.6+/-3.1 and None 2.7+/-3.2 (ANOVA, p<0.0001) and by DE diagnosis: C 2.7+/-2.9, non-SS KCS10.5+/-4.5 and SS14.0+/-3.4, differing significantly overall (Z=-8.6, p=0.000) and between diagnoses (X(2)=116.3, p=0.000). Watery eyes were reported primarily by non-SS KCS. Proposed screening criteria for the DEQ-5 are >6 for DE and >12 for suspected SS. CONCLUSIONS The DEQ-5, the sum of scores for frequency and PM intensity of dryness and discomfort plus frequency of watery eyes, effectively discriminated across self-assessed severity ratings and between patients with DE diagnoses. These results indicate that DEQ-5 scores >6 suggest DE and scores >12 may indicate further testing to rule out SS-DE.

Tear breakup dynamics: a technique for quantifying tear film instability.

Purpose. The purpose of this study was to develop a novel, quantitative measurement of tear film breakup dynamics (TBUD) to study the phenomenon of tear breakup in dry eye and control subjects and its impact on dry eye symptoms. Methods. Ten control and 10 dry eye subjects completed the Dry Eye (DEQ) and other questionnaires. After the instillation of sodium fluorescein, subjects kept the tested eye open for as long as possible, similar to a staring contest, while tear film breakup was videotaped (S-TBUD). The maximum blink interval (MBI) and tear breakup time (TBUT) were measured from digital movies by a masked observer. Individual frames of movies were converted to gray-scale images, maps of relative tear film fluorescence were generated, and the total area of tear breakup (AB) of the exposed cornea was quantified. Results. On average, dry eye subjects demonstrated a higher AB and shorter TBUT and MBI, but only the AB was significantly different (p = 0.023). Subjects most often used the descriptors stinging and burning to describe their sensations during staring trials. The AB showed a high correlation between eyes and with some DEQ symptom measures. Conclusions. These methods allow objective quantification and tracking of the phenomenon of tear breakup. Our results suggest that tear breakup stresses the corneal surface, resulting in stimulation of underlying nociceptors. The tear film of dry eye subjects was less stable than controls. They had a larger AB measured from the last video frame before MBI (i.e., just before blinking) than did controls. This perhaps reflects adaptation to the repeated stress of tear instability in dry eye.

Temporal progression and spatial repeatability of tear breakup

Purpose. This study used image analysis to compare the temporal progression and spatial reoccurrence of the area of tear film breakup (AB) in dry eye and normal subjects. Methods. Tear breakup was induced in 10 control and 10 dry eye subjects during the Staring Tear Breakup Dynamics (S-TBUD) test, which involves keeping one eye open for as long as possible, termed the maximum blink interval (MBI). Video imaging of tear film fluorescence measured the onset and progression of the AB. AB location and area were mapped. The progression of ABs from the first trial, the rate of tear breakup or dry area growth rate (DAGR), and the overlap of ABs in three successive trials 5 minutes apart were computed by custom MATLAB programs. Results. The final AB before the blink was significantly greater (average, 30.7% ± 12.5% vs. 16.1% ± 9.2%) and the MBI was significantly less (average, 19.5 ± 9.0 seconds vs. 56.5 ± 38.9 seconds) among dry eye subjects compared with controls (p < 0.05, Mann-Whitney U test). The DAGR was four times greater among dry eye subjects, who also showed significantly more tear breakup in the central cornea than controls (p < 0.0001, Mann-Whitney U test). When the final image from three successive trials was overlapped, tear breakup occurred more often in the same location in three trials than would be expected by the overlap of independent points. Conclusions. Structural influences such as the “black line” or corneal lid defects appeared to influence the recurrence of breakup in the same region. The S-TBUD quantitative image analysis technique demonstrates that the tear film of subjects with dry eye continues to rapidly destabilize after an initial first break; thus, a low TBUT was combined with a high DAGR. The central corneal region of subjects with dry eye appeared especially susceptible to increased tear breakup when compared with controls.

Symptoms of ocular irritation in patients diagnosed with dry eye.

PURPOSE The purpose of this study was to develop a pilot survey to evaluate ocular irritation symptom frequency, severity, and impact on daily activity in patients previously diagnosed with dry eye. METHODS Forty-five patients previously diagnosed with dry eye (ICD-9 code 375.15) completed the 17-item symptom survey. Analog-scale response questions concerning the frequency, severity, and effect on daily activity were asked for the following symptoms: dryness, scratchiness and soreness, burning and stinging, light sensitivity, blurry vision, and ocular itching. RESULTS Dryness and soreness were the most frequently reported symptoms of ocular irritation. Although the occurrence of symptoms of ocular irritation was reported as frequent by patients diagnosed with dry eye, the symptoms had minimal to moderate impact on daily activity. CONCLUSIONS Patient expression of the symptoms of dryness and soreness at more frequent and/or more severe levels may lend more validity to a diagnosis of dry eye.

Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance.

Purpose. To report on the development and validation of a short form of the Contact Lens Dry Eye Questionnaire (the CLDEQ-8) to enable it to reflect status of and change in overall opinion (“opinion”) of soft contact lenses (SCLs). Methods. Item reduction for the CLDEQ was achieved by correlation with overall opinion of SCLs at follow-up visits in a sample of 38 SCL wearers at one academic clinical site. The CLDEQ-8 score (frequency plus late day intensity of dryness, discomfort, and “blurry vision”; frequency of “closing eyes to rest them” and “removing CLs to relieve discomfort”) was then tested in 379 SCL wearers in a multicenter study with analysis stratified by opinion ratings at baseline and 2 weeks postrandomization to new silicone hydrogel SCLs. The sum of CLDEQ-8 scores (maximum 37) was correlated with opinion by Spearmans rank correlation coefficient and analyzed for change in opinion by analysis of variance (ANOVA). Results. The CLDEQ-8 scores in the validation sample were highly correlated with habitual baseline opinion (−0.44, p < 0.0001) and responsive to change in opinion postrandomization (−0.58, p < 0.0001). Baseline CLDEQ-8 scores by opinion status were as follows: Fair: 17.4 ± 8.7, Good 13.7 ± 6.4, Very Good 9.1 ± 4.7, and Excellent 6.4 ± 3.7 (ANOVA, F = 291.1, p < 0.0001). After 2 weeks, change in CLDEQ-8 scores by improvement status was as follows: Much Improved: −16.7 ± 10.0, Unchanged: −2.3 ± 5.0, to Much Worse +8.5 ± 5.8 (ANOVA, F = 16.5, p < 0.001). Conclusions. The CLDEQ-8 score significantly reflected baseline status and change in overall opinion after refitting with two types of silicone hydrogels. The CLDEQ-8 score is a valid outcome measure in SCL clinical trials to reflect opinion of SCLs.

Characteristics of corneal staining in hydrogel contact lens wearers

Corneal fluorescein staining is widely used in clinical practice and research, but little information exists on the distribution of staining in a large group of asymptomatic contact lens wearers. This cross-sectional study took place at 3 centers, and investigated the pattern of corneal fluorescein staining in both eyes of 98 hydrogel contact lens wearers. We also investigated the strategies used by three experienced clinicians to grade corneal staining. Overall corneal staining was graded using a scale from 0 to 4 in one-half steps, and five corneal zones, superior, inferior, nasal, temporal, and central, were also graded. The average overall staining grade for both eyes of our subjects was 0.50, with an average of 0.57 for the right eye and 0.44 for the left. This difference between the eyes was statistically significant (p = 0.011). In addition, a comparison of the zones within each eye showed a significant difference (p = 0.0001) among the zones. Corneal staining between the two eyes was also positively and significantly correlated (r = 0.58; p = 0.0001). Grading strategies among clinical investigators were significantly different (p = 0.0001), indicating a potential source of bias in multi-centered studies. The difference in corneal staining between the eyes may represent a source of systematic bias, and could be due to grading the right eye before the left. The correlation in corneal staining between the eyes indicates that the two eyes of a subject cannot serve as independent data points. One-third of the subjects who participated in this study had notable corneal staining. This finding underlines the importance of regularly checking corneal staining in clinical practice.