To assess the functional stabilizing potential and structural safety of 27-gauge microincision vitrectomy surgery (MIVS) in a targeted subgroup of patients with acute nonarteritic anterior ischemic optic neuropathy (NAION) presenting with peripapillary wrinkles (PPWs). In this prospective, nonrandomized, patient-choice controlled pilot study, 39 patients presenting with acute unilateral NAION and PPWs (within 21 days of onset) were allocated into a surgical group (27-gauge MIVS) and a medical control group (tapered oral prednisone). All participants additionally received oral methylcobalamin. Main outcome measures included changes from baseline in best-corrected visual acuity (BCVA), mean deviation (MD), and visual field index (VFI); clinically meaningful response rates (≥ 15-letter BCVA gain/loss, ≥ 10
Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) share similar fundus manifestations yet exhibit profound discrepancies in pathogenesis, therapeutic responsiveness, and long-term visual outcomes. To date, no vitreous-derived molecular biomarker can specifically distinguish the two disorders, and comparative proteomic research targeting this unmet clinical demand remains limited. Idiopathic macular hole (IMH) patients were recruited as the control group in the present study. We conducted comprehensive vitreous proteomic profiling via liquid chromatography-tandem mass spectrometry (LC-MS/MS) to screen differentially expressed proteins (DEPs) across all three groups. Candidate protein biomarkers were further validated in an independent patient cohort using enzyme-linked immunosorbent assay (ELISA), and their diagnostic discrimination capacity was evaluated through receiver operating characteristic (ROC) curve analysis. In total, 1,722 vitreous proteins were detected, among which 1,711 yielded reliable quantitative signals. Combined proteomic screening and independent validation demonstrated selective upregulation of vascular endothelial growth factor A (VEGFA) in the vitreous of nAMD patients, with comparable VEGFA concentrations detected in PCV and control subjects. In contrast, ubiquitin-conjugating enzyme E2 L3 (UBE2L3) was uniquely overexpressed only in PCV patients, while UBE2L3 levels remained statistically indistinguishable between nAMD and control cohorts. Receiver operating characteristic (ROC) curve analysis showed that VEGFA achieved an area under the curve (AUC) of 0.845 for discriminating nAMD from controls and 0.790 for distinguishing nAMD from PCV. For UBE2L3, the corresponding AUC values reached 0.810 (PCV vs. controls) and 0.840 (PCV vs. nAMD), respectively. Pathway enrichment analysis uncovered that nAMD is predominantly driven by disrupted energy metabolism and aberrant RNA splicing, while PCV is distinguished by excessive activation of ribosomal translational signaling cascades. These results highlight intrinsic molecular pathogenic disparities between the two choroidal vascular disorders. Collectively, nAMD and PCV display clearly divergent vitreous proteomic expression signatures. VEGFA and UBE2L3 could act as specific discriminatory biomarkers to stratify the two clinical subtypes. The dramatically divergent enriched signaling pathways further clarify the mechanistic basis underlying their disparate clinical phenotypes and treatment responsiveness. Taken together, the present work delivers robust experimental evidence to facilitate accurate clinical stratification and the design of personalized therapeutic regimens.
Background:Diabetic retinopathy is a leading cause of vision impairment, often progressing to neovascular glaucoma. Early detection of neovascularisation of the iris (NVI) is crucial for timely intervention. Traditional diagnostic methods, such as slit-lamp examination, have limitations in identifying early-stage NVI. This study presents a deep learning-based automated approach for analysing iris fluorescein angiography (IFA) images to detect and quantify peripupillary leakage, a key indicator of NVI. Methods:A dataset of 2,449 IFA images was used to train a YOLOv8n-based segmentation model for precise pupil localisation. A leakage circularity detection algorithm was developed to quantify peripupillary fluorescein leakage. The algorithm's performance was evaluated using an independent test set of 131 clinically standardized IFA images. Performance metrics included mean absolute error (MAE), mean absolute percentage error (MAPE), and intersection over union (IoU). Results were compared with manual annotations from two clinical experts. Results:The proposed method demonstrated a significant reduction in MAE (20.81 degrees) and MAPE (21.64%) compared to Clinical Staff 1 (MAE: 34.23 degrees, MAPE: 58.38%) and Clinical Staff 2 (MAE: 43.17 degrees, MAPE: 75.71%). The algorithm achieved an IoU of 39.3%, slightly lower than Clinical Staff 1 (44.5%) and Clinical Staff 2 (41.7%), indicating high segmentation accuracy but minor spatial misalignment. The inter-clinician agreement yielded an IoU of 54.8%, highlighting subjectivity in human assessments. Conclusions:The deep learning-based approach provides superior consistency and accuracy in quantifying peripupillary fluorescein leakage compared to manual expert annotations. While human experts demonstrated slightly higher spatial precision, the algorithm significantly reduces variability and subjectivity in leakage quantification. This automated method has the potential to enhance early detection of NVI, improve clinical workflow efficiency, and assist ophthalmologists in diagnosing DR. Further optimization will focus on refining spatial segmentation accuracy.
Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic nerve injury and vision loss in older individuals. However, the pathogenesis of NAION remains poorly understood, and no treatment has conclusively demonstrated efficacy. This study aimed to explore and describe the proteome of the vitreous humor in eyes with NAION. Ten patients diagnosed with NAION and ten comparative controls diagnosed with idiopathic epiretinal membranes were enrolled in this study. The vitreous proteomes of both groups were analyzed using liquid chromatography-tandem mass spectrometry, and multiple reaction monitoring was performed to validate the target proteins. A total of 815 proteins were identified in both groups, of which 155 were common to both groups. Among these, 98 proteins were significantly upregulated and 57 proteins were downregulated in the NAION group compared to those in the controls. NAION is associated with the increased expression of proteins involved in hemostasis and metabolic pathways. Additionally, extracellular matrix (ECM) remodeling molecules were downregulated in the NAION vitreous, which likely reflects increased vitreous liquefaction and alterations in vitreous biomechanics. This study provides a comprehensive proteomic profile of the vitreous humor in eyes with NAION and highlights the dysregulation of hemostasis, metabolic pathways, and ECM remodeling. These findings enhance our understanding of the molecular mechanisms underlying NAION and may pave the way for the development of novel biomarkers and therapeutic targets.
Diabetic retinopathy (DR) is one of the major complications of diabetes, resulting in severe vision loss. Traction retinal detachment (TRD) is the main factor affecting the effect of proliferative diabetic retinopathy (PDR) surgery. Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the proteomes of the vitreous in the TRD, vitreous hemorrhage (VH) and macular hole (MH) groups. By employing bioinformatics tools for GO and KEGG pathway annotation, as well as conducting protein-protein interaction(PPI) network analysis, we investigated the functional enrichment of proteins in the TRD vitreous and their associated pathways. Additionally, peptide center analysis was performed on the proteomic data to identify key differentially expressed proteins based on screening results. Bioinformatics analysis showed that DEPs is mainly enriched in the complement, the coagulation cascade systems and regulation of actin cytoskeleton. The protein interaction network analysis showed that the central proteins were mainly related to sphingolipid metabolism. APOA4, CHI3L1, LTBP2 were significantly up-regulated in TRD, which were related to the complement system, coagulation cascade and platelet activation, sphingolipid metabolism and other pathways. APOA4 and CHI3L1 protein in patients with TRD group raised significantly in the vitreous humor, shows the potential biomarkers for TRD.
To evaluate the clinical efficacy of conbercept combined with micropulse laser(MPL) in treating polypoidal choroidal vasculopathy (PCV). In this prospective, randomized controlled trial conducted from February 2023 to April 2024, 52 patients (52eyes) with PCV at Anhui NO.2 Provincial People’s hospital were enrolled. Participants were randomized into a conbercept monotherapy group (27cases, 27eyes) and a combination treatment group (conbercept plus micropulse laser(MPL); 25cases, 25eyes). After an initial series of three intravitreal injections, all patients followed the Treat Extend (T E) protocol. Aqueous humor samples were collected before each of the first three injections, and cytokines levels were measured after the sample collection. The combined treatment group received a 577 nm MPL application two weeks following the first injection. The best corrected visual acuity (BCVA) 、central macular thickness (CMT) and total macular volume (TMV) of each group were assessed monthly for three months. From the first to the third month post-injection, both treatment groups showed improvements in BCVA and reductions in CMT and TMV, with the combined treatment group demonstrating significantly greater improvements at each monthly evaluation (P < 0.05). Additionally, levels of aqueous humor cytokines, including VEGF-A, IL-5, MCP-1, and Ang-2, were significantly reduced in both groups. Reductions in VEGF-A and MCP-1 concentrations were positively correlated with improvements in BCVA, CMT, and TMV (P < 0.05). Conbercept combined with MPL therapy demonstrates superior clinical efficacy compared to intravitreal injection of Conbercept alone in patients with PCV. Furthermore, changes in VEGF-A and MCP-1 levels may serve as predictive markers for improvements in visual acuity and retinal morphology in these patients.
PURPOSE:To investigate the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) using circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements, circumpapillary vessel density (cpVD) and the corresponding/final visual outcomes at different stages of nonarteritic anterior ischemic optic neuropathy (NAION). METHODS:Thirty eyes of 30 patients with acute NAION were included. LogMAR best-corrected visual acuity(BCVA), mean deviation (MD) and visual field index (VFI), cpRNFL thickness and cpVD across different retinal layers were examined at baseline, 2 weeks and 1 month after diagnosis. Potential correlations between the Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters and visual outcomes were investigated in both acute and sub-acute NAION. RESULTS:Significant global and regional correlations in S-F relationship were identified exclusively in sub-acute stage (p < 0.05). However, among the OCTA parameters for the acute NAION, the temporal cpVD in superficial vessel complex (SVC) and inner retinal layer (IRL) exhibited positive correlations with corresponding and final visual acuity and visual field outcomes. In the sub-acute stage of NAION, the cpVD of global or temporal section in radial peripapillary capillary (RPC), SVC and IRL were positively correlated with visual outcomes. CONCLUSION:Significant longitudinal V-F relationships exist both globally and regionally, in acute and sub-acute NAION. The cpVD parameters of the SVC and IRL are potentially valuable for evaluating corresponding and final visual outcomes and highlights the importance of monitoring cpVD over cpRNFL thickness in acute NAION.
AimTo evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. MethodsThis study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. ResultsIncomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. ConclusionPeripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis.
Abstract Background We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. Methods A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. Results BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). Conclusions We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. Trial registration The trail has been registered at Chinese Clinical Trail Registry(https://www.chictr.org.cn) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.
Objective This study aimed to evaluate retinal vessel morphology in Non-arteritic Anterior Ischemic Optic Neuropathy (NAION) using Integrative Vessel Analysis (IVAN) and to explore the relationships between retinal vascular parameters and systemic factors related to NAION.Methods This case-control study included 120 eyes from 120 participants, categorized into control, hypertension, and NAION groups (40 eyes each). IVAN was used to measure retinal vessel caliber through the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).Results The mean CRAE and CRVE across all participants were 154.54 +/- 21.53 mu m and 252.22 +/- 15.88 mu m, respectively. NAION participants exhibited higher CRAE and CRVE compared to the control and hypertension groups. In the NAION group, body mass index (BMI) showed a negative correlation with CRAE and a positive correlation with CRVE.Conclusion IVAN serves as a reliable method for assessing retinal vascular caliber. Our findings suggest that retinal vascular caliber may provide valuable insights into the role of subclinical retinal vascular processes in the development of NAION.
Background Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. Case presentation A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. Conclusions To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied.
Background:Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV.Methods:Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis.Results:A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls.Conclusion:This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.
Purpose: The aim of this study was to explore whether there are interactions between genetic (ARMS2/HTRA1) and environmental factors (cigarette smoking) in the pathogenesis of age-related macular degeneration (AMD). Methods: Primary human retinal pigment epithelial (hRPE) cells were obtained from four donors’ eyes with AMD high-risk ARMS2/HTRA1 alleles, and two donors’ eyes with wild-type alleles were used as controls. The pooled serum from 32 smokers and 35 nonsmokers were collected and used separately to treat hRPE cells. The isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics was used to identify associated proteins and comparing the differences between AMD high-risk and low-risk HTRA1/ARMS2 alleles after exposure to smokers’ serum. Results: After stimulation with the smokers’ serum, 400 differentially expressed proteins (DEPs) were detected in the high-risk allele cells. Several DEPs are involved in neuronal protein degeneration and oxidative stress pathways. The smokers’ serum stimulation or HTRA1 overexpression can both upregulate caveolin-1, which was one of the DEPs. Besides, the smokers’ serum enhanced the phagocytosis of cultured human RPE cells. Conclusions: The study confirmed the AMD high-risk alleles, HTRA1, and cigarette smoking can promote AMD development by regulating caveolin-1 expression. Translational Relevance: AMD high-risk alleles and environmental risk factors can promote the occurrence and development of AMD by regulating caveolin-1 expression, upregulation of which will induce apoptotic cell death in response to cellular stress in early AMD conditions.