Choroidal thinning in myopia is associated with axial elongation and severity of myopic maculopathy.

High myopia can lead to pathologic myopia and visual impairment, whereas its causes are unclear. We retrospectively researched high myopia cases from patient records to investigate the association between axial elongation and myopic maculopathy. Sixty-four eyes were examined in patients who visited the department between July 2017 and June 2018, had an axial length of 26 mm or more, underwent fundus photography, and had their axial length measured twice or more. The average axial length was 28.29 ± 1.69 mm (mean ± standard deviation). The average age was 58.3 ± 14.4 years old. Myopic maculopathy was categorized as mild (grades 0 and 1) and severe (grades 2, 3, and 4). The severe group had longer axial lengths than the mild group (P < 0.05). Moreover, the severe group exhibited thinner choroidal thickness than the mild group (P < 0.05). When subjects were grouped by axial elongation over median value within a year, the elongation group showed thinner central choroidal thickness than the non-elongation group (142.1 ± 91.9 vs. 82.9 ± 69.8, P < 0.05). In conclusion, in patients with high myopia, the severity of maculopathy correlated with choroidal thickness and axial length. Thinner choroidal thickness was associated with axial elongation based on the baseline axial length.

Establishment of an in vitro choroid complex system for vascular response screening.

The choroid, a vascularized tissue situated between the retina and the sclera, plays a crucial role in maintaining ocular homeostasis. Despite its significance, research on choroidal abnormalities and the establishment of effective in vitro models have been limited. In this study, we developed an in vitro choroid model through the co-culture of human induced pluripotent stem cells (hiPSC)-derived endothelial cells (ECs) and mouse choroidal fibroblasts (msCFs) with hiPSC-derived retinal pigment epithelial (RPE) cells via a permeable membrane. This model, inclusive of ECs, CFs, and RPE cells, exhibited similarities with in vivo choroidal vessels, as confirmed through immunohistochemistry of extracellular matrix markers and vascular-related markers, as well as choroid angiogenesis sprouting assay analysis. The effectiveness of our in vitro model was demonstrated in assessing vascular changes induced by drugs targeting vasoregulation. Our model offers a valuable tool for gaining insights into the pathological mechanisms underlying choroid development and the progression of choroidal vascular diseases.

Slowing of Greater Axial Length Elongation Stemming from the Coronavirus Disease 2019 Pandemic with Increasing Time Outdoors: The Tokyo Myopia Study.

Purpose: To investigate the changes in axial length (AL) elongation and other ocular parameters before and during the coronavirus disease 2019 pandemic. Design: A longitudinal school-based study. Participants: Public elementary schoolchildren in Tokyo (grades 1-6; age, 6-12 years) participated in this study from 2018 to 2021. Methods: All participants underwent eye examinations and provided written consent to measurements of the noncycloplegic refraction and ocular biometry including AL, among others. The students' parents also completed a questionnaire about the students' lifestyles. We included the right eye in our analysis and compared the changes in the ocular parameters among the periods using a linear mixed-effects model for repeated measures and examined the univariate and step-wise multiple regression analyses to evaluate the associations between myopia and other covariates. Main Outcome Measures: Changes in AL elongation and other ocular parameters from 2018 to 2019 (prepandemic), that of 2019 to 2020 (immediately after the pandemic onset), and that of 2020 to 2021 (during the pandemic). Results: A total of 578 students before the pandemic period, 432 immediately after the pandemic onset, and 457 during the pandemic period were evaluated. The changes in the ALs and spherical equivalents (SEs) a year before, immediately after onset, and during the pandemic were 0.31 mm/-0.20 diopter, 0.38 mm/-0.27 diopter, and 0.28 mm/-0.47 diopter, respectively (ALs, P < 0.001; SEs, P = 0.014). The results of the questionnaire showed that time spent outdoors daily had changed during the 3 years to 79, 63, and 77 minutes/day, respectively (P < 0.001). Time spent using smartphones or tablets increased year by year to 41, 52, and 62 minutes/day (P < 0.001). The greatest AL elongation occurred during the period when the shortest amount of time was spent outdoors during the 3 years. Conclusions: These results suggested that the school closures and decreasing time spent outdoors might have caused greater AL elongation among schoolchildren in Tokyo; however, it is possible that, although the time spent in near work still increased, the return to the time spent outdoors to the prepandemic levels may have affected the slowing of AL elongation after lockdown. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Myopia Is an Ischemic Eye Condition: A Review from the Perspective of Choroidal Blood Flow.

Myopia is a common refractive error that affects a large proportion of the population. Recent studies have revealed that alterations in choroidal thickness (ChT) and choroidal blood flow (ChBF) play important roles in the progression of myopia. Reduced ChBF could affect scleral cellular matrix remodeling, which leads to axial elongation and further myopia progression. As ChT and ChBF could be used as potential biomarkers for the progression of myopia, several recent myopia treatments have targeted alterations in ChT and ChBF. Our review provides a comprehensive overview of the recent literature review on the relationship between ChBF and myopia. We also highlight the importance of ChT and ChBF in the progression of myopia and the potential of ChT as an important biomarker for myopia progression. This summary has significant implications for the development of novel strategies for preventing and treating myopia.

Single-cell RNA-sequencing reveals the transcriptional landscape of lacrimal gland in GVHD mouse model.

PURPOSE: To investigate the global transcriptional landscape of lacrimal gland cell populations in the GVHD mouse model. METHODS: Single-cell RNA sequencing and further bioinformatic analysis of dissociated lacrimal gland (LG) cells from the mouse model were performed. Parts of transcriptional results were confirmed by immunofluorescence staining. RESULTS: We identified 23 cell populations belonging to 11 cell types. In GVHD LG, the proportion of acinar cells, myoepithelial cells, and endothelial cells was remarkably decreased, while T cells and macrophages were significantly expanded. Gene expression analysis indicated decreased secretion function, extracellular matrix (ECM) synthesis, and increased chemokines of myoepithelial cells. A newly described epithelial population named Lrg1high epithelial cells, expressing distinct gene signatures, was exclusively identified in GVHD LG. The fibroblasts exhibited an inflammation gene pattern. The gene pattern of endothelial cells suggested an increased ability to recruit immune cells and damaged cell-cell junctions. T cells were mainly comprised of Th2 cells and effective memory CD8+ T cells. GVHD macrophages exhibited a Th2 cell-linked pattern. CONCLUSIONS: This single-cell atlas uncovered alterations of proportion and gene expression patterns of cell populations and constructed cell-cell communication networks of GVHD LG. These data may provide some new insight into understanding the development of ocular GVHD.

Electroencephalogram-detected stress levels in the frontal lobe region of patients with dry eye.

PURPOSE: To evaluate stress levels extracted from prefrontal electroencephalogram (EEG) signals and investigate their relationship with dry eye symptoms. METHODS: This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with aqueous tear-deficient dry eye (low Schirmer group), 25 eyes of 25 patients with short tear breakup time dry eye (short breakup time group), and 24 eyes of 24 individuals without dry eye. An EEG test, the Japanese version of the Ocular Surface Disease Index (OSDI), and a stress questionnaire were administered. EEG-detected stress levels were assessed under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. RESULTS: Stress levels were significantly lower when the eyes were closed than when they were open in all groups (all P < 0.05). Stress levels during eyes open under ocular surface anesthesia were significantly lower than those during eyes open without anesthesia only in the low Schirmer group; no differences were found between the short breakup time and control groups. OSDI scores were associated with EEG-detected stress levels (P = 0.06) and vital staining score (P < 0.05) in the low Schirmer group; they were not associated with EEG-detected stress (P > 0.05), but with subjective stress questionnaire scores and breakup time values in the short breakup time group (P < 0.05). CONCLUSIONS: In the low Schirmer group, peripheral nerve stimulation caused by ocular surface damage induced stress reactions in the frontal lobe, resulting in dry eye symptoms. Conversely, in the short breakup time group, the stress response in the frontal lobe was not related to symptom development.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

Evaluation of a new portable corneal topography system for self-measurement using smartphones: a pilot study.

PURPOSE: Herein, we propose the use of the "KeraVio Ring", which is a portable, selfie-based, smartphone-attached corneal topography system that is based on the Placido ring videokeratoscope. The goal of this study was to evaluate and compare corneal parameters between KeraVio Ring and conventional corneal tomography images. METHODS: We designed the KeraVio Ring as a device comprising 3D-printed LED rings for generating Placido rings that can be attached to a smartphone. Two LED rings are attached to a cone-shaped device, and both corneas are illuminated. Selfies were taken using the KeraVio Ring attached to the smartphone without assistance from any of the examiners. Captured Placido rings on the cornea were analysed by intelligent software to calculate corneal parameters. Patients with normal, keratoconus, or LASIK-treated eyes were included. Anterior segment optical coherence tomography (AS-OCT) was also performed for each subject. RESULTS: We found highly significant correlations between the steepest and flattest keratometry, corneal astigmatism, and vector components obtained with the KeraVio Ring and AS-OCT. In subjects with normal, keratoconus, and LASIK-treated eyes, the mean difference in corneal astigmatism between the two devices was -0.8 ± 1.4 diopters (D) (95% limits of agreement (LoA), -3.6 to 2.0), -1.8 ± 3.7 D (95% LoA, -9.1 to 5.5), and -1.5 ± 1.3 D (95% LoA, -4.0 to 1.1), respectively. CONCLUSIONS: The experimental results showed that the corneal parameters obtained by the KeraVio Ring were correlated with those obtained with AS-OCT. The KeraVio Ring has the potential to address an unmet need by providing a tool for portable selfie-based corneal topography.

Scleral remodeling during myopia development in mice eyes: a potential role of thrombospondin-1.

BACKGROUND: Scleral extracellular matrix (ECM) remodeling plays a crucial role in the development of myopia, particularly in ocular axial elongation. Thrombospondin-1 (THBS1), also known as TSP-1, is a significant cellular protein involved in matrix remodeling in various tissues. However, the specific role of THBS1 in myopia development remains unclear. METHOD: We employed the HumanNet database to predict genes related to myopic sclera remodeling, followed by screening and visualization of the predicted genes using bioinformatics tools. To investigate the potential target gene Thbs1, we utilized lens-induced myopia models in male C57BL/6J mice and performed Western blot analysis to detect the expression level of scleral THBS1 during myopia development. Additionally, we evaluated the effects of scleral THBS1 knockdown on myopia development through AAV sub-Tenon's injection. The refractive status and axial length were measured using a refractometer and SD-OCT system. RESULTS: During lens-induced myopia, THBS1 protein expression in the sclera was downregulated, particularly in the early stages of myopia induction. Moreover, the mice in the THBS1 knockdown group exhibited alterations in myopia development in both refraction and axial length changed compared to the control group. Western blotting analysis confirmed the effectiveness of AAV-mediated knockdown, demonstrating a decrease in COLA1 expression and an increase in MMP9 levels in the sclera. CONCLUSION: Our findings indicate that sclera THBS1 levels decreased during myopia development and subsequent THBS1 knockdown showed a decrease in scleral COLA1 expression. Taken together, these results suggest that THBS1 plays a role in maintaining the homeostasis of scleral extracellular matrix, and the reduction of THBS1 may promote the remodeling process and then affect ocular axial elongation during myopia progression.

Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men.

Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD+ intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD+ levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD+ content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD+ levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD+ biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

Tearful relations: oxidative stress, inflammation and eye diseases: [review] / Relações lacrimejantes: estresse oxidativo, inflamação e doenças oculares: [revisão]

Oxidative stress is caused by an imbalance between the production of reactive oxygen species and ability the biological systems' defense mechanisms necessary to eliminate the stress. It has been accepted that oxidative stress is involved in many acute and chronic diseases and even in normal aging. Recently, increased awareness of oxidative stress damage and its relation with ocular surface diseases incite researchers to discover possible mechanisms in the development of dry eye disease. This review focuses on the evaluation of the influence of oxidative stress on eye diseases emphasizing its relation with the pathogenesis of dry eye disease.

Estresse oxidativo é causado por um desequilíbrio entre a produção de espécies reativas do oxigênio e a habilidade dos mecanismos de defesa do sistema biológico necessários para eliminar este estresse. O estresse oxidativo tem sido aceito como um fator envolvido em várias doenças agudas, crônicas e até mesmo no envelhecimento fisiológico. Recentemente, o crescente conhecimento dos danos causados pelo estresse oxidativo e a sua relação com doenças da superfície ocular estimulou pesquisadores a descobrir possíveis mecanismos no desenvolvimento da doença do olho seco. Esta revisão tem como foco a avaliação da influência do estresse oxidativo nas doenças do olho e enfatiza a sua relação com a patogênese da doença do olho seco.

Estudo quantitativo da lágrima pelo teste de fenol vermelho na população brasileira / Quantitative tear study using the red phenol test in the Brazilian population

OBJETIVO: Determinar parâmetros normais do teste de fenol vermelho na população brasileira, e comparar entre diferentes raças, idade e sexo. MÉTODOS: Foram avaliados, com o teste de fenol vermelho, 280 indivíduos (560 olhos) da raça branca e 280 indivíduos (560 olhos) da raça não branca, que foram divididos de acordo com a idade e o sexo. Foram excluídos indivíduos com qualquer doença ocular, usuários de lente de contato e que usavam medicação ocular. RESULTADOS: Dos 1.120 olhos avaliados, o resultado médio foi de 19,77±7,90 mm. CONCLUSAO: O resultado médio encontrado foi um valor intermediário entre as duas populações previamente estudadas (japonesa e norte-americana).