Abstract:

Abstract:AIM: To investigate whether hypoxia-activated microglia drive pathological neovascularization through extracellular matrix (ECM) remodeling and endothelial integrin signaling, a mechanism that may function in parallel with vascular endothelial growth factor (VEGF) signaling. METHODS: The oxygen-induced retinopathy (OIR) mouse model was used. Retinal phenotypes were assessed by flat mounts, histology, and vascular leakage assays. Key pathways were screened by transcriptomics and validated via Western blot, immunofluorescence, and quantitative polymerase chain reaction (qPCR). In vitro, brain microvascular endothelial cells were treated with conditioned medium from hypoxic microglia (Hyp-CM), with cell migration and tube formation assessed. Interventions employed the integrin β3 (ITGB3) inhibitor cilengitide, the focal adhesion kinase (FAK) inhibitor PF-573228 and a neutralizing anti-VEGF antibody. In vivo, cilengitide was administered by intravitreal injection to evaluate its therapeutic effect on neovascularization. RESULTS: OIR retinas showed significant avascularity, pathological neovascularization, and barrier disruption. Transcriptomics revealed activation of ECM-receptor interaction and focal adhesion pathways, with upregulation of Fn1 and Itgb3. Increased protein levels of fibronectin (FN) and ITGB3, alongside elevated phosphorylation of FAK and protein kinase B (Akt), were confirmed in vivo. Activated microglia co-localized with upregulated FN and ITGB3. Conditioned medium from Hyp-CM activated the ITGB3–FAK–Akt pathway in endothelial cells and promoted their migration and tube formation. These effects were nearly abolished by cilengitide or PF-573228. VEGF neutralization partially reduced Hyp-CM-induced migration and tube formation. Intravitreal injection of cilengitide significantly reduced retinal neovascularization in OIR mice. CONCLUSION: Hypoxia-activated microglia promote pathological angiogenesis, and the FN/ITGB3/FAK/Akt axis is identified as a key mediator of this process, revealing a novel mechanism that operates in parallel with VEGF signaling. Targeting this “hypoxia–microglia–ECM–integrin” axis represents a promising therapeutic strategy to overcome anti-VEGF resistance in ischemic retinopathy.

Abstract:AIM: To analyze the healing effect of a new hyaluronic acid (HA) photo-crosslinked ocular adhesive for corneal and conjunctival wounds and evaluate its clinical potential in ocular surface reconstruction. METHODS: Male New Zealand rabbits were included. A full-thickness corneal wound was induced in the superior corneal limbus, and a 5×5 mm2 conjunctival flap was dissected while leaving intact the lateral limbus of the cornea. The rabbits were randomly divided into corneal and conjunctival wound groups, each containing three subgroups. Histological findings and transmission electron microscopy (TEM) were used to compare wound healing parameters of inflammation and collagen remodeling at 7 and 14d post-injury. RESULTS: Thirty rabbits (14–16 weeks old, 3.0±0.5 kg) were included and were randomly assigned to either a corneal injury group (n=15) or a conjunctival injury group (n=15). Each group was further divided into three subgroups: control, enbucrilate, and HA photo-crosslinked adhesive (HPCA) groups (n=5 each). Anterior chamber leakage was observed until the first day in the control group, whereas corneal wound recovery was observed in the other two adhesive groups. Rabbits in the enbucrilate group exhibited significantly higher numbers of infiltrating inflammatory cells compared to HPCA group at both days 7 and 14 post-injury, along with irregular collagen fiber rearrangement. The HPCA group had fewer infiltrating inflammatory cells in the corneal wound area compared to the control (P=0.043, 0.033 on days 7 and 14 post-injury, respectively) and enbucrilate groups (P=0.004, 0.017 on days 7 and 14 post-injury, respectively). It displayed significantly fewer infiltrating inflammatory cells in conjunctival tissue wounds than the other two groups (P=0.043 and 0.033 on day 7 post-injury, both P<0.001 on day 14 post-injury). The regenerated conjunctival tissue in the HPCA group displayed a uniform collagen arrangement, indicating smoother, regular wound healing. CONCLUSION: The HPCA causes less inflammatory infiltration and more uniform collagen fiber arrangement during corneal and conjunctival tissue wound healing than control and enbucrilate groups, indicating its usefulness for ocular surface reconstruction.

Abstract:AIM: To explore the regulatory effect of long non-coding RNA H19 on the Nod-like receptor protein 3 (NLRP3) inflammasome and its functional role in the progression of diabetic retinopathy (DR). METHODS: Wild-type and H19 knockout rats were subjected to a high-fat and high-sugar diet combined with streptozotocin injection to establish an in vivo diabetes mellitus (DM) model. In vitro, rat primary retinal microvascular endothelial (CP-R114) cells were cultured under high-glucose conditions to mimic the diabetic microenvironment. The MTS assay was performed to evaluate cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of indicators related to glucose metabolism, lipid metabolism, oxidative stress, and inflammation in rat retinal tissues and CP-R114 cells. Hematoxylin and eosin (HE) staining was applied to observe the pathological morphological changes in retinal tissues. qRT-PCR was conducted to quantify the mRNA expression of H19, S-adenosylhomocysteine hydrolase (SAHH), and S-adenosylmethionine-dependent methyltransferase 3 beta (DNMT3b) in rat retinas. Western blotting and immunofluorescence staining were further utilized to detect the protein expression of SAHH, DNMT3b, NLRP3, Caspase-1, and interleukin (IL)-1β in retinal tissues. RESULTS: In DM model rats, H19 knockout significantly improved glucose and lipid metabolic disorders and alleviated oxidative stress. Notably, H19 deficiency effectively ameliorated retinal tissue injury. The expression levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and pro-inflammatory factors were markedly downregulated in H19-silenced DM rats. Mechanistically, H19 knockout upregulated the expression of SAHH and DNMT3b, while inhibiting the expression of NLRP3 inflammasome-associated proteins in DM rats. Consistent with the in vivo findings, H19 silencing suppressed NLRP3 inflammasome activation and elevated SAHH and DNMT3b expression in high-glucose-stimulated CP-R114 cells. CONCLUSION: This study demonstrates that H19 knockout alleviates DR progression in diabetic rats by activating the SAHH/DNMT3b signaling pathway and inhibiting NLRP3 inflammasome activation. Therefore, targeting H19 represents a promising novel therapeutic strategy for the clinical treatment of DR.

Abstract:AIM: To investigate the molecular mechanism by which columbianadin (CBN) exerts its antitumor effects in retinoblastoma (RB). METHODS: Y79 and WERI-Rb-1 cells were used for in vitro assays. Cell viability under different concentrations of CBN was assessed. The effects of CBN on RB cell behaviors were examined. In vivo, the antitumor efficacy of CBN was evaluated using a xenograft tumor model in BALB/c nude mice. Bioinformatic analysis was performed to predict potential molecular targets of CBN. The role of DNA topoisomerase II alpha (TOP2A) in activating the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was further explored. RB cells were infected with a lentivirus to overexpress TOP2A or treated with a PI3K/AKT inhibitor to analyze cellular behavior. A xenograft model was established using Y79 cells overexpressing TOP2A to validate the in vitro findings under CBN treatment. RESULTS: CBN inhibited proliferation, migration, and invasion, and promoted apoptosis of Y79 and WERI-Rb-1 cells. In vivo, CBN markedly reduced tumor growth in nude mice. TOP2A was highly expressed in RB cells, and its expression was downregulated by CBN treatment. Mechanistically, TOP2A promoted the malignant behavior of RB cells and tumor growth by activating the PI3K/AKT pathway. CONCLUSION: CBN inhibits RB progression by downregulating TOP2A protein expression, thereby blocking activation of the PI3K/AKT signaling pathway. These findings suggest that CBN could be a viable therapeutic candidate for treating RB.

Abstract:AIM: To explore a novel morphological feature of the meibomian gland (MG) and evaluate its prevalence and diagnostic utility in Demodex blepharitis. METHODS: This study included an initial cohort examined for Demodex using in vivo confocal microscopy and an additional validation cohort examined using conventional light microscopy. The new Demodex-infected qualitative (DQ) dropout was defined as the appearance of one or more fully atrophied glands among relatively healthy MG. Diagnostic efficiency was assessed using a receiver operating characteristic (ROC) curve, and diagnostic consistency was tested using Cohen’s kappa. The association between ocular surface parameters and DQ dropout was assessed. RESULTS: The initial cohort included 105 participants, comprising 70 Demodex-positive (DP; 18 males and 52 females; median age, 38y; range, 21–51y) and 35 Demodex-negative (DN; 11 males and 24 females; median age, 33y; range, 24–55y) individuals. The DQ dropout feature was 64.3% and 2.8% in the DP and DN groups, respectively (P<0.001). ROC analysis yielded an area under the curve (AUC) of 0.807. Substantial inter-rater agreement was achieved in confirming DQ dropout, with a Cohen’s kappa of 0.617. In the validation cohort of 887 patients, DQ dropout prevalence remained higher in the DP group than in the DN group (59.9% vs 28.5%, P<0.001), with strong expert agreement (kappa=0.642, P<0.001), and an AUC of 0.671. A multivariable logistic regression model incorporating tear meniscus height, MG area, and energy curve achieved an AUC of 0.969. CONCLUSION: This novel morphological feature of DQ dropout is common in Demodex infection, demonstrating good diagnostic ability and substantial inter-observer agreement.

Abstract:AIM: To evaluate the efficacy, degradation characteristics, safety, and patient satisfaction of biodegradable amniotic lacrimal duct repair stent (ALDRS) in adult patients with acquired lacrimal obstruction. METHODS: A multicenter, retrospective cohort study. Patients were stratified by anatomical site and obstruction severity into three cohorts: incomplete upper lacrimal pathway obstruction (punctal, canalicular, or common canalicular, cohort 1), incomplete nasolacrimal duct obstruction (cohort 2), and complete nasolacrimal duct obstruction (cohort 3). The primary endpoint was anatomical patency on lacrimal irrigation at 6mo. Secondary endpoints included functional success, stent degradation, complications, and validated patient-reported outcomes. RESULTS: A total of 54 patients (54 eyes, 10 males) with a mean age of 53.36±12.42y (range 29–88) were enrolled. ALDRS insertion was successful in 98.15% of procedures. Complete degradation was observed in 90.74% of eyes at 30d and in 100% by 6mo, with no residual material. The overall anatomical patency rate at 6mo was 81.48%. By cohort, patency was 100% (11/11), 88.89% (16/18), and 68.00% (17/25) for cohort 1, 2, and 3, respectively. No granuloma, punctal laceration, or silicone tube related complications occurred. Pre-existing chronic dacryocystitis was an independent risk factor for reduced patency [B=0.607, 95% confidence interval (CI): 0.165–1.048, t=2.763, P=0.008]. Overall satisfaction was comparable among cohorts, with all patients ranking preoperative communication and explanation highest. CONCLUSION: Biodegradable ALDRS combines avoidance of secondary removal with promotion of epithelialization, offering a safe and patient friendly option for adult acquired lacrimal obstruction. Lacrimal probing with ALDRS achieves favorable outcomes in cohort 1 and 2. In cohort 3, ALDRS is best reserved as a prophylactic adjunct after dacryocystorhinostomy. Chronic dacryocystitis or severe lacrimal sac fibrosis compromises efficacy.

Abstract:AIM: To facilitate structure-function analysis by evaluating the compatibility of newly added 10 extra test points in early-stage glaucoma cases with optical coherence tomography (OCT) and OCT-angiography (OCTA) glaucoma parameters in clinical practice. METHODS: Cases diagnosed with primary open angle glaucoma underwent Humphrey 24-2C visual field (VF) test, OCT, and OCTA tests on the same day. The arithmetic average of the central 10 extra points in the 24-2C VF was calculated, and its compatibility with OCT and OCTA parameters was assessed. Patients with low signal strength OCT and OCTA images, high fixation losses in VF, intraocular pressure of 25 mm Hg and above, systemic vascular diseases [diabetes mellitus (DM), hypertension (HT)] were excluded from the study. RESULTS: Totally 68 early-stage glaucoma cases (68 right eyes, 37 males) were included with the mean age of 64.52±8.89y. In the Spearman correlation test, all OCT and OCTA parameters except inside disc vascular density showed a positive correlation with the mean of additional VF test points (P<0.05 for all parameters, P=0.114 for inside disc vascular density). In multiple linear regression analysis, superior hemifield vessel density and whole image vessel density percentages were found to be significantly associated with additional points (P=0.029, 0.039, respectively). CONCLUSION: It is known that specific regions of the macula may be sensitive to early-stage glaucomatous damage. This suggests that in early-stage glaucoma, attention should be paid to central points in addition to peripheral findings on VF. The compatibility of the mean of 24-2C SITA-Faster VF central extra points with the defined OCTA parameters may demonstrate the value of OCTA in diagnosis and follow-up in early stages for clinics without access to the new software VF devices.

Abstract:AIM: To evaluate and compare the efficacy and safety of two treat-and-extend (T&E) regimens (2- and 4-week intervals, Δ2w and Δ4w) of intravitreal conbercept injections in patients with neovascular age-related macular degeneration (nAMD). METHODS: This 24-month prospective randomized controlled trial at the First Affiliated Hospital of Chongqing Medical University included patients with nAMD. Eyes were randomly assigned (1:1) to receive intravitreal conbercept (0.5 mg) with T&E regimens using 2- or 4-week interval adjustments (Δ2w and Δ4w groups). Key outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), superficial vascular density (SVD), deep vascular density (DVD), and large-medium vascular density (LMVD) within the 3 mm macular foveal region. The primary endpoint was the mean change in BCVA from baseline to the 2-year follow-up (noninferiority cutoff: 4 letters). RESULTS: Ultimately, 61 participants (68 eyes) completed the 2-year study. Baseline characteristics were similar between the two groups. At week 96, the mean number of injections was 11.17±1.13 in the Δ2w group (36 eyes, with the mean age of 70.42±9.31y) and 9.84±1.02 in the Δ4w group (32 eyes, with the mean age of 71.25±9.99y; P<0.001). The mean changes in BCVA were 5.19±6.58 and 5.91±5.51 letters (P=0.528), and Δ4w being noninferior to Δ2w (difference: 0.71 letters; 95%CI: -3.67 to 2.24). The mean changes in CRT were -118.97±106.97 and -134.98±128.77 μm (P=0.406), and the mean changes in SFCT were -30.03±17.48 and -32.55±22.73 μm (P=0.538), respectively. No significant intergroup differences in vascular densities were observed. Type 1 macular neovascularization had a higher baseline BCVA and required more injections than those with other macular neovascularization subtypes. CONCLUSION: Intravitreal conbercept injections administered via 2- and 4-week intervals show similar efficacy and safety. The reduced injection frequency in the Δ4w regimen may help lower the overall treatment burden, and individualized therapy based on nAMD subtypes may further optimize clinical outcomes.

Abstract:AIM: To investigate the changes of fundus autofluorescence (FAF) patterns in myopic maculoschisis eyes with macular detachment (MD) following macular buckling (MB) surgery. METHODS: Patients who received MB surgery for myopic maculoschisis with MD between August 2018 and August 2020 were reviewed. All participants underwent comprehensive preoperative and postoperative ophthalmic evaluations. Autofluorescence (AF) imaging was conducted using a Spectralis HRA+optical coherence tomography (OCT) device. RESULTS: A total of 49 eyes (from 49 patients) were included. The mean age of participants was 55.02±11.21y (range: 31–77y), with 33 females (67.35%, F:M=2.1:1). The duration of postoperative follow-up was 32.61±16.00mo, with a range of 12 to 69mo. Three different preoperative AF patterns at the macula were identified: unremarkable AF (20 eyes, 40.8%), patchy hyper-AF (15 eyes, 30.6%), and diffuse hypo-AF (14 eyes, 28.6%). Compared with preoperative visual acuity, the mean visual improvement at final visit was 9.84±6.04, 16.60±6.87, and 12.27±5.61 (P<0.05) letters in the eyes with unremarkable AF, patchy hyper-AF, and diffuse hypo-AF, respectively. Early postoperative FAF imaging captured at 1mo after surgery revealed two different AF patterns in 36 eyes: unremarkable AF (10 eyes, 27.8%) and round-like hyper-AF (26 eyes, 72.2%). Furthermore, the above 26 eyes with round-like hyper-AF all evolved into unremarkable AF gradually during the following observation period. Particularly, a total of 13 eyes (26.5%) displayed retinal pigment epithelium (RPE) atrophy at the edge of buckle, which were first detected after a mean follow-up of 14.73±6.21mo. CONCLUSION: FAF patterns in myopic maculoschisis eyes with MD show potential as biomarkers for evaluating MB surgery. Postoperative RPE atrophy at the edge of buckle deserves vigilant clinical attention.

Abstract:AIM: To investigate the changes in corneal densitometry (CD) after small incision lenticule extraction combined with accelerated corneal cross-linking (SMILE Xtra) for correcting moderate to high myopia and to analyze their correlation. METHODS: In this non-randomized retrospective comparative study, participants who underwent surgery were enrolled in the standalone SMILE group and SMILE Xtra group, respectively. Preoperative and postoperative uncorrected visual acuity, spherical equivalent (SE), and CD values were recorded at 1, 3, 6, and 12mo. Measurements were taken in the central (0–2 mm), paracentral (2–6 mm), and peripheral (6–10 mm) zones, as well as in the anterior 120 μm, central, and posterior 60 μm layers of the cornea. A generalized linear mixed model (GLMM) was used to compare CD values between groups and at different time points, and the correlation between postoperative CD values and residual bed thickness (RBT) was analyzed. RESULTS: Totally 31 participants (62 eyes, mean age 20.32±2.76y) were in the standalone SMILE group and 28 participants (53 eyes, mean age 20.45±2.08y) in SMILE Xtra group. At 12mo postoperatively, there were no statistically significant differences in uncorrected visual acuity or SE between the two groups (P>0.05). Preoperative CD values in all regions showed no significant differences between groups (all P>0.05). In the central (0–2 mm) and paracentral (2–6 mm) zones, and the anterior, central, and total stromal layers, group, time, and interaction effects were all significant (all P<0.001). At 1, 3, and 6mo postoperatively, CD values in the SMILE Xtra group were significantly higher than those in the SMILE group within the 0–2 mm and 2–6 mm diameter ranges, as well as in the anterior, central, and total layers (all P<0.05). At 12mo postoperatively, CD values in the anterior layer remained significantly higher in the SMILE Xtra group compared to the SMILE group (P=0.007), whereas no statistically significant differences were observed in other diameter ranges or stromal layers (all P>0.05). Correlation analysis revealed that at 12mo postoperatively, CD values in all regions of both groups showed a significant positive correlation with RBT (all P<0.05), except for the anterior layer in the SMILE group, which showed no significant correlation with RBT (r=0.114, P=0.380). CONCLUSION: SMILE Xtra induces transient early increase in CD, primarily in the anterior and central layers. Although values stabilize or decline by 12mo postoperatively, the clinical significance of these long-term patterns requires cautious interpretation, considering the potential influence of post-surgical structural changes. Further research is necessary to fully elucidate the underlying contributions to these densitometric changes.

Abstract:AIM: To develop and externally validate a risk prediction model for adolescents wearing orthokeratology (OK) lenses to predict the probability of suboptimal control effects. METHODS: A retrospective analysis of myopic children who used OK lenses consistently for at least 18mo between January 2021 and March 2023 were conducted. Various ophthalmic examinations and recorded baseline parameters were performed. A risk prediction model was developed using multifactorial logistic regression analysis, and the model’s discrimination and calibration were assessed using the area under the receiver operating characteristic curve (AUC) and Brier score. RESULTS: The modeling group included 228 eyes (mean age, 10.46±1.99y; 55.7% males), with 120 right eyes (52.6%) and 108 left eyes (47.4%), and the validation group included 100 eyes. Anisometropia was absent in 174 eyes (76.3%) and present in 54 eyes (23.7%). The risk prediction model identified age, anisometropia, and corneal diameter as independent predictors for the control effect of OK lenses. The model showed good discrimination [AUC 0.781, 95% confidence interval (CI) 0.721–0.841] and acceptable calibration in derivation (Brier score 0.186) in the validation group. CONCLUSION: The study constructs a risk prediction model to forecast the likelihood that myopic adolescents will not achieve the ideal control effect after wearing OK lenses, offering proactive and effective guidance for frontline clinical practitioners in devising diagnostic and therapeutic strategies.

Abstract:AIM: To evaluate the efficacy of progressive defocus rigid gas permeable (DRGP) contact lenses in slowing down myopic progression and analyze the factors may influence axial length (AL) elongation in myopic children. METHODS: This was a retrospective study conducted on school-age children with myopia of -5.00 D or higher who were fitted with DRGP lenses. A matched control group wearing single-vision (SV) spectacles was selected based on comparable baseline age and refractive error. The AL was measured at baseline and at 6-month intervals thereafter. Changes in AL were compared between the groups. RESULTS: The DRGP lenses group comprised 56 subjects (39 females, mean age 11.96±2.32y), the SV spectacle group comprised 53 subjects (29 females, mean age 11.09±2.33y). After a 12-month follow-up period, the mean axial elongation was measured to be 0.19±0.13 mm in the DRGP group and 0.45±0.20 mm in the SV group, respectively (P<0.001). The use of DRGP lenses by children resulted in a 57.8% lower AL of the eye compared to the use of spectacles over the one-year period. Concurrently, the treatment effect was found to be negatively correlated with the baseline age (r=-0.46, P<0.001) and flat keratometry (r=-0.34, P=0.010). CONCLUSION: Daily wearing of the DRGP lenses significantly curbs axial elongation in children when compared with SV lenses.

Abstract:AIM: To compare the ocular surface phenotype and tear cytokine profile of primary biliary cholangitis (PBC) patients with and without concomitant Sjögren’s syndrome (SS). METHODS: This case-control study enrolled 21 PBC patients with SS (PBC-SS group), 23 PBC patients without SS (PBC-only group), and 20 age- and sex-matched healthy controls. All participants underwent standardized ocular surface assessments including Ocular Surface Disease Index (OSDI) questionnaire, lipid layer thickness (LLT), incomplete blink rate, tear meniscus height (TMH), non-invasive tear film breakup time (NIBUT), meibomian gland loss (MGL), Schirmer I test, and corneal fluorescein staining (CFS). Tear concentrations of six cytokines [interleukin (IL)-6, IL-8, IL-10, vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)] were measured using a customized ultra-sensitive quantitative antibody array (QAA-CUST) platform. RESULTS: The three groups were comparable in terms of age (54.2±8.6, 52.8±9.3, and 53.5±8.9y, respectively; P=0.873) and gender distribution (female predominance: 100%, 91.3%, and 95%; P=0.412). Compared to PBC-only patients, the PBC-SS group exhibited significantly worse ocular surface parameters, including higher OSDI scores (45.6±12.3 vs 28.4±9.7), lower Schirmer I values (3.8±2.1 vs 7.6±3.2 mm/5min), reduced TMH (0.18±0.06 vs 0.22±0.05 mm), and shorter NIBUT (4.2±1.8 vs 6.2±2.0s), all P<0.001. Both PBC groups showed reduced LLT and increased MGL compared to healthy controls (P<0.05), while CFS scores were similarly elevated in both PBC groups versus controls (P<0.001). Tear cytokine analysis revealed significantly higher levels of IL-6, IL-8, and VCAM-1, and lower levels of IL-10 in the PBC-SS group compared to the PBC-only group (all P<0.05). VEGF was elevated in both PBC groups versus controls (P<0.05). In PBC-SS patients, VCAM-1 demonstrated the strongest correlations with Schirmer I values (ρ=-0.71, P<0.001) and CFS scores (ρ=0.68, P<0.001). CONCLUSION: Compared to PBC-only patients, PBC patients with SS exhibit a distinct and more severe ocular surface phenotype characterized by pronounced aqueous tear deficiency and a unique tear inflammatory signature with elevated VCAM-1, IL-6, IL-8 and reduced IL-10. Tear cytokine profiling, particularly VCAM-1, may serve as a valuable non-invasive tool for identifying SS comorbidity in PBC patients and monitoring disease severity.

Abstract:AIM: To determine the distribution and normative range of corneal diameter in individuals aged over 60, and its association with demographic variables, certain comorbidities, anthropometric measurements, additional ocular biometric indices, and refractive errors. METHODS: This population-based cross-sectional study involved participants aged over 60 residing in Tehran, selected by a multi-stage cluster random sampling. Following the acquisition of informed consent, comprehensive ophthalmological and optometric evaluations, including slit lamp examination, visual acuity assessment, and refraction, were conducted. Ocular biometric parameters, including corneal diameter, were assessed using the Pentacam AXL. RESULTS: A total of 4596 eyes (2292 right eyes and 2304 left eyes) from 2414 older individuals were examined. The mean age with 95% confidence interval (CI) of the study participants was 66.74y (66.51–66.97y), with 58.68% identifying as female. The corneal diameter in the older population had a normal distribution, with a mean of 11.82 mm (95%CI: 11.80–11.84), and a normal range of 11.02–12.62 mm. According to the results of multiple linear regression, a deeper anterior chamber (b=0.30, P<0.001), a university education level (b=0.08, P=0.001), and hyperopia (b=0.04, P=0.005) exhibited a positive correlation with corneal diameter, whereas female gender (b=-0.05, P<0.001), a thicker cornea (b=-0.01, P<0.001), a higher mean keratometry (b=-0.09, P<0.001), and astigmatism (b=-0.03, P=0.013) demonstrated an inverse correlation with corneal diameter. The corneal power was the most important factor that influencing corneal diameter. Nonetheless, the variables of myopia, axial length, diabetes, blood pressure, body mass index (BMI), economic situation, and age exhibited no significant association with corneal diameter. CONCLUSION: The corneal diameter range measured by Pentacam AXL in the elderly population is greater than certain prior studies and lesser than others. The findings serve as a reference for clinicians assessing corneal diameter in the elderly for clinical application.

Abstract:AIM: To determine the annual trends and risk factors for delayed access to care in community hospitals across Central Thailand—an area with high occupational injury risk. METHODS: This retrospective cross-sectional study analyzed data from four community hospitals in Central Thailand over six years (October 1, 2018–September 17, 2024). Patients aged ≥20y with ocular injuries, identified via International Classification of Diseases-10 (ICD-10) codes, were included. Demographics, injury characteristics, and care-seeking behaviors were recorded. Delayed access was defined as presentation >24h post-injury. Linear and logistic regression models were used to identify associated risk factors. Annual fiscal trends were analyzed to assess year-to-year patterns in delayed healthcare access. RESULTS: Among 6571 ocular injury cases, 4034 (61.4%) were male, with median age 43y [interquartile range (IQR) 31–57y], and 3983 (79.3%) were manual laborers. Delayed healthcare access was observed in 2426 cases (36.9%). Significant risk factors included age ≥60y [aOR: 1.55; 95% confidence interval (CI): 1.32–1.82], visits to F2-level hospitals [adjusted odds ratio (aOR): 2.03; 95%CI: 1.73–2.38], and outpatient visits (aOR: 14.01; 95%CI: 12.18–16.12). In F2 hospitals, subgroup analysis revealed a U-shaped reduction in delayed healthcare access for ocular injuries during the COVID-19 pandemic (2019–2021), adjusted for age and gender. CONCLUSION: This first in-depth study of ocular injuries in Central Thailand’s community hospitals found persistently high delayed presentations, with older age, F2 hospital visits, and outpatient department (OPD) attendance as key contributing factors. The trend during the COVID-19 pandemic highlights the important role of lower-tier community hospitals in providing prompt and accessible care for patients. Strengthening healthcare infrastructure and public awareness is essential to ensure timely care and reduce preventable vision-related complications.

Abstract:AIM: To evaluate the efficacy and safety of scleral lenses (SLs) in patients with keratoconus. METHODS: Electronic databases including PubMed, Scopus, Web of Science, Embase, and Cochrane Library were systematically searched to find the articles on visual function and patient satisfaction following SLs fitting. A random-effects model was applied to specify the pooled values. RESULTS: Of 833 studies, 19 articles (704 eyes) and 14 studies (475 eyes) were included in qualitative and quantitative synthesis, respectively. Pooled mean difference (PMD) of best corrected visual acuity (BCVA) was -0.37 [95% confidence interval (CI), -0.48 to -0.26] logMAR in favor of SLs treatment. SLs markedly reduced ocular and corneal higher-order aberrations and increased the quality of vision. The overall pooled values for comfort, visual quality and patient satisfaction with SLs were 4.19 (95%CI, 3.83 to 4.55), 4.30 (95%CI, 3.97 to 4.64), and 80.83% (95%CI, 71.54% to 90.13%), respectively. The most reported complications were lens breakage (26.1%) and conjunctival injection (11.4%–15.8%). CONCLUSION: SLs fitting leads to improved visual outcomes and patient satisfaction in patients with keratoconus.

Abstract:AIM: To evaluate the pooled magnitude of retinopathy of prematurity (ROP) among infants’ populations in East Africa. METHODS: A literature search was conducted using PubMed/MEDLINE, Google Scholar, Scopus, and African Journals Online to identify studies from East African published up to August 2025 that reported the magnitude of ROP and its associated factors. The quality of the included cohort and cross-sectional studies was assessed using a modified Newcastle-Ottawa Scale. A random-effects Meta-analysis was used to estimate the pooled magnitude of ROP and adjusted odds ratios (aORs) for associated factors, with results presented using 95% confidence intervals (CI). Heterogeneity among studies was assessed using the I² statistic, and subgroup analysis and meta-regression were performed to explore its sources. Publication bias was assessed using funnel plots and Egger’s regression test. RESULTS: A total of 11 studies were included. The pooled magnitude of ROP in East Africa was 18% (95%CI: 13%–24%, I2=95.77%). The Meta-analysis result showed that infants who received oxygen therapy (pooled OR=4.61, 95%CI: 1.88–7.33), neonates with birth weight less than 1500 g (pooled OR=5.82, 95%CI: 2.89–8.75), and respiratory distress syndrome (pooled OR=3.92, 95%CI: 2.54–5.29) were factors associated with ROP. CONCLUSION: ROP is a significant public health concern in East Africa, affecting nearly one in five preterm infants. Policymakers and healthcare providers should prioritize evidence-based interventions targeting the prevention and early detection of ROP to mitigate its long-term impact on childhood blindness.

Abstract:Diabetic retinopathy (DR) is the leading cause of preventable blindness in working-age adults globally. Current therapies mainly target advanced vascular lesions, leaving early metabolic and inflammatory dysregulation unaddressed. Dysregulated lipid metabolism acts as a critical upstream initiator of DR, converging with oxidative stress and chronic inflammation to form a self-amplifying pathogenic loop driving retinal neurovascular degeneration. Peroxisome proliferator-activated receptors (PPARs) are master transcriptional regulators linking lipid metabolism, oxidative stress, and inflammation. This review systematically delineates the synergistic pathogenic network in DR, comprehensively discusses the pleiotropic retinal protective effects of PPARα and PPARγ, and summarizes the latest advances in PPAR-targeted nano-drug delivery systems that overcome the limitations of traditional agonists. Finally, we highlight key challenges and future directions to advance precision therapy for DR.

Abstract:AIM: To evaluate the long-term prognostic outcomes associated with different treatment regimens for PDR, including panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (anti-VEGF) therapy, vitrectomy, and combination approaches. METHODS: A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library from database inception through March 31, 2024, with manual supplementary screening extended to June 30, 2024. Randomized controlled trials (RCTs) and comparative observational studies that directly evaluated at least two treatment regimens with a minimum follow-up of 1y were included in the principal therapeutic synthesis; imaging, screening, epidemiologic, and disease-characterization studies were retained as contextual evidence. Owing to substantial clinical and methodological heterogeneity, findings were synthesized through structured narrative synthesis in accordance with SWiM guidance, with evidence certainty assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The evidence base comprised 20 studies encompassing 8742 participants and 9521 eyes. Major comparative trials, interpreted as moderate-certainty evidence, indicated that anti-VEGF therapy (ranibizumab) and PRP achieved broadly comparable long-term visual acuity outcomes in selected trial populations receiving structured follow-up. Anti-VEGF therapy was associated with better visual field preservation and a lower cumulative incidence of vision-impairing diabetic macular edema (DME) compared with PRP [22% vs 38%; hazard ratio (HR) 0.4, 95%CI: 0.3–0.7]. Combination therapy (PRP plus ranibizumab) demonstrated favorable neovascular regression in selected small comparative studies, and perioperative anti-VEGF adjuncts improved intraoperative conditions and reduced early postoperative hemorrhage in vitrectomy-treated eyes. CONCLUSION: Anti-VEGF therapy and PRP may provide broadly comparable long-term visual acuity outcomes in selected PDR patients, though important differences exist in treatment burden, visual field preservation, and complication profiles. Treatment selection should be individualized according to DME status, vitreous hemorrhage, tractional or fibrovascular components, prior PRP, anticipated adherence, and healthcare accessibility, with long-term surveillance remaining essential given the chronic and progressive nature of PDR.

Abstract:AIM: To evaluate the association between findings at the first retinopathy of prematurity (ROP) exam and the subsequent development of type 1 ROP in a large registry of infants. METHODS: A retrospective cohort study of the records of infants (n=1582) screened for ROP (2013–2022) was conducted using an ROP registry. Logistic regression using generalized estimating equations was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of developing type 1 ROP following any ROP at initial exam, or for infants who required a one-week follow-up exam following initial exam. RESULTS: Gestational age at delivery of 1582 infants (834 males) were 28.8±2.5wk. Infants with any ROP noted at initial exam had increased odds of developing type 1 ROP [OR=3.64, 95%CI (1.93, 6.88), P<0.001] compared to infants without any ROP noted at initial exam. Infants who required a one-week follow-up exam for any reason after initial ROP exam had even higher odds of developing type 1 ROP [OR=9.31, 95%CI (5.63, 15.4), P<0.001] compared to infants who did not require a one-week follow-up exam. CONCLUSION: Infants with ROP noted at initial exam and infants requiring a one-week follow-up exam are significantly more likely to develop type 1 ROP. When signs of ROP or concern for ROP are noted by the ophthalmologist at the first ROP exam, there is a significant increase in the likelihood of developing type 1 ROP. These data will assist ophthalmologists in informing families and neonatologists of the risk of ROP from the onset of ROP exams.

Abstract:AIM: To explore the efficacy of teprotumumab N01 (IBI311), an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, in thyroid eye disease (TED) patients who had failed glucocorticoids. METHODS: In this pilot case series study, patients with TED failing intravenous or oral glucocorticoid treatments were treated with teprotumumab N01 (10 mg/kg for the first infusion then 20 mg/kg every 3wk for subsequent 3 infusions). Proptosis, clinical activity score (CAS), Gorman diplopia score, magnetic resonance imaging (MRI), adverse events and laboratory tests were evaluated during the treatment. RESULTS: The patients’ mean age was 38.7y, 6 of 10 were female, and TED duration of these patients ranged from 0.8 to 5y. At week 12, 7 patients had proptosis response, 6 achieved a CAS of 0 or 1 and 5 achieved an overall response. For patients with proptosis improvement, MRI also showed consistent changes including volume decrease of extraocular muscles and orbital fat tissues. The incidence of adverse events was low. CONCLUSION: Teprotumumab N01 infusions result in proptosis response and clinical activity improvements accompanied with favorable safety profile in TED patients who had failed glucocorticoids. Randomized controlled trials will be conducted to further assess the efficacy and safety of teprotumumab N01 in TED patients.

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