Effects of corneal nerve density on the response to treatment in dry eye disease.

Purpose: To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment.

Design: Phase IV, double-masked, randomized clinical trial.

Participants: Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls.

Corneal inflammation after miniature keratoprosthesis implantation.

Purpose: To compare corneal inflammation after syngeneic and allogeneic penetrating keratoplasty (PK) with miniature Keratoprosthesis (m-KPro) implantation in mice.

Methods: BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or m-KPro implantation. Corneal inflammation was assessed by determining the frequencies of CD45(+) leukocytes, CD4(+) T cells, CD11b(+) cells, and Gr-1(+) granulocytes/monocytes by flow cytometry at 2, 4, and 8 weeks post transplantation.

Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation.

Purpose: To investigate the effect of host immunity (allospecific) and surgical manipulation (non-allospecific) on corneal endothelial cells (CECs) in corneal transplantation.

Methods: Draining lymph nodes and grafted C57BL/6 corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors (BALB/c) 1, 3, and 8 weeks after transplantation. We analyzed CEC apoptosis using an ex vivo cornea-in-the-cup assay, and visualized cell-to-cell junctions using immunohistochemical staining (ZO-1).

Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.

There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.

Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease.

Purpose: The aim of this study was to establish and characterize extraorbital lacrimal gland excision (LGE) as a model of aqueous tear-deficient dry eye disease in mice.

Methods: Female C57BL/6 mice at 6 to 8 weeks of age were randomized to extraorbital LGE, sham surgery, or scopolamine groups. Mice that underwent extraorbital LGE or sham surgery were housed in the standard vivarium.

Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease.

A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens.

The resolvin D1 analogue controls maturation of dendritic cells and suppresses alloimmunity in corneal transplantation.

Purpose: To analyze the effect of a resolvin D1 (RvD1) analogue (RvD1a) on dendritic cell maturation, T-cell sensitization, and allograft rejection in corneal allotransplantation.

Methods: The receptor expression of RvD1 (ALX/FPR2) on bone marrow-derived dendritic cells (BMDC) was measured using quantitative real-time PCR. We determined BMDC maturation after treatment with RvD1a using ELISA to measure interleukin (IL)-12 protein expression and flow cytometry to assess the expression of CD40, major histocompatibility complex (MHC) II, CD80, and CD86.

CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease.

Purpose: We characterized antigen-presenting cell (APC)-relevant chemokine receptor expression in dry eye disease (DED), and investigated the effect of topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity and dry eye disease severity.

Methods: We induced DED in female C57BL/6 mice. Chemokine receptor expression by corneal APCs was characterized using immunohistochemistry.

Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival.

Purpose: To investigate the effect of VEGF-C and VEGF-D blockade via soluble VEGFR-3 (sVEGFR-3) on T cell allosensitization, corneal neovascularization, and transplant survival.

Methods: Corneal intrastromal suture placement and allogeneic transplantation were performed on BALB/c mice to evaluate the effect of sVEGFR-3 on corneal neovascularization. Soluble VEGFR-3 trap was injected intraperitoneally to block VEGF-C/D (every other day starting the day of surgery).

Chromophobe renal cell carcinoma with sarcomatoid changes: case report and review of literature.

Chromophobe renal cell carcinoma (RCC), a subtype of RCC, accounts for 4-6% of all RCC and has better prognosis then conventional RCC. Sarcomatoid dedifferentiation is thought to represent the high-grade end of all subtypes. This makes chromophobe RCC with sarcomatoid changes a rare entity associated with poor prognosis in most studies.

Salty taste deficits in CALHM1 knockout mice.

Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds.

A novel murine model for keratoprosthesis.

Purpose: To establish a murine model for keratoprosthesis.

Methods: A miniature keratoprosthesis (m-KPro) device was created consisting of a poly[methyl methacrylate] front part and a titanium back plate, designed after the Boston KPro, which is in widespread clinical use. BALB/c mice were used and a 2 mm in diameter donor cornea was punched out.

A 30 mK, 13.5 T scanning tunneling microscope with two independent tips.

We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T.

A novel pro-angiogenic function for interferon-γ-secreting natural killer cells.

Purpose: To explore the function of natural killer (NK) cells in inflammatory angiogenesis in mice.

Methods: To study ocular angiogenic responses we used the cornea BFGF micropellet and the laser-induced choroidal neovascularization (CNV) mouse models (C57BL/6). To deplete NK cells in these models, we injected an anti-NK1.

Alkali burn to the eye: protection using TNF-α inhibition.

Purpose: The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-α) blockade.

Methods: Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn.

Expression of the chemokine decoy receptor D6 mediates dendritic cell function and promotes corneal allograft rejection.

Purpose: To identify the role of chemokine receptor 6 (D6) expression by dendritic cells (DCs) and its role in corneal transplant immunity.

Methods: Flow cytometry analysis was used to assess the expression level of the D6 chemokine receptor in different leukocyte populations and DC maturation following lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from wild-type (WT) or D6(-/-) mice (C57BL/6 background). Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed with bone marrow-derived DCs from WT or D6(-/-) mice to evaluate T-cell alloreactivity.

Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity.

Purpose: To determine the effects of topical Janus kinase inhibition on ocular surface inflammation and immunity.

Methods: Ophthalmic 0.003% tofacitinib (CP-690,550) was administered topically to inhibit Janus kinase activation at the ocular surface.

CCL-21 conditioned regulatory T cells induce allotolerance through enhanced homing to lymphoid tissue.

Regulatory T cells (Tregs) are instrumental in the induction and maintenance of tolerance, including in transplantation. Tregs induce allotolerance by interacting with APCs and T cells, interactions that require their proper homing to the lymphoid tissues. Using a well-characterized model of corneal allotransplantation, we demonstrate in this study that Tregs in the draining lymph nodes (LN) of allograft acceptors, but not rejectors, colocalize with APCs in the paracortical areas and express high levels of CCR7.

International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: proposed diagnostic criteria for chronic GVHD (Part I).

The International Chronic Ocular GVHD Consensus Group held 4 working meetings to define new diagnostic metrics for chronic ocular graft-versus-host disease (GVHD). After considering the factors currently used to diagnose chronic ocular GVHD, the Consensus Group identified 4 subjective and objective variables to measure in patients following allogeneic hematopoietic stem cell transplantation (HSCT): OSDI, Schirmer's score without anesthesia, corneal staining, and conjunctival injection. Each variable was scored 0-2 or 0-3, with a maximum composite score of 11.

Bilateral corneal ulceration in ocular graft-versus-host disease.

Purpose: To report on corneal ulceration in ocular graft-versus-host disease (GVHD).

Methods: This was a retrospective, observational case series investigating corneal ulceration and perforation in a cohort of ocular GVHD patients seen between June 2007 and October 2012.

Results: Four of 243 ocular GVHD patients developed corneal ulcerations attributable to ocular GVHD, and all four cases involved bilateral corneal ulceration.

What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease?

Purpose: To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED).

Design: Retrospective, clinic-based cohort study.

Methods: In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits.

Differentiation potential of limbal fibroblasts and bone marrow mesenchymal stem cells to corneal epithelial cells.

The cornea is covered by a stratified epithelium that is renewed by stem cells located in the peripheral region of the cornea known as the limbus. This stroma of the limbus contains stromal keratocytes that, when expanded in culture, are termed limbal fibroblasts (LFs). It is thought that LFs exhibit similar characteristics to bone marrow mesenchymal stem cells (BM MSCs) and help maintain the epithelial stem cell phenotype in the limbal region.