PurposeKeratoconus 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.MethodsIn 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.ResultsKeratoconus, 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.ConclusionThis 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00454-0.

BackgroundDiabetic 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.MethodsOCT 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.ResultsRetinal 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.ConclusionsThe 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00451-3.

PurposeTo describe the prevalence and clinical characteristics of focal choroidal excavation (FCE) in a large cohort of Chinese patients with choroidal osteoma (CO).MethodsOne 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.ResultsThe 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).ConclusionsThe 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00452-2.

BackgroundThe 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.MethodsIn 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.ResultsWe 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.ConclusionsOur 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00447-z.

BackgroundDiabetic keratopathy (DK) is a common ocular complication of diabetes, with its progression closely linked to autophagy regulation. This study aims to explore the role of long non-coding RNAs (lncRNAs) in modulating autophagy during diabetic pathogenesis, focusing on lncRNA general transcription factor IIIC subunit 1 (GTF3C1) and its potential as a therapeutic target for diabetic corneal neuropathy (DCN).MethodsHigh-throughput sequencing identified dysregulated lncRNAs in the trigeminal ganglia of diabetic mice. Functional validation included mechanistic studies on lncRNA GTF3C1, miR-542-3p, and autophagy-related targets. Autophagy activity, corneal nerve density, and epithelial healing were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and histology in diabetic models.ResultslncRNA GTF3C1 was significantly downregulated in diabetic trigeminal ganglion (TG). It functioned as a molecular sponge for miR-542-3p, alleviating its repression on GABA type A receptor-associated protein (GABARAP) and phosphatase and tensin homolog (PTEN), thereby enhancing autophagy activity. This process promoted corneal nerve fiber regeneration and epithelial wound healing in diabetic mice.ConclusionsOur findings highlight lncRNA GTF3C1 as a critical regulator of autophagy in diabetic corneal nerves, offering a potential diagnostic and therapeutic target for DCN. This study provides molecular insights into the pathogenesis of DCN and lays the groundwork for future clinical strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00448-y.

BackgroundThis retrospective study aimed to identify risk factors for subretinal fibrosis (SF) and evaluate the response to anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with myopic choroidal neovascularization (mCNV), with a specific focus on the role of dilated choroidal vessels (DCVs) in disease progression.MethodsIn this retrospective study, patients with high myopia (spherical equivalent < −6.0 D, pathological myopia, Asian ethnicity) and active mCNV lesions, diagnosed between 2021 to 2023, were evaluated. The location of DCVs and mCNV was assessed, and macular thickness, submacular choroid thickness, best-corrected visual acuity, CNV area, and flow density were measured at baseline and during follow-up. The presence of posterior staphyloma was evaluated at baseline. SF around the mCNV was evaluated lesions during follow-up. The time to SF detection was recorded using survival analysis. Risk factors for SF were analyzed using Kaplan–Meier and multivariable Cox regression analyses.ResultsA total of 46 eyes from 46 patients were included, with a mean age of 54.17 ± 14.37 years, and a baseline spherical equivalent of 12.36 ± 3.21 D. The logarithm of the minimum angle of resolution for the mean visual acuity was 0.70 (0.40–1.30), and the mean macular thickness was 313.11 ± 63.57 μm at baseline. DCV was detected in 29 of the 46 eyes (63.0%), and the median time to detect SF was 43.41 [95% confidence interval (CI): 37.27–49.55] months. Multivariable Cox regression analysis identified submacular DCV [hazard ratio (HR): 14.93, 95% CI: 5.72–38.91, P < 0.001) and absence of posterior staphyloma (HR: 43.48, 95% CI: 12.15–156.32, P = 0.002) as independent predictors of SF. The presence of DCV under the fovea compared to the peripheral zone achieved a poorer therapeutic response and was prone to progress to SF after anti-VEGF therapy (P = 0.041).ConclusionsSubmacular DCV is associated with poor therapeutic response to anti-VEGF therapy and an increased risk of SF in patients with mCNV.

PurposeTo assess the ability of corneal epithelial aberrations to discriminate forme fruste keratoconus (FFKC) and keratoconus (KC) from normal eyes.MethodsThis prospective, case-control study enrolled 91 right eyes from 91 normal participants, 87 eyes with FFKC and 148 eyes with KC. Epithelial aberrations for the 6-mm pupil were measured using an anterior segment optical coherence tomography (MS-39, CSO). The epithelial root mean square of higher and lower-order aberrations (total RMS), root mean square of higher-order aberrations (HOAs RMS, from the 3rd to the 7th Zernike polynomials), coma, trefoil, spherical aberration, and secondary astigmatism were recorded. Stepwise logistic regression was utilized to develop the epithelial aberrations index (EAI) for obtaining the optimal discriminant function to diagnose FFKC (EAI-FFKC) and KC (EAI-KC). Area under the receiver operating characteristic curve (AUC) analysis was used to determine the diagnostic accuracy of the indices.ResultsFFKC and KC eyes had significantly higher epithelial aberrations than normal eyes. Comparing FFKC with the normal group, epithelial HOAs RMS and coma attained AUC values of 0.714 and 0.788, respectively. The EAI-FFKC showed the highest discrimination ability to differentiate FFKC from normal eyes indicated by an AUC value of 0.822 with 77.0% sensitivity and 75.8% specificity. Comparing KC with the normal group, epithelial HOAs RMS attained AUC values of 0.976–0.998 with 95.2%–100% sensitivity and 92.3%–96.7% specificity, epithelial coma attained AUC values of 0.974–0.997 with 92.9%–100% sensitivity and 96.7%–98.9% specificity. The EAI-KC showed the highest discriminative ability to differentiate KC from normal eyes indicated by AUC of 0.996 with 98.6% sensitivity and 98.9% specificity.ConclusionEpithelial wavefront analysis can identify abnormal epithelial changes across all stages of KC, from very early to severe. Epithelial aberrations can be used as a diagnostic tool for KC and FFKC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40662-025-00449-x.

Macular hole surgery, primarily pars plana vitrectomy with internal limiting membrane peeling (ILM) and gas tamponade, has become the standard of care for full-thickness macular hole (FTMH). Despite the 85% to 95% anatomical closure rate, several aspects of the procedure are well accepted whereas some may remain controversial among vitreoretinal surgeons. An international panel of experts (IPE) comprising 27 experts from 10 countries/territories was established to evaluate a total of 38 consensus statements on ILM peeling extent, vital dye selection, face-down positioning requirements, tamponade options, timing of surgery and re-surgery, management of difficult and refractory cases, and adjuvant therapies. The objective is to synthesize evidence-based real-world practice recommendations from leading global experts to guide the management of FTMH. Of the 38 statements, the IPE reached consensus (75% voted as “Strong Agreement” or “Agreement”) on 29 (76.3%). The IPE emphasized the importance of individualized patient factors—such as hole size, chronicity, lens status, and preoperative visual acuity—in surgical planning and tempering patient’s postoperative expectations. There was strong agreement on the need of adequate peeling of the ILM, adjunctive measures including the inverted ILM flap, and face-down positioning for large and refractory FTMH. Controversial statements, such as the use of air tamponade or observation of small FTMH, not reaching consensus are identified. We hope the consensus statements agreed and disagreed by the IPE would help serve as good reference and guidelines in managing FTMH.

BackgroundTo analyze the fluid reservoir thickness over the whole cornea during scleral lens settling using wide-angle optical coherence tomography (OCT) images and customized computer software.MethodsA total of 75 participants were recruited – 29 (myopes) with regular corneas and 46 with irregular corneas (35 with keratoconus, and 11 post-keratoplasty). All participants were fitted with customized scleral lenses and anterior segment OCT (Tomey Casia 2) images were taken 0, 30, 60, 120, and 240 min after lens application at the dispensing visit. Customized software was used to automatically segment the anterior cornea and the posterior surface of the scleral lens and determine the fluid reservoir thickness at 17 corneal regions across a 12 mm diameter. ResultsFluid reservoir thickness decreased over time (P < 0.001) following an exponential decay, with no differences observed over time between the three groups (P = 0.97). The reduction in fluid reservoir thickness over four hours varied slightly between the central (149 ± 9 μm), mid-peripheral (139 ± 11 μm), and peripheral regions (131 ± 15 μm), P = 0.046. The fluid reservoir was thinnest in the superior mid-periphery for both the myopia and post-keratoplasty groups, and centrally for the keratoconus group. The fluid reservoir was thickest inferiorly for all groups, with the greatest level of asymmetry observed along the vertical meridian.ConclusionsFluid reservoir thickness decreased most rapidly during the first two hours of lens wear and followed an exponential decay for both regular and irregular corneas across all corneal locations. Fluid reservoir asymmetry was greatest along the vertical meridian with a thicker reservoir observed in the inferior corneal regions.

BackgroundAnti-angiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) is currently the first-line treatment for macular edema (ME), but the specific metabolic changes in the aqueous humor (AH) after intravitreal anti-VEGF injections remain poorly understood.MethodsA total of 120 AH samples from 60 ME patients before and after anti-VEGF treatment were collected from the ophthalmology clinic and ward of the Eye Hospital of Wenzhou Medical University. Non-targeted metabolomics analysis of the AH samples was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify metabolite differences before and after anti-VEGF treatment in patients with different ME etiologies.ResultsDistinct metabolomic profiles were observed between pre- and post-treatment samples. A total of 145 significantly altered metabolites were identified after anti-VEGF treatment, with 84 upregulated metabolites related to carbohydrate and amino acid metabolism, and 61 downregulated metabolites involved in amino acid metabolism. Both common and etiology-specific metabolic alterations were observed. In age-related macular degeneration (AMD)-ME, treatment-induced metabolic changes mainly involved amino acid metabolism, whereas in branch retinal vein occlusion (BRVO)-ME, lipid metabolism was primarily affected. Diabetic macular edema (DME) patients showed more complex metabolic alterations, involving amino acid, lipid and carbohydrate metabolism.ConclusionsIntravitreal anti-VEGF injections significantly alter AH metabolites in ME patients. These findings provide insight into underlying metabolic processes in ME pathogenesis and treatment efficacy.