Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings.
Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5 ؉/؉ , T cells from CCR5 ؊/؊ mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-⌬32/⌬32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of CCR5 in human T cells results in enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2 protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation. Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5 had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5 expression also promoted IL-2-dependent events, including CD25 expression, STAT5 phosphorylation, and T cell proliferation. We therefore suggest that by influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2-dependent events, CCR5 may play a critical role in T cell responses. In accord with our prior inferences from geneticepidemiologic studies, such CCR5-dependent responses might constitute a viral entry-independent mechanism by which CCR5 may influence HIV-AIDS pathogenesis.
Purpose To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in retinal hemisphere corresponding abnormal visual hemifield; and that there are significant associations between reduced retinal sensitivity (RS) in abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere. Design prospective, non-randomized, case-control study. Participants Thirty eyes of 30 glaucoma patients with visual field loss confined to a single hemifield, and 27 eyes of 27 controls. Methods Normal and glaucomatous eyes underwent Spectral-domain optical coherence tomography (SDOCT) and standard automated perimetry. Doppler SDOCT with a double-circle scanning pattern was used to measure RBF. RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) values were calculated. The retinal sensitivity values were converted to 1/Lambert. Analysis of variance and regression analyses were performed. Main outcome measures Total and hemispheric retinal sensitivity, RBF, RNFL and GCC values. Results The total RBF (34.6±12.2μL/min) and venous cross sectional area (0.039±0.009mm2) were reduced (p<0.001) in glaucoma compared with controls (46.5±10.6; 0.052±0.012mm2). Mean RBF was reduced in abnormal hemisphere compared to the opposite hemisphere (15.3±5.4 vs 19.3±8.4μL/min, p=0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0±20.2, 103.7±20.6μm, p=0.002; 77.6±12.1 and 83.6±10.1μm, p=0.04). The RBF was correlated with RNFL (r=0.41, p=0.02) and GCC (r=0.43, p=0.02), but not the retinal sensitivity (r=0.31, p=0.09) in the abnormal hemisphere. The RBF (19.3±8.4μL/min), RNFL (103.7±20.6μm) and GCC (83.6±10.1μm) were reduced (p<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2±5.3μL/min; 124.8±9.6μm; 96.1±5.7μm respectively). Conclusions In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF, and RNFL and GCC loss are also observed in the perimetrically-normal hemisphere of glaucomatous eyes.
Purpose To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD-OCT) measurements at baseline visit. Design Multi-center longitudinal observational study. Glaucoma suspects and pre-perimetric glaucoma participants in the Advanced Imaging for Glaucoma Study. Methods The optic disc, the peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) were imaged with FD-OCT VF was assessed every 6 months. Conversion to perimetric glaucoma was defined by VF pattern standard deviation (PSD) or glaucoma hemifield test (GHT) outside normal limits on 3 consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. Predictive accuracy was measured by the area under the receiver-operating-characteristic curve (AUC). Results Of 513 eyes (309 participants), 55 eyes (46 participants) experienced VF conversion during 41 ± 23 months of follow-up. Significant (p<0.05, Cox regression) FD-OCT risk factors included all GCC, NFL, and disc variables, except for horizontal cup-to-disc ratio. GCC focal loss volume (FLV) was the best single predictor of conversion (AUC=0.753, p<0.001 for test against AUC = 0.5). Those with borderline or abnormal GCC-FLV had a 4-fold increase in conversion risk after 6 years (Kaplan-Meier). Optimal prediction of conversion was obtained using the glaucoma composite conversion index (GCCI) based on a multivariate Cox regression model that included GCC-FLV, inferior NFL quadrant thickness, age, and VF PSD. GCCI significantly improved predictive accuracy (AUC=0.783) over any single variable (p=0.04). Conclusions Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and pre-perimetric glaucoma patients.
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