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Many forms of artificial sight recovery, such as electronic implants and optogenetic proteins, generally cause simultaneous, rather than complementary firing of on- and off-center retinal cells. Here, using virtual patients-sighted individuals viewing distorted input-we examine whether plasticity might compensate for abnormal neuronal population responses. Five participants were dichoptically presented with a combination of original and contrast-reversed images. Each image (I) and its contrast-reverse (I') was filtered using a radial checkerboard (F) in Fourier space and its inverse (F'). [I * F'] + [I' * F] was presented to one eye, and [I * F] + [I' * F'] was presented to the other, such that regions of the image that produced on-center responses in one eye produced off-center responses in the other eye, and vice versa. Participants continuously improved in a naturalistic object discrimination task over 20 one-hour sessions. Pre-training and post-training tests suggest that performance improvements were due to two learning processes: learning to recognize objects with reduced visual information and learning to suppress contrast-reversed image information in a non-eye-selective manner. These results suggest that, with training, it may be possible to adapt to the unnatural on- and off-cell population responses produced by electronic and optogenetic sight recovery technologies.

Primary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.

ObjectiveTo compare intraocular pressures (IOPs) estimated by rebound and applanation tonometry for dogs with lens instability.Animals66 dogs.ProceduresMedical records of dogs examined between September 2012 and July 2018 were reviewed for diagnoses of anterior (ALL) or posterior (PLL) lens luxation or lens subluxation.ResultsEstimates of IOP obtained with rebound and applanation tonometry significantly differed from each other for all types of lens instability considered collectively (mean ± SE difference between tonometric readings, 8.1 ± 1.3 mm Hg) and specific types of lens instability considered individually (mean ± SE difference between tonometric readings: ALL, 12.8 ± 2.5 mm Hg; PLL, 5.9 ± 1.7 mm Hg; subluxation, 2.8 ± 0.8 mm Hg). Median (range) differences between rebound and applanation tonometer readings for dogs with ALL was 5 mm Hg (-9 to 76 mm Hg), with PLL was 3 mm Hg (-1 to 19 mm Hg), and with lens subluxation was 3 mm Hg (-9 to 18 mm Hg). In eyes with ALL, rebound tonometer readings exceeded applanation tonometer readings on 44 of 60 (73%) occasions.Conclusions and clinical relevanceRebound tonometry yielded higher estimates of IOP than did applanation tonometry in eyes with ALL and with all types of lens luxation considered collectively. Estimates of IOP in eyes with lens instability should ideally be obtained with both rebound and applanation tonometers. Veterinarians with only one type of tonometer should interpret results for dogs with lens instability concurrent with physical examination findings.

Depth perception emerges from the development of binocular neurons in primary visual cortex. Vision is required for these neurons to acquire their mature responses to visual stimuli. The prevailing view is that vision does not influence binocular circuitry until the onset of the critical period, about a week after eye opening, and that plasticity of visual responses is triggered by increased inhibition. Here, we show that vision is required to form binocular neurons and to improve binocular tuning and matching from eye opening until critical period closure. Enhancing inhibition does not accelerate this process. Vision soon after eye opening improves the tuning properties of binocular neurons by strengthening and sharpening ipsilateral eye cortical responses. This progressively changes the population of neurons in the binocular pool, and this plasticity is sensitive to interocular differences prior to critical period onset. Thus, vision establishes binocular circuitry and guides binocular plasticity from eye opening.

This study tested the hypothesis that diabetes promotes a greater than normal cytosolic calcium level in rod cells that activates a Ca2+-sensitive protease, calpain, resulting in oxidative stress and inflammation, two pathogenic factors of early diabetic retinopathy. Nondiabetic and 2-month diabetic C57Bl/6J and calpain1 knockout (Capn1-/-) mice were studied; subgroups were treated with a calpain inhibitor (CI). Ca2+ content was measured in photoreceptors using Fura-2. Retinal calpain expression was studied by quantitative RT-PCR and immunohistochemistry. Superoxide and expression of inflammatory proteins were measured using published methods. Proteomic analysis was conducted on photoreceptors isolated from untreated diabetic mice or treated daily with CI for 2 months. Cytosolic Ca2+ content was increased twofold in photoreceptors of diabetic mice as compared with nondiabetic mice. Capn1 expression increased fivefold in photoreceptor outer segments of diabetic mice. Pharmacologic inhibition or genetic deletion of Capn1 significantly suppressed diabetes-induced oxidative stress and expression of proinflammatory proteins in retina. Proteomics identified a protein (WW domain-containing oxidoreductase [WWOX]) whose expression was significantly increased in photoreceptors from mice diabetic for 2 months and was inhibited with CI. Knockdown of Wwox using specific siRNA in vitro inhibited increase in superoxide caused by the high glucose. These results suggest that reducing Ca2+ accumulation, suppressing calpain activation, and/or reducing Wwox up-regulation are novel targets for treating early diabetic retinopathy.

The article focuses on a 21-year-old horse with a 3-week history of increased ocular opacity and swelling in the left eye, providing relevant clinical history, including a prior diagnosis of equine protozoal myeloencephalitis (EPM) and the use of flunixin meglumine. It mentions the horse, retired to a pasture setting, underwent a physical and neurologic examination at the referral hospital, revealing intermittent weakness and ataxia attributed to the historical EPM diagnosis.

Hydrogels, with their distinctive three-dimensional networks of hydrophilic polymers, drive innovations across various biomedical applications. The ability of hydrogels to absorb and retain significant volumes of water, coupled with their structural integrity and responsiveness to environmental stimuli, renders them ideal for drug delivery, tissue engineering, and wound healing. This review delves into the classification of hydrogels based on cross-linking methods, providing insights into their synthesis, properties, and applications. We further discuss the recent advancements in hydrogel-based drug delivery systems, including oral, injectable, topical, and ocular approaches, highlighting their significance in enhancing therapeutic outcomes. Additionally, we address the challenges faced in the clinical translation of hydrogels and propose future directions for leveraging their potential in personalized medicine and regenerative healthcare solutions.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Background: A higher prevalence of ophthalmological alterations in systemic inflammatory diseases has been demonstrated. Objectives: Our objectives were to determine anterior segment findings and corneal properties in alopecia areata (AA). Methods: This is a case-control study. Severe AA patients (Severity of Alopecia Tool > 50%) and non-AA subjects underwent a general ophthalmological examination, a Pentacam and Corvis scheimpflug technology examination (Oculus Optikgeräte GmbH, Wetzlar, Germany). Visual acuity, refractive error, corneal aesthesiometry, and biomechanical and topographic variables were registered. Results: In total, 25 AA patients (50 eyes; 50.6 ± 8.1 years) and 29 controls (58 eyes; 49.4 ± 8.6 years) were included. AA patients had decreased corneal sensitivity, more corneal staining, and a more advanced cataract (p ≤ 0.004). The anterior topographic flat meridian, mean anterior keratometry, and maximum keratometric point were increased in AA (p ≤ 0.040), while pachymetry values were thinner (p ≤ 0.001). Keratoconus index and Belin/Ambrosio-enhanced ectasia total deviation display were increased (p ≤ 0.007). Two eyes with a topographic diagnosis of keratoconus and four eyes with subclinical keratoconus were detected in AA. Applanation lengths were smaller in AA (p ≤ 0.029). The Corvis Biomechanical Index was increased in AA (p = 0.022). Conclusions: AA patients have reduced corneal sensitivity and increased corneal staining. Topographic and biomechanical parameters are altered, and there could be a higher risk of keratoconus, thus possibly requiring routine ophthalmological examination.

Zoonotic sporotrichosis, a subcutaneous mycosis caused by Sporothrix brasiliensis, has become hyperendemic and a serious public health issue in Brazil and an emerging disease throughout the world. Typical sporotrichosis is defined as fixed or lymphocutaneous lesion development, however, reports of atypical presentations have been described in hyperendemic areas, which may result in a worse prognosis. Thus, considering an increase in atypical cases and in more severe extracutaneous cases and hospitalizations reported in Brazil, we aimed to perform a systematic review to search for hypersensitivity reactions (HRs) and extracutaneous presentations associated with zoonotic sporotrichosis. A systematic review was performed, following the PRISMA guidelines to search for atypical/extracutaneous cases (mucosal, osteoarthritis, HRs, pulmonary, meningeal) of zoonotic sporotrichosis. A total of 791 published cases over 26 years (1998–2023) in eleven Brazilian states were reviewed. Most cases corresponded to a HR (47%; n = 370), followed by mucosal (32%; n = 256), multifocal (8%; n = 60), osteoarthritis (7%; n = 59), meningeal (4%; n = 32), and pulmonary (2%; n = 14) infections. When available (n = 607), the outcome was death in 7% (n = 43) of cases. Here, we show a frequent and worrisome scenario of zoonotic sporotrichosis in Brazil, with a high and dispersed incidence of atypical/extracutaneous cases throughout the Brazilian territory. Therefore, educational measures are necessary to make health professionals and the overall population aware of this fungal pathogen in Brazil as well as in other countries in the Americas.

Cone photoreceptors provide the foundation of most of human visual experience, but because they are smaller and less numerous than rods in most mammalian retinas, much less is known about their physiology. We describe new techniques and approaches which are helping to provide a better understanding of cone function. We focus on several outstanding issues, including the identification of the features of the phototransduction cascade that are responsible for the more rapid kinetics and decreased sensitivity of the cone response, the roles of inner-segment voltage-gated and Ca2+-activated channels, the means by which cones remain responsive even in the brightest illumination, mechanisms of cone visual pigment regeneration in constant light, and energy consumption of cones in comparison to that of rods.

PurposeTo evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.DesignSecondary analysis of a randomized controlled trial.ParticipantsPatients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.MethodsFrom 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Main outcome measuresVision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).ResultsAmong 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).ConclusionsAmong patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

PurposeTo evaluate in glaucoma patients the feasibility and use of remote monitoring of intraocular pressure (IOP) with an implanted telemetry sensor during the coronavirus disease 2019 (COVID-19) lockdown.DesignCross-sectional study.ParticipantsPatients previously implanted with a telemetric IOP sensor (Eyemate; Implandata GmbH) were included.MethodsIntraocular pressure measurements acquired by the patients during the lockdown were collected by physicians who were located remotely. A questionnaire was sent to 10 participating study centers to evaluate the clinical impact of remote monitoring of IOP via the IOP sensor system.Main outcome measuresNumber of patients who obtained home IOP measurements.ResultsData were available from all centers and from 37 eyes of 37 patients (16 patients with a sulcus-based sensor and 21 patients with a suprachoroidal sensor). Thirty-four patients obtained IOP measurements during the lockdown. Mean age of the patients was 69.3 ± 9.6 years, and 48.6% were women. A total of 8415 IOP measurements from 370 measurement days were obtained. Based on remote IOP measurements, treatment was changed in 5 patients. In another 5 patients, treatment change was considered when physicians received the IOP measurements after the lockdown. Nine of the 10 study centers judged remote IOP measurements to have a clinical impact.ConclusionsThese results show the feasibility of patient-acquired measurement of IOP in conjunction with remote IOP monitoring by physicians with an implantable sensor. The data obtained impacted clinical decision making, including adjustment of ocular hypotensive therapy and avoiding unnecessary office visits during the COVID-19 pandemic.

PurposeThis study investigated the initial feasibility of using femtosecond laser trabeculotomy (FLT) to create open channels through the trabecular meshwork into Schlemm's canal to lower intraocular pressure (IOP) in a perfused anterior segment model.MethodsHuman anterior segments (12 eyes) were assigned to either treatment (n = 6) or sham treatment (n = 6) groups. Both groups were perfused until a baseline IOP was recorded upon which a direct FLT treatment or a sham treatment was administered. IOP was recorded before and after the treatment. Spectral domain optical coherence tomography and second harmonic generation imaging we used to investigate the FLT channels.ResultsIn the FLT group, there was a significant mean decrease in the IOP of 22% compared with the pre-FLT IOP (7.13 ± 2.95 mm Hg to 5.34 ± 1.62 mm Hg; P < 0.05). In the control group, the post-sham IOP remained relatively unchanged compared with the pre-sham IOP (6.39 ± 3.69 mm Hg to 6.67 ± 4.12 mm Hg).ConclusionsThe results of this study indicate that FLT treatment can significantly decrease the IOP in a perfusion model and may provide a potential noninvasive treatment option for primary open angle glaucoma.Translational relevanceInvestigating the use of femtosecond lasers for photodisrupting the trabecular meshwork can lead to a clinically relevant alternative to current glaucoma procedures.

Participants with autism spectrum disorder (ASD) (n = 121, mean [SD] age: 14.6 [8.0] years) and typically developing (TD) controls (n = 40, 16.4 [13.3] years) were presented with a series of videos representing biological motion on one side of a computer monitor screen and non-biological motion on the other, while their eye movements were recorded. As predicted, participants with ASD spent less overall time looking at presented stimuli than TD participants (P

We extend decades of research on infants' visual processing by examining their eye gaze during viewing of natural scenes. We examined the eye movements of a racially diverse group of 4- to 12-month-old infants (N = 54; 27 boys; 24 infants were White and not Hispanic, 30 infants were African American, Asian American, mixed race and/or Hispanic) as they viewed images selected from the MIT Saliency Benchmark Project. In general, across this age range infants' fixation distributions became more consistent and more adult-like, suggesting that infants' fixations in natural scenes become increasingly more systematic. Evaluation of infants' fixation patterns with saliency maps generated by different models of physical salience revealed that although over this age range there was an increase in the correlations between infants' fixations and saliency, the amount of variance accounted for by salience actually decreased. At the youngest age, the amount of variance accounted for by salience was very similar to the consistency between infants' fixations, suggesting that the systematicity in these youngest infants' fixations was explained by their attention to physically salient regions. By 12 months, in contrast, the consistency between infants was greater than the variance accounted for by salience, suggesting that the systematicity in older infants' fixations reflected more than their attention to physically salient regions. Together these results show that infants' fixations when viewing natural scenes becomes more systematic and predictable, and that predictability is due to their attention to features other than physical salience. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PurposeWe sought to characterize juxtapapillary (JP) and non-JP microvasculature dropout in patients with primary open-angle glaucoma and to compare their rate of retinal nerve fiber layer (RNFL) thinning.DesignRetrospective cohort study.MethodsA total of 141 eyes with primary open-angle glaucoma with ≥4 serial optical coherence tomography (OCT) images after initial OCT angiography for ≥2 years were included. Based on OCT angiography imaging, the 3 groups were matched by age and visual field mean deviation: JP group (parapapillary deep-layer microvasculature dropout in contact with the optic disc boundary, n = 47), non-JP group (dropout not reaching the optic disc boundary, n = 47), and no-dropout group (lacking the dropout, n = 47). The RNFL thinning rate was compared among the 3 groups.ResultsThe rate of RNFL thinning tended to be fastest in the JP group followed by the non-JP group and no-dropout group in all areas except the temporal and nasal sectors. Post hoc analysis revealed that the JP group had significantly faster RNFL thinning than did the no-dropout group in the global area and the inferotemporal and inferonasal sectors (P < .05). When subgroup analysis was performed for subjects in which the main sector of dropout was the inferotemporal sector, the JP group had significantly faster RNFL thinning than the other 2 groups in the corresponding inferotemporal sector (P < .001).ConclusionEyes with JP microvasculature dropout showed faster RNFL thinning than eyes without dropout. These findings suggest that deep-layer microvasculature dropout, especially in contact with the optic disc boundary, is associated with rapid glaucoma progression.

Ocular graft versus host disease (OGvHD) develops after allogeneic hematopoietic stem cell transplantation (HSCT) and manifests as ocular surface inflammatory disease. This study evaluated the efficacy of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) to inhibit OGvHD. A major histocompatibility mismatch chronic OGvHD murine model was evaluated. 7 days after HSCT, mice were dosed subconjunctivally with scAAV8-HLA-G1/5 (1 x 109 vg/eye), topical cyclosporine (twice daily), or left untreated. Body weights and tear production (red thread test) were recorded, and eyelid, corneal opacity, and corneal fluorescein retention were scored through day 44 after HSCT. Tissues were collected for vector biodistribution, ocular histology, and immunofluorescence. Compared with untreated HSCT eyes, those dosed with scAAV8-HLA-G1/5 had significantly reduced clinical inflammatory signs of OGvHD. On histology, eyes that received scAAV8-HLA-G1/5 or cyclosporine had a significantly lower mean limbal mononuclear cell count when compared with non-treated HSCT eyes. HLA-G immunofluorescence was detected in the subconjunctiva and peripheral cornea in HSCT animals treated with scAAV8-HLA-G1/5. Vector genomes were detected in the lacrimal gland, but not in the other tested organs. These results provide evidence that subconjunctival AAV targets ocular surface and corneal disease and support that HLA-G-based gene therapy may be an effective treatment for OGvHD.

Abstract Background To analyze the relationship between axial length and levels of high-density lipoprotein (HDL) cholesterol in children. Methods A retrospective, hospital-based cross-sectional research with 69 right eyes from 69 children who underwent health examination by Zhejiang Provincial People’s Hospital was carried out. The participants were split into three groups: Group A (axial length 24 mm). Demographic epidemiological information, blood biochemical parameters and ophthalmic characteristics including refractive status and ocular geometric parameters were obtained and analyzed. Results 69 right eyes from 69 patients (25 males and 44 females) with a median age of 10.00 years old (IQR: 8.00–11.00 years) were included in the study. Within Group A, there were a total of 17 individuals; Group B consisted of 22 individuals; Group C included 30 individuals. The mean axial length of three groups was 22.148(0.360), 23.503(0.342) and 24.770(0.556) mm, respectively (p

BackgroundBacillus cereus (Bc) can cause self-limiting gastrointestinal infections, but when infecting the eye, can cause rapid and irreversible blindness. This study investigated whether clinical ocular and gastrointestinal Bc isolates differed in terms of virulence-related genotypes and endophthalmitis virulence.MethodsTwenty-eight Bc ocular, gastrointestinal, and laboratory reference isolates were evaluated. Hemolysis assays were performed to assess potential differences in hemolytic activity. The presence of twenty Bc virulence-related genes was assessed by PCR. A subset of ocular and gastrointestinal isolates differing in PCR positivity for 5 virulence genes was compared to strain ATCC14579 in an experimental murine model of endophthalmitis. At 8 hours post infection, retinal function was evaluated by electroretinography, and intraocular bacterial concentrations were determined by plate counts.ResultsGastrointestinal Bc isolates were more hemolytic than the Bc ocular isolates and ATCC14579 (p < 0.0001). Bc ocular isolates were more frequently PCR-positive for capK, cytK, hblA, hblC, and plcR compared to the gastrointestinal isolates (p ≤ 0.0002). In the endophthalmitis model, mean A-wave retention did not differ significantly between eyes infected with ATCC14579 and eyes infected with the selected ocular or gastrointestinal isolates (p ≥ 0.3528). Similar results were observed for mean B-wave retention (p ≥ 0.0640). Only one diarrheal isolate showed significantly greater B-wave retention when compared to ATCC14579 (p = 0.0303). No significant differences in mean A-wave (p ≥ 0.1535) or B-wave (p ≥ 0.0727) retention between the selected ocular and gastrointestinal isolates were observed. Intraocular concentrations of ATCC14579 were significantly higher than the selected ocular isolate and 3 of the gastrointestinal isolates (p ≤ 0.0303). Intraocular concentrations of the selected ocular isolate were not significantly different from the gastrointestinal isolates (p ≥ 0.1923).ConclusionsAmong the subset of virulence-related genes assessed, 5 were significantly enriched among the ocular isolates compared to gastrointestinal isolates. While hemolytic activity was higher among gastrointestinal isolates, retinal function retention and intraocular growth was not significantly different between the selected ocular and gastrointestinal isolates. These results suggest that Bc strains causing gastrointestinal infections, while differing from ocular isolates in hemolytic activity and virulence-related gene profile, are similarly virulent in endophthalmitis.

Microemulsions are a promising drug delivery system that can be used to enhance the bioavailability, solubility, and therapeutic efficacy of hydrophilic drugs. The downside of hydrophilic drugs is the poor solubility in lipid-based media; therefore, they require frequent dosing or high doses to achieve the therapeutic level. This may lead to unintended adverse effects and poor patient compliance Microemulsions can improve drug delivery by incorporating hydrophilic drugs within a thermodynamically stable and transparent oil-in-water emulsion. This can optimize the drug's solubility and permeability, leading to enhanced bioavailability and therapeutic efficacy. This review provides an insight to various routes of administration for delivering hydrophilic drugs using microemulsion. It will explore the use of microemulsion for oral, nasal, transdermal, and ocular delivery. The review also discusses the advantages, disadvantages and the physicochemical properties associated with each one of it. Overall, the article aims to provide a comprehensive overview of the use of microemulsions as a drug delivery system for hydrophilic drugs administered via different routes.

AbstractDelivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.

ObjectivePrevious studies have shown that approximately 39%–65% of patients with childhood-onset systemic lupus erythematosus (cSLE) have damage in at least one organ. Data on risk factors for organ damage in cSLE remain limited, especially in Asian populations. This study was conducted to evaluate the incidence of cSLE and identify the risk factors for accumulated organ damage in patients with cSLE.MethodsThis was a retrospective study. Patients aged 1) with an incidence rate of 5.7 events per 100 person-years. The most frequent type of organ damage was ocular (11.1%), followed by musculoskeletal (8.9%) and neurological (7.4%). High disease activity at diagnosis (SLEDAI-2K ≥ 12) (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.32–7.68), infection (OR 3.73, 95% CI 1.60–8.67), and mycophenolate mofetil use (OR 3.62, 95% CI 1.45–9.03) were predictors of organ damage. The median time to disease damage in patients with SLEDAI-2K scores ≥12 at diagnosis was 6.5 years (95% CI 5.77–7.36; P = 0.004).ConclusionPhysicians should be aware of organ damage in patients with cSLE, particularly those with high disease activity at initial presentation, those who are receiving mycophenolate mofetil therapy, and those with an infection.

Meibomian gland dysfunction (MGD) is a prevalent worldwide eye disorder that causes eye irritation, inflammation, chronic dryness, and blurred vision. Traditional therapies offer temporary improvement, but their efficacy varies in severe MGD cases. Ocular intense pulsed light (IPL) has emerged as a novel therapy, providing long-term symptom relief and shorter treatment durations compared to traditional approaches. However, the impact of IPL on the bacterial community within the eyes remains limited. To address this, we conducted a preliminary study using metagenomics and next-generation sequencing. We compared the bacterial eyelash communities of Thai females with severe MGD before and after 2-4 IPL treatments, and against a group of healthy females. Our findings revealed higher bacterial diversity in healthy individuals compared to severe MGD cases. IPL treatments increased diversity in the MGD group, making their core bacterial community more similar to that of healthy subjects. Notably, the presence of Koribacteraceae in severe MGD and Bifidobacterium in healthy individuals and post-IPL-treated MGD exemplified this shift. Clustering analysis showed a closer relationship between post-IPL-treated MGH and healthy subjects, while the pre-IPL treatment group formed a separate branch. These results suggest that IPL treatment can reshape the eyelash microbiome in MGD cases, but further research is needed to understand the implications and the microbiome’s role in MGD pathogenesis and treatment response.

Purpose: Optic nerve avulsion (ONA) is a rare but serious presentation of ocular trauma. This study investigates the presenting characteristics and etiologies of all cases of ONA over an 8-year-period at a tertiary eye care center in the Middle East.Methods: The medical records of patients diagnosed with ONA at an Ophthalmic Emergency Department between November 2014 and November 2022 were analyzed in this retrospective cohort study. Data were collected on patient age, sex, affected eye, cause of injury and imaging studies. The best-corrected visual acuity (BCVA) at presentation and at the last follow-up visit, and the duration of follow-up were documented.Results: The study sample was comprised of 44 eyes of 43 patients with ONA with median age of 16.5 (9.3– 26.8) years ranging from 2 years old to 70 years old. There were (35;79.5%) males and (9; 20.5%) females. Most cases presented with an affected left eye (27; 61.4%) followed by the right eye (16; 36.4%) and only one patient (2.3%) had bilateral ONA. The most common cause of trauma resulting in ONA was a metallic object (8;18.2%). This study demonstrates the value of multi-sequence Magnetic resonance imaging (MRI) in the setting of unexplained vision loss when other modalities are inadequate or inconclusive.Conclusion: Ophthalmic morbidity resulting from ONA can be devastating. Metallic object injuries were the most prevalent cause of ONA. The presence of associated media opacities challenges the initial diagnosis of ONA. In the vast majority of cases, the vision ended as no light perception (NLP), indicating permanent vision impairment. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate intraoperative and postoperative complications and outcomes following subconjunctival enucleations with and without third eyelid removal in domestic rabbits. ANIMALS 18 client-owned rabbits with ocular disease confined to the globe that underwent 20 subconjunctival enucleation procedures at a veterinary teaching hospital. METHODS Records were retrospectively reviewed for all enucleations performed at a veterinary teaching hospital from 2014 to 2022. A standard subconjunctival enucleation procedure was performed in all cases, with third eyelid removal in 2 surgeries and without third eyelid removal in the remaining 18 surgeries. Outcomes were assessed on the basis of observations in medical records and owner follow-up. RESULTS 20 total enucleations were included. Reported reasons for enucleation included suspected or confirmed ocular Encephalitozoon cuniculi infection in 9 rabbits, refractory glaucoma in 4 rabbits, and various intraoculardiseases in 5 rabbits. The only intraoperative complication reported was hemorrhage during the third eyelid removal in 1 surgery. Postoperative complications included serous to mucoid discharge from the surgical site in 8 of 20 surgeries and swelling at the surgery site in 2 of the 8 cases that had discharge. Postoperative swelling spontaneously resolved within 3 months of surgery; postoperative discharge spontaneously resolved within 10 months of surgery. CLINICAL RELEVANCE Subconjunctival enucleation with or without third eyelid removal in rabbits may be a viable enucleation technique to reduce the risk for intraoperative hemorrhage, but it can result in postoperative complications, including transient discharge and swelling at the surgical site. [ABSTRACT FROM AUTHOR]

Loss of facial structures has a physical, social and psychological impact on affected individuals. Ocular trauma caused by assaults, falls, road traffic accidents, and household or work-related accidents may necessitate eye enucleation. Enucleation is also performed to treat severe infections of the eye, intraocular tumours and painful blind eyes. This procedure can result in post-enucleation socket syndrome with facial disfigurement and severely compromising facial aesthetics. Our patient complained of facial disfigurement because of a defect associated with the right eye. History and clinical features were suggestive of post-enucleation socket syndrome. The defect was rehabilitated with an ocular prosthesis. The rehabilitation procedure provided satisfactory results and a happy patient with good aesthetics. Maxillofacial prosthesis can restore and rehabilitate lost facial structures with artificial substitutes and helps in regaining patient's natural appearance, the health of adjoining structures and subsequently, provide physical, social and psychological well-being. [ABSTRACT FROM AUTHOR]

Purpose of Review: There is controversy surrounding the true incidence of ocular infection in patients with candidemia and the best approach to screening for this condition. Recent Findings: Multiple studies have been published recently, updating our understanding of the epidemiology and risk factors for endogenous ocular candidiasis. Summary: Ocular candidiasis has an overall low prevalence but remains a clinically relevant and important disease entity among patients with candidemia, especially among those patients infected with Candida albicans and patients with indwelling central venous catheters, comorbid immunosuppression, or intravenous drug use. [ABSTRACT FROM AUTHOR]

There is a lack of reports describing ultrasonographic and histopathologic features of ocular diseases in donkeys. The present study aimed to document ultrasonographic and histopathologic changes associated with common ocular diseases in donkeys. The study included 45 donkeys (64 eyes) with ocular diseases that had reached the end of their working lives and requested to be used for educational and research purposes. Complete clinical, ophthalmic, ultrasonographic, gross pathologic and histopathologic examinations were included. Ocular abnormalities were documented, tabulated, and analyzed. Seventy-five ocular abnormalities were diagnosed with multiple involvements within the same eye including anterior uveitis (n = 13; 22.8%), cataract (n = 57; 76%), retinal detachment (n = 3; 4%), lens and phthisis bulbi (n = 2; 2.6%). Descriptive ultrasonographic findings of ocular abnormalities were included. Gross pathologic and histopathology findings confirmed the ultrasonography findings. Ultrasonography provided a clinically useful tool offering insight into detailed intraocular structures especially with opacification of the dioptric structures of the eye. [ABSTRACT FROM AUTHOR]

Background: Equine recurrent uveitis (ERU) is the leading cause of blindness for horses; previous research implicated the leopard complex spotting allele (LP) as a genetic risk factor for insidious uveitis in the Appaloosa. There is limited information about risk in the Knabstrupper. Objective: To evaluate clinical manifestations, disease frequency and potential risk factors for ERU in Knabstrupper horses. Study design: Cross‐sectional study. Methods: Ocular examinations were performed on 116 horses, and based on identified anomalies, horses were classified as suspect, ERU‐affected or having no clinical signs. Microagglutination testing (MAT) of serum assessed exposure to Leptospira spp. Clinical signs, age, sex, base colour, coat pattern, LP and PATN1 genotypes, percent white at birth, progressive roaning and Leptospira were assessed as risk factors using multivariable exact logistic regression, accounting for clustering at the barn level. Additionally, a pedigree analysis was performed (n = 20 cases and 21 controls), and coefficients of coancestry (CC) and inbreeding were calculated. Results: Prevalence of insidious uveitis in this sample of Knabstruppers was 20.7%. Similar to findings for Appaloosas, LP homozygotes had higher odds of uveitis compared with true solid (N/N) horses (LP/LP OR = 7.64, 95% CI [0.8 to +INF], p = 0.04) and age was also identified as a risk factor. After accounting for LP, the 16–20 age group had higher odds compared with the youngest group (OR = 13.36, 95% CI [1.4–213.4], p = 0.009). The distributions of average CC were significantly different between cases and controls (p = 0.01). Main limitations: A relatively small sample size decreased the power for detecting additional associations. The progressive nature of insidious uveitis may have prevented identification of younger affected horses. Conclusions: Our data support genotyping for LP to assess risk of ERU in Knabstruppers. Additional studies are necessary to develop more robust risk models across LP breeds for earlier detection and improved clinical management. [ABSTRACT FROM AUTHOR]

Copyright of Izmir Katip Celebi University Faculty of Health Sciences Journal / İzmir Katip Çelebi Üniversitesi Sağlık Bilimleri Fakültesi Dergisi is the property of Izmir Katip Celebi University, Faculty of Health Sciene Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Veterinary antiparasitic drugs are widely used in countries and regions in which parasitic diseases are endemic, which leads to the risk of accidental ingestion and poisoning in humans. Case presentation: A 40-year-old male patient with a history of cirrhosis sought medical attention on November 25, 2021, due to progressive vision loss. He had previously taken triclabendazole and bithionol and was diagnosed with toxic optic neuropathy on examination. Steroid, neurotonic, and high-pressure oxygen therapy were ineffective. Conclusions: Triclabendazole and bithionol have potential risk of optic neurotoxicity and should be considered for enhanced supervision and warning labels. [ABSTRACT FROM AUTHOR]

Purpose: To report the normative ocular and periocular anthropometric measurements in an Australian cohort and investigate how these may be affected age, gender, and ethnicity. Methods: Prospective study of patients presenting to the Royal Adelaide Hospital. Patient with orbital or eyelid disease, previous surgery, craniofacial abnormalities, pupil abnormalities, strabismus, and poor image quality was excluded. Standardised photographs were taken in a well-illuminated room. A green dot with a diameter of 24 mm was placed on the participant's foreheads for calibration between pixels and millimetres. Ocular and periocular landmarks were segmented to calculate the periorbital measurements. Independent sample t test was used to compare male and female subjects, Pearson's correlation was used to correlate periocular dimensions with age, and ANOVA with Bonferroni was used to compare periocular dimension between ethnic groups. Results: Seven hundred and sixty eyes from 380 participants (215 female, mean age 58 ± 18 years) were included. The mean marginal reflex distance (MRD) 1 was 3.5 mm and decreased with increasing age (r = − 0.09, p = 0.01) and MRD 2 was 5.2 mm. Compared to Caucasians, African subjects had a significantly larger interpupillary distance and outer intercanthal distance, whereas East Asians had a significantly larger inner intercanthal distance (p < 0.05). The values of marginal reflex distance 2, palpebral fissure height, horizontal palpebral aperture, inner intercanthal distance, interpupillary distance and outer intercanthal distance were significantly higher in male subjects than female subjects (p < 0.05). Conclusions: Normative periocular dimensions may vary according to age, gender, and ethnicity. An understanding of normal periocular dimensions is important in the evaluation of orbital disease across different ethnic groups and may serve as reference points for oculoplastic surgery and industry. [ABSTRACT FROM AUTHOR]

To assess the pediatric anterior segment characteristics in ocular pathology using spectral domain optical coherence tomography (SD-OCT). This case series follows 115 eyes of 78 children (2–17 years) with anterior segment pathology in an academic facility. The anterior segment OCT (AS-OCT) analysis was done using the Optopol Revo 80 high-resolution SD-OCT using an imaging adapter. All pathological features visible on imaging were observed, studied, tabulated, and analyzed. The average age was 11.84 years, with 44 males and 34 females. The primary clinical diagnosis was cataract in 40 (34.8%) eyes, followed by corneal disease in 28 (24.3%) eyes, glaucoma in 18 (15.7%) eyes, and trauma in 15 (13%) eyes. Systemic diseases were associated with 20.9% of the cases. The most common imaging pathology observed was lens opacification in 43 (37.4%), increased reflectivity of the cornea in 31 (28.2%), corneal stromal thinning in 34 (29.6%), increased corneal thickness in 28 (24.3%), a shallow anterior chamber in 17 (14.8%), and cells in the anterior chamber in 18 (15.7%) eyes, along with a multitude of other findings. This study demonstrates that anterior segment OCT is a useful non-contact technique for the detailed anatomic and pathologic assessment of pediatric ocular diseases. [ABSTRACT FROM AUTHOR]

A esporotricose é uma micose causada por fungos da espécie Sporothrix, sendo predominante em regiões tropicais e subtropicais. Em 80% dos casos, os pacientes apresentam a forma linfocutânea. O comprometimento sistêmico é raro, estando associado, geralmente, à imunodepressão. O objetivo deste trabalho é relatar um caso de esporotricose disseminada com comprometimento ocular em paciente imunocompetente. Paciente do sexo masculino, 41 anos, auxiliar de pedreiro, apresentou lesão ulcerada em dorso da mão esquerda, após acidente perfurocortante com espinho. Após dois meses, ocorreu o surgimento de novas lesões em membro superior direito, com posterior disseminação para tórax, abdome e membros inferiores, de aspecto papulonodular com conteúdo purulento que rompiam e tornavam-se ulceradas e crostosas. Referia também febre e perda de peso no período. Além disso, relatava sensação de ardência e redução da acuidade visual do olho direito, com presença de drenagem de conteúdo com aspecto purulento e exposição do conteúdo uveal. Etilista de grande monta e tabagista. Sorologia para HIV 1 e 2 não reagente. Cultura de fragmentos de pele e de secreção ocular com crescimento de Sporothrix spp. Foi realizada evisceração ocular e tratamento sistêmico com anfotericina B, evoluindo melhora clínica completa das lesões, com alta hospitalar e seguimento ambulatorial em uso de itraconazol. A esporotricose ocular é uma apresentação rara da doença, predominando o comprometimento conjuntival e mais raramente uveíte, iridociclite e coroidite. No caso em questão, o paciente apresentava extenso comprometimento local, com completa desorganização das estruturas oculares e necessidade de evisceração ocular, condição rara descrita. Não havia descrição de trauma ocular, o que, associado ao comprometimento cutâneo, sugere acometimento ocular por disseminação sistêmica. O tratamento envolve o uso de antifúngico sistêmico e controle da condição imunossupressora, caso exista. Para o caso, pela gravidade, foi optado por fazer anfotericina B, com boa resposta clínica. Possivelmente, a baixa suspeição diagnóstica no início do quadro influenciou na gravidade apresentada. Consideramos que o diagnóstico de esporotricose deve ser aventado em pacientes com comprometimento ocular sugestivo de processo infeccioso, especialmente em regiões hiperendêmicas para esta infecção fúngica.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Purpose This study aimed to investigate the course of uveal manifestations in a cohort of patients who underwent surgery for ulcerative colitis (UC), highlighting the diverse spectrum of associated eye disorders and alerting clinicians of their significance. Patients and methods A retrospective observational study was conducted on 40 UC patients with ocular manifestations who underwent one-stage laparoscopic restorative proctocolectomy according to the European Crohn's and Colitis Organization (ECCO) guidelines. Ophthalmic examinations were performed preoperatively and postoperatively during the 6-month follow-up period. Anterior uveitis attacks were graded based on the presence of cells or flares, vitreous haze indicates intermediate uveitis while posterior uveitis was indicated by retinitis or choroiditis, or both. Recurrence was a Standardization of Uveitis Nomenclature (SUN) grading system score greater than or equal to 2+ for anterior chamber cells or vitreous haze. Results Postoperatively, uveitis regression was observed in ~60% of the patients, 25% showed a stationary course, and 15% exhibited progression. After surgery, more patients had lower Standardization of Uveitis Nomenclature grades for anterior chamber cells, flares, and vitreous haze than at baseline. Conclusion Ulcerative colitis can manifest with various ophthalmic manifestations ranging from nonspecific to severe, affecting visual prognosis or remaining asymptomatic. In our study most patients who underwent colonic surgery got benefits in the form of not only decreasing the severity of disease activity but also a decrease in the recurrence rate postsurgical. [ABSTRACT FROM AUTHOR]

The human eye is a consolidated organ with delicate structures and unique immune privileges. Ocular diseases are intractable due to the intrinsic biological barriers within the eyeball. Hydrogels are excellent drug-carrying substances with soft material and excellent properties. They have been extensively used to deliver drugs into ocular tissue via iontophoresis devices. Ophthalmic iontophoresis is an electrochemical technique using tiny electrical currents to deliver drugs into the eye non-invasively. The early infantile iontophoresis technique often required long applying time to achieve therapeutic dose in the posterior ocular segment. The potential limitations in the initial drug concentration and the maximum safe currents would also impede the efficiency and safety of iontophoresis. Moreover, the poor patient compliance always leads to mechanical damage to the cornea and sclera during application. Advantageously, the flexible drug-carrying hydrogel can be in direct contact with the eye during iontophoresis, thereby reducing mechanical damage to the ocular surface. Moreover, the water absorption and adjustable permeability of hydrogels can reduce the electrochemical (EC) reactions and enhance the efficiency of iontophoresis. In this review, we focus on recent developments of hydrogels iontophoresis in ophthalmologic practice. Refinements of the knowledge would provide an outlook for future application of hydrogels in treating ocular disease. [ABSTRACT FROM AUTHOR]

Posterior blepharitis and dry eye are common disorders with meibomian gland dysfunction (MGD), a principal driver of their pathophysiology. Meibomian gland dysfunction is increasingly prevalent in older populations with contributory hormonal imbalances. The abnormal meibum in MGD has been documented to have an excess of cholesterol with a resultant disruption of the lipid layer of the tear film. This leads to tear film instability due to the inadequate trapping of the aqueous portion of the tear film with resultant evaporative dry eye. Significant morbidity may follow MGD with ocular surface inflammation disrupting both social and work function. Rosacea is a common chronic inflammatory condition of the central face but can have ocular and systemic inflammatory associations. It is especially prevalent in North European populations and can have onset at any age, but commonly presents between thirty and fifty years of age. In ocular rosacea, MGD is a recognised manifestation as is dyslipidaemia. Ocular rosacea can predate cutaneous disease. As yet, there is no directly reported evidence of the efficacy of the early identification and treatment of ocular rosacea with associated dyslipidaemia and systemic inflammation. We posit that MGD in ocular rosacea sufferers may be a marker for dysregulated cholesterol synthesis and inflammation, and that statins maybe a potential therapy. This article introduces potential strategies to utilise ocular rosacea MGD as a possible marker for ophthalmologists, cardiologists, and primary healthcare physicians to treat rosacea-associated dyslipidaemia and systemic inflammation. This could aid in overall cardiovascular morbidity and mortality control for rosacea sufferers, potentially at an earlier age, while also addressing their tear film de-stabilisation through cholesterol lowering and inflammation reduction. [ABSTRACT FROM AUTHOR]

The maintenance of stable visual perception across eye movements is hypothesized to be aided by extraretinal information (e.g., corollary discharge [CD]). Previous studies have focused on the benefits of this information for perception at the fovea. However, there is little information on the extent that CD benefits peripheral visual perception. Here we systematically examined the extent that CD supports the ability to perceive transsaccadic changes at the fovea compared to peripheral changes. Human subjects made saccades to targets positioned at different amplitudes (4° or 8°) and directions (rightward or upward). On each trial there was a reference point located either at (fovea) or 4° away (periphery) from the target. During the saccade the target and reference disappeared and, after a blank period, the reference reappeared at a shifted location. Subjects reported the perceived shift direction, and we determined the perceptual threshold for detection and estimate of the reference location. We also simulated the detection and location if subjects solely relied on the visual error of the shifted reference experienced after the saccade. The comparison of the reference location under these two conditions showed that overall the perceptual estimate was approximately 53% more accurate and 30% less variable than estimates based solely on visual information at the fovea. These values for peripheral shifts were consistently lower than that at the fovea: 34% more accurate and 9% less variable. Overall, the results suggest that CD information does support stable visual perception in the periphery, but is consistently less beneficial compared to the fovea.

PurposeTo explore the effect of gaze direction and eyelid closure on intraocular pressure (IOP).MethodsEleven patients with primary open-angle glaucoma previously implanted with a telemetric IOP sensor were instructed to view eight equally-spaced fixation targets each at three eccentricities (10°, 20°, and 25°). Nine patients also performed eyelid closure. IOP was recorded via an external antenna placed around the study eye. Differences of mean IOP between consecutive gaze positions were calculated. Furthermore, the effect of eyelid closure on gaze-dependent IOP was assessed.ResultsThe maximum IOP increase was observed at 25° superior gaze (mean ± SD: 4.4 ± 4.9 mm Hg) and maximum decrease at 25° inferonasal gaze (-1.6 ± 0.8 mm Hg). There was a significant interaction between gaze direction and eccentricity (P = 0.003). Post-hoc tests confirmed significant decreases inferonasally for all eccentricities (mean ± SEM: 10°: -0.7 ± 0.2, P = 0.007; 20°: -1.1 ± 0.2, P = 0.006; and 25°: -1.6 ± 0.2, P = 0.006). Eight of 11 eyes showed significant IOP differences between superior and inferonasal gaze at 25°. IOP decreased during eyelid closure, which was significantly lower than downgaze at 25° (mean ± SEM: -2.1 ± 0.3 mm Hg vs. -0.7 ± 0.2 mm Hg, P = 0.014).ConclusionsOur data suggest that IOP varies reproducibly with gaze direction, albeit with patient variability. IOP generally increased in upgaze but decreased in inferonasal gaze and on eyelid closure. Future studies should investigate the patient variability and IOP dynamics.

PrecisA lower baseline corneal hysteresis and a decrease in corneal resistance factor (CRF) over time are associated with higher risk of visual field progression in glaucomatous and glaucoma suspect eyes.PurposeThe aim was to investigate the longitudinal change in CRF and cornea hysteresis (CH) as risk factors for visual field progression.Materials and methodsIn this prospective observational cohort study, 72 eyes of 48 glaucoma or glaucoma suspect patients were followed for an average of 4.5 years. Baseline and follow-up CH and CRF measurements were performed with the Ocular Response Analyzer (Reichert Ophthalmic Instruments Inc., Depew, N.Y.). Evaluation of rates of visual field change during follow-up was performed using visual field mean deviation. Univariable and multivariable linear mixed models assessed the relationship of visual field progression with baseline CRF and CH as well as with changes in CRF and CH.ResultsThe mean baseline CH was 9.0 (95% confidence interval: 8.6-9.4)  mm Hg and the mean baseline CRF was 9.3 (95% confidence interval: 8.8-9.9) mm Hg. There was no statistically significant difference in average CH and CRF measurements over time. In multivariable modeling adjusting for age, race, and mean intraocular pressure during follow-up, each 1 mm Hg lower in baseline CH and 1 mm Hg decrease in CRF over time were associated with a 0.12 (P=0.042) and 0.14 dB/year (P=0.007) faster rate of visual field mean deviation loss, respectively. Similar findings were found in glaucoma eyes but not found in glaucoma suspect eyes.ConclusionVisual field progression was associated with a lower baseline CH and a decrease in CRF over time. Assessment of corneal resistance and elasticity at baseline and during follow-up examinations should be considered to identify those eyes at highest risk of visual field progression.

Rod photoreceptors can be saturated by exposure to bright background light, so that no flash superimposed on the background can elicit a detectable response. This phenomenon, called increment saturation, was first demonstrated psychophysically by Aguilar and Stiles and has since been shown in many studies to occur in single rods. Recent experiments indicate, however, that rods may be able to avoid saturation under some conditions of illumination. We now show in ex vivo electroretinogram and single-cell recordings that in continuous and prolonged exposure even to very bright light, the rods of mice from both sexes recover as much as 15% of their dark current and that responses can persist for hours. In parallel to recovery of outer segment current is an ∼10-fold increase in the sensitivity of rod photoresponses. This recovery is decreased in transgenic mice with reduced light-dependent translocation of the G protein transducin. The reduction in outer-segment transducin together with a novel mechanism of visual-pigment regeneration within the rod itself enable rods to remain responsive over the whole of the physiological range of vision. In this way, rods are able to avoid an extended period of transduction channel closure, which is known to cause photoreceptor degeneration.SIGNIFICANCE STATEMENT Rods are initially saturated in bright light so that no flash superimposed on the background can elicit a detectable response. Frederiksen and colleagues show in whole retina and single-cell recordings that, if the background light is prolonged, rods slowly recover and can continue to produce significant responses over the entire physiological range of vision. Response recovery occurs by translocation of the G protein transducin from the rod outer to the inner segment, together with a novel mechanism of visual-pigment regeneration within the rod itself. Avoidance of saturation in bright light may be one of the principal mechanisms the retina uses to keep rod outer-segment channels from ever closing for too long a time, which is known to produce photoreceptor degeneration.

Purpose/aimThe optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference.Materials and methodsMRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21 mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation.ResultsFor both groups, ON path was nearly straight (

Decoding behavior, perception or cognitive state directly from neural signals is critical for brain-computer interface research and an important tool for systems neuroscience. In the last decade, deep learning has become the state-of-the-art method in many machine learning tasks ranging from speech recognition to image segmentation. The success of deep networks in other domains has led to a new wave of applications in neuroscience. In this article, we review deep learning approaches to neural decoding. We describe the architectures used for extracting useful features from neural recording modalities ranging from spikes to functional magnetic resonance imaging. Furthermore, we explore how deep learning has been leveraged to predict common outputs including movement, speech and vision, with a focus on how pretrained deep networks can be incorporated as priors for complex decoding targets like acoustic speech or images. Deep learning has been shown to be a useful tool for improving the accuracy and flexibility of neural decoding across a wide range of tasks, and we point out areas for future scientific development.

Safe and effective molecular therapeutics for prophylactic treatment of retinal degenerative diseases are greatly needed. Disruptions in the clearance of all-trans-retinal (atRAL) by the visual (retinoid) cycle of the retina can lead to the accumulation of atRAL and its condensation products known to initiate progressive retinal dystrophy. Retinylamine (Ret-NH2) and its analogues are known to be effective in lowering the concentration of atRAL within the eye and thus preventing retinal degeneration in mouse models of human retinopathies. Here, we chemically modified Ret-NH2 with amino acids and peptides to improve the stability and ocular bioavailability of the resulting derivatives and to minimize their side effects. Fourteen Ret-NH2 derivatives were synthesized and tested in vitro and in vivo. These derivatives exhibited structure-dependent therapeutic efficacy in preventing light-induced retinal degeneration in Abca4-/-Rdh8-/- double-knockout mice, with the compounds containing glycine and/or L-valine generally exhibiting greater protective effects than Ret-NH2 or other tested amino acid derivatives of Ret-NH2. Ret-NH2-L-valylglycine amide (RVG) exhibited good stability in storage; and effective uptake and prolonged retention in mouse eyes. RVG readily formed a Schiff base with atRAL and did not inhibit RPE65 enzymatic activity. Administered by oral gavage, this retinoid also provided effective protection against light-induced retinal degeneration in Abca4-/-Rdh8-/- mice. Notably, the treatment with RVG had minimal effects on the regeneration of 11-cis-retinal and recovery of retinal function. RVG holds promise as a lead therapy for effective and safe treatment of human retinal degenerative diseases.

PurposeThe aim was to determine whether 24-hour recording of intraocular pressure (IOP)-related ocular dimensional changes with a contact lens sensor (CLS, Triggerfish) is associated with the rate of visual field (VF) progression in primary open-angle glaucoma (POAG) patients.DesignThis was a retrospective, observational cohort study.ParticipantsPatients with POAG were included from the Glaucoma Clinic and Diagnostic Innovations in Glaucoma Study at the Hamilton Glaucoma Center at University of California, San Diego.MethodsA session of 24-hour CLS recording was acquired for 1 eye from each patient. The mean follow-up time was 9.9±4.0 years. The association between CLS variables and rate of change of mean deviation was determined by univariate and multivariate mixed linear regression models.ResultsThirty-two patients, aged 69.8±13.6 years were included, 50% were female. An average of 11.6±5.6 standard automated perimetry examinations was available with a mean rate of mean deviation progression of -0.2±0.4 dB/year. Mean IOP was 17.8±4.2 mm Hg. The mean number of IOP-lowering medications were 1.2±1.0. Each 10-unit larger nocturnal variability of IOP-related ocular dimensional changes measured by CLS recording was significantly associated with -0.25±0.11 dB faster VF loss in POAG patients (P=0.035).ConclusionsTwenty-four-hour CLS recording of IOP-related ocular dimensional change was associated with faster VF progression. Such CLS recordings are useful to assess the risk of in progression in POAG patients.

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development.SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca2+ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex.

The adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain. The transplantation of embryonic interneurons has been shown to restore juvenile plasticity to the adult host visual cortex. It is unclear whether transplanted interneurons directly mediate the renewed cortical plasticity or whether these cells act indirectly by modifying the host interneuron circuitry. Here we find that the transplant-induced reorganization of mouse host circuits is specifically mediated by Neuregulin (NRG1)/ErbB4 signaling in host parvalbumin (PV) interneurons. Brief visual deprivation reduces the visual activity of host PV interneurons but has negligible effects on the responses of transplanted PV interneurons. Exogenous NRG1 both prevents the deprivation-induced reduction in the visual responses of host PV interneurons and blocks the transplant-induced reorganization of the host circuit. While deletion of ErbB4 receptors from host PV interneurons blocks cortical plasticity in the transplant recipients, deletion of the receptors from the donor PV interneurons does not. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating the function of host PV interneurons.

Differences in patient characteristics between the PTVT and TVT Studies, including the level of preoperative intraocular pressure, contributed to the differences in surgical failure rates in each trial.