Abstract:AIM: To construct an intelligent segmentation scheme for precise localization of central serous chorioretinopathy (CSC) leakage points, thereby enabling ophthalmologists to deliver accurate laser treatment without navigational laser equipment. METHODS: A dataset with dual labels (point-level and pixel-level) was first established based on fundus fluorescein angiography (FFA) images of CSC and subsequently divided into training (102 images), validation (40 images), and test (40 images) datasets. An intelligent segmentation method was then developed, based on the You Only Look Once version 8 Pose Estimation (YOLOv8-Pose) model and segment anything model (SAM), to segment CSC leakage points. Next, the YOLOv8-Pose model was trained for 200 epochs, and the best-performing model was selected to form the optimal combination with SAM. Additionally, the classic five types of U-Net series models [i.e., U-Net, recurrent residual U-Net (R2U-Net), attention U-Net (AttU-Net), recurrent residual attention U-Net (R2AttU-Net), and nested U-Net (UNet++)] were initialized with three random seeds and trained for 200 epochs, resulting in a total of 15 baseline models for comparison. Finally, based on the metrics including Dice similarity coefficient (DICE), intersection over union (IoU), precision, recall, precision-recall (PR) curve, and receiver operating characteristic (ROC) curve, the proposed method was compared with baseline models through quantitative and qualitative experiments for leakage point segmentation, thereby demonstrating its effectiveness. RESULTS: With the increase of training epochs, the mAP50-95, Recall, and precision of the YOLOv8-Pose model showed a significant increase and tended to stabilize, and it achieved a preliminary localization success rate of 90% (i.e., 36 images) for CSC leakage points in 40 test images. Using manually expert-annotated pixel-level labels as the ground truth, the proposed method achieved outcomes with a DICE of 57.13%, an IoU of 45.31%, a precision of 45.91%, a recall of 93.57%, an area under the PR curve (AUC-PR) of 0.78 and an area under the ROC curve (AUC-ROC) of 0.97, which enables more accurate segmentation of CSC leakage points. CONCLUSION: By combining the precise localization capability of the YOLOv8-Pose model with the robust and flexible segmentation ability of SAM, the proposed method not only demonstrates the effectiveness of the YOLOv8-Pose model in detecting keypoint coordinates of CSC leakage points from the perspective of application innovation but also establishes a novel approach for accurate segmentation of CSC leakage points through the “detect-then-segment” strategy, thereby providing a potential auxiliary means for the automatic and precise real-time localization of leakage points during traditional laser photocoagulation for CSC.

Abstract:AIM: To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model, with a focus on dry eye-like alterations. METHODS: Male C57BL/6J mice (10–12 weeks old) were randomly assigned to control or restraint stress (RS) groups. The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior. Behavioral testing, tear secretion measurement, and corneal Oregon Green Dextran (OGD) staining were performed. Postmortem analyses included histological evaluation of lacrimal glands, goblet cell quantification using periodic acid-Schiff staining, and assessment of key inflammatory and apoptotic markers: interleukin (IL)-17, matrix metalloproteinases (MMP)-3, MMP-9, IL-13, interferon (IFN)-γ, and cleaved caspase-3 and -8. RESULTS: Repeated RS induced depression-like behavior and significant ocular surface changes. RS-treated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17, MMP-3, and MMP-9 (P<0.05). Goblet cell density and IL-13 protein expression were reduced, while IFN-γ protein expression was elevated (P<0.05). Cleaved caspase-3 and -8 levels were significantly increased in both cornea and conjunctiva. Tear volume and lacrimal gland size were unchanged; however, mild inflammatory infiltration was observed in lacrimal glands. CONCLUSION: Repeated RS leads to ocular surface inflammation and dry eye-like pathology, including corneal barrier disruption, goblet cell loss, and epithelial apoptosis. These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.

Abstract:AIM: To investigate whether vaccinia-related kinase 1 (VRK1) mediates transforming growth factor-beta2 (TGF-β2)-caused epithelial-mesenchymal transition (EMT) and inflammatory responses in retinal pigment epithelial (RPE) cells through regulating snail family transcriptional repressor 1 (SNAI1), and to validate its role in a proliferative vitreoretinopathy (PVR) mouse model. METHODS: Human RPE cell line ARPE-19 cells were treated with TGF-β2 to construct an EMT model. Western blot detected VRK1 level. The effects of VRK1 on SNAI1 expression and biological behavior of ARPE-19 cells were detected by immunofluorescence, ELISA, Transwell, and scratch assay, and the interaction between VRK1 and SNAI1 was confirmed through immunoprecipitation. A PVR mouse model was constructed, and the effects of VRK1 or/and SNAI1 on retinal damage were assessed by pathologic staining. Inflammatory factors and EMT-related proteins were assessed with ELISA and Western blot. RESULTS: VRK1 was upregulated in ARPE-19 cells after TGF-β2 treatment. Overexpression of VRK1 increased cell viability, promoted cell migration and EMT, and the levels of inflammatory factors. Silencing of VRK1 reversed the above indexes. There was a direct interaction between VRK1 and SNAI1, and overexpresssion SNAI1 weakened the impacts of silencing of VRK1. In PVR mice, silencing of VRK1 ameliorated retinal structural damage, decreased proinflammatory factor levels, and suppressed SNAI1 and mesenchymal marker expression. SNAI1 overexpression antagonized the protective effects of silencing VRK1 and exacerbated EMT and inflammatory responses. CONCLUSION: VRK1 plays a key role in retinal structural and inflammatory damage in PVR mice by regulating SNAI1 and mediating TGF-β2-caused EMT and inflammatory responses in RPE cells.

Abstract:AIM: To investigate the effects of zingerone (ZO) on the retina in diabetic rats. METHODS: A total of 70 rats were randomly selected and divided into seven groups [diabetic group (Dm+; n=10), diabetic+metformin group (Dm+Met; n=10), diabetic+ZO25 group (Dm+ZO25; n=10), diabetic+ZO50 group (Dm+ZO50; n=10), diabetic+metformin group+ZO 50 Group (Dm+Met+ZO50; n=10)]. Diabetes was induced by streptozotocin (STZ), and metformin and two different doses of ZO were administered via gavage. Retinal tissues were evaluated by histopathological and immunohistochemical analyses. RESULTS: In diabetic rats, severe retinal inflammation, tissue necrosis, and increased tumor necrosis factor-α (TNF-α) expression were observed. ZO administration reduced these effects in a dose-dependent manner. Protective effects of metformin alone were limited, and no synergistic benefit was observed in ZO+Met groups. Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity. Additionally, elevated 8-OHdG and c-Jun N-terminal kinase (JNK) expressions in diabetic retinopathy models were significantly reduced by ZO treatment. CONCLUSION: ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.

Abstract:AIM: To assess the success rate of lacrimal sac hydrostatic pressure application (HPA) maneuver, a conservative office procedure for treatment of congenital nasolacrimal duct obstruction (CNLDO). METHODS: The medical records of pediatric patients, 36mo old or younger, diagnosed with CNLDO between the years 2016-2022, were retrospectively reviewed. In all children, HPA was performed by a pediatric ophthalmologist. Success was defined as the resolution of epiphora and discharge within 48h of the intervention. RESULTS: A total of 281 eyes (194 patients) with CNLDO underwent HPA. Follow-up data were available for 261 eyes (179 patients, 50.3% male) and these patients were included in the analysis. The mean follow-up time was 11.6±13mo. Ninety-seven patients (54.2%) had unilateral nasolacrimal duct obstruction, while 82 patients (45.8%) had bilateral CNLDO. The mean age at the time of HPA was 5.8±5.9mo. Complete resolution of symptoms was achieved in 102 (39.1%) eyes. Patients 6mo old or younger at the time of HPA had a significantly higher success rate compared to patients older than 6mo (43.7% vs 30.9%, P=0.04). Younger age at the time of pressure application was associated with a higher resolution rate of CNLDO (OR 0.93, P=0.004). Sex assigned at birth, prematurity, laterality of the obstruction and type of symptoms (epiphora, discharge) were not correlated with success. A second HPA was performed in 46 eyes, with resolution of symptoms in 12 eyes (26.1%). CONCLUSION: Hydrostatic pressure applied on the lacrimal sac by an experienced ophthalmologist or an experienced pediatrician may be an effective treatment for CNLDO. We recommend HPA as an initial active conservative approach in all pediatric patients with CNLDO, especially those younger than 6mo.

Abstract:AIM: To investigate the characteristics and associated factors of intraocular lens (IOL) tilt and decentration after transscleral suture-fixated IOL surgery in congenital ectopia lentis (CEL). METHODS: CEL patients undergoing transscleral suture-fixated IOL surgery were divided into two groups based on implanted IOL type (three-piece IOL or one-piece IOL). The IOL tilt and decentration at 3-month and 1-year postoperative were measured. Multivariate regression analyses were performed to identify the associated factors of IOL tilt and decentration as well as longitudinal changes. RESULTS: The 61 CEL patients (mean age 9.07±5.05y) in three-piece IOL (M/F: 14/7) group had a greater tilt than those with one-piece IOL (M/F: 28/12) group both at 3-month postoperative (horizontal: P=0.024; vertical: P=0.048) and 1-year postoperative (horizontal: P=0.011; vertical: P=0.001). Three-piece IOL group had a greater longitudinal change between 3-month postoperative to 1-year postoperative in IOL tilt (horizontal: P=0.028; vertical: P=0.026) and a greater longitudinal change in horizontal IOL decentration than one-piece IOL group (P<0.05). The longer axial length (AL) was associated with the longitudinal changes in IOL tilt (P=0.039), while the three-piece IOL was associated with the longitudinal changes in horizontal IOL decentration 1-year postoperatively (P=0.011). CONCLUSION: IOL tilt is greater in the three-piece IOL group than that in the one-piece IOL group 1-year postoperatively. The three-piece IOL is associated with greater longitudinal changes of IOL decentration, while longer AL is associated with longitudinal changes of IOL tilt. For CEL patients, more stable IOL type should be selected and patients with longer AL warrant closer monitoring.

Abstract:AIM: To evaluate the differences and consistency of vault measurements obtained by Scheimpflug tomography (Pentacam), anterior segment optical coherence tomography (AS-OCT, CASIA II), and ultrasound biomicroscopy (UBM) following implantable collamer lens (ICL) V4c implantation. METHODS: Vault measurements were acquired using three modalities: Pentacam, CASIA II AS-OCT, and UBM. Repeated-measures analysis of variance was used to compare the vault values obtained by the three devices. The correlation and consistency of measurements among the three instruments were assessed using the Pearson correlation coefficient, intraclass correlation coefficient (ICC), and Bland-Altman plots. RESULTS: This retrospective study enrolled 210 myopic eyes of 210 patients (158 women and 52 men) who underwent ICL implantation: 108 eyes had a myopic ICL V4c implanted, and 102 eyes had a toric ICL V4c implanted. The mean vault values measured by Pentacam, CASIA II, and UBM were 452.64±204.20 μm, 538.57±203.54 μm, and 560.95±227.54 μm, respectively, with statistically significant differences among the three groups (P<0.05). Pearson correlation analysis showed strong positive correlations between vault values measured by different instruments (all P<0.001). ICC results indicated good consistency among the three measurement modalities (all P<0.001). Stratified analysis revealed that when the vault value was ≤250 μm, the correlation and consistency of measurements across the three instruments were lower than those in the medium and high vault subgroups. CONCLUSION: Vault values measured by Pentacam are lower than those obtained by CASIA II and UBM, with UBM yielding the highest mean vault values. Measurements from the three instruments are not interchangeable but can serve as mutual references due to their significant correlation and good overall consistency. Pentacam and CASIA II demonstrate the highest consistency in vault measurement. Notably, when the vault value is ≤250 μm, the consistency between Pentacam and the other two instruments decreases significantly.

Abstract:AIM: To evaluate the clinical outcomes of a new minimally invasive technique using horizontal mattress sutures and Hoffman pockets for four-point refixation of dislocated four-haptic intraocular lenses (IOLs). METHODS: This retrospective consecutive case series included eyes with dislocated Akreos AO60 IOLs underwent scleral refixation using a horizontal mattress double-needle suture technique with intralamellar knot burial via Hoffman pockets. Clinical outcomes assessed included pre- and postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP), spherical equivalent (SE), suture duration, IOL centration, and perioperative complications. RESULTS: A total of 10 eyes from 10 patients (6 males) were included. The mean age at the time of IOL refixation was 53.10±13.07y (range: 28–68y). The mean interval between initial IOL implantation and dislocation was 8.44±3.54y. The mean postoperative follow-up duration was 11.45±10.30mo. Surgical time averaged 15.3±1.77min, with no intraoperative complications. The mean axial length was 27.16±4.35 mm, with high myopia (HM) as the leading comorbidity (4/10 eyes). Postoperative BCVA significantly improved compared to preoperative values (P=0.025). Postoperative SE was significantly improved compared with preoperative (P=0.01). All IOLs remained centered throughout follow-up. CONCLUSION: This minimally invasive four-point scleral fixation technique offers a safe and effective refixation strategy for dislocated four-haptic IOLs. The horizontal mattress suture configuration combined with Hoffman pockets facilitates durable centration, avoids conjunctival dissection, and could be adopted into routine surgical practice.

Abstract:AIM: To compare the efficacy of goniosynechialysis (GSL) under a microscope alone (GM) and under direct gonioscopy (GG) for chronic angle-closure glaucoma (CACG) coexisted with cataract. METHODS: A prospective, single-center, and randomized controlled trial was conducted. Patients diagnosed as CACG and cataract were randomly allocated into either GM group or GG group. In GM group, the range of peripheral anterior synechiae (PAS) was confirmed through gonio-lens after phacoemulsification with intraocular lens implantation (PEI). PAS was separated only under a microscope. After separating the closed angle of 360° by this method, we used a surgical gonioscope to confirm the PAS range. If any remaining PAS was present, we would separate them with an iris repositor under the direct gonio-lens until angle of 360° was reopened. In GG group, PAS was separated under direct gonioscopy after PEI until angle of 360° was reopened. The range of residual PAS after GSLs was the primary outcome. Intraoperative complications (hyphema), intraocular pressure (IOP) and anti-glaucoma medication usage after operation were the secondary outcomes. RESULTS: Sixty eyes were included, each group comprising 30 eyes. The average age [GM group: 66.3±6.8y (12 males), GG group: 67.6±8.9y (7 males), P=0.550], the baseline IOP (GM group: 29.6±11.5 mm Hg, GG group: 32.4±12.2 mm Hg, P=0.366) and the average initial PAS extent (GM group: 8.9±2.6h, GG group: 9.4±2.5h, P=0.425) were similar in the two groups. In GM group, the PAS range reduced from 8.9±2.6h before operation to 7.2±2.9h after PEI and 3.3±2.2h after GSL. In GG group, the PAS range reduced from 9.4±2.5h before operation to 7.5±2.9h after PEI and 0.1±0.3h after GSL. The PAS after PEI was significantly reduced compared to the pre-operative PAS in both groups (all P<0.001). The extent of residual PAS after GSL in GM group was larger than that in GG group with significant statistical difference (P<0.001). Patients who underwent GSL without a gonioscope were more likely to develop hyphema than those who underwent GSL under direct gonioscopy. The difference of hyphema grade between the two groups was statistically significant (P=0.019). CONCLUSION: PEI alone can not open 360° of angle completely. PEI+GSL significantly reduced PAS range. But for patients with CACG, GSL under a microscope alone is more difficult to separate stable PAS completely and adequately than GSL under direct gonioscopy.

Abstract:AIM: To explore the repeatability, reproducibility, and agreement in the measurement of the choroidal vascularity index (CVI) for different swept-source optical coherence tomography (OCT) devices and between OCT and OCT angiography (OCTA) images. METHODS: Two swept-source OCT imaging systems, VG200I and Topcon DRI OCT Triton, were used to capture OCT and OCTA images in triplicate. The first and third images were taken by one operator, and the second image was taken by another operator. The built-in software was used to calculate the CVI from the OCTA images (CVI-OCTA), and a custom-designed algorithm was used to calculate the CVI from the OCT images (CVI-OCT). Repeatability and reproducibility were assessed with the intraclass correlation coefficient (ICC), and agreement between devices and between OCT and OCTA were evaluated with Bland-Altman analysis. RESULTS: Sixty-eight eyes from 35 adults (17 females) were included in the analysis. The average age of the participants was 23.6±2.3y, with an average spherical equivalent refraction of -3.08±2.47 D and an average AL of 25.21±1.20 mm. Both OCT devices demonstrated high repeatability and reproducibility in measuring the CVI-OCTA (all ICCs>0.894 across five choroidal regions) and CVI-OCT (all ICCs>0.838). Furthermore, the between-device agreement in measuring the CVI-OCT was good [mean difference (MD) ranging from -2.32% to -3.07%], but that in measuring the CVI-OCTA was poor (MD, 1.48% to -7.43%). Additionally, the between-imaging agreement (CVI-OCTA versus CVI-OCT) was poor for both devices (Triton, MD, 6.05% to 12.68%; VG200I, MD, 6.67% to 12.09%). CONCLUSION: Both OCT devices and the two analytical methods demonstrate good stability. The inter-device consistency of CVI-OCT is good, while the inter-device consistency of CVI-OCTA and the consistency between the two analytical methods in the same device are both poor.

Abstract:AIM: To investigate the sex-specific correlation between systemic factors and retinal neurovascular alterations in individuals with type 1 diabetes mellitus (T1DM) who do not exhibit signs of diabetic retinopathy (DR). METHODS: A cohort participant without DR diagnosed with T1DM, underwent comprehensive ophthalmologic evaluation, optical coherence tomography angiography retinal structural and microvascular density analysis, and systemic parameter assessment. Multiple linear regression analysis was used to investigate the impact of systemic parameters on retinal alterations in distinct gender groups. RESULTS: A total of 182 individuals were included, consisting of 85 males (mean age 23.28±12.75y) and 97 females (mean age 22.98±13.68y). Males exhibited significantly greater thickness in both the internal retinal layer and the entire retina compared to females (P<0.01), whereas females had higher densities of deep retinal vessels and choroidal capillaries (P<0.05). Additionally, glycemic control was found to have a notable influence on retinal thickness in males (P<0.05), while insulin function had a more pronounced impact on retinal structure in females (P<0.01). Furthermore, a significant correlation was observed between thyroid function markers and retinal parameters in both male and female (P<0.05). CONCLUSION: Sex differences in alterations in retinal structure and microcirculation are observed in individuals with T1DM prior to the development of clinical DR, with a noted association between these changes and systemic parameters.

Abstract:AIM: To evaluate the predictive value of pan-immune-inflammation value (PIV) in the diagnosis of proliferative diabetic retinopathy (PDR) and its association with the stage of PDR. METHODS: This observational case-control study included participants who underwent routine complete blood count testing. Inflammation-related indices, including neutrophil-to-lymphocyte ratio, systemic immune-inflammation index (SII), and PIV, were derived and analyzed. Receiver operating characteristic curve (ROC) analysis was applied to assess the diagnostic performance of these indices in distinguishing patients with PDR, with sensitivity, specificity, area under ROC, and optimal threshold values calculated. In addition, binary logistic regression analysis was performed to evaluate the association between inflammatory indices and PDR stage. RESULTS: This study included 205 patients: 60 with diabetes without retinopathy (mean age: 61.81±10.76y), 80 with PDR (mean age: 61.63±10.03y) and 65 healthy controls (mean age: 59.52±5.88y). The PDR group had significantly higher white blood cell (WBC, P<0.001), monocyte (MONO, P=0.009) and neutrophil (NEU) counts (P<0.001). SII and PIV had the highest sensitivity and area under ROC for predicting patients with PDR (0.822, 0.846, respectively). The optimal cut-off values for discriminating patients with PDR were determined to be >527.12 and >299.08 for SII and PIV, respectively. The logistic regression analysis demonstrated that a decrease in lymphocyte (LYM) count and an increase in platelet count (PLT), glycated haemoglobin (HbA1c), SII, and PIV were all significantly associated with the development of high-risk PDR (all P<0.05). PIV was more stable than independent MONO, LYM, PLT and NEU levels in predicting both the diagnosis and stage of PDR. The optimal cut-off value for PIV to discriminate patients with high-risk PDR was found to be >345.87 area under ROC=0.871, with sensitivity of 0.827 and specificity of 0.812. CONCLUSION: PIV is a reliable, valuable, and inexpensive blood index that can be used for early detection and staging of PDR. PIV may therefore be essential to be used for the follow-up of diabetic patients.

Abstract:AIM: To explore the factors influencing the treatment duration and visual prognosis of cytomegalovirus (CMV) retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: All participants received ganciclovir intravenous infusion or oral and intravitreal injection of ganciclovir (IVG) 3 mg twice a week for 4 consecutive times (induction phase). The affected eyes were divided into stop treatment group (Group A), continue treatment group (Group B), and relapse after treatment group (Group C) according to whether local therapy could be terminated at the end of the induction phase and whether CMVR recurred within 3mo after the termination of local therapy. RESULTS: The study included 31 participants (48 eyes) diagnosed with CMVR including 11 males and 20 females. The mean age was (28±8.2)y. There were 17 cases of binocular disease (34 eyes) and 14 cases of monocular disease (14 eyes). Visual acuity improved in 26 eyes (54.1%), remained unchanged in 9 eyes (18.8%), and decreased in 13 eyes (27.1%). The peak value of blood CMV in Group B was significantly higher than that in Group A (P=0.013). The number of eyes with anterior chamber inflammation in Group C was significantly lower than that in Groups A and B (P=0.015, P=0.016). The average number of interval days was higher in Group A than in Group B. For Group A, there was a strong positive correlation between the number of eyes with CMV positive blood (r=0.712, P=0.031) and visual acuity changes. For Group B, there was a moderately strong positive correlation between the days of blood CMV after transplantation (r=0.371, P=0.043) and the times of injections. For Group C, there was a strong positive correlation between the peak value of blood CMV (r=0.719, P=0.029) and the times of injection. CONCLUSION: Systemic use of antivirals combined with intravitreal injection of antivirals is effective for patients with CMVR after allo-HSCT surgery. Patients with shorter interval days, higher peak or more days of blood CMV need more injections. Patients with positive blood CMV at initial diagnosis have worse visual prognosis.

Abstract:AIM: To investigate the association between anti-DFS70 antibody positivity and ocular parameters, specifically, the choroidal vascularity index (CVI) and other optical coherence tomography (OCT) metrics, in a healthy population. METHODS: This age- and sex-matched case-control study enrolled 84 healthy individuals with positive anti-DFS70 antibody findings and 84 healthy negative controls. All participants underwent detailed ophthalmological examinations, including biometry and OCT imaging. Anti-DFS70 positivity was determined by indirect immunofluorescence and scored semi-quantitatively (1+ to 3+). CVI was calculated from OCT images using a standardized protocol with Image J software. Statistical analyses, including Student’s t-test, Mann-Whitney U test, Spearman correlation, and logistic regression, were used to compare groups and identify predictive factors. RESULTS: The individuals who tested positive and negative for anti-DFS70 included in the study were matched for age (median age=47y) and sex (F:M=7:1). CVI was significantly lower in the anti-DFS70-positive group compared to the negative group. A higher anti-DFS70 antibody titer was significantly associated with decreased subfoveal and nasal choroidal thickness (P=0.016 and P=0.014, respectively). In univariate regression analysis, CVI was the only significant predictor of anti-DFS70 positivity [odds ratio (OR)=0.02, P=0.025]. Multivariate analysis revealed a positive correlation between macular thinning outside the subfoveal area and anti-DFS70 status (P<0.05). CONCLUSION: Our study demonstrates a novel association between anti-DFS70 antibody positivity and reduced choroidal vascularity in healthy individuals. These findings suggest that anti-DFS70 antibodies may be associated with subtle choroidal vascular changes detectable by OCT, even in asymptomatic individuals. Further longitudinal research is warranted to clarify the underlying mechanisms and long-term clinical significance of these ocular changes.

Abstract:AIM: To investigate the effects of binocular fusional C-optotypes (positive/negative) and 2D planar C-optotypes on the amplitude and stability of transient accommodation (TAC) in adults, and to provide a basis for non-contact myopia intervention. METHODS: This was a self-controlled study. Using red-blue 3D technology, four experimental stages were set up: Test A [fixating on the 1 m negative fusional C-optotypes, 8△ base-in (BI)], Test B (fixating on the 5 m planar C-optotypes), Test C (fixating on the 1 m planar C-optotypes), and Test D [fixating on the 1 m positive fusional C-optotypes, 20△ base-out (BO)]. A WAM-5500 open-field autorefractor was used to measure TAC and accommodative microfluctuations [evaluated via interquartile range (IQR) and median-based coefficient of variation (CVmed)]. Additionally, the convergence accommodation to convergence (CA/C) ratio was calculated, and a visual fatigue questionnaire was administered to assess participants’ subjective visual comfort. RESULTS: A total of 21 subjects (7 males, 14 females; aged 23-41y) with normal binocular visual function were enrolled. The results showed that the TAC increased gradually across the four stages, and these values were Test A (-0.35±0.26 D)0.05), but the fluctuation stability of Test D showed a significant difference between the first 20s and the second 20s (P=0.017). The CA/C ratio was significantly higher in Test D (0.05±0.02 D/△) than in Test A (0.03±0.02 D/△, P=0.007), indicating stronger accommodation-convergence linkage during positive fusional fixation. The visual fatigue scores of all stages were low (median 0-1), with Test D slightly higher than Test B and Test C (P<0.05). No linear correlation was found between TAC and age (all r<0.1, P>0.05). CONCLUSION: Negative fusional C-optotypes induce ciliary muscle relaxation to reduce TAC, while positive fusional C-optotypes enhance accommodation-convergence coordination to increase TAC. The red-blue 3D-based non-contact training mode exhibits good safety (median visual fatigue scores: 0-1 across all tests) and provides a novel dual-directional (relaxation-activation) strategy for myopia prevention and control.

Abstract:AIM: To evaluate the differences in near point of convergence (NPC), fusional vergence, saccadic eye movements, versional eye movements, and heterophoria between patients diagnosed with Parkinson’s disease (PD) and healthy subjects. METHODS: A cross-sectional comparative study was conducted, enrolling two cohorts: a PD group and a healthy control group. The PD group was recruited via non-random convenience sampling, while the control group was selected randomly from individuals without PD. All participants were screened according to predefined inclusion and exclusion criteria before undergoing a comprehensive optometric assessment, which included measurements of uncorrected visual acuity, corrected visual acuity, and objective and subjective refraction. Subsequently, binocular vision function evaluations were performed, covering NPC measurement, fusional vergence reserve assessment at both distance and near, saccadic eye movement testing, and versional eye movement and heterophoria assessment. RESULTS: A total of 42 PD patients and 41 healthy controls were included in the final analysis. The two groups were well-matched in terms of sex distribution [29 males (69.0%) in the PD group vs 29 males (70.7%) in the control group, P=0.867] and mean age (55.3±9.6y in the PD group vs 54.9±9.8y in the control group, P=0.866). The prevalence of abnormal versional eye movements was significantly higher in the PD group than in the control group (23.81%, 95%CI: 12.05%-39.45% vs 7.32%, 95%CI: 1.54%-19.92%; P=0.025). Near exophoria was more prevalent in PD patients (61.90%, 95%CI: 45.64%-76.43%) than in controls (17.07%, 95%CI: 7.15%-32.06%), with a significant difference [odds ratio (OR)=7.99; 95%CI: 2.83-21.99; P<0.001]. The mean NPC was significantly greater (more receded) in the PD group than in the control group (9.01±3.74 cm vs 7.20±2.15 cm; P=0.007). A statistically significant positive correlation was observed between PD severity and NPC values (Pearson’s correlation coefficient=0.309; P=0.046). Except for distance base-out break and distance base-out recovery values, all other fusional vergence parameters were significantly lower in the PD group than in the control group (P<0.05). The mean saccadic test score was significantly lower in PD patients than in controls (3.29±0.57 vs 3.78±0.42; P<0.001). Among all fusional vergence indices, near base-in blur yielded the highest area under the curve (AUC=0.877), with a sensitivity of 69% and specificity of 90%, followed by distance base-out blur (AUC=0.824, sensitivity=97.6%, specificity=66.7%), near base-out blur (AUC=0.814, sensitivity=76.2%, specificity=72.7%), near base-out break (AUC=0.749, sensitivity=78.6%, specificity=67.6%), and near base-out recovery (AUC=0.749, sensitivity=95.2%, specificity=50%). CONCLUSION: PD is associated with significant binocular vision function impairment, with receded NPC and reduced near fusional vergence reserves being the most prominent disorders. These findings highlight the potential value of binocular vision assessment as a non-invasive biomarker for the early detection and clinical monitoring of PD.

Abstract:AIM: To determine the prevalence of tropia, phoria, and abnormality of near point of convergence (NPC), along with associated ocular symptoms, in high school students. METHODS: This cross-sectional study was conducted in Erbil, Iraq. The target population consisted of high school students selected through a multi-stage cluster sampling method. Comprehensive visual examinations were performed for all students, including measurement of uncorrected and corrected visual acuity, objective and subjective refraction, and distance and near cover tests. NPC was evaluated using a single 6/12 visual target mounted on a centrally positioned Gulden fixation stick. Ocular symptoms were investigated through interviews. RESULTS: Of the 996 selected students, 921 participated in the study. Of them, 543 (58.96%) were female, and their ages ranged from 13 to 22y. The prevalence of tropia was 3.58% [95% confidence interval (CI): 2.38%–4.78%], observed in 3.44% of males and 3.68% of females. Exotropia (1.95%, 95%CI: 1.06%–2.85%) was more common than esotropia (1.52%, 95%CI: 0.73%–2.31%). The 15.42% (95%CI: 13.09%–17.75%) of students had phoria. Exophoria (13.79%, 95%CI: 11.56%–16.02%) was significantly more prevalent than esophoria (1.63%, 95%CI: 0.81%–2.45%). The prevalence of NPC abnormality in the total study population was 24.97% (95%CI: 22.18%–27.77%). It was 26.72% (95%CI: 22.26%–31.18%) in males and 23.76% (95%CI: 20.18%–27.34%) in females (P=0.307). The most common symptom in phoria was headache (86.62%, 95%CI: 81.02%–92.22%), followed by tired or sore eyes (61.97%, 95%CI: 53.99%–69.96%). The most common symptoms in tropia were blurry vision (93.94%, 95%CI: 79.77%–99.26%) and difficulty concentrating (87.88%, 95%CI: 76.74%–99.01%). CONCLUSION: Among Erbil’s high school students, the prevalence of strabismus, particularly the exodeviation type, is relatively high, and a significant percentage of students have NPC abnormalities. Addressing and correcting these binocular vision problems, due to their associated visual symptoms, can lead to an improvement in students’ quality of life and academic performance.

Abstract:AIM: To investigate the causal effect of obesity on cataract risk and explores the potential mediating roles of metabolites using Mendelian randomization (MR). METHODS: Summary-level data from large-scale genome-wide association studies to examine the relationship between obesity and cataract were utilized. Obesity-related traits, including body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC). A two-sample MR approach was employed to assess the causal effect of obesity on cataract risk, while potential mediators were identified from suitable genome-wide association studies (GWAS) datasets. Additionally, a metabolic pathway analysis was conducted. RESULTS: An increase of 1 standard deviation (SD) in BMI, WHR, and WC was associated with a significantly higher risk of cataract (BMI: odds ratio (OR) 1.0017, 95% confidence interval (CI): 1.0001–1.0032, P=0.0320; WHR: OR 1.0029, 95%CI: 1.0006–1.0051, P=0.0129; WC: OR 1.0020, 95%CI: 1.0001–1.0038, P=0.0390]. These associations remained robust after adjusting for confounding factors in multivariable MR analysis. Furthermore, a two-step MR analysis identified eight potential metabolic mediators, with one mediator showing a significant causal role in the relationship between obesity and cataract. CONCLUSION: This work highlights the importance of addressing obesity as a modifiable risk factor for cataracts, particularly through metabolic pathways.

Abstract:AIM: To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization (MR) approach. METHODS: Publicly available genome-wide association study (GWAS) datasets were utilized for this two-sample MR analysis. Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository, and myopia-related GWAS data were obtained from the FinnGen project. Single nucleotide polymorphisms (SNPs) associated with inflammatory cytokines were systematically selected as instrumental variables (IVs) based on three rigorous criteria: relevance, independence, and exclusion of pleiotropy. Five MR methods were employed for causal inference: the inverse-variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger regression, weighted median estimator, simple mode, and weighted mode approaches. Sensitivity analyses were performed to evaluate the robustness of the causal estimates. RESULTS: A total of 773 myopia-associated SNPs were identified. MR analysis revealed that higher levels of macrophage inflammatory protein 1-α (MIP-1α) were associated with a 17% reduced risk of myopia [odds ratio (OR)=0.83; 95% confidence interval (CI): 0.69-0.99; P<0.05]. In contrast, elevated levels of eotaxin (OR=1.26; 95%CI: 1.07-1.47; P<0.01), stromal cell-derived factor-1α (SDF-1α; OR=1.68; 95% CI: 1.08-2.62; P<0.05), and interleukin-2 receptor subunit alpha (IL-2Rα; OR=1.25; 95%CI: 1.01-1.53; P<0.05) were significantly associated with an increased risk of myopia. Sensitivity analyses confirmed the reliability of these results. CONCLUSION: This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia. MIP-1α may act as a protective factor against myopia, while eotaxin, SDF-1α, and IL-2Rα are potential risk factors for myopia. These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia, offering novel insights for the development of preventive and therapeutic strategies for myopia.

Abstract:AIM: To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy (TAO). METHODS: This case-control study retrieved clinical data from 2018 to 2023. A total of 2591 patients were enrolled, including 197 patients with TAO (case group) and 2394 patients with hyperthyroidism without TAO (control group). Serum lipid parameters, including triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the HDL/total cholesterol ratio, as well as thyroid function markers, were compared between the two groups. Correlation analyses were performed to evaluate the associations between serum lipid levels and key ocular manifestations of TAO, including exophthalmos degree, clinical activity score, and disease severity. Furthermore, Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) datasets, with hyperthyroidism as the exposure variable and serum lipid parameters as the outcome variables, to infer the causal relationship between hyperthyroidism, lipid metabolism, and TAO progression. RESULTS: The TAO group consisted of 101 males and 96 females, while the hyperthyroidism group included 706 males and 1688 females. Compared with the control group, patients with TAO had significantly higher levels of triglycerides (1.83±1.21 vs 1.40±1.08 mmol/L, P<0.01), total cholesterol, LDL, and HDL. Correlation analysis showed that triglyceride levels were positively correlated with exophthalmos degree, whereas HDL levels were inversely correlated with exophthalmos degree. No significant associations were found between serum lipid levels and clinical activity score (P>0.1). MR analysis confirmed that hyperthyroidism exerted a causal effect in reducing serum triglycerides [inverse-variance weighting odds ratio (OR)=0.035, 95% confidence interval (CI): 0.01-0.12] and total cholesterol (OR=0.085, 95%CI: 0.02-0.34), with no evidence of horizontal pleiotropy (MR-PRESSO P>0.05). CONCLUSION: Elevated serum triglyceride levels are an independent risk factor for TAO severity, especially exophthalmos, and triglyceride metabolism is inversely regulated by thyroid function.

Abstract:AIM: To perform a bibliometric analysis of publications focusing on inflammatory mechanisms in glaucoma, thereby comprehensively understanding the current research status and identifying potential frontier directions for future studies. METHODS: A systematic search was conducted in the Web of Science Core Collection (WoSCC) database to retrieve relevant literature published from January 1, 2000, to August 31, 2025 (data accessed on September 12, 2025). Multiple data visualization tools were employed to conduct in-depth analyses of the included publications, covering aspects such as publication quantity and quality, evolutionary trends of research hotspots, keyword co-occurrence networks, and collaborative patterns among countries/regions, institutions, and authors. RESULTS: A total of 3381 articles related to glaucoma inflammation were extracted from WoSCC. The analysis showed that the USA had the highest research output in this field (29.04%, n=982), followed by China (18.40%, n=622) and UK (6.01%, n=203). Based on citation frequency and burst intensity, the USA also ranked as the most influential country. Baudouin C and Sun X were identified as the most productive authors, while Journal of Glaucoma and Investigative Ophthalmology & Visual Science were the journals with the highest number of published relevant articles. Additionally, keyword analysis revealed that “neuroinflammation”, “retinal ganglion cells (RGCs)”, “pathophysiology”, and “traditional Chinese medicine” are emerging research hotspots in the field of immune-inflammatory responses in glaucoma. CONCLUSION: This study presents a comprehensive bibliometric overview of research on glaucoma-related inflammation, indicating that this field has received extensive scientific attention with a steady upward trend in research activity. Furthermore, it establishes a theoretical basis for the development of neuroinflammation-targeted therapeutic strategies for glaucoma and emphasizes the necessity of strengthening interdisciplinary collaboration to promote the clinical translation of research findings.

Abstract:AIM: To assess the current research status and emerging trends of the choriocapillaris (CC) by bibliometric analysis. METHODS: Publications spanning from January 2013 to May 2023 were retrieved on June 27th, 2023, using the Web of Science Core Collection. Bibliometric and visualized analyses were performed employing the bibliometrix, CiteSpace and VOSviewer. RESULTS: A total of 1563 papers met the inclusion criteria, and a publication growth trend was observed. The United States was the leading country in the CC field. Retina and Investigative Ophthalmology & Visual Science stood out as highly impactful and prolific journals. Research topics in the CC field encompassed choroidal neovascularization, choroidal thickness, central serous chorioretinopathy, age-related macular degeneration, myopia, choroidal vascularity index, and diabetic retinopathy, based on the co-citation analysis. The keyword “high myopia” experienced a burst lasting until 2023. CONCLUSION: In the past decade, research in the field of CC has flourished due to recent advancements in choroidal imaging; with focus shifting towards elucidating its role in various diseases. This will provide novel insights into managing chorioretinal diseases and vision-preserving interventions.

Abstract:Growth hormone-releasing hormone (GHRH) is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones. In recent years, studies have found that GHRH possesses functions like anti-inflammation, promoting cell proliferation, and facilitating cell migration. It participates in regulating the development of uveitis and diabetic retinopathy. Additionally, it also has an impact on the development of retinal ganglion cells by modulating the inflammatory response and mediating the immune response. Given the important roles of GHRH in ophthalmic diseases, elucidating the molecular regulation of the GHRH-GHRH receptor (GHRHR) signal and the innovative development of intervention pathways that directly or indirectly target GHRH serve as strong evidence of how basic research guides innovation and translation. In this review, research reports on GHRH in ophthalmic diseases including retinal diseases and uveitis were summarized and analyzed.

Abstract:To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted a comprehensive review of current literature, focusing on viral entry pathways, receptor expression in ocular tissues, and associated clinical manifestations. This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular, histological, or clinical evidence. The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2 (ACE2), including transmembrane serine protease 2 (TMPRSS2), CD147, alanyl aminopeptidase N (ANPEP), dipeptidyl peptidase 4 (DPP4), angiotensin II receptor type 2 (AGTR2), and polymeric immunoglobulin receptor (PIGR), which are expressed in retinal, conjunctival, corneal, limbal, and photoreceptor cells. The virus may also reach ocular structures via neurovascular invasion. Clinically, patients with coronavirus disease 2019 (COVID-19) may present with a broad spectrum of ophthalmic manifestations, including conjunctivitis, hyperreflective lesions in the inner retinal layers, flame-shaped hemorrhages, cotton-wool spots, retinal pallor, hard exudates, and various forms of maculopathy, such as paracentral acute middle maculopathy and acute macular neuroretinopathy (AMN). These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury. Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis, appropriate ophthalmologic care, and the prevention of long-term visual sequelae in patients affected by COVID-19.

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