Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance. CONCLUSIONS: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Static Perimetry in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) Study: Assessment Through 2 Years.

PURPOSE: To evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa. DESIGN: Prospective, observational cohort study. METHODS: A total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America. SP, BCVA, full-field stimulus thresholds, spectral domain optical coherence tomography macular scans, and fundus-guided mesopic microperimetry were performed at baseline and annually. The main outcome measures were total hill of vision (VTOT), hill of vision in the central 30° (V30), VTOT minus V30 (VPERIPH), and mean sensitivity. RESULTS: The average decline (95% CI) was 2.05 (1.40, 2.70) decibel-steradian (dB-sr)/y for VTOT, 0.48 (0.32, 0.65) dB-sr/y for V30, 1.53 (0.97, 2.08) dB-sr/y for VPERIPH, and 0.55 (0.40, 0.71) dB/y for mean sensitivity. Average percentage decline per year was 8.3 (5.5, 11.1) for VTOT, 5.2 (3.0, 7.4) for V30, 16.0 (9.5, 22.0) for VPERIPH, and 5.1 (3.5, 6.7) for mean sensitivity. Changes from baseline to year 2 in all SP measures were highly correlated (r's ranging from 0.52 [V30 vs VPERIPH] to 0.98 [VTOT vs VPERIPH]). CONCLUSIONS: Quantitative measures of SP declined significantly over 2 years in USH2A-related retinal degeneration. The annual percentage rate of change was greatest for VTOT and VPERIPH, whereas V30 and mean sensitivity changed least, reflecting earlier and more severe peripheral degeneration compared with central loss.

Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study.

PURPOSE: To describe tear concentrations of IL-1ß, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. METHODS: Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer's test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). RESULTS: Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= -0.24, p = 0.006), IL-10 (r= -0.25, p = 0.005) and IFNγ (r= -0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= -0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). CONCLUSIONS: Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED.

Association of Tear Osmolarity With Signs and Symptoms of Dry Eye Disease in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: To determine the relationships of (1) tear osmolarity (TO) levels with the severity of signs and symptoms of dry eye disease (DED) and (2) changes in TO with changes in signs and symptoms. Methods: Patients (N = 405) with moderate to severe DED in the Dry Eye Assessment and Management (DREAM) Study were evaluated at baseline and at six and 12 months. Associations of TO with signs and symptoms were evaluated using Pearson correlation coefficient (r) and regression models. Results: The mean (standard deviation [SD]) TO was 303 (16) mOsm/L at baseline and 303 (18) mOsm/L at both six and 12 months. TO was higher in older patients (306 mOsm/L for ≥70 years vs. 300 mOsm/L for <50 years; P = 0.01) and those with Sjögren's disease (311 vs. 302 mOsm/L; P < 0.0001). TO did not differ between patients randomized to placebo and omega-3 fatty acid supplementation. TO was weakly correlated with conjunctival (r = 0.18; P < 0.001) and corneal staining scores (r = 0.17; P < 0.001), tear film break-up time (r = 0.06; P = 0.03), and Schirmer test score (r = -0.07; P = 0.02) but not with Ocular Surface Disease Index scores (r = 0.03; P = 0.40). Changes in signs and were not significantly correlated with change in TO at six or 12 months. Conclusions: Within DREAM, TO was weakly correlated with DED signs, explaining <5% variability in signs. Changes in tear osmolarity were not associated with changes in signs and symptoms of DED, indicating that the association may not be causal.

Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment.

PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤ 20/50 (n = 376), and 5.8 (6.6) letters in eyes with clinical VA ≥ 20/40 (n = 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P = 0.06). CONCLUSIONS: On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study.

OBJECTIVES: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study. METHODS: Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines). RESULTS: No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (-36.6 vs. 24.5%, P =0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P =0.02, n=68); at 12 months, they did not differ ( P ≥0.18). No other differences between the treatment groups were detected. CONCLUSIONS: ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

Correlation of Measures From the OCULUS Keratograph and Clinical Assessments of Dry Eye Disease in the Dry Eye Assessment and Management Study.

PURPOSE: The purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease. METHODS: Participants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (r s ); 95% confidence intervals (95% CI) accounted for intereye correlation. RESULTS: Among 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation r s = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (r s = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (r s = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (r s from -0.07 to 0.05). CONCLUSIONS: In the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

Association of Severity of Dry Eye Disease with Work Productivity and Activity Impairment in the Dry Eye Assessment and Management Study.

PURPOSE: To evaluate the association of dry eye disease (DED) severity with work productivity and activity impairment. DESIGN: Longitudinal, observational study within a randomized clinical trial. PARTICIPANTS: People with moderate to severe DED who enrolled in the multicenter Dry Eye Assessment and Management (DREAM) study. METHODS: Participants completed the Work Productivity and Activity Impairment questionnaire at 0, 6, and 12 months and were assessed in parallel for symptoms and signs (conjunctival and corneal staining, tear film break-up time [TBUT], and Schirmer test) of DED. Associations of work productivity and activity impairment with symptom and signs were evaluated with linear regression models using generalized estimating equations and controlling for demographics and comorbidities. MAIN OUTCOME MEASURES: Work productivity (employment, absenteeism, presenteeism, overall work impairment) and activity impairment. RESULTS: Among 535 participants at baseline, 279 (52%) were employed, and mean activity impairment was 24.5%. Among those employed, the mean score was 2% for absenteeism, 18% for presenteeism, and 19.6% for overall work impairment. Higher Ocular Surface Disease Index (OSDI) symptom scores were associated with greater absenteeism, presenteeism, and activity impairment. Overall work impairment and activity impairment were greater by 4.3% and 4.8%, respectively, per 10-unit difference in OSDI score (P < 0.001). Longitudinal increases (worsening) in OSDI scores were associated with increasing impairment in work and non-work-related activity: 2.0% and 3.1% per 10 units in OSDI, respectively (P < 0.01). Worse corneal staining and TBUT were associated with higher overall work impairment and activity level (P ≤ 0.04). However, longitudinal changes in these two signs were not associated with changes in work productivity or activity impairment. CONCLUSIONS: Worse symptoms of DED are associated with decreased work productivity and activity level, both cross-sectionally (interindividually) and longitudinally within person (intraindividually). Corneal staining and TBUT are associated with interindividual differences but not intraindividual changes in work productivity and activity impairment.

Associations Between Systemic Omega-3 Fatty Acid Levels With Moderate-to-Severe Dry Eye Disease Signs and Symptoms at Baseline in the Dry Eye Assessment and Management Study.

PURPOSE: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study. METHODS: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated. RESULTS: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3. CONCLUSION: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.

Ocular Discomfort and Quality of Life Among Patients in the Dry Eye Assessment and Management Study.

PURPOSE: To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED). METHODS: This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine). RESULTS: The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)]. CONCLUSIONS: Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.

Association of meibomian gland morphology with symptoms and signs of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

PURPOSE: To describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology. METHODS: Cross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex. RESULTS: Among 268 patients, no MG features were associated with symptom scores (p > 0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and ≥ 3.2 s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p = 0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p = 0.02). Longer Schirmer test wetting lengths (0-5, >5-10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p = 0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p = 0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p = 0.006) in the upper lid. CONCLUSION: In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.

Climatic and Environmental Correlates of Dry Eye Disease Severity: A Report From the Dry Eye Assessment and Management (DREAM) Study.

Purpose: Correlate climate, weather parameters, and environmental exposures with the severity of symptoms and signs of dry eye disease (DED) in Dry Eye Assessment and Management (DREAM) study participants. Methods: Participants from five distinct climates completed the Ocular Surface Disease Index (OSDI) and were examined for corneal and conjunctival staining, tear breakup time (TBUT), and Schirmer's testing at baseline, 3, 6, and 12 months. Climate, weather parameters, and pollutants including ozone (O3), carbon monoxide (CO), nitrous oxides (NO2, NOx, NOy), sulfur dioxide (SO2), particulate matter, and optical depth were obtained from governmental databases. Multivariate analysis and partial correlation coefficients (ρ) were used to assess associations, adjusted for age, sex, and the presence of Sjögren disease. Results: Among 535 participants, 81% were female and mean age was 58 years. Participants from the Mediterranean climate demonstrated better corneal fluorescein staining, better TBUT, and higher Schirmer's test scores throughout the calendar year (each P < 0.0001). Greater corneal fluorescein staining was associated with lower humidity (P < 0.0038). TBUT measurements positively correlated with temperature, humidity, and dewpoint and inversely correlated with NO2 levels (P < 0.0038). Paradoxically, some airborne pollutants were associated with less severe signs of dry eye (P < 0.0038). Windspeed was not correlated with signs of DED, and OSDI scores did not correlate with individual environmental exposures. Conclusions: Dry eye signs differed between climates and local humidity levels. With the exception of NO2, airborne pollutants were not associated with detrimental dry eye features. Translational Relevance: These results support limiting dry air exposure for patients with DED.

Visual Impairment Is More Common in Parkinson's Disease and Is a Risk Factor for Poor Health Outcomes.

BACKGROUND: Visual impairment is associated with hip fracture, depression, anxiety, and dementia in the general population, and many causes of visual impairment are preventable or treatable with early detection. However, the prevalence, outcomes, and healthcare utilization patterns associated with visual impairment have not been examined in Parkinson's disease (PD). METHODS: We performed a cross-sectional analysis of all Medicare beneficiaries with complete data in 2014 and longitudinal analysis of beneficiaries with PD from 2010 to 2014. We used diagnosis and procedure codes to identify PD, visual impairment, eye exams, hip fracture, and neuropsychiatric disorders. We compared the prevalence of visual impairment using logistic regression and used Cox proportional hazards regression to examine visual impairment and incident hip fracture, depression, anxiety, dementia, and death. We also examined the frequency of eye exams in PD using repeated-measures logistic regression. RESULTS: Among 26,209,997 Medicare beneficiaries in 2014, visual impairment was significantly more prevalent in PD (1.7%) than non-PD (0.71%) (adjusted odds ratio, 1.60; 95% confidence interval [CI], 1.56-1.65). In a longitudinal cohort of 542,224 Medicare beneficiaries with PD, less than 60% had a yearly eye exam. Visual impairment associated with increased hazard of depression (hazard ratio [HR], 1.23; 95% CI, 1.14-1.32), anxiety (HR, 1.34; 95% CI, 1.24-1.43), dementia (HR, 1.28; 95% CI, 1.21-1.36), and death (HR, 1.49; 95% CI, 1.44-1.55). CONCLUSION: Visual impairment is more common in PD than the general population and is associated with negative PD-related outcomes. Understanding the mechanisms for these relationships is important for guiding future interventions to improve health outcomes in PD. © 2020 International Parkinson and Movement Disorder Society.

The Dry Eye Assessment and Management (DREAM) extension study - A randomized clinical trial of withdrawal of supplementation with omega-3 fatty acid in patients with dry eye disease.

PURPOSE: To determine effects of continued or discontinued use of omega-3 (ω3) fatty acid supplements through a randomized withdrawal trial among patients assigned to ω3 supplements in the first year of the DREAM study. METHODS: Patients who were initially assigned to ω3 (3000 mg) for 12 months in the primary trial were randomized 1:1 to ω3 active supplements or placebos (refined olive oil) for 12 more months. The primary outcome was change in the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included change in conjunctival staining, corneal staining, tear break-up time, Schirmer test, and adverse events. RESULTS: Among 22 patients assigned to ω3 and 21 to placebo supplements, the mean change in OSDI score between month 12 and 24 was similar between treatment groups (mean difference in change -0.6 points, 95% confidence interval [CI], (-10.7, 9.5), p = 0.91). There were no significant differences between groups in mean change in conjunctival staining (difference in mean change -0.5 points; 95% CI (-1.2, 0.3)), corneal staining (-0.3 points; 95% CI (-1.2, 0.3)), tear break-up time (-0.8 s; 95% CI (-2.6, 0.9)) and Schirmer test (0.6 mm, 95% CI (-2.0, 3.2)). Rates of adverse events were similar in both groups. CONCLUSION: Among patients who received ω3 supplements for 12 months in the primary trial, those discontinuing use of ω3 for an additional 12 months did not have significantly worse outcomes compared to those who continued use of ω3. ClinicalTrials.gov number NCT02128763.

Impact of Dry Eye on Visual Acuity and Contrast Sensitivity: Dry Eye Assessment and Management Study.

SIGNIFICANCE: Identification of the association of specific signs of dry eye disease with specific visual function deficits may allow for more targeted approaches to treatment. PURPOSE: The purpose of this study was to explore the association of dry eye signs and symptoms with visual acuity (VA) and contrast sensitivity in the Dry Eye Assessment and Management study. METHODS: Baseline data from participants in the Dry Eye Assessment and Management study were used in this secondary cross-sectional analysis. Standardized procedures were used to obtain results on the Ocular Surface Disease Index (OSDI), high-contrast logMAR VA, contrast sensitivity, tear film debris, tear breakup time (TBUT), corneal fluorescein staining, meibomian gland evaluation, conjunctival lissamine green staining, and Schirmer test scores. Generalized linear models that included age, refractive error status, and cataract status were used to assess the association between VA and contrast sensitivity with OSDI score and each dry eye sign. The Hochberg procedure was used to account for multiple comparisons. RESULTS: Among 487 participants (974 eyes), worse VA was associated with worse mean score on the OSDI vision subscale (39.4 for VA 20/32 or worse vs. 32.4 for VA 20/16 or better; adjusted linear trend, P = .02); scores were not associated with contrast sensitivity. Severe meibomian gland plugging and abnormal secretions were associated with worse mean log contrast sensitivity (1.48 for severe vs. 1.54 for not plugged [P = .04] and 1.49 for obstructed vs. 1.57 for clear [P = .002], respectively). Longer TBUT was associated with better mean log contrast sensitivity (1.57 for TBUT >5 seconds and 1.51 for TBUT ≤2 seconds, P < .0001). CONCLUSIONS: Worse VA rather than worse contrast sensitivity drives vision-related symptoms in dry eye. Greater tear film instability was associated with worse contrast sensitivity.

Grading and baseline characteristics of meibomian glands in meibography images and their clinical associations in the Dry Eye Assessment and Management (DREAM) study.

PURPOSE: To describe and evaluate a comprehensive grading system for meibomian gland (MG) digital infrared images developed for the Dry Eye Assessment and Management (DREAM) Study. METHODS: Cross-sectional study. Reading Center (RC) certified readers independently evaluated MG features of both lids from meibography images of dry eye disease subjects. Dropout areas were measured using planimetry software. Inter-reader and grade-regrade agreement and comparison of meiboscale scores (Meiboscale©; Pult) from clinical centers to RC percent dropout and of MG features with clinical parameters were evaluated. RESULTS: Among 551 eyes of 277 patients at baseline, 62 (11%) upper lid and 5 (1%) lower lid images were missing. Lid eversion was poor in 63 (13%) of upper lids compared to 15 (3%) of lower lids. Intraclass correlation for inter-reader and grade-regrade agreement was moderate to substantial for most MG features. MG features were more frequent in the upper lid (p < 0.001), except for dropout glands, gaps, fluffy gland areas and dropout areas. Clinic meiboscale score was associated with RC percent dropout (p < 0.001), a clinic score of 0% having a mean RC score of 19%, and a clinic score of >75% having a mean RC score of 66%. MG plugging was associated with ghost glands (p = 0.009), dropout glands (p < 0.001) and a composite severity score (p = 0.02); turbid and absent secretions were associated with ghost glands (p = 0.046). CONCLUSION: RC readers identified MG features with good reproducibility. Upper lids had more MG features. RC dropout areas correlated well with clinic meiboscale scores. Ghost glands were associated with paste like and absent meibomian secretions.

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.

A new scale for the assessment of conjunctival bulbar redness.

PURPOSE: Current scales for assessment of bulbar conjunctival redness have limitations for evaluating digital images. We developed a scale suited for evaluating digital images and compared it to the Validated Bulbar Redness (VBR) scale. METHODS: From a digital image database of 4889 color corrected bulbar conjunctival images, we identified 20 images with varied degrees of redness. These images, ten each of nasal and temporal views, constitute the Digital Bulbar Redness (DBR) scale. The chromaticity of these images was assessed with an established image processing algorithm. Using 100 unique, randomly selected images from the database, three trained, non-physician graders applied the DBR scale and printed VBR scale. Agreement was assessed with weighted Kappa statistics (Kw). RESULTS: The DBR scale scores provide linear increments of 10 from 10-100 when redness is measured objectively with an established image processing algorithm. Exact agreement of all graders was 38% and agreement with no more than a difference of ten units between graders was 91%. Kw for agreement between any two graders ranged from 0.57 to 0.73 for the DBR scale and from 0.38 to 0.66 for the VBR scale. The DBR scale allowed direct comparison of digital to digital images, could be used in dim lighting, had both temporal and nasal conjunctival reference images, and permitted viewing reference and test images at the same magnification. CONCLUSION: The novel DBR scale, with its objective linear chromatic steps, demonstrated improved reproducibility, fewer visualization artifacts and improved ease of use over the VBR scale for assessing conjunctival redness.