Journal of Ocular Pharmacology and Therapeutics最新文献

{"title":"Formulation Advances in Posterior Segment Ocular Drug Delivery.","authors":"Tumpa Sarkar, Niva Rani Gogoi, Bani Kumar Jana, Bhaskar Mazumder","doi":"10.1089/jop.2024.0153","DOIUrl":"https://doi.org/10.1089/jop.2024.0153","url":null,"abstract":"<p><p>Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as <i>in-situ</i> gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023588","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":"Comment on: \"Duration of Bare Sclera Pterygium Surgery Combined with Mitomycin C with and Without Tranexamic Acid: A Randomized Double-Blind Controlled Trial\".","authors":"Thiago Gonçalves Dos Santos Martins","doi":"10.1089/jop.2024.0204","DOIUrl":"https://doi.org/10.1089/jop.2024.0204","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023639","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":"Chlorhexidine Compared with Povidone-Iodine in Intravitreal Injection: A Systematic Review and Meta-Analysis.","authors":"Matheus Ribeiro Barbosa Cruz, Dillan Cunha Amaral, Ocílio Ribeiro Gonçalves, Laura Goldfarb Cyrino, Lucas Macedo Nascimento, Francisco Victor Carvalho Barroso, Ricardo Noguera Louzada, Tiago Nelson de Oliveira Rassi, Denisse J Mora-Paez, Jaime Guedes, Mauricio B Pereira","doi":"10.1089/jop.2024.0141","DOIUrl":"https://doi.org/10.1089/jop.2024.0141","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Povidone-iodine (PI) is the standard antiseptic for intravitreal injections (IVIs), while chlorhexidine (CHX) is a potential alternative. The efficacy of PI versus CHX in preventing endophthalmitis remains debated, with studies showing mixed results. <b><i>Objective:</i></b> To compare the effectiveness of using PI compared with CHX in IVI procedures regarding endophthalmitis rates, culture-positive endophthalmitis rates, and changes in visual acuity. <b><i>Methods:</i></b> A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched the PubMed, EMBASE, Cochrane, and Web of Science databases for studies using PI compared with CHX in the IVI procedure. Statistical analysis was done using R software. <b><i>Results:</i></b> Four studies encompassing 453,340 eyes were included. The pooled results showed no statistical differences in endophthalmitis rates [odds ratio (OR): 1.26; 95% confidence interval (CI): 0.53-3.00]. In those who received the CHX group, there was no decrease in the rates of culture-positive endophthalmitis (OR: 2.04; 95% CI: 0.76-5.47), and the pooled results revealed no statistical differences in the mean change in visual acuity between the CHX and PI groups at final follow-up [mean difference: -0.02; 95% CI: -0.40 to 0.36]. Significant heterogeneity was identified in the post-procedure endophthalmitis rate and culture-positive endophthalmitis rate. <b><i>Conclusions:</i></b> Despite finding a trend toward higher rates of endophthalmitis with CHX, there are no statistical differences in using PI compared with CHX. However, our results are limited due to high heterogeneity. PI remains the gold standard, and a widespread shift to CHX cannot be justified based on the findings of this analysis.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006773","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":"Molecular Mechanisms of Vitamin E in Ocular Neurodegenerative Disorders: An Update on the Emerging Evidence and Therapeutic Implications.","authors":"Muhammad Zulfiqah Sadikan, Lidawani Lambuk, Nurhidayah Reshidan, Haryati Ahmad Hairi, Afiqq Aiman Abd Ghapor, Rohimah Mohamud, Nurul Alimah Abdul Nasir","doi":"10.1089/jop.2024.0125","DOIUrl":"https://doi.org/10.1089/jop.2024.0125","url":null,"abstract":"<p><p>Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950396","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 Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study.","authors":"Gautier Hoarau, Anne-Laurence Best, Sourour Zina-Meziou, Maya Benali-Abdallah, Mhamed Loukil, Magalie Bouvet, Emmanuel Barreau, Antoine Rousseau, Marc Labetoulle","doi":"10.1089/jop.2024.0099","DOIUrl":"10.1089/jop.2024.0099","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. <b><i>Methods:</i></b> A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. <b><i>Results:</i></b> A significant improvement of COSP (<i>p</i> < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. <b><i>Conclusion:</i></b> The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"24-32"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583354","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":"Selective Tissue Penetration of the Corneal Layers of Cyclosporin 2% Associated with Miglyol in Rabbits.","authors":"Gladys Gress, Fabien Lamoureux, Julien Bourgain, Ariella Ganem, Christophe Arnoult, Julie Gueudry, Marc Muraine","doi":"10.1089/jop.2024.0087","DOIUrl":"10.1089/jop.2024.0087","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Cyclosporin A (CsA) is a drug used to prevent immune rejection in corneal transplantation. Most grafts performed today are endothelial grafts which are complicated with poor penetration of CsA into the endothelium due to its hydrophobicity. To improve CsA penetration into the corneal a new ocular formulation of CsA 2% with Miglyol was developed and is commercially available. The purpose of this pharmacokinetic study was to determine the concentrations of CsA in all layers of the cornea, in particular in the endothelium after topical administration of CsA 2%-Miglyol in rabbits. <b><i>Methods:</i></b> Sixteen rabbits were divided in 4 groups according to the time from the last instillation of CsA 2%-Miglyol to corneal sampling. Rabbit eyes received one drop of CsA twice a day for 5 days. Corneal tissue and plasma samples were collected at 2, 6, 12, and 24 h. CsA concentrations were measured using liquid chromatography-tandem mass spectrometry method. <b><i>Results:</i></b> Maximum concentrations (Cmax) of CsA were obtained in corneal tissues within 2 h after the last instillation of CsA 2%-Miglyol, except in the endothelium (12 h). Cmax were 59.75 ± 12.09 ng/mg, 15.66 ± 4.31 ng/mg, 5.17 ± 0.88 ng/mg, and 2.65 ± 0.47 ng/mg for the epithelium, endothelium, anterior stroma and posterior stroma. CsA concentrations remained high over a 24-h in all corneal layers. <b><i>Conclusions:</i></b> The topical application of CsA 2%-Miglyol allowed a high concentration of CsA in the corneal endothelium. The good penetration of CsA into the endothelium suggests that this formulation can be effective to prevent endothelial graft rejection.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"17-23"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007130","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":"Acknowledgment of Reviewers 2024.","authors":"","doi":"10.1089/jop.2024.85690.revack","DOIUrl":"https://doi.org/10.1089/jop.2024.85690.revack","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":"41 1","pages":"39-40"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189706","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":"Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay.","authors":"Mohammed Bouhajib, Zia Tayab, Chantal Di Marco, Dennis Dong-Kyun Suh","doi":"10.1089/jop.2024.0113","DOIUrl":"10.1089/jop.2024.0113","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Previous pharmacokinetic studies conducted on atropine sulfate ophthalmical solution have utilized bioanalytical assays that lacked sufficient sensitivity to fully characterize the complete pharmacokinetic profile. To address these limitations, Pharma Medica Research Inc. has developed and validated an ultrasensitive bioanalytical method capable of accurately quantifying the active enantiomer, L-hyoscyamine, with a very low limit of quantitation of 0.500 pg/mL. The objective of this study was to evaluate the pharmacokinetics of L-hyoscyamine in healthy subjects using a highly sensitive bioanalytical assay. <b><i>Methods:</i></b> Ten subjects were administered 0.3 mg of Isopto Atropine solution into the conjunctival sac of the eye. Blood samples were taken as early as 2 min and up to 24 h following administration. The plasma samples were assayed for L-hyoscyamine using a chiral method with an analytical range of 0.500-500 pg/mL. The pharmacokinetic parameters were estimated using both a noncompartmental and compartmental approach. <b><i>Results:</i></b> The pharmacokinetics of L-hyoscyamine were fully characterized as there were no samples that were below the limit of quantitation following dosing. Using noncompartmental analysis, the mean C_max was 467.9 ± 159.4 pg/mL with a median (range) T_max of 0.5 (0.08-1) h. The mean area under the concentration-time curve was 1668.96 ± 436.02 h·pg/mL and the mean half-life was 3.91 ± 1.16 h. Overall, the study drug was well tolerated and no serious adverse events were reported. <b><i>Conclusion:</i></b> Through the utilization of a proprietary ultrasensitive bioanalytical method, a comprehensive investigation into the pharmacokinetics of L-hyoscyamine has been successfully conducted. This advanced method offers significant potential for optimizing study designs and facilitating in-depth examinations of the pharmacokinetics of ocularly administered atropine formulations.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"1-7"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375553","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":"Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension.","authors":"Carl Erb, Fotis Topouzis, Hari Jayaram, Fanny Allan, Sylvie Nisslé, Francisco J Muñoz-Negrete, Ingeborg Stalmans","doi":"10.1089/jop.2024.0092","DOIUrl":"10.1089/jop.2024.0092","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Pharmacokinetic evaluation of ocular penetration and systemic accumulation of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel). <b><i>Methods:</i></b> In a preclinical study, pigmented rabbits received a single ocular administration of PFB 0.01% gel (<i>N</i> = 15) or preserved bimatoprost 0.01% or 0.03% ophthalmic solution [PB 0.01% (<i>N</i> = 15) or PB 0.03% (<i>N</i> = 15)]. The aqueous humor, iris, and ciliary body were analyzed for bimatoprost+bimatoprost free acid. In a Phase 1, randomized, open-label clinical study, healthy participants received PFB 0.01% gel (<i>N</i> = 20) or PB 0.01% (<i>N</i> = 20) daily in each eye (Days 1-15). Bimatoprost levels in human plasma were analyzed on Days 1 and 15. All serological analyses used validated methods. Adverse events were collected throughout and ocular assessments were performed on Days 1 and 15. <b><i>Results:</i></b> In the preclinical study, Cmax (bimatoprost+bimatoprost free acid) for PFB 0.01% gel, PB 0.01%, and PB 0.03% was 50.2, 26.3, and 59.9 ng/mL; AUC_0.5-8 h was 134.0 ng·h/mL, 67.0 ng·h/mL, and 148.0 ng·h/mL. In the clinical study, systemic exposure to bimatoprost (AUC_0-last) on Days 1 and 15 was lower for PFB 0.01% gel (0.5248 and 0.5645 ng·min/mL) than PB 0.01% (0.8461 and 0.7551 ng·min/mL), with no systemic accumulation of bimatoprost in either group. There were no clinically important differences between groups in ocular or systemic tolerability in the clinical study and no serious adverse events. <b><i>Conclusions:</i></b> PFB 0.01% gel showed improved ocular penetration compared with PB 0.01%. Systemic absorption was comparable, with a favorable clinical safety profile, supporting PFB 0.01% gel as a potential treatment for glaucoma and ocular hypertension.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"8-16"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605046","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":"Duration of Vascular Endothelial Growth Factor Suppression after Intravitreal Injection of Faricimab in Macaque Eyes.","authors":"Riko Matsumoto, Shumpei Obata, Masashi Kakinoki, Osamu Sawada, Ikuo Kawamoto, Mitsuru Murase, Masahito Ohji","doi":"10.1089/jop.2024.0138","DOIUrl":"10.1089/jop.2024.0138","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To evaluate the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal faricimab (IVF) injection. <b><i>Methods:</i></b> Faricimab (6 mg/50 µL) was injected into the vitreous cavity of the right eye of 6 macaques. Aqueous humor samples (150 μL) were collected from both eyes immediately before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after injection. The VEGF concentrations in the aqueous humor were measured using an enzyme-linked immunosorbent assay. <b><i>Results:</i></b> The VEGF was undetectable until 4 weeks after IVF injection in 4 eyes and until 6 weeks in the remaining 2 eyes. The mean duration of complete VEGF suppression was 4.7 weeks (range, 4-6 weeks). The VEGF concentration did not decrease in the aqueous humor of the non-injected fellow eyes. <b><i>Conclusions:</i></b> Faricimab effectively suppressed the VEGF concentrations in the aqueous humor of macaques for an average of 4.7 weeks after a single intravitreal injection. It did not reduce the VEGF concentrations in the aqueous humor of the fellow eyes.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"33-38"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365590","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}