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Aggarwal S, Jakobiec F, Hamrah P. Bilateral adult epibulbar xanthogranulomas suspicious for Erdheim-Chester disease.. Cornea. 2014;33(10):1113–7.

PURPOSE: The aim of this study was to report the clinical, imaging, and histopathological findings of bilateral, conjunctival adult-onset xanthogranulomas that raised the prospect of a mild form of Erdheim-Chester disease. METHODS: This is a case report. RESULTS: A 35-year-old white male complaining of ocular irritation, presented with bilateral, nasal and temporal, yellow, elevated conjunctival lumps first noticed 1.5 years back, which were not associated with other ocular findings. The lesions were firm, attached to the underlying episclera, and measured 1.1 × 0.9, 1.1 × 0.8, 1.2 × 0.5, and 0.5 × 0.5 cm in the temporal and nasal right and left eyes, respectively. Each mass was fleshy with vascularity at the peripheral margin. Histopathologic evaluation after excisional biopsy revealed lipidized xanthoma cells, multiple Touton giant cells, and lymphocytes. Immunohistochemical staining was positive for adipophilin (lipid), CD68, CD163 histiocytes, CD3 T cells (with CD8 cytotoxic T cells > CD4 T-helper cells), and virtually no CD20 B cells or IgG4 plasma cells. The patient later acquired similar xanthogranulomatous subcutaneous lesions on the extremities. Positron emission tomography scans showed sclerosis in the medullary cavities of the tibia and the radius of both legs and arms, and an absence of retroperitoneal lesions. A normal serum immunoelectrophoresis and the absence of a BRAF gene mutation were demonstrated. CONCLUSIONS: Adult-onset xanthogranuloma can present as a solitary conjunctival mass without periocular or orbital involvement. The clinical, histopathologic, and radiologic findings in this case are suggestive of Erdheim-Chester disease without displaying any life-threatening lesions to date. Histopathologic and imaging studies can help in obtaining a diagnosis. Ophthalmologists should be aware that xanthogranulomatous conditions may have potential systemic implications, and a thorough systemic evaluation is recommended for lesions that initially seemed to be isolated in nature.

Van Tyne D, Gilmore M. Friend turned foe: evolution of enterococcal virulence and antibiotic resistance. Annu Rev Microbiol. 2014;68:337–56.
The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci.
Scotti F, Maestroni A, Palini A, Introini U, Setaccioli M, Lorenzi M, Zerbini G. Endothelial progenitor cells and response to ranibizumab in age-related macular degeneration.. Retina. 2014;34(9):1802–10.

BACKGROUND: Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV. METHODS: The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab. RESULTS: When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell-derived factor 1, but not of monocytic EPCs. CONCLUSION: The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell-derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.

Yonekawa Y, Kim I, Gragoudas E, Njauw CN, Tsao H, Jakobiec F, Stacy R. Aggressive skull base metastasis from uveal melanoma: a clinicopathologic study. Eur J Ophthalmol. 2014;24(5):811–3.
PURPOSE: We present the clinical, pathologic, and genetic findings of the first reported case of choroidal melanoma that developed a late recurrence and aggressive metastasis to the skull base without evidence of hepatic involvement. METHODS: Retrospective chart review and clinicopathologic correlation of ocular and brain tissue, including sequencing of BAP1 for mutations. RESULTS: A 55-year-old woman was diagnosed with choroidal melanoma and treated with proton radiotherapy. Six years later, she developed a rapidly growing local recurrence involving the ciliary body and iris. Upon enucleation, histopathology revealed an iris and ciliary body epithelioid melanoma that was contiguous with the previously treated, regressed spindle cell choroidal melanoma. Imaging was initially negative for brain involvement. Two months later, she developed cranial neuropathies and was found to have a large skull base lesion that required surgical debulking for pain palliation. Histopathology confirmed the lesion to be metastatic melanoma. Both ocular and brain tumor specimens were wild-type for BAP1. Throughout her course, she developed no hepatic metastases. CONCLUSIONS: Uveal melanoma may metastasize to the skull base. The present case was characterized by delayed onset and unusual aggressiveness of the metastatic disease, and lack of BAP1 mutation. The unusual course highlights a unique phenotype that may reflect an alternate molecular mechanism for metastatic disease.
Arafat S, Robert MC, Shukla A, Dohlman C, Chodosh J, Ciolino J. UV cross-linking of donor corneas confers resistance to keratolysis.. Cornea. 2014;33(9):955–9.

PURPOSE: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. METHODS: Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1% riboflavin/20% dextran), and irradiated with ultraviolet A (UV-A) light (λ = 370 nm, irradiance = 3 mW/cm) for various durations. The combined effect of UV-A and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37°C with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. RESULTS: Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 ± 2.6 hours (P < 0.0001). The corneal tissues' resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P > 0.05). γ-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (P = 0.43). CONCLUSIONS: Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A.