C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK's role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.

BACKGROUND: Pyogenic lacrimal gland abscesses are uncommon and thus may not be immediately clinically recognized without a high index of suspicion. FINDINGS: We present two patients with preseptal cellulitis and characteristic low-attenuation fluid collections in the lacrimal glands demonstrated on computed tomography (CT). CONCLUSIONS: Lacrimal gland abscesses should be considered when dacryoadenitis is refractory to medical treatment. Indeed, these cases highlight the value of prompt recognition of lacrimal abscess through ophthalmologic referral and the use of diagnostic imaging. Both patients were successfully treated via incision and drainage.

INTRODUCTION: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. AREAS COVERED: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. EXPERT OPINION: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

PURPOSE: To evaluate treatment options for vitreomacular traction (VMT). METHODS: A retrospective, consecutive case series and a literature search with Boolean search logic. A random-effects meta-analysis was conducted to combine the rates of VMT resolution per treatment. Patients from studies analyzed were placed into cohorts based on the treatment received. RESULTS: CASE SERIES: Zero of 10 control, 3 of 7 intravitreal ocriplasmin (IVO, P = 0.10), 7 of 8 intravitreal expansile gas (pneumatic vitreolysis, PV, P < 0.01), and 10 of 10 pars plana vitrectomy (P < 0.01)-treated eyes experienced VMT release (VMTr) at Day 28. No patients developed retinal tears or detachment. One PV-treated (12.5%) eye developed a macular hole. Meta-analysis: Twenty-three of 131 prospective or retrospective and consecutive articles were included. Sixty-three eyes were treated with PV, 726 eyes were treated with intravitreal ocriplasmin, and 253 eyes were characterized as the control group (saline injection). The weighted rate of VMT resolution for the control group was 0.09 (95% confidence interval [CI]: 0.06-0.13), PV was 0.84 (95% CI: 0.76-0.92), and intravitreal ocriplasmin was 0.26 (95% CI: 0.23-0.29). CONCLUSION: Our analysis found that PV releases VMT in most patients and suggest that PV may be as effective or superior to nonsurgical options for VMTr at Day 28 with a similar risk profile.

Uveitis is a common and serious complication of juvenile idiopathic arthritis. Up to 75% of all cases of anterior uveitis in childhood are associated with juvenile idiopathic arthritis. Despite the remarkable progress in early detection and treatment of inflammation, vision-threatening complications of uveitis still occur in almost 60% of patients. Structural complications include band keratopathy, maculopathy (macular edema, macular cysts, and epiretinal membrane), glaucomatous optic neuropathy, and cataracts. The management of complications in juvenile idiopathic arthritis is usually complex and requires early surgical intervention. In this paper, we review the general concepts of common ocular complications seen in patients with JIA-associated uveitis, with special attention to the recent diagnostic and preferred treatment approaches at the Massachusetts Eye Research and Surgery Institution. Received 9 March 2015; revised 30 September 2015; accepted 30 October 2015; published online 14 January 2016.

In March 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting.

The repair of wounds through collective movement of epithelial cells is a fundamental process in multicellular organisms. In stratified epithelia such as the cornea and skin, healing occurs in three steps that include a latent, migratory, and reconstruction phases. Several simple and inexpensive assays have been developed to study the biology of cell migration in vitro. However, these assays are mostly based on monolayer systems that fail to reproduce the differentiation processes associated to multilayered systems. Here, we describe a straightforward in vitro wound assay to evaluate the healing and restoration of barrier function in stratified human corneal epithelial cells. In this assay, circular punch injuries lead to the collective migration of the epithelium as coherent sheets. The closure of the wound was associated with the restoration of the transcellular barrier and the re-establishment of apical intercellular junctions. Altogether, this new model of wound healing provides an important research tool to study the mechanisms leading to barrier function in stratified epithelia and may facilitate the development of future therapeutic applications.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

PURPOSE: To evaluate the incidence of remission among patients with intermediate uveitis; to identify factors potentially predictive of remission. DESIGN: Retrospective cohort study. METHODS: Involved eyes of patients with primary noninfectious intermediate uveitis at 4 academic ocular inflammation subspecialty practices, followed sufficiently long to meet the remission outcome definition, were studied retrospectively by standardized chart review data. Remission of intermediate uveitis was defined as a lack of inflammatory activity at ≥2 visits spanning ≥90 days in the absence of any corticosteroid or immunosuppressant medications. Factors potentially predictive of intermediate uveitis remission were evaluated using survival analysis. RESULTS: Among 849 eyes (of 510 patients) with intermediate uveitis followed over 1934 eye-years, the incidence of intermediate uveitis remission was 8.6/100 eye-years (95% confidence interval [CI], 7.4-10.1). Factors predictive of disease remission included prior pars plana vitrectomy (PPV) (hazard ratio [HR] [vs no PPV] = 2.39; 95% CI, 1.42-4.00), diagnosis of intermediate uveitis within the last year (HR [vs diagnosis >5 years ago] =3.82; 95% CI, 1.91-7.63), age ≥45 years (HR [vs age <45 years] = 1.79; 95% CI, 1.03-3.11), female sex (HR = 1.61; 95% CI, 1.04-2.49), and Hispanic race/ethnicity (HR [vs white race] = 2.81; 95% CI, 1.23-6.41). Presence/absence of a systemic inflammatory disease, laterality of uveitis, and smoking status were not associated with differential incidence. CONCLUSIONS: Our results suggest that intermediate uveitis is a chronic disease with an overall low rate of remission. Recently diagnosed patients and older, female, and Hispanic patients were more likely to remit. With regard to management, pars plana vitrectomy was associated with increased probability of remission.