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Proliferative vitreoretinopathy is a disease process that follows the proliferation of ectopic cell sheets in the vitreous and/or periretinal area, causing periretinal membrane formation and traction, in patients with rhegmatogenous retinal detachments. Currently, vitreous surgery is the standard treatment; however, the results aren't satisfactory given the vision loss that ensues and that redetachment is relatively common. It is becoming clearer that there exists an interplay between various cytokines/growth factors, matrix proteins, and the different cell types that drive the undesirable formation of periretinal membranes. This fundamental understanding is aiding in identifying different adjunct agents that can block the cellular events intrinsic to proliferative vitreoretinopathy. In this review, we describe the current understanding on the pathogenesis and discuss how the fundamental understanding of the biochemical/molecular events is instrumental in developing the novel treatment strategies that are also highlighted.

PURPOSE: Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for wound healing and tissue regeneration. In the present study, we investigated the impact of corneal injury on the homeostasis of endogenous MSCs, and the potential of MSCs to home to injured tissue and promote corneal repair. METHODS: Corneal injury in mice was induced by thermal cauterization. Circulating MSCs were quantified by flow cytometric analysis. Ex vivo expanded red Q-dot-labeled or GFP+ bone marrow-derived MSCs were intravenously injected after injury and detected using epifluorescence microscopy. Corneal fluorescein staining was performed to evaluate epithelial regeneration. RESULTS: Following the induction of corneal injury in mice, a 2-fold increase in the frequency of circulating endogenous MSCs was observed within 48 hours of injury, which was accompanied by increased levels of the stem cell chemoattractants, substance P and SDF-1, in both the injured cornea and blood. Systemically administered MSCs homed to the injured cornea, but not to the normal cornea, and showed long-term survival. In addition, in the setting of corneal injury, MSC administration showed significant and rapid corneal epithelial regeneration. CONCLUSIONS: These findings provide novel evidence that corneal injury causes significant mobilization of endogenous MSCs into blood, and that MSCs home specifically to the injured cornea and promote regeneration, highlighting the therapeutic implications of MSC-mediated tissue repair in corneal injury.

The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.

UNLABELLED: Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United States-all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546 and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift in dprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition. IMPORTANCE: Invasive methicillin-resistant Staphylococcus aureus (MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistant S. aureus (VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546 from enterococcal donors. All acquisitions of Tn1546 so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

Surgery for traumatic cataracts is a potentially complex procedure. Clinically, traumatic cataracts may be difficult to thoroughly assess due to the presence of other significant ocular damage including corneal scars, posterior synechiae, and vitreous hemorrhage. Frequently, surgery involves surprises regarding the integrity of the posterior capsule and zonular structure. Careful ophthalmic imaging using ultrasound technologies may result in finer pre-operative detail regarding lens support structures, and may therefore give the surgeon the advantage when planning surgery. Imaging techniques most applicable to pre-operative evaluation include B scan ultrasound, 20MHz ultrasound, and ultrasound biomicroscopy. Important modifications to technique that can be made depending on the integrity of lens support structures include adjustment of wound location, adjustment in the technique for cataract removal, and possible use of a capsular tension ring.

Optical coherence tomography (OCT) has been routinely used to obtain high spatial resolution images of the retina and choroid non-invasively. Within the past decade, a fourth-generation OCT device using Fourier domain (FD) analysis has been developed that provides higher velocity and higher axial resolution images with better reproducibility than the previous generation time domain (TD) OCT technology. This review addresses the use of fourth-generation, FD ocular OCT in patients with multiple sclerosis.

PURPOSE: In performing search tasks, the visual system encodes information across the visual field at a resolution inversely related to eccentricity and deploys saccades to place visually interesting targets upon the fovea, where resolution is highest. The serial process of fixation, punctuated by saccadic eye movements, continues until the desired target has been located. Loss of central vision restricts the ability to resolve the high spatial information of a target, interfering with this visual search process. We investigate oculomotor adaptations to central visual field loss with gaze-contingent artificial scotomas. METHODS: Spatial distortions were placed at random locations in 25° square natural scenes. Gaze-contingent artificial central scotomas were updated at the screen rate (75 Hz) based on a 250 Hz eye tracker. Eight subjects searched the natural scene for the spatial distortion and indicated its location using a mouse-controlled cursor. RESULTS: As the central scotoma size increased, the mean search time increased [F(3,28) = 5.27, p = 0.05], and the spatial distribution of gaze points during fixation increased significantly along the x [F(3,28) = 6.33, p = 0.002] and y [F(3,28) = 3.32, p = 0.034] axes. Oculomotor patterns of fixation duration, saccade size, and saccade duration did not change significantly, regardless of scotoma size. CONCLUSIONS: There is limited automatic adaptation of the oculomotor system after simulated central vision loss.

PURPOSE: To measure natural image search performance in patients with central vision impairment. To evaluate the performance effect for a JPEG based image enhancement technique using the visual search task. METHODS: One hundred and fifty JPEG images were presented on a touch screen monitor in either an enhanced or original version to 19 patients (visual acuity 0.4-1.2 logMAR, 6/15 to 6/90, 20/50 to 20/300) and seven normally sighted controls (visual acuity -0.12 to 0.1 logMAR, 6/4.5 to 6/7.5, 20/15 to 20/25). Each image fell into one of three categories: faces, indoors, and collections. The enhancement was realized by moderately boosting a mid-range spatial frequency band in the discrete cosine transform (DCT) coefficients of the image luminance component. Participants pointed to an object in a picture that matched a given target displayed at the upper-left corner of the monitor. Search performance was quantified by the percentage of correct responses, the median search time of correct responses, and an 'integrated performance' measure - the area under the curve of cumulative correct response rate over search time. RESULTS: Patients were able to perform the search tasks but their performance was substantially worse than the controls. Search performances for the three image categories were significantly different (p <= 0.001) for all the participants, with searching for faces being the most difficult. When search time and correct response were analyzed separately, the effect of enhancement led to increase in one measure but decrease in another for many patients. Using the integrated performance, it was found that search performance declined with decrease in acuity (p = 0.005). An improvement with enhancement was found mainly for the patients whose acuity ranged from 0.4 to 0.8 logMAR (6/15 to 6/38, 20/50 to 20/125). Enhancement conferred a small but significant improvement in integrated performance for indoor and collection images (p = 0.025) in the patients. CONCLUSION: Search performance for natural images can be measured in patients with impaired vision to evaluate the effect of image enhancement. Patients with moderate vision loss might benefit from the moderate level of enhancement used here.

Herpes simplex keratitis (HSK) is a major cause of corneal blindness in the world. Following the primary infection, the virus enters into a latent phase. Recurrent infectious or immune keratitis cause structural damage to the cornea, scarring, and may lead to blindness. Several commercially available topical and oral antiviral drugs for HSK are currently available. However, toxicity and low patient compliance hamper their use in HSK. Further, oral antiviral drugs alone are not always effective in HSK. Thus, there had been a need for safe and effective topical antiviral agents against HSK. Systemic ganciclovir has been in use for the treatment of cytomegalovirus infections. Recently, topical ganciclovir has become available for use in patients with HSK. Ganciclovir 0.15% ophthalmic gel has been shown to be both safe and effective against viruses of the herpes family. Topical ganciclovir ophthalmic gel is well tolerated and does not cause significant toxic effects on the ocular surface. Several multicenter studies have revealed the potential role of ganciclovir ophthalmic gel in the treatment and prophylaxis of epithelial HSK. In this paper, we have reviewed the pharmacology, efficacy, side effects, and the role of ganciclovir ophthalmic gel 0.15% in the treatment of acute herpetic keratitis.

PURPOSE: The purpose of this study was to determine the Ca(2+)-dependent cellular signaling pathways used by histamine to stimulate conjunctival goblet cell secretion. METHODS: Cultured rat goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured by loading cultured cells with the Ca(2+) sensitive dye fura-2. The level of [Ca(2+)](i) was measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2 was depleted using small interfering RNA (siRNA). RESULTS: Histamine-stimulated conjunctival goblet cell secretion of high molecular weight glycoproteins was blocked by removal of extracellular Ca(2+) and depletion of ERK2 by siRNA. Histamine increase in [Ca(2+)](i) was desensitized by repeated addition of agonist and blocked by a phospholipase C antagonist. Histamine at higher doses increased [Ca(2+)](i) by stimulating influx of extracellular Ca(2+), but at a lower dose released Ca(2+) from intracellular stores. Activation of each histamine receptor subtype (H(1)-H(4)) increased [Ca(2+)](i) and histamine stimulation was blocked by antagonists of each receptor subtype. The H(2) receptor subtype increase in [Ca(2+)](i) was cAMP dependent. CONCLUSIONS: We conclude that histamine activates phospholipase C to release intracellular Ca(2+) that induces the influx of extracellular Ca(2+) and activates ERK1/2 to stimulate conjunctival goblet cell mucous secretion, and that activation of all four histamine receptor subtypes can increase [Ca(2+)](i).

BACKGROUND: Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC) axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP) are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α) as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death. METHODOLOGY/PRINCIPAL FINDINGS: Episcleral vein cauterization (EVC) caused intraocular pressure (IOP) to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH). Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs. CONCLUSIONS/SIGNIFICANCE: Ocular hypertension (OHT) triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.

The diagnosis of many neuro-ophthalmic conditions is facilitated with neuro-imaging. The two main modalities are Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Clinicians who refer patients for either of these techniques must not only know which of them to choose, but also where the imaging should be performed (e.g. brain, orbit), whether or not contrast is indicated, and if angiography should be supplemented. These complexities often result in imaging studies that are either unneeded or unhelpful. The goal of this manuscript is to provide a practical set of guidelines for the general ophthalmologist of how to choose the correct parameters for neuro-imaging studies.

PURPOSE: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. METHODS: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. RESULTS: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of "mixed" concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott's methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. CONCLUSIONS: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses.

The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.