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.

Utility of scores to predict alcohol use after liver transplant (lt): take them with a grain of salt.

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month 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, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict 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 (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

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.

Gaze Scanning at Street Crossings by Pedestrians With Homonymous Hemianopia With and Without Hemispatial Neglect.

Purpose: To investigate compensatory gaze-scanning behaviors during street crossings by pedestrians with homonymous hemianopia (HH) and hemispatial neglect (HSN). Methods: Pedestrians with right homonymous hemianopia (RHH) and left homonymous hemianopia without (LHH) and with left spatial-neglect (LHSN) walked on city streets wearing a gaze-tracking system that also captured scene videos. Street-crossing instances were manually annotated, and horizontal gaze scan of magnitude ≥20° and scanning rates were compared within-subject, between the side of the hemifield loss (BlindSide) and the other side (SeeingSide). Proportion of instances with scans to both the left and the right side at nonsignalized crossings (indicative of safe scanning behavior) were compared among the three subject groups. Results: Data from 19 participants (6 LHH, 7 RHH, and 6 with mild [4] or moderate [2] LHSN), consisting of 521 street-crossing instances of a total duration of 201 minutes and 5375 gaze scans, were analyzed. The overall gaze magnitude (mean [95% confidence interval (CI)]) was significantly larger toward the BlindSide (40.4° [39.1°-41.9°]) than the SeeingSide (36° [34.8°-37.3°]; P < 0.001). The scanning rate (mean [95% CI] scans/min) toward the BlindSide (14 [12.5-15.6]) was significantly higher than the SeeingSide (11.5 [10.3°-12.9°]; P < 0.001). The scanning rate in the LHSN group (10.7 [8.9-12.8]) was significantly lower than the LHH group (14 [11.6-17.0]; P = 0.045). The proportion of nonsignalized crossings with scans to both sides was significantly lower in LHSN (58%; P = 0.039) and RHH (51%; P = 0.003) than LHH (75%) participants. Conclusions: All groups demonstrated compensatory scanning, making more gaze scans with larger magnitudes to the blind side. Mild to moderate LHSN adversely impacted the scanning rate.

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.

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.

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.

Feasibility of Magnetic Levator Prosthesis Frame Customization Using Craniofacial Scans and 3-D Printing.

Purpose: To determine the feasibility of a custom frame generation approach for nonsurgical management of severe blepharoptosis with the magnetic levator prosthesis (MLP). Methods: Participants (n = 8) with severe blepharoptosis (obscuring the visual axis) in one or both eyes who had previously been using a non-custom MLP had a craniofacial scan with a smartphone app to generate a custom MLP frame. A magnetic adhesive was attached to the affected eyelid. The custom MLP frame held a cylindrical magnet near the eyebrow above the affected eyelid, suspending it in the magnetic field while still allowing blinking. The spectacle magnet could be rotated manually, providing adjustable force via angular translation of the magnetic field. Fitting success and comfort were recorded, and interpalpebral fissure (IPF) was measured from video frames after 20 minutes in-office and one-week at-home use. Preference was documented, custom versus non-custom. Results: Overall, 88% of patients (7/8) were successfully fitted with a median 9/10 comfort (interquartile 7-10) and median ptosis improvement of 2.3 mm (1.3-5.0); P = 0.01). Exact binomial testing suggested, with 80% power, that the true population success rate was significantly greater than 45% (P = 0.05). Five participants took the custom MLP home for one week, with only one case of mild conjunctival redness which resolved without treatment. Highest to lowest force modulation resulted in a marginally significant median IPF adjustment of 1.5 mm (0.8 to 2.7; P = 0.06). All preferred the custom frame. Conclusions: The three-dimensional custom MLP frame generation approach using a smartphone app-based craniofacial scan is a feasible approach for clinical deployment of the MLP. Translational Relevance: First demonstration of customized frame generation for the MLP.

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.

Recurrent, Multisubtype Posttransplant Lymphoproliferative Disorder Masquerading as Inflammatory Bowel Disease.

Posttransplant lymphoproliferative disorder (PTLD) is a severe posttransplant complication that occurs because of immunosuppression within the first year; however, recurrent PTLD or development of multiple histologic subtypes are rare. Our case demonstrates a renal transplant recipient with rare, recurrent PTLD with multiple histologic subtypes (monomorphic and polymorphic PTLD) despite a previous response to rituximab and resolution of inflammatory changes on endoscopy. It is essential that clinicians maintain a high suspicion for PTLD when caring for patients with previous transplantation and that they have a lower threshold for biopsy with endoscopic findings of nonspecific inflammatory changes.

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.

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.

Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?

Genomic sequencing, bioinformatics, and initial speciation (e.g., relative abundance) of the commensal microbiome have revolutionized the way we think about the "human" body in health and disease. The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases, including those impacting the esophagus. Although relatively stable, there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome (EM) and the host. These changes are thought to be a product of age, diet, antibiotic and other medication use, oral hygiene, smoking, and/or expression of antibiotic products (bacteriocins) by other flora. These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation, systemic inflammation, and ultimately disease progression. Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is, therefore, not merely the result of esophageal mucosal exposure to corrosives (i.e., acid). Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade. Here, we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief (i.e., acid suppression).

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.

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.

Inpatient Virtual Vision Clinic Improves Access to Vision Rehabilitation Before and During the COVID-19 Pandemic.

OBJECTIVE: To describe and evaluate a secure video call system combined with a suite of iPad vision testing apps to improve access to vision rehabilitation assessment for inpatients. DESIGN: Retrospective. SETTING: Two acute care inpatient rehabilitation hospitals and 1 long-term acute care (LTAC) hospital. PARTICIPANTS: Records of inpatients seen by the vision service. INTERVENTIONS: Records from a 1-year telemedicine pilot performed at acute rehabilitation (AR) hospital 1 and then expanded to AR hospital 2 and LTAC hospital during coronavirus disease 2019 (COVID-19) were reviewed. In the virtual visits, an occupational therapist measured the patients' vision with the iPad applications and forwarded results to the off-site Doctor of Optometry (OD) for review prior to a video visit. The OD provided diagnosis and education, press-on prism application supervision, strategies and modifications, and follow-up recommendations. Providers completed the telehealth usability questionnaire (10-point scale). MAIN OUTCOME MEASURES: Vision examinations per month at AR hospital 1 before and with telemedicine. RESULTS: With telemedicine at AR hospital 1, mean visits per month significantly increased from 10.7±5 to 14.9±5 (P=.002). Prism was trialed in 40% of cases of which 83% were successful, similar to previously reported in-person success rates. COVID-19 caused only a marginal decrease in visits per month (P=.08) at AR1, whereas the site without an established program (AR hospital 2) had a 3-4 week gap in care while the program was initiated. Cases at the LTAC hospital tended to be more complex and difficult to manage virtually. The telehealth usability questionnaire median category scores were 7 for Ease of Use, 8 for Interface Quality, 6 for Reliability, and 9 for Satisfaction and Future Use. CONCLUSIONS: The virtual vision clinic process improved inpatient access to eye and visual neurorehabilitation assessment before and during the COVID-19 quarantine and was well accepted by providers and patients.

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.

IGFBP-1 Expression Promotes Tamoxifen Resistance in Breast Cancer Cells via Erk Pathway Activation.

Insulin-like growth factor (IGF) system plays a significant role in many cellular processes, including proliferation, and survival. In estrogen receptor positive breast cancer, the level of circulating IGF-1 is positively associated with the incidence and at least 50% of cases have elevated IGF-1R signaling. Tamoxifen, a selective estrogen receptor modulator and antagonist for estrogen receptor alpha (ERα) in breast tissue, is a commonly prescribed adjuvant treatment for patients presenting with ERα-positive breast cancer. Unfortunately, tamoxifen resistance is a frequent occurrence in patients receiving treatment and the molecular mechanisms that underlie tamoxifen resistance not adequately defined. It has recently been reported that the inhibition of IGF-1R activation and the proliferation of breast cancer cells upon tamoxifen treatment is mediated by the accumulation of extracellular insulin-like growth factor binding protein 1 (IGFBP-1). Elevated IGFBP-1 expression was observed in tamoxifen-resistant (TamR) MCF-7 and T-47D cells lines suggesting that the tamoxifen-resistant state is associated with IGFBP-1 accumulation. MCF-7 and T-47D breast cancer cells stably transfected with and IGFBP-1 expression vector were generated (MCF7-BP1 and T47D-BP1) to determine the impact of breast cancer cell culture in the presence of increased IGFBP-1 expression. In these cells, the expression of IGF-1R was significantly reduced compared to controls and was similar to our observations in tamoxifen-resistant MCF-7 and T-47D cells. Also similar to TamR breast cancer cells, MCF7-BP1 and T47D-BP1 were resistant to tamoxifen treatment, had elevated epidermal growth factor receptor (EGFR) expression, increased phospho-EGFR (pEGFR), and phospho-Erk (pErk). Furthermore, tamoxifen sensitivity was restored in the MCF7-BP1 and T47D-BP1 upon inhibition of Erk phosphorylation. Lastly, the transient knockdown of IGFBP-1 in MCF7-BP1 and T47D-BP1 inhibited pErk accumulation and increased tamoxifen sensitivity. Taken together, these data support the conclusion that IGFBP-1 is a key component of the development of tamoxifen resistance in breast cancer cells.

Using an Automated Hirschberg Test App to Evaluate Ocular Alignment.

A smartphone app has been developed to perform the automated photographic Hirschberg test for objective measurement of ocular misalignment. By computing the difference in corneal reflection generated by the phone camera flash relative to the iris center based on high resolution images, the app can measure misalignment with a much higher precision than the naked eye performing the Hirschberg test. It has been validated in a previous clinical evaluation study by comparing to the clinical gold standard-prism and alternate cover test. The goal of this article is to describe the testing techniques regarding how to use the app to measure ocular alignment for different fixation distances, without or with cover to break fusion, as well as angle kappa, so that users can use the app to perform equivalent tests typically done in clinic using prisms.

Glucose-dependent GPER1 expression modulates tamoxifen-induced IGFBP-1 accumulation.

G protein-coupled estrogen receptor 1 (GPER1) is a seven-transmembrane receptor that mediates rapid cell signaling events stimulated by estrogens. While the role that GPER1 has in the modulation of E2-responsive tissues and cancers is well documented, the molecular mechanisms that regulate GPER1 expression are currently not well defined. The recently identified GPER1-dependent mechanism of tamoxifen action in breast cancer cells underscores the importance of identifying mechanisms that regulate GPER1 expression in this cell type. We hypothesized that GPER1 expression in breast cancer cells is sensitive to [D-glucose] and provide data showing increased GPER1 expression when cells were cultured in low [D-glucose]. To determine if the observed accumulation of GPER1 was AMP-activated protein kinase (AMPK)-dependent, small molecule stimulation or inhibition of AMPK was performed. AMPK inhibition decreased GPER1 accumulation in cells grown in low [D-glucose] while the AMPK-activating compound AICAR increased GPER1 accumulation in cells grown in high [D-glucose] media. Additionally, transfection of cells with a plasmid expressing constitutively active AMPK resulted in increased GPER1 accumulation. To determine if [D-glucose]-dependent GPER1 accumulation altered breast cancer cell response to tamoxifen, cells grown in the presence of decreasing [D-glucose] were co-treated with tamoxifen and IGFBP-1 transcription was measured. The results from these experiments reveal that D-glucose deprivation increased GPER1-mediated and tamoxifen-induced IGFBP-1 transcription suggesting that [D-glucose] may increase breast cancer cell sensitivity to tamoxifen. Taken together, these results identify a previously unknown mechanism that regulates GPER1 expression that modifies one aspect tamoxifen action in breast cancer cells.