{"title":"Alterations of the Enteric Virome in Vogt-Koyanagi-Harada Disease.","authors":"Mingzhu Liu, Jiawei Geng, Siyan Jin, Ping Hu, Xia Wang, Xiaoli Liu","doi":"10.1167/iovs.66.6.15","DOIUrl":"10.1167/iovs.66.6.15","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the enteric virome characteristics of Vogt Koyanagi Harada (VKH) disease and its potential role in this disease.</p><p><strong>Methods: </strong>Shotgun metagenomic sequencing was used to detect the enteric virome and 16S rRNA to detect the bacteriome in new-onset, untreated patients with VKH (n = 25) and age- and sex-matched healthy controls without autoimmune diseases (n = 25).</p><p><strong>Results: </strong>Patients with VKH exhibited different enteric viral communities from healthy controls, characterized by decreased richness of core viral communities (present in > 80% of samples) and increased richness of common viral communities (present in 50%-80% of samples). Notably, within the core virus community, bacteriophage richness was markedly reduced, whereas eukaryotic virus richness significantly increased in patients with VKH. The case-control analysis identified 42 differentially abundant viruses, including a decrease in crAss-like phages, the eukaryotic virus Moumouvirus_moumou, and an enrichment of the Chlamydiamicrovirus_CPG1. Most of the differential phages predominantly targeted bacteria from the phyla Pseudomonadota and Firmicutes. The gut virome-bacteria community correlation analysis revealed a shift in the interactions between the core viruses and bacterial communities. Additionally, Wroclawvirus PA5oct (a Pseudomonas phage) correlated with leukotrichia, a clinically relevant symptom of VKH (P = 0.042). The impact of multiple Pseudomonas phages on the host folate biosynthesis was significantly enhanced in patients with VKH. Moreover, the protein (Earp361-372) encoded by VKH-enriched Pseudomonas was identified to share homology with the melanin antigen gp10044-59.</p><p><strong>Conclusions: </strong>The gut virome of patients with VKH differs significantly from healthy controls, suggesting its disturbance may contribute to gut microbiome imbalance and VKH development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jérémy De Abreu, Aymeric Paillisser, Florence Berquet, Stephen Hogg, Emanuele Trucco, Martial H Geiser, Aurélien Pichon, Michael Furian, Emeric Stauffer, Benoit Champigneulle, Julien Vincent Brugniaux, Thomas J Macgillivray, Samuel Vergès, Christophe Chiquet
{"title":"Changes in Retinal Vasculature Phenotype and Choroidal Blood Flow at High Altitude in Healthy Lowlanders.","authors":"Jérémy De Abreu, Aymeric Paillisser, Florence Berquet, Stephen Hogg, Emanuele Trucco, Martial H Geiser, Aurélien Pichon, Michael Furian, Emeric Stauffer, Benoit Champigneulle, Julien Vincent Brugniaux, Thomas J Macgillivray, Samuel Vergès, Christophe Chiquet","doi":"10.1167/iovs.66.6.50","DOIUrl":"10.1167/iovs.66.6.50","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to characterize changes in retinal vessel diameters and choroidal blood flow in healthy lowlanders during a high-altitude expedition.</p><p><strong>Methods: </strong>Ocular examination, fundus images acquired using a handheld camera, and laser Doppler flowmetry (LDF) measurements within the subfoveal choroid (blood flow = ChBF, blood velocity = ChVel, and blood volume = ChVol) were carried out at 200 m and after 9 days at 5100 m in 11 healthy participants. Fundus images were analyzed with the semi-automatic software Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) version 3.2 to quantify retinal vessel parameters: the central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE), and arterial and venular tortuosity. Hematocrit and hemoglobin concentrations were also measured at both altitudes.</p><p><strong>Results: </strong>Corneal thickness increased slightly at altitude (median = 536 µm, interquartile range = 25-75%: [521-571] at 200 m vs. 561 µm [540-574] at 5100 m, P = 0.004). No participant was affected by high-altitude retinopathy. From 200 m to 5100 m, ChVol and ChBF decreased significantly (-31% [43-22], P = 0.003 and -13% [22-8], P = 0.01, respectively), ChVel increased (+17% [10-44], P = 0.003), and CRVE (+10% [3-14], P = 0.04) and venular tortuosity (+142% [71-168], P = 0.04) increased significantly. The altitude-induced increase in hematocrit correlated negatively with the decrease in ChBF (r = -0.88, P < 0.001) and positively with the increase in CRVE (r = 0.88, P = 0.01).</p><p><strong>Conclusions: </strong>Acute high-altitude exposure leads to a decrease of ChBF (partly related to a decrease in blood volume) and an increase in retinal vein diameter and tortuosity. The physiological consequences of these changes on retinal blood flow and retinal function remain to be explored.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"50"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myopia Development During Transition From Kindergarten to Early Grades in Elementary School: Population-Based Evidence From an Epidemic Area in Taiwan.","authors":"Yu-Chieh Yang, Der-Chong Tsai, Shao-You Fang, Hsin-Yu Yang, Chiao-Yu Wang, Chia-Wei Lee, Pei-Wei Huang, Mong-Ping Shyong, Yen-Lin Chen, Nai-Wei Hsu","doi":"10.1167/iovs.66.6.48","DOIUrl":"10.1167/iovs.66.6.48","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the incidence of myopia, its association, and refractive progression among kindergarten non-myopic children after entering elementary schools in Yilan, Taiwan.</p><p><strong>Methods: </strong>A cohort study was conducted on first- and second-grade elementary school students. Ocular examinations and caregiver-administered questionnaires were performed between December 2023 and March 2024, with data linked to kindergarten records from Yilan Myopia Vision Improvement Program (YMVIP). Myopia was defined as spherical equivalent (SE) ≤ -0.5 diopters (D), and premyopia as -0.5 D < SE ≤ 0.75 D.</p><p><strong>Results: </strong>Of 1754 enrolled students, 1680 (95.73%) underwent ocular examinations, and 1554 (88.55%) were linked to kindergarten data. Among 1428 non-myopic preschoolers, the incidence density of myopia was 8.70% per person-year (95% confidence interval [CI] = 7.60%-9.80%). Children with incident myopia had a more negative baseline SE (0.33 ± 0.50 D vs. 1.02 ± 0.80 D, P < 0.001) and greater annual myopic progression (-0.60 ± 0.42 D/year vs. -0.20 ± 0.34 D/year). A multiple logistic regression model identified risk factors for incident myopia as premyopia in preschool (odds ratio [OR] = 9.641, 95% CI = 5.936-15.660, P < 0.001), having two myopic parents (OR = 1.819, 95% CI = 1.003-3.297, P = 0.049), and older age at the time of the elementary school examination (OR = 1.635, 95% CI = 1.224-2.183, P = 0.001). Spending more than 30 minutes/day outdoors on weekdays in preschool was protective against myopia (OR = 0.528, 95% CI = 0.366-0.762, P = 0.001).</p><p><strong>Conclusions: </strong>The incidence density of myopia in Yilan County was 8.70% per person-year. Risk factors included premyopia, having myopic parents, and less outdoor time in kindergarten.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"48"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zixin Fan, Shuo Yang, Xiaofeng Lu, Sifan Zhang, Xianlu Zeng, Lin Lin, Duo Yuan, Jian Zeng, Guoming Zhang
{"title":"Alteration of Tear Metabolomics Profiling in Infants With Retinopathy of Prematurity.","authors":"Zixin Fan, Shuo Yang, Xiaofeng Lu, Sifan Zhang, Xianlu Zeng, Lin Lin, Duo Yuan, Jian Zeng, Guoming Zhang","doi":"10.1167/iovs.66.6.61","DOIUrl":"10.1167/iovs.66.6.61","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the characteristics of metabolomic profile in the tears from infants with retinopathy of prematurity (ROP) and further define noninvasive biomarkers.</p><p><strong>Methods: </strong>This prospective study included 94 eyes from 47 premature infants. Tear samples from 23 infants with ROP (15 treatment-requiring ones [ROP (t)] and 8 non-treatment-requiring ones [ROP (nt)]) and 24 infants without ROP were collected with Schirmer strips after topical anesthesia. Detailed fundus examination upon pupil dilation were conducted, with data on demographics and birth history recorded. Untargeted tear metabolomic analysis based on ultra-performance liquid chromatography-mass spectrometry was performed.</p><p><strong>Results: </strong>Adjusted by sex, postmenstrual age, gestational age, and birth weight, among 145 metabolites quantified, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, caffeine, and trehalose were identified to be upregulated in the tears from infants with ROP when compared to those from premature infants with non-ROP, whereas uric acid, dihomo-γ-linolenic acid, nootkatone, pyridoxal, ornithine, 6-keto-prostaglandin F1 alpha, adenosine, and tetrahydrocortisol were downregulated (all adjusted false discovery rate [FDR adj] < 0.05). Nine and one dysregulated metabolites were further found in the ROP (t) and ROP (nt) subgroups, respectively. Some of these metabolites exhibited expression levels correlated with postmenstrual age, gestational age, birth weight, and ROP severity in varying degrees. The dysregulated tear metabolites were fundamentally related to vitamin B6, purine, caffeine, arginine, and starch and sucrose metabolism pathways. The 6-keto-prostaglandin F1 alpha obtained the best performance in classifying premature infants with and without ROP (area under the curve [AUC] of 0.893 [range = 0.800-0.986], P < 0.001).</p><p><strong>Conclusions: </strong>Dysregulated tear metabolites in ROP exhibited abundance correlated with severity of the disease and might be noninvasive biomarkers that potentially serve as complementary screening tools.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"61"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyperopic Eyes Are Structurally More Dynamic Than Myopic Eyes During Accommodation: An In Vivo Investigation.","authors":"Tuyishime Didier Fidele Uwacu, Saugat Bhattacharyya, Kathryn J Saunders, Julie-Anne Little","doi":"10.1167/iovs.66.6.51","DOIUrl":"10.1167/iovs.66.6.51","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of different refractive errors on accommodative structural changes remains unclear. Novel swept-source imaging technology in anterior segment optical coherence tomography (AS-OCT) has enabled in vivo investigation of the accommodating eye. This study investigated ocular structural change and corresponding functional responses during accommodation in individuals with emmetropia, myopia, and hyperopia.</p><p><strong>Methods: </strong>Adults (n = 46; mean age, 22.15 ± 3.00 years) with normal accommodation and a wide range of refractive errors (spherical equivalent refraction [SER]: -7.50 D to +7.88 D) were recruited. CASIA2 AS-OCT measured anterior segment changes during accommodation stimulated by the use of inbuilt accommodative targets and bespoke external stimuli at five different accommodative demands (0 D, 2 D, 3 D, 4 D, and 6 D) and under cycloplegia. Simultaneously, changes in refractive state were measured using the PowerRefractor3 photorefraction system.</p><p><strong>Results: </strong>Lens thickness (LT), anterior chamber depth (ACD), lens diameter (LD), anterior segment length (ASL), anterior lens radius of curvature (ALRC), and posterior lens radius of curvature (PLRC) changed significantly during accommodation (all P < 0.001). Accommodative changes in LT, ACD, and ASL were significantly associated with the level of SER (all P < 0.05), as more hyperopic eyes showed significantly greater per-diopter change than myopic eyes in LT (P = 0.014) and ACD (P = 0.039) for comparatively similar accommodative response (P > 0.9). The analysis of lens position showed that cycloplegia induced posterior displacement of the lens. The CASIA2 internal accommodative target and the external proximal target induced similar structural and functional accommodative responses.</p><p><strong>Conclusions: </strong>There are significant differences between structural changes seen in accommodating eyes with different types and magnitudes of refractive error, with hyperopic eyes showing greater changes in LT and ACD than myopic eyes during accommodation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"51"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chia-Ying Tsai, Wei-Lun Huang, Shang-Chih Yang, Bo-Da Huang, Vladlen Klochkov, Shu-Lang Liao, Albert Y Wu, Wei-Li Chen
{"title":"Human Platelet Lysate Treatment for Exposure Keratopathy: An In Vivo Confocal Microscopy and Anterior Segment OCT Study.","authors":"Chia-Ying Tsai, Wei-Lun Huang, Shang-Chih Yang, Bo-Da Huang, Vladlen Klochkov, Shu-Lang Liao, Albert Y Wu, Wei-Li Chen","doi":"10.1167/iovs.66.6.73","DOIUrl":"10.1167/iovs.66.6.73","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effects of topical human platelet lysate (HPL) on exposure keratopathy (EK) in a rabbit model, with a focus on its anti-inflammatory and anti-dehydration properties on the cornea.</p><p><strong>Methods: </strong>Short-term exposure keratopathy was induced in New Zealand albino rabbits by keeping the eyelids open for four hours, followed by eyelid closure for another four hours, during which the treatment was applied. HPL, fetal bovine serum (FBS), or preservative-free artificial tears (PFAT) were administered every 15 minutes, and corticosteroid was applied every one hour during the treatment period. Corneal thickness changes and epithelial defects were assessed using anterior segment optical coherence tomography (AS-OCT) and fluorescein staining. In vivo confocal microscopy (IVCM) was used to evaluate inflammatory cell infiltration, whereas immunohistochemistry (IHC) was performed to confirm the presence of CD8+ T cells, neutrophils, and macrophages and the cell proliferation marker Ki67.</p><p><strong>Results: </strong>After completing the treatment, no significant difference in fluorescein staining was observed among the four groups. However, AS-OCT revealed more effective recovery of corneal thinning in the HPL- and FBS-treated groups, including improvements in epithelial, stromal, and total corneal thickness. IVCM revealed significantly reduced infiltration of inflammatory cells in the HPL-, FBS-, and corticosteroid-treated groups compared to the PFAT-treated group across the central cornea, peripheral cornea, and conjunctiva. IHC for CD8+ T cells, neutrophils, and macrophages showed similar findings. HPL-treated groups showed more Ki-67-positive cells compared to the PFAT- and corticosteroid-treated groups.</p><p><strong>Conclusions: </strong>HPL treatment effectively reduced inflammation, promoted the recovery of corneal thickness, and induced cellular proliferation after dehydration, demonstrating its potential as a treatment for EK.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"73"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianqi Chen, Xiaohua Zhuo, Yangjiani Li, Yingting Zhu, Zhidong Li, Xinyue Shen, Yehong Zhuo, Hongmei Tan, Lei Lei
{"title":"Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Genes Associated With POAG.","authors":"Jianqi Chen, Xiaohua Zhuo, Yangjiani Li, Yingting Zhu, Zhidong Li, Xinyue Shen, Yehong Zhuo, Hongmei Tan, Lei Lei","doi":"10.1167/iovs.66.6.7","DOIUrl":"10.1167/iovs.66.6.7","url":null,"abstract":"<p><strong>Purpose: </strong>Genome-wide association studies have identified numerous loci associated with POAG. However, functional insights remain limited owing to challenges from noncoding regions and complex linkage disequilibrium. We aimed to bridge these gaps in POAG by integrating genomic and multitissue transcriptomic data and identifying novel systemic regulatory genes.</p><p><strong>Methods: </strong>We analyzed POAG genomic data from FinnGen and expression quantitative trait loci data from GTEx v8 for cross-tissue transcriptome-wide association studies. The Unified Test for Molecular Signature identified cross-tissue associations, complemented by single-tissue Transcriptome-wide association studies using Functional Summary-based Imputation for tissue-specific insights, and the Multi-marker Analysis of Genomic Annotation validated and refined results. Significant findings from the Unified Test for Molecular Signature, Functional Summary-based Imputation, and Multi-marker Analysis of Genomic Annotation were intersected to identify robust candidate genes, followed by summary data-based Mendelian randomization and colocalization analyses to explore their functional implications.</p><p><strong>Results: </strong>Six candidate genes (AFAP1, CALCRL, KREMEN1, MTMR3, GFPT1, and TRIOBP) were identified with intersection evidence. Among these, CALCRL, MTMR3, and GFPT1 were novel. Summary data-based Mendelian randomization confirmed that AFAP1 (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.78-0.88), CALCRL (OR, 0.86; 95% CI, 0.79-0.94), KREMEN1 (OR, 0.86; 95% CI, 0.77-0.97), and MTMR3 (OR, 0.77; 95% CI, 0.63-0.93) exhibited protective effects, and GFPT1 (OR, 1.34; 95% CI, 1.13-1.59) was identified as a risk role for POAG.</p><p><strong>Conclusions: </strong>This study identified six genes associated with POAG, three of which were novel, offering novel insights into its genetic architecture and systemic regulatory mechanisms.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingling Yan, Ce Wu, Xiaona Liu, Pengfei Han, Jie Zhang, Zhipeng Gao, Xiaona Li, Weiyi Chen
{"title":"The Efficiency and Safety of Oxygen-Supplemented Accelerated Scleral Cross-Linking in Rabbits.","authors":"Lingling Yan, Ce Wu, Xiaona Liu, Pengfei Han, Jie Zhang, Zhipeng Gao, Xiaona Li, Weiyi Chen","doi":"10.1167/iovs.66.6.10","DOIUrl":"10.1167/iovs.66.6.10","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the efficacy and safety of accelerated scleral collagen cross-linking (SXL) with supplemental oxygen.</p><p><strong>Methods: </strong>The rabbit scleral tissues were randomly divided into seven different SXL protocols, including traditional (T)-SXL (3 mW/cm2 for 30 minutes, 3*30) and accelerated (A)-SXL (30 mW/cm2 for 3, 5, or 8 minutes, respectively, with or without supplemental oxygen). The control group received no ultraviolet-A (UVA) radiation. The tangent modulus of scleral strip was determined by uniaxial tensile test. The protocol with better mechanical property and shorter cross-linking time in vitro was selected for immediate safety assessment using electroretinogram (ERG) in vivo, hematoxylin and eosin (H&E) staining and TUNEL assay in vitro.</p><p><strong>Results: </strong>The tangent modulus was significantly greater in all SXL groups compared to the control group. The equatorial sclera showed a larger stiffening effect than the posterior. In the equatorial sclera, extending the irradiation time in normoxic A-SXL can result in a further enhancement of the stiffening effect. The tangent modulus was enhanced by 92% in the hyperoxic A-SXL group (30*3) compared with the normoxic A-SXL (30*3) group, and achieved the same mechanical performance as the T-SXL group. The oxygen supplementation did not play a role in further improving he stiffening effect at the posterior sclera. The ERG and H&E staining indicated no abnormalities in the sclera and retina. Apoptosis was only observed in the outer layer of the sclera in the A-SXL groups.</p><p><strong>Conclusions: </strong>A-SXL protocol of 30 mW/cm2 can improve the mechanical properties of the sclera. In particular, the protocol of 30 mW/cm2 for 3 minutes with supplemental oxygen showed excellent cross-linking efficacy with shorter surgical time and was relatively safe.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Second-Generation PDE 5 Inhibitor, Avanafil, on Retinal Function: Studies From Ex Vivo ERG.","authors":"Sama Saeid, Frans Vinberg, Ari Koskelainen","doi":"10.1167/iovs.66.6.14","DOIUrl":"10.1167/iovs.66.6.14","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates whether avanafil, a second-generation phosphodiesterase 5 (PDE5) inhibitor, exhibits reduced off-target effects on retinal function compared to first-generation inhibitors, by quantifying its impact on photoreceptor and bipolar cell signaling using transretinal electroretinography (tERG).</p><p><strong>Methods: </strong>We conducted ex vivo tERG using wild-type C57BL/6J and Gnat-/- mice. The dark-adapted isolated retinas were stimulated with 530-nm full-field flashes of light while perfused with controlled avanafil concentrations at 0.1, 0.3, 1, 3, and 10 µM. The inhibition constant of avanafil for light-activated phosphodiesterase 6 (PDE6) was determined from flash responses for rods and cones. The effects of avanafil on bipolar cell signaling were also assessed.</p><p><strong>Results: </strong>Avanafil exhibited dose-dependent inhibition of rod and cone phototransduction, characterized by slower response kinetics and reduced amplitude of dim flash responses. The inhibition constants for light-activated PDE6 were determined to be 1.74 µM for rods and 6.3 µM for cones. This study demonstrated that avanafil does not inhibit spontaneous PDE6 activity, and it has a lower inhibitory effect on light-activated PDE6 compared to other PDE5 inhibitors like sildenafil and zaprinast. Additionally, we conclude that avanafil primarily impacts photoreceptor cells, with no significant direct effect on rod bipolar cell signaling.</p><p><strong>Conclusions: </strong>This study provides quantitative insights into avanafil's impact on retinal function, supporting the hypothesis that it has reduced off-target effects on PDE6 and retinal signaling.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}