Jason J. Nichols

The lack of association between signs and symptoms in patients with dry eye disease

Background: The purpose of this report was to examine the relation between clinical tests and dry eye symptoms in patients with dry eye disease. Methods: Seventy-five patients with dry eye disease (ICD-9 code 375.15) were included in these analyses. There was no specific entry criterion for enrollment in addition to a previous dry eye diagnosis in this clinic-based sample. Patients represented varying types and severity of dry eye disease and were previously diagnosed by clinic attending doctors in this university clinic setting. The study examination included a symptom interview that assessed dryness, grittiness, soreness, redness, and ocular fatigue. The interview was followed by a clinical dry eye examination conducted in the following sequence: meibomian gland assessment, tear meniscus height, tear breakup time test, fluorescein staining, the phenol red thread test, Schirmer test, and rose bengal staining. Partial Spearman correlation coefficients, the Wilcoxon rank sum test, χ2 test, and multivariate logistic regression were used to evaluate the relationship between dry eye tests and symptoms. Results: Symptoms were generally not associated with clinical signs in patients with dry eye disease. There were no significant correlations between signs and symptoms after adjustment for age and artificial tear use. The rank of each clinical test result did not statistically differ when stratified by the presence of patient symptoms in Wilcoxon rank sum analyses. Likewise, the frequency of patient symptoms did not differ statistically when stratified by a positive clinical test result in χ2 analyses. In multivariate logistic regression analyses, no clinical test significantly predicted frequently reported symptoms after adjustment for age and artificial tear use. Conclusions: These results suggest a poor relation between dry eye tests and symptoms, which represents a quandary in dry eye clinical research and practice.

The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD

Scientists have been interested in studying the secretions of the meibomian glands for many years, 1– 8 and diseases associated with the meibomian glands (e.g., cancers, posterior blepharitis) have been noted in the medical literature since at least the early part of the 20th Century. 9 –13 However, the term “meibomian gland dysfunction” (MGD) was only introduced by Korb and Henriquez in 1980. 14 The terminology “meibomian gland disease” was later introduced by Bron et al. 15 as an umbrella term to indicate any disease affecting the meibomian glands (see Definition and Classification). Although the etiology of MGD may differ from that of aqueous-deficient dry eye disease (which is due to insufficient lacrimal gland production), the two conditions share many clinical features, including symptoms of ocular surface irritation and visual fluctuation, altered tear film stability, and potential ocular surface compromise. When MGD is of sufficient degree, it may give rise to the second major subtype of dry eye disease, evaporative dry eye. 16 These subtypes are not mutually exclusive, as has been acknowledged. 16

Frequency of and factors associated with contact lens dissatisfaction and discontinuation.

Purpose: To determine the frequency of and factors associated with contact lens dissatisfaction and discontinuation. Methods: A cross-sectional survey of 730 subjects was conducted using a self-administered survey instrument. The survey collected information about present age and sex, history of contact lens wear, types of lenses worn, age at starting wear, current wearing schedule (hours per day, days per week), self-perceived contact lens satisfaction, and contact lens-related problems. A variety of statistical analyses including analysis of variance, logistic regression, and repeated-measures logistic regression were used to model the data. Results: Current or previous experience with contact lenses was reported by 453 (62%) of the subjects. Of these subjects, 119 (26.3%) reported that contact lenses were not the ideal form of visual correction for them (contact lens dissatisfaction) and another 109 (24.1%) had permanently discontinued contact lens wear. Dissatisfied contact lens wearers had reduced self-reported wearing times compared with satisfied contact lens wearers. Previous lens wearers were more likely than current lens wearers to be men, older (by ∼9.5 years), have started contact lens wear at a later age (∼4-5 years later), and have tried either rigid or both soft and rigid lenses. The primary self-reported reason for both contact lens dissatisfaction and discontinuation was ocular symptoms (dryness and discomfort), followed by preference for another corrective modality. Conclusion: A significant number of contact lens wearers are not satisfied with contact lenses and are at risk for discontinuation.

Frequency of dry eye diagnostic test procedures used in various modes of ophthalmic practice.

Purpose. There are many suggested dry eye diagnostic test batteries in the literature. However, clinicians use a wide variety of dry eye diagnostic tests in clinical practice due to a number of factors, including time constraints. In addition, there has been no systematic description of the standard of care in diagnosing dry eye in the literature. The purpose of this study is to determine the type and frequency of dry eye diagnostic tests used in various modes of ophthalmic practice across a spectrum of dry eye severity. Methods. A total of 467 patient charts (patients with a previous dry eye diagnosis) were reviewed retrospectively to determine diagnostic test frequency. In reviewing patient charts, the following tests were identified as performed or not performed: symptom assessment, fluorescein staining, tear break-up time (TBUT), Schirmer test, rose bengal staining, and “tear assessment” (including quantity and quality of the tear meniscus). Results. Dry eye diagnostic tests were used in the following frequencies across all modes of practice: symptom assessment (82.8%), fluorescein staining (55.5%), TBUT (40.7%), tear assessment (22.2%), Schirmer test (8.5%), and rose bengal staining (4.9%). When the clinics are pooled, two test procedures were used with the highest frequency (38.9%). The most commonly performed two-test procedure combination was a symptom assessment combined with fluorescein staining of the cornea (43.7%). Conclusions. Symptom assessment plays a large role in the diagnosis of dry eye. The current clinical standard of care for dry eye diagnosis includes the performance of at least one test procedure in addition to a symptom assessment.

Evaluation of tear film interference patterns and measures of tear break-up time.

Purpose. The purpose of this study was to compare the agreement within and between examiners when evaluating real-time and digital photographs of TearScope Plus tear film interference patterns. We also evaluated between-examiner agreement of noninvasive digital tear break-up time (NITBUT) using the TearScope, the relation between NITBUT and tear film interference patterns, and the relation between NITBUT and tear break-up time (TBUT). Methods. Forty nondry eye patients were seen for digital imaging of the tear film using the TearScope Plus mounted on a slit-lamp with the EyeCap Ophthalmic Image Capture System. Two independent examiners first assessed the tear interference pattern in real-time and then captured the patterns and NITBUT digitally for a period of approximately 60 s. Each image series was later graded for interference pattern and NITBUT by the two independent, masked examiners. Results. Within-examiner comparisons of real-time and digital tear pattern photograph grading showed moderate to substantial agreement for experienced examiners (kappa for examiner 1 = 0.76 and kappa for examiner 2 = 0.55). Between-examiner agreement when grading tear patterns was also substantial in real-time (kappa = 0.72) and moderate when using digital photography (kappa = 0.59). The between-examiner mean NITBUT was 11.2 ± 6.8 s and the 95% limits of agreement between examiners were −19.2 to +9.2 s. The mean TBUT was 7.6 ± 10.4 s, and it was on average 3.7 ± 12.0 s shorter than NITBUT (p = 0.06). Thicker tear film interference patterns graded photographically were associated with longer NITBUTs for both examiners (p = 0.001). Conclusions. There is moderate to substantial within- and between-examiner agreement when comparing real-time and digital tear interference patterns photographs when using the TearScope. Although there is considerable between-examiner variability with the NITBUT test, the thicker lipid layer tear patterns tend to be associated with longer NITBUTs.

Between-Eye Asymmetry in Keratoconus

Purpose. To report baseline differences between eyes on key variables in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort compared with a retrospectively assembled group of myopic contact lens wearers without ocular disease. Methods. A total of 1,079 keratoconus patients who had not undergone a penetrating keratoplasty in either eye before their baseline visit were enrolled and examined at baseline. Records from 330 contact lens-wearing myopes were reviewed. Corneal curvature (keratometry), visual acuity, refractive error (manifest refraction), and corneal scarring were measured. Results. The mean differences between keratoconic eyes are as follows (better eye–worse eye for each variable, separately). Flat keratometry: −3.59 ±4.46 D and steep keratometry: −4.35 ±4.41 D; high-contrast best-corrected visual acuity: 7.30 ±6.83 letters; low-contrast best-corrected visual acuity: 8.53 ±7.51 letters; high-contrast entrance visual acuity: 9.03 ±8.40 letters; low-contrast entrance visual acuity: 9.43 ±7.88 letters; spherical equivalent refractive error: 3.15 ±3.84 D; and refractive cylinder power 1.55 ±1.42 D. Twenty-one percent of the keratoconus patients had corneal scarring in only one eye. There is an association between patient-reported unilateral eye rubbing and greater asymmetry in corneal curvature, and between a history of unilateral eye trauma and greater asymmetry in corneal curvature and refractive error, with the rubbed/traumatized eye being the steeper eye most of the time. Conclusions. Keratoconus is asymmetric in the CLEK Study sample.

Application of a novel interferometric method to investigate the relation between lipid layer thickness and tear film thinning.

PURPOSE The lipid layer of the tear film forms a barrier to evaporation. Evaporation is a major cause of tear thinning between blinks and tear breakup. The purpose of this study was to investigate the relation between tear film thinning and lipid layer thickness before and after instillation of an emulsion eye drop. METHODS Fifty non-contact lens wearers were studied. Spectral interferometry was used to measure the thinning rate of the precorneal tear film for up to 19 seconds after a blink. Simultaneously, lipid layer thickness was measured based on an absolute reflectance spectrum. After a 2-minute recovery, the measurement was repeated. A drop of the lipid emulsion was then instilled; 15 minutes later, two interferometry measurements were performed similarly. RESULTS A histogram of thinning rates was fitted by a bimodal distribution with narrow and broad peaks corresponding to slow and rapid thinning, respectively. The correlation between repeated thinning rate measurements was modest, but repeatability was considerably more significant when analyzed in terms of the slow/rapid dichotomy. Similarly, the correlation between thinning rate and lipid thickness was modest but was more evident when analyzed in terms of the slow/rapid dichotomy. Instillation of an emulsion eye drop significantly increased the thickness of the lipid layer but did not significantly alter the thinning rate. CONCLUSIONS The proposed slow/rapid dichotomy of thinning rates presumably relates to a good/poor barrier to evaporation of the lipid layer. The imperfect correlation between thinning rate and lipid thickness indicates that other factors, such as the composition and structure of the lipid layer, are important (e.g., sufficient polar lipids may be needed to form good interface between nonpolar lipids and the aqueous layer).

The Contribution of Lipid Layer Movement to Tear Film Thinning and Breakup

PURPOSE To investigate whether the tear film thinning between blinks is caused by evaporation or by tangential flow of the tear film along the surface of the cornea. Tangential flow was studied by measuring the movement of the lipid layer. METHODS Four video recordings of the lipid layer of the tear film were made from 16 normal subjects, with the subjects keeping their eyes open for up to 30 seconds after a blink. To assess vertical and horizontal stretching of the lipid layer and underlying aqueous layer, lipid movement was analyzed at five positions, a middle position 1 mm below the corneal center, and four positions respectively 1 mm above, below, nasal, and temporal to this middle position. In addition, in 13 subjects, the thinning of the tear film after a blink was measured. RESULTS The total upward movement could be fitted by the sum of an exponential decay plus a slow steady drift; this drift was upward in 14 of 16 subjects (P = 0.002). Areas of thick lipid were seen to expand causing upward or downward drift or horizontal movement. The velocity of the initial rapid upward movement and the time constant of upward movement were found to correlate significantly with tear film thickness but not with tear-thinning rate. CONCLUSIONS Analysis indicated that the observed movement of the lipid layer was too slow to explain the observed thinning rate of the tear film. In the Appendix, it is shown that flow under a stationary lipid layer cannot explain the observed thinning rate. It is concluded that most of the observed tear thinning between blinks is due to evaporation.

Contributions of evaporation and other mechanisms to tear film thinning and break-up.

Purpose. To evaluate the contribution of three mechanisms—evaporation of the tear film, inward flow of water into the corneal epithelium or contact lens, and “tangential flow” along the surface of epithelium or contact lens—to the thinning of the tear film between blinks and to tear film break-up. In addition to a discussion of relevant studies, some previously unpublished images are presented illustrating aspects of tear film break-up. Contributions of Three Mechanisms to Tear Film Break-Up. Inward flow of water into the epithelium or contact lens is probably unimportant, and a small flow in the opposite direction may actually occur. Tangential flow is probably important in certain special cases of tear film break-up—at the black line near the tear meniscus, over surface elevations, after partial blinks, and from small thick lipid spots in the tear film. In all these special cases it is argued that tangential flow is important initially, but evaporation may be needed for final thinning to break-up. It is argued that most of the observed tear film thinning between blinks is due to evaporation, rather than tangential flow, and that large “pool” break-up regions are the result of evaporation over an extended area. Conclusion. Evaporation in our “free-air” conditions may be four to five times faster than the average of the values reported in the literature when air currents are prevented by preocular chambers. However, recent evaporation measurements using “ventilated chambers” give higher values, which may correspond better to free-air conditions. Thus evaporation may be fast enough to explain many cases of tear film break-up, and to give rise to considerable increases in the local osmolarity of the tear film between blinks.

TFOS DEWS II Definition and Classification Report

The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research.