Racial and Ethnic Differences in the Association Between Diabetes Mellitus and Dry Eye Disease.

Purpose:To examine the association between dry eye and diabetes mellitus among a large North Carolina patient population. Methods:A retrospective cross-sectional study of patients seen within the University of North Carolina medical system between July 1, 2008, and September 1, 2017, was performed. De-identified medical records contained within the Carolina Data Warehouse of adult patients who have had an ocular evaluation were studied. Four categories of disease states were identified by ICD-9 and ICD-10 codes. Patients were grouped based on being diagnosed with Dry Eye Disease (ICD-9: 375.15, 370.33, and ICD-10: H04.12, H16.221), Diabetes Mellitus (ICD-9: 250.00-250.93 and ICD-10: E08-E11, E13), neither, or both diseases. Odds ratios of the association between diabetes and dry eye were calculated for the following racial/ethnic groups: Non-Hispanic White, Non-Hispanic Black/African American, Asian, and Hispanic. Results:A total of 81,480 patients were included in the analysis; of those, 8978 patients had dry eye disease and 18,361 patients had diabetes. The remaining 54,141 patients had neither disease. Dry eye prevalence among patients with diabetes was 14.39% (95% CI: 13.89-14.91%) and 10.11% (95%CI: 9.88-10.35%) among patients without diabetes. The odds of a patient with diabetes having dry eye are 1.15 (95% CI: 1.09-1.21) times that of a patient without diabetes. Asian patients with diabetes demonstrated the highest odds of having dry eye at 1.49 (95% CI: 1.12-1.98). Conclusions:Dry eye is common among patients with diabetes, and the association between these diseases is strongest among Asian patients. Race and ethnicity are important demographic factors that may guide providers in the diagnosis and treatment of dry eye in the setting of diabetes.

The Correlation Between Dry Eyes, Anxiety and Depression: The Sicca, Anxiety and Depression Study.

PURPOSE: To determine whether improvement in the severity of dry eye disease (DED) symptoms correlates with improvement in anxiety and depression. METHODS: This prospective interventional case series recruited 45 adults with evidence of DED. Patients were administered the University of North Carolina Dry Eye Management Scale (DEMS), Generalized Anxiety Disorder 7-item scale (GAD-7), and Personal Health Questionnaire Depression Scale (PHQ-8) to evaluate the severity of DED symptoms, anxiety, and depression, respectively. Standard of care treatment was provided for patients for 3 to 6 months, followed by re-administration of the DEMS, GAD-7, and PHQ-9 surveys. Statistical analysis was performed to assess the relationships between changes in survey scores. RESULTS: Participants had a mean age of 65.5 (SD, 13.3) years, and 37 (84.6%) were women. Seven patients were lost to follow-up. DEMS and GAD-7 significantly improved from 5.8 ± 1.8 to 4.6 ± 0.2.2 (P = 0.01) and from 5.6 ± 5.5 to 3.3 ± 4.6 (P = 0.05), respectively. Changes in DEMS correlated with changes in PHQ-8 (ρ = 0.3 P = 0.05), but not with changes in GAD-7 (ρ = 0.2 P = 0.3). Changes in DEMS correlated with changes in both PHQ-8 and GAD-7 in the subgroup of patients without prior depression or anxiety diagnosis (ρ = 0.6, P = 0.002; ρ = 0.4, P = 0.02). A multivariate analysis showed that the relationship between DEMS, PHQ-8, and GAD-7 was independent of a prior diagnosis of depression or anxiety and of the presence of comorbidities. CONCLUSIONS: There is a significant correlation between the severity of DED and symptoms of depression and anxiety. Effective DED treatment could have a positive impact on the symptoms of depression and anxiety.

Association Between Dry Eye Disease and Migraine Headaches in a Large Population-Based Study.

Importance: Reports in the literature have conflicting findings about an association between dry eye disease (DED) and migraine headaches. Objective: To determine the strength of the association between DED and migraine headaches. Design, Setting, and Participants: This retrospective case-control study included 72 969 patients older than 18 years from University of North Carolina-affiliated health care facilities from May 1, 2008, through May 31, 2018. Deidentified aggregate patient data were queried; data were analyzed from June 1 through June 30, 2018. Exposures: Diagnosis of migraine headache. Main Outcomes and Measures: Odds ratios calculated between DED and migraine headaches for participants as a whole and stratified by sex and age group. Results: The base population consisted of 72 969 patients, including 41 764 men (57.2%) and 31 205 women (42.8%). Of these, 5352 patients (7.3%) carried a diagnosis of migraine headache, and 9638 (13.2%) carried a diagnosis of DED. The odds of having DED given a diagnosis of migraine headaches was 1.72 (95% CI, 1.60-1.85) times higher than that of patients without migraine headaches. After accounting for multiple confounding factors, the odds of having DED given a diagnosis of migraine headaches was 1.42 (95% CI, 1.20-1.68) times higher than that of patients without migraine headaches. Conclusions and Relevance: These findings suggest that patients with migraine headaches are more likely to have comorbid DED compared with the general population. Although this association may not reflect cause and effect if unidentified confounders account for the results, these data suggest that patients with migraine headaches may be at risk of carrying a comorbid diagnosis of DED.

Intraoperative optical coherence tomography-assisted retrocorneal fibrous membrane biopsy and excision.

PURPOSE: We report a case of retrocorneal fibrous membrane (RCFM) formation following penetrating keratoplasty (PK) and intraoperative optical coherence tomography (OCT)-guided excision of this membrane. OBSERVATIONS: A 68-year-old woman with primary open angle glaucoma and corneal decompensation of the right eye secondary to tube shunt presented for 3-month follow-up of PK. On examination of the right eye, the patient was noted to have a glassy pupillary membrane with traction on the iris. Anterior segment OCT confirmed a membrane connecting the iris to host cornea. The patient underwent biopsy and excision of the membrane assisted by intraoperative OCT. Pathological examination was consistent with Descemet's membrane proliferation. We suspect that this membrane represents retained host's Descemet's membrane following corneal transplantation. CONCLUSIONS: This case highlights the existence of RCFM formation in the context of retained host cornea following PK and the role of intraoperative OCT in management.

Loss of ß Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1-Like Ocular Disease in Mice.

Human subjects with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional ßENaC MG knockout (KO) mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. ßENaC MG KO mice exhibited a striking age-dependent, female-predominant MG dysfunction phenotype, with white toothpaste-like secretions observed obstructing MG orifices at 7 weeks of age. There were compensatory increases in tear production but higher tear sodium and indexes of mucin concentration in ßENaC MG KO mice. Histologically, MG acinar atrophy was observed with ductal enlargement and ductal epithelial hyperstratification. Inflammatory cell infiltration was observed in both MG and conjunctiva of ßENaC MG KO mice. In older ßENaC MG KO mice (5 to 11 months), significant ocular surface pathologies were noted, including corneal opacification, ulceration, neovascularization, and ectasia. Inflammation in MG and conjunctiva was confirmed by increased cytokine gene and protein expression and positive Ly-6B.2 immunostaining. Cell proliferation assays revealed lower proliferation rates of MG cells derived from ßENaC MG KO than control mice, suggesting that ßENaC plays a role in cell renewal of mouse MG. Loss of ßENaC function resulted in MG disease and severe ocular surface damage that phenocopied aspects of human pseudohypoaldosteronism-1 MG disease and was sex dependent.

Determination of the Minimal Clinically Important Difference of the University of North Carolina Dry Eye Management Scale.

PURPOSE: To establish an initial estimation of the MCID of the University of North Carolina Dry Eye Management Scale (UNC DEMS) and assess its association with patient perceptions of symptom change. METHODS: Thirty-three patients (33.3% men, 67.7% women, mean age 60.5 yrs) with previous DEMS scores were recruited from a UNC ophthalmology clinic in spring 2014. We used anchor-based methods, categorizing important symptom change, to compare the change in the DEMS scores across visits to patient assessments of change; linear regression coefficients estimated the MCID. We correlated clinical assessments, patient perceptions, and DEMS scores. RESULTS: DEMS score changes correlated with global anchors [-0.4229 (P = 0.014)]. Unadjusted linear regression yielded a beta coefficient of -0.54 (confidence interval, -0.97 to -0.12, R = 0.18, P = 0.014), which estimated the DEMS MCID. Adjusting the regression model for days since the last visit and DEMS score improved the association (beta = -0.56; confidence interval, -0.99 to -0.13; R = 0.43; P = 0.013). Descriptive statistics produced an MCID of 1 point. Patients said that 2 points would represent a significant change. The DEMS modestly correlated with the Schirmer test (-0.4045, P = 0.0266), Oxford Grading Scheme (+0.3713, P = 0.0364), and tear breakup time (-0.3559, P = 0.0456). CONCLUSIONS: The UNC DEMS is a valid, responsive patient-reported outcome measure instrument, which is easy to use in the clinic and capable of showing an MCID of 1 point.

Screening for Diabetic Retinopathy: Strategies for Improving Patient Follow-up.

Diabetic retinopathy is a leading cause of preventable blindness. Timely screening and treatment prevent morbidity, though low follow-up rates remain problematic. Feasible and efficacious methods for increasing screening follow-up rates include patient education, a streamlined referral and scheduling process, and collaboration with local ophthalmologists and primary care providers.

Spontaneous Canalicular Plug Erosion After Punctal Plug Placement.

PURPOSE: To describe a case of keratoconjunctivitis sicca treated with punctal plug placement with the first reported complication of subsequent plug erosion through the canaliculus and extrusion through the lid. METHODS: Punctal plugs were placed in a patient with Sjogren syndrome for treatment of keratoconjunctivitis sicca. More than 12 years later, the plug was noted to have eroded through the canaliculus and extruded through the conjunctiva and lid. RESULTS: The extruded plug was removed, and punctal cautery was performed on 2 other puncta with improved symptom control. CONCLUSIONS: Plug extrusion through the conjunctiva and lid is a possible consequence of punctal plug placement.

Survey of Molds in California Processing Tomatoes.

From 2009 to 2011, freshly harvested processing tomatoes from California commercial fields were surveyed for mold species present in the mature fruit. Molds were recovered from the majority of fruit that had visual symptoms of black mold and other decays and from about a quarter of randomly sampled, asymptomatic fruit. Alternaria, Fusarium, and Geotrichum spp. were the most commonly recovered fungi in both symptomatic and random samples. Based on pairwise statistical analysis, the frequencies of 2 different fungal genera in a composite 11 kg-sample were, in general, statistically independent events, with the exception of a weak association between the incidence of Geotrichum with Alternaria, Cladosporium, or Stemphylium. The mold genera distribution data in this study provide the processing tomato industry with a valuable informational resource that can be used in the management of fungal infection in both the crop and in the final thermally processed finished product. Because of the relative abundance of these fungi, this survey supported the development of genera-specific immunochromatographic diagnostic assays to detect and quantify mold occurrence in Californian processing tomatoes as a potential alternative to the current subjective visual methods, which are characterized by imprecision and nonuniform species sensitivity. A simulation of 1 million 11 kg-composite samples based upon the distributional survey data projected that a multiantibody immunochromatographic assay using monoclonal antibodies for Alternaria, Cladosporium, Fusarium, and Geotrichum could successfully detect the presence of mold in 94% of moldy processing tomato samples collected randomly at harvest.

Characterization of Rat Meibomian Gland Ion and Fluid Transport.

PURPOSE: We establish novel primary rat meibomian gland (MG) cell culture systems and explore the ion transport activities of the rat MG. METHODS: Freshly excised rat MG tissues were characterized as follows: (1) mRNA expression of selected epithelial ion channels/transporters were measured by RT-PCR, (2) localization of epithelial sodium channel (ENaC) mRNAs was performed by in situ hybridization, and (3) protein expression and localization of ßENaC, the Na+/K+/Cl- cotransporter (NKCC), and the Na+/K+ ATPase were evaluated by immunofluorescence. Primary isolated rat MG cells were cocultured with 3T3 feeder cells and a Rho-associated kinase (ROCK) inhibitor (Y-27632) for expansion. Passaged rat MG cells were cultured as planar sheets under air-liquid interface (ALI) conditions for gene expression and electrophysiologic studies. Passaged rat MG cells also were cultured in matrigel matrices to form spheroids, which were examined ultrastructurally by transmission electron microscopy (TEM) and functionally using swelling assays. RESULTS: Expression of multiple ion channel/transporter genes was detected in rat MG tissues. ß-ENaC mRNA and protein were localized more to MG peripheral acinar cells than central acinar cells or ductular epithelial cells. Electrophysiologic studies of rat MG cell planar cultures demonstrated functional sodium, chloride, and potassium channels, and cotransporters activities. Transmission electron microscopic analyses of rat MG spheroids revealed highly differentiated MG cells with abundant lysosomal lamellar bodies. Rat MG spheroids culture-based measurements demonstrated active volume regulation by ion channels. CONCLUSIONS: This study demonstrates the presence and function of ion channels and volume transport by rat MG. Two novel primary MG cell culture models that may be useful for MG research were established.

Instrument development of the UNC Dry Eye Management Scale.

PURPOSE: Dry eye disease (DED) is a common ocular disease that can have adverse effects on quality of life. Our aim was to develop a single-item questionnaire that is reliable, patient-driven, and clinic friendly to assess DED symptoms and their effect on quality of life to help support the management of patients with DED. METHODS: An initial dry eye questionnaire was created and administered to 18 patients with DED followed by a 15-minute cognitive interviewing session. This questionnaire was then refined using feedback obtained from the cognitive interview and was termed the University of North Carolina Dry Eye Management Scale (UNC DEMS). Field testing was then performed on 66 patients (46 with DED and 20 without DED) to determine the validity and test-retest reliability of the UNC DEMS compared with the current gold standard, the Ocular Surface Disease Index (OSDI). Pearson correlation coefficients were calculated between the UNC DEMS, OSDI, and other DED measures to assess criterion-related validity. Reliability coefficients were estimated for test-retest reliability. RESULTS: Comparing the UNC DEMS with the OSDI across all study participants, the correlation coefficient was 0.80 (P < 0.001). Comparing the UNC DEMS with the OSDI in the DED group, the correlation coefficient was 0.69 (P < 0.001). The test-retest reliability coefficient of the UNC DEMS was estimated to be 0.90. CONCLUSIONS: The UNC DEMS is a valid, reliable questionnaire that can be efficiently administered in a busy clinical practice and can be used to support the management of patients with DED.

Subcutaneous and periorbital emphysema following dental procedure.

Subcutaneous emphysema following a dental procedure is a relatively uncommon phenomenon that may produce a dramatic clinical presentation. The advent of high-powered dental equipment that uses directed and highly pressurized air has increased the risk of this complication, but few cases have been described in the ophthalmic literature. The authors present a case of subcutaneous periorbital emphysema in a young woman following a dental procedure. Aside from a temporary ptosis, there were no other ophthalmic complications. An attempt to decompress the air produced minimal relief. The condition resolved spontaneously within 1 week.

Perceptions of dry eye disease management in current clinical practice.

OBJECTIVE: To assess the perceptions of eye care providers regarding the clinical management of dry eye. METHODS: Invitations to complete a 17-question online survey were mailed to 400 members of the North Carolina Ophthalmology and Optometry Associations including community optometrists, comprehensive ophthalmologists, and cornea specialists. RESULTS: The survey was completed by 100 eye care providers (25% response rate). Providers reported burning (46.5%) as the most frequent symptom described by patients, followed by foreign body sensation (30.3%) and tearing (17.2%). Most respondents (80.8%) listed artificial tears as the recommended first-line treatment, even though providers reported high failure rates for both artificial tears and cyclosporine A (Restasis). Rheumatoid arthritis, Sjögren syndrome, affective disorders such as anxiety and depression, history of photorefractive surgery, smoking, and thyroid disease were acknowledged as common comorbid conditions. CONCLUSIONS: The survey provided an informative snapshot into the preferences of eye care providers concerning the diagnosis and management of dry eye disease. Overall, burning was the most common symptom reported by patients. Providers relied more on patient history in guiding their clinical decisions than objective signs. The survey underscores the incongruence when comparing subjective symptoms with objective signs, thereby highlighting the urgent need for the development of reliable metrics to better quantify dry eye symptoms and also the development of a more sensitive and specific test that can be used as the gold standard to diagnose dry eye.

Autoimmunity in the pathogenesis and treatment of keratoconjunctivitis sicca.

Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. Keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren's syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets.

A review of quality of life measures in dry eye questionnaires.

PURPOSE: Dry eye disease (DED) is an ocular disease that affects 5% to 17% of the US population. Because of the negative effects of DED on patients' quality of life (QOL), disease-specific questionnaires that assess QOL in patients with dry eyes are essential in the monitoring and management of this chronic ocular condition. This review provides clinicians and researchers with a summary of the current questionnaires available for assessing QOL in patients with dry eyes. METHODS: A systematic review of the literature was performed in March 2013. RESULTS: There are only 2 validated, reliable dry eye questionnaires with QOL measures currently available for clinic use: the Ocular Surface Disease Index (OSDI) and the Impact of Dry Eye on Everyday Life questionnaire (IDEEL). Multiple other dry eye questionnaires assess some degree of QOL, but they have either not been tested for validity and reliability or are limited in QOL measures they assess. CONCLUSIONS: The OSDI and IDEEL are validated, reliable disease-specific questionnaires that assess QOL measures in patients with DED. Because of its extensive development process and multiple QOL measures, the IDEEL offers a more thorough assessment of the effect of DED on QOL for clinical trials, whereas the OSDI may be the more convenient option for clinical use as a result of its shorter completion time. Other questionnaires used to assess QOL in DED (eg, 25-item National Eye Institute Visual Function Questionnaire and Texas Eye Research and Technology Center DEQ) are fairly limited in this assessment. Finally, because of the negative effects of DED on QOL, this review emphasizes the importance of including QOL measures in future questionnaires for the monitoring and management of DED.

Ocular disease, knowledge and technology applications in patients with diabetes.

An estimated 25.8 million children and adults in the United States, approximately 8.3% of the population, have diabetes. Diabetes prevalence varies by race and ethnicity. African Americans have the highest prevalence (12.6%), followed closely by Hispanics (11.8%), Asian Americans (8.4%) and whites (7.1%). The purpose of this article was to discuss the ocular complications of diabetes, the cultural and racial differences in diabetes knowledge and the role of telemedicine as a means to reach the undeserved who are at risk of complications. Information on the pathophysiology of ocular disease in patients with diabetes and the role of telemedicine in diabetes care was derived from a literature review. National Institutes of Health online resources were queried to present data on the racial and cultural understandings of diabetes and diabetes-related complications. The microvascular ocular complications of diabetes are discussed for retinopathy, cataracts, glaucoma and ocular surface disease. Racial and cultural differences in knowledge of recommended self-care practices are presented. These differences, in part, may explain health disparities and the increased risk of diabetes and its complications in rural minority communities. Finally, advances in telemedicine technology are discussed that show improvements in metabolic control and cardiovascular risk in adults with type 2 diabetes. Improving provider and patient understanding of diabetes complications may improve management and self-care practices that are important for diabetes control. Telemedicine may improve access to diabetes specialists and may improve self-management education and diabetes control particularly in rural and underserved communities.

Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract.

BACKGROUND: Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context. OBJECTIVES: To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials. SELECTION CRITERIA: We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data were available. We did not perform a sensitivity analysis. MAIN RESULTS: Nine trials involving 117,272 individuals of age 35 years or older are included in this review. The trials were conducted in Australia, Finland, India, Italy, the United Kingdom and the United States, with duration of follow-up ranging from 2.1 to 12 years. The doses of antioxidant vitamins were higher than the recommended daily allowance. There was no evidence of effect of antioxidant vitamin supplementation in reducing the risk of cataract, cataract extraction, progression of cataract or in slowing the loss of visual acuity. In the pooled analyses, there was no evidence of effect of beta-carotene supplementation in reducing the risk of cataract (two trials) (relative risk (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.08; n = 57,703) or in reducing the risk of cataract extraction (three trials) (RR 1.00, 95% CI 0.91 to 1.10; n = 86,836) or of vitamin E supplementation in reducing the risk of cataract (three trials) (RR 0.97, 95% CI 0.91 to 1.04; n = 50,059) or of cataract extraction (five trials) (RR 0.98, 95% CI 0.91 to 1.05; n = 83,956). The proportion of participants developing hypercarotenodermia (yellowing of skin) while on beta-carotene ranged from 7.4% to 15.8%. AUTHORS' CONCLUSIONS: There is no evidence from RCTs that supplementation with antioxidant vitamins (beta-carotene, vitamin C or vitamin E) prevents or slows the progression of age-related cataract. We do not recommend any further studies to examine the role of antioxidant vitamins beta-carotene, vitamin C and vitamin E in preventing or slowing the progression of age-related cataract. Costs and adverse effects should be weighed carefully with unproven benefits before recommending their intake above recommended daily allowances.