Aging: A Predisposition to Dry Eyes

Dry eye syndrome is a disease of the ocular surface and tear film that is prevalent in older adults. Even though the degree of visual acuity loss in dry eye patients is commonly mild-to-moderate, in the aging population, this minimal change in visual status can lead to a significant decrease in visual function and quality of life. A healthy ocular surface is maintained by appropriate tear production and tear drainage, and deficiencies in this delicate balance can lead to dryness. In the aging eye, risk factors such as polypharmacy, androgen deficiency, decreased blink rates, and oxidative stress can predispose the patient to developing dry eye that is frequently more severe, has higher economic costs, and leads to worse consequences to the well-being of the patient. Understanding why elderly patients are at higher risk for developing dry eyes can provide insights into the diagnosis and management of the growing number of older adults struggling with dry eye and minimize the burden of disease on our aging population

Topical rosiglitazone is an effective anti-scarring agent in the cornea

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas

Differences in the TGF-␤1-Induced Profibrotic Response of Anterior and Posterior Corneal Keratocytes In Vitro

PURPOSE. To characterize phenotypic differences between anterior and posterior corneal keratocytes after stimulation with the profibrotic agent transforming growth factor-beta1 (TGF-␤1) in vitro. METHODS. Sixteen corneas from healthy felines were obtained immediately after death. Lamellar dissection was performed to separate the anterior and posterior stroma at approximately 50% depth either manually (n ϭ 2) or with a Moria microkeratome (300-m head; n ϭ 14). Cells from the anterior and posterior stroma were cultured separately but under identical conditions. Using immunohistochemistry and Western blot techniques, Ki-67 staining and relative expression of Thy-1, alpha smooth muscle actin (␣-SMA), and fibronectin were assessed after stimulation with different TGF-␤1 concentrations. In addition, anterior and posterior cells cultured in different concentrations of TGF-␤1 were wounded with a razor blade, and the wound area and time to closure were determined. RESULTS. Stimulation by all concentrations of TGF-␤1 increased the proportion of Ki-67-positive cells in anterior and posterior cell cultures, but this increase was noted earlier in posterior cells than in anterior cells. Increasing TGF-␤1 concentration also increased the relative expression of Thy-1, ␣-SMA, and fibronectin in anterior and posterior fibroblasts. However, anterior cells expressed these fibrotic markers at lower TGF-␤1 concentrations than did posterior keratocytes. After mechanical wounding, posterior cells closed the wound area faster than did anterior cells at all concentrations of TGF-␤1. CONCLUSIONS. The present experiments show that anterior and posterior corneal keratocytes exhibit different sensitivities to the profibrotic growth factor TGF-␤1. This heterogeneity of keratocyte response may impact wound closure after mechanical wounding. (Invest Ophthalmol Vis Sci

Ochrobactrum anthropi Keratitis with Focal Descemet’s Membrane Detachment and Intracorneal Hypopyon

Purpose. To describe a unique case of O. anthropi keratitis associated with a rare manifestation of Descemet’s membrane detachment and intracorneal hypopyon and to discuss challenges in diagnosis and management. Methods. Best-corrected visual acuity was measured with Snellen letters. Corneal scrapings were performed and aerobic, viral, herpetic, acid-fast bacilli, Acanthamoeba, and fungal stains and cultures were obtained. Following evisceration, tissue was evaluated for histologic features and again stained for bacteria, mycobacteria, Acanthamoeba, fungi, and viral particles. Results. Initial presentation to our institute was notable for a corneal ulcer, focal Descemet’s membrane detachment, and intracorneal hypopyon. Speciation of initial corneal scrapes revealed Ochrobactrum anthropi and initial management included fortified tobramycin. Despite medical therapy, the patient developed a corneal perforation and required subsequent evisceration. Conclusion. O. anthropi is an emerging ocular pathogen that has not been previously reported in cases of keratitis. As this pathogen becomes increasingly recognized as a source of ocular infections, it is important to identify and treat aggressively to avoid vision-threatening disease

The Diagnostic and Therapeutic Challenges of Posttraumatic Iris Implantation Cysts: Illustrative Case Presentations and a Review of the Literature

Posttraumatic iris implantation cysts are rare ocular findings that are often associated with poor visual outcomes. Iris implantation cysts can present clinicians with diagnostic and therapeutic challenges given their variable presentations and frequently destructive nature. In this paper, we provide descriptions of two unusual cases of posttraumatic iris implantation cysts. The first case is of a recurrent keratin-filled iris implantation cyst that developed after open globe injury and intraocular implantation of cilia and was treated with cyst debulking procedures, injections of 5-Fluorouracil, and iridocyclectomy. The second case is of recurrent posttraumatic serous iris implantation cysts that were treated with laser, cyst aspiration, and injections of 5-Fluorouracil. We use these cases as a platform to discuss the different manifestations of implantation cysts, the roles of anterior segment optical coherence tomography, ultrasound biomicroscopy, and histopathology in facilitating timely and accurate diagnosis and review the range of available therapeutic modalities. We discuss conservative treatment approaches, including the novel use of 5-Fluorouracil therapy as an adjunct therapy, as well as more aggressive surgical excision requiring ocular reconstruction. Through a discussion of these cases and review of the literature, we provide recommendations to assist clinicians in managing this uncommon but vision-threatening condition and minimizing complications

Keratocyte apoptosis and not myofibroblast differentiation mark the graft/host interface at early time-points post-DSAEK in a cat model.

To evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK).DSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA) and fibronectin with DAPI counterstain.At all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells.OCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes

Differences in the TGF-β1–Induced Profibrotic Response of Anterior and Posterior Corneal Keratocytes In Vitro

In response to TGF-β1 stimulation of cultured keratocytes, posterior cells demonstrate greater Ki-67 staining at earlier time points and close mechanically induced wounds faster, whereas anterior cells are more sensitive to the myofibroblast-transforming effects of TGF-β1. This heterogeneity of keratocyte response to profibrotic stimuli may have implications on wound-healing responses after procedures that differentially affect anterior and posterior portions of the cornea