Eye and Vision最新文献

Objective: To investigate the relationship between leukocyte telomere length (LTL), a biomarker of cellular aging, and both the incidence and severity of age-related cataract (ARC) across cohorts from the UK and China.

Methods: The multicenter, multiethnic cohort study involved 122,932 healthy individuals with a mean age of 56.27 years from the UK Biobank, a community-based cohort, and 53 cataract patients with a mean age of 71.74 years from a hospital-based cohort in China. LTL was measured using validated polymerase chain reaction techniques. ARC was assessed using a combination of self-reported data, medical records, and operation codes. In the Chinese cohort, lens morphological features and opacities were evaluated using Scheimpflug imaging. Associations between LTL and ARC were analyzed using Cox proportional hazards models, logistic regression, and restricted cubic splines. A phenome-wide association study (PheWAS) was conducted to validate the association between LTL and cataract in the UK Biobank cohort.

Results: Over a median follow-up time of 11.18 years, 4,089 incident ARC cases were documented in the UK cohort. Longer LTL was associated with a lower incidence of ARC [hazard ratio (HR) = 0.93, 95% confidence interval (CI): 0.91 to 0.96; P < 0.001]. Restricted cubic splines indicated an L-shaped association between LTL and ARC (P for nonlinearity = 0.03), where ARC risk decreased with longer LTL until a threshold before plateauing. The PheWAS provided support for the association between LTL and cataract (P = 2.36 × 10⁻⁶) across 1,011 phecodes in the UK Biobank. In the Chinese cohort, LTL was negatively correlated with average lens density (β = - 0.32, 95% CI: - 0.61 to - 0.04; P = 0.03).

Conclusions: Longer LTL is associated with a reduced risk and severity of ARC, suggesting shared biological pathways between telomere attrition and lens aging. This supports the lens as a unique window for studying systemic aging and LTL as an index of modifiable health behaviors influencing cataract development.

Background: While parental astigmatism is a known risk factor for childhood astigmatism, the molecular genetic basis remains elusive. Previous genetic studies, largely confined to adult corneal and refractive astigmatism (CA and RA), did not address internal astigmatism (IA) and astigmatism vector components. We aimed to determine whether genes previously identified to have associations with corneal curvature (CR), CA, and RA in adults similarly occur for CR, CA, RA, IA, and astigmatism vector components (J0 and J45) in children.

Methods: Fourteen polymorphisms in nine loci were genotyped in 2167 Chinese children. Linear and logistic regression analyses were conducted to evaluate the association of the polymorphisms with CR, CA, RA, IA, and astigmatism vector components, which were determined by keratometry, cycloplegic refraction, or Fourier transformation.

Results: FMNL2 rs1579050 was associated with CA (additive: β = 0.158, P = 0.0028; dominant: β = 0.163, P = 0.0034), J0_(CA) (additive: β = 0.081, P = 0.0031), and an increased risk of dichotomous RA (additive: OR = 1.609, P = 0.0028; dominant: OR = 1.671, P = 0.0020), whereas NHSL1 rs4896367 was associated with J0_(IA) (recessive: β = 0.058, P = 0.0002) and a lower risk of dichotomous IA (recessive: OR = 0.577, P = 0.0007). PDGFRA rs2228230 was also associated with J0_(IA) (dominant: β = -0.034, P = 0.0012). The predisposition to CA and RA increased with the risk alleles of FMNL2 rs1579050.

Conclusions: These findings reveal genetic contributions to childhood astigmatism and demonstrate that vector-based decomposition may facilitate more precise mapping of its genetic determinants.

Background: Due to the lack of quality-controlled quantitative data on meibomian gland (MG) morphology in children and adolescents, this study aims to establish a Children and Adolescents Meibomian Gland (CAMG) dataset.

Methods: A total of 1114 quality-controlled upper eyelid infrared images were collected from 730 children and adolescent subjects using the Oculus Keratograph 5 M. Images underwent preprocessing and multi-stage expert quality control screening before segmentation. Morphological parameters including gland area, gland dropout ratio, gland length and width, number of glands, and total glands ratio were extracted using an AI model. The dataset, comprising images, annotations, and demographic information, is openly accessible on Figshare, with AI model codes available on GitHub to support research reproducibility and algorithm optimization.

Results: The dataset includes 1114 high-resolution quality-controlled upper eyelid images from 730 subjects (mean age 11.80 ± 2.39 years; 46.77% male), accompanied by AI-assisted segmentation annotations and corresponding morphological measurements. The U-Net segmentation model achieved an accuracy of 97.49%, a Dice coefficient of 89.72%, and an intersection over union (IoU) of 81.67%. Quantitative analysis revealed that MG parameters remained relatively stable in adolescents compared to children. Females exhibited significantly wider and larger MGs than males. Similar sex-related differences were also observed in the central five MGs. Males exhibited a higher MG count compared to females.

Conclusions: CAMG is a publicly available MG dataset for children and adolescents to support AI-based individualized clinical assessments. The dataset's transparent quality control processes establish a foundation for epidemiological research, promoting cross-institutional collaboration and AI-driven advancements in ophthalmology.

Opsins are universal photoreceptive proteins in animals. Rhodopsin is the best-studied opsin and functions as a visual sensor in rod cells of human and mouse retinas. Rhodopsin produces an active state upon photoreception, which triggers the signal transduction cascade to evoke a hyperpolarizing response of the cells. This active state is a metastable intermediate and cannot convert back to the dark state by either photoreaction or thermal reaction. Thus, vertebrate rhodopsin is categorized as a mono-stable opsin. Recent accumulation of genomic information in animals has expanded the known repertoires of opsin genes, which are responsible for visual and non-visual photoreceptive functions. The analysis of these opsins revealed that many opsins, including non-visual opsins such as Opn4 and Opn5, form a stable active state upon photoreception and this active state can photo-convert back to the dark state. These opsins have the property of photoreversibility between the dark and active states and thus are categorized as bistable opsins. In addition, we previously identified a different type of non-visual opsin, Opn5L1, whose activity is controlled by a photocyclic reaction. This photocyclic reaction is quite similar to that of channelrhodopsin and is achieved by a special mechanism involving a cysteine residue at position 188 that has not been observed in any other opsins so far. This review would like to focus on the unique photocyclic animal opsin in the context of the diversity of visual and non-visual opsins and also discuss the possibility of designing "artificial photocyclic opsins" from natural opsins for potential application in optogenetic gene therapy.

Purpose: To investigate the 2-year myopia control efficacy of Lenslet-ARray-Integrated (LARI) lenses with positive (PLARI) and negative (NLARI) power lenslets and the effect of switching lens designs.

Methods: A total of 218 children, who were randomly assigned to wear PLARI, NLARI, or single-vision (SV) lenses in Phase 1 continued in this randomized, double-masked extended trial for an additional year (Phase 2). Participants were randomly assigned to one of six groups: SV to PLARI, SV to NLARI, PLARI to PLARI (P-PLARI), PLARI to NLARI (P-NLARI), NLARI to PLARI (N-PLARI), and NLARI to NLARI (N-NLARI). In year 2, the change in spherical equivalent refraction (SER) and axial elongation (AE) from the SV group were extrapolated based on published data [the extrapolated single vision (ESV) group]. Linear models were used to determine differences in SER changes and AE among groups in 2 years and in Phase 2 only.

Results: After 2 years, the SER changes (- 0.87 ± 0.68 D, - 0.64 ± 0.86 D, - 0.68 ± 0.54 D, and - 0.75 ± 0.62 D, respectively) and AE (0.44 ± 0.33 mm, 0.33 ± 0.32 mm, 0.36 ± 0.23 mm, and 0.39 ± 0.25 mm, respectively) of P-PLARI, P-NLARI, N-PLARI, and N-NLARI were significantly smaller than those in the ESV group (SER: - 1.24 ± 0.77 D, all P < 0.05; AE: 0.63 ± 0.33 mm, all P < 0.001). In Phase 2, there was no significant difference in SER changes among the four LARI groups and ESV group (P = 0.58). In Phase 2, AE of the P-NLARI and N-PLARI groups was significantly smaller than the ESV group (P < 0.001 and P = 0.001), and AE of the P-PLARI and N-NLARI groups were slightly smaller than that of ESV group (P = 0.054 and P = 0.10), but there were no significant differences in AE among the four LARI groups (all P > 0.05).

Conclusions: Wearing LARI lenses for 2 years effectively slowed myopia progression and AE. Switching to another LARI design after 1 year improved myopia control efficacy, in terms of AE, during the second year, but not SER progression.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2200057210. Registered 03 March 2022, https://www.chictr.org.cn/bin/project/edit?pid=152900 .

Purpose: This study uses optical coherence tomography angiography (OCTA) topographical cluster analysis to localise where vascular changes occur during the isometric hand-grip test (IHGT) in eyes with neovascular age-related macular degeneration (AMD).

Methods: This prospective study included single eyes from 44 participants with neovascular AMD. Systemic blood pressure (BP) and macular 6 × 6 mm OCTA scans were obtained before the IHGT, during the IHGT, and after the IHGT. The main outcome was the change in processed OCTA signal (%), measured within high-density (126 × 126) grids and analysed by topographical clusters across the superficial retina, deep retina, and choriocapillaris. Results were compared against test-retest thresholds to differentiate true IHGT-induced changes from measurement variability.

Results: The IHGT increased systolic (13.83 [3.28, 24.39] mmHg) and diastolic BP (7.04 [3.57, 10.52] mmHg; P < 0.01). Adjusted for test-retest thresholds, the IHGT increased processed OCTA signal (12.84 [8.49, 26.77] %, P < 0.0001) at nasal clusters in the superficial retina. These changes were moderately correlated with systolic BP increases (Spearman r = 0.43, P < 0.05), but not with diastolic BP. No changes were observed in the deep retina or choriocapillaris. Systemic BP and processed OCTA signal returned to baseline within 30 s after IHGT release.

Conclusion: Hand-squeezing temporarily increases processed OCTA signal in the nasal superficial retina. This response may serve as a valuable marker of vascular function. Consequently, caution is warranted when interpreting OCTA following BP changes, such as those induced by physical activity or medication changes.

Purpose: Diabetic keratopathy, a common ocular complication of diabetes, is characterized predominantly by corneal epithelial damage and peripheral nerve injury. This study examined the role of adiponectin (ADPN) in regulating the repair of the diabetic corneal epithelium and accompanying nerve injuries.

Methods: RNA sequencing was performed on total RNA isolated from corneal epithelium of streptozotocin (STZ)-induced type 1 diabetic mice and type 2 diabetic BKS.Cg-Dock7m +/+ Leprdb/Nju (db/db) mice to identify differentially regulated pathways and interactions. ADPN receptor expression was assessed. Recombinant ADPN, ADPN receptor 1/2 siRNA, and a phosphorylated AKT (p-AKT) inhibitor were then utilized in diabetic mice and in human corneal epithelial cells (HCECs) cultured under high-glucose conditions to evaluate corneal wound healing responses.

Results: ADPN receptor expression and p-AKT levels were downregulated in corneas of diabetic mice and in HCECs exposed to high glucose. Treatment with recombinant ADPN accelerated repair of corneal epithelial and nerve damage in both type 1 and type 2 diabetic mice, enhanced HCEC proliferation and migration under high-glucose conditions and activated AKT signaling. ADPN treatment also reduced neutrophil infiltration and inflammatory factor expression during wound repair. These beneficial effects were abolished by ADPN receptor 1 knockdown or AKT inhibition.

Conclusions: Our results demonstrate that ADPN promotes the corneal epithelium and nerve regeneration in diabetic mice via activation of the AdipoR1/AKT signaling axis and suppression of inflammatory responses. These findings identify ADPN as a promising therapeutic candidate for promoting corneal epithelial wound healing in diabetic conditions.

Background: Opn3 is a non-visual blue light-sensitive opsin that has recently been reported to have an expansive repertoire of biological functions. To investigate the function of Opn3-expressing cells, we aimed to generate a system in which Opn3-expressing cells can be targeted by site-specific gene recombination.

Methods: Opn3-phiC31o knock-in (KI) mice were generated using the CRISPR-Cas9 method. The phiC31o-poly(A) cassette was inserted into the translation start site in exon 1. Opn3 mRNA and phiC31o mRNA were visualized by in situ hybridization (ISH). 5' rapid amplification of cDNA end (5' RACE) analysis was performed using RNAs from wild-type mouse cerebral cortex and cerebellum to identify the transcription start site of Chml, predicted to be shared with the transcription start site of Opn3. Cold-induced decrease in body temperature was monitored with a telemetric probe to confirm the phenotype of Opn3 knockout. To examine the phiC31o integrase-mediated recombination, Opn3-phiC31o mice were crossed with the ROSA26 ^{MultiFPsΔPuro} reporter and cyan fluorescent protein, mCerulean, expression was labeled by immunohistochemistry.

Results: The expression pattern of phiC31o mRNA was consistent with that of Opn3 mRNA in Opn3-phiC31o heterozygous mouse brains, indicating that phiC31o mRNA is expressed under the control of the Opn3 promoter. Based on the public database, the transcription start site of exon 1 of Opn3 is identical to that of Chml, suggesting that phiC31o KI disrupts Chml expression. However, Opn3-phiC31o homozygous mice sustained Chml expression, and the transcription start site of Chml was confirmed to be located 112 bp upstream of the predicted second exon. Opn3-phiC31o homozygous mice showed a larger decrease in body temperature under cold exposure compared to wild-type controls. In addition, these mice also exhibited a refractive myopia phenotype. These findings confirmed the functional knockout of Opn3. Double transgenic mice of Opn3-phiC31o and ROSA26 ^{MultiFPsΔPuro} reporter showed mCerulean expression mainly in the olfactory bulb, cerebral cortex, thalamus, and cerebellum. The recombination efficiency was 30% to 44% in the cerebellum.

Conclusions: Opn3-phiC31o KI mice were successfully generated. We can generate Opn3 null mice that does not disrupt Chml by preparing homozygotes of Opn3-phiC31o. We have deposited the sequences including the newly found transcription start site of Chml.

Fungal endophthalmitis represents one of the most challenging intraocular infections to diagnose and manage in ophthalmology. Despite advances in diagnostic techniques and treatment options, numerous controversies persist regarding optimal approaches to this sight-threatening condition. Due to the low incidence and significant variation in the severity and time of presentations, no large-scale randomized controlled trials have been done. Therefore, identifying controversies and deliberating the best approach to diagnosing and treating fungal endophthalmitis by international experts would help establish consensus statements that can guide clinical practice. The Asia-Pacific Academy of Professors in Ophthalmology (AAPPO), Asia-Pacific Vitreo-Retina Society (APVRS), and Asia-Pacific Society of Ocular Inflammation and Infection (APSOII) saw this critical gap and formed an international panel of experts comprising 24 experts to establish 20 consensus statements. While there is consensus on the need for early diagnosis and prompt administration of antifungal therapy, there are conflicting views on the optimal diagnostic approach to be taken, the role and timing of performing vitrectomy, and the use of systemic antifungal agents. A particularly contested topic is the role of corticosteroids. In establishing the 20 consensus statements, these thus serve as guidelines for diagnosing and managing fungal endophthalmitis.

Neuropathic corneal pain (NCP) refers to spontaneous corneal pain in the absence of stimuli arising from corneal nerve dysfunction with no clinically observable ocular surface abnormalities. It is debilitating with difficult-to-manage symptoms-burning pain, photophobia, and irritation being profound. However, evidence-based clinical recommendations for the management of NCP remain scarce. Given the established role of vitamins in various neuropathies and associations between vitamin deficiencies and NCP in the literature, vitamin supplementation represents a potential therapeutic avenue that has yet to be adequately investigated in the context of NCP. This narrative review provides an overview of the therapeutic potential of vitamins B3, B12 and D as treatment in NCP, drawing evidence from both preclinical animal and clinical studies. It discusses the potential mechanisms of action rendered by various vitamins in alleviating NCP and includes the suppression of inflammation, neuroinflammation, mitochondrial dysfunction, oxidative stress, as well as the modulation of neurodegeneration and nociception dysregulation. Furthermore, we offer insight on future directions needed for vitamin supplementation to serve as mainstream treatment for NCP. Future research should also aim to establish optimal treatment protocols, including dosing regimens, treatment duration and administration methods for each vitamin.