Combined Epithelial, Stromal, and Anterior Chamber Ingrowth After Penetrating Keratoplasty.

PURPOSE: To present a case of primary graft failure after penetrating keratoplasty found to have epithelial ingrowth into the host stroma on histopathologic analysis. METHODS: This is a single observational case report. RESULTS: We herein describe the clinical course of a case of primary graft failure after penetrating keratoplasty. The corneal button was sent for histopathologic analysis. Analysis of the patient's failed corneal button revealed circumferential epithelial full-thickness wound invasion and stromal epithelial invasion into corneal stroma. CONCLUSIONS: Based on histopathologic analysis and this patient's presentation, the stromal ingrowth followed recipient epithelial invasion of the wound and stromal invasion through clefts in the donor corneal edges. Cases of primary graft failure should be assessed for histopathologic evidence of epithelial stromal ingrowth, despite its rarity. To our knowledge, epithelial ingrowth into the corneal donor stroma after penetrating keratoplasty has not been previously reported.

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.

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.

SSEA4 is a potential negative marker for the enrichment of human corneal epithelial stem/progenitor cells.

PURPOSE: To examine the expression of stage-specific embryonic antigen-4 (SSEA4) in the epithelium of the human ocular surface and characterize SSEA4(+) and SSEA4(-) limbal epithelial cells. METHODS: SSEA4 expression in the human cornea and limbus was examined by RT-PCR and immunohistochemistry. SSEA4(+) and SSEA4(-) cells were then separated by using magnetic beads. The phenotypes of these two cell populations were evaluated on the basis of cell size, clonogenic assay, and expression of putative limbal stem cell (LSC) and corneal epithelial differentiation markers. RESULTS: SSEA4 was expressed in all layers of the corneal and anterior limbal epithelia. Discrete clusters of SSEA4(+) cells were present in the central and posterior limbal epithelia. SSEA4(+) cells accounted for an average of 40% of the total limbal epithelial cells. The SSEA4(-) population contained five times more small cells (≤11 µm in diameter) than did the SSEA4(+) population. The expression levels of the putative LSC markers ABCG2, ΔNp63α, and cytokeratin (K)14 were significantly higher in the SSEA4(-) population than in the SSEA4(+) population. The SSEA4(-) cells also expressed a significantly higher level of N-cadherin, but a lower level of the differentiation marker K12. The colony-forming efficiency in the SSEA4(-) population was 25.2% (P = 0.04) and 1.6-fold (P < 0.05) higher than in the unsorted population and the SSEA4(+) population, respectively. CONCLUSIONS: SSEA4 is highly expressed in differentiated corneal epithelial cells, and SSEA4(-) limbal epithelial cells contain a higher proportion of limbal stem/progenitor cells. SSEA4 could be used as a negative marker to enrich the isolation of LSCs.

Reversal of nicotine-induced alveolar lipofibroblast-to-myofibroblast transdifferentiation by stimulants of parathyroid hormone-related protein signaling.

Nicotine exposure disrupts the parathyroid hormone-related protein (PTHrP)-driven alveolar epithelial-mesenchymal paracrine-signaling pathway, resulting in the transdifferentiation of pulmonary lipofibroblasts (LIFs) to myofibroblasts (MYFs), which seems to be central to altered pulmonary development and function in infants born to mothers who smoke during pregnancy. Modulation of PTHrP-driven signaling can almost completely prevent nicotine-induced LIF-to-MYF transdifferentiation. However, once this process has occurred, whether it can be reversed is not known. Our objective was to determine if nicotine-induced LIF-to-MYF transdifferentiation could be reversed by specifically targeting the PTHrP-mediated alveolar epithelial-mesenchymal paracrine signaling. WI38 cells, a human embryonic pulmonary fibroblast cell line, were initially treated with nicotine for 7 days and LIF-to-MYF transdifferentiation was confirmed by determining the downregulation of the key lipogenic marker, peroxisome proliferator-activated receptor gamma (PPARgamma) and upregulation of the key myogenic marker, alpha-smooth muscle actin (alphaSMA). Because downregulation of the PPARgamma signaling pathway is the key determinant of LIF-to-MYF transdifferentiation, cells were treated with three agonists of this pathway, PTHrP, dibutryl cAMP (DBcAMP), or rosiglitazone (RGZ) for 7 days, and the expression of the PTHrP receptor, PPARgamma, alphaSMA, and calponin was determined by Western analysis and immunohistochemistry. Simultaneously, fibroblast function was characterized by measuring their capacity to take up triglycerides. Nicotine-induced LIF-to-MYF transdifferentiation was almost completely reversed by treatment with RGZ, PTHrP, or DBcAMP, as determined by protein and functional assays. Using a specific molecular approach and targeting specific molecular intermediates in the PTHrP signaling pathway, to our knowledge, this for the first time, demonstrates the reversibility of nicotine-induced LIF-to-MYF transdifferentiation, suggesting not only the possibility of prevention but also the potential for reversal of nicotine-induced lung injury.