American Journal of Ophthalmology最新文献

{"title":"Large recurrent stromal iris cyst successfully treated with aspiration and irrigation of 100% ethanol and fluorescein.","authors":"Cody Lo,Abdullah Al-Hammadi,Abdullah Al-Kaabi","doi":"10.1016/j.ajo.2025.12.037","DOIUrl":"https://doi.org/10.1016/j.ajo.2025.12.037","url":null,"abstract":"","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"84 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choroidal Macrovessel Complicated by Choroidal Neovascularisation","authors":"Giuseppe Maria ALBANESE , Georges CAPUTO , Youssef ABDELMASSIH","doi":"10.1016/j.ajo.2025.12.033","DOIUrl":"10.1016/j.ajo.2025.12.033","url":null,"abstract":"","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"283 ","pages":"Pages e3-e4"},"PeriodicalIF":4.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathology of the Outer Retina: Crosstalk With the Immune System","authors":"Gerhild Wildner ,&nbsp;Miranda Gehrke ,&nbsp;Olaf Strauß","doi":"10.1016/j.ajo.2025.12.032","DOIUrl":"10.1016/j.ajo.2025.12.032","url":null,"abstract":"<div><h3>Objective</h3><div>The retinal pigment epithelium (RPE) forms the outer blood-retina barrier. This barrier separates the retina from the choriocapillaris, as well as the immune system. The RPE contributes to the immune privilege of the eye by communicating with the local and systemic immune systems via various receptors and soluble factors. We recently described the expression and upregulation of the transcription factor FoxP3 in stressed RPE cells <em>in vivo</em> and <em>in vitro</em>. FoxP3 was initially described as being specific to regulatory T cells. Based on the hypothesis that different FoxP3 variants are expressed in RPE cells, we investigated the subcellular localization of FoxP3 using a panel of nine antibodies raised against different FoxP3 epitopes in ARPE-19 cells.</div></div><div><h3>Design</h3><div>We investigated cytokine secretion and FoxP3 expression in stressed and unstressed ARPE-19 cells.</div></div><div><h3>Methods</h3><div>Culture supernatants from ARPE-19 cells treated with LPS or with mechanical disruption of the cell layer were investigated for cytokine secretion using a multiplex assay. The cells were then stained with immunofluorescent antibodies that target different FoxP3 domains and phosphorylation sites to detect the intracellular localization of FoxP3.</div></div><div><h3>Main outcome measures</h3><div>Detection of FoxP3 at the subcellular level by identifying different epitopes on the protein.</div></div><div><h3>Results</h3><div>Stressed ARPE-19 cells upregulate inflammatory cytokines (IL-6 and MCP-1), which correspond with FoxP3 localization patterns in the cytoplasm and nucleus (phosphorylated FoxP3), depending on the epitope detected by the antibodies.</div></div><div><h3>Conclusions</h3><div>Stressed RPE cells switch from a tolerogenic to an effector phenotype, yet they immediately re-establish immune privilege by upregulating the transcription factor FoxP3, similar to T cells in the immune system. These different FoxP3 detection patterns suggest an RPE-specific role in maintaining the immune barrier, as well as in other non-T cell tissues that express FoxP3.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 56-65"},"PeriodicalIF":4.2,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Peripapillary and Macular Microvascular Changes Following Ruthenium-106 Plaque Brachytherapy For Uveal Melanomas","authors":"Mai A. Abdelkader,&nbsp;Shaymaa H. Salah,&nbsp;Salma F. Al-Etr,&nbsp;Layla El Qadi,&nbsp;Islam Y. Swaify,&nbsp;Tamer A. Macky,&nbsp;Hany Hamza,&nbsp;Abdussalam M. Abdullatif","doi":"10.1016/j.ajo.2026.01.001","DOIUrl":"10.1016/j.ajo.2026.01.001","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate early peripapillary and macular microvascular changes following ruthenium-106 (Ru-106) episcleral plaque brachytherapy for uveal melanoma using optical coherence tomography angiography (OCTA).</div></div><div><h3>Design</h3><div>Prospective case series.</div></div><div><h3>Subjects</h3><div>Twenty-four eyes of 24 patients with extramacular uveal melanoma treated with Ru-106 plaque brachytherapy at Cairo University Ocular Oncology Service.</div></div><div><h3>Methods</h3><div>All patients underwent ophthalmic evaluation and OCTA imaging at baseline, 3 months, and 6 months post-treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Quantitative OCTA parameters included vessel density (VD) in the superficial (SCP), deep (DCP), and radial peripapillary capillary (RPC) plexuses, as well as foveal avascular zone (FAZ) area. Radiation doses to the tumor apex, fovea, and optic nerve were also recorded.</div></div><div><h3>Results</h3><div>Mean best-corrected visual acuity (BCVA) declined from 0.44 ± 0.30 logMAR at baseline to 0.78 ± 0.72 at 6 months (<em>p</em> = .028). Tumor height decreased significantly (<em>p</em> &lt; .001). No clinical signs of radiation maculopathy or optic neuropathy were detected at 6 months. RPC density showed an early significant reduction (49.06 ± 2.77% to 44.95 ± 4.65% at 3 months, <em>p</em> &lt; .001), with no further decline at 6 months; this loss was greater in tumors &lt; 2 disc diameters from the optic disc. SCP showed localized reductions (46.23 ± 3.73% at baseline, 43.96 ± 5.15% at 3 months and 44.64 ± 4.26% at 6 months, <em>p</em> = .083). By contrast, DCP density declined progressively and diffusely (45.17 ± 4.86% to 44.90 ± 4.87% at 3 months and 42.23 ± 3.68% at 6 months, <em>p</em> = .017), accompanied by significant FAZ enlargement (0.25 ± 0.12 to 0.34 ± 0.11 mm², <em>p</em> &lt; .001). Higher optic nerve radiation doses correlated with RPC loss (<em>r</em> = 0.492, <em>p</em> = .014) and poorer BCVA at 3 months (<em>r</em>=-0.454, <em>p</em> = .026) and 6 months (<em>r</em>=-0.412, <em>p</em> = .045), whereas macular doses showed no significant correlation. Tumor location influenced vascular response, with post-equatorial tumors showing greater DCP compromise, and pre-equatorial tumors exhibiting more SCP reduction. Systemic comorbidities did not significantly alter outcomes.</div></div><div><h3>Conclusions</h3><div>Ru-106 brachytherapy induces early, subclinical microvascular injury detecTable by OCTA. RPC changes are early and strongly correlate with optic nerve radiation dose and visual decline, SCP changes are localized, while DCP demonstrates progressive and generalized loss. Tumor location influenced injury patterns, reflecting differential radiation exposure. OCTA may serve as a noninvasive biomarker for early detection and risk stratification of radiation-induced microvascular injury.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 133-143"},"PeriodicalIF":4.2,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"En Face Optical Coherence Tomography and OCT Angiography in the Pathoanatomy of Inflammatory Macular Disease","authors":"Alessandro Feo ,&nbsp;David Sarraf","doi":"10.1016/j.ajo.2025.12.031","DOIUrl":"10.1016/j.ajo.2025.12.031","url":null,"abstract":"<div><h3>Purpose</h3><div>To review the pivotal role of en face optical coherence tomography (OCT) and OCT angiography (OCTA) in elucidating the pathoanatomy, diagnostic markers, and clinical management of inflammatory macular diseases. These noninvasive modalities provide depth-resolved, layer-specific visualization of structural and vascular alterations, enhancing our understanding of disease mechanisms and facilitating monitoring of disease activity and therapeutic response.</div></div><div><h3>Methods</h3><div>This perspective article synthesizes recent advances in multimodal imaging (MMI) with emphasis on en face OCT and OCTA across the spectrum of posterior noninfectious and infectious uveitic disorders. Representative diseases include multiple evanescent white dot syndrome (MEWDS), punctate inner choroidopathy (PIC), and idiopathic multifocal choroiditis (iMFC), acute zonal occult outer retinopathy (AZOOR), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and its chronic variants, serpiginous choroiditis (SC), acute syphilitic posterior placoid chorioretinopathy (ASPPC), and Vogt-Koyanagi-Harada (VKH) disease. Imaging signatures were reviewed in relation to pathophysiology, differential diagnosis, and clinical management.</div></div><div><h3>Results</h3><div>En face OCT delineates disease-specific topographic patterns: “dots and spots” in MEWDS, hyperreflective plaques in PIC/iMFC, trizonal maps in AZOOR, sharply demarcated placoid lesions in APMPPE, geographic patterns in SC, and concentric hyperreflective “fingerprint” rings in VKH. OCTA provides complementary vascular insights, distinguishing preserved vs impaired choriocapillaris (CC) flow and revealing disease-driven ischemia. MEWDS typically demonstrates preserved CC perfusion, in contrast to the flow deficits of APMPPE, relentless placoid chorioretinitis, and SC. In PIC/iMFC, OCTA enables detection of inflammatory choroidal neovascularization (iCNV), while in ASPPC and VKH, it captures reversible or persistent CC flow voids following appropriate systemic therapy. Structural-vascular correlation permits differentiation between ischemic and nonischemic disorders, recognition of masquerades, and monitoring of subclinical disease activity.</div></div><div><h3>Conclusions</h3><div>En face OCT and OCTA have redefined the diagnostic and management landscape of inflammatory macular diseases by providing rapid, reproducible, and layer-specific structural-vascular information. Their disease-specific signatures enhance accuracy, support treatment decisions, and improve monitoring of progression and complications such as inflammatory CNV. Integration of these tools into routine multimodal imaging protocols is essential, while future research should prioritize standardization of acquisition and interpretation criteria, quantitative biomarkers, and expanded use of widefield technologies to capture peripheral and longitudinal disease dynamics.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 110-122"},"PeriodicalIF":4.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OCT Imaging of Macular Hole Containing a Gas Bubble after Retinal Detachment Repair","authors":"Lauren C. Kiryakoza ,&nbsp;Jason Fan","doi":"10.1016/j.ajo.2025.12.036","DOIUrl":"10.1016/j.ajo.2025.12.036","url":null,"abstract":"","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"283 ","pages":"Page e5"},"PeriodicalIF":4.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven-Year Clinical Outcomes and Optical Quality of Implantable Collamer Lens Implantation Versus KLEx for Myopia Correction","authors":"Mingrui Cheng ,&nbsp;Mingwei Li ,&nbsp;Guanghan Xu ,&nbsp;Boliang Li ,&nbsp;Yinjie Jiang ,&nbsp;Yadi Lei ,&nbsp;Yanyu Qi ,&nbsp;Xun Chen ,&nbsp;Xiaoying Wang","doi":"10.1016/j.ajo.2025.12.027","DOIUrl":"10.1016/j.ajo.2025.12.027","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to compare the seven-year clinical outcomes of Implantable Collamer Lens (ICL) implantation and keratorefractive lenticule extraction (KLEx) for the correction of myopia in patients with anisometropia, with a focus on evaluating long-term refractive stability, visual quality, and patient satisfaction.</div></div><div><h3>Setting</h3><div>Eye and ENT Hospital of Fudan University, Shanghai, China.</div></div><div><h3>Design</h3><div>Retrospective contralateral eye comparative case series</div></div><div><h3>Methods</h3><div>The study encompassed 50 eyes from 25 myopic patients. The eye with the higher degree of myopia underwent ICL implantation, while the contralateral eye underwent KLEx surgery. Comprehensive preoperative evaluations included assessments of visual acuity, refractive error, corneal topography, and endothelial cell density. ICL V4c implantation and KLEx were performed following standardized surgical protocols. Postoperative follow-up evaluations at 1 month and 7 years included measurements of visual acuity, refractive stability, wavefront aberrations, retinal image quality, and patient-reported visual disturbances.</div></div><div><h3>Results</h3><div>At the 7-year follow-up, both groups demonstrated high levels of safety visually and physiologically at 7 years, with safety indices of 1.23 ± 0.27 in the ICL group vs 1.08 ± 0.12 in the KLEx group, and endothelial cell density of 2654.96 ± 225.98 cells/mm² in the ICL group vs 2576.92 ± 241.78 cells/mm² in the KLEx group. Efficacy also presented high efficacy indices of 1.13 ± 0.22 in the ICL group and 0.95 ± 0.15 in the KLEx group. Refractive stability was maintained in both groups, although axial length increased marginal significantly in the ICL group (0.35 ± 0.33 mm vs. 0.21 ± 0.21 mm, <em>P</em> = 0.002). ICL exhibited superior visual outcomes, as evidenced by lower intraocular scattering (OSI: 1.13 ± 0.42 vs. 1.57 ± 0.62, <em>P</em> = 0.012) and a higher Strehl ratio (0.20 ± 0.03 vs. 0.16 ± 0.03, <em>P</em> = 0.024). KLEx was associated with lower whole-eye higher-order aberrations for a 3 mm pupil diameter (0.10 ± 0.06 µm vs. 0.12 ± 0.14 µm, <em>P</em> = 0.043). No significant differences were observed in disk halo size or pupil dynamics between the two groups.</div></div><div><h3>Conclusions</h3><div>Both ICL and KLEx are effective for long-term myopia correction, with ICL offering superior visual quality and stability, particularly in patients with high myopia. The combination of these techniques in anisometropic patients is feasible and provides a personalized treatment approach, ultimately enhancing overall visual outcomes and patient satisfaction.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 144-152"},"PeriodicalIF":4.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative Epiretinal Membrane After Fovea-sparing Versus Standard Internal Limiting Membrane Peeling for Myopic Traction Maculopathy","authors":"Akihiko Shiraki ,&nbsp;Nobuhiko Shiraki ,&nbsp;Kotaro Tsuboi ,&nbsp;Masaki Fukushima ,&nbsp;Ryota Akai ,&nbsp;Tomoko Ueda-Consolvo ,&nbsp;Yuichiro Ishida ,&nbsp;Keita Baba ,&nbsp;Kentaro Abe ,&nbsp;Hisashi Fukuyama ,&nbsp;Yuki Yamamoto ,&nbsp;Yuki Otsuka ,&nbsp;Ryuya Hashimoto ,&nbsp;Motohiro Kamei ,&nbsp;Hirokazu Sakaguchi ,&nbsp;Fumi Gomi ,&nbsp;Yasushi Ikuno ,&nbsp;Takatoshi Maeno ,&nbsp;Yusuke Oshima ,&nbsp;Jay Chhablani ,&nbsp;Taku Wakabayashi","doi":"10.1016/j.ajo.2025.12.028","DOIUrl":"10.1016/j.ajo.2025.12.028","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the incidence and outcomes of postoperative epiretinal membrane (ERM) formation after fovea-sparing internal limiting membrane peeling (FSIP) and standard internal limiting membrane (ILM) peeling in eyes with myopic traction maculopathy (MTM).</div></div><div><h3>Design</h3><div>Multicenter, retrospective clinical cohort study (Schisis report no. 4).</div></div><div><h3>Methods</h3><div>Patients with MTM who underwent pars plana vitrectomy (PPV) at 10 institutions between June 2008 and July 2024, with at least 12 months of follow-up, were included. Postoperative ERM was identified on optical coherence tomography (OCT) and graded using the Govetto classification. The main outcomes were the 12-month incidence of postoperative ERM and postoperative visual outcomes.</div></div><div><h3>Results</h3><div>We included a total of 206 eyes (201 patients); 46 eyes treated with FSIP and 160 eyes treated with standard ILM peeling. Of the 206 eyes, postoperative ERM developed in 16 eyes (7.8%) at 12 months: 8 eyes (17.4%) in the FSIP group and 8 eyes (5.0%) in the standard ILM peeling group. The incidence of postoperative ERM was significantly higher in the FSIP group than in the standard ILM peeling group (<em>P</em> = .014), and univariable logistic regression analysis revealed that FSIP was significantly associated with postoperative ERM at 12 months (OR = 4.00, 95% CI = 1.39-11.55, <em>P</em> = .009). Of the 8 eyes with postoperative ERM after FSIP, 6 eyes showed stage 1 ERM and 2 eyes showed stage 2 ERM. Of the 8 eyes with postoperative ERM after standard ILM peeling, 7 eyes showed stage 1 ERM and 1 eye showed stage 2 ERM. No additional surgery was required for postoperative ERM during 12 months. Postoperative logarithm of minimum angle of resolution visual acuity at 12 months did not differ significantly between eyes with (0.50 ± 0.43) and without ERM (0.42 ± 0.52; <em>P</em> = .517). The incidence of postoperative macular hole (MH) was lower in the FSIP group (2.2%) than in the standard ILM peeling group (12.8%), although the difference was not statistically significant (<em>P</em> = .071).</div></div><div><h3>Conclusions</h3><div>FSIP increased the incidence of postoperative ERM compared with standard ILM peeling, but most ERMs were subclinical and did not affect vision. Despite the elevated ERM risk, the potential benefit of FSIP in reducing postoperative macular hole formation may outweigh its drawbacks.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 123-132"},"PeriodicalIF":4.2,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Guided Endpoint Selection for Neuroprotection Trials in Glaucoma","authors":"Douglas R. da Costa ,&nbsp;Rafael Scherer ,&nbsp;Swarup S. Swaminathan ,&nbsp;Henry Tseng ,&nbsp;Felipe A. Medeiros","doi":"10.1016/j.ajo.2025.12.038","DOIUrl":"10.1016/j.ajo.2025.12.038","url":null,"abstract":"<div><h3>Objective</h3><div>Standard Automated Perimetry (SAP) is the primary method for monitoring glaucoma progression and an established functional endpoint in clinical trials. A ≥7 dB loss in at least five prespecified test locations has been proposed as a potential endpoint for glaucoma trials, but identifying such vulnerable points in advance remains a major challenge. We developed an artificial intelligence model that uses baseline SAP data to predict the locations most likely to progress, enabling a targeted approach to endpoint selection in neuroprotection trials.</div></div><div><h3>Design</h3><div>Retrospective cohort study to predict progression.</div></div><div><h3>Subjects</h3><div>A total of 82,449 SAP tests from 14,237 eyes of 10,533 subjects with open-angle glaucoma across three independent datasets: the Bascom Palmer Ophthalmic Registry, the Duke Glaucoma Registry, and the University of Washington Humphrey Visual Field.</div></div><div><h3>Methods</h3><div>A graph attention network was trained on Bascom Palmer Ophthalmic Registry data, split at the patient level into development and internal validation datasets, to predict progression risk at each SAP location using baseline total deviation values and anatomically informed graph connectivity. For each eye, the five highest-risk points (High-5) were identified and compared with global mean deviation (MD) and the five lowest-risk points (Low-5). The model was applied without retraining to the Duke Glaucoma Registry and University of Washington Humphrey Visual Field cohorts for external validation.</div></div><div><h3>Main Outcome Measures</h3><div>Model ranking performance, neighborhood hit rate, rates of change at High-5, Low-5, and MD, discrimination by area under the receiver operating characteristic curve, and time to repeatable ≥7 dB decline.</div></div><div><h3>Results</h3><div>In progressing eyes, mean slopes at High-5 were −2.05 to −2.32 dB/y, four to five times steeper than Low-5 (−0.45 to −0.66; <em>P</em> &lt; .001) and approximately twice that of MD (−0.93 to −1.14; <em>P</em> &lt; .001). Area under the receiver operating characteristic curve for discriminating progressors from nonprogressors ranged from 0.883 to 0.937 for High-5, outperforming Low-5 (0.668-0.731; <em>P</em> &lt; .001) and MD (0.871-0.911; <em>P</em> = .003). Nearly all progressors reached the High-5 ≥7 dB threshold during follow-up.</div></div><div><h3>Conclusions</h3><div>The artificial intelligence-based model identified the most vulnerable visual field locations from baseline data. The High-5 metric provides a proof-of-concept framework consistent with regulatory concepts of functional endpoints and shows improved sensitivity to progression, supporting more efficient neuroprotection trials and personalized glaucoma monitoring.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 88-100"},"PeriodicalIF":4.2,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dazdotuftide: Novel Treatment for Noninfectious Uveitis with Superior Intraocular Pressure Safety Profile: A Randomized Clinical Trial","authors":"DAVID S CHU ,&nbsp;EDMUND TSUI ,&nbsp;LANA M RIFKIN ,&nbsp;ALAN G PALESTINE ,&nbsp;CADMUS RICH ,&nbsp;JENNIFER E THORNE ,&nbsp;DAPHNE HAIM-LANGFORD ,&nbsp;ZOHAR MILMAN ,&nbsp;EMILEE FULCHER ,&nbsp;RON NEUMANN ,&nbsp;MARC D DE SMET","doi":"10.1016/j.ajo.2025.12.034","DOIUrl":"10.1016/j.ajo.2025.12.034","url":null,"abstract":"<div><h3>PURPOSE</h3><div>To evaluate the safety and efficacy of dazdotuftide (TRS01 eye drops), a novel, steroid-free, anti-inflammatory drug in patients with active anterior noninfectious uveitis (NIU), following previous studies in which it had shown a favorable risk/benefit profile with regards to safety and specifically intraocular pressure (IOP) safety profile.</div></div><div><h3>DESIGN</h3><div>A randomized, double-masked, multicenter, active-controlled phase 3 trial.</div></div><div><h3>PARTICIPANTS</h3><div>Adults (≤75 years of age) and pediatric patients, with active anterior NIU, with or without uveitic glaucoma, on stable medical therapy for NIU or who had received no prior therapy, requiring further treatment for an active NIU flare-up. Patients eligible for inclusion had Anterior Chamber Cell (ACC) Grade 2 or Grade 3 on Visual Analog Scale in the study eye.</div></div><div><h3>METHODS</h3><div>Patients were randomized 2:1 to topical TRS01 1% or prednisolone acetate 1% administered 4 times daily for 28 days. Key ocular assessments included slit-lamp examination, ocular pain, Best Corrected Visual Acuity, IOP and dilated ophthalmoscopy.</div></div><div><h3>MAIN OUTCOME MEASURES</h3><div>Resolution of inflammation (ACC = 0), clinically meaningful improvement of ACC, ocular pain, flare, and IOP changes on Day 28.</div></div><div><h3>RESULTS</h3><div>The Full Analysis Set included 136 patients; the mean age was 43 years in the TRS01 arm and 42 years in the prednisolone acetate arm. 48% of TRS01 vs 68% of prednisolone acetate patients achieved ACC Grade = 0 on Day 28 (95.1% Confidence Interval (CI): −0.37, −0.02; <em>P</em> = .0311) and 64% of TRS01 vs 89% prednisolone acetate patients experienced clinically meaningful improvement of ACC Grade = 0 or 1, ie, ≤5 cells (95.1% CI: −0.33, −0.06; <em>P</em> = .0049). While TRS01 was found to be inferior to topical steroids to control ACC, TRS01 was noninferior to topical steroids to control flare and ocular pain and exhibited a superior IOP safety compared to topical steroids. For patients who reached ACC = 0, TRS01-treated patients benefited from statistically significantly improved safety outcomes for IOP (including change from baseline and at each IOP threshold evaluated [<em>P</em> &lt; .05]) versus steroid-treated patients.</div></div><div><h3>CONCLUSIONS</h3><div>TRS01 offers the potential to serve as an effective and safe treatment option in NIU that meets the urgent need for a drug that controls inflammation without the steroids’ associated risk of IOP elevation.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 78-87"},"PeriodicalIF":4.2,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}