{"title":"<i>In Vitro</i> Efficacy of Miltefosine Against Clinical Isolates of <i>Acanthamoeba</i> spp. from Patients with Keratitis.","authors":"Lakshminarayanan Gowtham, Savitri Sharma, Bhupesh Bagga","doi":"10.1080/08820538.2025.2467272","DOIUrl":"10.1080/08820538.2025.2467272","url":null,"abstract":"<p><strong>Purpose: </strong>The US Food and Drug Administration (USFDA) granted the miltefosine orphan drug designation in 2016 for treating <i>Acanthamoeba</i> keratitis. This study evaluates miltefosine's <i>in vitro</i> efficacy against clinical isolates of <i>Acanthamoeba</i> from patients with keratitis and its safety profile in human corneal epithelial cell line to rationalize its localized ocular application.</p><p><strong>Methods: </strong><i>Acanthamoeba</i> spp. isolated from corneal scrapings of keratitis patients (<i>n</i> = 17) were cultured axenically, genotyped, and tested for miltefosine's minimal cysticidal and trophozoicidal concentrations (MCC and MTC) by microbroth dilution method. Safer concentrations of miltefosine were determined using human corneal epithelial (HCE) cells at four incubation points. Trophozoites and cysts of one of the isolates, <i>A. castellanii</i>, were challenged on confluent monolayers of HCE in the presence and absence of miltefosine for 24 h. Cytopathic effects were evaluated using microscopic analysis.</p><p><strong>Results: </strong>The majority of <i>Acanthamoeba</i> isolates tested were T4 genotypes (94.11%). MTC<sub>90</sub> and MCC<sub>90</sub> of miltefosine were 0.125 and 4 mg/mL, respectively. Miltefosine was found safe on HCE at 0.0625 and 0.125 mg/mL for 4 and 0.25 h, respectively. Microscopical findings showed that <i>A. castellanii</i> trophozoites destroyed the cellular structures of HCE within 24 h without miltefosine. Drug pre-treatment prevented the initiation of infection at both the tested concentrations (0.0625 and 0.125 mg/mL) upto 24 h.</p><p><strong>Conclusion: </strong>Miltefosine was effective against <i>Acanthamoeba</i> trophozoites and cysts <i>in vitro</i> with >30-fold higher cidal concentration for cysts compared to trophozoites. An effective trophozoicidal concentration of miltefosine (0.125 mg/mL), found to be safe for HCEs, suggests its potential utility as an adjunct treatment for <i>Acanthamoeba</i> keratitis.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"767-774"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503857","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-06-20DOI: 10.1080/08820538.2025.2521942
Mohammad Javed Ali
{"title":"Lacrimal History - Part 19: Doyens of Dacryology Series - René-Jacques Croissant de Garengeot (1688-1759) and His 1723 Treatise, 'Traité des Operations de Chirurgie'.","authors":"Mohammad Javed Ali","doi":"10.1080/08820538.2025.2521942","DOIUrl":"10.1080/08820538.2025.2521942","url":null,"abstract":"","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"691-694"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336840","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2024-11-22DOI: 10.1080/08820538.2024.2432904
Oliwia Kamieniecka
{"title":"Susac Syndrome: A Multidisciplinary Approach to Diagnosis and Management with an Emphasis on Ophthalmic Involvement.","authors":"Oliwia Kamieniecka","doi":"10.1080/08820538.2024.2432904","DOIUrl":"10.1080/08820538.2024.2432904","url":null,"abstract":"<p><strong>Background: </strong>Susac syndrome is a rare autoimmune microangiopathy that affects the small vessels of the retina, brain, and inner ear, leading to a characteristic triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. The syndrome often presents diagnostic challenges due to its overlapping symptoms with other conditions. Immunosuppressive therapies remain the cornerstone of treatment.</p><p><strong>Methods: </strong>A retrospective review of the literature from PubMed (1998-2024).</p><p><strong>Results: </strong>Special emphasis is placed on the role of ophthalmologists, who play a pivotal role in the diagnostic process. This article provides a comprehensive overview of the disease, focusing on the pathogenesis, clinical presentation, diagnostic process, and treatment approaches.</p><p><strong>Conclusion: </strong>By highlighting the role of ophthalmologists in recognizing and managing Susac Syndrome, this review underscores the importance of a multidisciplinary approach to improve outcomes in this complex, multisystem disease.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"727-732"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688687","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-02-24DOI: 10.1080/08820538.2025.2468381
Isana Nakajima, Koji Yoshino, Hideki Tsuji
{"title":"Incidence and Management of Retinopathy and Uveitis in Patients Receiving BRAF/MEK Inhibitor Therapy.","authors":"Isana Nakajima, Koji Yoshino, Hideki Tsuji","doi":"10.1080/08820538.2025.2468381","DOIUrl":"10.1080/08820538.2025.2468381","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the clinical features of ocular adverse events in patients receiving BRAF/MEK inhibitor therapy.</p><p><strong>Methods: </strong>In this retrospective study, 65 patients were treated with BRAF/MEK inhibitors (dabrafenib/trametinib or encorafenib/binimetinib).</p><p><strong>Results: </strong>Of the 65 patients, 28 had malignant melanoma and 37 had non-melanoma malignancies. Bilateral MEK-associated retinopathy was observed in nine cases; none experienced vision loss due to MEK-associated retinopathy. Uveitis was diagnosed in four patients (6.1%), three of whom presented with Vogt-Koyanagi-Harada (VKH)-like uveitis. All VKH-like uveitis cases were observed in patients with melanoma and their incidences were significantly higher in these patients than in those without melanoma (<i>p</i> = .04). Treatment with corticosteroids resulted in either resolution or control of symptoms in all cases of VKH-like uveitis, enabling continuation of BRAF/MEK inhibitor therapy.</p><p><strong>Conclusion: </strong>VKH-like uveitis was found to be significantly more frequent in patients with melanoma than in those with other malignancies.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"775-781"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483911","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":"Potential Involvements of Anterior Segment Dysgenesis-Associated Genes in Primary Congenital Glaucoma.","authors":"Goutham Pyatla, Samir Bera, Ashish Mishra, Anil K Mandal, Subhabrata Chakrabarti","doi":"10.1080/08820538.2024.2435944","DOIUrl":"10.1080/08820538.2024.2435944","url":null,"abstract":"<p><strong>Background: </strong>The anterior segment of the eye plays a crucial role in maintaining the normal intraocular pressure and vision. Developmental defects in the anterior segment structures lead to anterior segment dysgenesis (ASD) and primary congenital glaucoma (PCG), which share overlapping clinical features. Several genes have been mapped and characterized in ASD, some of which are also involved in other glaucoma phenotypes. PCG exhibits genetic heterogeneity like ASD, but the known genes do not account for the entire genetic basis of the disease. Considering the significant phenotypic and genotypic overlap between ASD and PCG, this article explores the possible involvements of ASD-associated genes in PCG pathogenesis.</p><p><strong>Methods: </strong>A nonsystematic search in PubMed was performed using various combinations of keywords related to ASD, glaucoma, genetics, and molecular mechanisms, and articles published up until March 2024 were considered. Specifically, information pertaining to ASD-associated genes (<i>FBN1, FOXE3, HMX1, LMX1B, MAF, OTX2, PAX6, PITX2, PITX3, PRDM5, PRSS56, RAX, SLC4A11, SOX2, TRIM44, VAX1</i>, and <i>WT1</i>) was extracted, and their expressions were determined from the GTEx and EMBL-EBI Expression Atlas. Interactions of these genes were determined through the Ingenuity Pathway Analysis software.</p><p><strong>Results: </strong>Most of the ASD-associated genes were found to be highly expressed in the early embryonic stages. Interactome analysis revealed that <i>TRIM44, PAX6, WT1, SOX2, OTX2, PRDM5</i>, and <i>FBN1</i> interacted through the NFκB and Akt/PI3K pathways, either directly, or through interactions with other partners. <i>FOXC1, PITX2</i>, and <i>HMX1</i> interacted through Wnt and Hedgehog signaling pathways. Both ASD and PCG present similar clinical features and harbor mutations in genes that are implicated in both these conditions. Collectively, we constructed a hypothetical model and proposed two parallel mechanisms comprising the defects in the anterior chamber angle and cell death in PCG pathogenesis.</p><p><strong>Conclusions: </strong>Our findings suggest that complex interplay of these ASD-associated genes and their interactions could potentially result in defects in the anterior chamber angle and trabecular meshwork and induce cell death, resulting in PCG pathogenesis.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"733-742"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802225","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-03-17DOI: 10.1080/08820538.2025.2471443
Ryung Lee, Joshua Ong, Ethan Waisberg, Thomas Mader, John Berdahl, Alex Suh, Nicholas Panzo, Hamza Memon, Ritu Sampige, Blake Katsev, Cihan Mehmet Kadipasaoglu, Christopher E Mason, Afshin Beheshti, Sara R Zwart, Scott M Smith, Andrew G Lee
{"title":"Potential Risks of Ocular Molecular and Cellular Changes in Spaceflight.","authors":"Ryung Lee, Joshua Ong, Ethan Waisberg, Thomas Mader, John Berdahl, Alex Suh, Nicholas Panzo, Hamza Memon, Ritu Sampige, Blake Katsev, Cihan Mehmet Kadipasaoglu, Christopher E Mason, Afshin Beheshti, Sara R Zwart, Scott M Smith, Andrew G Lee","doi":"10.1080/08820538.2025.2471443","DOIUrl":"10.1080/08820538.2025.2471443","url":null,"abstract":"<p><strong>Purpose: </strong>Many fundamental cellular and molecular changes are known to occur in biological systems during spaceflight, including oxidative stress, DNA damage, mitochondrial damage, epigenetic factors, telomere lengthening, and microbial shifts. We can apply the consequences of these molecular changes in ocular cells, such as the retinal ganglion cells and corneal epithelium, to identify ophthalmologic risks during spaceflight. This review aims to discuss the potential molecular changes in greater detail and apply the principles to ocular cells and ophthalmic disease risk in astronauts.</p><p><strong>Methods: </strong>A targeted, relevant search of the literature on the topic and related topics of ocular surface and spaceflight was conducted with scholarly databases PubMed, Web of Science, and Embase from inception to July2024 with search terms \"oxidative stress\"; \"DNA damage\"; \"Mitochondrial Dysfunction\"; \"Epigenetics\"; \"Telomeres\"; \"Microbiome\"; \"ocular cells\"; \"spaceflight\"; \"microgravity\"; \"radiation.\"</p><p><strong>Results: </strong>A total of 115 articles were included following screening and eligibility assessment. Key findings include molecular changes and their contributions to ophthalmic diseases like cataracts, spaceflight-associated neuro-ocular syndrome, and dry eye syndrome.</p><p><strong>Conclusion: </strong>This review provides a comprehensive overview of risks to vision associated with long-duration spaceflight missions beyond low Earth orbit (LEO). Further investigation into targeted countermeasures is imperative to mitigate vision-threatening sequelae in astronauts undertaking deep-space exploration.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"756-766"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650659","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-06-30DOI: 10.1080/08820538.2025.2524935
Mohammad Javed Ali
{"title":"Lacrimal History - Part 21: Doyens of Dacryology Series - Baron Guillaume Dupuytren (1777-1835) and His Gold and Silver Lacrimal Cannulas.","authors":"Mohammad Javed Ali","doi":"10.1080/08820538.2025.2524935","DOIUrl":"10.1080/08820538.2025.2524935","url":null,"abstract":"","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"699-708"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529512","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":"Long-Term Outcomes of Trabeculectomy with Collagen Matrix Implant as a Bevacizumab Depot.","authors":"Faisal Thattaruthody, Natasha Gautam Seth, Parul Ichhpujani, Srishti Raj, Sushmita Kaushik, Surinder Singh Pandav","doi":"10.1080/08820538.2025.2488888","DOIUrl":"10.1080/08820538.2025.2488888","url":null,"abstract":"<p><strong>Purpose: </strong>To report the long-term outcomes of trabeculectomy with collagen implant as bevacizumab depot in eyes with uncontrolled glaucoma.</p><p><strong>Method: </strong>In this retrospective non-comparative interventional study, medical records of patients (age ≥18 years) who underwent trabeculectomy with Ologen implant as bevacizumab depot for uncontrolled glaucoma with ≥ 2 years follow-up were reviewed. The underlying etiology, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of anti-glaucoma medications (AGM) were recorded at baseline. Postoperatively, BCVA, IOP, AGMs, complications, and re-surgery were noted on day 1, 1-week, 1-, 3-, 6- months, 1-, 2-, 3-, 4-, 5-years and at final follow-up after 24 months. The main outcomes measured were IOP, number of AGM, and cumulative probability of overall success after 2 years.</p><p><strong>Results: </strong>Forty-three eyes of 43 patients with a mean age of 54.79 ± 17.27 years were included. The mean follow-up was 62.9 ± 27.42 (24-108) months. The mean pre-operative IOP was 29.23 ± 10.09 mmHg with an average of 4.3 ± 1.2 AGM. The mean IOP and number of AGM were significantly reduced in all follow-up visits (<i>p</i> < .0001) following surgery. The complete success was 48.8% and 48.5% at 2-year and 5-year respectively. The cumulative probability of overall success was 95%, 85%, 80%, and 71% at 2-5-, 7-, and 9-years respectively. A total of 24 complications were noted in 15 eyes in early postoperative days, and all were managed conservatively. The failure was noticed in 6 (17.2%) eyes at 5-year study visits.</p><p><strong>Conclusion: </strong>The use of ologen implant as a drug depot for bevacizumab in trabeculectomy was safe and had a good long-term outcome.</p>","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"795-801"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812263","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-05-13DOI: 10.1080/08820538.2025.2505340
Mohammad Javed Ali
{"title":"Lacrimal History - Part 20: Doyens of Dacryology Series - Antoine Maítre-Jan (1650-1725) and His 1707 Monograph, 'Traité des Maladies de L'oeil'.","authors":"Mohammad Javed Ali","doi":"10.1080/08820538.2025.2505340","DOIUrl":"10.1080/08820538.2025.2505340","url":null,"abstract":"","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"695-698"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029333","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}
Seminars in OphthalmologyPub Date : 2025-11-01Epub Date: 2025-06-05DOI: 10.1080/08820538.2025.2516367
Mohammad Javed Ali
{"title":"Lacrimal History - Part 18: Doyens of Dacryology Series - Jacques François-Marie Duverney (1661-1748) and His First Description of the Horner-Duverney Muscle.","authors":"Mohammad Javed Ali","doi":"10.1080/08820538.2025.2516367","DOIUrl":"10.1080/08820538.2025.2516367","url":null,"abstract":"","PeriodicalId":21702,"journal":{"name":"Seminars in Ophthalmology","volume":" ","pages":"687-690"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226554","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}