Frontiers in ophthalmology最新文献

Clinical relevance: This study compares a novel photoscreening device with a previously validated one in a school-age population. It highlights a tendency of the new device to underestimate myopic spherical equivalent and overestimate hyperopic cases.

Purpose: To compare the PlusoptiX A16 and Vision Screener V100 photoscreeners in a study population of school-age children.

Methods: One hundred and thirty-three children, with a mean age of 6.4 ± 0.5 years, were evaluated using both the PlusoptiX A16 and Vision Screener V100 photoscreeners. The measurements were taken in random order in a room with diminished ambient lighting.

Results: The mean refractive error values for the M component were 0.27 ± 0.67D (PlusoptiX A16) and 0.21 ± 0.58D (Vision Screener V100). For the J0 component, means were 0.16 ± 0.38D (PlusoptiX A16) and 0.06 ± 0.33D (Vision Screener V100) and for theJ45 component the means were 0.03 ± 0.17D (PlusoptiX A16) and 0.06 ± 0.22D (Vision Screener V100). When compared both instruments, statistically significant differences were observed for the M (p=0.017) and J0 (p=0.004) components. The agreement rates between PlusoptiX A16 and Vision Screener V100 across different refractive components were 80.5% for sphere, 82.0% for cylinder, and 40.6% for axis when considering a range of ±0.75 D for sphere and cylinder and ±25.0 degrees for cylinder axis. Simultaneously considering all three conditions, the overall agreement was 73.7%.

Conclusion: The Vision Screener V100, while generally aligning well with PlusoptiX A16, tends to underestimate myopic spherical equivalent, overestimate hyperopic cases, and underestimate J0 astigmatism.

UV light is known to cause damage to biomolecules in living tissue. Tissues of the eye that play highly specialised roles in forming our sense of sight are uniquely exposed to light of all wavelengths. While these tissues have evolved protective mechanisms to resist damage from UV wavelengths, prolonged exposure is thought to lead to pathological changes. In the lens, UV light exposure is a risk factor for the development of cataract, which is a condition that is characterised by opacity that impairs its function as a focusing element in the eye. Cataract can affect spatially distinct regions of the lens. Age-related nuclear cataract is the most prevalent form of cataract and is strongly associated with oxidative stress and a decrease in the antioxidant capacity of the central lens region. Since UV light can generate reactive oxygen species to induce oxidative stress, its effects on lens structure, transparency, and biochemistry have been extensively investigated in animal models in order to better understand human cataract aetiology. A review of the different light exposure models and the advances in mechanistic understanding gained from these models is presented.

Purpose: To describe the construction and diagnostic accuracy of a modularized, virtual reality (VR)-based, pupillometer for detecting relative afferent pupillary defect (RAPD) in unilateral optic neuropathies, vis-à-vis, clinical grading by experienced neuro-ophthalmologists.

Methods: Protocols for the swinging flashlight test and pupillary light response analysis used in a previous stand-alone pupillometer was integrated into the hardware of a Pico Neo 2 Eye^® VR headset with built-in eye tracker. Each eye of 77 cases (mean ± 1SD age: 39.1 ± 14.9yrs) and 77 age-similar controls were stimulated independently thrice for 1sec at 125lux light intensity, followed by 3sec of darkness. RAPD was quantified as the ratio of the direct reflex of the stronger to the weaker eye. Device performance was evaluated using standard ROC analysis.

Results: The median (25th - 75th quartiles) pupil constriction of the affected eye of cases was 38% (17 - 23%) smaller than their fellow eye (p<0.001), compared to an interocular difference of +/-6% (3 - 15%) in controls. The sensitivity of RAPD detection was 78.5% for the entire dataset and it improved to 85.1% when the physiological asymmetries in the bilateral pupillary miosis were accounted for. Specificity and the area under ROC curve remained between 81 - 96.3% across all analyses.

Conclusions: RAPD may be successfully quantified in unilateral neuro-ophthalmic pathology using a VR-technology-based modularized pupillometer. Such an objective estimation of RAPD provides immunity against biases and variability in the clinical grading, overall enhancing its value for clinical decision making.

Intraocular foreign bodies (IOFBs) remain a severe complication of ocular trauma commonly encountered worldwide. This literature review aimed to discuss current practice patterns, areas of controversy, and advances in the management of IOFBs. Injuries involving IOFBs carry significant ocular morbidity and management can be extremely challenging. A systematic approach to preoperative evaluation and IOFB surgical management is detailed in this article and should be applied in each case. The location and composition of an IOFB have important implications on surgical approach and timing, especially in cases of toxic metals and vegetable matter. The advantages, disadvantages, and previous literature regarding immediate versus delayed foreign body removal are presented. Surgical approaches are described, with an emphasis on posterior chamber IOFB management and removal via pars plana vitrectomy. Final visual acuity is variable, but approaches have been used to prognosticate outcomes including the Ocular Trauma Score. By synthesizing current IOFB literature, the goal is to provide practitioners with guidance that will maximize the chances of surgical success and patient outcomes.

Aim: Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs.

Methods: A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023.

Results: We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 - 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an "ab externo" approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection.

Conclusion: The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.

Correlating damage outcomes to a retinal laser exposure is critical for diagnosis and choosing appropriate treatment modalities. Therefore, it is important to understand the causal relationships between laser parameters, such as wavelength, power density, and length of exposure, and any resulting injury. Differentiating photothermal from photochemical processes in an in vitro retinal model using cultured retinal pigment epithelial cells would be a first step in achieving this goal. The first-order rate constant of Arrhenius has been used for decades to approximate cellular thermal damage. A modification of this equation, called the damage integral (Ω), has been used extensively to predict the accumulation of laser damage from photothermal inactivation of critical cellular proteins. Damage from photochemical processes is less well studied and most models have not been verified because they require quantification of one or more uncharacterized chemical species. Additionally, few reports on photochemical damage report temperature history, measured or simulated. We used simulated threshold temperatures from a previous in vitro study to distinguish between photothermal and photochemical processes. Assuming purely photochemical processes also inactivate critical cellular proteins, we report the use of a photothermal Ω and a photochemical Ω that work in tandem to indicate overall damage accumulation. The combined damage integral (Ω_CDI) applies a mathematical switch designed to describe photochemical damage relative to wavelength and rate of photon delivery. Although only tested in an in vitro model, this approach may transition to predict damage at the mammalian retina.

Purpose: To evaluate the accuracy of the new Tono-Vera rebound tonometer (Reichert Inc, Buffalo, NY) compared to Goldmann Applanation Tonometry.

Methods: This prospective, observational, cross-sectional study was designed in accordance with ANSI Z80.10-2014 and ISO 8612-2009 guidelines for tonometer comparison. Intraocular Pressure (IOP) was measured by Goldmann Applanation and Tono-Vera on 160 eyes of 160 subjects. Corneal Astigmatism and Central Corneal Thickness were also measured. A single investigator (CN) conducted all measurements. The average of two measurements from each tonometer was used in the analysis. Bland-Altman plots, total least squares regression analysis, and simple linear regression were used to evaluate agreement between the tonometers.

Results: Average IOP values from Goldmann Applanation and Tono-Vera were not significantly different (19.17 and 19.03 respectively, p=0.40, paired t-test). The total least squares regression analysis indicated strong agreement between the two tonometers (slope +0.97, offset +0.49 mmHg, standard deviation 2.11 mmHg). There were 2 IOP measurement pairs that exceeded the ± 5 mmHg limits of agreement required in ANSI Z80.10-2014 and ISO 8612-2009, which is within the range of acceptability specified in the standards.

Conclusion: We evaluated IOP measurements by Tono-Vera Rebound Tonometer vs Goldmann Applanation Tonometry for eyes with a wide range of IOP values and found no statistically significant differences in the results. Tono-Vera meets the requirements of ANSI Z80.10-2014 and ISO 8612-2009, demonstrating accuracy comparable to Goldmann tonometry.

Photobiomodulation (PBM) refers to the process in which wavelengths of light are absorbed by intracellular photoacceptors, resulting in the activation of signaling pathways that culminate in biological changes within the cell. PBM is the result of low-intensity light-induced reactions in the cell in contrast to thermal photoablation produced by high-intensity lasers. PBM has been effectively used in the clinic to enhance wound healing and mitigate pain and inflammation in musculoskeletal conditions, sports injury, and dental applications for many decades. In the past 20 years, experimental evidence has shown the benefit of PBM in increasing numbers of retinal and ophthalmic conditions. More recently, preclinical findings in ocular models have been translated to the clinic with promising results. This review discusses the preclinical and clinical evidence of the effects of PBM in ophthalmology and provides recommendations of the clinical use of PBM in the management of ocular conditions.

Introduction: Evidence in non-ocular tissues indicate that the antioxidant glutathione (GSH) may be regulated in a circadian manner leading to the idea that GSH levels in the lens may also be controlled in a circadian manner to anticipate periods of oxidative stress.

Methods: Male rat Wistar lenses (6 weeks) were collected every 4 hours over a 24-hour period at 6am, 10am, 2pm, 6pm, 10pm and 2am and quantitative-PCR, western blotting and immunohistochemistry performed to examine the expression of core clock genes and proteins (BMAL1, CLOCK, CRY1-2, PER 1-3) and their subcellular localisation over a 24-hour period. Western blotting of lenses was also performed to examine the expression of NRF2, a transcription factor involved in regulating genes involved in GSH homeostasis and GSH related enzymes (GCLC, GS and GR) over the 24-hour period. Finally, HLPC was used to measure GSH levels in the aqueous humour and lenses every 4 hours over a 24-hour period.

Results: The rat lens contains the core molecular components of a circadian clock with the expression of core clock proteins, NRF2 and GSH related enzymes fluctuating over a 24-hour period. BMAL1 expression was highest during the day, with BMAL1 localised to the nuclei at 10am. NRF2 expression remained constant over the 24-hour period, although appeared to move in and out of the nuclei every 4 hours. GSH related enzyme expression tended to peak at the start of night which correlated with high levels of GSH in the lens and lower levels of GSH in the aqueous humour.

Conclusion: The lens contains the key components of a circadian clock, and time-of-day differences exist in the expression of GSH and GSH related enzymes involved in maintaining GSH homeostasis. GSH levels in the rat lens were highest at the start of night which represents the active phase of the rat when high GSH levels may be required to counteract oxidative stress induced by cellular metabolism. Future work to directly link the clock to regulation of GSH levels in the lens will be important in determining whether the clock can be used to help restore GSH levels in the lens.

The eye lens is a transparent, ellipsoid tissue in the anterior chamber that is required for the fine focusing of light onto the retina to transmit a clear image. The focusing function of the lens is tied to tissue transparency, refractive index, and biomechanical properties. The stiffness and elasticity or resilience of the human lens allows for shape changes during accommodation to focus light from objects near and far. It has long been hypothesized that changes in lens biomechanical properties with age lead to the loss of accommodative ability and the need for reading glasses with age. However, the cellular and molecular mechanisms that influence lens biomechanical properties and/or change with age remain unclear. Studies of lens stiffness and resilience in mouse models with genetic defects or at advanced age inform us of the cytoskeletal, structural, and morphometric parameters that are important for biomechanical stability. In this review, we will explore whether: 1) tissue level changes, including the capsule, lens volume, and nucleus volume, 2) cellular level alterations, including cell packing, suture organization, and complex membrane interdigitations, and 3) molecular scale modifications, including the F-actin and intermediate filament networks, protein modifications, lipids in the cell membrane, and hydrostatic pressure, influence overall lens biomechanical properties.