Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The near transparency of inner retinal cells is advantageous for vision, as light must pass through them to reach the photoreceptors, but it has prevented them from being directly imaged in vivo. Here we show that the individual somas of neurons within the retinal ganglion cell (RGC) layer can be imaged with a modification of confocal AOSLO, in both monkeys and humans. Human images of RGC layer neurons did not match the quality of monkey images for several reasons, including safety concerns that limited the light levels permissible for human imaging. We also show that the same technique applied to the photoreceptor layer can resolve ambiguity about cone survival in age-related macular degeneration. The capability to noninvasively image RGC layer neurons in the living eye may one day allow for a better understanding of diseases, such as glaucoma, and accelerate the development of therapeutic strategies that aim to protect these cells. This method may also prove useful for imaging other structures, such as neurons in the brain.

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PurposeThe retinoid cycle maintains vision by regenerating bleached visual pigment through metabolic events, the kinetics of which have been difficult to characterize in vivo. Two-photon fluorescence excitation has been used previously to track autofluorescence directly from retinoids and pyridines in the visual cycle in mouse and frog retinas, but the mechanisms of the retinoid cycle are not well understood in primates.MethodsWe developed a two-photon fluorescence adaptive optics scanning light ophthalmoscope dedicated to in vivo imaging in anesthetized macaques. Using pulsed light at 730 nm, two-photon fluorescence was captured from rods and cones during light and dark adaptation through the eye's pupil.ResultsThe fluorescence from rods and cones increased with light exposure but at different rates. During dark adaptation, autofluorescence declined, with cone autofluorescence decreasing approximately 4 times faster than from rods. Rates of autofluorescence decrease in rods and cones were approximately 4 times faster than their respective rates of photopigment regeneration. Also, subsets of sparsely distributed cones were less fluorescent than their neighbors immediately following bleach at 565 nm and they were comparable with the S cone mosaic in density and distribution.ConclusionsAlthough other molecules could be contributing, we posit that these fluorescence changes are mediated by products of the retinoid cycle. In vivo two-photon ophthalmoscopy provides a way to monitor noninvasively stages of the retinoid cycle that were previously inaccessible in the living primate eye. This can be used to assess objectively photoreceptor function in normal and diseased retinas.

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Objectives: The aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)Yguided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. Materials and Methods: This is a retrospective analysis of 115 women (mean age, 42 years; range, 27Y54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean T SD total volume and number of treated fibroids (per patient) were 89 T 94 cm 3 and 2.2 T 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. Results: Magnetic resonance imagingYguided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% T 15% (range, 38%-100%). Mean applied energy level was 5400 T 1200 J, and mean number of sonications was 74 T 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. Conclusions: With technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials.