Two-Year Progression of Dry Eye Disease in Dry Eye Assessment and Management Study.

PURPOSE: The purpose of this study was to evaluate the progression of dry eye disease (DED) symptoms and signs over 2 years through a secondary analysis of data collected from the Dry Eye Assessment and Management study. METHODS: Participants who were assigned to omega-3 fatty acid in the first year were rerandomized in the second year to either continue with omega-3 fatty acid or switch to placebo. At baseline, 3, 6, 12, 18, and 24 months, DED symptoms were evaluated by using the Ocular Surface Disease Index and the Brief Ocular Discomfort Index (BODI). DED signs were assessed using conjunctival staining, corneal staining, tear break-up time, Schirmer testing, and keratography measures. Medication usage was documented at each visit. Because the treatment and placebo groups displayed no statistical differences in both signs and symptoms, data from the 43 participants were combined to assess longitudinal changes in symptoms and signs. RESULTS: At 3 months after omega-3 fatty acid treatment, there were significant improvements from baseline in Ocular Surface Disease Index and Brief Ocular Discomfort Index scores (all P ≤ 0.002) and less use of artificial tears or gel ( P = 0.02), but between 3 and 24 months, no significant changes in symptoms and treatments were observed ( P ≥ 0.06). Except for a significant improvement in conjunctival staining score over 2 years ( P = 0.001), there were no significant sign changes in corneal staining ( P = 0.32), tear break-up time ( P = 0.43), Schirmer test ( P = 0.09), and additional measures (all P ≥ 0.07). CONCLUSIONS: We did not observe a progression of DED signs or symptoms over a 2-year period, except for a probable placebo response in symptoms in the first 3 months and an improvement in conjunctival staining score.

A New Screening Questionnaire to Identify Patients With Dry Eye With a High Likelihood of Having Sjögren Syndrome.

PURPOSE: To develop a screening questionnaire to identify patients with dry eye with a high likelihood of having underlying Sjögren syndrome (SS). METHODS: This was a cross-sectional study of participants with dry eye complaints who were self-referred or referred by an ophthalmologist to the Sjögren's International Collaborative Clinical Alliance study. Symptoms and ocular surface examination findings were candidate predictors. Univariable and multivariable logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of a symptom and/or ocular sign with SS. Area under the receiver operating characteristic curve (AUC) was used to summarize the predictive ability of different regression models and the derived likelihood score. RESULTS: Four questions were statistically significant in the final multivariable model: 1) Is your mouth dry when eating a meal? [Yes = OR 1.63 (1.18-2.26)]; 2) Can you eat a cracker without drinking a fluid or liquid? [No = OR 1.46 (1.06-2.01)]; 3) How often do you have excessive tearing? [None of the time = OR 4.06 (1.81-9.10)]; and 4) Are you able to produce tears? [No = OR 2.24 (1.62-3.09)]. The SS likelihood score had an AUC of 0.70 (95% CI, 0.66-0.73), and when including tear break-up time and conjunctival staining, it yielded an AUC of 0.79 (95% CI, 0.77-0.82). CONCLUSIONS: This questionnaire can be used to identify patients with dry eye with a high likelihood of having SS. With future refinement and validation, this screening tool could be used alone or in combination with examination findings to identify patients with SS earlier, thereby facilitating better clinical outcomes.

Prevalence of Novel Candidate Sjögren Syndrome Autoantibodies in the Penn Sjögren's International Collaborative Clinical Alliance Cohort.

PURPOSE: To evaluate the prevalence of novel candidate autoantibodies associated with Sjögren syndrome (SS) and their ability to identify those with SS among participants with dry eye enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) study at the University of Pennsylvania (Penn). METHODS: All participants previously underwent a full ocular and systemic evaluation for possible SS as part of the SICCA study. An enzyme-linked immunosorbent assay was used to detect IgG, IgA, and IgM autoantibodies to salivary protein 1 (SP-1), parotid secretory protein (PSP), and carbonic anhydrase 6 from previously banked baseline serum samples from SICCA study participants enrolled at Penn. The prevalence rate of each autoantibody, calculated by considering the presence of any isotype as antibody positive, was compared between participants with dry eye with SS (n = 81) or without SS (n = 129) using the Fisher exact test. RESULTS: The prevalence of SP-1 IgM autoantibodies was higher in those with SS compared with those without SS (14% vs. 5%; P = 0.03). Similarly, the prevalence of PSP IgA autoantibodies was higher in those with SS compared with non-SS dry eye participants (21% vs. 11%; P = 0.048). There was no statistically significant difference in the prevalence of carbonic anhydrase 6 autoantibodies between those with or without SS (15% vs. 20%; P = 0.36). CONCLUSIONS: In the Penn SICCA cohort, SP-1 IgM and PSP IgA autoantibodies were more prevalent in the serum of SS-related dry eye participants compared with those without SS. Further longitudinal studies are needed to determine the clinical significance of these findings.

Prevalence of Novel Candidate Sjogren Syndrome Autoantibodies in the Dry Eye Assessment and Management (DREAM) Study.

PURPOSE: To evaluate the prevalence of novel candidate Sjogren syndrome (SS) autoantibodies [salivary protein-1 (SP-1), parotid secretory protein, carbonic anhydrase 6] in the DRy Eye Assessment and Management (DREAM) cohort, a study evaluating the effectiveness of omega-3 fatty acid supplements for the treatment of dry eye. METHODS: Participants underwent ocular surface examinations and serological testing for traditional and novel SS autoantibodies. Dry eye assessment and management participants were categorized into the following 3 groups: 1) no history of SS or other autoimmune diseases and negative traditional SS autoantibodies (n = 352); 2) no history of SS but a history of other autoimmune diseases (n = 66); and 3) those who met the 2012 American College of Rheumatology SS classification criteria (n = 52). RESULTS: Eleven percent had a history of SS, and 6% of those without a history of SS most likely had undiagnosed SS. The SS group had a higher prevalence of SP-1 autoantibodies than the group without SS or other autoimmune diseases (33% vs. 19%; P = 0.02) but had no difference in carbonic anhydrase 6 (P = 0.31) or parotid secretory protein autoantibodies (P = 0.33). Participants who were positive for the traditional autoantibodies alone or positive for both traditional and novel autoantibodies had the highest scores for corneal (P = 0.002) and conjunctival staining (P < 0.001). CONCLUSIONS: Data from this multicenter, prospective study demonstrated that one of the novel candidate autoantibodies, SP-1, is associated with underlying SS and that novel autoantibodies may be associated with worse ocular surface disease. Future longitudinal studies are needed to evaluate their utility in screening patients with dry eye for SS.

Survey of Ophthalmologists Regarding Practice Patterns for Dry Eye and Sjogren Syndrome.

OBJECTIVE: To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS) workup. METHODS: An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data. RESULTS: Four hundred seventy-four survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS workups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS. CONCLUSIONS: Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an underreferral of dry eye patients for SS workups, which is contributing to the continued underdiagnosis of the disease. Most respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.

Use of Crossed Polarizers to Enhance Images of the Eyelids.

PURPOSE: To describe imaging of the external eye with Crossed Polarizers to enhance clinically important features in digital photographs of the eyelids. METHODS: External photographs with and without crossed polarizing filters were taken of patients with blepharitis and controls with no clinical eye pathology. RESULTS: Photographing eyelid skin through Crossed Polarizers decreased reflections on the skin surface and improved visualization of eyelid telangiectasias and blood vessels in patients with a broad range of skin pigmentation and ethnicities. CONCLUSIONS: The use of Crossed Polarizers in imaging the external eye reduces reflections and glare from the eyelid skin and margins, thereby allowing for a more detailed evaluation of underlying structures and analysis of images. These findings suggest that including Crossed Polarizers in clinical photography has informative applications for assessing eyelid disease.

Assessment of signs of anterior blepharitis using standardized color photographs.

PURPOSE: To describe a standardized technique for acquiring and viewing photographic images of eyelids, assess the reproducibility and validity of a grading protocol for signs of anterior blepharitis, and to explore whether the signs depend on the eyelid or the area of the eyelid assessed. METHODS: Subjects with anterior blepharitis ranging from none to severe were examined by ophthalmologists at clinical sites. Digital images of the eyelids of subjects were acquired using a protocol that allowed for the calibration of color and luminance. Three ophthalmologists at a centralized reading center applied a novel protocol for grading features of anterior blepharitis from the digital images viewed on color-calibrated monitors. The agreement among graders was assessed using percent agreement and weighted kappa statistics (Kw), and the correlation of photographic and clinical gradings was assessed using Spearman correlation coefficients. RESULTS: Agreement among graders was excellent (Kw > 0.80) on the number of eyelid margin vessels and was substantial (Kw between 0.61 and 0.80) for erythema, collarettes, number of engorged vessels, and number of lashes. Grading of the photographic images and the clinical assessments of erythema and lid debris were moderately correlated (r = 0.27-0.45). The grades for different features depended on whether the upper or lower eyelid, eyelid skin or lid margin, and central or lateral lid were assessed. CONCLUSIONS: The application of a protocol to obtain and display calibrated digital images of eyelids supports the standardized assessment of anterior blepharitis in clinical care and research studies.