The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.

In the central and peripheral nervous systems, the myelin sheath promotes neuronal signal transduction. The thickness of the myelin sheath changes during development and in disease conditions like multiple sclerosis. Such changes are routinely detected using electron microscopy through g-ratio quantification. While g-ratio is one of the most critical measurements in myelin studies, a major drawback is that g-ratio quantification is extremely laborious and time-consuming. Here, we report the development and validation of MyelTracer, an installable, stand-alone software for semi-automated g-ratio quantification based on the Open Computer Vision Library (OpenCV). Compared with manual g-ratio quantification, using MyelTracer produces consistent results across multiple tissues and animal ages, as well as in remyelination after optic nerve crush, and reduces total quantification time by 40-60%. With g-ratio measurements via MyelTracer, a known hypomyelination phenotype can be detected in a Williams syndrome mouse model. MyelTracer is easy to use and freely available for Windows and Mac OS X (https://github.com/HarrisonAllen/MyelTracer).

Objective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. Results: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.

PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.

PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

PURPOSE: Characteristics of periodic flares of dry eye disease (DED) are not well understood. We conducted a rapid evidence assessment to identify evidence for and characteristics of DED flares. METHODS: Literature searches were performed in Embase® via Ovid®, MEDLINE®, and PubMed®. Clinical trials and observational studies published 2009-2019 were included if they investigated patients aged ≥18 years with clinically diagnosed DED who experienced a flare, defined as a temporary or transient episode of increased ocular discomfort, typically lasting days to a few weeks. Triggers of flares, patient-reported outcomes (symptoms), clinician-measured outcomes (signs), and changes in tear molecules were captured. RESULTS: Twenty-one publications that included 22 studies met inclusion criteria. Five observational studies described evidence of DED flares in daily life, 5 studies reported changes following cataract/refractive surgery in patients with preoperative DED, and 12 studies employed controlled environment (CE) models. Real-world triggers of DED flares included air conditioning, wind, reading, low humidity, watching television, and pollution. CE chambers (dry, moving air) and surgery also triggered DED flares. Exacerbations of symptoms and signs of DED, assessed through varied measures, were reported during flares. Across studies, matrix metalloproteinase-9 and interleukin-6 increased and epidermal growth factor decreased during DED flares. CONCLUSIONS: Evidence from 22 studies identified triggers and characteristics of DED flares. Further research is needed to assist clinicians in early diagnosis and treatment of patients experiencing flares.

Importance: Gait dysfunction is common in older people with visual impairment and is a major cause of falls. Objective: To compare 3-year longitudinal changes in gait measures across the spectrum of baseline visual field (VF) damage in glaucoma. Design, Setting, and Participants: A post hoc analysis was designed on September 1, 2018, following a prospective cohort study, which enrolled older adults with glaucoma or suspected glaucoma from September 2013 to March 2015 and followed up for up to 3 years. Baseline VF damage was defined by integrated VF (IVF) sensitivity and categorized as normal/mild (IVF >28 dB), moderate (IVF, 23-28 dB), and severe (IVF, <23 dB). Each participant walked on an electronic walkway back and forth twice at normal pace each study year. Linear mixed-effects models evaluated longitudinal change in gait outcomes (1) stratified within each VF severity category and (2) across the range of IVF sensitivity. Analysis took place from October 2019 to October 2020. Main Outcomes and Measures: Three-year changes in 7 gait assessments under usual-pace walking, including base support and its coefficient of variation, stride length and its coefficient of variation, stride velocity and its coefficient of variation, and cadence. Results: Of 241 participants, the mean (SD) age was 70.8 (7.7) years, 116 (48.2%) were women, and 70 (29.0%) were African American. When comparing longitudinal gait changes over 3 years across the spectrum of IVF sensitivity, each 5-unit (dB) decrement was associated with more rapid declines in stride velocity (-0.05 z score unit/y; 95% CI, -0.09 to -0.01; P = .01) and cadence (-0.07 z score unit/y; 95% CI, -0.10 to -0.03; P < .001). When evaluating gait changes within each glaucoma severity group, shorter stride length was associated with persons with normal/mild (-0.06 z score unit/y; 95% CI, -0.10 to -0.03; P = .001), moderate (-0.08 z score unit/y; 95% CI, -0.12 to -0.04; P < .001), and severe VF damage (-0.16 z score unit/y; 95% CI, -0.24 to -0.07; P < .001), while stride velocity (-0.18 z score unit; 95% CI, -0.28 to -0.07; P = .002) and slower cadence (-0.15 z score unit; 95% CI, -0.25 to -0.04; P = .006) were associated with those with severe VF damage. Conclusions and Relevance: At worse levels of baseline VF damage, patients with glaucoma in this study demonstrated an exacerbated decline in walking speeds (ie, stride velocity and cadence), indicating that mobility speeds decrease faster over time in older adults with glaucoma.

PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets. METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups. RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2% when all three risk factors were present versus 4.4% when none were present (c-index = 0.737, 95% CI: 0.608, 0.865; p < 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475). CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.

Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2-11.9%) than developed countries (0.02-7.9%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.

Müller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2'-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.

PURPOSE: To report refractive error findings in Baltimore City schoolchildren who failed school-based vision screenings. METHODS: In this cross-sectional analysis, students pre-kindergarten through 8th grade who failed screenings during school years 2016-2019 received an eye examination, including non-cycloplegic autorefraction and visual acuity (VA) measurements. Refractive error was identified when there was at least: -0.50 diopter (D) spherical equivalent (SE) myopia, +0.50D SE hyperopia, 1.00D astigmatism, or 1.00D anisometropia in either eye. Generalized estimating equation models were used to identify factors associated with clinically significant refractive error, defined as decreased VA and more severe refractive error. RESULTS: Of 7520 students who failed screening, 6627 (88%) were analyzed. Clinically significant refractive error and any refractive error were found in 2352 (35.5%) and 5952 (89.8%) students, respectively. Mild myopia (45%, -0.50 D to <-3.00 D SE) and low astigmatism (47%, 1.00 D to <3.00 D cylinder) were the most prevalent types of refractive error. Proportions of students with myopia increased with higher grade levels (Ptrend<0.001). Myopia and astigmatism were more common in black and Latinx. Risk factors for clinically significant refractive error included higher grades (odds ratios [OR] ranged from 1.30 to 2.19 compared with 1st grade, P < .05) and Latinx ethnicity (OR = 1.31, 95%CI: 1.08-1.59). CONCLUSION: A Baltimore school-based vision program identified a substantial number of students with refractive error in a high-poverty urban community. Over 1/3 students who failed vision screening had clinically significant refractive error, with black and Latinx students at higher risk of having myopia and astigmatism.

PURPOSE: Many clinicians treat unilateral amblyopia with glasses alone and initiate patching when needed; others start glasses and patching simultaneously. In this study, we reviewed the outcomes of the two approaches at our institution. DESIGN: Retrospective nonrandomized clinical trial. METHODS: Setting: Institutional practice. PATIENT POPULATION: All patients diagnosed with amblyopia at Boston Children's Hospital between 2010 and 2014. INCLUSION CRITERIA: Unilateral amblyopia (visual acuity (VA) 20/40 to 20/200 with interocular difference ≥3 lines,) age 3 to 12 years, with a 6-month follow-up visit. EXCLUSION CRITERIA: Deprivation amblyopia, prior amblyopia treatment, treatment other than patching, surgery. Patients were categorized as "simultaneous treatment" (concurrent glasses and patching therapy at their first visit) or "sequential treatment" (glasses alone at first visit, followed by patching therapy at second visit.) Observation procedures: Patient demographics, VA, and stereopsis were compared. OUTCOME MEASURES: VA and stereopsis at the last visit on treatment. RESULTS: We identified 98 patients who met inclusion criteria: 36 received simultaneous treatment and 62 sequential treatment. Median amblyopic eye VA improved similarly between the simultaneous (∆0.40; interquartile range [IQR], 0.56-0.30 logMAR) and sequential (∆0.40; IQR, 0.52-0.27 logMAR) groups. Patients without stereopsis at first visit had better stereopsis outcomes with sequential treatment (5.12 [IQR, 4.00-7.51] log stereopsis) compared with simultaneous treatment (8.01 [IQR, 5.65-9.21]) log stereopsis, P = 0.046). CONCLUSIONS: VA improved approximately 4 lines regardless of treatment type. For children without stereopsis at first presentation, sequential patching yielded better stereopsis outcomes. These findings require further validation and highlight the importance of evaluating stereopsis in future studies.

Clinical and histopathologic case of an eyelid eccrine poroma, a benign adnexal neoplasm rarely found on the periorbital skin.

BACKGROUND: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. METHODS: Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. RESULTS: Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. CONCLUSIONS: This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.

PURPOSE: To explore stakeholders' perceptions of a school-based vision programme (SBVP). METHODS: We conducted 20 focus groups with 105 parents and teachers at schools in Baltimore, MD, that participated in a SBVP. Facilitators used a semi-structured interview guide to discuss participants' perceptions of the SBVP. Focus groups were audio-recorded, transcribed, and coded using inductive thematic analysis. RESULTS: Participant perceptions fell into three categories: benefits of school-based eye care, limitations of school-based eye care, and observation of impact. The majority of participants had positive comments about the programme; benefits included convenience (location, time, and cost), the comprehensive nature of the programme, the quality of the eyeglasses and ability to receive replacements, and a positive screening/exam experience. Limitations of programme impact were related to communication and organisation, the time to receive the glasses, missed instructional time, and uncertainty about screenings. Observations of impact included academic and classroom improvements, as well as visual and other health improvements. CONCLUSION: Parents and teachers reported mostly positive perceptions regarding the SBVP. Their appreciation for the convenience underscores that location, cost, time, and comprehensive services are crucial aspects for implementing a successful programme. To maximize impact, programs must also implement robust communication campaigns that integrate into the schools' workflow to help parents and teachers stay engaged in the process from start to finish.

Purpose: Determine the risk of immunomodulatory therapy (IMT) for COVID-19 infection morbidity.Method: A telemedicine survey on patients of a referral uveitis clinic was performed. Signs of infection, habits, and hospitalizations during the 7 months of the COVID-19 pandemic prior to the study date were recorded. Suggestive findings in chest CT scan and/or positive RT-PCR were considered as confirmed COVID-19 infection while those with only suggestive symptoms were considered as suspected cases. Risk factors including sanitary measures and IMT were compared between patients with confirmed cases and patients without infection.Result: 694 patients were included. Eight patients were identified as confirmed cases and 22 patients as suspected cases of COVID-19 infection. Close contact with infected persons was the only significant risk factor for contracting COVID-19.Conclusion: Using IMT did not affect hospitalization and/or ICU admission and can thus be continued during the pandemic, provided that instructions for preventive measures are followed.

Graft-versus-host disease is a common complication following allogeneic hematopoetic stem cell transplantation that can affect multiple organ systems, including the eyes. Ocular GVHD (oGVHD) is characterized by a T cell-mediated immune response that leads to immune cell infiltration and inflammation of ocular structures, including the lacrimal glands, eyelids, cornea and conjunctiva. oGVHD has a significant negative impact on visual function and quality of life and successful management requires a multi-disciplinary approach with frequent monitoring. Here, we review the pathophysiology and clinical presentation of oGVHD, along with current therapeutic strategies based on our clinical experience and the reported literature.

PURPOSE: To report the results of a clinical study designed to evaluate the accuracy of the blinq pediatric vision scanner, which detects amblyopia and strabismus directly by means of retinal polarization scanning, unlike other vision screening devices, which infer possible disease based on detection of refractive risk factors. METHODS: Subjects 1-20 years of age were prospectively enrolled in this cross-sectional diagnostic accuracy study with planned enrollment of 200. All enrolled subjects were tested by individuals masked to the diagnosis, followed by complete ophthalmologic examination by pediatric ophthalmologists masked to the screening result. Patients previously treated for amblyopia or strabismus were analyzed separately. RESULTS: The study cohort comprised 193 subjects, 53 of whom had been previously treated, leaving 140 treatment-naïve subjects, including 65 (46%) with amblyopia or strabismus, 11 (8%) with risk factors/suspected binocular vision deficit without amblyopia/strabismus, and 64 (46%) controls. Sensitivity was 100%, with all 66 patients with referral-warranted ocular disease referred. Five patients with intermittent strabismus receiving pass results were deemed "acceptable pass" when considering patient risk factors and amblyogenic potential. Specificity was 91%, with 7 incorrect referrals. Subanalysis of children aged 2-8 years (n = 92) provided similar results (sensitivity 100%; specificity 89%). CONCLUSIONS: In this study cohort, the blinq showed very high sensitivity and specificity for detecting referral-warranted amblyopia and strabismus. Implementation of the device in vision screening programs could lead to improved rates of disease detection and reduction in false referrals.

Importance: There is scant rigorous evidence about the real-world mobility benefit of electronic mobility aids. Objective: To evaluate the effect of a collision warning device on the number of contacts experienced by blind and visually impaired people in their daily mobility. Design, Setting, and Participants: In this double-masked randomized clinical trial, participants used a collision warning device during their daily mobility over a period of 4 weeks. A volunteer sample of 31 independently mobile individuals with severe visual impairments, including total blindness and peripheral visual field restrictions, who used a long cane or guide dog as their habitual mobility aid completed the study. The study was conducted from January 2018 to December 2019. Interventions: The device automatically detected collision hazards using a chest-mounted video camera. It randomly switched between 2 modes: active mode (intervention condition), where it provided alerts for detected collision threats via 2 vibrotactile wristbands, and silent mode (control condition), where the device still detected collisions but did not provide any warnings to the user. Scene videos along with the collision warning information were recorded by the device. Potential collisions detected by the device were reviewed and scored, including contacts with the hazards, by 2 independent reviewers. Participants and reviewers were masked to the device operation mode. Main Outcomes and Measures: Rate of contacts per 100 hazards per hour, compared between the 2 device modes within each participant. Modified intention-to-treat analysis was used. Results: Of the 31 included participants, 18 (58%) were male, and the median (range) age was 61 (25-73) years. A total of 19 participants (61%) had a visual acuity (VA) of light perception or worse, and 28 (90%) reported a long cane as their habitual mobility aid. The median (interquartile range) number of contacts was lower in the active mode compared with silent mode (9.3 [6.6-14.9] vs 13.8 [6.9-24.3]; difference, 4.5; 95% CI, 1.5-10.7; P < .001). Controlling for demographic characteristics, presence of VA better than light perception, and fall history, the rate of contacts significantly reduced in the active mode compared with the silent mode (β = 0.63; 95% CI, 0.54-0.73; P < .001). Conclusions and Relevance: In this study involving 31 visually impaired participants, the collision warnings were associated with a reduced rate of contacts with obstacles in daily mobility, indicating the potential of the device to augment habitual mobility aids. Trial Registration: ClinicalTrials.gov Identifier: NCT03057496.

PURPOSE: To evaluate outcomes of botulinum toxin (BTX) injection of the inferior oblique (IO) muscle. DESIGN: Retrospective case series. METHODS: Setting: Single center, ophthalmology department at Boston Children's Hospital. STUDY POPULATION: All patients treated with IO muscle injection of BTX (onabotulinumtoxinA) between 2010 and 2020. OBSERVATION PROCEDURE: Sensorimotor evaluations at short-term (<2 months), medium-term (2-4 months), and long-term (≥4 months) intervals. OUTCOME MEASURE: Primary outcomes included median improvement in V-pattern strabismus and primary position hypertropia. Secondary outcomes included IO muscle overaction. Wilcoxon signed-rank tests were performed to identify differences before and after injection. RESULTS: Record review identified 20 patients with a median age of 4.5 (range, 1-69) years. Median BTX dose injected (31 IO muscles) was 5.0 (range, 3.0-7.0) units. Indications included V-pattern strabismus (N = 8), hypertropia (N = 7), or both (N = 5). Median long-term interval was 6.4 (range, 4.1-26.6) months. Injections were concurrent with treatment of horizontal strabismus in all but 3 cases. Median V-pattern magnitude changed from 10 prism diopters (PD) preoperatively to 0 PD short-term (P = .006) and 3.5 PD long-term (P = .34). Median hypertropia changed from 8.5 PD preoperatively to 1.5 PD short-term (P = .01) and 8 PD long-term (P = .87). Median IO muscle overaction grade improved significantly at short-term (P < .001) and long-term (P = .007) intervals. There were no complications associated with the IO muscle injections. CONCLUSIONS: BTX injection of the IO muscles can be a useful adjunct to the management of V-pattern strabismus. Intervention for primary position hypertropia may be helpful for short-term relief with no expectation of long-term benefit.

A 10-month-old girl presented with eyelid edema and erythema that did not improve with systemic antibiotics. Due to a lack of improvement, MRI was performed to avoid ionizing radiation from CT. An orbital abscess was recognized and drained. However, the abscess recurred 2 times. CT scan was performed and a tract in the sphenoid bone helped to diagnose a congenital dural sinus tract with dermoid. Definitive surgery was performed with neurosurgery to remove the entire tract including cutaneous connection. CT scan proved critical to diagnosis and should be considered in infants in select cases despite the concern for ionizing radiation in this vulnerable age group.

BACKGROUND: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of end stage kidney disease (ESKD) in individuals with type 1 diabetes at advanced kidney disease stage. METHODS: Gene-based exome array analysis of 15,449 genes in 5 large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time-to-ESKD, testing the top gene in a 6th cohort (N=2,372/1,115 events all cohorts) and replicating in two retrospective case-control studies (N=1,072 cases, 752 controls). Deep resequencing of the top associated gene in 5 cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. RESULTS: Protein coding variants in the hydroxysteroid 17-beta dehydrogenase 14 gene (HSD17B14), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (N=4,196; p-value=3.3x10-7). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other chronic kidney disease-associated renal pathologies. CONCLUSIONS: HSD17B14 gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.

Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.