Angiogenesis underlies the majority of eye diseases that result in catastrophic loss of vision. Recent evidence has implicated the integrins r4P3 and Cv435 in the angiogenic process. We examined the expression of C4133 and CX485 in neovascular ocular tissue from patients with subretinal neovascularization from age-related macular degeneration or the presumed ocular histoplasmosis syndrome or retinal neovascularization from proliferative diabetic retinopathy (PDR). Only rv13 was observed on blood vessels in ocular tissues with active neovascularization from patients with age-related macular degeneration or presumed ocular histoplasmosis, whereas both aP3 and aP5 were present on vascular cells in tissues from patients with PDR Since we observed both integrins on vascular cells from tissues of patients with retinal neovascularization from PDR, we examined the effects of a systemically administered cyclic peptide antagonist of aM83 and C4185 on retinal angiogenesis in a murine model. This antagonist specifically blocked new blood vessel formation with no effect on established vessels. These results not only reinforce the concept that retinal and subretinal neovascular diseases are distinct pathological processes, but that antagonists of a433 and/or aC45 may be effective in treating individuals with blinding eye disease associated with angiogenesis.The pathological growth of new blood vessels underlies most eye diseases that cause catastrophic loss of vision. The leading cause of blindness in individuals over the age of 55 is agerelated macular degeneration (ARMD); under 55 years of age, the leading cause is proliferative diabetic retinopathy (PDR) (1). The two diseases are further distinguished by the specific site of new blood vessel growth; ARMD is characterized by choroidal neovascularization (2), whereas in PDR retinal blood vessels proliferate along the surface of the retina and into the posterior vitreous (3). [The posterior eye has a dual blood supply consisting of (i) the retinal blood vessels that branch from the central retinal artery and supply the inner one-third of the retina and (ii) the choroid that forms an extensive subretinal vascular plexus and nourishes the outer two-thirds of the retina.] While ARMD and PDR are prototypic diseases for choroidal and retinal neovascularization, respectively, other conditions can selectively cause angiogenesis of either vasculature. In general, diseases of a degenerative (e.g., ARMD, pathological myopia) or inflammatory [e.g., presumed ocular histoplasmosis syndrome (POHS)] nature manifest as choroidal neovascularization, whereas ischemic diseases (e.g., PDR, retinopathy of prematurity, sickle cell retinopathy) result in retinal angiogenesis. Although a number of recent studies have demonstrated an association between elevated intraocular levels of vascular endothelial growth factor (VEGF) and ischemia-related retinal neovascularization (4-6), very little is known about the mechanism underlying vasoproliferation in these neovascular eye diseases.

Purpose Accurate and timely organs‐at‐risk (OARs) segmentation is key to efficient and high‐quality radiation therapy planning. The purpose of this work is to develop a deep learning‐based method to automatically segment multiple thoracic OARs on chest computed tomography (CT) for radiotherapy treatment planning. Methods We propose an adversarial training strategy to train deep neural networks for the segmentation of multiple organs on thoracic CT images. The proposed design of adversarial networks, called U‐Net‐generative adversarial network (U‐Net‐GAN), jointly trains a set of U‐Nets as generators and fully convolutional networks (FCNs) as discriminators. Specifically, the generator, composed of U‐Net, produces an image segmentation map of multiple organs by an end‐to‐end mapping learned from CT image to multiorgan‐segmented OARs. The discriminator, structured as an FCN, discriminates between the ground truth and segmented OARs produced by the generator. The generator and discriminator compete against each other in an adversarial learning process to produce the optimal segmentation map of multiple organs. Our segmentation results were compared with manually segmented OARs (ground truth) for quantitative evaluations in geometric difference, as well as dosimetric performance by investigating the dose‐volume histogram in 20 stereotactic body radiation therapy (SBRT) lung plans. Results This segmentation technique was applied to delineate the left and right lungs, spinal cord, esophagus, and heart using 35 patients’ chest CTs. The averaged dice similarity coefficient for the above five OARs are 0.97, 0.97, 0.90, 0.75, and 0.87, respectively. The mean surface distance of the five OARs obtained with proposed method ranges between 0.4 and 1.5 mm on average among all 35 patients. The mean dose differences on the 20 SBRT lung plans are −0.001 to 0.155 Gy for the five OARs. Conclusion We have investigated a novel deep learning‐based approach with a GAN strategy to segment multiple OARs in the thorax using chest CT images and demonstrated its feasibility and reliability. This is a potentially valuable method for improving the efficiency of chest radiotherapy treatment planning.

Objective To evaluate the association of subretinal hyper-reflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar in the Comparison of Age related Macular Degeneration Treatments Trials (CATT) Design Prospective cohort study within a randomized clinical trial. Participants The 1185 participants in CATT. Methods Participants were randomly assigned to ranibizumab or bevacizumab treatment monthly or as-needed. Masked readers graded scar and GA on fundus photography and fluorescein angiography images, SHRM on time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1mm2, or outside the center 1mm2 were obtained on SD-OCT images at 56 (n=76) and 104 (n=66) weeks. VA was measured by certified examiners. Main Outcome Measures SHRM presence, location and size, and associations with VA, scar, and GA. Results Among all CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than eyes with SHRM that resolved (64% vs. 31%; p<0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n=76) and 104 (n=66), mean [SE] VA letter score was 73.5 [2.8], 73.1 [3.4], 65.3 [3.5], and 63.9 [3.7] when SHRM was absent, present outside the central 1mm2, present within the central 1mm2 but not the foveal center, or present at the foveal center (p=0.02). SHRM was present at the foveal center in 43 (30%), within the central 1mm2 in 21 (15%) and outside the central 1mm2 in 19 (13%). When SHRM was present, the median maximum height in microns under the fovea, within the central 1 mm2 including the fovea and anywhere within the scan was 86; 120; and 122, respectively. VA was decreased with greater SHRM height and width (p<0.05). Conclusions SHRM is common in eyes with NVAMD and often persists after anti-VEGF treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM height and width were associated with worse VA. SHRM is an important morphological biomarker in eyes with NVAMD.

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

No abstract