Summary The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Here, we build a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual’s methylome ages, which we show is impacted by gender and genetic variants. Furthermore, we show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. Our model highlights specific components of the aging process and provides a quantitative read-out for studying the role of methylation in age-related disease.

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The nuclei of the outer nuclear layer are significantly attenuated in eyes with disciform age-related macular degeneration, while the ganglion cell and inner nuclear layers are relatively preserved. These findings suggest that replacement of outer nuclear function, by either retinal transplantation or implantation of the intraocular retinal prosthesis, might be a feasible therapeutic option for patients with this condition.

Although the nuclei of the outer nuclear layer in eyes with GA were markedly attenuated, the nuclei of the inner nuclear layer were relatively preserved. There was also a significant reduction in ganglion cells in GA eyes, but considerable numbers remained even in the areas of complete retinal pigment epithelium atrophy. This finding suggests that therapies aimed at replacing outer nuclear function (such as neural retinal and retinal pigment epithelium transplantation or implantation of the intraocular retinal prosthesis) may be feasible for restoring vision in these patients.

Manual and semiautomated grading methods showed similar levels of reproducibility for assessing areas of decreased autofluorescence in patients with Stargardt disease phenotype. Excellent agreement and reproducibility were observed for well demarcated lesions.

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.

Quantifying preserved retinal pigment epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is highly reproducible. These variables would be potential anatomic outcome measures for CHM clinical trials and could be studied and tracked longitudinally in choroideremia.

Citation: Yehoshua Z, Gregori G, Sadda SR, et al. Comparison of drusen area detected by spectral domain optical coherence tomography and color fundus imaging. Invest Ophthalmol Vis Sci. 2013;54;4:24294: -24344: . DOI:10.1167 PURPOSE. To compare the measurements of drusen area from manual segmentation of color fundus photographs with those generated by an automated algorithm designed to detect elevations of the retinal pigment epithelium (RPE) on spectral domain optical coherence tomography (SD-OCT) images. METHODS.Fifty eyes with drusen secondary to nonexudative age-related macular degeneration were enrolled. All eyes were imaged with a high-definition OCT instrument using a 200 3 200 A-scan raster pattern covering a 6 mm 3 6 mm area centered on the fovea. Digital color fundus images were taken on the same day. Drusen were traced manually on the fundus photos by graders at the Doheny Image Reading Center, whereas quantitative OCT measurements of drusen were obtained by using a fully automated algorithm. The color fundus images were registered to the OCT data set and measurements within corresponding 3-and 5-mm circles centered at the fovea were compared. . The mean differences between color images and the SD-OCT (color À SD-OCT) were 0.36 (60.93) (P ¼ 0.008) for the 3-mm circle and 1.26 (61.38) (P < 0.001) for the 5-mm circle measurements. Intraclass correlation coefficients of agreements for 3-and 5-mm measurements were 0.599 and 0.540, respectively. RESULTS. The mean areas (6SD [rangeCONCLUSIONS. There was only fair agreement between drusen area measurements obtained from SD-OCT images and color fundus photos. Drusen area measurements on color fundus images were larger than those with SD-OCT scans. This difference can be attributed to the fact that the OCT algorithm defines drusen in terms of RPE deformations above a certain threshold, and will not include small, flat drusen and subretinal drusenoid deposits. The two approaches provide complementary information about drusen.