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Claudia M Prospero Ponce, William Stevenson, Rachel Gelman, Daniel R Agarwal, John B Christoforidis Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA Abstract: Enzymatic vitreolysis is currently the focus of attention around the world for treating vitreomacular traction and full-thickness macular hole. Induction of posterior vitreous detachment is an active area of developmental clinical and basic research. Despite exerting an incompletely elucidated physiological effect, ocriplasmin (also known as microplasmin) has been recognized to serve as a well-tolerated intravitreal injection for the treatment of vitreomacular traction and full-thickness macular hole. There are several unexplored areas of intervention where enzymatic vitreolysis could potentially be used (ie, diabetic macular edema). Recent promising studies have included combinations of enzymatic approaches and new synthetic molecules that induce complete posterior vitreous detachment as well as antiangiogenesis. Although no guidelines have been proposed for the use of ocriplasmin, this review attempts to aid physicians in answering the most important question, “Who is the best candidate?” Keywords: vitreomacular traction, macular hole, enzymatic vitreolysis, ocriplasmin-best candidate, diabetic macular edema, future management

William Stevenson, Claudia M Prospero Ponce, Daniel R Agarwal, Rachel Gelman, John B Christoforidis Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA Abstract: Epiretinal membrane (ERM) is a disorder of the vitreomacular interface characterized by symptoms of decreased visual acuity and metamorphopsia. The diagnosis and classification of ERM has traditionally been based on clinical examination findings. However, modern optical coherence tomography (OCT) has proven to be more sensitive than clinical examination for the diagnosis of ERM. Furthermore, OCT-derived findings, such as central foveal thickness and inner segment ellipsoid band integrity, have shown clinical relevance in the setting of ERM. To date, no OCT-based ERM classification scheme has been widely accepted for use in clinical practice and investigation. Herein, we review the pathogenesis, diagnosis, and classification of ERMs and propose an OCT-based ERM classification system. Keywords: macular pucker, cellophane macular reflex, preretinal macular fibrosis, optical coherence tomography, central foveal thickness, inner segment ellipsoid band

William Stevenson, Hasanain Shikari, Ujwala S Saboo, Francisco Amparo, Reza Dana Cornea Service, Massachusetts Eye and Ear Infirmary, Boston, MA, USA 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. The median length of time from the diagnosis of ocular GVHD to the diagnosis of the first corneal ulceration was 317 days (range 168–434). The median length of time between the diagnosis of corneal ulceration in each patient's first and second eye was 248 days (range 9–645). Outcomes varied from complete resolution with medical treatment to corneal perforation necessitating penetrating keratoplasty. In cases of corneal perforation, the median length of time from the diagnosis of corneal ulceration to perforation was 10 days (range 0–20). Common clinical features included: centrally or paracentrally located ulcerations and perforations, concomitant dry eye, and the use of topical or systemic corticosteroids. Conclusion: Frequent follow-up and bilateral monitoring are highly recommended in cases of ocular GVHD-associated stromal thinning, as bilateral involvement or rapid progression to corneal perforation can occur. Keywords: graft-versus-host disease, ocular graft-versus-host disease, corneal ulceration, corneal perforation

BackgroundSeveral protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas.PurposeOur purpose was to determine whether coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior.MethodsWe evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis.ResultsIn A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity.ConclusionThese findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.