Eye and Vision最新文献

Background: Intravitreal anti-vascular endothelial growth factor (VEGF) agents improve visual acuity in diabetic macular edema (DME). However, resistance, non-response, or recurrence occurs in many patients. Predictive biomarkers for anti-VEGF response are lacking. We aim to identify cytokine markers predictive of anti-VEGF response and elucidate cytokines involved in poor-response DME pathogenesis.

Methods: A luminex assay was carried out to measure the concentration of cytokines in the aqueous humor. A predictive model based on baseline cytokines was constructed in a discovery set that comprised 46 responders and 20 non-responders. In addition, an analysis of baseline cytokines of 15 responders and 12 non-responders was conducted as a validation set. The performance of the nomogram was determined using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness of fit test.

Results: Baseline concentrations of angiogenesis-related cytokines VEGF (P < 0.0001), placenta growth factor (PIGF) (P < 0.0001), angiopoietin-2 (Ang-2) (P < 0.0001), inflammatory factor interleukin-6 (IL-6) (P < 0.0001), IL-8 (P < 0.0001), chemokine monocyte chemoattractant protein-1 (MCP-1) (P < 0.0001), and adhesion factor intercellular adhesion molecule-1 (ICAM-1) (P < 0.001) were significantly increased compared to controls. The prediction nomogram model included five baseline cytokines: VEGF, IL-6, Ang-2, MCP-1, and ICAM-1 were constructed. The AUC for the discovery set was 0.85 (95% CI: 0.74-0.96) and for the internal validation was 0.84, indicating that the prediction model has good predictive accuracy. The Hosmer-Lemeshow goodness of fit test showed good model calibration (P = 0.295). The levels of Ang-2 (P = 0.0042), IL-6 (P < 0.0001), IL-8 (P < 0.0001), MCP-1 (P < 0.0001), and PIGF (P < 0.0001) were still significantly increased at the 6-month timepoint after multiple injections of anti-VEGF drugs for non-response group patients.

Conclusion: The baseline cytokine-based model helped to assess the individual probability of response to anti-VEGF therapy. There are cytokines beyond VEGF that are involved in the pathogenesis of DME, therapeutic regimens targeting these cytokines may improve the visual acuity and reduce macular edema.

Background: International guidelines recommend at least 150 min of weekly moderate-to-vigorous physical activity (MVPA), but whether concentrated versus distributed activity patterns differ in their associations with age-related eye diseases remains unclear.

Methods: This prospective cohort study included 86,271 UK Biobank participants free of age-related eye diseases at baseline. Physical activity was assessed using wrist-mounted triaxial accelerometers (Axivity AX3) over seven consecutive days. Two MVPA thresholds were examined: ≥ 150 min/week (primary) and ≥ 300 min/week (secondary). Participants were categorized as: inactive (below threshold), weekend warriors (WW; meeting threshold with ≥ 50% MVPA concentrated within 1-2 days), or regularly active (meeting threshold without WW criteria). Cox proportional hazards regression models were used to assess associations over a median follow-up of 7.9 years.

Results: At the ≥ 150 min/week threshold, both WW (hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.84-0.94, P < 0.001) and regularly active patterns (HR = 0.93, 95% CI: 0.87-0.99, P = 0.028) were associated with a reduced risk of cataract compared to inactivity. The WW pattern was also associated with a reduced risk of diabetic retinopathy (DR, HR = 0.74, 95% CI: 0.55-0.99, P = 0.043) and age-related macular degeneration (AMD, HR = 0.85, 95% CI: 0.75-0.97, P = 0.016). Direct comparisons between the WW and regularly active patterns showed no significant differences for these conditions (all P > 0.05), except for a nominal difference in glaucoma (P = 0.036). At the ≥ 300 min/week threshold, only the WW pattern remained significantly associated with reduced risk of cataract (HR = 0.91, 95% CI: 0.86-0.97, P = 0.002) and glaucoma (HR = 0.86, 95% CI: 0.75-0.97, P = 0.019).

Conclusion: Both the WW and regularly active patterns demonstrate protective associations with age-related eye diseases compared to inactivity, with no statistically significant differences between the two active groups for most outcomes. These findings suggest that the WW approach is a viable and flexible alternative for individuals who find it difficult to maintain daily physical activity.

Background: Keratoconus (KC) is a vision-threatening condition with a higher prevalence and earlier onset in males than in females. The study aims to investigate sex-associated transcriptomic features of KC and assess whether sex hormones modulate stromal remodelling.

Methods: We performed whole-transcriptome sequencing of human corneal tissues from patients with KC and matched controls (n = 20; five males and five females per group), followed by weighted gene co-expression network analysis, Gene Ontology, Kyoto Encyclopaedia of Genes and Genomes enrichment, and competitive endogenous RNA (ceRNA) network construction. Our findings were functionally probed in primary human corneal stromal fibroblasts (HCSFs) using testosterone, β-oestradiol, and their antagonists. Key nodes were validated by reverse transcription-quantitative polymerase chain reaction analysis, Western blotting, and immunofluorescence.

Results: Across 17,496 genes, we identified 3,345 differentially expressed genes (adjusted P < 0.01, |log₂ fold-change|≥ 2). Module analyses highlighted pathways related to intracellular transport, energy metabolism, and hormone responses. Sex-stratified analyses revealed male-specific up-regulation of gonadal development programs and female-specific down-regulation of immune and hormonal processes. In HCSFs, testosterone down-regulated type I collagen but up-regulated type III collagen and α-smooth muscle actin; these effects were mitigated by flutamide. Conversely, oestrogen inhibition reproduced altered stromal remodelling, which was rapidly reversed by β-oestradiol. A female-specific ceRNA axis (circEPB41L2_0001-miR-942-5p-DCP1A) was identified and validated by performing perturbation experiments.

Conclusions: KC exhibited sex-biased molecular programs consistent with androgen-driven and oestrogen-deficiency-related stromal remodelling. These findings elucidate hormone-driven mechanisms underlying KC and suggest that sex-associated hormonal regulation could inform future personalised therapeutic strategies.

Background: Low concentration atropine is widely prescribed to slow myopia progression in children, yet its short-term retinal and choroidal effects remain incompletely understood. This study aimed to evaluate short-term effects of a range of low atropine concentrations on axial length, retinal and choroidal thickness, and microvasculature.

Methods: In this double-masked, randomized study, twenty healthy adults received a single instillation of placebo, 0.01%, 0.025%, 0.05%, or 0.1% atropine in the right eye across five separate sessions. Retinal and choroidal thickness in the central 1.0 mm diameter and 1.0-3.0 mm annulus, perfusion density in the superficial and deep vascular complex and choriocapillaris in the central 1.0 mm and 1.0-2.5 mm annulus, foveal avascular zone and axial length were assessed at baseline and 1 h and 24 h after instillation.

Results: Participant mean age was 25.5 ± 3.4 years and mean refraction was - 1.9 ± 2.2 D. No significant changes in retinal or choroidal thickness or axial length were observed for any concentration or time point (P > 0.05). The superficial vascular plexus perfusion density in the 1.0-2.5 mm annulus showed significant decrease (P = 0.02) with time after atropine instillation, but not with concentration (P > 0.05); post hoc analysis showed significant decrease from baseline at 1 h (P = 0.03) compared to 24 h (P = 0.28).

Conclusion: These findings indicate that a single instillation of 0.01%-0.1% atropine does not alter axial length or retinal or choroidal thickness over 24 h, but may transiently affect superficial retinal perfusion in a time-dependent manner. Characterizing these short-term effects is important for a better understanding of the physiological responses to atropine in clinical and research settings.

Background: Choroideremia is an X-linked chorioretinal dystrophy with well-characterized progression in affected males but variable phenotypes in female carriers. Understanding the phenotypic spectrum in female carriers is important for prognosis, monitoring, and trial design. This study aims to delineate the natural history of retinal phenotypes and visual function loss in female choroideremia carriers and establish an improved fundus grading system for disease stratification and prognostic prediction.

Methods: This single-center, longitudinal and cross-sectional, retrospective study included 64 genetically confirmed female choroideremia carriers. Clinical data included genotype, age, best-corrected visual acuity, color fundus photography, fundus autofluorescence, visual field testing, and full-field electroretinography. A novel fundus phenotypic grading system was proposed based on fundus autofluorescence and fundus color photographs, which included four types: granular (merged fine/coarse patterns), severe peripapillary atrophy (highlighting severe peripapillary atrophy as a crucial feature), localized atrophy, and widespread atrophy. The agreement between measurement-based grading and visual grading was assessed.

Results: Visual acuity and fundus phenotypes showed moderate interocular symmetry, while visual field and electroretinography metrics showed high interocular symmetry. At baseline, phenotypes included granular (76.3%), severe peripapillary atrophy (7.5%), localized atrophy (10.8%), and widespread atrophy (5.4%). Longitudinally, the granular type remained stable, while other types progressed, with a mean atrophy expansion rate of 3.1 mm²/year. Age did not correlate with visual function decline, and neither age nor genotype was linked to the severe fundus phenotype. Baseline phenotype was the strongest predictor of prognosis. Excellent agreement (weighted κ = 0.93) was observed between the measurement-based and visual grading methods.

Conclusions: We proposed a novel fundus grading system for choroideremia carriers and demonstrated its strong clinical utility and prognostic value. The granular type confers a favorable prognosis, whereas the other three types exhibit progressive deterioration. Baseline phenotypic grading is the best indicator of long-term outcomes, underscoring its value in clinical monitoring and therapeutic trial design.

Background: Glaucoma filtration surgery (GFS) often fails because of excessive scar formation driven by inflammation and fibroblast activation. Although the stimulator of interferon genes (STING) pathway is involved in inflammatory responses, its role in post-surgical fibrosis remains unclear.

Methods: A mouse GFS model was established in wild-type (WT) and STING-knockout (STING-KO) animals. A parallel cohort of WT mice received a single intraoperative subconjunctival injection of the STING inhibitor H151. Bleb survival, intraocular pressure, histopathology, collagen deposition, and inflammatory/fibrotic markers were evaluated for 28 days. RNA sequencing, Western blotting, and ELISA were employed to profile the p38/MAPK axis. Primary human Tenon's capsule fibroblasts were treated with angiotensin II in the presence or absence of STING silencing or H151 to corroborate mechanisms in vitro.

Results: STING expression was markedly up-regulated in fibroblasts within human and mice post-GFS tissues. STING-KO mice exhibited prolonged bleb survival together with reduced collagen deposition and fibroblast activation. RNA-sequencing revealed that STING deletion significantly altered the p38 mitogen-activated protein kinase (MAPK) pathway. Mechanistically, STING deficiency suppressed p38 MAPK phosphorylation, leading to decreased levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α, IL-18, and IL-1β, as well as the fibrogenic factors α-SMA, collagen I, fibronectin, connective tissue growth factor, and collagen type III alpha 1 at the surgical sites. Consistently, the selective STING inhibitor H151 recapitulated these effects by suppressing p38 MAPK signaling and markedly reducing fibrotic scarring.

Conclusions: STING deficiency alleviates scar formation after GFS by suppressing p38 MAPK pathway. Targeting STING/p38 axis may improve surgical outcomes by modulating the balance between inflammation and tissue repair.

Background: Mounting evidence indicates metabolic dysregulation in diabetic corneal neuropathy (DCN). This study elucidates how the chromatin remodeler Brahma-related gene 1 (BRG1) orchestrates glycolytic reprogramming to drive neurodegeneration and epithelial repair defects in DCN.

Methods: Type 1 diabetic mice were established via streptozotocin (STZ) injection. Glycolysis was inhibited using 2-deoxy-D-glucose (2-DG) to assess its role in DCN pathogenesis. BRG1 expression was modulated by subconjunctival plasmid delivery (overexpression/knockdown). Pathway screening identified BRG1 downstream effectors, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) inhibition (LY294002) confirmed regulatory hierarchy. Glycolytic flux was evaluated via Western blotting and immunofluorescence; corneal nerve integrity and epithelial healing were assessed by βIII-tubulin staining and sodium fluorescein assay.

Results: Hyperglycemia upregulated BRG1 and glycolytic enzymes in diabetic corneal nerves. BRG1 overexpression exacerbated epithelial repair delay and neurodegeneration, while knockdown partially reversed damage. BRG1 overexpression activated PI3K/AKT transcription, and PI3K/AKT inhibition did not alter BRG1 levels but rescued BRG1-induced pathologies.

Conclusions: Glycolytic reprogramming is a critical driver of DCN progression. BRG1 activates PI3K/AKT signaling to enhance glycolytic flux, thereby regulating DCN pathogenesis. Targeting this axis may offer novel therapeutic strategies.

Background: Age-related eye diseases (AREDs) are leading causes of visual impairment worldwide. With global population aging, understanding their epidemiological trends and socioeconomic disparities is crucial for public health planning and equitable resource allocation.

Methods: We conducted a secondary epidemiological analysis of AREDs using data from the Global Burden of Disease (GBD) Study 2021. We evaluated years lived with disability (YLDs) and age-standardized YLD rates (ASYR) and conducted trend analysis using Joinpoint regression. Cross-country inequalities were assessed using the slope index of inequality (SII) and concentration index, with correlation and regression analyses examining associations with the socio-demographic index (SDI).

Results: Global YLDs for AREDs increased from 78.503 to 100.006, while ASYR decreased from 112.815 to 92.803 per 100,000 populations between 1990 and 2021. Despite a global increase in the relative burden of glaucoma, both absolute and relative inequalities for age-related macular degeneration (AMD) and cataracts decreased. Low-SDI countries showed slight improvements in reducing these inequalities. The SII for AREDs improved in lower-SDI countries between 1990 and 2021, with reductions in AMD (from - 9.250 to - 6.033), cataract (from - 258.131 to - 173.762), and glaucoma (from - 21.090 to - 20.064). The concentration index for AMD and cataract decreased from - 0.167 and - 0.335 in 1990 to - 0.129 and - 0.272 in 2021, respectively, while the concentration index for glaucoma increased from - 0.208 to - 0.263, Regional disparities in the AREDs burden were evident, with most regions showing improved inequality in lower-SDI countries as reflected in both the SII and concentration index.

Conclusions: Despite global improvements in the relative burden of AREDs, significant socioeconomic and geographical inequalities persist, particularly in low-SDI regions. Targeted public health strategies and strengthened eye care systems are urgently needed to address these disparities and achieve equitable eye health outcomes worldwide.

Myopia, or near-sightedness, is a growing global concern as its incidence rate continues to dramatically rise. It has been linked to significant ocular morbidity and reduced quality of life. Despite this, much is still largely unknown about the development of and the mechanisms driving the pathogenesis of myopia. As such, myopia prevention and myopia mitigation treatment strategies are occasionally ineffective, can be difficult to adhere to, and have diminishing returns over time. Recently, non-visual opsins (OPN3, OPN4, and OPN5) have emerged as potentially impacting myopia regulation. This narrative review aims to summarize the current understanding of the non-visual opsins and how they might influence myopia. In addition, this review explores how utilizing this knowledge can help develop promising future treatment strategies to reduce the incidence and severity of myopia.

Background: To investigate whether postural changes in retinal vascular parameters, measured using smartphone-based imaging, differ between healthy individuals and patients with diabetes mellitus (DM), and whether these changes independently predict diabetic retinopathy (DR) progression over a 5-year period.

Methods: Retinal images were captured using a smartphone with a clip-on adapter lens in sitting and supine positions. Vascular parameters (caliber, fractal dimension, tortuosity, branching) were quantified using the Singapore I Vessel Assessment software. Cross-sectional analyses compared postural-induced vascular responses between 38 healthy controls and 49 DM participants. DM participants were followed for 5 years, with DR progression defined as ≥ 2-step increase in severity on the Early Treatment Diabetic Retinopathy Study scale. Cox proportional hazards models evaluated associations between baseline postural changes and DR progression.

Results: Healthy controls exhibited significant arteriolar and venular constriction upon moving from sitting to supine (P < 0.05). In contrast, participants with DM showed diminished or paradoxical responses that did not reach statistical significance. Significant linear trends were observed for arteriolar caliber, fractal dimension, and simple tortuosity across healthy controls, DM with and without DR (all P-trend < 0.05). Greater arteriolar tortuosity was associated with a 2.41-fold higher risk of DR progression (HR = 2.41, 95% CI: 1.37-4.23; P = 0.002), while wider venular branching angles correlated with a 45% lower risk (HR = 0.55, 95% CI: 0.35-0.87; P = 0.011). Adding these parameters improved predictive discrimination beyond established factors (arteriolar tortuosity: C-statistic 0.630-0.740; venular branching angle: 0.630-0.683; P < 0.05).

Conclusions: Smartphone-based imaging of retinal vascular responses to postural changes provides additional prognostic value for DR progression, potentially enhancing early risk stratification and proactive management.