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.
Ultrasound images were obtained of the medial gastrocnemius at different ankle joint positions with the knee extended. Fascicle length and deep fascicle angle were measured in five normally developing adults (mean age 33 years, age range 24 to 36 years) and in five normally developing children (mean age 7.8 years, age range 7 to 11 years), and in seven children with spastic diplegia (mean age 10 years, age range 6 to 13 years). These architectural variables were similar in the groups of normally developing adults and children. Importantly, no statistical difference could be found between the normally developing children and those with diplegia for fascicle length. Deep fascicle angles were reduced significantly in the clinical group at a particular ankle joint angle but not at the resting angles. The difference in deep fascicle angles is explained as a function of resting muscle length and is not attributed any clinical importance. Our results do not explain the structural origin of muscle contracture explicitly. However, they do indicate that most of the fixed shortness in the medial gastrocnemii of ambulant children with spastic diplegia is not due to reduced muscle fascicle length. We suggest that muscle contracture may be better explained in terms of shortness of the aponeuroses of pennate muscles, such as the medial gastrocnemius, through reduced muscle fascicle diameter.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.
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