Utility of scores to predict alcohol use after liver transplant: Take them with a grain of salt.

The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. After LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol testing. Patients with alcohol-associated liver disease were stratified by < or > 6 months of sobriety before listing. Those with <6 months were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was the utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict a return to alcohol use (+phosphatidylethanol) within 1 year after LT. Of the 365 LT, 86 had > 6 months of sobriety, and 85 had <6 months of sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, the return to drinking was similar in the AH (24%) compared to <6-month non-AH (15%) and >6-month alcohol-associated liver disease (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict a return to alcohol was low (accuracy 61%-63%) with poor sensitivity (46% and 37%), specificity (67%-68%), positive predictive value (22%-26%) with moderate negative predictive value (81%-83%), respectively with higher negative predictive values (95%) in predicting a return to heavy drinking. Both SALT and HRAR scores had good negative predictive value in identifying patients at low risk for recidivism.

Clinical Report: Clinician Feedback on the Magnetic Levator Prosthesis.

SIGNIFICANCE: Stakeholder engagement has been identified by national health organizations as a crucial step to successful translation of new health care treatments. In this clinical report, clinician-stakeholder feedback is presented for the magnetic levator prosthesis (MLP), a promising noninvasive spectacle device that restores eyelid motility with magnetic force. PURPOSE: This study aimed to evaluate MLP clinical need and translational barriers. METHODS: Ten vision rehabilitation optometrists who attended an educational presentation on the MLP and participated in a hands-on workshop in the fitting of a patient were invited to complete an anonymous online survey. Ten multiple-choice items gathered data on estimated patient need, current approaches, main barriers to MLP, temporary versus chronic use, cost barriers, and need for insurance coverage. Open fields allowed for additional comments. RESULTS: Nine of 10 specialists completed the survey. Of those, seven answered that they could potentially see at least 1 to 5 patients for ptosis management within a year. The most common ptosis management options reported were the ptosis crutch, taping the eyelid open, and oxymetazoline drops, all with six responses each. Seven clinicians indicated that cost was a main concern. If cost to patient was not a barrier, all indicated they would be at least somewhat likely to try the MLP (1) for temporary management of ptosis, (2) as a pre-surgical trial, and (3) for long-term management of ptosis, with more selecting extremely likely and very likely than somewhat likely. Main comments were expressing enthusiasm for the technology and that it would be more appealing for patients if covered by insurance. CONCLUSIONS: This clinical report suggests that the main barriers to clinical success of the MLP may be cost and insurance coverage, appearance of the device, and self-application. Possible solutions are cost-benefit analysis research, engineering efforts to reduce spectacle magnet size and improve the ease of eyelid magnet application.

Reduction in Nosocomial Infections in Patients With Cirrhosis During the COVID-19 Era Compared with Pre-COVID-19: Impact of Masking and Restricting Visitation.

Nosocomial infections (NIs) in critically ill patients with cirrhosis result in higher death and transplant delisting. NIs are promoted by staff, visitors, and the environment, all of which were altered to reduce pathogen transmission after COVID-19. Two cohorts of intensive care unit patients with cirrhosis from March 2019 to February 2020 (pre-COVID, n = 234) and March 2020 to March 2021 (COVID era, n = 296) were included. We found that despite a higher admission MELD-Na, qSOFA, and WBC count and requiring a longer intensive care unit stay, COVID-era patients developed lower NIs (3% vs 10%, P < 0.001) and had higher liver transplant rates vs pre-COVID patients. COVID-era restrictions could reduce NIs in critically ill patients with cirrhosis.

Effects of Perceptual-motor Training on Collision Judgments with Peripheral Prism Expanded Vision.

SIGNIFICANCE: Peripheral prisms (p-prisms) improve blind-side detection of hazards in hemianopia by shifting the image of the hazard into the intact visual field. Collision judgments can be made accurately after detection by using a gaze shift to fixate the hazard in the prism-free portion of the lens, but this is slow relative to normal peripheral vision. A prior study found that prism adaptation for visual direction did not occur with general wear. We developed a perceptual-motor training regimen that resulted in accurate pointing at p-prism targets after six 1-hour sessions. PURPOSE: This study aimed to determine if improvements in pointing accuracy from perceptual-motor training generalized to collision judgments during simulated walking. METHODS: Participants with hemianopia (n = 13) made collision judgments in virtual reality for a person appearing 0.4 to 13.5° from the walking path. Judgments were measured under fixed gaze, requiring collision judgments via the p-prism image only, and free gaze, representing a more natural scenario. Measurements were made without and with p-prisms immediately after fitting, after a 2-week acclimation, after training, and 3 months later. Controls (n = 13) did one visit without p-prisms. RESULTS: Controls had 100% detection and symmetrically distributed collision judgments for the central 33 and 36% of hazards under fixed gaze and free gaze, respectively. In hemianopia, the seeing side was not different from controls. Blind-side detection was reduced without p-prisms to 40% fixed gaze and 82% free gaze and improved with p-prisms to 99% fixed gaze and 97% free gaze (P < .001). When first worn, fixed-gaze prism side collisions were 63 versus 37% on the seeing side and 41 versus 39% for free gaze (P < .001). There was a small improvement for fixed gaze after the 2-week acclimation (53%, P < .001), but no improvements from training or an additional 3 months of use. CONCLUSIONS: P-prisms improved detection, but collision judgments were inaccurate when seen only via the p-prisms and did not improve with perceptual-motor training. Patients should continue to be advised to turn their head and eyes to fixate the hazard after detection.

Investigating differences between tamoxifen resistant and sensitive breast cancer cells with flow cytometry.

The active metabolite of tamoxifen, 4-hydroxytamoxifen, functions as an anti-estrogen in breast cancer cells and thus inhibits proliferation. While tamoxifen continues to be successfully used to treat estrogen-dependent breast cancer, most patients receiving treatment will develop chemoresistance over time. Two commonly reported biomarkers of tamoxifen resistance are decreased expression of insulin-like growth factor 1 receptor (IGF-1R) and increased expression of epidermal growth factor receptor (EGFR). In prior work we have shown that these receptors facilitate chemoresistance and have unique regulatory functions measurable in resistant cell lines compared with nonresistant. Thus, we hypothesized that these receptors and a newly identified biomarker, integrin ß1, may be used to search for the presence of resistant breast cancer cells within a population of cells that are sensitive to tamoxifen therapy. We tested this by designing a straightforward cell-labeling approach to measure differences in the receptor expression of resistant vs. sensitive cells cytometrically. Our results show that separation is possible when observing the expression of IGF-1R as well as integrin ß1. Interestingly, we found no detectable difference in EGFR expression between tamoxifen resistant and -sensitive cells when measured with cytometry despite the fact that EGFR is upregulated in resistant cells. Our long-term goal is to utilize sorting to isolate tamoxifen resistant subpopulations of cells by receptor expression level. Isolating rare resistant cells that reside within a population of drug-sensitive cells will offer new insights into why chemoresistance occurs.

A smartphone ocular alignment measurement app in school screening for strabismus.

BACKGROUND: Strabismus is the leading risk factor for amblyopia, which should be early detected for minimized visual impairment. However, traditional school screening for strabismus can be challenged due to several factors, most notably training, mobility and cost. The purpose of our study is to evaluate the feasibility of using a smartphone application in school vision screening for detection of strabismus. METHODS: The beta smartphone application, EyeTurn, can measure ocular misalignment by computerized Hirschberg test. The application was used by a school nurse in a routine vision screening for 133 elementary school children. All app measurements were reviewed by an ophthalmologist to assess the rate of successful measurement and were flagged for in-person verification with prism alternating cover test (PACT) using a 2.4Δ threshold (root mean squared error of the app). A receiver operating characteristic (ROC) curve was used to determine the best sensitivity and specificity for an 8Δ threshold (recommended by AAPOS) with the PACT measurement as ground truth. RESULTS: The nurse obtained at least one successful app measurement for 93% of children (125/133). 40 were flagged for PACT, of which 6 were confirmed to have strabismus, including 4 exotropia (10△, 10△, 14△ and 18△), 1 constant esotropia (25△) and 1 accommodative esotropia (14△). Based on the ROC curve, the optimum threshold for the app to detect strabismus was determined to be 3.0△, with the best sensitivity (83.0%), specificity (76.5%). With this threshold the app would have missed one child with accommodative esotriopia, whereas conventional screening missed 3 cases of intermittent extropia. CONCLUSIONS: Results support feasibility of use of the app by personnel without professional training in routine school screenings to improve detection of strabismus.

Case Series: Periodic Accommodative Fluctuations after Concussion.

SIGNIFICANCE: This is the first report recording an accommodative disorder after concussion characterized by periodic moderately sized myopic refractive error fluctuations without measurable other features of spasm of the near reflex. PURPOSE: Objectively document a class of accommodative dysfunction that may be related to concussion. CASE REPORTS: Case 1 involved two sports-related concussions 2 months apart with symptoms of headache and variable blur. Refractive stability was measured 28 months after injury with a binocular open-field refractometer documenting fluctuations from -0.25 to -1.75 D occurring 10 times during 4.2 seconds of recording with no evident miosis or convergent strabismus. The symptoms resolved with 1% atropine × 3 weeks. Case 2 involved a concussive blast injury (improvised explosive device) 7 years prior with symptoms of headache behind the eyes and occasional variable blur and reduced tolerance of electronic displays and other visually intensive tasks. Refractive fluctuations from +0.50 to -2.00 D occurred seven times over 44 seconds of recording with no appreciable miosis or change of interpalpebral fissure. The signs and symptoms were unresponsive to seven occupational therapy sessions involving task modifications and accommodative vision therapy activities. CONCLUSIONS: In patients complaining of blurry vision, a careful evaluation of the stability of accommodation is indicated.

Measuring Virtual Reality Headset Resolution and Field of View: Implications for Vision Care Applications.

SIGNIFICANCE: To judge the feasibility of virtual reality (VR) headsets for vision testing and treatment of binocular vision disorders and low vision, angular resolution (logMAR) and field of view must be known and may not be reliably provided. This is the first study to measure the limitations of VR systems for eye care applications. PURPOSE: This study aimed to measure, in a sample of VR headsets, eye-to-screen distance and other physical and optical characteristics needed to calculate minimum angular resolution in logMAR and field of view in determining feasibility for vision applications. METHODS: Eye-to-screen distance was measured, and logMAR, field of view, and maximum convergence demand were calculated for two standalone VR devices, Oculus Rift DK2 and HTC Vive, and, for four smartphone VR headsets, Zeiss VR1, Samsung Gear VR, VR Box, and SunnyPeak, each paired with four high-resolution smartphones, Samsung Galaxy S7/S8, iPhone X, and LG VR30. RESULTS: On average, the smallest letter that could be displayed in VR was 0.41 ± 0.09 (20/51), ranging from 0.59 (20/78) in the DK2 to 0.28 (20/39) in VR Box with S7. Mean field of view was 50.2 ± 4.8°, ranging from 39.6° in the VR Box with S7 to 55° in the HTC Vive. The mean field of view when used as a low vision aid was 23.0° and 12.7° for 2.2× and 4×, respectively. The mean maximum near convergence demand produced for a 60-mm interpupillary distance was 38.6 ± 10.1Δ. CONCLUSIONS: The minimum angular resolution in logMAR of current VR technology is insufficient for visual acuity testing and may be insufficient for standalone treatment of amblyopia. Field of view during movie watching or gaming is about half that reported by manufacturers but adequate for some types of visual field testing. Use for vergence testing and training is a concern for headsets with long eye-to-screen distance or interpupillary distances <60 mm.

Fluorescence lifetime shifts of NAD(P)H during apoptosis measured by time-resolved flow cytometry.

Autofluorescence from the intracellular metabolite, NAD(P)H, is a biomarker that is widely used and known to reliably screen and report metabolic activity as well as metabolic fluctuations within cells. As a ubiquitous endogenous fluorophore, NAD(P)H has a unique rate of fluorescence decay that is altered when bound to coenzymes. In this work we measure the shift in the fluorescence decay, or average fluorescence lifetime (1-3 ns), of NAD(P)H and correlate this shift to changes in metabolism that cells undergo during apoptosis. Our measurements are made with a flow cytometer designed specifically for fluorescence lifetime acquisition within the ultraviolet to violet spectrum. Our methods involved culture, treatment, and preparation of cells for cytometry and microscopy measurements. The evaluation we performed included observations and quantification of the changes in endogenous emission owing to the induction of apoptosis as well as changes in the decay kinetics of the emission measured by flow cytometry. Shifts in NAD(P)H fluorescence lifetime were observed as early as 15 min post-treatment with an apoptosis inducing agent. Results also include a phasor analysis to evaluate free to bound ratios of NAD(P)H at different time points. We defined the free to bound ratios as the ratio of 'short-to-long' (S/L) fluorescence lifetime, where S/L was found to consistently decrease with an increase in apoptosis. With a quantitative framework such as phasor analysis, the short and long lifetime components of NAD(P)H can be used to map the cycling of free and bound NAD(P)H during the early-to-late stages of apoptosis. The combination of lifetime screening and phasor analyses provides the first step in high throughput metabolic profiling of single cells and can be leveraged for screening and sorting for a range of applications in biomedicine. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Peripheral Prisms Improve Obstacle Detection during Simulated Walking for Patients with Left Hemispatial Neglect and Hemianopia.

SIGNIFICANCE: The first report on the use of peripheral prisms (p-prisms) for patients with left neglect and homonymous visual field defects (HVFDs). PURPOSE: The purpose of this study was to investigate if patients with left hemispatial neglect and HVFDs benefit from p-prisms to expand the visual field and improve obstacle detection. METHODS: Patients (24 with HVFDs, 10 of whom had left neglect) viewed an animated, virtual, shopping mall corridor and reported if they would have collided with a human obstacle that appeared at various offsets up to 13.5° from their simulated walking path. There were 40 obstacle presentations on each side, with and without p-prisms. No training with p-prisms was provided, and gaze was fixed at the center of expansion. RESULTS: Detection on the side of the HVFD improved significantly with p-prisms in both groups, from 26 to 92% in the left-neglect group and 43 to 98% in the non-neglect group (both P < .001). There was a tendency for greater improvement in the neglect patients with p-prisms. For collision judgments, both groups exhibited a large increase in perceived collisions on the side of the HVFD with the prisms (P < .001), with no difference between the groups (P = .93). Increased perceived collisions represent a wider perceived safety margin on the side of the HVFD. CONCLUSIONS: Within the controlled conditions of this simulated, collision judgment task, patients with left neglect responded well to initial application of p-prisms exhibiting improved detection and wider safety margins on the side of the HVFD that did not differ from non-neglect patients. Further study of p-prisms for neglect patients in free-gaze conditions after extended wear and in real-world mobility tasks is clearly warranted.

Patching for Diplopia Contraindicated in Patients with Brain Injury?

PURPOSE: Patching for double vision is a common palliative treatment for head-trauma patients with acquired strabismus when prisms are not feasible. METHODS: We review literature on spatial neglect and discuss possible effects of monocular occlusion on spatial attention. RESULTS: Patching the left eye has been shown to worsen spatial judgments in some brain-injured patients with left neglect by inhibiting the right superior colliculus further impairing contralateral leftward orienting (the Sprague Effect). CONCLUSIONS: Because more peripheral parts of the visual field increasingly project to the contralateral superior colliculus with the temporal crescent being entirely contralateral, avoiding patching of the temporal crescent was advised, and in most cases can be achieved by taping off the spectacle lens and avoiding an elastic eye patch.

Loss of interleukin-21 receptor activation in hypoxic endothelial cells impairs perfusion recovery after hindlimb ischemia.

OBJECTIVE: Surgical hindlimb ischemia (HLI) in mice has become a valuable preclinical model to study peripheral arterial disease. We previously identified that the different phenotypic outcomes after HLI across inbred mouse strains is related to a region on the short arm of mouse chromosome 7. The gene coding the interleukin-21 receptor (IL-21R) lies at the peak of association in this region. APPROACH AND RESULTS: With quantitative real-time polymerase chain reaction, we found that a mouse strain with a greater ability to upregulate IL-21R after HLI had better perfusion recovery than a strain with no upregulation after HLI. Immunofluorescent staining of ischemic hindlimb tissue showed IL-21R expression on endothelial cells (ECs) from C57BL/6 mice. An EC-enriched fraction isolated from ischemic hindlimb muscle showed higher Il-21R levels than an EC-enriched fraction from nonischemic limbs. In vitro, human umbilical vein ECs showed elevated IL-21R expression after hypoxia and serum starvation. Under these conditions, IL-21 treatment increased cell viability, decreased cell apoptosis, and augmented tube formation. In vivo, either knockout Il21r or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) in C57BL/6 mice resulted in less perfusion recovery after HLI. Both in vitro and in vivo modulation of the IL-21/IL-21R axis under hypoxic conditions resulted in increased signal transducer and activator of transcription 3 phosphorylation and a subsequent increase in the B-cell lymphoma leukemia-2/BCL-2-associated X protein ratio. CONCLUSION: Our data indicate that IL-21R upregulation and ligand activation in hypoxic ECs may help perfusion recovery by limiting/preventing apoptosis and favoring cell survival and angiogenesis through the signal transducer and activator of transcription 3 pathway.

Endothelial interleukin-21 receptor up-regulation in peripheral artery disease.

In most patients with symptomatic peripheral artery disease (PAD), severe stenosis in or occlusion of the major blood vessels that supply the legs make the amount of distal blood flow dependent on the capacity to induce angiogenesis and collateral vessel formation. Currently, there are no medications that improve perfusion to the ischemic limb, and thus directly treat the primary problem of PAD. A recent report from our group in a pre-clinical mouse PAD model showed that interleukin-21 receptor (IL-21R) is up-regulated in the endothelial cells from ischemic hindlimb muscle. We further showed that loss of IL-21R resulted in impaired perfusion recovery in this model. In our study, we sought to determine whether IL-21R is present in the endothelium from ischemic muscle of patients with PAD. Using human gastrocnemius muscle biopsies, we found increased levels of IL-21R in the skeletal muscle endothelial cells of patients with PAD compared to control individuals. Interestingly, PAD patients had approximately 1.7-fold higher levels of circulating IL-21. These data provide direct evidence that the IL-21R pathway is indeed up-regulated in patients with PAD. This pathway may serve as a therapeutic target for modulation.

Fluorescence lifetime excitation cytometry by kinetic dithering.

Flow cytometers are powerful high-throughput devices that capture spectroscopic information from individual particles or cells. These instruments provide a means of multi-parametric analyses for various cellular biomarkers or labeled organelles and cellular proteins. However, the spectral overlap of fluorophores limits the number of fluorophores that can be used simultaneously during experimentation. Time-resolved parameters enable the quantification of fluorescence decay kinetics, thus circumventing common issues associated with intensity-based measurements. This contribution introduces fluorescence lifetime excitation cytometry by kinetic dithering (FLECKD) as a method to capture multiple fluorescence lifetimes using a hybrid time-domain approach. The FLECKD approach excites fluorophores by delivering short pulses of light to cells or particles by rapid dithering and facilitates measurement of complex fluorescence decay kinetics by flow cytometry. Our simulations demonstrated a resolvable fluorescence lifetime value as low as 1.8 ns (±0.3 ns) with less than 20% absolute error. Using the FLECKD instrument, we measured the shortest average fluorescence lifetime value of 2.4 ns and found the system measurement error to be ±0.3 ns (SEM), from hundreds of monodisperse and chemically stable fluorescent microspheres. Additionally, we demonstrate the ability to detect two distinct excited state lifetimes from fluorophores in single cells using FLECKD. This approach presents a new ability to resolve multiple fluorescence lifetimes while retaining the fluidic throughput of a cytometry system. The ability to discriminate more than one average fluorescence lifetime expands the current capabilities of high-throughput and intensity-based cytometry assays as the need to tag one single cell with multiple fluorophores is now widespread.

A Magnetic Actuator Device for Fully Automated Blinking in Total Bidirectional Eyelid Paralysis: First Proof of Concept in a Human Participant.

Purpose: Currently, no solution exists to restore natural eyelid kinematics for patients with complete eyelid paralysis due to loss of function of both the levator palpebrae superioris and orbicularis oculi. These rare cases are prone to complications of chronic exposure keratopathy which may lead to corneal blindness. We hypothesized that magnetic force could be used to fully automate eyelid movement in these cases through the use of eyelid-attached magnets and a spectacle-mounted magnet driven by a programmable motor (motorized magnetic levator prosthesis [MMLP]). Methods: To test this hypothesis and establish proof of concept, we performed a finite element analysis (FEA) for a prototype MMLP to check the eyelid-opening force generated by the device and verified the results with experimental measurements in a volunteer with total bidirectional eyelid paralysis. The subject was then fitted with a prototype to check the performance of the device and its success. Results: With MMLP, eye opening was restored to near normal, and blinking was fully automated in close synchrony with the motor-driven polarity reversal, with full closure on the blink. The device was well tolerated, and the participant was pleased with the comfort and performance. Conclusions: FEA simulation results conformed to the experimentally observed trend, further supporting the proof of concept and design parameters. This is the first viable approach in human patients with proof of concept for complete reanimation of a bidirectionally paretic eyelid. Further study is warranted to refine the prototype and determine the feasibility and safety of prolonged use. Translational Relevance: This is first proof of concept for our device for total bidirectional eyelid paralysis.

Referral to hepatology is lower in patients with excessive alcohol use who have mental health disorders despite a high fibrosis-4 index.

BACKGROUND: Alcohol use disorder (AUD) is a multifaceted disease, and integration of AUD treatment between mental health and hepatology is necessary to improve outcomes. We aimed to ascertain whether patients with excessive alcohol use (EAU) and high FIB-4, which is a non-invasive method to identify advanced liver disease, are appropriately referred to hepatology and detect which clinical barriers, if any, might pertain. METHODS: Records of patients with excessive alcohol use between 2013 and 2023 were extracted from a large public system. Demographics, alcohol-related hospitalizations, mental health conditions, Charlson comorbidity index (CCI) and referral patterns were evaluated. Comparisons were made between those referred to hepatology versus not. RESULTS: 1131 subjects showed evidence of EAU but on further review, 189 were in alcohol-remission. The remaining 942 (636 men, age 55.7 ± 14.5 years, 548 white, 363 black, 19 Hispanic) subjects with CCI 2.61 ± 2.23 were further analyzed for FIB-4 score and referral patterns. 316 patients had active EAU and a high FIB-4, of whom only 116 (37%) were referred to hepatology. Patients with alcohol-related mental health concerns and admitted for trauma were less likely to be referred. Logistic regression showed referral was higher with alcohol-related liver hospitalizations (OR: 9.25, 95% CI: 4.90-17.47, p < 0.001), higher CCI (OR: 6.23, 95% CI: 3.00-12.94, p < 0.0001) and lower with mental health admissions (OR: 0.36, 95% CI: 0.15-0.48, p < 0.001) or mental health diagnoses (OR: 0.36, 95% CI: 0.15-0.82, p = 0.02) and increasing age (OR: 0.95, 95% CI: 0.92-0.97, p < 0.001). CONCLUSIONS: In a large public health system, almost 63% of patients with EAU and FIB-4 >2.67 are not referred to hepatology for evaluation. Patients not referred were more likely to have alcohol-related mental-health hospitalizations and mental health diagnoses, while those with liver-related hospitalizations and comorbidities were more likely to be referred. Greater education of mental health providers and for teams taking care of inpatients admitted with alcohol-related mental health concerns would better integrate care and improve outcomes for patients with higher risk for advanced liver disease.

Gaze Scanning on Mid-Block Sidewalks by Pedestrians With Homonymous Hemianopia With or Without Spatial Neglect.

Purpose: The purpose of this study was to investigate gaze-scanning by pedestrians with homonymous hemianopia (HH) when walking on mid-block sidewalks. Methods: Pedestrians with right homonymous hemianopia (RHH), and left homonymous hemianopia (LHH) without and with left spatial neglect (LHSN) walked on city streets wearing a gaze-tracking system. Gaze points were obtained by combining head movement and eye-in-head movement. Mixed-effects regression models were used to compare horizontal gaze scan magnitudes and rates between the side of the hemi-field loss (BlindSide) and the seeing side (SeeingSide), among the three subject groups, and between mid-block walking and street crossing segments. Results: A total of 7021 gaze scans were obtained from 341 minutes of mid-block walking videos by 19 participants (6 with LHH, 7 with RHH, and 6 with LHSN). The average gaze magnitude and scanning rate in mid-block segments were significantly higher towards the BlindSide than the SeeingSide in LHH (magnitude larger by 1.9° (degrees), P = 0.006; scan rate higher by 4.2 scans/minute, P < 0.001) and RHH subjects (magnitude larger by 3.3°, P < 0.001; scan rate higher by 3.2 scans/minute, P = 0.002), but they were not significantly different in LHSN subjects. The scanning rate, in terms of scans/minute (mean, 95% confidence interval [CI]) was significantly lower in LHSN subjects (mean = 6.9, 95% CI = 5.6-8.7) than LHH (mean = 10.2, 95% CI = 8.0-13.1; P = 0.03) and RHH (mean = 11.1, 95% CI = 9.0-13.7; P = 0.007) subjects. Compared to street-crossings, the scan rate during the mid-block segments was lower by 3.5 scans/minute (P < 0.001) and the gaze magnitude was smaller by 3.8° (P < 0.001) over the 3 groups. Conclusions: Evidence of compensatory scanning suggests a proactive, top-down mechanism driving gaze in HH. The presence of spatial neglect (SN) appeared to negatively impact the top-down process.

An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Re-Animation in Severe Blepharoptosis: Design and Proof-of-Concept.

Purpose: Blepharoptosis is a common oculoplastic condition causing incomplete opening of the upper eyelid. Surgical approaches, the mainstay for correction, often fail to improve blink function. The purpose of this study was to develop a nonsurgical treatment option for severe ptosis that allows blink re-animation. Methods: Magnetic force required to perform blink re-animation was characterized by evaluation of eye-opening and closing using inter-palpebral fissure (IPF) outcomes with various combinations of eyelid array and box magnets. Optimal size of the spectacle magnet that achieved forces required for optimal blink dynamics was selected using simulation. The adjustable magnetic levator prosthesis (aMLP) included an eyelid array magnet and an adjustable rotating spectacle magnet that allowed change in the magnetic direction, thus changing the net magnetic interactive force between the magnets. The clinical feasibility of aMLP in improving eye opening without limiting eye closing was evaluated in patients with ptosis through a proof-of-concept study using IPF and comfort outcomes. Results: Optimal eye opening and closing was achieved by a magnet-array combination providing 45 grams of surface force (gF) in the tested ptosis population. The aMLP was able to modulate eye opening and closing with change in rotation of the spectacle magnet in two patients with ptotis. The best fitting of an aMLP improved IPF opening without limiting eye closing and with good comfort reported. Conclusions: Preliminary results suggest that the an aMLP can correct ptosis without adversely affecting blink function. Further evaluation in a larger patient population is warranted. Translational Relevance: A nonsurgical, proof of concept, adjustable magnetic treatment option for blink re-animation in patients with severe ptosis is presented.

An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Reanimation in Severe Blepharoptosis II: Randomized Evaluation of Angular Translation.

Purpose: Examine the effect of force modulation via angular translation of a static magnetic field for customizable treatment of severe blepharoptosis. Methods: Prototype adjustable-force magnetic levator prostheses (aMLP) consisted of a spectacle-mounted magnet in rotatable housing and small eyelid-attached magnets embedded in a biocompatible polymer. Interpalpebral fissure (IPF) of 17 participants with severe blepharoptosis was continuously measured for one minute at five spectacle magnet angles, with order randomized and participant and data analyst masked. The hypothesis that angular position affected opening IPF (o-IPF), minimum blink IPF (m-IPF), and comfort ratings (1-10) was tested. Results: The aMLP improved o-IPF from 4.5 mm without the device to 6.2 mm on the lowest force setting (P < 0.001) and 7.1 mm on the highest setting (P < 0.001) and allowed for complete volitional blink regardless of setting (average m-IPF 0.4 mm and no change with aMLP; P = 0.76). Spontaneous blink without the device (2.0 mm) was affected on the highest force setting (m-IPF 3.9 mm; P < 0.001) but only marginally so on the lowest setting (3.0 mm; P = 0.06). Comfort (7.6/10) did not vary with the angle (P > 0.36). Profile analysis found substantial individual responses to angle (P < 0.001), confirming the value of customization. Conclusions: Angular translation provided adjustable force, which had a statistically and clinically meaningful impact on eye opening and the completeness of the spontaneous blink. This quantitative evidence supports continued use of the angular translation mechanism for force adjustment in the customizable magnetic correction of severe blepharoptosis. Translational Relevance: Evidence for the benefit of customizable magnetic force via angular translation in a larger sample of participants than reported previously.

Development and 5-year Evaluation of Diagnosis-Specific Protocols for Visual Neuro-Rehabilitation in a Multicenter Inpatient Rehabilitation Network.

Objective: To provide a retrospective evaluation of a new eye and vision rehabilitation care pathway in a U.S. multi-site inpatient rehabilitation network involving the occupational therapy (OT) staff and a consulting doctor of optometry (OD) specializing in vision rehabilitation. Design: Retrospective study. Setting: Two Inpatient Rehabilitation Facilities (IRFs) and 1 Long Term Acute Care Hospital (LTACH). Participants: There were 2083 records reviewed (44% women, avg. age 59 years). The most common diagnoses were hemispatial neglect (19.2%), homonymous field defects (18.5%), and oculomotor cranial nerve palsies (16.7%) (N=2083). Interventions: Clinical care was reviewed where diagnosis-specific protocols were developed and training was provided to OTs in order to reinforce OD-prescribed interventions during daily treatment sessions, including (1) third, fourth, and sixth ocular cranial nerve palsies (OCNPs) with prisms fitted for full time, postural adaptation training, and oculomotor re-education using pursuits, saccades, head-rotations, and binocular vision exercises including alternate cover and vergence; (2) homonymous hemianopia with training awareness of field loss, eccentric viewing, and fitting of Peli lens for optical field expansion; and (3) prism adaptation therapy (PAT) for left hemispatial neglect. Main Outcome Measures: Frequency of diagnoses. Hypothesis: Diagnoses with developed protocols were most common. Secondarily, feasibility and efficacy by anonymous OT survey. Results: 2083 vision consults were performed over 5 years. The most common diagnoses were hemispatial neglect (n=399, 19.2%), homonymous field defects (n=386, 18.5%), and OCNPs (n=347, 16.7%). None of the OTs reported the protocols were infeasible and 63% (IQR 38%-69%) reported their patients benefited from the interventions. The survey suggested prism for OCNPs helped in 42%, and Peli lens and PAT both helped in 38%. Conclusions: Data support the feasibility of this inpatient eye and vision rehabilitation care pathway which may be used as a foundation for creating or refining similar programs elsewhere. Uniform administration of IRF-based visual neuro-rehabilitation care could provide a substrate for future clinical trials to evaluate efficacy.