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Nguyen VD, Duong H, Lee MC, Chen JH, Huang WC, Chen HE, Lin JC, Wang JY, Lee CH. Two-drug versus three-drug regimens for treating Mycobacterium avium complex infection: A systematic review and meta-analysis. J Infect Public Health 2025; 18:102711. [PMID: 40024220 DOI: 10.1016/j.jiph.2025.102711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 02/14/2025] [Accepted: 02/16/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND Mycobacterium avium complex (MAC) infection, requiring prolonged treatment with an antibiotic combination, is an emerging public health concern. METHODS This meta-analysis compared the efficacy of 2-drug regimens with that of 3-drug regimens in bacteriological responses, acquired macrolide resistance (AMR), and mortality among adult patients with disseminated MAC infection (DMAC) and MAC pulmonary disease (MAC-PD). RESULTS Seven randomized controlled trials (RCTs) and 3 non-RCT studies, encompassing 1369 patients, were included. Treating DMAC with 2-drug regimens was associated with comparable bacteriological responses (odds ratio (OR) = 0.76, 95 % confidence interval (CI) = 0.48-1.18, P = .22) and mortality (OR = 1.29, 95 % CI = 0.59-2.83, P = .52), but had a higher risk of AMR (OR = 2.99, 95 % CI = 1.10-8.13, P = .03). For MAC-PD, 2-drug regimens were noninferior to 3-drug regimens in bacteriological responses (OR = 0.82, 95 % CI = 0.53-1.25, P = .35) and AMR (risk differences (RD) = 0.01, -0.02 to 0.05, P = .39), with no observed mortalities. Although not statistically significant compared to the 3-drug regimen, the macrolide-rifamycin regimen resulted in attenuated bacteriological responses (OR = 0.51, 95 % CI = 0.14-1.90, P = .32). However, the proportion of patients with bacteriological response (OR = 1.54, 95 % CI = 0.78-2.93, P = .23) and AMR risk (RD = 0.01, -0.02 to 0.04, P = .50) was not different between those under the macrolide-ethambutol regimen and those under 3-drug regimens. CONCLUSIONS The macrolide-ethambutol 2-drug regimen may be a viable alternative option for treating MAC-PD, whereas DMAC can be preferably managed with a 3-drug regimen.
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Affiliation(s)
- Van-Dong Nguyen
- International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Intensive Care Unit, Danang Hospital, Danang, Viet Nam
| | - Hai Duong
- Department of Community Health, School of Medicine, Vietnam National University, Ho Chi Minh City, Viet Nam
| | - Ming-Chia Lee
- Department of Pharmacy, New Taipei City Hospital, New Taipei City, Taiwan; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Jin-Hua Chen
- Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan; Institutional Research Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan
| | - Wei-Chang Huang
- Division of Pulmonary Immunology & Infectious Diseases, Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsiao-En Chen
- Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Jung-Chun Lin
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Hsin Lee
- Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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2
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Raju P, Yu M. Clinical Applications of the Cone Contrast Test in Ophthalmology and Neurology. J Clin Med 2025; 14:3079. [PMID: 40364109 PMCID: PMC12072747 DOI: 10.3390/jcm14093079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/15/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
Color vision is a critical aspect of human visual perception, yet traditional assessments often lack quantitative precision. The Rabin Cone Contrast Test and its successors offer objective, standardized measurements of cone-specific contrast sensitivity. These tests improve the detection and classification of color vision deficiencies and can facilitate the monitoring of color vision deficits in inherited retinal diseases, cone dystrophies, optic neuropathies, and brain injuries. Integrating quantitative color vision testing into clinical practice presents a more reliable, reproducible, and functionally relevant evaluation, highlighting its value in disease diagnosis, characterization, and management.
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Affiliation(s)
- Priya Raju
- School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Minzhong Yu
- Department of Ophthalmology and Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44106, USA
- Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, OH 44195, USA
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Han KE, Yoon H, Choi H, Lee JE, Kim SJ. Factors affecting visual outcome in patients with toxic optic neuropathy caused by ethambutol. Sci Rep 2025; 15:6257. [PMID: 39979502 PMCID: PMC11842782 DOI: 10.1038/s41598-025-90663-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 02/14/2025] [Indexed: 02/22/2025] Open
Abstract
This study aims to investigate prognostic factors for visual recovery in patients with ethambutol-induced toxic optic neuropathy (EON) by analyzing visual field (VF) tests, retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT), and other variables. We retrospectively reviewed 46 eyes of 23 patients with EON who had been followed up for more than six months. Patients were categorized into recovery (n = 12) and non-recovery (n = 11) groups based on visual recovery at six months after discontinuation of ethambutol. In the recovery group, initial best-corrected visual acuity (BCVA) and VF tests were better (p < 0.001), body weight (p = 0.04) was higher and the number of patient with diabetes (p = 0.007) was lower than in the non-recovery group. Baseline BCVA, VF tests, inferior and nasal RNFL thickness were correlated with visual outcomes. Univariate analysis showed that younger age (p = 0.024), higher body weight (p = 0.033), better initial BCVA (p < 0.001), better VF tests (p = 0.007), no hypertension (p = 0.044) and no diabetes (p = 0.009) were significant associated with a good visual outcomes. Multivariate analysis confirmed baseline BCVA as the only significant prognostic factor. Better BCVA at baseline are associated with favorable visual outcomes in EON patients. VF parameters, age, hypertension, diabetes, and body weight could also be considered possible predictors. Although RNFL thickness has significant correlation with visual outcomes, it does not appear to be a reliable factor to predict visual recovery.
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Affiliation(s)
- Kwang Eon Han
- Department of Ophthalmology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Heejin Yoon
- Department of Ophthalmology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Heeyoung Choi
- Department of Ophthalmology, School of Medicine, Pusan National University, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Ji-Eun Lee
- Department of Ophthalmology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su-Jin Kim
- Department of Ophthalmology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
- Department of Ophthalmology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, 20-Geumo-ro, Mulgeum-eup, Yangsan, 50612, Gyeongsangnam-do, South Korea.
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4
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Diab A, Dickerson H, Al Musaimi O. Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis. Pharmaceuticals (Basel) 2025; 18:70. [PMID: 39861133 PMCID: PMC11768153 DOI: 10.3390/ph18010070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 12/12/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Mycobacterium tuberculosis infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in Mycobacterium tuberculosis. This review provides a comprehensive analysis of these drugs and their molecular mechanisms. Isoniazid, thioamides, and delamanid primarily disrupt mycolic acid synthesis, with recent evidence indicating that delamanid also inhibits decaprenylphosphoryl-β-D-ribose-2-epimerase, thereby impairing arabinogalactan biosynthesis. Cycloserine remains the sole approved drug that inhibits peptidoglycan synthesis, the foundational layer of the mycobacterial cell wall. Furthermore, ethambutol interferes with arabinogalactan synthesis by targeting arabinosyl transferase enzymes, particularly embB- and embC-encoded variants. Beyond these, six promising molecules currently in Phase II clinical trials are designed to target arabinan synthesis pathways, sutezolid, TBA 7371, OPC-167832, SQ109, and both benzothiazinone derivatives BTZ043 and PBTZ169, highlighting advancements in the development of cell wall-targeting therapies.
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Affiliation(s)
- Ahmad Diab
- School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
| | - Henry Dickerson
- School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
| | - Othman Al Musaimi
- School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
- Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK
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5
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Ageed A, Aslam MD, El Haouari S. Acquired Dyschromatopsia and Its Link to Drug Toxicity. Cureus 2024; 16:e76190. [PMID: 39840156 PMCID: PMC11749246 DOI: 10.7759/cureus.76190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2024] [Indexed: 01/23/2025] Open
Abstract
Colour vision defects (CVDs) can be both congenital and acquired, with acquired dyschromatopsia often associated with medication toxicity. This review explores various standardised colour vision tests used to detect these defects, including the Ishihara plate test, Farnsworth-Munsell 100 hue test, and anomaloscopes. These methods are evaluated for their effectiveness in diagnosing CVDs, particularly in acquired conditions. Specific focus is given to medications known to induce dyschromatopsia, including chloroquine and hydroxychloroquine (CQ/HCQ), digoxin, ethambutol (EMB), and phosphodiesterase-5 (PDE-5) inhibitors. CQ/HCQ primarily causes tritan defects at early stages of retinal toxicity and progresses to red-green defects with more advanced retinopathy. Digoxin-induced CVDs are typically temporary red-green defects linked to the inhibition of Na+/K+ ATPase in retinal cells. EMB, used to treat tuberculosis, is associated with blue-yellow (tritan) dyschromatopsia, likely due to optic neuropathy. PDE-5 inhibitors, such as sildenafil, cause transient blue-tinted vision due to their effect on the phototransduction cascade in cones. Although most drug-induced CVDs are reversible upon discontinuation, CQ/HCQ toxicity often leads to irreversible damage. This review underscores the importance of colour vision monitoring in patients on long-term medication therapy to detect early toxicity and prevent irreversible damage.
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Affiliation(s)
- Ahmed Ageed
- Medicine and Surgery, University Hospitals of Leicester NHS Trust, Leicester, GBR
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Warwick AM, Bomze HM, Wang L, Hao Y, Stinnett SS, Gospe SM. Hypoxia-mediated rescue of retinal ganglion cells deficient in mitochondrial complex I is independent of the hypoxia-inducible factor pathway. Sci Rep 2024; 14:24114. [PMID: 39406814 PMCID: PMC11480089 DOI: 10.1038/s41598-024-75916-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 10/09/2024] [Indexed: 10/19/2024] Open
Abstract
Continuous exposure to environmental hypoxia (11% O2) has been shown to markedly slow the progressive degeneration of retinal ganglion cells (RGCs) in a mouse model of mitochondrial optic neuropathy with RGC-specific deletion of the key mitochondrial complex I accessory subunit ndufs4. As a first step toward identifying the therapeutic mechanism of hypoxia in this model, we conducted a series of experiments to investigate the role of the hypoxia-inducible factor (HIF) regulatory pathway in RGC neuroprotection. Vglut2-Cre; ndufs4loxP/loxP mice were crossed with strains bearing floxed alleles of the negative HIF regulatory vhl or of the two major HIF α-subunit isoforms, Hif1α and Hif2α. Deletion of vhl within ndufs4-deficient RGCs failed to prevent RGC degeneration under normoxia, indicating that HIF activation is not sufficient to achieve RGC rescue. Furthermore, the rescue of ndufs4-deficient RGCs by hypoxia remained robust despite genetic inactivation of Hif1α and Hif2α. Our findings demonstrate that the HIF pathway is entirely dispensable to the rescue of RGCs by hypoxia. Future efforts to uncover key HIF-independent molecular pathways induced by hypoxia in this mouse model may be of therapeutic relevance to mitochondrial optic neuropathies such as Leber hereditary optic neuropathy.
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Affiliation(s)
- Alexander M Warwick
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA
| | - Howard M Bomze
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA
| | - Luyu Wang
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA
| | - Ying Hao
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA
| | - Sandra S Stinnett
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA
| | - Sidney M Gospe
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC, 27710, USA.
- Department of Ophthalmology, Box 3712 Med Center, Duke University, 2351 Erwin Road, Durham, NC, 27710, USA.
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7
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Shin HJ, Costello F. Imaging the optic nerve with optical coherence tomography. Eye (Lond) 2024; 38:2365-2379. [PMID: 38961147 PMCID: PMC11306400 DOI: 10.1038/s41433-024-03165-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 06/03/2024] [Accepted: 06/04/2024] [Indexed: 07/05/2024] Open
Abstract
Optical coherence tomography (OCT) is a non-invasive imaging technology, which may be used to generate in vivo quantitative and qualitative measures of retinal structure. In terms of quantitative metrics, peripapillary retinal nerve fiber layer (pRNFL) thickness provides an indirect evaluation of axonal integrity within the optic nerve. Ganglion layer measures derived from macular scans indirectly reflect retinal ganglion cell status. Notably, ganglion layer indices are platform dependent and may include macular ganglion cell inner plexiform layer (mGCIPL), ganglion cell layer (GCL), and ganglion cell complex (GCC) analyses of thickness or volume. Interpreted together, pRNFL thickness and ganglion layer values can be used to diagnose optic neuropathies, monitor disease progression, and gauge response to therapeutic interventions for neuro-ophthalmic conditions. Qualitative assessments of the optic nerve head, using cross-sectional transverse axial, en face, and circular OCT imaging, may help distinguish papilledema from pseudopapilloedema, and identify outer retinal pathology. Innovations in OCT protocols and approaches including enhanced depth imaging (EDI), swept source (SS) techniques, and angiography (OCTA) may offer future insights regarding the potential pathogenesis of different optic neuropathies. Finally, recent developments in artificial intelligence (AI) utilizing OCT images may overcome longstanding challenges, which have plagued non-vision specialists who often struggle to perform reliable ophthalmoscopy. In this review, we aim to discuss the benefits and pitfalls of OCT, consider the practical applications of this technology in the assessment of optic neuropathies, and highlight scientific discoveries in the realm of optic nerve imaging that will ultimately change how neuro-ophthalmologists care for patients.
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Affiliation(s)
- Hyun Jin Shin
- Konkuk University School of Medicine, Chungju city, Republic of Korea
- Department of Ophthalmology, Konkuk University Medical Center, Seoul, Republic of Korea
- Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
- Institute of Biomedical Science & Technology, Konkuk University, Seoul, Republic of Korea
| | - Fiona Costello
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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8
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Chapelle AC, Rakic JM, Plant GT. Utility of ganglion cells for the evaluation of anterior visual pathway pathology: a review. Acta Neurol Belg 2024; 124:1113-1123. [PMID: 38538906 DOI: 10.1007/s13760-024-02522-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/01/2024] [Indexed: 07/25/2024]
Abstract
The management of optic neuropathy is fundamental to neuro-ophthalmic practice. Following the invention of the ophthalmoscope, clinicians, for a century or more, relied upon fundus examination in the evaluation of optic neuropathy. However, the advent of optical coherence tomography, based on the principle of backscattering of light and interferometry, has revolutionized the analysis of optic nerve and retinal disorders. Optical coherence tomography has proven of particular value in the measurement, at the micron level, of the peripapillary retinal nerve fibre layer and the ganglion cell layer. These measurements have proven critical in the differential diagnosis and monitoring of optic neuropathy. Specifically, thinning of the peripapillary nerve fibre layer provides evidence of axonal loss affecting any sector of the optic nerve. Thinning of the macular ganglion cell layer, on the other hand, shows a more precise correlation with visual deficits due to retrograde degeneration following optic nerve damage, although limited to central retina. In daily practise, optical coherence tomography is of great value in assessing the diagnosis, prognosis and response to treatment in optic neuropathy. Particular advances have been made, for example, in the assessment of optic neuritis, papilloedema and chiasmal compression which have translated to everyday practice. As with any other imaging technology the clinician must have a clear understanding of acquisition artefacts. A further issue is the relatively limited normative database in sub-populations such as the young and individuals with a refractive error > + 5 or < -5 dioptres.
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Affiliation(s)
- Anne-Catherine Chapelle
- Department of Ophthalmology, Central University Hospital of Liège, University of Liège, Avenue de L'hôpital, 4000, Liège, Belgium.
| | - Jean-Marie Rakic
- Department of Ophthalmology, Central University Hospital of Liège, University of Liège, Avenue de L'hôpital, 4000, Liège, Belgium
| | - Gordon Terence Plant
- Department of Neurodegeneration and Rehabilitation, Faculty of Brain Sciences, UCL Institute of Neurology, University College London, London, WC1N 3BG, UK
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Kulniwatcharoen P, Hansapinyo L, Chattipakorn N, Chattipakorn SC. Potential underlying mechanisms of ethambutol induced optic neuropathy: Evidence from in vitro to clinical studies. Food Chem Toxicol 2023; 182:114176. [PMID: 37949203 DOI: 10.1016/j.fct.2023.114176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/01/2023] [Accepted: 11/02/2023] [Indexed: 11/12/2023]
Abstract
Ethambutol is an antibiotic widely used for treatment of Mycobacterium species. Although it is safe to use in patients, the ocular toxic impact, including optic neuropathy and retinopathy, can be observed in patients using ethambutol. After discontinuation of the drug, the ocular toxic effects can be reversible in some patients, but some are not. Ethambutol-induced optic neuropathy has been recognized for more than six decades and the prevalence of optic neuropathy from a standard dose of ethambutol has been reported as 0.7-1.29%. Several factors associated with ethambutol-induced optic neuropathy include dosage/duration of drug, the medical conditions of patients such as renal and hepatic dysfunction and preexisting mitochondrial mutations. Currently, there is no specific treatment and prevention of ethambutol-induced optic neuropathy. In addition, the potential underlying mechanisms of ethambutol-induced optic neuropathy is still unclear. Therefore, this review aimed to summarize and discuss evidence from clinical, in vitro, and in vivo studies in order to explore the potential pathophysiology of ethambutol-induced optic neuropathy. Any contradictory findings are also included and discussed. The insights gained from the review will facilitate the discovery of novel approaches for prevention and treatment of optic neuropathy-induced by ethambutol.
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Affiliation(s)
- Pichaya Kulniwatcharoen
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Linda Hansapinyo
- Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
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Camacho DK, Go CC, Chaqour B, Shindler KS, Ross AG. Emerging Gene Therapy Technologies for Retinal Ganglion Cell Neuroprotection. J Neuroophthalmol 2023; 43:330-340. [PMID: 37440418 PMCID: PMC10527513 DOI: 10.1097/wno.0000000000001955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/15/2023]
Abstract
ABSTRACT Optic neuropathies encompass a breadth of diseases that ultimately result in dysfunction and/or loss of retinal ganglion cells (RGCs). Although visual impairment from optic neuropathies is common, there is a lack of effective clinical treatments. Addressing a critical need for novel interventions, preclinical studies have been generating a growing body of evidence that identify promising new drug-based and cell-based therapies. Gene therapy is another emerging therapeutic field that offers the potential of specifically and robustly increasing long-term RGC survival in optic neuropathies. Gene therapy offers additional benefits of driving improvements following a single treatment administration, and it can be designed to target a variety of pathways that may be involved in individual optic neuropathies or across multiple etiologies. This review explores the history of gene therapy, the fundamentals of its application, and the emerging development of gene therapy technology as it relates to treatment of optic neuropathies.
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Affiliation(s)
- David K. Camacho
- F. M. Kirby Center for Molecular Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Cammille C. Go
- F. M. Kirby Center for Molecular Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Brahim Chaqour
- F. M. Kirby Center for Molecular Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Kenneth S. Shindler
- F. M. Kirby Center for Molecular Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Departments of Ophthalmology and Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Ahmara G. Ross
- F. M. Kirby Center for Molecular Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Departments of Ophthalmology and Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
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11
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Liou RHC, Chen SW, Cheng HC, Wu PC, Chang YF, Wang AG, Fann MJ, Wong YH. The efficient induction of human retinal ganglion-like cells provides a platform for studying optic neuropathies. Cell Mol Life Sci 2023; 80:239. [PMID: 37540379 PMCID: PMC10403410 DOI: 10.1007/s00018-023-04890-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/29/2023] [Accepted: 07/19/2023] [Indexed: 08/05/2023]
Abstract
Retinal ganglion cells (RGCs) are essential for vision perception. In glaucoma and other optic neuropathies, RGCs and their optic axons undergo degenerative change and cell death; this can result in irreversible vision loss. Here we developed a rapid protocol for directly inducing RGC differentiation from human induced pluripotent stem cells (hiPSCs) by the overexpression of ATOH7, BRN3B, and SOX4. The hiPSC-derived RGC-like cells (iRGCs) show robust expression of various RGC-specific markers by whole transcriptome profiling. A functional assessment was also carried out and this demonstrated that these iRGCs display stimulus-induced neuronal activity, as well as spontaneous neuronal activity. Ethambutol (EMB), an effective first-line anti-tuberculosis agent, is known to cause serious visual impairment and irreversible vision loss due to the RGC degeneration in a significant number of treated patients. Using our iRGCs, EMB was found to induce significant dose-dependent and time-dependent increases in cell death and neurite degeneration. Western blot analysis revealed that the expression levels of p62 and LC3-II were upregulated, and further investigations revealed that EMB caused a blockade of lysosome-autophagosome fusion; this indicates that impairment of autophagic flux is one of the adverse effects of that EMB has on iRGCs. In addition, EMB was found to elevate intracellular reactive oxygen species (ROS) levels increasing apoptotic cell death. This could be partially rescued by the co-treatment with the ROS scavenger NAC. Taken together, our findings suggest that this iRGC model, which achieves both high yield and high purity, is suitable for investigating optic neuropathies, as well as being useful when searching for potential drugs for therapeutic treatment and/or disease prevention.
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Affiliation(s)
- Roxanne Hsiang-Chi Liou
- Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
| | - Shih-Wei Chen
- Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
- Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
| | - Hui-Chen Cheng
- Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
- Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, 112, Taiwan, ROC
- Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
- Program in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Pei-Chun Wu
- Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
| | - Yu-Fen Chang
- LumiSTAR Biotechnology, Inc., Taipei, 115, Taiwan, ROC
| | - An-Guor Wang
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, 112, Taiwan, ROC
- Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
| | - Ming-Ji Fann
- Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
- Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC
| | - Yu-Hui Wong
- Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC.
- Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC.
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12
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Cen LP, Park KK, So KF. Optic nerve diseases and regeneration: How far are we from the promised land? Clin Exp Ophthalmol 2023; 51:627-641. [PMID: 37317890 PMCID: PMC10519420 DOI: 10.1111/ceo.14259] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 05/10/2023] [Accepted: 05/18/2023] [Indexed: 06/16/2023]
Abstract
The retinal ganglion cells (RGCs) are the sole output neurons that connect information from the retina to the brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss and axon damage, and lead to partial or total loss of vision, which is an irreversible process in mammals. The accurate diagnoses of optic neuropathies are crucial for timely treatments to prevent irrevocable RGCs loss. After severe ON damage in optic neuropathies, promoting RGC axon regeneration is vital for restoring vision. Clearance of neuronal debris, decreased intrinsic growth capacity, and the presence of inhibitory factors have been shown to contribute to the failure of post-traumatic CNS regeneration. Here, we review the current understanding of manifestations and treatments of various common optic neuropathies. We also summarise the current known mechanisms of RGC survival and axon regeneration in mammals, including specific intrinsic signalling pathways, key transcription factors, reprogramming genes, inflammation-related regeneration factors, stem cell therapy, and combination therapies. Significant differences in RGC subtypes in survival and regenerative capacity after injury have also been found. Finally, we highlight the developmental states and non-mammalian species that are capable of regenerating RGC axons after injury, and cellular state reprogramming for neural repair.
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Affiliation(s)
- Ling-Ping Cen
- Department of Neuro-Ophthalmology, Joint Shantou International Eye Centre of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Kevin K. Park
- Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Kowk-Fai So
- Guangzhou-HongKong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China
- Aier School of Ophthalmology, Changsha Aier Hospital of Ophthalmology, Changsha, China
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13
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Srithawatpong S, Chaitanuwong P, Yospaiboon Y. Factors Affecting Visual Recovery in Patients with Ethambutol-Induced Optic Neuropathy. Clin Ophthalmol 2023; 17:545-554. [PMID: 36798797 PMCID: PMC9925387 DOI: 10.2147/opth.s401916] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 01/27/2023] [Indexed: 02/11/2023] Open
Abstract
Purpose To study visual recovery and identify the factors that may affect it in patients with ethambutol-induced optic neuropathy (EON). Patients and Methods Medical charts of patients who developed optic neuropathy after ethambutol (EMB) treatment for tuberculosis infection were retrospectively reviewed. Demographic details and clinical data were examined to assess visual recovery after discontinuation of ethambutol treatment. The univariate and multivariate relationships between various factors and visual recovery were evaluated using regression analysis. Results Of 5394 patients diagnosed with tuberculosis infection and treated with EMB, 23 patients (0.43%) were diagnosed with EON. Logistic regression analysis found that female sex was the categorical factor significantly associated with good visual recovery with an odds ratio of 12.0 (95% confidence interval 1.56, 92.29; p = 0.02), while linear regression analysis identified good initial visual acuity as the numerical factor significantly related with it (p < 0.001). After adjustment with multivariate analysis, initial visual acuity was found to be the only significant factor associated with visual recovery. All patients with initial visual acuity of better than 20/200 at first visit achieved good visual recovery. Conclusion The incidence of EON in patients treated with EMB was 0.43% in this hospital-based study. Good visual recovery was noted in 39.13% of these patients, and initial visual acuity was the factor that affected visual recovery. It is recommended that patients on EMB have regular screening by an ophthalmologist for early detection of the disease, and if it is discovered, that the use of the drug be immediately discontinued in order to prevent potentially devastating visual loss.
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Affiliation(s)
- Supaporn Srithawatpong
- Department of Ophthalmology, Rajavithi Hospital, Ministry of Public Health, Bangkok, Thailand,Department of Ophthalmology, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Pareena Chaitanuwong
- Department of Ophthalmology, Rajavithi Hospital, Ministry of Public Health, Bangkok, Thailand,Department of Ophthalmology, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Yosanan Yospaiboon
- Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand,Correspondence: Yosanan Yospaiboon, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, 123 Mitraparb Highway, Khon Kaen, 40002, Thailand, Tel +66-4336-3010, Fax +66-4334-8383, Email
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14
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Ambika S, Lakshmi KP, Gopal M, Noronha OV. Visual outcomes of toxic optic neuropathy secondary to Ethambutol: A retrospective observational study from India, an endemic country. Indian J Ophthalmol 2022; 70:3388-3392. [PMID: 36018127 DOI: 10.4103/ijo.ijo_2996_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Purpose Ethambutol (EMB) is one of the first-line drugs used for treating tuberculosis. Vision loss due to optic nerve toxicity is a well-known potential side effect of the drug. Our aim was to evaluate the clinical features and visual outcomes of patients with EMB optic neuropathy (EON). Methods A retrospective, observational, single-center study of all patients who were diagnosed to have EON during January 2017-December 2019 was done. All these patients were screened in the Department of Neuro-ophthalmology at a referral tertiary eye care institution in India. Clinical features, visual outcomes, and neuroimaging findings of these patients were analyzed. Results Two hundred and fifty-six eyes of 128 patients were included. Of these, 73 were male and 55 were female. Mean age was 50.55 ± 15 years. Mean visual acuity at presentation was 1.12 ± 0.45 logarithm of the minimum angle of resolution (logMAR). One hundred and forty three eyes had normal optic disk on presentation, 111 had disk pallor, and two eyes had disk edema. The most common field defect was central/paracentral scotoma (26.2%) followed by temporal defects (24.6%). Magnetic resonance imaging (MRI) brain and orbit showed optic nerve signals in 19.6% and chiasmal signals in 5.2%. At the final follow-up, a ≥2-line vision improvement was noted in 161 eyes (62.9%), which was statistically significant. Conclusion Multiple prognostic factors were analyzed to predict the visual recovery of EON. We observed that patients presenting with visual acuity worse than 6/60 had poor visual outcome and long duration of follow-up showed better visual recovery, proving the possibility of a gradual recovery pattern of EON. Interestingly, we found in our study that the chances of favorable visual outcome were directly proportionate to early diagnosis and cessation of EMB.
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Affiliation(s)
- Selvakumar Ambika
- Department of Neuro-Ophthalmology, Sankara Nethralaya- A Unit of Medical Research Foundation, Chennai, Tamil Nadu, India
| | - K Padma Lakshmi
- Department of Neuro-Ophthalmology, Sankara Nethralaya- A Unit of Medical Research Foundation, Chennai, Tamil Nadu, India
| | - Madhumita Gopal
- Department of Neuro-Ophthalmology, Sankara Nethralaya- A Unit of Medical Research Foundation, Chennai, Tamil Nadu, India
| | - Olma V Noronha
- Department of Radiology, Sankara Nethralaya- A Unit of Medical Research Foundation, Chennai, Tamil Nadu, India
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15
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Kaur P, Singh S, Kaur K, Mahesh KV, Tigari B, Sehgal V, Takkar A, Mehta S, Singh R, Malhotra S. The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review. Neuroophthalmology 2022; 46:304-313. [PMID: 36337233 PMCID: PMC9635551 DOI: 10.1080/01658107.2022.2100916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
Abstract
Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.
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Affiliation(s)
- Prabhjit Kaur
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sofia Singh
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kirandeep Kaur
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Karthik Vinay Mahesh
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Basavaraj Tigari
- Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vineet Sehgal
- Department of Neurologist, Sehgals Neuro and Child Care Center, Amritsar, Punjab, India
| | - Aastha Takkar
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sahil Mehta
- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ramandeep Singh
- Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Samir Malhotra
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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16
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Buelens T, Fils JF, Willermain F. Posterior segment spectral domain oct in the differential diagnosis of bilateral temporal optic neuropathy and its correlation with visual acuity. Int Ophthalmol 2022; 42:3877-3889. [PMID: 35809163 DOI: 10.1007/s10792-022-02408-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/13/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE To identify the underlying etiologies and to evaluate the differential diagnostic value of posterior segment spectral domain OCT measurements and their correlation with best-corrected visual acuity (BCVA) in a group of patients with OCT documented bilateral optic neuropathy limited to the temporal quadrants. METHODS Retrospective study. RESULTS We included 61 patients: 35 presented with presumed "classic" acquired mitochondrial optic neuropathy (MON) (18 nutritional, 11 toxic, 6 mixed toxic-nutritional) and 2 with suspected hereditary MON. Nine patients were identified as 'MON mimickers' (especially multiple sclerosis), and 4 were found to have a mixed mechanism, while 11 remained undiagnosed. Across all etiologies, the strongest positive relationship between BCVA and tested OCT parameters was with macular GCL (ganglion cell layer) and GCIPL (combined ganglion cell and inner plexiform layer) volumes rather than peripapillary retinal nerve fiber layer (RNFL) thicknesses (all statistically significant). There was an inverse relationship between BCVA and inner nuclear layer (INL) volumes, with significant differences for BCVA and all tested OCT parameters between eyes with and without INL microcystoid lesions. OCT (absolute values and intereye differences) was not helpful in distinguishing between presumed acquired mitochondrial disease and patients with multiple sclerosis without optic neuritis. However, significantly greater intereye differences in global RNFL and inner plexiform layer and GCIPL volumes were found in patients with a previous history of unilateral optic neuritis. CONCLUSIONS The strongest positive relationship with BCVA was found for macular GCL and GCIPL volumes. OCT could not differentiate between acquired mitochondrial disease and multiple sclerosis without optic neuritis.
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Affiliation(s)
- Tom Buelens
- CHU St Pierre and Brugmann, Department of Ophthalmology, 322 rue Haute, 1000, Brussels, Belgium.
| | | | - François Willermain
- CHU St Pierre and Brugmann, Department of Ophthalmology, 322 rue Haute, 1000, Brussels, Belgium
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17
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Sen S, Mandal S, Banerjee M, Gk R, Saxena A, Aalok SP, Saxena R. Ethambutol-induced optic neuropathy: Functional and structural changes in the retina and optic nerve. Semin Ophthalmol 2022; 37:730-739. [PMID: 35699333 DOI: 10.1080/08820538.2022.2085517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUD Ethambutol hydrochloride (EMB) is used in the treatment of tuberculosis and is used as first line modality in combination with other medications. Ethambutol optic neuropathy (EON) is a rare but well-recognised adverse ocular event in patients who receive ethambutol for the treatment of mycobacterial infections and may be potentially devastating with reversible to irreversible changes in visual acuity. KEY FINDINGS Optical coherence tomography has been used to evaluate the thickness of retinal nerve fibre and ganglion cell layers to look for degenerative changes and early markers. Electrophysiological tests like multifocal electroretinogram, visual evoked potentials and visual fields have been used to understand the functional changes associated with established EON and also whether these can be used to detect subclinical EON and correlate them with the structural changes. In this review, we have summarised evidence published till December 2021 related to evaluation of structural and functional changes in the retina and optic nerve in eyes with EON.
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Affiliation(s)
- Sagnik Sen
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
| | - Sohini Mandal
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
| | - Mousumi Banerjee
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
| | - Ranjitha Gk
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
| | | | | | - Rohit Saxena
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
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18
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Buelens T, Scifo L, Valyi Z, Willermain F. Sarcoidosis revealed by simultaneous optic nerve and eyelid involvement: A case report. Am J Ophthalmol Case Rep 2022; 26:101451. [PMID: 35252626 PMCID: PMC8889372 DOI: 10.1016/j.ajoc.2022.101451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 02/11/2022] [Accepted: 02/20/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose Ocular disease can be the initial manifestation in patients with sarcoidosis. It is most often associated with uveitis, but eyelid or optic nerve disease can also be presenting features. Although uncommon and easy to overlook in a patient presenting with visual loss, paying attention to the presence of eyelid granulomas in our patient proved to be very helpful in our diagnostic work up for optic neuropathy. Observations A young otherwise healthy patient was addressed with a 3 month history of bilateral painless visual loss. At presentation, best-corrected visual acuity was counting fingers in both eyes. Anterior segment slit-lamp examination was completely normal in both eyes. Eye fundus examination revealed subtle optic disc swelling in the left eye. Interestingly, flesh-colored nodular eyelid lesions were found bilaterally. Basic work-up for optic neuropathy showed elevated levels of serum lysozyme and serum angiotensin converting enzyme. More importantly, a biopsy specimen of an eyelid nodule demonstrated multiple non-necrotizing granulomas, a hallmark sign of sarcoidosis. Despite a delay in treatment of several months after onset of symptoms, response to systemic corticosteroids was prompt and important with visual acuity improving to 20/20 in both eyes as well as complete resorption of all eyelid lesions. Conclusion and importance In the diagnostic work-up for optic neuropathy, the answer can sometimes be hiding where it's least expected: the possible presence of eyelid lesions should not be overlooked as they may orient us towards sarcoidosis as an underlying etiology.
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19
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Gene therapy restores mitochondrial function and protects retinal ganglion cells in optic neuropathy induced by a mito-targeted mutant ND1 gene. Gene Ther 2022; 29:368-378. [PMID: 35383288 PMCID: PMC9233058 DOI: 10.1038/s41434-022-00333-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 03/19/2022] [Accepted: 03/24/2022] [Indexed: 11/21/2022]
Abstract
Therapies for genetic disorders caused by mutated mitochondrial DNA are an unmet need, in large part due barriers in delivering DNA to the organelle and the absence of relevant animal models. We injected into mouse eyes a mitochondrially targeted Adeno-Associated-Virus (MTS-AAV) to deliver the mutant human NADH ubiquinone oxidoreductase subunit I (hND1/m.3460G>A) responsible for Leber’s hereditary optic neuropathy, the most common primary mitochondrial genetic disease. We show that the expression of the mutant hND1 delivered to retinal ganglion cells (RGC) layer colocalizes with the mitochondrial marker PORIN and the assembly of the expressed hND1 protein into host respiration complex I. The hND1 injected eyes exhibit hallmarks of the human disease with progressive loss of RGC function and number, as well as optic nerve degeneration. We also show that gene therapy in the hND1 eyes by means of an injection of a second MTS-AAV vector carrying wild type human ND1 restores mitochondrial respiratory complex I activity, the rate of ATP synthesis and protects RGCs and their axons from dysfunction and degeneration. These results prove that MTS-AAV is a highly efficient gene delivery approach with the ability to create mito-animal models and has the therapeutic potential to treat mitochondrial genetic diseases.
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20
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Orssaud C, Nguyen D, Rouzaud C, Pavie J, Pinot J, Lortholary O, Bremond-Gignac D, Robert M. Dépistage et prévention des neuropathies optiques toxiques aux anti-mycobactériens : proposition de recommandations. J Fr Ophtalmol 2022; 45:495-503. [DOI: 10.1016/j.jfo.2021.08.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/31/2021] [Accepted: 08/31/2021] [Indexed: 11/26/2022]
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21
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Sheng WY, Wu SQ, Su LY, Zhu LW. Ethambutol-induced optic neuropathy with rare bilateral asymmetry onset: A case report. World J Clin Cases 2022; 10:663-670. [PMID: 35097092 PMCID: PMC8771374 DOI: 10.12998/wjcc.v10.i2.663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/12/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ethambutol-induced optic neuropathy (EON) most commonly manifests as bilateral symmetrical loss of vision and often cause serious and irreversible visual impairment because of the lack of early detection and effective treatment. We followed a case of EON with rare binocular asymmetric clinical manifestations and observed the changes of visual function and retinal structure after drug withdrawal, so as to further understand the clinical characteristics of this disease.
CASE SUMMARY A 54-year-old man complained of gradual visual decline in the left eye. The patient presented with best-corrected visual acuity of 20/20 in the right eye and 20/50 in the left eye. Color vision examination revealed difficulty in reading green color plates in the left eye. The visual field manifested as concentric contraction in the left eye. After nearly a month of drug withdrawal, the right eye had a similar decline in visual function. At the last visit, 19 mo after drug withdrawal, the visual function significantly recovered in both eyes. During follow-up optical coherence tomography (OCT) examination, both eyes manifested the thickness of the retinal nerve fiber layer from mild thickening to thinning and finally temporal atrophy, and the ganglion cell-inner plexiform layer showed significant thinning. The difference was that a reversible structural disorder in the outer retina of the nasal macula was detected in the left eye by macular high-definition OCT.
CONCLUSION Nephropathy and high blood pressure, which damage the retinal microcirculation, may cause damage to the outer layer of the retina. Ethambutol may influence photoreceptor as well as retinal ganglion cells.
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Affiliation(s)
- Wen-Yan Sheng
- Department of Ophthalmology, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Shuang-Qing Wu
- Department of Ophthalmology, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Ling-Ya Su
- Department of Ophthalmology, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Li-Wei Zhu
- Department of Ophthalmology, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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22
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Toxic Optic Neuropathy. Neuroophthalmology 2022. [DOI: 10.1007/978-981-19-4668-4_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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23
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Nguyen LM, Nguyen NTT, Nguyen TTT, Nguyen TT, Nguyen DTC, Tran TV. Occurrence, toxicity and adsorptive removal of the chloramphenicol antibiotic in water: a review. ENVIRONMENTAL CHEMISTRY LETTERS 2022; 20:1929-1963. [PMID: 35369683 PMCID: PMC8956153 DOI: 10.1007/s10311-022-01416-x] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 02/11/2022] [Indexed: 05/08/2023]
Abstract
Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, hydrogen bonding, and electrostatic interactions. We also discuss isotherms, kinetics, thermodynamic data, selection of eluents, desorption efficiency, and regeneration of adsorbents. Porous carbon-based adsorbents exhibit excellent adsorption capacities of 500-1240 mg g-1. Most adsorbents can be reused over at least four cycles.
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Affiliation(s)
- Luan Minh Nguyen
- Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
- Department of Chemical Engineering and Processing, Nong Lam University, Thu Duc District, Ho Chi Minh City, 700000 Vietnam
| | - Ngoan Thi Thao Nguyen
- Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
- Department of Chemical Engineering and Processing, Nong Lam University, Thu Duc District, Ho Chi Minh City, 700000 Vietnam
| | - Thuy Thi Thanh Nguyen
- Department of Chemical Engineering and Processing, Nong Lam University, Thu Duc District, Ho Chi Minh City, 700000 Vietnam
- Faculty of Science, Nong Lam University, Thu Duc District, Ho Chi Minh City, 700000 Vietnam
| | - Thuong Thi Nguyen
- Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
| | - Duyen Thi Cam Nguyen
- Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
| | - Thuan Van Tran
- Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh, District 4, Ho Chi Minh City, 755414 Vietnam
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Abri Aghdam K, Aghajani A, Razi-Khosroshahi M, Soltan Sanjari M, Chaibakhsh S, Falavarjani KG. Optical Coherence Tomography Angiography and Structural Analyses of the Pale Optic Discs: Is It Possible to Differentiate the Cause? Curr Eye Res 2021; 46:1876-1885. [PMID: 33980086 DOI: 10.1080/02713683.2021.1929331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: To compare the optic nerve head (ONH) structure and microvasculature in patients with optic atrophy due to non-arteritic anterior ischemic optic neuropathy (NAION), compressive optic neuropathy (CON), methanol-induced optic neuropathy (MION), and traumatic optic neuropathy (TON) using optical coherence tomography angiography.Methods: In this comparative, cross-sectional study, 32 eyes with NAION, 18 eyes with CON, 32 eyes with MION, 23 eyes with TON, and 55 normal eyes were enrolled. Radial peripapillary capillary (RPC) vessel density, peripapillary retinal nerve fiber layer (RNFL) thickness, disc area, cup volume, and cup/disc area ratio were obtained using the RTVue XR Avanti system (Optovue Inc., Fremont, CA, USA).Results: RPC vessel density and peripapillary RNFL thickness in all patients were significantly lower than normal subjects. A positive correlation was found between the RPC vessel density and peripapillary RNFL thickness in normal subjects and all study groups. The positive correlation between the inside and outside disc RPC vessel density was only found in the NAION (r = 0.36, P = .042) and MION (r = 0.42, P = .018) groups. No significant difference was found among the groups in terms of peripapillary and inside disc vascular densities (all P > .05). Disc area and cup volume in patients with MION was larger than the values in patients with NAION (P = .018) and TON (P = .044) and normal subjects (P = .015). The discriminating features among the study groups were the larger cup volume and cup/disc area ratio in patients with MION, and lower RNFL thickness in patients with TON.Conclusions: There was a positive correlation between the RNFL thickness and peripapillary RPC vessel density regardless of the cause of optic disc pallor. Structural evaluation of the ONH seems to be a better way to differentiate the cause of optic nerve head atrophy than the microangiographic changes.
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Affiliation(s)
- Kaveh Abri Aghdam
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Aghajani
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Marjan Razi-Khosroshahi
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Soltan Sanjari
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Chaibakhsh
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Khalil Ghasemi Falavarjani
- Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.,Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
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Abstract
SIGNIFICANCE Nutritional and toxic optic neuropathies are rare disorders characterized by visual impairment due to optic nerve damage by a toxin, usually with coexisting nutritional deficiencies. Its pathophysiology is still unclear, and multiple mechanisms implicated act synergistically to bring about this condition. The decline in its incidence and its confusing clinical appearance make diagnosing nutritional and toxic optic neuropathies challenging. PURPOSE This is an observational clinical case report of an atypical clinical case of a nutritional and toxic optic neuropathy with a subacute presentation and papilledema at the time of diagnosis. The patient provided written informed consent for medical information and images to be published. CASE REPORT A 47-year-old man presented with progressive, painless bilateral decrease in central vision over 15 days. The patient had a long-standing history of alcohol abuse and was a heavy smoker. The examination revealed dyschromatopsia, 20/400 visual acuity on both eyes, and no relative afferent pupillary defect. Funduscopy revealed bilateral papilledema. A visual field test showed generalized depression with centrocecal involvement in the left eye. Laboratory studies evidenced decreased vitamin B12/B1 and red blood cell folate levels, increased acute phase reactants, hypertransaminasemia, and macrocytic anemia. Serologies and methanol in urine were negative. After the discontinuation of tobacco use and alcohol accompanied by vitamin supplementation, our patient's visual field, visual acuity, and papilledema improved remarkably. After 5 months, visual acuity and funduscopy were normal. CONCLUSIONS Although some hallmark signs were visible in this case, its subacute presentation and the presence of papilledema at diagnosis caused some diagnostic uncertainty. Nutritional and toxic optic neuropathy is a rare and challenging diagnosis because of a lack of biomarkers. Eye care clinicians should consider nutritional and toxic optic neuropathies to prevent severe and irreversible visual damage resulting from underdiagnosis and mismanagement.
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Huang TL, Lin YW, Wang JK. Ethambutol optic neuropathy with correspondent chiasmitis manifestation in magnetic resonance imaging. Taiwan J Ophthalmol 2021; 12:343-346. [PMID: 36248082 PMCID: PMC9558461 DOI: 10.4103/tjo.tjo_27_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 06/07/2021] [Indexed: 11/09/2022] Open
Abstract
We present a case of an older patient with toxic chiasmatic optic neuropathy accompanied by bitemporal hemianopia associated with ethambutol use. The patient experienced gradual visual defect recovery that was concurrent with an improvement of chiasmal enhancement in the repeat magnetic resonance imaging performed at his 6-month follow-up. However, his visual field pattern sharply changed to left inferior homonymous quadrantanopia because of a new episode of occipital lobe infarction. After 2 years, the patient's visual function reached the best-corrected visual acuity of 20/20 in both eyes, although he had the sequela of homonymous quadrantanopia related to the infarction. Optical coherence tomography revealed that the loss on the macular ganglion cell–inner plexiform layer was related to retrograde transsynaptic degeneration caused by ethambutol-related chiasmopathy.
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27
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Kim US, Mahroo OA, Mollon JD, Yu-Wai-Man P. Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance. Front Neurol 2021; 12:661938. [PMID: 34093409 PMCID: PMC8175861 DOI: 10.3389/fneur.2021.661938] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/06/2021] [Indexed: 11/24/2022] Open
Abstract
Retinal ganglion cells (RGCs) are the bridging neurons that connect the retinal input to the visual processing centres within the central nervous system. There is a remarkable diversity of RGCs and the various subtypes have unique morphological features, distinct functions, and characteristic pathways linking the inner retina to the relevant brain areas. A number of psychophysical and electrophysiological tests have been refined to investigate this large and varied population of RGCs. Technological advances, such as high-resolution optical coherence tomography imaging, have provided additional tools to define the pattern of RGC involvement and the chronological sequence of events in both inherited and acquired optic neuropathies. The mechanistic insights gained from these studies, in particular the selective vulnerability and relative resilience of particular RGC subtypes, are of fundamental importance as they are directly relevant to the development of targeted therapies for these invariably progressive blinding diseases. This review provides a comprehensive description of the various types of RGCs, the developments in proposed methods of classification, and the current gaps in our knowledge of how these RGCs are differentially affected depending on the underlying aetiology. The synthesis of the current body of knowledge on the diversity of RGCs and the pathways that are potentially amenable to therapeutic modulation will hopefully lead to much needed effective treatments for patients with optic neuropathies.
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Affiliation(s)
- Ungsoo Samuel Kim
- Kim's Eye Hospital, Seoul, South Korea
- John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
- Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom
- Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
- *Correspondence: Ungsoo Samuel Kim
| | - Omar A. Mahroo
- Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
- Institute of Ophthalmology, University College London, London, United Kingdom
- Section of Ophthalmology, King's College London, St. Thomas' Hospital Campus, London, United Kingdom
| | - John D. Mollon
- Department of Psychology, University of Cambridge, Cambridge, United Kingdom
| | - Patrick Yu-Wai-Man
- John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
- Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom
- Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
- Institute of Ophthalmology, University College London, London, United Kingdom
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28
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Yoo YJ, Hwang JM, Yang HK. Pupillary light reflex in ethambutol-induced optic neuropathy. Sci Rep 2020; 10:21601. [PMID: 33303779 PMCID: PMC7730149 DOI: 10.1038/s41598-020-77160-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 11/02/2020] [Indexed: 01/12/2023] Open
Abstract
We evaluated changes in the pupillary light reflex (PLR) of ethambutol (EMB)-induced optic neuropathy and analyzed the correlations between PLR parameters and other structural changes in EMB-induced optic neuropathy. This retrospective, observational, case–control study involved thirty-two eyes of 17 patients with EMB-induced optic neuropathy (EON group), sixty eyes of 60 patients without EMB-induced optic neuropathy (non-EON group) while taking ethambutol, and forty-five eyes of 45 normal controls. PLR was measured by digital pupillometry. The clinical characteristics, optical coherence tomography measurements and PLR parameters including pupil diameter, constriction latency, constriction ratio/velocity, and dilation velocity were noted. The differences in PLR measurements were compared among the three groups. Correlations between PLR parameters and other structural parameters in EMB-induced optic neuropathy were evaluated. The pupillary constriction ratio, constriction and dilation velocities were significantly reduced in the EON group compared to the non-EON group and controls (all P < 0.05). In EMB-induced optic neuropathy, average outer macular ganglion cell layer (mGCL) thickness showed a significant correlation with the pupillary constriction ratio (ß = 4.14, P = 0.003) and maximal constriction velocity (ß = 1.08, P < 0.001). This study confirmed that pupillary constriction and dilation velocities were significantly decreased in patients with EMB-induced optic neuropathy, compared to normal controls. Digital pupillometry may be a useful tool in the evaluation of EMB-induced optic neuropathy.
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Affiliation(s)
- Yung-Ju Yoo
- Department of Ophthalmology, Kangwon National University Hospital, Kangwon National University Graduate School of Medicine, Chuncheon, Korea
| | - Jeong-Min Hwang
- Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, 173 Beon-gil, Bundang-gu, Gumi-ro, Seongnam, Gyeonggi-do, 13620, Korea
| | - Hee Kyung Yang
- Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, 173 Beon-gil, Bundang-gu, Gumi-ro, Seongnam, Gyeonggi-do, 13620, Korea.
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29
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Lock JH, Irani NK, Newman NJ. Neuro-ophthalmic manifestations of mitochondrial disorders and their management. Taiwan J Ophthalmol 2020; 11:39-52. [PMID: 33767954 PMCID: PMC7971441 DOI: 10.4103/tjo.tjo_68_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 09/23/2020] [Indexed: 12/30/2022] Open
Abstract
The visual system has high metabolic requirements and is therefore particularly vulnerable to mitochondrial dysfunction. The most commonly affected tissues include the extraocular muscles, photoreceptors, retinal pigment epithelium, optic nerve and visual cortex. Hence, the most common manifestations of mitochondrial disorders are progressive external ophthalmoplegia, macular pattern dystrophy, pigmentary retinopathy, optic neuropathy and retrochiasmal visual field loss. With the exception of Leber hereditary optic neuropathy and stroke-like episodes seen in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes, the majority of neuro-ophthalmic manifestations have an insidious onset. As such, some patients may not recognize subtle progressive visual symptoms. When mitochondrial disorders are highly suspected, meticulous examination performed by an ophthalmologist with targeted ancillary testing can help confirm the diagnosis. Similarly, neuro-ophthalmic symptoms and signs may be the first indication of mitochondrial disease and should prompt systemic investigations for potentially life-threatening associations, such as cardiac conduction defects. Finally, the ophthalmologist can offer symptomatic treatments for some of the most disabling manifestations of these disorders.
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Affiliation(s)
- Jane H Lock
- Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia.,Department of Ophthalmology, Sir Charles Gairdner Hospital, Perth, WA, Australia.,Department of Ophthalmology, Perth's Children's Hospital, Perth, WA, Australia
| | - Neha K Irani
- Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia.,Department of Neurology, Fiona Stanley Hospital, Perth, WA, Australia.,Department of Neurology, Joondalup Health Campus, Perth, WA, Australia
| | - Nancy J Newman
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA.,Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.,Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA
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30
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Chen X, Di H, Hong Y, Zhang C. Late-stage sequela of an isolated optic neuropathy after acute magnesium valproate overdose: A case report. Eur J Ophthalmol 2020; 32:1120672120974943. [PMID: 33222509 DOI: 10.1177/1120672120974943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Magnesium valproate is a valproic acid (VPA) derivative that is widely used for the treatment of epilepsy and bipolar disorders. Acute overdose of VPA may cause complicated systemic syndromes; however, the reports of ocular sequelae caused by toxic optic neuropathy (TON) are rare. CASE PRESENTATION We present a case of a 19-year-old female with bilateral damage to visual function after acute VPA overdose. She was comatose and received systemic treatments for 1 month, during which she suffered a substantial loss of visual function without any evident neurological sequelae. The first recorded visual acuity was no light perception in the right eye (OD) and hand motion in the left eye (OS). Her best-corrected visual acuity improved to 20/100 OS after 4 months of hyperbaric oxygen therapy and neurotrophic treatments. Her visual field was limited to an inferior nasal area OS. Therefore, a diagnosis of TON was made. Her visual function remained stable in the left eye, but did not recover in the right eye during the 5-month follow-up. We found damage to the optic nerve pathway during ophthalmic examinations. CONCLUSION We report a rare case of TON caused by acute VPA overdose. Hyperbaric oxygen therapy, and neuroprotective and neurotrophic treatments might be effective at the early stage but cannot fully reverse the damage to the optic nerve. The present case indicates the potential neurotoxicity of VPA. It is crucial to determine the severity of an isolated optic nerve sequela caused by VPA overdose, though it might be rare as observed in previous reports. Further confirmation of the likelihood of its causation and its pathophysiology is needed in the future.
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Affiliation(s)
- Xuhao Chen
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, China
| | - Haohao Di
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, China
- Department of Ophthalmology, Zhengzhou Second Hospital, Henan, China
| | - Ying Hong
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, China
| | - Chun Zhang
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, China
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31
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Roda M, di Geronimo N, Pellegrini M, Schiavi C. Nutritional Optic Neuropathies: State of the Art and Emerging Evidences. Nutrients 2020; 12:E2653. [PMID: 32878163 PMCID: PMC7551088 DOI: 10.3390/nu12092653] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/27/2020] [Accepted: 08/28/2020] [Indexed: 12/19/2022] Open
Abstract
Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. In particular, recent studies have focused on possible pathogenetic mechanisms, and on novel diagnostic and therapeutic strategies in order to prevent the onset, make a prompt diagnosis and an accurate nutritional supplementation, and to avoid irreversible optic nerve atrophy. Nowadays, there is clear evidence of the role of cobalamin, folic acid, thiamine, and copper, whereas further studies are needed to define the role of niacin, riboflavin, and pyridoxine. This review aims to summarize the etiology, diagnosis, and treatment of nutritional optic neuropathy, and it is addressed not only to ophthalmologists, but to all physicians who could come in contact with a patient with a possible nutritional optic neuropathy, being a fundamental multidisciplinary approach.
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Affiliation(s)
- Matilde Roda
- Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy; (N.d.G.); (M.P.); (C.S.)
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32
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Ma J, Micieli JA. Severe Vision Loss in a Man With Heavy Tobacco and Alcohol Consumption. JAMA Ophthalmol 2020; 138:915-916. [PMID: 32556063 DOI: 10.1001/jamaophthalmol.2020.0900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Affiliation(s)
- Jingyi Ma
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Jonathan A Micieli
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
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33
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Manu MS, Mehta K, Das M, Balakrishnan S, Sunil kumar M, Rakesh P, Sindhu M, Valamparampil MJ, Neena P, Satyanarayana S. Ocular adverse events in drug sensitive TB patients on daily fixed dose combination anti-TB drugs: A record review study from Kerala, India. ACTA ACUST UNITED AC 2020; 67:216-221. [DOI: 10.1016/j.ijtb.2020.02.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 09/16/2019] [Accepted: 02/20/2020] [Indexed: 12/13/2022]
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34
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Kwon YS, Kwon BS, Kim OH, Park YE, Shim TS, Chong YP, Jo KW. Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease. J Korean Med Sci 2020; 35:e59. [PMID: 32141249 PMCID: PMC7061143 DOI: 10.3346/jkms.2020.35.e59] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 12/11/2019] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB. METHODS Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation. RESULTS The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045). CONCLUSION These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.
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Affiliation(s)
- Yong Shik Kwon
- Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Byoung Soo Kwon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Ock Hwa Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yea Eun Park
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Sun Shim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Kyung Wook Jo
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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35
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Affiliation(s)
- Tatsuya Fujikawa
- Departments of General Internal Medicine (Fujikawa) and Ophthalmology (Sogabe), Mitoyo General Hospital, Kanonji, Kagawa, Japan
| | - Yuka Sogabe
- Departments of General Internal Medicine (Fujikawa) and Ophthalmology (Sogabe), Mitoyo General Hospital, Kanonji, Kagawa, Japan
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36
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Ismail NA, Ismail F, Joseph L, Govender N, Blows L, Kaniga K, Omar SV. Epidemiological cut-offs for Sensititre susceptibility testing of Mycobacterium tuberculosis: interpretive criteria cross validated with whole genome sequencing. Sci Rep 2020; 10:1013. [PMID: 31974497 PMCID: PMC6978314 DOI: 10.1038/s41598-020-57992-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 01/08/2020] [Indexed: 11/20/2022] Open
Abstract
Universal drug susceptibility testing (DST) is an important requirement of the End TB Strategy. The Sensititre broth micro-dilution assay (BMD) tests multiple drugs quantitatively. We defined interpretive criteria for this assay and analysed genotypic-phenotypic relationships. 385 Mycobacterium tuberculosis clinical isolates were processed for BMD and whole genome sequencing. The epidemiological cut-off value 99% (ECV99) amongst genotypically wild type (gWT) strains defined susceptibility. Minimum inhibitory concentration distributions of the resistance-associated variants (RAVs) for each drug were analysed. Susceptibility (µg/mL) criteria were determined as follows: rifampicin (≤0.125), isoniazid (≤0.25), ethambutol (≤2.0), moxifloxacin (≤0.5), levofloxacin (≤1.0), amikacin (≤2.0), kanamycin (≤8.0), capreomycin (≤4.0), clofazimine (≤0.25) and linezolid (≤2.0). Most drugs showed clear separation between gWT and RAV. Isoniazid showed a tri-modal pattern with 14/17 strains at ECV99 harbouring a fabG1 c. -15C > T RAV. Ethambutol RAVs at embB codons 306, 405 and 497 were responsible for resistance and showed differential distributions. Moxifloxacin RAVs (gyrA codon 90) were a dilution or two higher than the ECV99 while gyrB RAVs were uncommon and showed drug specific resistance propensity. Interpretive criteria established were robust facilitating progress towards universal DST and individualised precision medicine. This study demonstrates the value of quantitative DST to accurately interpret mutation data.
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Affiliation(s)
- Nazir A Ismail
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa.
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
- Department of Internal Medicine, University of Witwatersrand, Johannesburg, South Africa.
| | - Farzana Ismail
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa
| | - Lavania Joseph
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa
| | - Netricia Govender
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa
| | - Linsay Blows
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa
| | - Koné Kaniga
- Janssen Research & Development, Titusville, NJ, United States of America
| | - Shaheed V Omar
- National Institute for Communicable Diseases, Centre for Tuberculosis, Johannesburg, South Africa
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37
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Ostroumova OD, Chikh EV, Rebrova EV, Ryazanova AY, Arzhimatova GS, Moshetova LK. [Drug-induced toxic optic neuropathy]. Vestn Oftalmol 2020; 136:156-164. [PMID: 32779471 DOI: 10.17116/oftalma2020136041156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Drug-induced optic neuropathy is a group of disorders in which medications cause degeneration of the optic nerve. The true prevalence of drug-induced neuropathy has not been studied, although the percentage of patients who develop optic nerve damage is known for individual medications. The common pathophysiological mechanisms are believed to be mitochondrial damage and imbalance of intracellular and extracellular free radical homeostasis. Typical symptoms of drug-induced neuropathy are reduced visual acuity in the central area, which is often bilateral, visual field disturbances, dyschromatopsia, and edema of the optic nerve head. Early detection of drug-induced optic neuropathy can potentially prevent or minimize serious complications. For patients who develop drug-induced optic neuropathy, treatment is based on timely diagnosis and cancellation of the provoking drug. In most patients, vision usually recovers a few weeks or months after discontinuation of previous therapy, but there have been cases of irreversible vision loss. In addition to withdrawal of the drug that caused optic nerve lesion, treatment of drug-induced neuropathy may include use of drugs and treatment methods prescribed by neurologists for peripheral neuropathy, however, such treatment is seldom based on evidence.
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Affiliation(s)
- O D Ostroumova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Russian Medical Academy of Continuing Professional Education, Moscow, Russia
| | - E V Chikh
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - E V Rebrova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - A Y Ryazanova
- Volgograd State Medical University, Volgograd, Russia
| | - G Sh Arzhimatova
- Russian Medical Academy of Continuing Professional Education, Moscow, Russia
- S.P. Botkin City Clinical Hospital, Moscow, Russia
| | - L K Moshetova
- Russian Medical Academy of Continuing Professional Education, Moscow, Russia
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38
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Grohmann SM, Berman A, Grassi MA. Linezolid-induced photoreceptor dysfunction masquerading as autoimmune retinopathy. Doc Ophthalmol 2019; 140:77-82. [PMID: 31587118 DOI: 10.1007/s10633-019-09725-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 09/17/2019] [Indexed: 10/25/2022]
Abstract
PURPOSE To report a case of linezolid-induced reversible retinopathy. METHODS Case report with literature review. RESULTS Clinical examination and imaging are presented over a 7-month interval, from initial presentation to subsequent follow-up (6 months after discontinuation of linezolid). The subject was found to have not only an optic neuropathy but also severe reversible photoreceptor dysfunction as demonstrated by electrophysiologic testing. Upon discontinuation of linezolid, not only did the patient's visual acuity, visual fields, and visual evoked potential significantly improve, but the electroretinogram did as well. CONCLUSIONS Linezolid has previously been reported to cause a toxic optic neuropathy. Reversible photoreceptor dysfunction on full-field electroretinography has never been reported in conjunction with linezolid toxicity. This novel case suggests that linezolid toxicity should be considered in cases of photoreceptor dysfunction.
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Affiliation(s)
| | - Andrew Berman
- Northwestern Lake Forest Hospital, Lake Forest, IL, USA
| | - Michael A Grassi
- Grassi Retina, Naperville, IL, USA. .,Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855, W Taylor St., Chicago, IL, 60612, USA.
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Abstract
PURPOSE OF REVIEW The diagnosis of visual loss from toxic-metabolic and hereditary optic neuropathies may be delayed in some cases because of a failure to elicit important information in the clinical history or to recognize typical examination findings. An understanding of the features specific to each type of toxic-metabolic and hereditary optic neuropathy, and of the underlying mechanism of insult to the optic nerve, could lead to earlier recognition, diagnosis, and treatment (when available). RECENT FINDINGS Understanding of the role of mitochondria in toxic-metabolic and hereditary optic neuropathies is growing, particularly regarding the mechanism of insult of certain agents (medications and toxins) and of vitamin B12 deficiency. New developments in the quest for treatment for hereditary optic neuropathy, specifically Leber hereditary optic neuropathy, are being seen. SUMMARY Toxic-metabolic and hereditary optic neuropathies present in a similar fashion, with painless, progressive, bilateral visual loss with dyschromatopsia and cecocentral visual field defects. The associated retinal ganglion cell and axonal loss is typically due to mitochondrial dysfunction caused by an exogenous agent (toxic), by insufficient or deficient substrate (metabolic or nutritional), or by abnormal proteins or mitochondrial structure determined by a genetic mutation (hereditary).
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40
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Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation. Optom Vis Sci 2019; 95:468-474. [PMID: 29683987 DOI: 10.1097/opx.0000000000001216] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
SIGNIFICANCE This case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy. PURPOSE To present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations. CASE REPORT A case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g. CONCLUSIONS We recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.
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Affiliation(s)
- Bradley Bishop
- Department of Small Animal Clinical Sciences College of Veterinary MedicineUniversity of FloridaGainesvilleFloridaUSA
| | - Stuart Walton
- Department of Small Animal Clinical Sciences College of Veterinary MedicineUniversity of FloridaGainesvilleFloridaUSA
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Abstract
SIGNIFICANCE Peripapillary retinal nerve fiber layer (RNFL) thickness measurements may be influenced by the range and severity of lesions that are observed distinctively in each retinal disease. PURPOSE We investigated the effects of various macular (central serous chorioretinopathy, macular hole, epiretinal membrane, wet age-related macular degeneration) and retinal vascular (branch retinal vein occlusion, central retinal vein occlusion, diabetic macular edema) diseases on peripapillary RNFL thickness measurements using spectral-domain optical coherence tomography. METHODS Six hundred thirty-one eyes from 464 patients with various retinal diseases and 167 controls of similar age were included in this retrospective study. Using spectral-domain optical coherence tomography, we measured the thickness of the macula and the RNFL in both various retinal disease eyes and normal control eyes. Four sectorial and average RNFL thicknesses were compared between each disease and age-matched control eyes. The macular thicknesses were also compared. RESULTS In the macular disease group, superior (P = .033) and temporal (P = .024) quadrant RNFL thicknesses of central serous chorioretinopathy and temporal (P < .001) quadrant RNFL thicknesses of epiretinal membrane were greater than the age-matched control eyes. No RNFL measurements in macular hole or wet age-related macular degeneration differed significantly from the controls. In the retinal vascular disease group, all sectorial and average RNFL thicknesses of diabetic macular edema and central retinal vein occlusion were greater than those of the controls (all P < .05). In branch retinal vein occlusion, superior (P = .012) and temporal (P < .001) quadrant RNFL thicknesses were greater than those of the controls. CONCLUSIONS Peripapillary RNFL thickness measurements may be influenced by the range and severity of lesions that are observed distinctively in each retinal disease. It also appeared that macular disease had a local effect on RNFL thickness, whereas retinal vascular disease had a diffuse effect on RNFL thickness.
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Agashe P, Doshi A. Linezolid induced optic neuropathy in a child treated for extensively drug resistant tuberculosis: A case report and review of literature. Saudi J Ophthalmol 2019; 33:188-191. [PMID: 31384167 PMCID: PMC6664266 DOI: 10.1016/j.sjopt.2018.10.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 08/10/2018] [Accepted: 10/30/2018] [Indexed: 11/22/2022] Open
Abstract
Linezolid induced optic neuropathy occurring after prolonged use of the drug is rarely reported in the paediatric age group. We report a case of Linezolid induced optic neuropathy in a child treated for extensively drug resistant tuberculosis. The optic neuropathy completely reversed with good improvement in vision after stopping the drug, which to the best of our knowledge has not been reported before.
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Affiliation(s)
- Prachi Agashe
- K.B. Haji Bachooali Eye Hospital, 58/60, Jehangir Merwanji Street, Opposite K.E.M Hospital, Parel, Mumbai 400012, India
- Advanced Eye Hospital and Institute, 30, The Affaires, Palm Beach Road, Sector-17, Sanpada, Navi Mumbai 400 705, India
| | - Ashish Doshi
- K.B. Haji Bachooali Eye Hospital, 58/60, Jehangir Merwanji Street, Opposite K.E.M Hospital, Parel, Mumbai 400012, India
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Karakurt Y, Süleyman H, Keskin Cimen F, Tasli G, Ucak T, Icel E, Kurt N. The effects of lutein on optic nerve injury induced by ethambutol and isoniazid: an experimental study. Cutan Ocul Toxicol 2018; 38:136-140. [PMID: 30362367 DOI: 10.1080/15569527.2018.1539010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
AIM Ethambutol and isoniazid are two major effective first line agents in tuberculosis treatment having some visual adverse effects. We aimed to determine the protective effects of lutein on oxidative optic neuropathy induced by ethambutol and isoniazid in an experimental model. MATERIAL AND METHOD Totally 24 albino Wistar male rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), 50 mg/kg ethambutol +50 mg/kg isoniazid administered group (EI), 0.5 mg/kg lutein +50 mg/kg ethambutol +50 mg/kg isoniazid administered group (LEI-05) and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), total glutathione (GSH), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed at the end of the study. RESULTS Serum and tissue IL-1β, TNF-α and MDA levels were the highest in EI group which were significantly lower in lutein administered group. On the other hand, serum and tissue total GSH levels were the lowest in EI group which were significantly higher in Lutein administered group. In histopathological evaluations, there were significant differences between EI group and all other three groups with edema and hemorrhage in connective tissue covering optic nerve, dilated and congested capillary, decrease in astrocytes and oligodendrocytes. CONCLUSION Isoniazid and ethambutol induced toxic optic neuropathy although not common, may have some potential devastating effects on vision. Lutein is determined as an effective agent in prevention of isoniazid and ethambutol induced toxic optic neuropathy.
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Affiliation(s)
- Yucel Karakurt
- a Department of Ophthalmology , Erzincan University , Erzincan , Turkey
| | - Halis Süleyman
- b Department of Pharmacology , Erzincan University , Erzincan , Turkey
| | | | - Gamze Tasli
- a Department of Ophthalmology , Erzincan University , Erzincan , Turkey
| | - Turgay Ucak
- a Department of Ophthalmology , Erzincan University , Erzincan , Turkey
| | - Erel Icel
- a Department of Ophthalmology , Erzincan University , Erzincan , Turkey
| | - Nezahat Kurt
- d Department of Biochemistry , Atatürk University , Erzurum , Turkey
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Teng D, Peng CX, Qian HY, Li L, Wang W, Wang JQ, Chen B, Zhou HF, Wei SH. Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies. Int J Ophthalmol 2018; 11:1643-1648. [PMID: 30364163 DOI: 10.18240/ijo.2018.10.11] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 07/13/2018] [Indexed: 01/10/2023] Open
Abstract
AIM To evaluate the structural injure patterns in peripapillary retinal fiber layer (pRNFL), retinal ganglion cell layer (RGCL) and their correlations to visual function in various mitochondrial optic neuropathies (MON) to offer help to their differential diagnosis. METHODS Totally 32 MON patients (60 eyes) were recruited within 6mo after clinical onsets, including 20 Leber hereditary optic neuropathy (LHON) patients (37 eyes), 12 ethambutol-induced optic neuropathy (EON) patients (23 eyes), and 41 age-gender matched healthy controls (HC, 82 eyes). All subjects had pRNFL and RGCL examinations with optic coherence tomography (OCT) and visual function tests. RESULTS In the early stages of MON, the temporal pRNFL thickness decreased (66.09±22.57 µm), but increased in other quadrants, compared to HC (76.95±14.81 µm). The other quadrants remaining stable for LHON and EON patients besides the second hour sector of pRNFL thickness reduced and the temporal pRNFL decreased (56.78±15.87 µm) for EON. Total macular thickness in MON reduced remarkably (279.25±18.90 µm; P=0.015), which mainly occurring in the inner circle (3 mm diameter of circle) and the nasal temporal sectors in the outer circle (5.5 mm diameter of circle), in contrast to those in HC. RGCL thickness reduced in each sector of the macula (61.90±8.73 µm; P≤0.001). It strongly showed the correlationship of best corrected visual acuity (R=0.50, P=0.0003) and visual field injury (R=0.54, P=0.0002) in MON patients. CONCLUSION OCT is a potential tool for detecting structural alterations in the optic nerves of various MON. Different types of MON may have different damage patterns.
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Affiliation(s)
- Da Teng
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
| | - Chun-Xia Peng
- Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
| | - Hai-Yan Qian
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
| | - Li Li
- Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
| | - Wei Wang
- Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China
| | - Jun-Qing Wang
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
| | - Bing Chen
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
| | - Huan-Fen Zhou
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
| | - Shi-Hui Wei
- Ophthalmology Department, Chinese PLA General Hospital, Beijing 100853, China
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Kogachi K, Ter-Zakarian A, Asanad S, Sadun A, Karanjia R. Toxic medications in Leber's hereditary optic neuropathy. Mitochondrion 2018; 46:270-277. [PMID: 30081212 DOI: 10.1016/j.mito.2018.07.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 05/23/2018] [Accepted: 07/31/2018] [Indexed: 12/18/2022]
Abstract
Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder characterized by acute bilateral vision loss. The pathophysiology involves reactive oxygen species (ROS), which can be affected by medications. This article reviews the evidence for medications with demonstrated and theoretical effects on mitochondrial function, specifically in relation to increased ROS production. The data reviewed provides guidance when selecting medications for individuals with LHON mutations (carriers) and are susceptible to conversion to affected. However, as with all medications, the proven benefits of these therapies must be weighed against, in some cases, purely theoretical risks for this unique patient population.
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Affiliation(s)
- Kaitlin Kogachi
- Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033, USA.
| | - Anna Ter-Zakarian
- Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033, USA
| | - Samuel Asanad
- Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033, USA; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, 800 South Fairmount Avenue, Suite 215, Pasadena, CA 91105, USA
| | - Alfredo Sadun
- Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033, USA; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, 800 South Fairmount Avenue, Suite 215, Pasadena, CA 91105, USA
| | - Rustum Karanjia
- Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033, USA; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, 800 South Fairmount Avenue, Suite 215, Pasadena, CA 91105, USA; The Ottawa Eye Institute, University of Ottawa, 501 Smyth Rd, Ottawa, ON K1H 8M2, Canada; Ottawa Hospital Research Institute, 1053 Carling Avenue, Ottawa, ON K1Y 4E9, Canada
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The structure and diffusion behaviour of the 1:1 copper(II) complex of ethambutol in aqueous solution. J Mol Liq 2018. [DOI: 10.1016/j.molliq.2018.04.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Park SJ, Jung JU, Kang YK, Chun BY, Son BJ. Toxic Optic Neuropathy Caused by Chlorfenapyr Poisoning. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2018. [DOI: 10.3341/jkos.2018.59.11.1097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Su Jin Park
- Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea
- Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea
| | - Jae Uk Jung
- Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea
- Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea
| | - Yong Koo Kang
- Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea
- Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea
| | - Bo Young Chun
- Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea
- Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea
| | - Byeong Jae Son
- Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu, Korea
- Department of Ophthalmology, Kyungpook National University Hospital, Daegu, Korea
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Schaaf HS, Garcia-Prats AJ, McKenna L, Seddon JA. Challenges of using new and repurposed drugs for the treatment of multidrug-resistant tuberculosis in children. Expert Rev Clin Pharmacol 2017; 11:233-244. [DOI: 10.1080/17512433.2018.1421067] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- H. Simon Schaaf
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Anthony J. Garcia-Prats
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | | | - James A. Seddon
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Centre for International Child Health, Department of Paediatrics, Imperial College London, London, UK
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