Spectral analysis of heart rate variability (HRV) might provide an index of relative sympathetic (SNS) and parasympathetic nervous system (PNS) activity during exercise. Eight subjects completed six 17-min submaximal exercise tests and one resting measurement in the upright sitting position. During submaximal tests, work rate (WR) was increased for the initial 3 min in a ramp fashion until it reached constant WRs of 20 W, or 30, 60, 90, 100, and 110% of the predetermined ventilatory threshold (Tvent). Ventilatory profile and alveolar gas exchange were monitored breath by breath, and beat-to-beat HRV was measured as R-R intervals of an electrocardiogram. Spectral analysis was applied to the HRV from 7 to 17 min. Low-frequency (0-0.15 Hz) and high-frequency (0.15-1.0 Hz) areas under power spectra (LO and HI, respectively) were calculated. The indicator of PNS activity (HI) decreased dramatically (P less than 0.05) when the subjects exercised compared with rest and continued to decrease until the intensity reached 60% Tvent. The indicator of SNS activity (LO/HI) remained unchanged up to 100% Tvent, whereas it increased abruptly (P less than 0.05) at 110% Tvent. The results suggested that (cardiac) PNS activity decreased progressively from rest to a WR equivalent to 60% Tvent, and SNS activity increased only when exercise intensity exceeded Tvent.

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.

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