Kelly K. 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 Repeatability of Clinical Measurements of Dry Eye

Purpose: The repeatability of individual dry eye diagnostic tests has been reported in the literature on normal samples of patients and to a lesser degree in dry eye patients. In this study, the repeatability of a battery of clinical diagnostic tests for dry eye was assessed on mild to moderate dry eye patients. Methods: A dry eye examination was performed on 75 patients on two occasions by a single examiner. The battery of dry eye tests included symptom assessment, contact lens and medical history, slit-lamp biomicroscopic evaluation of the eyelids, evaluation of Meibomian glands, assessment of tear film quality, tear meniscus height, assessment of blink quality, fluorescein tear breakup time (TBUT), fluorescein and rose bengal staining of the cornea and conjunctiva, phenol red thread test, and Schirmer test. Results: The repeatability of subjective report of dryness (κw = 0.62) and grittiness (κw = 0.73) was moderate to high. In contrast, the repeatability of Meibomian gland disease classification (κw = 0.20), presence or absence of inferior corneal fluorescein staining (κ = 0.25), and inferior conjunctival rose bengal staining (κ = 0.21) was poor. When a summed staining score of corneal and conjunctival regions was evaluated, weighted κ reliability was fair. The repeatability of tear breakup time was substantial [95% limits of agreement −5.71 to 5.83 seconds; intraclass coefficient coefficient (ICC) 0.65], and improved when the two timed readings were averaged. Repeatability of the Schirmer test is more variable as wetting scores increase. When the average Schirmer scores ≤10 mm were evaluated, moderate repeatability was demonstrated, indicating that the test performs better with more advanced disease. Conclusion: Although patient-reported symptoms are moderately repeatable from visit to visit, many of the procedures clinically used to diagnose and monitor dry eye syndromes are largely unrepeatable.

The International Workshop on Meibomian Gland Dysfunction: Executive Summary

DOI:10.1167/iovs.10-6997a Investigative Ophthalmology & Visual Science, Special Issue 2011, Vol. 52, No. 4 Copyright 2011 The Association for Research in Vision and Ophthalmology, Inc. 1922 ドライアイ疾患の原因としては、マイボーム腺機能不全 (MGD)がおそらく最も多い。この疾患によって数百万人 もの健康と幸福が損なわれているにもかかわらず、MGD の定 義、分類、診断、治療について世界的なコンセンサスはない。 そうしたコンセンサスに達する目的で、非営利団体である Tear Film and Ocular Surface Society( TFOS; http://www. tearfilm.org)が International Workshop on Meibomian Gland Dysfunction(国際マイボーム腺機能不全ワークショップ、 www.tearfilm.org/mgdworkshop/index.html)を起ち上げた。こ のワークショップの目的は以下の通りである:

An objective approach to dry eye disease severity.

PURPOSE A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity. METHODS Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated. RESULTS Osmolarity was found to have the highest correlation coefficient to disease severity (r(2) = 0.55), followed by conjunctival staining (r(2) = 0.47), corneal staining (r(2) = 0.43), OSDI (r(2) = 0.41), meibomian score (r(2) = 0.37), TBUT (r(2) = 0.30), and Schirmer result (r(2) = 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds. CONCLUSIONS Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.).

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.

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction

The goals of the subcommittee were to review the current practice and published evidence of medical and surgical treatment options for meibomian gland dysfunction (MGD) and to identify areas with conflicting, or lack of, evidence, observations, concepts, or even mechanisms where further research is required. To achieve these goals, a comprehensive review of clinical textbooks and the scientific literature was performed and the quality of published evidence graded according to an agreed on standard, using objective criteria for clinical and basic research studies adapted from the American Academy of Ophthalmology Practice Guidelines1 (Table 1). It should be noted that, in many of the clinical textbooks and previous reports, terminology is often interchanged and the management of anterior and posterior blepharitis and/or meibomitis is often considered concurrently. Thus, a broad scope of documents was reviewed in this process. Consistency in terminology and global adoption of the term “meibomian gland dysfunction” would significantly aid clinical research and clinical care in MGD going forward. Table 1. Grading Level of Evidence of Clinical and Basic Research Studies1

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.

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

Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications

Purpose:  To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic‐based population.

Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye.

Purpose: To investigate the safety and efficacy of diquafosol tetrasodium, a P2Y2 receptor agonist that stimulates fluid and mucin secretion on the ocular surface, as a novel topical treatment of dry eye disease. Methods: Subjects with dry eye (n = 527) were evaluated in a randomized, double-masked, parallel-group trial comparing 24 weeks of treatment with 2 concentrations of diquafosol (1% and 2%) versus placebo instilled 4 times daily. Corneal staining, conjunctival staining, Schirmer tests, and subjective symptoms of dry eye were evaluated. Use of artificial tears was permitted as necessary. Results: Subjects treated with 2% diquafosol had significantly lower corneal staining scores compared with placebo at the 6-week, primary efficacy time point (P < 0.001), and superiority continued throughout the 24-week study. Reductions in corneal staining were observed as early as after 2 weeks of treatment, were maintained throughout the 24-week study, and were observed to worsen slightly (toward baseline) when diquafosol treatment was discontinued (week 25). Results for conjunctival staining were consistent with those observed for corneal staining. Schirmer scores at week 6 were significantly higher with diquafosol treatment than with placebo (P \H 0.030). The percentage of subjects with clearing of foreign body sensation (score of 0) was higher at week 6 in subjects treated with 2% diquafosol (21%) compared with placebo (15%), but the difference did not achieve significance (P = 0.193). Significant differences in favor of diquafosol were observed for clearing of foreign body sensation and for worst symptom in secondary data analyses. Conclusion: Diquafosol tetrasodium was well tolerated and was superior to placebo (vehicle) in reducing corneal staining and in relieving certain patient symptoms. Diquafosol has a favorable risk/benefit profile in a broad spectrum of patients with dry eye disease and is a novel topical treatment of dry eye.