Investigative ophthalmology & visual science最新文献

{"title":"Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.","authors":"Somayeh Piroozmand, Hamid Latifi-Navid, Zahra-Soheila Soheili, Saman Hosseinkhani, Shahram Samiei, Amir Barzegar Behrooz, Hamid Ahmadieh, Andrea Leonardi, Saeid Ghavami, Nader Sheibani","doi":"10.1167/iovs.67.5.4","DOIUrl":"https://doi.org/10.1167/iovs.67.5.4","url":null,"abstract":"<p><strong>Purpose: </strong>Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression.</p><p><strong>Methods: </strong>We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure.</p><p><strong>Results: </strong>EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions.</p><p><strong>Conclusions: </strong>This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"4"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effects of Riboflavin-UVA and Rose Bengal-Green Light Cross-Linking on Corneal Neovascularization.","authors":"Merve Oral, Duygu Dayanir, Gökce Nur Arik Erol, Mehmet Cüneyt Özmen","doi":"10.1167/iovs.67.5.16","DOIUrl":"https://doi.org/10.1167/iovs.67.5.16","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to compare the effects of riboflavin-ultraviolet A (RF/UVA) cross-linking (CXL) and rose bengal-green light (RB/green light) CXL on corneal neovascularization (CNV) in rat eyes.</p><p><strong>Methods: </strong>Forty Wistar albino rats underwent CNV induction by corneal suture placement and were randomized into four groups: control, RF/UVA CXL, RB/green light CXL, and green light alone. Treatments were administered on day 3. Anterior segment (AS) photographs and AS-optical coherence tomography (AS-OCT) images were obtained on days 0, 3, 7, and 14, with days 7 and 14 defined as endpoints. Right corneas were analyzed using immunohistochemistry (IHC) for vascular endothelial growth factor (VEGF), lymphatic vessel endothelial hyaluronan receptor (LYVE-1), and CD68, along with hematoxylin & eosin (H&E) staining and TUNEL assay. Left corneas were evaluated with ELISA for VEGF and CD68 levels.</p><p><strong>Results: </strong>The least CNV area was observed in the RF/UVA group on days 7 and 14 (P = 0.002 and P < 0.001, respectively). The RB/green light CXL group also demonstrated CNV area than the green light alone group on day 7 (P < 0.001). ELISA revealed significantly lower VEGF levels in all treatment groups compared with controls on day 7, whereas this reduction persisted only in the RF/UVA CXL group on day 14 (P < 0.001 and P = 0.049, respectively). VEGF and LYVE-1 immunostaining were significantly lower in the RF/UVA CXL group compared with the green light group at both time points. CD68 staining was reduced in both CXL groups. TUNEL analysis showed the highest keratocyte apoptotic index in the RF/UVA CXL group, followed by the RB/green light CXL group (both P < 0.001).</p><p><strong>Conclusions: </strong>Both CXL modalities suppressed inflammation and were effective in reducing hemangiogenesis, and lymphangiogenesis; however, the RF/UVA CXL group demonstrated superior overall efficacy than the RB/green light CXL group.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"16"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot Study of Patient-Reported Outcomes in Stargardt Disease: Correlation With Functional and Structural Findings.","authors":"Johnson Hoang, Iden Amiri, Lauren Dimalanta, Alessandro Iannaccone, Alice Yang Zhang","doi":"10.1167/iovs.67.5.15","DOIUrl":"https://doi.org/10.1167/iovs.67.5.15","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the impact of Stargardt disease (STGD) on activities of daily living and mental health, correlating patient-reported outcome (PRO) measures from the Michigan Retinal Degeneration (MRDQ) and Vision-Related Anxiety Questionnaires (MVAQs) with clinical data.</p><p><strong>Methods: </strong>Patients with STGD with biallelic pathogenic ABCA4 mutations were recruited from the University of North Carolina (UNC) at Chapel Hill and Foundation Fighting Blindness (FFB) databases. Participants completed MRDQ and MVAQ testing. Best-corrected visual acuity (BCVA), electroretinogram (ERG), and fundus autofluorescence (FAF) were retrospectively analyzed for UNC patients.</p><p><strong>Results: </strong>Fifty participants (mean age = 48.8 ± 18.5) were included. Median θ for MRDQ: central vision (0.138), color vision (0.143), contrast sensitivity (0.122), and photosensitivity (0.185). Median MVAQ θ scores for cone- and rod-related anxiety were 0.005 and -0.055, respectively. The following additional analyses were performed using the UNC subset of participants (n = 12): BCVA correlated with contrast sensitivity (P = 0.027). Rod ERG response correlated with scotopic vision (P = 0.044). Central FAF lesion extent correlated with central vision (P = 0.039) and contrast sensitivity (P = 0.032). Rod-related anxiety correlated with rod ERG response (P = 0.048), color vision (P < 0.001), contrast sensitivity (P < 0.001), photopic peripheral vision (P < 0.001), cone-related anxiety (P < 0.001), photosensitivity (P = 0.014), mesopic peripheral vision (P < 0.001), and scotopic vision (P < 0.001). Cone-related anxiety correlated with color vision (P = 0.026), contrast sensitivity (P = 0.013), photopic peripheral vision (P < 0.001), mesopic peripheral vision (P < 0.001), and scotopic vision (P < 0.001).</p><p><strong>Conclusions: </strong>In patients with STGD, structural and functional measures correlated with reduced functional vision and increased vision-related anxiety per PRO criteria. These findings provide insight into patient-perceived disease burden and may help inform future STGD interventions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"15"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Neurophysiological Parameters in Young Patients With Type 1 Diabetes.","authors":"Marie Elise Wistrup Torm, Jesper Johannesen, Thomas W Gardner, Javad Nouri Hajari, Oliver Niels Klefter, Michael Larsen","doi":"10.1167/iovs.67.5.3","DOIUrl":"https://doi.org/10.1167/iovs.67.5.3","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy has prominent microvascular manifestations, but preclinical studies also find neuroglial cell abnormalities. This study aimed to examine retinal electrophysiological characteristics and their relation to diabetes duration and glycemia history in type 1 diabetes (T1D).</p><p><strong>Methods: </strong>This cross-sectional study included 69 patients with T1D aged 6-32 (mean 16) years in equally sized subgroups of T1D duration <5 months, approximately 5 years, 10 years or 15 years. Exclusion criteria were chronic disease other than T1D, and retinal disease other than fundus photographic evidence of diabetic retinopathy. Comparison was made with 54 age-matched healthy subjects aged 8-34 (mean 17) years. Examinations included fundus imaging, electroretinography (ERG), dark adaptometry, and structural and angiographic optical coherence tomography.</p><p><strong>Results: </strong>In patients with T1D, ERG implicit times of the dark-adapted 85 troland seconds (Td·s) a-wave and light-adapted flicker 85 Td·s wave increased with T1D duration in simple linear regression (P = 0.041 and 0.027, respectively). In patients with >4 years T1D duration, implicit times of flicker 16 Td·s and flicker 32 Td·s in dim ambient lighting increased with higher aggregate HbA1c means (P = 0.018 and 0.036, respectively). For all T1D patients, implicit times of dark-adapted 85 Td·s a-wave and b-wave increased with higher blood glucose (P = 0.041 and 0.023, respectively). Dark adaptation rod intercept and retinal thicknesses were comparable between the groups.</p><p><strong>Conclusions: </strong>This study of young T1D patients with little or no fundus photographic signs of retinopathy showed that selected ERG implicit times were longer with higher previous HbA1c levels and longer diabetes duration.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"3"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binocular Afferent Synchrony During Development and in Amblyopia: Evidence From Dominance-Referenced Multichannel Visual Evoked Potentials.","authors":"Di Chang, Yuying Han, Yachen Wang, Zhihan Liu, Dengxin Gao, Shuzhen Li, Mofan Wen, Ziwei Shang, Xiaohui Zhang, Zhijie Li, Tao Fu","doi":"10.1167/iovs.67.5.7","DOIUrl":"https://doi.org/10.1167/iovs.67.5.7","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to test whether binocular afferent synchrony differs within the visual critical period (CP), beyond the CP, and in amblyopia using dominance-referenced multichannel visual evoked potentials (mcVEPs), and to assess the translational value of interocular timing asymmetries.</p><p><strong>Methods: </strong>We enrolled 117 participants: 33 healthy children and 28 children with amblyopia (all within the CP) and 56 healthy adults (post-CP). Pattern-reversal (PR-VEP) and flash VEP (F-VEP) responses were recorded at O1/Oz/O2 referenced to Fz. Lateral channels were relabeled relative to each participant's dominant eye (dominance-referenced analysis). Primary outcomes were interocular P100 latency difference (indexing synchrony) and N75-P100 amplitude (indexing response balance).</p><p><strong>Results: </strong>In healthy children, PR-VEPs showed no significant interocular P100 latency differences at either lateral electrode and bilaterally symmetric amplitudes, consistent with preserved synchrony during the CP. Healthy adults exhibited a contralateral latency advantage (shorter P100 for the eye contralateral to the recording electrode) and a dominant-eye amplitude bias, indicating post-CP asynchrony and ocular-dominance asymmetry. In amblyopic children, both PR-VEPs and F-VEPs demonstrated prolonged P100/P2 latency (≈10-12 ms delay) and reduced N75-P100/N2-P2 amplitudes in the amblyopic (non-dominant) eye across hemispheres, reflecting marked disruption of binocular timing and response symmetry.</p><p><strong>Conclusions: </strong>Interocular latency asynchrony derived from mcVEPs offers a noninvasive, objective readout of binocular afferent timing that may assist in amblyopia stratification and inform timing-targeted, individualized interventions. Longitudinal and interventional studies are warranted to establish causal links between synchrony and cortical plasticity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"7"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent Degeneration of Photoreceptors and Retinal Pigment Epithelium: Multimodal Imaging Evidence From Choroideremia Carriers.","authors":"Xiaoxu Han, Yang Yu, Xing Wei, Zixi Sun, Hui Li, Xuan Zou, Ruifang Sui","doi":"10.1167/iovs.67.5.10","DOIUrl":"https://doi.org/10.1167/iovs.67.5.10","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize retinal structural alterations and elucidate underlying pathogenesis in female carriers of choroideremia (CHM) using multimodal imaging.</p><p><strong>Methods: </strong>This single-center retrospective study analyzed 100 eyes of 50 genetically confirmed female CHM carriers. Clinical evaluation comprised genotype, age, visual acuity, color fundus photography, fundus autofluorescence (FAF), infrared reflectance, and optical coherence tomography (OCT). Retinal lesions were identified and classified using point-to-point co-localization analysis across modalities.</p><p><strong>Results: </strong>The mean age of carriers was 39.6 ± 17.8 years (range 3.2-80.3 years). All eyes exhibited varying degrees of retinal abnormalities. Most common findings included yellowish changes on color photographs, mottled areas of hyper- and hypo-autofluorescence on FAF, and isolated interdigitation zone (IZ) loss on OCT. Chorioretinal atrophy beyond the peripapillary region, indicating a severe phenotype, was observed in 18% of eyes. Five characteristic degenerative lesions were identified: Type A, isolated IZ loss; Type B, hyper-autofluorescent spots corresponding to presumed photoreceptor loss; Type C, drusen-like deposits; Type D, degeneration of the retinal pigment epithelium (RPE) and RPE-photoreceptor interface; and Type E, outer retinal degeneration. Type B lesions suggest that photoreceptor loss may precede RPE loss at specific loci. Type A lesions were the earliest abnormality, significantly associated with milder phenotypes, indicating the RPE-photoreceptor interface is the initial site of pathology. In contrast, Type D and E lesions were associated with severe phenotypes.</p><p><strong>Conclusions: </strong>Identified hyper-autofluorescence lesions corresponding to presumed photoreceptor loss indicate independent degeneration of photoreceptors and RPE. These findings suggest that future therapeutic approaches should concurrently target both cellular components.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"10"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Myopia Control Spectacle Lenses on Peripheral Refraction and Contrast: Insights From Optical Modeling.","authors":"Yongji Liu, Xiaoyang Hu, Xiaoqin Chen, Xiaoyan Yang, Dongyu Liu, Tianrui He, Lihua Li","doi":"10.1167/iovs.67.5.14","DOIUrl":"https://doi.org/10.1167/iovs.67.5.14","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate potential optical cues underlying myopia control effects by examining how lenslet-array spectacle lenses influence peripheral refraction and image contrast.</p><p><strong>Methods: </strong>Three commercial lenslet-array spectacle lenses-MiyoSmart, Stellest, and diverse segmented defocus optics-were reconstructed in Zemax OpticStudio, together with a conventional single vision (SV) lens as a reference. The reconstructed lenses were coupled with the Navarro eye model to simulate spectacle wearing after experimental validation of the lens models. Optical performance was evaluated under both distance and near viewing conditions with accommodative lags of 0.50 diopters (D) and 1.00 D. Peripheral refraction components (M and J0) were derived from wavefront data. Point spread functions and modulation transfer functions were obtained, with the area under the modulation transfer function curve subsequently calculated.</p><p><strong>Results: </strong>Simulated and experimental point spread functions showed strong agreement, confirming the reliability of the constructed spectacle models. Compared with the SV lens, the lenslet-array introduced M fluctuations (within ±0.25 D), manifesting as alternating positive and negative shifts relative to the SV baseline. Only the Stellest lens exhibited minimal myopic defocus over a limited eccentricity range, while the other designs failed to induce peripheral myopic defocus. In the horizontal meridian between 12.5° and 17.5° eccentricity, lenslet-array lenses exhibited reduced contrast at low spatial frequencies (≤6 cycles/degree) but increased cutoff frequencies and relatively enhanced contrast at higher frequencies (9-15 cycles/degree). Similar patterns were observed under near viewing with a 0.50 D accommodative lag.</p><p><strong>Conclusions: </strong>The myopia control efficacy of lenslet-array lenses may not be fully explained by the peripheral myopic defocus hypothesis. Instead, the observed reduction in low spatial frequency contrast, coupled with an elevated cutoff frequency that preserves high-frequency information, may provide the critical optical cues for slowing myopia progression. These hypothesized mechanisms warrant further clinical investigation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"14"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors and Structural Impact of Macular Edema in Preterm Infants: An OCT-Based Cohort Study.","authors":"Weiming Yang, Xiaohong Zhou, Yian Li, Xiaojing Cai, Chenhao Yang","doi":"10.1167/iovs.67.5.12","DOIUrl":"https://doi.org/10.1167/iovs.67.5.12","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate risk factors for macular edema (ME) and its impact on foveal development in preterm infants using handheld optical coherence tomography (OCT) and clinical data.</p><p><strong>Methods: </strong>This retrospective cohort included 106 preterm infants who underwent routine retinopathy of prematurity screening with RetCam 3 and OCT. Clinical variables were collected from records. ME was classified by OCT morphology. Quantitative foveal parameters-central foveal thickness (CFT), foveal inner retinal thickness (FIRT), foveal outer retinal thickness (FORT), mean parafoveal thickness (MPFT), mean parafoveal inner retinal thickness (MPIRT), foveal depth (FD), and foveal angle (FA)-were measured. Logistic regression identified ME risk factors, and linear and mixed-effects models assessed structural impact.</p><p><strong>Results: </strong>Of 106 infants, 27 developed ME (25.5%), and 79 served as controls (74.5%). Infants with resolved ME showed persistent abnormalities, including increased CFT (β = 43.40, P < 0.001), FORT (β = 27.67, P < 0.001), MPFT (β = 109.91, P < 0.001), and FA (β = 20.82, P < 0.001). MPIRT was also increased (β = 58.70, P = 0.002), whereas FD and FIRT did not differ significantly. Independent risk factors for ME included higher postmenstrual age at OCT, longer phototherapy, respiratory support, and moderate-to-high nutritional risk. Birth weight, gestational age, and Apgar scores were not significant predictors.</p><p><strong>Conclusions: </strong>ME in preterm infants is associated with persistent foveal abnormalities despite apparent resolution on OCT. Its development is more closely related to postnatal systemic factors-including nutrition, respiratory support, and phototherapy-than to perinatal indices, supporting risk-based OCT monitoring and longer follow-up.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"12"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Time to See\" in Infantile Nystagmus.","authors":"Katherine Ward, Lee McIlreavy, Matt J Dunn, Christopher M Harris, Fergal A Ennis, Jonathan T Erichsen","doi":"10.1167/iovs.67.5.17","DOIUrl":"https://doi.org/10.1167/iovs.67.5.17","url":null,"abstract":"<p><strong>Purpose: </strong>Interventions that dampen the involuntary eye oscillation in infantile nystagmus (IN) often only elicit modest improvement in visual acuity (VA), even when subjective improvement is reported. Unique to nystagmus, the repeated movement of the fovea away from the intended visual target introduces a temporal dimension to vision. We hypothesized that the viewing time required to resolve optotype stimuli is increased in people with IN and that this measure of \"time to see\" increases with IN severity.</p><p><strong>Methods: </strong>Exposure duration thresholds (viewing times) were measured psychophysically for 18 individuals with IN and 14 controls for an optotype orientation discrimination task at spatial frequencies varying relative to each participant's VA. Viewing times were measured at two gaze positions (toward the IN null zone, where waveform intensity is lower, and away from the null zone, where intensity is higher) to establish the effect of IN severity as quantified by intensity.</p><p><strong>Results: </strong>Exposure duration thresholds were significantly longer in those with IN than controls (P = 0.027) and increased significantly with IN intensity (P = 0.034). Both effects were greatest for optotypes sized at participant-relative VA.</p><p><strong>Conclusions: </strong>\"Time to See\" is increased in IN and is sensitive to within-participant changes in IN severity, suggesting that exposure duration threshold could be a useful measure of visual function in people with IN.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYCN Amplification Drives Ferroptosis Susceptibility via Cysteine Metabolism in Retinoblastoma.","authors":"Yi Chen, Hanyue Xu, Lirong Xiao, Yifan Zhang, Yuzhu Gao, Shulei Man, Dongyue Wang, Kefan Mou, Yufan Huang, Naihong Yan, Ming Zhang","doi":"10.1167/iovs.67.5.9","DOIUrl":"https://doi.org/10.1167/iovs.67.5.9","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate whether MYCN amplification enhances ferroptosis susceptibility in retinoblastoma (RB) and to elucidate the key regulatory mechanisms.</p><p><strong>Methods: </strong>MYCN-amplified Y79 and MYCN copy-number gain WERI-RB1 cells were treated with ferroptosis inducers imidazole ketone erastin (IKE) and RSL3. MYCN was silenced using short hairpin RNA (shRNA) lentiviral transduction, followed by RNA sequencing, real-time quantitative PCR, and western blot. Amino acid deprivation and propargylglycine (PAG) treatment were applied to probe cysteine metabolic pathways. Glutathione (GSH), malondialdehyde (MDA), and ferrous iron (Fe2+) levels were measured, and ultrastructural changes were examined by transmission electron microscopy. An orthotopic xenograft model was used to assess the effect of IKE, PAG, and their combination on tumor growth.</p><p><strong>Results: </strong>MYCN amplification correlated with increased ferroptosis sensitivity, which was reduced by MYCN knockdown. Transcriptome analysis identified dysregulation of cysteine/methionine metabolism, with decreased xCT subunits and cystathionine γ-lyase (CTH) expression. PAG potentiated IKE-induced ferroptosis and triggered cell death alone, while MYCN depletion attenuated lipid peroxidation, restored GSH, and reduced Fe2+ accumulation. In vivo, IKE, PAG, and IKE+PAG all significantly inhibited intraocular tumor growth.</p><p><strong>Conclusions: </strong>MYCN promotes ferroptosis in RB via xCT and transsulfuration pathways. Targeting the MYCN-xCT-transsulfuration axis may offer a novel therapeutic approach for MYCN-amplified RB.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 5","pages":"9"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}