The purpose of this study is to assess the relationship between self-reported uveitis and purported demographic and clinical risk factors, using an American adult population extracted from the National Health and Nutrition Examination Survey (NHANES) for the years 2009 and 2010. This is a cross-sectional, population-based study using a sample of 5106 subjects between 20 and 69 years old. The main outcome for our study was the self-report of a diagnosis of uveitis. The demographic analysis included age, gender, and ethnicity. Potential predictors were having a diagnosis of ankylosing spondylitis (AS), ulcerative colitis (UC), or Crohn’s disease (CD); a history of cigarette smoking; vitamin D deficiency; and different mental health measures. Univariate and multivariate analyses were conducted using RStudio. Of the 5106 participants, 27 had reported a diagnosis of uveitis, showing an adjusted prevalence of 5.4 per 1000 subjects (95% CI 3.4–8.5/1000). Increased age was associated with higher uveitis prevalence in the multivariate analysis (odds ratio [OR] = 1.04, 95% CI 1.01–1.07; p = 0.02). Positive smoking history was reported in 59.2% of patients. Multivariate analysis comparing smoking with the presence of uveitis showed an OR of 3.18 (95% CI 1.59–6.37; p = 0.003), adjusting for age and gender. Moreover, 11.1% of the participants from the uveitis group self-reported a diagnosis of AS and 11.7% informed a diagnosis of UC and 7.1% of CD. The ORs were of 16.64 (95% CI 3.64-76.09; p = 0.001), 11.34 (95% CI 2.69-47.88; p = 0.003), and 22.16 (95% CI 2.64-186.17; p = 0.007), respectively when compared with the non-uveitis group in the multivariate analysis. Age, cigarette smoking, AS, UC, and CD are positively associated with self-reported uveitis. There is previous evidence that smoking and female gender are positive risk factors for uveitis, as well as evidence that HLA-B27-positive spondyloarthritides have the highest association with non-infectious uveitis in the adult population in North America and Europe. However, there are no prior studies that have utilized a representative US population-based sample to validate these findings. The present study supports smoking as a risk factor, which has clinical relevance since this is a modifiable habit.

Summary Corneal scarring due to injury is a leading cause of blindness worldwide and results from dysregulated inflammation and angiogenesis during wound healing. Here we demonstrate that the extracellular matrix metalloproteinase MMP12 (macrophage metalloelastase) is an important regulator of these repair processes. Chemical injury resulted in higher expression of the fibrotic markers α-smooth muscle actin and type I collagen, and increased levels of angiogenesis in corneas of Mmp12^−/− mice compared with corneas of wild-type mice. In vivo, we observed altered immune cell dynamics in Mmp12^−/− corneas by confocal imaging. We determined that the altered dynamics were the result of an altered inflammatory response, with delayed neutrophil infiltration during the first day and excessive macrophage infiltration 6 days later, mediated by altered expression levels of chemokines CXCL1 and CCL2, respectively. Corneal repair returned to normal upon inhibition of these chemokines. Taken together, these data show that MMP12 has a protective effect on corneal fibrosis during wound repair through regulation of immune cell infiltration and angiogenesis.

Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically,miR-199Bis extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in whichmiR-199Bhypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, includingSnai1andZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.

Purpose of Review: This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody–drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs). Recent Findings: ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity. Summary: Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.