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2014

Lefebvre D, Robinson-Bostom L, Migliori M. Cellular neurothekeoma of the eyelid: a unique internal palpebral presentation. Ophthalmic Plast Reconstr Surg. 2014;30(4):e91–2.
A 50-year-old woman presented with a mass lesion of the inferolateral palpebral conjunctiva similar in appearance to a chalazion, but unusual enough in presentation that excisional biopsy was initially performed. Histopathologic analysis revealed a dermal fibrohistiocytic neoplasm consistent with cellular neurothekeoma. Neurothekeoma is a benign tumor; the cellular variant is rare and of unclear histogenesis. Completely internal eyelid location is particularly rare, with other identifiable case reports of cellular neurothekeoma palpebrae referring to external or unspecified eyelid location. This case provides an example of the chalazion as masquerader and re-emphasizes the importance of maintaining a broad differential diagnosis and high index of suspicion regarding atypically appearing chalazia.
Yadav P, Jakobiec F, De Castro D, Mendoza P, Fay A. Extruded, partially disintegrated, poly-HEMA orbital implant (AlphaSphere). Ophthalmic Plast Reconstr Surg. 2014;30(4):e86–91.
A 54-year-old diabetic man underwent enucleation for endophthalmitis. Secondary implantation of a 2-hydroxyethyl methacrylate (HEMA) sphere (AlphaSphere, Addition Technology) was performed 2 weeks later. Six weeks after insertion, noninfectious disintegration of sutured tissue planes represented by Tenon's capsule, rectus muscle, and conjunctiva occurred, requiring removal of the fragmenting implant before uncontrolled extrusion occurred. Histopathologic analysis revealed an absence of infectious pathogens and no tissue necrosis, but rather breakup of the implant material that elicited a granulomatous response with sparse T-lymphocytes and almost no polymorphonuclear leukocytes. This distinctively designed poly-HEMA orbital implant incited a dramatic and irreversible host tissue response. Investigation of other cases will be necessary to determine the frequency of such a complication and should include rigorous histopathologic techniques.
Villarreal G, Chatterjee A, Oh S, Oh DJ, Kang MH, Rhee D. Canonical Wnt signaling regulates extracellular matrix expression in the trabecular meshwork.. Invest Ophthalmol Vis Sci. 2014;

PURPOSE. Canonical Wnt signaling has emerged as a critical regulator of aqueous outflow facility and intraocular pressure (IOP). In this study, we examine the role of canonical Wnt signaling on extracellular matrix (ECM) expression in the trabecular meshwork (TM) and explore the molecular mechanisms involved. METHODS. β-catenin localization in human TM tissue was examined using immunofluorescent staining. Primary human TM cells were incubated with lithium chloride (LiCl) and the effect on active β-catenin expression was assessed by immunoblot. Adenovirus expressing a dominant-negative TCF4 mutant that lacks a β-catenin binding domain was used. Changes in the levels of the microRNA-29 (miR-29) family and ECM proteins were determined by real-time quantitative PCR and immunoblot analysis, respectively. RESULTS. β-catenin was expressed throughout the TM, with localization primarily to the plasma membrane. Incubation of TM cells with lithium chloride increased the expression of active β-catenin. Lithium chloride treatment upregulated miR-29b expression, and suppressed the levels of various ECM proteins under both basal and TGF-β2 stimulatory conditions. Infection of TM cells with a dominant-negative TCF4 mutant induced ECM levels without a significant change in the expression of the miR-29 family. CONCLUSIONS. Collectively, our data identify the canonical Wnt signaling pathway as an important modulator of ECM expression in the TM and provide a mechanistic framework for its regulation of outflow facility and IOP.

Sadaka A, Palmer K, Suzuki T, Gilmore M. In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection. PLoS One. 2014;9(10):e110872.
PURPOSE: To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. METHODS: For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. RESULTS: Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. CONCLUSION: Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.
Yamaguchi T, Calvacanti B, Cruzat A, Qazi Y, Ishikawa S, Osuka A, Lederer JA, Hamrah P. Correlation between Human Tear Cytokine Levels and Cellular Corneal Changes in Patients with Bacterial Keratitis by In Vivo Confocal Microscopy.. Invest Ophthalmol Vis Sci. 2014;

Purpose: To investigate bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs). Methods: Fifty-four (13 BK, 13 contralateral, 28 healthy controls) tear samples were collected prospectively and analyzed by multiplex microbeads assay. IVCM of the central cornea was performed on the same day and assessed for corneal nerve and DC alterations Results: Interleukin (IL)-1β, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6±26.8 ρg/ml, 7,174±2,430, 810±315, P=0.04, P<0.001 and P<0.001), compared to healthy controls (13.0±4.0 ρg/ml, 171.8±32.1, 56.5±33.8). CCL-2, IL-10 and IL-17a were elevated only in contralateral eyes (813±478 ρg/ml, 86.7±38.3, 3,350±881, P=0.02, P=0.01, P=0.04), compared to controls (73.7±25.3 ρg/ml, 17.5 ±4.9, 1,350±337). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in both affected (551±231 ρg/ml, P=0.02) and contralateral unaffected eyes (545±298 ρg/ml, P=0.03), compared to controls (31.3±12.4 ρg/ml). The density of DCs was significantly increased in both affected (226.9±37.3 cells/mm2, P<0.001) and unaffected eyes (122.3±23.7 cells/mm2, P<0.001) compared to controls (22.7±5.9 cells/mm2). Subbasal nerve density significantly decreased in affected eyes (3,337±1,615 μm/mm2, P<0.001) and contralateral eyes (13,230±1,635 μm/mm2, P<0.001) compared to controls (21,200±545 μm/mm2). IL-1β, IL-6 and IL-8 were significantly correlated with DC density (R=0.40, R=0.55 and R=0.31, all P<0.02) and nerve density (R=-0.30, R=-0.53 and R=-0.39, all P<0.01). Conclusions: Pro-inflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM.

Schroedl F, Kaser-Eichberger A, Schlereth S, Bock F, Regenfuss B, Reitsamer H, Lutty G, Maruyama K, Chen L, Lütjen-Drecoll E, Dana R, Kerjaschki D, Alitalo K, De Stefano ME, Junghans B, Heindl L, Cursiefen C. Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.. Invest Ophthalmol Vis Sci. 2014;55(10):6440–2.

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.

Van Tyne D, Gilmore M. A delicate balance: maintaining mutualism to prevent disease.. Cell Host Microbe. 2014;16(4):425–7.

The intestinal microbial ecosystem is complex, and few of the principles that contribute to homeostasis in health are well understood. Pham et al. (2014) show that a network including the epithelial interleukin-22 receptor protects against infection with the opportunistic pathogen Enterococcus faecalis through promotion of host-microbiota mutualism.

Yonekawa Y, Kim I. Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration.. Cold Spring Harb Perspect Med. 2014;

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies.