Improving awareness, identification, and management of meibomian gland dysfunction.

Ocular surface disorder--and dry eye, in particular--is a leading reason for visits to eye care professionals. It has been generally accepted that meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye, as well as being associated with aqueous-deficient dry eye. Yet, researchers and clinicians have lacked a global consensus on the definition of MGD, its epidemiology, pathophysiology, and management. Various systemic diseases and medications have been associated with the progression of both dry eye and MGD, as have several ocular disorders beyond those directly affecting the surface. It is in the best interest of patients for clinicians to be able to better identify and diagnose MGD, differentiating it from other ocular surface disorders, and to recognize the effects of MGD on the ocular surface, and thus initiate appropriate therapy. This CME activity provides expert insight into the Tear Film and Ocular Surface Society's International Workshop on MGD consensus report, offering practical application of its findings to better manage MGD patient care, particularly for those patients facing or undergoing ocular surgery.

The effect of time on grading corneal fluorescein and conjunctival lissamine green staining.

PURPOSE: To explore the effect of time on grading corneal fluorescein and conjunctival lissamine green staining in dry eye disease (DED). METHODS: Photographs of 68 subjects with non-Sjogren's DED (nSS DED) and 32 with Sjogren's DED (SS DED) were taken of corneal fluorescein staining, then conjunctival lissamine green staining every 30 s for at least 5 min. Photographs of one randomly selected eye were then randomly ordered and graded on a scale from 0 to 5 (severe staining) by two clinicians, masked to both site and subject. The average time required to reach the maximum grade of staining (Gmax) was calculated. RESULTS: The median time (upper and lower quartiles) to corneal fluorescein Gmax was 2.6 (1.3-5.3) minutes for nSS DED and 3.8 (2.6-5.4) minutes for SS DED, a statistically significant difference (Mann Whitney U test, p = 0.018). In contrast, the median time to the Gmax for lissamine green staining of the nasal and temporal conjunctiva was 0.5 (0.5-1.1 nasal, 0.5-0.8 temporal) minutes for nSS DED and 0.5 (0.5-0.8 nasal, 0.5-0.5 temporal) minutes for SS DED subjects, which was not statistically significant (p ≥ 0.383). CONCLUSIONS: The time required to reach the maximum grade of corneal fluorescein staining, but not conjunctival lissamine green staining, varied widely and was significantly longer in subjects with Sjögren's Syndrome. Early observation of corneal fluorescein staining can lead to under-grading, which may impact the diagnosis and assessment of treatment in DED. Further study of the best time to assess corneal fluorescein staining in various DED populations is warranted.

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.

Perspective on Systematic Medical Literature Reviews and Meta-Analyses.

PURPOSE: This study sought to identify factors contributing to the inadequacies of systematic reviews and meta-analyses (SRMAs) published in the ophthalmology literature. DESIGN: Perspective. METHODS: Review and synthesis of selective literature, with interpretation and perspective. RESULTS: Although recommendations for the design, conduct, assessment of quality, and risk of bias of systematic reviews have been widely available, some recent publications illustrate a serious potential failing in this domain: inclusion of refuted science, lack of citation of post-publication correspondence and failure to use ≥1 alternative search strategy. CONCLUSIONS: Examples of inadequacies of peer review in medical literature and perpetuation of erroneous science by unfiltered inclusion in subsequent systematic reviews have been identified, and the problem can be traced to authors, peer reviewers, and editors of journals. This perspective identifies and analyzes several possible causes of the problem and recommends some specific corrective actions to improve the quality and accuracy of such reviews.

Review and analysis of grading scales for ocular surface staining.

Vital dye staining has been used for over a century to assess the severity of ocular surface disease. However, despite common usage, a universally accepted "gold standard" grading scale does not exist for corneal and conjunctival staining, which can impact the ability to diagnose and monitor ocular surface conditions such as dry eye. The Food and Drug Administration (FDA) and other international regulatory agencies rely on ocular surface staining as a primary endpoint for new drug approvals, so that absence of a "gold standard" scale may affect approval of new drug treatments. To begin to address this problem, we review existing, published grading scales in an integrated fashion, highlighting their differences and similarities to emphasize common themes and the methods and elements that are important in creating a standardized scale. Our goal is to aid the field in moving towards an accepted standardized grading scale for ocular surface staining that can be applied in clinic and research settings for a variety of ocular conditions.

Development and validation of a short global dry eye symptom index.

ABSTRACT we have developed and evaluated the repeatability of a short questionnaire based on a visual analog scale (VAS) to quantify the frequency and severity of symptoms of dry eye syndrome (DES). The "Symptom Assessment iN Dry Eye" (SANDE) questionnaire utilizes a 100 mm horizontal VAS technique to quantify patient symptoms of ocular dryness and/or irritation. Fifty-two subjects with DES were prospectively enrolled and followed-up at 2 and 4 months with repeated administrations of the SANDE questionnaire and clinical ocular surface evaluation. Subjects demonstrated a wide range of symptom scores indicative of the variability of the disease. Analyses comparing the repeatability of SANDE scores from baseline to the 2-month follow-up indicated a significant downward regression of scores toward the mean. In contrast, repeatability measures were consistently good for questionnaires administered within a few days of one another (ICC ranging from 0.53 to 0.76). Bland-Altman analysis demonstrated that 50% of repeated SANDE symptom scores were within 10 mm of each other, 80% were within 20 mm, and 95% were within less than 30 mm. These data describe good repeatability for the SANDE symptom score when repeated assessments are made within a few days. The results are encouraging and suggest that further refinement and testing of the SANDE questionnaire in larger populations may result in a reliable questionnaire to detect change in irritative symptoms over time.

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.

TFOS DEWS II Report Executive Summary.

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Secretoglobins: sexually dimorphic expression of androgen-binding protein mRNA in mouse lacrimal glands.

PURPOSE: This study was conducted to seek sex differences in mRNA expression in normal mouse lacrimal glands. Gene expression differences in the lacrimal gland may contribute to susceptibility to lacrimal gland or ocular surface disease. METHODS: A differential display analysis was performed on poly(A)+ RNA isolated from male and female Swiss Webster mouse exorbital lacrimal glands. Four potential gender-specific products were subcloned and sequenced. Full-length cDNAs of each product were obtained using RACE-PCR. 32P-labeled fragments of each clone were hybridized to a blot of male and female mouse poly(A)+ RNA isolated from harderian, lacrimal, submandibular, sublingual, and parotid glands and the liver. RESULTS: GenBank database alignments indicated that the four clones were members of the secretoglobin family. The most closely related sequences were the mouse salivary androgen-binding protein (ABP) subunits alpha, beta, and gamma. We named the four lacrimal clones the delta, epsilon, zeta, and eta subunits of ABP. Northern blot analysis showed that mRNAs for each of these four ABP subunits were lacrimal-gland-specific. The delta and zeta subunits of ABP were expressed primarily in male mouse lacrimal gland. CONCLUSIONS: Sequence attributes predict that the ABP subunits expressed in lacrimal glands comprise proteins that are secreted in tears. These data imply compositional differences in ABPs secreted by mouse lacrimal and submandibular glands, and in ABPs secreted by male and female mouse lacrimal glands.

The relative burden of dry eye in patients' lives: comparisons to a U.S. normative sample.

PURPOSE: To assess the relative burden of dry eye in daily life by comparing Short Form-36 (SF-36) responses from individuals with and without dry eye against U.S. norms. METHODS: Assessment of 210 people, 130 with non-Sjogren's keratoconjunctivitis sicca (non-SS KCS), 32 with Sjogren's Syndrome (SS), and 48 control subjects. The study population data and published normative SF-36 data were compared. Dry eye severity was assessed by recruited severity (control, non-SS KCS, SS), patient self-report (none, very mild/mild, moderate, severe/extremely severe), and clinician-report (none, mild, moderate, severe). Age- and gender-matched norms were compared with all defined severity groups. RESULTS: Compared with the norms, control subjects scored higher on all SF-36 scales. Effect size (ES) ranged from 0.15 to 0.52. Non-SS KCS patients had lower Role-Physical (ES=-0.07), Bodily Pain (ES=-0.08), and Vitality (ES=-0.11) scores, indicating more dry eye impact on those areas versus the norm. All SF-36 scale scores except Mental Health (ES=0.12) were lower in the SS group than the adjusted norm (ES range: -0.16 to -0.99). Regardless of severity classification, mild patients consistently had lower Role-Physical and Bodily Pain scores than the norm, suggesting impact on daily roles (ES < 0.2). Patients with moderately severe disease also experienced less vitality and poorer general health. The group with severe disease scored lower than the norm across all domains (ES range: -0.14 to -0.91) except Role-Emotional (ES=0.13) and Mental Health (ES=0.23). CONCLUSIONS: These results indicate dry eye's negative impact on everyday life, particularly in daily activities. Further research using disease-specific measures to examine dry eye's impact is underway.

Clinical guidelines for management of dry eye associated with Sjögren disease.

PURPOSE: To provide a consensus clinical guideline for management of dry eye disease associated with Sjögren disease by evaluating published treatments and recommending management options. DESIGN: Consensus panel evaluation of reported treatments for dry eye disease. METHODS: Using the 2007 Report of the International Workshop on Dry Eye (DEWS) as a starting point, a panel of eye care providers and consultants evaluated peer-reviewed publications and developed recommendations for evaluation and management of dry eye disease associated with Sjögren disease. Publications were graded according to the American Academy of Ophthalmology Preferred Practice Pattern guidelines for level of evidence. Strength of recommendation was according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: The recommendations of the panel are briefly summarized herein. Evaluation should include symptoms of both discomfort and visual disturbance as well as determination of the relative contribution of aqueous production deficiency and evaporative loss of tear volume. Objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage should be used to stage severity of dry eye disease to assist in selecting appropriate treatment options. Patient education with regard to the nature of the problem, aggravating factors, and goals of treatment is critical to successful management. Tear supplementation and stabilization, control of inflammation of the lacrimal glands and ocular surface, and possible stimulation of tear production are treatment options that are used according to the character and severity of dry eye disease. SUMMARY: Management guidelines for dry eye associated with Sjögren's disease are presented.

mRNA encoding a new lipolytic enzyme expressed in rabbit lacrimal glands.

PURPOSE: In previous work, lacrimal glands of female mice were shown to express an mRNA encoding pancreatic lipase-related protein 1 (PLRP1), a member of the triacylglycerol lipase family. To investigate the hypothesis that lacrimal glands express mRNAs encoding other lipolytic enzymes, the present study was conducted to look for triacylglycerol lipase-related mRNAs in the lacrimal glands of rabbits. METHODS: Degenerate polymerase chain reaction (PCR) primers were designed based on two conserved amino acid motifs, RITGLD, and DI/(F)Y/(F)PNGG, in the triacylglycerol lipase family. Lacrimal gland cDNAs were amplified, and the expected 200-bp products were subcloned and sequenced. One product encoded a new lipase-related sequence, which was termed lacrimal lipase (LL). The complete cDNA sequence of rabbit LL was determined, and labeled LL cDNA was used to probe RNA blots of several rabbit tissues and a genomic DNA blot. RESULTS: BLAST database searches indicated that the predicted amino acid sequence of LL is related to phosphatidylserine phospholipase A(1) (PS-PLA1) and to members of the triacylglycerol lipase family. Labeled LL cDNA hybridized to a 2.1-kb message in RNA blots of rabbit lacrimal gland, harderian gland, heart, liver, and pancreas. These blots demonstrated no gender-based differential expression in rabbit lacrimal or harderian glands. Hybridization of labeled LL cDNA to a genomic DNA blot suggested that LL was a single-copy gene. CONCLUSIONS: Male and female rabbit lacrimal glands expressed an mRNA encoding LL, a new predicted member of the triacylglycerol lipase family.