Eye and Vision最新文献

Photoreception is common in animals without a visual system. In animals with visual systems, it is sometimes presumed that the same photoreceptors and pathways will accommodate both visual and non-visual light detection. However, mounting evidence reveals that most animals exhibit broad extra-visual photoreceptive functions that are wholly independent of the visual system. One of these functions is the synchronization of the circadian clock to light-dark signals, or photoentrainment. In mammals, behavioral photoentrainment is achieved exclusively through visual and non-visual opsin proteins within the retina, and molecular photoentrainment of individual cells occurs using non-visual opsins in some peripheral tissues. This is in contrast to insects and fish where nearly all peripheral organs are directly photoentrainable. This review will summarize the family of opsins in mammals and focus on the role of non-visual opsins in circadian photoreception. Particular emphasis will be given to photoentrainment in other vertebrates in order to compare and contrast the use of the wide range of non-visual opsins in circadian photoentrainment throughout the animal kingdom.

Purpose: To assess the functional and ocular surface anti-inflammatory outcomes of epithelium-off accelerated corneal cross-linking (ACXL) in adolescents with progressive keratoconus associated with allergic ocular surface disease and dry eye disease (DED) characterized by elevated tear matrix metalloproteinase-9 (MMP-9) concentrations.

Methods: Prospective interventional case series of 30 eyes from 15 patients (mean age 16.41 ± 2.36 years; Krumeich stage II) undergoing epi-off ACXL. Outcomes at baseline and 1, 3, 6, and 12 months included corrected distance visual acuity (CDVA), maximum keratometry (Kmax), minimum corneal thickness (MCT), computerized non-invasive tear break-up time (cBUT), Ocular Surface Disease Index (OSDI), and tear MMP-9 (point-of-care test). In vivo qualitative confocal microscopy (IVCM) investigation provided supportive imaging. Paired t-tests were used and results reported with 95% confidence intervals (CI).

Results: CDVA improved to 0.09 logMAR at 12 months (≈ 0.81 decimal; 95% CI: 0.10-0.08 logMAR; P < 0.001). Kmax decreased from 55.00 to 53.75 D (95% CI: 53.55-53.95 D; Δ =  - 1.25 D; P < 0.001), indicating ectasia stabilization. cBUT increased from 10.11 to 14.41 s (95% CI: 14.11-14.71; P < 0.01). OSDI decreased to 12.15 (95% CI: 11.65-12.65). Tear MMP-9 levels diminished from 64.79 to 16.15 ng/mL (P < 0.0001) and the proportion < 38.6 ng/mL reached 86.7% of the study cohort at 12 months. IVCM documented disappearance of inflammatory infiltrates. No postoperative persistent adverse events occurred.

Conclusions: Epi-off ACXL stabilized ectasia, improving visual and ocular surface outcomes, markedly lowering tear MMP-9 levels. Although exploratory, these findings are consistent with a potential ocular surface anti-inflammatory and neuromodulatory role of ACXL, meriting validation in studies involving inflammatory DED beyond keratoconus.

Opsin 5 (OPN5), also known as neuropsin, is a violet/ultraviolet (UV) light-sensitive G protein-coupled receptor (GPCR) conserved across vertebrates. Most mammals possess a single OPN5 gene (OPN5m), whereas non-mammalian species also express OPN5L1 and OPN5L2 with distinct molecular properties. Mammalian OPN5 (OPN5m) functions as a non-visual photopigment, expressed in diverse extra-retinal tissues including the skin, testis, and brain. Recent studies reveal species-specific signaling: human OPN5m preferentially activates Gq-mediated Ca²⁺ signaling, mouse OPN5m couples with Gi to reduce cyclic adenosine monophosphate (cAMP), avian OPN5m engages either Gi or Gq depending on species and tissue, and amphibian/fish OPN5m homologs primarily signal through Gq pathways. These diverse signaling modes underlie a wide range of physiological functions, such as circadian photoentrainment, thermoregulation, vascular development, myopia suppression, corneal wound healing, seasonal reproduction in birds, and light-dependent hormone release in fish pituitary. As modern artificial lighting and indoor lifestyles limit violet light exposure, insufficient OPN5m activation may contribute to emerging health issues, particularly the global rise in myopia. This review provides an updated overview of the molecular diversity, expression patterns, signaling mechanisms, and physiological roles of OPN5m across species, and discusses its potential clinical relevance in the context of changing light environments.

Background: Extranasal neurostimulation is a promising therapy for aqueous-deficient dry eye (ADDE), but neural adaptation and optimal treatment duration remain poorly characterized. This study investigated duration-dependent neural sensitivity dynamics to formulate an optimized cyclic treatment regimen.

Methods: In this prospective, randomized, open-label trial, 50 ADDE patients (Schirmer test: 2-5 mm) were assigned to 2-week or 4-week bilateral extranasal neurostimulation (twice daily). Participants were followed for 6 weeks post-treatment. The primary outcomes were neural sensitivity changes (Δ Schirmer) and short-term recovery (6 weeks after stimulation cessation). Secondary endpoints included subjective symptoms and objective signs.

Results: Distinct neural adaptation patterns were observed. The 4-week group exhibited reversible neural adaptation, with an attenuated stimulation response at treatment completion (Δ Schirmer: 1.18 ± 4.17 mm, P = 0.051, Cohen's d = 0.28) that fully recovered after the 6-week intermission (post-stimulation Schirmer: 10.90 ± 7.29 mm vs. initial 12.42 ± 6.67 mm, P = 0.90, η²p = 0.092). This reversible adaptation was associated with sustained improvements in tear film stability [fluorescent tear film break-up time (FBUT): 6.27 ± 2.49 s vs. baseline 3.18 ± 1.36 s, P < 0.001, η²p = 0.235] and tear volume [tear meniscus height (TMH): 0.25 ± 0.05 mm vs. 0.19 ± 0.02 mm, P < 0.001, η²p = 0.26]. Critically, this reversible adaptation pattern was exclusive to the 4-week protocol. The 2-week protocol showed preserved stimulation responses during treatment (Δ Schirmer: 3.22 ± 6.54 mm, P < 0.001, Cohen's d = 0.49) but developed persistent neural hyposensitivity (8.76 ± 5.95 mm vs. initial 14.88 ± 8.69 mm, P < 0.001, η²p = 0.24). Its clinical benefits, though significant for FBUT (5.20 ± 2.81 s vs. baseline 2.86 ± 1.01 s, P < 0.001, η²p = 0.109), were less pronounced than in the 4-week group, and TMH showed no sustained increase (0.21 ± 0.04 mm vs. baseline 0.19 ± 0.03 mm, P = 0.11, η²p = 0.112). Both protocols demonstrated excellent safety and high patient satisfaction.

Conclusions: Based on neural adaptation and recovery characteristics, a cyclic regimen of 4-week extranasal neurostimulation followed by a 6-week intermission is proposed as a potentially effective and sustainable clinical strategy for managing ADDE. This approach synchronizes treatment with the nervous system's intrinsic recovery cycles, addressing limitations of continuous stimulation paradigms.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2500100816). Registered on 15 April 2025 (retrospectively registered), https://www.chictr.org.cn/bin/project/edit?pid=265888 .

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 .