Accuracy and Reproducibility of Virtual Reality Perimetry in Children.

PURPOSE: To determine normal threshold values for the 24-2 program of the VisuALL-K (Olleyes, Inc), a portable static automated virtual reality perimeter that uses a video game-based testing modality on an updated version of the algorithm and to repeat the test to assess retest variability. METHODS: This prospective cohort study included 19 participants (aged 8 to 17 years) with healthy afferent systems. Participants performed two 24-2 automated perimetry tests on the virtual reality perimeter device. RESULTS: Mean age was 12.7 ± 2.5 years; 53% were boys and 47% were girls. Mean test location threshold was 30.5 ± 4.0 dB for test 1 and 31.3 ± 2.8 dB for test 2. Sensitivity decreased with eccentricity as expected (-0.17 dB per degree). Bland-Altman analysis showed a repeatability coefficient of ±5.1 dB for mean deviation, meaning that 95% of retest values were within ±5 dB of the threshold value for the first test. Higher thresholds for the first test regressed toward the mean values in the second test, indicating a learning effect. Intraclass correlation coefficient for mean deviation between test 1 and test 2 was 0.70 (0.55 to 0.80, P < .0001). Mean time to completion for the virtual reality perimeter was 5.1 ± 1.5 min/eye. CONCLUSIONS: The VisuALL-K virtual reality perimeter provided an assessment of the visual field in normal children aged 8 to 17 years. A shallow hill of vision was demonstrated. A notable learning effect was demonstrated, with repeatability difference wider than other published head-mounted display perimeters. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XX-XX.].

Visualization of Optic Nerve Structural Patterns in Papilledema Using Deep Learning Variational Autoencoders.

Purpose: To visualize and quantify structural patterns of optic nerve edema encountered in papilledema during treatment. Methods: A novel bi-channel deep-learning variational autoencoder (biVAE) model was trained using 1498 optical coherence tomography (OCT) scans of 125 subjects over time from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and 791 OCT scans of 96 control subjects from the University of Iowa. An independent test dataset of 70 eyes from 70 papilledema subjects was used to evaluate the ability of the biVAE model to quantify and reconstruct the papilledema spatial patterns from input OCT scans using only two variables. Results: The montage color maps of the retinal nerve fiber layer (RNFL) and total retinal thickness (TRT) produced by the biVAE model provided an organized visualization of the variety of morphological patterns of optic disc edema (including differing patterns at similar thickness levels). Treatment effects of acetazolamide versus placebo in the IIHTT were also demonstrated in the latent space. In image reconstruction, the mean signed peripapillary retinal nerve fiber layer thickness (pRNFLT) difference ± SD was -0.12 ± 17.34 µm, the absolute pRNFLT difference was 13.68 ± 10.65 µm, and the RNFL structural similarity index reached 0.91 ± 0.05. Conclusions: A wide array of structural patterns of papilledema, integrating the magnitude of disc edema with underlying disc and retinal morphology, can be quantified by just two latent variables. Translational Relevance: A biVAE model encodes structural patterns, as well as the correlation between channels, and may be applied to visualize individuals or populations with papilledema throughout treatment.

Evaluation of Virtual Reality Perimetry and Standard Automated Perimetry in Normal Children.

Purpose: The Olleyes VisuALL-K is a pediatric videogame-based static threshold perimeter using a virtual reality headset. We determined normal threshold sensitivities for the 24-2 test locations using the virtual reality perimetry (VRP) and also tested patients on the Humphrey Field Analyzer (HFA). Patient satisfaction for the two instruments was compared. Methods: This exploratory study tested 50 normal pediatric participants aged 8 to 17 years on the HFA and VRP. The main outcome measure was threshold sensitivity at the 24-2 test locations for the two instruments. Results: The mean participant age was 13.0 ± 2.6 years; 50% were female. The threshold values for VRP are reported as measured on the device and after conversion to an HFA-equivalent scale. Age-adjusted thresholds showed a mean sensitivity of 31.8 ± 1.1 dB (46.1 ± dB HFA equivalent) diminution from the maximum light intensity in the VRP and 31.0 ± 1.5 dB diminution from the maximum light intensity in the HFA; interparticipant variability in mean threshold sensitivity was 2.7 ± 0.4 dB for the VRP and 2.7 ± 0.6 dB for the HFA. The HFA demonstrated decreased threshold sensitivity with increasing eccentricity, whereas the VRP threshold did not seem to vary with eccentricity. Mild age effects on threshold sensitivity were seen in the VRP and the HFA (R2 = 0.11, P < 0.001 and R2 = 0.05, P < 0.05, respectively). The mean time to completion for VRP and HFA was 7.6 ± 1.5 and 5.3 ± 0.9 min/eye, respectively (P < 0.0001). Patient satisfaction scores favored VRP (P < 0.01) despite the longer test duration. Conclusions: The Olleyes game-based VRP and HFA can be used to map out the peripheral vision in normal children. The VRP has a higher patient satisfaction when used in children than the HFA. The portability of the test allows it to be performed in a myriad of environments, lending a flexibility that can benefit this population. Translational Relevance: This virtual reality perimetry device provides an alternative to the Humphrey Field Analyzer for children.

Effect of prophylactic laser during small-gauge vitrectomy for epiretinal membranes.

PURPOSE: To determine the rate of post-operative retinal detachment after elective pars plana vitrectomy for epiretinal membrane, and to test for the mitigating effect of prophylactic endolaser. METHODS: We identified 459 eyes of 411 patients undergoing vitrectomy for epiretinal membrane at Vanderbilt University Medical Center between January 2010 and May 2017. Patients who underwent concurrent endolaser without any identified retinal break were included in the exposure cohort. Patients who underwent no prophylactic retinopexy or ablation were included in the unexposed cohort. Exposure data, demographic data, and outcome data were tabulated for comparison. RESULTS: The final analysis included 343 eyes of 343 patients. Approximately 7% of eyes undergoing ERM surgery were found to have a full-thickness retinal break which was not seen preoperatively. The overall rate of postoperative RD was 2.04%. Postoperative retinal detachment occurred in 0 of the 34 eyes exposed to prophylactic laser, and in 7 of the 309 control eyes. Odds ratio was found to be 0.60 (p = 0.598 (95%CI 0.0327-10.7), p = 0.72), indicated the results were not statistically significant. DISCUSSION: Looking at patients undergoing routine vitrectomy surgery for epiretinal membrane, no retinal detachments occurred in the group receiving prophylactic treatment, though this association did not reach statistical significance. With modern surgical techniques, post-operative retinal detachment remains relatively rare after vitrectomy for ERM though a thorough intraoperative exam is critical to identify occult retinal breaks.

SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis.

The HDL receptor scavenger receptor class B type I (SR-BI) plays crucial roles in cholesterol homeostasis, lipoprotein metabolism, and atherosclerosis. Hepatic SR-BI mediates reverse cholesterol transport (RCT) by the uptake of HDL cholesterol for routing to the bile. Through the selective uptake of HDL lipids, hepatic SR-BI modulates HDL composition and preserves HDL's atheroprotective functions of mediating cholesterol efflux and minimizing inflammation and oxidation. Macrophage and endothelial cell SR-BI inhibits the development of atherosclerosis by mediating cholesterol trafficking to minimize atherosclerotic lesion foam cell formation. SR-BI signaling also helps limit inflammation and cell death and mediates efferocytosis of apoptotic cells in atherosclerotic lesions thereby preventing vulnerable plaque formation. SR-BI is emerging as a multifunctional therapeutic target to reduce atherosclerosis development.

Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis.

Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes. Akt displays isoform-specific effects on atherogenesis, which vary with different vascular cell types. Loss of macrophage Akt2 promotes the anti-inflammatory M2 phenotype and reduces atherosclerosis. However, Akt isoforms are redundant with regard to apoptosis. c-Jun NH2-terminal kinase (JNK) is a pro-apoptotic effector of the UPR, and the JNK1 isoform opposes anti-apoptotic Akt signaling. Loss of JNK1 in hematopoietic cells protects macrophages from apoptosis and accelerates early atherosclerosis. IκB kinase α (IKKα, a member of the serine/threonine protein kinase family) plays an important role in mTORC2-mediated Akt signaling in macrophages, and IKKα deficiency reduces macrophage survival and suppresses early atherosclerosis. Efferocytosis involves the interaction of receptors, bridging molecules, and apoptotic cell ligands. Scavenger receptor class B type I is a critical mediator of macrophage efferocytosis via the Src/PI3K/Rac1 pathway in atherosclerosis. Agonists that resolve inflammation offer promising therapeutic potential to promote efferocytosis and prevent atherosclerotic clinical events. (Circ J 2016; 80: 2259-2268).