Journal of Ocular Pharmacology and Therapeutics最新文献

{"title":"NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs.","authors":"Corinna Galli, Elena Bastia, Douglas A Hubatsch, Carol Toris, Shan Fan, Andrea Unser, Feryan Ahmed, Karen Y Torrejon, Francesco Impagnatiello","doi":"10.1089/jop.2023.0102","DOIUrl":"10.1089/jop.2023.0102","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To determine NCX 470 (0.1%) and Lumigan^® (bimatoprost ophthalmic solution, 0.01%-LUM) intraocular pressure (IOP)-lowering activity after single or repeated (5 days) dosing along with changes in aqueous humor (AH) dynamics. <b><i>Methods:</i></b> Ocular hypotensive activity of NCX 470 and LUM was compared with vehicle (VEH) in Beagle dogs using TonoVet^®. Non-human primates (NHP) and bioengineered three-dimensional (3D) human Trabecular Meshwork/Schlemm's Canal (HTM/HSC™) constructs exposed to transforming growth factor-<i>β</i>2 (TGF<i>β</i>2) were used to monitor NCX 470 and LUM-induced changes in AH dynamics. <b><i>Results:</i></b> NCX 470 (30 μL/eye) showed greater IOP reduction compared with LUM (30 μL/eye) following single AM dosing [maximum change from baseline (CFB_max) = -1.39 ± 0.52, -6.33 ± 0.73, and -3.89 ± 0.66 mmHg (mean ± standard error of the mean) for VEH, NCX 470, and LUM, respectively]. Likewise, repeated 5 days daily dosing of NCX 470 resulted in lower IOP than LUM across the duration of the study (average IOP decrease across tests was -0.45 ± 0.22, -6.06 ± 0.15, and -3.60 ± 0.22 mmHg for VEH, NCX 470, and LUM, respectively). NCX 470 increased outflow facility (Cfl) <i>in vivo</i> in NHP (Cfl_VEH = 0.37 ± 0.09 μL/min/mmHg and Cfl_NCX470 = 0.64 ± 0.17 μL/min/mmHg) as well as <i>in vitro</i> (C_HTM/HSC) in HTM/HSC constructs (C_HTM/HSC__VEH = 0.47 ± 0.02 μL/min/mm²/mmHg and C_HTM/HSC__NCX470 = 0.76 ± 0.03 μL/min/mm²/mmHg). In addition, NCX 470 increased uveoscleral outflow (Fu_VEH = 0.62 ± 0.26 μL/min and Fu_NCX470 = 1.53 ± 0.39 μL/min with episcleral venous pressure of 15 mmHg) leaving unaltered aqueous flow (AHF_VEH = 2.03 ± 0.22 μL/min and AHF_NCX470 = 1.93 ± 0.31 μL/min) in NHP. <b><i>Conclusions:</i></b> NCX 470 elicits greater IOP reduction than LUM following single or repeated dosing. Data in NHP and 3D-HTM/HSC constructs suggest that changes in Cfl and Fu account for the robust IOP-lowering effect of NCX 470.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"389-396"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2024.0083","DOIUrl":"10.1089/jop.2024.0083","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"325-326"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Risk Factors and Complications of Anterior Migration of Ozurdex Implant: Lessons Learnt from the Previous Reports.","authors":"Hui Gim Khor, Pooi Wah Lott, Azida Juana Wan Ab Kadir, Sujaya Singh, Tajunisah Iqbal","doi":"10.1089/jop.2023.0012","DOIUrl":"10.1089/jop.2023.0012","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Ozurdex had shown promising anatomical and functional outcomes in managing refractory Irvine-Gass syndrome over the years. Burgeoning usage of Ozurdex has prompted the study of its related complications, particularly the anterior chamber migration of the implant. <b><i>Methods:</i></b> Literature reviews on the anterior chamber migration of the Ozurdex via PubMed, EBSCO, and TRIP databases were searched from 2012 to 2020. The predisposing factors, outcomes, and management of such cases were evaluated. <b><i>Results:</i></b> A total of 54 articles consisting of 105 cases of anterior migration of Ozurdex were included in this analysis. The vitrectomized eye and compromised posterior capsule were highly associated with this complication. About 81.9% of the cases had cornea edema upon presentation, with 31.4% of them ending up with cornea decompensation despite intervention. Although there was high intraocular pressure reported initially in 22 cases, only 2 cases required glaucoma filtration surgeries in which they had preexisting glaucoma. Numerous techniques of repositioning or surgical removal of the implant were described but they were challenging and the outcomes varied. <b><i>Conclusions:</i></b> A noninvasive method of manipulating the Ozurdex into the vitreous cavity via the \"Trendelenburg position, external pressure with head positioning\" maneuvers is safe yet achieves a favorable outcome. Precaution must be taken whenever offering Ozurdex to the high-risk eyes. Prompt repositioning or removal of the implant is crucial to deter cornea decompensation. Clinical Trial Registration number: NMRR-22-02092-S9X (from the Medical Research and Ethics Committee (MREC), Ministry of Health, Malaysia).</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"342-360"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10552017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.","authors":"Guanghao Qin, Jiayan Chen, Liangzhe Li, Yifan Qi, Yimeng Chen, Qing Zhang, Yi Wu, Yue You, Lanting Yang, Naici Guo, Salissou Moutari, Shaochong Bu, Jonathan E Moore, Ling Xu, Wei He, Sile Yu, Xingru He, Emmanuel Eric Pazo","doi":"10.1089/jop.2023.0098","DOIUrl":"10.1089/jop.2023.0098","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. <b><i>Methods:</i></b> In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. <b><i>Results:</i></b> The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm², and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, <i>P</i> = 0.172) and CNFD (21.46 ± 8.41, <i>P</i> = 0.163). Finally, at week 8, all parameters had significant improvements. <b><i>Conclusion:</i></b> Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"370-378"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of HDAC1 and 3 in the Presence of Systemic Inflammation Reduces Retinal Degeneration in a Model of Dry Age-Related Macular Degeneration.","authors":"Shahid Husain, Elisabeth Obert, Sudha Singh, Gloriane Schnabolk","doi":"10.1089/jop.2023.0163","DOIUrl":"10.1089/jop.2023.0163","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Previously, we identified increased retinal degeneration and cytokine response in a mouse model of dry age-related macular degeneration (AMD) in the presence of systemic inflammation from rheumatoid arthritis (RA). Histone deacetylases (HDACs) regulate cytokine production by reducing acetylation and are found to be dysregulated in inflammatory diseases, including RA and AMD. Therefore, this current study investigates the effect of HDAC inhibition on AMD progression in the presence of systemic inflammation. <b><i>Methods:</i></b> Collagen induced arthritis (CIA) was induced in C57BL6J mice, followed by sodium iodate (NaIO₃)-induced retinal degeneration. Mice were treated with a selective HDAC class I inhibitor, MS-275, and retinal structure [optical coherence tomography (OCT)], function (electroretinography), and molecular changes quantitative real-time polymerase chain reaction (RT-qPCR, Western Blot) were assessed. <b><i>Results:</i></b> NaIO₃ retinal damage was diminished in CIA mice treated with MS-275 (<i>P</i> ≤ 0.05). While no significant difference was observed in retinal pigment epithelium (RPE) function, a trend in increased c-wave amplitude was detected in CIA + NaIO₃ mice treated with MS-275. Finally, we identified decreased <i>Hdac1</i>, <i>Hdac3</i>, and <i>Cxcl9</i> expression in CIA + NaIO₃ mouse RPE/choroid when treated with MS-275 (<i>P</i> ≤ 0.05). <b><i>Conclusions:</i></b> Our data demonstrate that HDAC inhibition can reduce the additive effect of NaIO₃-induced retinal degeneration in the presence of systemic inflammation by CIA as measured by OCT analysis. In addition, HDAC inhibition in CIA + NaIO₃ treated mice resulted in reduced cytokine production. These findings are highly innovative and provide additional support to the therapeutic potential of HDAC inhibitors for dry AMD treatment.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"397-406"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Experimental Corneal Neovascularization by the Tight Junction Protein ZO-1.","authors":"Qingying Yao, Hongya Wu, Hang Ren, Jiufa Cao, Ying Shao, Gaoqin Liu, Peirong Lu","doi":"10.1089/jop.2023.0162","DOIUrl":"10.1089/jop.2023.0162","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To explore the effects of the tight junction protein zonula occludens 1 (ZO-1) on experimental corneal neovascularization (CNV). <b><i>Methods:</i></b> CNV models were established in the left eyes of BALB/c mice using NaOH. Anti-ZO-1 neutralizing antibody was topically applied to the burnt corneas after modeling thrice a day for 1 week. CD31 expression was analyzed to calculate the ratio of CNV number to area using a corneal whole-mount fluorescent immunohistochemical assay. Messenger ribonucleic acid (mRNA) and protein expression levels of ZO-1, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), phosphorylated protein kinase C (pPKC), and clusterin in burned corneas were detected by reverse transcriptase polymerase chain reaction (PCR) and western blot analyses. Infiltration of neutrophils, macrophages, and progenitor cells was examined by flow cytometry. <b><i>Results:</i></b> CNV was obviously greater in 45 s than in 15 s alkali injury group. In another experiment, CNV was obviously greater in the ZO-1 antibody group than in the vehicle-treated group. Corneal mRNA and protein expression levels of VEGF, IL-1β, IL-6, IL-8, IL-18, and MCP-1 were significantly higher in the ZO-1 antibody group than in the control group. Infiltration of neutrophils, macrophages, and progenitor cells was significantly greater in the ZO-1 antibody group than in the control group. TNF-α expression was much higher in 45 s than in 15 s alkali injury group. However, protein expression of pPKC and clusterin was much lower in 45 s than in 15 s alkali injury group. <b><i>Conclusions:</i></b> Anti-ZO-1 neutralizing antibody-treated mice exhibited enhanced alkali-induced CNV through enhanced intracorneal infiltration of progenitor and inflammatory cells.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":"40 6","pages":"379-388"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2024.0054","DOIUrl":"10.1089/jop.2024.0054","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"259-260"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Complexities of Severe Acute Respiratory Syndrome Coronavirus 2: A Comprehensive Ophthalmic and Systemic Perspective.","authors":"Piergiorgio Neri, Yanny Perez, Aniruddha Agarwal, Francesco Pichi","doi":"10.1089/jop.2024.0037","DOIUrl":"10.1089/jop.2024.0037","url":null,"abstract":"<p><p>The editorial explores the profound implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which emerged in December 2019 and rapidly evolved into a global health crisis. Despite initial focus on respiratory symptoms, the virus revealed significant ocular implications, prompting a reevaluation of the eye's role in its transmission, diagnosis, and systemic effects. The paradoxical nature of SARS-CoV-2-simultaneously novel and familiar within the coronavirus family-has been central to guiding the global medical response, including the swift development of vaccines. The pandemic has intensified research into the eye's susceptibility to viral infections, enhancing our understanding of virus-host interactions and the systemic impacts of viral diseases. The editorial delves into the pathophysiology of SARS-CoV-2, highlighting its potential to trigger autoinflammatory and autoimmune reactions with significant ocular repercussions. It examines the rapid vaccine development and deployment, the associated ocular side effects, and the ongoing research necessary to mitigate these outcomes. As the World Health Organization declared the end of COVID-19 as a public health emergency, the focus has shifted toward understanding the virus's long-term implications, including its effects on ocular health. This work underscores the critical role of interdisciplinary collaboration in addressing the systemic impacts of viral infections. It emphasizes the importance of ophthalmology in the broader context of public health and highlights the need for continued vigilance, research, and adaptation in a postpandemic world. The editorial calls for an integrated approach to health care, emphasizing the lessons learned from the SARS-CoV-2 pandemic to prepare for future health challenges, with a particular focus on the intersection of virology, immunology, and ophthalmology.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"253-258"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AG-920 (Articaine) Ophthalmic Solution: A Masked, Active-Controlled Evaluation of Its Local Anesthetic Efficacy and Safety in Pediatric Patients.","authors":"Victor H Gonzalez, Martin Uram, Audrey Schupp, Michelle Widmann, Gary D Novack","doi":"10.1089/jop.2023.0187","DOIUrl":"10.1089/jop.2023.0187","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> The safety and efficacy of a novel topical ocular anesthetic (AG-920 sterile ophthalmic solution, 8%) was previously evaluated in adults. For both clinical and regulatory purposes, this new agent was evaluated in children. <b><i>Methods:</i></b> This was a Phase 3, randomized, active-controlled, single-masked, parallel-group design study in healthy pediatric subjects performed at a private practice retina clinic in the United States. The safety and anesthetic efficacy of AG-920 was compared with proparacaine hydrochloride ophthalmic solution 0.5% in 60 children undergoing ophthalmic examinations. The primary efficacy endpoint was whether the investigator was able to perform the eye examination. <b><i>Results:</i></b> In all subjects in each treatment group, the investigator was able to perform the eye examination without additional local anesthetic. There were no adverse events reported in this study. In both the study eye and fellow eye, there were no notable changes after dosing, and both treatment groups were similar. All external eye exams in all subjects in both treatment groups were normal. <b><i>Conclusions:</i></b> In this pediatric population aged 7 months to >11 years, AG-920 was therapeutically equivalent to marketed proparacaine with respect to having an ophthalmic examination performed without needing additional local anesthetic. Further, AG-920 was well tolerated, and there were no clinically significant safety findings.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"293-296"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Emulsions: A Viable Approach for Ocular Drug Delivery.","authors":"Amol Chhatrapati Bisen, Saurabh Srivastava, Anjali Mishra, Sachin Nashik Sanap, Arpon Biswas, Abhijit Deb Choudhury, Ayush Dubey, Neeraj Mohan Gupta, Karan Singh Yadav, Madhav Nilakanth Mugale, Rabi Sankar Bhatta","doi":"10.1089/jop.2023.0166","DOIUrl":"10.1089/jop.2023.0166","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"261-280"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}