Abstract Background This study aimed to observe the safety and effectiveness of combined phacoemulsification and goniosynechialysis (PEI-GSL) in patients with primary angle-closure glaucoma (PACG) and coexisting cataracts. Methods This multicenter prospective study enrolled 289 consecutive patients with PACG and cataracts who were treated using PEI-GSL between November 1, 2022 and March 12, 2024. All patients underwent comprehensive ocular evaluations at baseline, at 1 week, and at 1, 3, 6, and 12 months postoperatively. Complete success was defined as achieving an intraocular pressure (IOP) of 6–18 mmHg without antiglaucoma medications or reoperation. Qualified success was similarly defined but allowed antiglaucoma medications. Results Among patients with PACG, 237 (82.0%) of 289 completed a 12-month follow-up. The baseline IOP decreased from 22.9 ± 10.2 to 14.0 ± 3.1 mmHg at 12 months, and the number of antiglaucoma medications declined from 2.08 ± 1.23 to 0.14 ± 0.52. The complete and qualified success rates were 80.6% and 88.3%, respectively. Postoperative complications occurred in 49 (17.0%) patients; while 3 (1.0%) patients underwent yttrium-aluminum-garnet (YAG) laser capsulotomy and 6 (2.1%) required glaucoma surgery. Multivariate Cox regression analysis revealed that the anterior chamber depth ( P = 0.044) and axial length ( P = 0.050) were positively associated with qualified success. The complete and qualified success rates among patients with advanced PACG were 78.2% and 87.9%, respectively. Conclusion We demonstrated that PEI-GSL is an effective and safe treatment for patients with PACG and coexisting cataracts, even in advanced stages.
To compare the axial length (AL) elongation between orthokeratology (OK) and highly aspherical lenslets (HAL) in children with myopia. This retrospective study included children with spherical equivalent refraction (SER) ranging from − 0.50 to − 9.00 D who were treated with OK lenses or HAL spectacles. Propensity score matching (PSM) was performed to balance baseline characteristics, including age, SER, sex, and baseline AL. The primary outcome was the 12-month AL elongation. Subgroup analyses were conducted according to age (8–9, 10–11, and 12–14 years) and refractive error categories (mild: − 0.50 to − 3.00 D; moderate: − 3.00 to − 5.00 D; high: − 5.00 to − 9.00 D). After PSM, 3,122 matched pairs (n = 6,244) with balanced baseline characteristics were included. Overall, OK group had greater AL elongation over 12 months than the HAL group (0.20 ± 0.18 mm vs. 0.15 ± 0.17 mm; P < 0.001). In age-stratified analyses, the OK group demonstrated greater AL elongation than the HAL group among younger children, including those aged 8–9 years (0.26 ± 0.18 mm vs. 0.19 ± 0.18 mm; P < 0.001) and 10–11 years (0.17 ± 0.17 mm vs. 0.12 ± 0.17 mm; P < 0.001). By contrast, no significant between-group difference was observed in children aged 12–14 years (P = 0.305). SER-stratified analyses revealed a refractive-error-dependent pattern. In children with mild myopia (− 0.50 to − 3.00 D), the OK group demonstrated greater AL elongation than the HAL group (P < 0.001). By contrast, among children with high myopia (− 5.00 to − 9.00 D), the OK group had lower AL elongation than the HAL group (P < 0.001), while no significant difference was observed for moderate myopia (P = 0.950). Subgroup analyses were performed using a propensity score-matched cohort. HAL were associated with less AL elongation in younger children and those with mild myopia, whereas OK lenses were associated with less AL elongation in children with high myopia. No significant differences between treatment modalities were observed in children with moderate myopia or in older children.
Age-related macular degeneration (AMD) is a leading cause of visual impairment; however, robust drug targets for primary prevention remain elusive. This study aimed to identify candidate genetic loci and putative genetically supported proteins for AMD through integrative genomics and proteomics. A genome-wide association study (GWAS) meta-analysis (28,543 cases and 1,072,092 controls) was performed to identify risk loci, followed by proteome-wide Mendelian randomization (MR), colocalization, and multi-omics summary-data-based MR with heterogeneity in dependent instruments (SMR-HEIDI) analyses to infer genetically supported proteins. Functional characterization included gene enrichment, single-cell RNA sequencing, mediation across 731 immunophenotypes, and a mouse knockout assessment. Druggability was evaluated using the Drug–Gene Interaction Database. The GWAS meta-analysis identified 10 candidate genetic loci for AMD (including three previously reported and seven newly identified loci). Proteome-wide MR and colocalization analyses uncovered 23 genetically supported plasma proteins (11 risk and 12 protective factors). Multi-omics SMR-HEIDI analysis prioritized LAMC2 and PLTP as first-tier risk genes, which was consistently supported across protein, expression, and methylation levels. Single-cell RNA sequencing revealed cell-type-specific enrichment of key genes in monocytes and stromal/progenitor-like cells within AMD retinas, and subsequent mediation analysis identified specific immune traits, most notably regulatory T-cell subsets, as potential partial mediators of AMD risk. Druggability assessment identified 15 target genes, and bioinformatic enrichment nominated cyclophosphamide. Given the toxicity profile of cyclophosphamide, this computational finding serves strictly as a pathway indicator, reinforcing the broader therapeutic relevance of modulating the identified immune-related targets. Our integrative analyses identified candidate genetic loci and genetically supported proteins for AMD, providing a foundation for translating genomic findings toward primary prevention. The exploratory nature of this study highlights the need to experimentally validate the proposed targets and underlying mechanisms.
This study aimed to explore the risk factors associated with bilateral involvement and to develop a predictive model for visual prognosis in Chinese patients with non-arteritic anterior ischemic optic neuropathy (NAION). In this retrospective database-related meta-analysis, we retrospectively identified patients with NAION from the Chinese Neuro-Ophthalmic Diseases project database between September 2020 and December 2024. The clinical characteristics of the patients were summarized. Logistic and stepwise regression analyses were performed to identify the factors associated with bilateral involvement. Patients were randomly divided into training (75
Abstract Background The purpose of this study was to characterize the longitudinal refractive outcomes of orbital decompression in thyroid eye disease (TED), compare refractive trajectories across decompression strategies, and identify the anatomical correlates and baseline predictors of postoperative refractive changes. Methods This retrospective longitudinal study included 57 eyes of 46 patients with moderate-to-severe TED who underwent orbital decompression. Comprehensive ophthalmic evaluations including eyelid position parameters, refractive and axial measurements, and corneal biomechanical and tomographic assessments were performed preoperatively and during postoperative follow-up. Postoperative observations were analyzed using generalized estimating equations (GEE) models with restricted cubic splines, with time treated as a continuous variable to allow flexible modeling of temporal patterns. Multivariate GEE models were used to compare decompression strategies, evaluate associations between postoperative ocular biometric changes and postoperative refractive changes, and identify baseline predictors of clinically significant postoperative myopic drift. Results Orbital decompression was associated with a biphasic pattern of refractive change characterized by an initial myopic shift, followed by partial hyperopic recovery over time ( P < 0.001), with the greatest myopic shift occurring at approximately 2–3 months postoperatively. The refractive trajectories differed significantly across decompression strategies. Compared with one-wall decompression, two-wall decompression demonstrated a greater magnitude and more rapid progression of refractive change, as well as an increased risk of clinically significant myopic drift, independent of decompression extent. Standardized GEE analyses identified postoperative changes in measured axial length as the strongest correlate of postoperative refractive change ( P < 0.001). Additional associations were observed for changes in exophthalmos, eyelid position, corneal biomechanics, and corneal tomographic parameters. Several baseline ocular biometric parameters were independently associated with susceptibility to clinically significant postoperative myopic drift. Conclusions Orbital decompression induces dynamic postoperative refractive changes that vary according to decompression strategy and individual ocular characteristics. Postoperative refractive changes appeared to peak at approximately 2–3 months and partially recovered thereafter, with refractive status gradually approaching relative stabilization over time, suggesting that definitive refractive correction may be better deferred until postoperative stabilization. These findings provide clinically relevant insights into postoperative refractive behavior and may support individualized surgical planning and perioperative management for TED.
Abstract Background To assess the long-term effects of orthokeratology (ortho-k) lenses with varying back optic zone diameters (BOZDs) on corneal biomechanical properties and explore their relationship with myopia control. Methods This 1-year prospective, randomized, double-blind, self-controlled study enrolled 36 myopic children aged 9–12 years. Thirty subjects (60 eyes) completed the 1-year follow-up period. The subjects were randomly fitted with a 5-mm BOZD (5BOZD) lens in one eye and a 6-mm BOZD (6BOZD) lens in the fellow eye. Corneal biomechanics were measured using Corvis ST at baseline and at 1 day, 7 days, 1 month, 6 months, and 12 months after ortho-k wear. Axial length (AL) was measured at baseline, 6 months, and 12 months after ortho-k wear, and AL elongation (ΔAL) was calculated relative to baseline. Statistical analyses were performed to compare intergroup differences and examine the correlations between ΔAL and changes in biomechanical parameters. Results ΔAL was significantly smaller in the 5BOZD groups compared to the 6BOZD groups at both 6 and 12 months ( P < 0.05). The stiffness parameter at first applanation (SP-A1) significantly increased at 6 months in both groups ( P < 0.05). At 12 months, the first applanation time (A1 time) and integrated radius significantly increased, while the first applanation velocity (A1 velocity) and stress–strain index (SSI) significantly decreased in both groups ( P < 0.05). In the 6BOZD group, ΔAL showed a significant positive correlation with ΔA1 time at 6 and 12 months (r 6m = 0.385, r 12m = 0.424, P < 0.05). Conclusions Long-term ortho-k therapy increased SP-A1, A1 time, integrated radius, and decreased A1 velocity, reflecting enhanced corneal resistance and elasticity. Compared to the 5BOZD lens, the traditional 6BOZD lens demonstrated relatively greater corneal elasticity, possibly reducing myopia control efficacy. A smaller BOZD may offset these corneal biomechanical changes and improve the management of myopia. Trial registration Chinese Clinical Trial Registry (ChiCTR2200061048).
Abstract Background Identifying individuals at high risk of axial elongation is crucial for managing adults with high myopia, as further elongation substantially increases the risk of vision-threatening complications. This study aimed to identify the optimal predictors for axial elongation in this population. Methods This prospective cohort study enrolled 1025 eyes from 532 adults with high myopia (18–60 years). We evaluated the predictive performance of nine candidate variables for rapid axial elongation, defined as a 2-year axial elongation of at least 0.10 mm. Predictors were selected using bidirectional stepwise regression. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and the incremental value of the new model was quantified using integrated discrimination improvement (IDI). Results The mean annual axial elongation rate was 0.020 ± 0.051 mm/year, and 24.78% of eyes developed rapid axial elongation. Stepwise regression constructed a full model (AUC = 0.811) including six predictors—age, sex, axial length, best-corrected visual acuity, choroidal thickness (ChT), and vascularity index. ChT showed the highest individual discriminative ability (AUC = 0.728), followed by age (AUC = 0.666). Removing age or ChT from the full model reduced the AUCs to 0.735 and 0.753, respectively (both P < 0.001), with IDIs of − 0.116 and − 0.095 (both P < 0.001). In contrast, excluding sex only resulted in an IDI of − 0.008 (P = 0.032). Simplified models combining age and ChT, with or without sex, showed discrimination comparable to that of the full model, with only modest reductions in predictive performance (IDIs: − 0.028 and − 0.033, respectively; both P < 0.05). In the bivariate model, the predictive cut-off of ChT decreased progressively with age, ranging from 187 µm at age 20 to 29 µm at age 60. The results remained consistent in sensitivity analyses using alternative axial elongation definitions (0.05 mm and 0.15 mm). Nonlinear relationship analyses revealed that thinner choroids were associated with faster axial elongation rate only below an inflection point. Conclusions ChT and age are the optimal predictors for axial elongation in adults with high myopia. These findings establish their dominant role in personalized management and support further investigation into choroidal architecture to guide proactive, choroid-centered strategies. Trial Registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR2100047424).
BACKGROUND:Atropine is an effective agent for myopia control; however, clinical reports have indicated potential side effects associated with inducing or exacerbating dry eye disease (DED). It remains unclear whether the therapeutic targets involved in atropine-mediated myopia control overlap with those potentially associated with ocular surface effects. Therefore, this study aimed to characterise the shared or distinct target landscape and plausible molecular pathways through which atropine may contribute to myopia control while also being associated with dry eye-related symptoms. METHODS:In silico analysis was performed to explore the molecular interactions of atropine in controlling myopia and DED. The target lists for atropine, myopia, and DED were sourced from six public databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified common and unique pathways. A protein-protein interaction (PPI) network was created and analysed using Cytoscape to identify hub genes using six ranking algorithms. Targets were stratified into shared Class I and myopia-prioritised Class II categories by integrating retinal and pan-ocular expression data. Molecular docking and molecular dynamics (MD) simulations were conducted to assess the binding affinities of atropine to prioritised targets. RESULTS:A total of 57 shared Class I and 19 Class II myopia-prioritised targets were identified; 19 hub genes were consistently ranked across the six algorithms. Class I targets converge on inflammatory and extracellular-matrix-remodelling pathways. Evidence of ocular expression supports the biological relevance of the prioritised targets in both classes. Docking showed favourable atropine binding to representative Class I targets (EGFR, MMP2, MMP9, and MAPK1) and Class II candidates (PIK3R1 and AKR1B1). MD simulations supported stable complexes for eight atropine-target pairs, with MM-PBSA binding free energy estimates supporting the computational prioritisation. CONCLUSIONS:Shared Class I targets may potentially link the effects of atropine on both myopia control and DED, along with Class II targets specific to myopia, thereby generating testable hypotheses regarding the dual ocular effects of atropine and informing future mechanistic and translational studies.
Abstract Background This study aimed to evaluate the individual and joint effects of reduced visual acuity (VA) and restricted visual field (VF) on the reading performance of Chinese readers under standardized low-vision simulation. Methods Eighty-one adults were randomized to three simulated distance VA levels using Bangerter foils: normal VA (≤ 0.30 logMAR), mild VA impairment (VAI) (0.30 logMAR< VA ≤ 0.52 logMAR), and moderate VAI (> 0.52 logMAR). VF was simulated as normal, moderate VF impairment (VFI) (20° radius), or severe VFI (10° radius) using specially designed goggles. Reading speed (RS) was measured using the Chinese International Reading Speed Texts (IReST). Maximum reading speed (MRS), reading acuity (RA), and critical print size (CPS) were measured using the Chinese Reading Acuity Chart. RS and MRS were analyzed using linear mixed-effects models, whereas RA and CPS were analyzed using generalized estimating equations with a gamma distribution and log link. Results Reduced VA and restricted VF significantly decreased RS and MRS. Compared with normal VA, mild VAI reduced RS by 80.6 characters per minute (cpm, 95% CI: − 98.4 to − 62.7) and MRS by 52.9 cpm (95% CI: − 65.3 to − 40.6), while moderate VAI reduced MRS by 63.3 cpm (95% CI: − 75.6 to − 50.9). Moderate VFI and severe VFI reduced RS by 9.5 cpm (95% CI: − 16.7 to − 2.4) and 38.1 cpm (95% CI: − 45.3 to − 31.0), and reduced MRS by 11.0 cpm (95% CI: − 19.0 to − 3.1) and 25.2 cpm (95% CI: − 33.1 to − 17.3), respectively. Under combined impairment, participants with mild VAI and severe VFI demonstrated an additional reduction in RS of − 20.1 cpm (95% CI: − 30.2 to − 10.0). Additional reductions in MRS were observed in participants with moderate VAI combined with moderate VFI (− 20.6 cpm; 95% CI: − 31.8 to − 9.4) and severe VFI (− 40.0 cpm; 95% CI: − 51.2 to − 28.8). RA and CPS were primarily influenced by VA. VF restriction only showed small effects on RA and no meaningful effect on CPS. Conclusions Both reduced VA and VF constriction significantly impaired reading performance, with VA loss emerging as the dominant factor. Under standardized simulation of low-vision conditions, combined impairments produced additional reductions in RS and MRS. These findings support the evaluation of reading performance in low-vision rehabilitation and earlier visual rehabilitation in patients with combined VA and VF impairments. Trial registration The study was registered with the Chinese Clinical Trial Registry (ChiCTR2400080206).
Abstract Background The effects of ON and OFF retinal pathway stimulation on lens-induced myopia (LIM) in mammalian models remain unclear. This study examined refractive, choroidal, and dopamine (DA)-related responses to artificial dynamic ON and OFF stimulation during the development of LIM in guinea pigs. Methods Sixty-three guinea pigs were randomly assigned to ON, OFF, and natural control (NC) stimulation for 12 h/day over 7 days. LIM was induced using a − 4.0 D monocular lens. Refraction, axial length (AL), choroidal thickness (ChT), and choroidal blood perfusion (ChBP) were assessed before and after treatment. DA and metabolites were measured by high-performance liquid chromatography (HPLC), interocular differences were calculated, and choroidal proteomes were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) based bioinformatics analysis. Results ON stimulation significantly reduced myopic shift compared with NC and OFF stimulation (Δ refraction: − 2.13 ± 0.40 D vs. − 4.03 ± 0.35 D and − 3.98 ± 0.50 D, respectively; both P < 0.01). No significant differences in AL were observed among groups. OFF stimulation uniquely preserved ChBP (ΔChBP: 0.51% ± 2.18%), significantly different from ON (− 6.11% ± 1.76%, P = 0.0330) and NC (− 7.78% ± 1.44%, P = 0.0057). OFF stimulation also showed less choroidal thinning (ΔChT: − 3.06 ± 2.23 μm) compared to NC (− 12.35 ± 2.7 μm, P = 0.0171). In non-lens eyes, ON stimulation produced higher ChBP than NC or OFF stimulation, and ChT changes were positively correlated with ChBP under all conditions (P < 0.0001). Retinal 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly higher in the ON group (17.65 ± 12.67) than in the NC group (− 25.75 ± 9.23, P = 0.0095). Vitreal DA markers showed no significant differences among groups. Proteomic analysis revealed distinct choroidal remodeling signatures among ON, OFF, and NC groups, with ON stimulation associated with the smallest number of differentially expressed proteins and a relatively preserved pattern of collagen and fibrillin expression compared with more pronounced extracellular matrix (ECM) depletion under NC and over-compensatory ECM upregulation under OFF stimulation. Conclusions ON and OFF stimulation differentially regulated ocular responses to myopia. ON stimulation was associated with attenuated myopic shift and increased retinal DOPAC levels, suggesting enhanced DA metabolism. OFF stimulation was associated with preserved ChT and ChBP, accompanied by upregulation of ECM components. These findings suggest that effective myopia control strategies may require coordinated engagement of both ON- and OFF-pathway-mediated mechanisms.
Abstract Background To investigate the correlation between choroidal vasculature characteristics and the formation of macular neovascularization (MNV) in patients with chronic central serous chorioretinopathy (CSC), based on widefield indocyanine green angiography (WF-ICGA). Methods This was a retrospective, observational study. Patients with chronic CSC with complete medical records and multimodal imaging conducted between September 2022 and June 2025, were included. Eyes with chronic CSC were divided into the MNV and non-MNV groups based on the presence or absence of MNV. WF-ICGA was performed to obtain choroidal characteristics, including vortex vein (VV), dominant VV (DVV), posterior VV, intervortex venous anastomosis (IVA), and age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA). Choroidal characteristics were quantitatively and qualitatively assessed and compared between eyes with and without MNVs. Results A total of 293 eyes from 212 patients (164 males, 77.36%) were analyzed. Of these, 96 presented with secondary MNV (32.76%), whereas 197 did not. Compared with that of the non-MNV group, the MNV group exhibited a more advanced age and worse visual acuity (all P < 0.001). Regarding choroidal characteristics, MNV cases more frequently exhibited an asymmetric distribution pattern (P = 0.032), solitary DVV (P = 0.041), superotemporal DVV location (P = 0.005), macular IVA (P = 0.027), and ASHS-LIA (P < 0.001). In the generalized linear-mixed model, which was adjusted for age, sex, and symptom duration, the occurrence of MNV correlated with the presence of superotemporal DVV, macular IVA, and ASHS-LIA (P < 0.001, P = 0.003, and P = 0.011, respectively). Conclusion WF-ICGA-derived choroidal vascular characteristics were identified as potential biomarkers for the development of MNV in eyes with chronic CSC. The presence of superotemporal DVV, macular IVA, and ASHS-LIA may serve as independent associated factors for predicting the development of MNV.
To investigate the precision (intraobserver repeatability and interobserver reproducibility) of the AL550, an automated biometer that integrates optical low-coherence reflectometry with Placido-disk topography, and to assess the inter-device agreement with the IOLMaster 700. This prospective study enrolled 112 healthy participants. Each participant underwent three consecutive right-eye measurements by two operators with different levels of experience using the AL550 to assess intraobserver and interobserver variability. Additionally, three measurements were obtained by a skilled operator using the IOLMaster 700 for inter-device comparison. The parameters assessed included axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), flattest, steepest, and mean keratometry (Kf, Ks, and Km), astigmatism, and corneal diameter (CD). Measurement precision was analyzed using the within-subject standard deviation (Sw), test–retest repeatability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Inter-device agreement was assessed using paired t-tests and Bland–Altman analysis. The AL550 demonstrated excellent repeatability and reproducibility across all parameters, with low Sw, TRT, and CoV values, and ICCs exceeding 0.939. Inter-device agreement with the IOLMaster 700 was excellent for most parameters, with narrow 95
This study aimed to evaluate the association between long-term blood pressure (BP) variability (BPVR) and visual field (VF) progression in patients with primary open-angle glaucoma (POAG). In this prospective cohort study, linear mixed-effect models were used to assess the associations between BP metrics and VF progression rates. BPVR and intraocular pressure (IOP) variability during the follow-up period were calculated by dividing the respective standard deviation values by the mean values. Correlated non-fluctuating BP metrics (baseline, mean, maximum, and minimum BP) were combined using principal component analysis separately for systolic BP (SBP) and diastolic BP (DBP). The first principal component was included as a covariate. Interactions between covariates and time from baseline were modelled to evaluate their effects on VF progression rates. A total of 157 eyes of 157 patients with POAG (mean baseline age, 56.3 ± 13.6 years) were included. VF progression was observed in 71 eyes (45
Abstract Background To compare the utility of single-capture ultra-widefield optical coherence tomography angiography (UWF-OCTA) and UWF-OCTA plus UWF colour fundus photography (UWF-CFP) versus UWF fluorescein angiography (UWF-FA) in detecting retinal capillary haemangiomas (RCHs) in von Hippel‒Lindau disease (VHL) and to explore the associations of RCH multimodal imaging features. Methods In this observational cross-sectional study, all enrolled eyes underwent single-capture UWF-OCTA (29 × 24 mm). RCHs suspected on UWF-CFP with eye-steering were further checked using regional UWF-OCTA scans. UWF-FA was used for comparison. Independent observers performed the RCH detection and characterisation using different imaging methods. The detection performance was compared, and logistic regression was used to identify the factors associated with leakage. Results Thirty-nine eyes of 21 patients with VHL were included in this study. At the eye level, UWF-OCTA plus UWF-CFP exhibited a similar performance to UWF-FA in detecting RCH involvement (87.2% vs. 89.7%, P = 0.319) and the median number of RCHs per eye (2 vs. 2, P = 0.252). However, the RCH involvement rate (61.5% vs. 89.7%, P < 0.001) and number of RCHs per eye (1 vs. 2, P = 0.003) were lower with single-capture UWF-OCTA than with UWF-FA. At the RCH level, UWF-OCTA plus UWF-CFP showed slightly lower detection rates than did UWF-FA, albeit without statistical significance (86.8% vs. 93.4%, P = 0.057). Single-capture UWF-OCTA detected significantly fewer RCHs than did UWF-FA (51.7% vs. 93.4%, P < 0.001). RCHs were classified according to OCTA B-scan characteristics. Types 1 (48.8%) and 2 (18.1%) RCHs exhibited a nodular appearance with protrusion into the vitreous cavity and compression of the outer retina, respectively. Type 3 RCHs (28.3%) displayed flat growth patterns, whereas type 4 RCHs (4.7%) breached the inner limiting membrane. Logistic regression revealed that RCH size > 0.5 mm was associated with hyperfluorescence with leakage (odds ratio [OR]: 10.987; 95% confidence interval [CI]: 1.747 to 69.090; P = 0.011), whereas type 3 RCH was associated with lower odds of leakage than type 1 (OR: 0.083; 95% CI: 0.026 to 0.267; P < 0.001). Conclusions A screening strategy integrating UWF-OCTA and UWF-CFP, instead of 150° single-capture UWF-OCTA alone, is reliable for non-invasive detection of RCHs in patients with VHL. OCTA-derived features, particularly the morphological subtype, may replace FA in assessing RCH activity and guiding the management of ocular VHL.
Abstract Background Although ocular manifestations of neurofibromatosis type 1 (NF1) have been described extensively in Western cohorts, systematic data in Asian populations remain limited, and age-related phenotypic variations have not been comprehensively characterized. This study investigated the prevalence and multidimensional characteristics of NF1-related ocular manifestations in Asian populations, using age-stratified analysis of uveal and retinal abnormalities. Methods In this cross-sectional study, 228 Chinese patients with NF1 underwent comprehensive ophthalmic evaluations. Examinations included slit-lamp biomicroscopy, ultra-widefield (UWF) fundus photography, near-infrared reflectance (NIR) imaging, and optical coherence tomography (OCT) to assess retinal and uveal abnormalities. Results A total of 228 patients with NF1 (46.1% male; median age 14 years) were enrolled. Lisch nodules were detected in 82.82% of patients, with highest prevalence during puberty and greater counts in older individuals (P < 0.001). Lisch nodules showed a tendency for inferior distribution and likely progressive darkening with age. Choroidal abnormalities were identified in 89.94% of patients, exceeding the prevalence of Lisch nodules (P < 0.001). Both the number and area of choroidal abnormalities correlated positively with age (P < 0.001), with predominant distribution at the posterior pole. Retinal vascular abnormalities (RVAs), retinal astrocytic hamartomas (RAHs), and iris mammillations were observed in 9.47%, 1.83%, and 8.37% of patients, respectively. Conclusions In Asian patients with NF1, older individuals exhibited a greater burden of uveal abnormalities. Lisch nodules demonstrated preliminary evidence of an age-dependent darkening phenotype. Choroidal abnormalities were more prevalent than Lisch nodules and consistently present across age groups, making them valuable diagnostic markers in paediatric patients. Compared with Western cohorts, Chinese paediatric patients with NF1 exhibited earlier onset of both Lisch nodules and choroidal abnormalities. These findings refine ethnicity-specific ocular profiles of NF1 and underscore the importance of timely ophthalmic surveillance, particularly in children.
Abstract Background Myopia is a global public health issue, necessitating effective control strategies. Defocus incorporated multiple segments (DIMS) and highly aspherical lenslet (HAL) spectacle lenses, as well as their combination with low-concentration atropine (0.01%), have been shown to control myopia effectively. However, direct comparisons among these regimens, DIMS, HAL, DIMSA (DIMS + atropine), and HALA (HAL + atropine), are lacking. In this real-world study, we compared their effectiveness in slowing myopia progression. Methods This single-center retrospective cohort study included 347 children (694 eyes) aged 6–14 years who received one of the four interventions for at least 1 year. The primary outcome was the annual change in axial length (AL). The secondary outcome was the annual change in spherical equivalent refraction (SER). The treatment response was categorized as good, fair, or poor. Linear mixed models and generalized estimating equations were used for analysis, adjusting for covariates. Results After adjustment, annual axial elongation differed significantly among the groups (P < 0.001), with marginal means of 0.23 mm (DIMS), 0.15 mm (HAL), 0.20 mm (DIMSA), and 0.12 mm (HALA). Post hoc comparisons revealed that both HAL and HALA were superior to DIMS (P < 0.001) and that HALA was superior to DIMSA (P = 0.022). Adding 0.01% atropine to either optical monotherapy did not provide a significant additional benefit in terms of mean AL or SER outcomes. Compared with DIMS, HALA significantly increased the odds of a good response for AL (OR = 4.34, P < 0.001) and SER (OR = 5.85, P < 0.001), whereas this effect was not observed with DIMSA. Older age independently predicted better response (AL: OR = 1.46/year; SER: OR = 1.26/year; both P < 0.001). Conclusions In this non-randomized real-world comparison, HAL monotherapy was associated with slower SER progression, compared with DIMS. Although adding atropine did not improve mean outcomes, HALA showed the highest likelihood of a good response, suggesting a clinically meaningful benefit in response distribution. Although HALA did not consistently outperform HAL monotherapy across analyses, its advantage in achieving favourable individual responses supports its consideration for children requiring maximal intervention. These findings require confirmation in prospective randomized trials.
Abstract Background Sickle cell retinopathy (SCR) is a well-documented and potentially vision-threatening presentation of sickle cell disease (SCD). In this article, we provide a comprehensive review of the management options for non-proliferative sickle cell retinopathy (NPSR) and proliferative sickle cell retinopathy (PSR) based on the existing ophthalmic literature. Main text The mainstay of NPSR treatment focuses on preventing progression to PSR by identifying and altering modifiable risk factors. Once NPSR progresses to PSR, suppression of vascular endothelial growth factor (VEGF) expression with laser photocoagulation or intravitreal anti-VEGF injections can be considered. While no standard criteria exist for timing and type of intervention, both treatment modalities have been utilized for advanced PSR. In contemporary practice, scatter laser photocoagulation is performed far more commonly than the historically described feeder-vessel photocoagulation. Surgical management typically includes pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV-SB and are generally indicated in PSR for non-clearing vitreous hemorrhage, tractional or rhegmatogenous retinal detachment (RD), and epiretinal membrane formation. Conclusion There is currently no consensus on standard guidelines for the management of SCR. Evidence suggests that surgical intervention can improve vision in advanced stages of PSR and that anti-VEGF therapy may have a role in treatment. However, studies in the ophthalmic literature are limited by relatively small sample sizes and difficulty accounting for a patient’s prior medical or surgical interventions. Additionally, more robust studies are required to determine the long-term efficacy and safety of anti-VEGF in SCR. A multidisciplinary team approach to SCR and SCD remains the cornerstone of management for this systemic disease.
Abstract Background Fuchs endothelial corneal dystrophy (FECD) is characterized by progressive endothelial dysfunction and corneal edema. Reliable objective biomarkers for grading disease severity are currently evolving. Corneal backscatter may reflect edema-related changes in corneal transparency and could serve as an additional objective measure of FECD severity across different edema stages. The purpose of this study was to evaluate the potential of corneal backscatter as a biomarker for severity of FECD. Methods In this retrospective, observational, single-center cross-sectional study, 99 eyes of 67 patients with FECD were divided into three groups depending on the presence of clinical, subclinical or no corneal edema. The corrected distance visual acuity (CDVA) was obtained and Scheimpflug tomography was performed. Subclinical corneal edema was diagnosed if more than one of the following criteria were present in Scheimpflug tomography: loss of regular isopachs, displacement of the thinnest point of the cornea, and focal posterior corneal surface depression. Clinical corneal edema was diagnosed by slit-lamp biomicroscopy. The primary outcome was the difference in total corneal backscatter in the central 2-mm zone. Secondary analyses were the correlation of corneal backscatter to CDVA, tomographic parameters such as central corneal thickness (CCT) and thinnest corneal thickness (TCT), as well as their diagnostic accuracy and predictive potential to differentiate between edema severity. Results The total central corneal backscatter was significantly higher among eyes with high edema severity (P < 0.05). Differences in corneal backscatter between subgroups diminished with increasing depth of corneal layer and towards the periphery. The anterior (Marginal R2 = 0.260; P < 0.001) and total (Marginal R2 = 0.208; P < 0.001) corneal backscatter in the central 2-mm zone correlated well with CDVA. Corneal backscatter showed a higher correlation with CDVA than CCT (Marginal R2 = 0.198; P < 0.001) and TCT (Marginal R2 = 0.096; P = 0.004). Central corneal backscatter in the anterior 120 µm demonstrated moderate diagnostic accuracy for distinguishing subclinical corneal edema from no edema (threshold = 31.2 GSU; AUC = 0.73) or clinical edema (threshold = 34.9 GSU; AUC = 0.76). Conclusions Our study corroborates that corneal backscatter values increase with increasing corneal edema stage and therefore present a potential adjunctive biomarker to assess FECD severity in addition to edema status and clinical gradings.
Abstract Purpose To investigate the 1-year preventive efficacy of dual-surface aberration-increasing (DSAI) lenses on axial elongation and refractive change in non-myopic children. Methods This was a 2-year randomized, controlled, prospective trial with a planned interim analysis at the 1-year follow-up to assess the preliminary efficacy and safety of DSAI lenses. One hundred children aged 6–12 years with cycloplegic spherical equivalent refraction between −0.50 diopters (D) and + 2.00 D, classified as non-myopic, were recruited. Participants were randomly assigned to wear either DSAI spectacle lenses or single-vision (SV) spectacle lenses in daily life. The primary outcomes were axial elongation and refractive change relative to baseline measurements, with axial elongation considered the main structural outcome in the results. Results Enrolment commenced in June 2023. One hundred participants were recruited, and 92 (DSAI group: n = 46, mean ± standard deviation age: 8.15 ± 1.49 years; SV group: n = 46, 8.32 ± 1.62 years) completed the 1-year follow-up. No intervention-related adverse events were observed during the study period. Participants in the DSAI group exhibited significantly less axial elongation (difference: 0.15 mm; 95% confidence interval [CI]: 0.06 to 0.24 mm; P = 0.002) and refractive change (difference: −0.26 D; 95% CI: −0.50 to −0.02 D; P = 0.032) than those in the SV group. Subgroup analysis showed that emmetropic children, older children (8.1–12.0 years), and those wearing lenses for longer durations (≥ 11 h/day) in the DSAI group had significantly less model-adjusted axial elongation than the corresponding SV subgroups (all P < 0.05). Conclusion The 1-year interim results suggest that DSAI lenses help to slow axial elongation and refractive change in non-myopic children, with a relatively greater effect observed in emmetropic children, older children, and those who wore the lenses for longer durations. Trial Registration This trial is registered at Chinese Clinical Trial Registry with trial registration number: ChiCTR2300078464.
Abstract Most animals sense light through opsins, which are photosensitive G protein–coupled receptors that utilize light information to regulate various physiological functions. In vertebrates, a representative example of such functions is vision, which is based on photoreception by visual opsins expressed in rod and cone photoreceptor cells of the retina. Accumulating photobiological evidence has gradually revealed the significance of the molecular properties of these opsins, as well as those of signal transduction–related molecules such as transducin, rhodopsin kinases, and arrestins, and their collective contribution to the functional characteristics of retinal photoreceptor cells. Furthermore, electrophysiological studies of animal photoreception have demonstrated that pineal-related organs in many vertebrates exhibit photosensitivity. Consequently, these organs are referred to as the “third eye,” in addition to the bilateral eyes. Light responses in pineal-related organs have been electrophysiologically described across various vertebrates, from lampreys to birds. In particular, species ranging from lampreys to lizards commonly exhibit two characteristic types of responses: “achromatic” and “chromatic.” Since the 1990s, genome projects have identified numerous opsin genes in diverse animal species and revealed their remarkable diversity. This has led to rapid advances in the study of “non-visual” opsins and their associated physiological functions. Along with these developments, the opsin repertoire in pineal-related organs has been shown to differ from that in the eyes. In this article, we review electrophysiological evidence of photosensitivity in pineal-related organs and describe the molecular basis underlying this sensitivity. Furthermore, we discuss the role of the pineal-specific opsin parapinopsin, which possesses molecular properties distinct from those of visual opsins, in photoreceptor cells, as well as examples of its application in optogenetics. Overall, this review highlights the molecular and physiological significance of pineal opsins and emphasises their emerging potential in optogenetic applications.
