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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.

We present a refinement of the Fisk-Parker hybrid field of Burger and Hitge which now includes a region bordering the solar rotational equator where magnetic field footpoint motion occurs only through diffusive reconnection. The hybrid field, therefore, only occurs above a certain latitude in a given hemisphere, and in the equatorial region the field is a pure Parker field. We also propose a simple qualitative model for the solar cycle dependence of the hybrid field, taking into account changes in the tilt angle of the heliospheric current sheet and the latitudinal extend of the polar coronal hole on the photosphere and on the source surface over the course of a solar activity cycle. We find that the amplitude of magnetic field fluctuations for assumed solar minimum parameters would not be observable above the background noise (see Roberts and coworkers). We also show that for these parameters, periodicities associated with differential footpoint motion would be barely distinguishable from rigid rotation at the solar equatorial rate. We point out that the question of periodicities in magnetic field data is perhaps more complicated than previously thought. We confirm the result of Burger and Hitge that a Fisk-type heliospheric magnetic field provides a natural explanation for the observed linear relationship between the amplitude of the recurrent cosmic-ray variations and the global latitude gradient (see Zhang). We show that this relationship holds for helium, protons, and electrons. Moreover, we show that the constant of proportionality is larger when qA > 0 than when qA < 0, as inferred from observations by Richardson and coworkers.

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.