Eye and Vision最新文献

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.

Purpose: This study investigated how aspheric lens design changes the corneal power distribution and how such changes are associated with the axial elongation in myopic children who underwent orthokeratology.

Methods: This retrospective study of 116 eyes from children aged 8-13 years were enrolled and fitted with three types of lenses: fully spherical lenses (Alpha, n = 45), those with an aspheric alignment curve (AC) and a spherical base curve (BC) (Dreamlite, n = 37), and lenses with a partly aspheric BC and an aspheric AC (Myok, n = 34). Axial lengths were measured at baseline, 6 and 12 months. Corneal topography maps obtained at baseline and after 1 month of lens wear were analyzed with Fourier decomposition: the F0 (spherical), F1 (asymmetry), F2 (regular astigmatism), and F3 (higher-order irregularity) components were extracted and quantified across ten concentric rings with 0.5 mm width.

Results: The 1-year axial elongation was 0.26 ± 0.21 mm, 0.16 ± 0.19 mm, and 0.10 ± 0.19 mm for the Alpha, Dreamlite, and Myok groups, respectively (P < 0.001). In the 1-month maps, F0 and F1 peaked at the mid-periphery, and declined peripherally. Dreamlite exhibited F0 values greater than those of Alpha (mean difference: 0.02-0.46 D) within the central 2 mm (P < 0.01) and lower than Myok's values (mean difference: 0.66-1.05 D) in the peripheral 3 to 4.5 mm (P < 0.01). Dreamlite also displayed greater F1 compared to Alpha (mean difference: 0.68-0.78 D) within the 1 to 2 mm rings (P < 0.01) but showed no significant difference from Myok. F2 and F3 remained flat and small. Three components, F0, F1, and F3, were negatively associated with axial elongation in these children (P < 0.001).

Conclusion: Lenses featuring an aspheric AC resulted in reduced axial elongation and increased spherical power and asymmetry in the central cornea, while lenses with a partly aspherical BC improved spherical power in the mid-periphery. A smaller axial elongation was associated with greater post treatment central cornea asymmetry.

Purpose: Keratoconus is a progressive corneal ectatic disorder characterized by thinning and irregularity of the cornea, significantly impairing visual acuity. Recent studies have explored how non-ectatic conditions, such as dry eye and tear film instability and alteration of the ocular surface microenvironment, contribute to the development and progression of keratoconus. This comprehensive review aims to investigate the complex relationship between keratoconus and ocular surface diseases by examining the microenvironmental changes that occur on the ocular surface throughout the course of keratoconus, as well as the related clinical implications.

Methods: In this PROSPERO-registered study (ID: CRD42025643808), PubMed, Scopus, Cochrane, Embase, Web of Science, and Google Scholar were thoroughly searched to retrieve all pertinent papers published up to January 2025. The retrieved publications were then reviewed, and the eligible ones were included.

Results: Keratoconus, with a similar inflammatory profile to that of ocular surface disease, has elevated Interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-9, contributing to extracellular matrix degradation and stromal thinning. Tear film instability, altered lipid secretion, and oxidative stress exacerbate disease progression. These findings suggest that keratoconus is not only a biomechanical disorder but also an inflammation-driven one.

Conclusion: This study comprehensively reviews the intricate relationship between the ocular surface microenvironment and keratoconus. Managing this microenvironment in keratoconus patients, as well as inflammation, oxidative stress, and tear film dysfunction, can potentially improve patient outcomes.

Background: Diabetic retinopathy (DR) is often diagnosed many years after diabetes onset, highlighting the need for early diagnosis. The current study aimed to assess whether texture analysis of computed optical coherence tomography (OCT) retinal images can identify (very) early retinal changes. We previously reported retinal texture changes in a type 1 diabetes animal model. This study extends this approach to a type 2 diabetes model exhibiting subtler, more gradually developing retinal alterations to further explore its potential for detecting texture changes when DR-related retinal alterations are minor, strengthening its promising value.

Methods: OCT scans and electroretinograms were acquired at baseline and 4, 8, and 12 weeks after initiating the diabetes induction protocol. Automated OCT segmentation, retinal thickness computation, and texture analysis were performed. Blood-retinal barrier permeability, glial reactivity, neuroinflammation, and nitrosative stress were assessed.

Results: Retinal texture was affected in the inner plexiform layer and inner/outer photoreceptor segments. At weeks 8 and 12, autocorrelation, cluster prominence, correlation, homogeneity, information measure of correlation II, inverse difference moment normalised, inverse difference normalised, and sum average texture metrics significantly increased/decreased. Importantly, seven of these metrics were also altered in our previous study with type 1 diabetic animals. Type 2 diabetic retinas presented subtle thinning and impaired function, along with a slight reduction in tight junction proteins immunoreactivity, without affecting the blood-retinal barrier.

Conclusions: The findings from this study indicate that texture analysis can identify subtle retinal changes during early, clinically silent stages of disease, when biological alterations remain minimal. This highlights its potential utility for the early diagnosis of diabetic retinopathy, though further clinical validation is needed.

Purpose: To describe the prevalence and clinical characteristics of focal choroidal excavation (FCE) in a large cohort of Chinese patients with choroidal osteoma (CO).

Methods: One hundred and thirty-two eyes of 110 Chinese patients diagnosed with CO were enrolled. The prevalence and clinical characteristics of FCE were studied. Univariate and multivariate linear regression analyses were used to identify the factors associated with the occurrence of FCE. Furthermore, FCEs were divided into two types based on their location: Type 1 (at the edge of the tumor) and Type 2 (inside the tumor), and their clinical features were analyzed.

Results: The prevalence of FCE was 46.2% in 132 eyes with CO. Eyes with FCEs demonstrated a longer disease duration (P < 0.01), worse BCVA (P = 0.01), longer greatest tumor linear dimension (P < 0.01), larger total tumor area (P < 0.01) and decalcification area (P < 0.01), and a higher incidence of outer retinal tubulation (ORT) (P = 0.01). Only disease duration (P = 0.025) was significantly correlated with the occurrence of FCE. Patients with Type 2 FCEs had a larger greatest linear dimension of FCEs and a higher likelihood of ORT, choroidal neovascularization, disruption of the external limiting membrane, and inner retina compared with those with Type 1 FCEs (all P < 0.05).

Conclusions: The duration is associated with the development of FCE in CO. The different types of FCE may indicate varying stages of CO, suggesting the occurrence and enlargement of FCE in CO are associated with the lateral expansive growth of the tumor. Comprehensive optical coherence tomography evaluation of tumor margins and extramacular regions during initial assessment and regular follow-up is recommended to enable early FCE detection (particularly Type 2), allowing timely identification of CNV and other complications for prompt vision-preserving intervention.

Background: The visual pathway, consisting of the eye, optic nerve, and brain, serves as a valuable model for studying neural regeneration. The exceptional regenerative capacity of the zebrafish visual system enables detailed investigation of neural repair mechanisms in vivo. Although the transparency of zebrafish larvae permits real-time imaging of axonal regeneration following transection, previous methodological limitations such as pigment interference and suboptimal imaging protocols have hindered high-resolution analyses of structural recovery and cellular interaction throughout the entire visual pathway after optic nerve injury. This study aimed to overcome these barriers and enable comprehensive assessment of visual pathway regeneration.

Methods: In this study, we dissect the regenerative processes underlying structural recovery and cellular interplay across the entire visual pathway in larval zebrafish with an optic nerve transection model, using two-photon imaging and optokinetic response assays. Data were analyzed via multi-factorial ANOVA, unpaired t-tests, or Welch's t-test.

Results: We developed a longitudinal imaging platform by integrating two-photon microscopy (930 nm excitation), pigment suppression with phenylthiourea (PTU), and multi-axis positioning to observe visual pathway regeneration in vivo in zebrafish larvae at cellular resolution. This system enabled high-resolution imaging of the entire visual pathway, capturing the dynamics of green fluorescent protein (GFP)-labeled retinal ganglion cell (RGC) axons, optic nerve projections, and tectal reinnervation following optic nerve transection. Notably, enucleation of the contralateral eye resulted in aberrant optic nerve regrowth and impaired visual recovery after transection, indicating that guidance cues from the contralateral eye were essential for successful functional optic nerve regeneration. Additionally, the optimized two-photon imaging protocol allowed direct in vivo visualization of cellular interactions, revealing the rapid recruitment of DsRed-labeled neutrophils to the injured retina, optic nerve, and tectum during the repair process in double-transgenic Tg(lyz:DsRed); Tg(isl2b.2:Gal4-VP16; myl7:EGFP); Tg(4XnrUAS:GFP) larvae.

Conclusions: Our optimized imaging platform visualizes the entire visual pathway and cell interactions during regeneration, revealing contralateral eye is essential for functional recovery following optic nerve transection. Combined with multi-omics and calcium imaging, this approach potentially provides a powerful platform to decipher the cellular and molecular mechanisms of zebrafish eye-brain pathway reconstruction and offers insights into therapeutic targets for human optic neuropathies.