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SummaryPathologic angiogenesis mediated by abnormally polarized macrophages plays a central role in common age-associated diseases such as atherosclerosis, cancer, and macular degeneration. Here we demonstrate that abnormal polarization in older macrophages is caused by programmatic changes that lead to reduced expression of ATP binding cassette transporter ABCA1. Downregulation of ABCA1 by microRNA-33 impairs the ability of macrophages to effectively efflux intracellular cholesterol, which in turn leads to higher levels of free cholesterol within senescent macrophages. Elevated intracellular lipid polarizes older macrophages to an abnormal, alternatively activated phenotype that promotes pathologic vascular proliferation. Mice deficient for Abca1, but not Abcg1, demonstrate an accelerated aging phenotype, whereas restoration of cholesterol efflux using LXR agonists or miR-33 inhibitors reverses it. Monocytes from older humans with age-related macular degeneration showed similar changes. These findings provide an avenue for therapeutic modulation of macrophage function in common age-related diseases.

To describe clinical findings, histopathologic changes, and risk factors for pyogenic granuloma formation complicating silicone punctal plug therapy.Retrospective observational case series.Between November 2000 and April 2004, 903 silicone punctal plugs of the same brand were inserted in 404 subjects. Cases associated with pyogenic granuloma formation were identified and reviewed. Granulation tissue was obtained from 10 patients for histopathologic examination. Multiple risk regression analyses identified factors related to pyogenic granuloma development and factors associated with histologic patterns.Pyogenic granuloma development led to the extrusion of 4.2% of all plugs placed in a median time period of 141 days. All patients presented with varying degrees of plug extrusion. Similar distributions of partial and complete plug extrusions, as well as bilateral and unilateral plug extrusions, were seen. Findings at presentation ranged from a subclinical pyogenic granuloma causing partial plug extrusion to a pyogenic granuloma in the punctum with a ring of fibrovascular tissue retaining a completely extruded plug. Histopathologic examination revealed two patterns, representing either acute pyogenic granuloma or involuting pyogenic granuloma. Pyogenic granulomas resolved after 3.1 +/- 1.3 weeks in all patients after plug removal. Multiple regression analysis revealed that large plug size was associated with increased pyogenic granuloma formation (P.0001). Partial or complete plug extrusion was associated with active or involuting pyogenic granuloma, respectively (P = .023).Pyogenic granuloma-related spontaneous plug extrusions may be more common than previously thought and can present with a range of clinical findings. The degree of plug extrusion correlates with the histopathologic pattern. Larger plug size and sharp edges in plug geometry may be responsible for pyogenic granuloma formation.

PURPOSE To report a case of asymmetric retinopathy of prematurity associated with a peripapillary staphyloma. METHODS Case report. RESULTS A 1,545-g male infant was born at 34 weeks' gestation. He was noted on initial examination to have a peripapillary staphyloma in the left eye and immature retinal vasculature in zone 2 of both eyes. Follow-up examination at 16 weeks of age showed a normal right eye with full vascularization and zone 2, stage 2 retinopathy of prematurity in the left eye. CONCLUSION To our knowledge, this is the first reported case of peripapillary staphyloma in which only the affected eye developed retinopathy of prematurity.

Purpose To evaluate the use of the Boston keratoprosthesis type I implantation in patients with mucous membrane pemphigoid (MMP). Methods Retrospective review of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness as a result of MMP who underwent Boston keratoprosthesis type I implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December 31, 2009. The main outcome measures were best-corrected visual acuity, keratoprosthesis retention, and postoperative complications. Results The mean age of patients was 71.3 years (range, 55-94 years), and the mean duration of their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity after the surgery improved to 20/200 or better in 6 eyes (75%) and to 20/40 or better in 3 eyes (37.5%). Only 1 of 6 eyes (16.7%) was able to maintain visual acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the 8 Boston keratoprosthesis type I devices (62.5%) extruded or had to be replaced during a mean follow-up time of 1.7 ± 1.7 years. Loss of vision to worse than 20/200 during the follow-up period occurred because of keratoprosthesis type I extrusion, end-stage glaucoma, and retinal or choroidal detachment. Conclusions The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are guarded and, as judged from the literature, less favorable than those with the Boston keratoprosthesis type II for the same disease.