We describe the design and performance of a hand-held actively stabilized tool to increase accuracy in micro-surgery or other precision manipulation. It removes involuntary motion such as tremor by actuating the tip to counteract the effect of the undesired handle motion. The key components are a three-degree-of-freedom piezoelectric manipulator that has 400 μm range of motion, 1 N force capability, and bandwidth over 100 Hz, and an optical position measurement subsystem that acquires the tool pose with 4 μm resolution at 2000 samples/s. A control system using these components attenuates hand motion by at least 15 dB (a fivefold reduction). By considering the effect of the frequency response of Micron on the human visual feedback loop, we have developed a filter that reduces unintentional motion, yet preserves intuitive eye-hand coordination. We evaluated the effectiveness of Micron by measuring the accuracy of the human/machine system in three simple manipulation tasks. Handheld testing by three eye surgeons and three non-surgeons showed a reduction in position error of between 32% and 52%, depending on the error metric.

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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.

The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

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Background and Objective-In laser retinal photocoagulation, hundreds of dot-like burns are applied. We introduce a robot-assisted technique to enhance the accuracy and reduce the tedium of the procedure.Materials and Methods-Laser burn locations are overlaid on preoperative retinal images using common patterns such as grids. A stereo camera/monitor setup registers and displays the planned burn locations overlaid on real-time video. Using an active handheld micromanipulator, a 7×7 grid of burns spaced 650 μm apart is applied to both paper slides and porcine retina in vitro using 30 ms laser pulses at 532 nm. Two scenarios were tested: unaided, in which the micromanipulator is inert and the laser fires at a fixed frequency, and aided, in which the micromanipulator actively targets burn locations and the laser fires automatically upon target acquisition. Error is defined as the distance from the center of the observed burn mark to the preoperatively selected target location.Results-An experienced retinal surgeon performed trials with and without robotic assistance, on both paper slides and porcine retina in vitro. In the paper slide experiments at an unaided laser repeat rate of 0.5 Hz, error was 125±62 μm with robotic assistance and 149±76 μm without (p < 0.005), and trial duration was 70±8 s with robotic assistance and 97±7 s without (p < 0.005). At a repeat rate of 1.0 Hz, error was 129±69 μm with robotic assistance and 166±91 μm without (p < 0.005), and trial duration was 26±4 s with robotic assistance and 47±1 s without (p < 0.005). At a repeat rate of 2.0 Hz on porcine retinal tissue, error was 123±69 μm with robotic assistance and 203±104 μm without (p < 0.005).Conclusion-Robotic assistance can increase the accuracy of laser photocoagulation while reducing the duration of the operation.

We report four children aged 11-18 1/2 yr first seen 7-14 yr after the diagnosis of insulin-dependent diabetes. At presentation, all had marked short stature, two had hepatomegaly, and the older three had delayed adolescence. They had been severely underinsulinized. Initial funduscopy demonstrated only occasion microaneurysms in two children and a single intraretinal hemorrhage in another. The youngest was normal. Improved control required large increases in insulin dosage. Growth rate improved significantly and hepatomegaly regressed. Puberty progressed rapidly in two older patients with poor final height. Paradoxically, with improved control, retinopathy progressed rapidly with appearance of multiple microaneurysms, nerve fiber layer infarctions, intraretinal microangiopathic changes, hemorrhages, exudates, and macular edema in all the patients and severe proliferation changes in three. One child with proliferative retinopathy in both eyes developed vitreous hemorrhage and blindness in one eye. Two required panretinal photocoagulation with no further progression of their retinopathy. These rapidly progressive retinal changes remain unexplained. We advise caution when correcting metabolic derangements of diabetic patients who have been poorly controlled for a prolonged period.