Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia.

PURPOSE: To characterize the angiogenic and inflammatory vitreous biomarker profiles in a spectrum of ischemic retinopathies, including neovascular glaucoma. METHODS: This institutional review board-approved study retrospectively analyzed 80 undiluted vitreous samples obtained during pars vitrectomy. The specimens were frozen (-80°C) and sent for concentration analysis of 34 proteins by Bio-Plex Pro assays. Specimens were divided into four groups: patients undergoing epiretinal membrane (ERM) peeling and/or macular hole (MH) surgery with no history of diabetes (non-DM group), patients undergoing ERM peeling, and/or MH surgery with a history of diabetes (DM group), patients with proliferative diabetic retinopathy (PDR group), and patients with neovascular glaucoma (NVG group). Parametric and nonparametric analyses of demographics and cytokine levels were performed using SPSS. RESULTS: There were no significant differences in demographics among cohorts. Numerous proteins were significantly elevated between non-DM and DM (G-CSF, sCD40L, Endoglin, IL-6, placental growth factor [PlGF], VEGF-D), DM and PDR (leptin, IL-8, PlGF, VEGF-A), and PDR and NVG (G-CSF, leptin, TIE-2, sCD40L, EGF, HB-EGF, IL-6, IL-8, PlGF, TNF-α). Only PlGF was significantly elevated between each successive cohort. The most potent drivers of NVG were PlGF, VEGF-A, IL-6, and IL-8. CONCLUSIONS: While the role of angioproliferative growth factors is well documented in ischemic retinopathy, our study delineates the importance of inflammatory and previously underreported angiogenic proteins. It also demonstrates a significant incremental increase in certain factors with increasing levels of ischemia. Both of these findings may guide the development of future therapies for ischemic retinopathies.

Analysis of choroidal morphologic features and vasculature in healthy eyes using spectral-domain optical coherence tomography.

OBJECTIVE: To analyze the morphologic features and vasculature of the choroid in healthy eyes using spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Cross-sectional retrospective review. PARTICIPANTS: Forty-two healthy subjects (42 eyes) with no ocular disease who underwent high-definition scanning with Cirrus high-definition OCT (Carl Zeiss Meditec, Inc., Dublin, CA) at the New England Eye Center, Boston, Massachusetts, between November 2009 and September 2010. METHODS: The SD OCT images were evaluated for morphologic features of the choroid, including the shape of the choroid-scleral border, location of the thickest point of choroid, and regions of focal choroidal thinning. Total choroidal thickness and large choroidal vessel layer thickness were measured by 2 independent observers experienced in analyzing OCT images using the Cirrus linear measurement tool at the fovea, 750 µm nasal and temporal to the fovea. Custom software was used to calculate the ratio of choroidal stroma to the choroidal vessel lumen. MAIN OUTCOME MEASURES: Qualitative assessment of the choroidal morphologic features, quantitative analysis of choroidal vasculature, and use of novel automated software to determine the ratio of choroidal stromal area to the area of choroidal vessel lumen. RESULTS: The 42 subjects had a mean age of 51.6 years. All subjects (100%) had a so-called bowl or convex shape to the choroid-sclera junction, and the thickest point of the choroid was under the fovea in 88.0% of the subjects. The mean choroidal thickness was 256.8 ± 75.8 µm, mean thickness of the large choroidal vessel layer was 204.3 ± 65.9 µm, and that of the medium choroidal vessel layer-choriocapillaris layer was 52.9 ± 20.6 µm beneath the fovea. The ratio of large choroidal vessel layer thickness to the total choroidal thickness beneath the fovea was 0.7 ± 0.06. The software-generated ratio of choroidal stromal area to the choroidal vessel lumen area was 0.27 ± 0.08, suggesting that choroidal vessel lumen forms a greater proportion of the choroid than the choroidal stroma in healthy eyes. CONCLUSIONS: This is the first study to describe the morphologic features and vasculature of the choroid in healthy eyes from 1-line raster scans obtained using SD OCT. The method described holds promise and has immediate clinical usefulness in recognizing subtle changes in choroidal morphologic features and the role of choroidal angiopathy in various disease states that, in the future, may inform new treatment methods. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Lipofuscin and the principles of fundus autofluorescence: a review.

Fundus autofluorescence is a non-invasive imaging modality that measures lipofuscin that has accumulated in the retinal pigment epithelium (RPE). Excessive lipofuscin in the RPE is a common pathway found in several diseases including Stargardt's disease and age-related macular degeneration. This review discusses the role of photooxidative damage in the development of lipofuscin and the principles of fundus autofluorescence.

A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude.

The transcription factor Clock (Clk) plays a critical role in animal circadian rhythms. Genetic studies defining its function have relied on two dominant negative alleles, one in Drosophila and one in mice. Here we describe a novel recessive allele of Drosophila Clock, Clk(ar). Homozygous Clk(ar) flies are viable and behaviorally arrhythmic. The Clk(ar) phenotype is caused by a splice site mutation that severely disrupts splicing and reduces Clk activity. Despite the behavioral arrhythmicity, molecular oscillations are still detectable in Clk(ar) flies. Transcription analysis indicates potent effects of Clk(ar) on levels and amplitude of transcriptional oscillations. Taken together with other data, we propose that Clk makes a major contribution to the strength and amplitude of circadian rhythms.