Diabetes mellitus has profound effects on multiple organ systems; however, the loss of vision caused by diabetic retinopathy might be one of the most impactful in a patient's life. The retina is a highly metabolically active tissue that requires a complex interaction of cells, spanning light sensing photoreceptors to neurons that transfer the electrochemical signal to the brain with support by glia and vascular tissue. Neuronal function depends on a complex inter-dependency of retinal cells that includes the formation of a blood-retinal barrier. This dynamic system is negatively affected by diabetes mellitus, which alters normal cell-cell interactions and leads to profound vascular abnormalities, loss of the blood-retinal barrier and impaired neuronal function. Understanding the normal cell signalling interactions and how they are altered by diabetes mellitus has already led to novel therapies that have improved visual outcomes in many patients. Research highlighted in this Review has led to a new understanding of retinal pathophysiology during diabetes mellitus and has uncovered potential new therapeutic avenues to treat this debilitating disease.

Acute isolated optic neuritis can be the initial presentation of demyelinating inflammatory central nervous system disease related to multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to the well-characterized brain and spinal cord imaging features, important and characteristic differences in the radiologic appearance of the optic nerves in these disorders are being described, and magnetic resonance imaging (MRI) of the optic nerves is becoming an essential tool in the differential diagnosis of optic neuritis. Whereas typical demyelinating optic neuritis is a relatively mild and self-limited disease, atypical optic neuritis in NMO and MOG-AD is potentially much more vision-threatening and merits a different treatment approach. Thus, differentiation based on MRI features may be particularly important during the first attack of optic neuritis, when antibody status is not yet known. This review discusses the optic nerve imaging in the major demyelinating disorders with an emphasis on clinically relevant differences that can help clinicians assess and manage these important neuro-ophthalmic disorders. It also reviews the utility of optic nerve MRI as a prognostic indicator in acute optic neuritis.

INTRODUCTION: Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and myopathic disorders. Moebius syndrome is one type of CFW. In this study we explored the utility of electrodiagnostic studies (EDx) in the evaluation of individuals with CFW. METHODS: Forty-three subjects enrolled prospectively into a dedicated clinical protocol and had EDx evaluations, including blink reflex and facial and peripheral nerve conduction studies, with optional needle electromyography. RESULTS: MBS and hereditary congenital facial paresis (HCFP) subjects had low-amplitude cranial nerve 7 responses without other neuropathic or myopathic findings. Carriers of specific pathogenic variants in TUBB3 had, in addition, a generalized sensorimotor axonal polyneuropathy with demyelinating features. Myopathic findings were detected in individuals with Carey-Fineman-Ziter syndrome, myotonic dystrophy, other undefined myopathies, or CFW with arthrogryposis, ophthalmoplegia, and other system involvement. DISCUSSION: EDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.

The assessment of tear fluid components is a common and valuable approach to understanding ocular surface disease and testing the efficacy of novel therapeutic strategies. However, the interpretation and utility of the findings can be limited by changes in the composition of the tear film, particularly in studies requiring repetitive patient sampling. Here, tear samples were collected twice within a one-hour interval to evaluate the short-term reproducibility of an immunoassay aimed to measure the amount of MUC5AC mucin. We found no statistical difference in total protein or MUC5AC content between the two consecutive collections of tear fluid, although the inter-individual variability in each group was high, with coefficients of variation exceeding 30% and 50%, respectively. Scatterplots showed a significant correlation in both protein and MUC5AC following collection within a one-hour interval. These data indicate that, regardless of the high inter-individual variability, repeated collection of tear fluid within an hour interval produces reproducible intra-individual data in terms of MUC5AC mucin content, and suggest that the normal mucin composition of the tear fluid can be re-established within an hour of the initial collection.

Fuchs endothelial corneal dystrophy (FECD) is an age-related disease whereby progressive loss of corneal endothelial cells (CEnCs) leads to loss of vision. There is currently a lack of therapeutic interventions as the etiology of the disease is complex, with both genetic and environmental factors. In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectively eliminating senescent cells using the senolytic cocktail of dasatinib and quercetin attenuated UVA-induced fibrosis, highlighting the potential for a new therapeutic intervention for FECD.

Daily activities require the constant searching and tracking of visual targets in dynamic and complex scenes. Classic work assessing visual search performance has been dominated by the use of simple geometric shapes, patterns, and static backgrounds. Recently, there has been a shift toward investigating visual search in more naturalistic dynamic scenes using virtual reality (VR)-based paradigms. In this direction, we have developed a first-person perspective VR environment combined with eye tracking for the capture of a variety of objective measures. Participants were instructed to search for a preselected human target walking in a crowded hallway setting. Performance was quantified based on saccade and smooth pursuit ocular motor behavior. To assess the effect of task difficulty, we manipulated factors of the visual scene, including crowd density (i.e., number of surrounding distractors) and the presence of environmental clutter. In general, results showed a pattern of worsening performance with increasing crowd density. In contrast, the presence of visual clutter had no effect. These results demonstrate how visual search performance can be investigated using VR-based naturalistic dynamic scenes and with high behavioral relevance. This engaging platform may also have utility in assessing visual search in a variety of clinical populations of interest.

PURPOSE: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. STUDY DESIGN: Crowdsourced observational study. METHODS: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. RESULTS: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97-0.98]), body mass index (1.04 [1.01-1.07]), brain disease (0.38 [0.15-0.98]), collagen disease (0.30 [0.13-0.68]), mental illness other than depression and schizophrenia (0.65 [0.45-0.93]), cataract surgery (0.12 [0.02-0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34-0.88]), current (0.47 [0.38-0.57]) or past (0.58 [0.43-0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05-1.81]), <6 h (1.24 [1.01-1.52]) and >9 h (1.34 [1.04-1.72]) sleep time, and water intake (0.97 [0.94-0.98]). CONCLUSION: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment.

BACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups-fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (-425 steps/d, 95% confidence interval (CI) = -793, -57), daily active minutes (-13 min/d, 95% CI = -21, -6), and daily moderate and vigorous physical activity (MVPA) minutes (-3 MVPA minutes/d, 95% CI = -5, 0) over the 3-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3-year period, while minimal changes were observed in FoF.

The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.

-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 () murine model, harboring a recessive mutation in the mouse ortholog of , has been a well-studied disease model and recently evaluated as a therapeutic model for -associated retinal degenerations. This study aims to draw parallels between human and mouse -related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human -related disease, was curated to identify further valuable correlates between human and mouse disease. Results of this study validate the slow progression of -associated disease in humans and the mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of -associated retinopathies.