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Hopkinson A, Figueiredo FC. A Narrative Review of Amniotic Membrane Transplantation in Ocular Surface Repair: Unveiling the Immunoregulatory Pathways for Timely Intervention. Ophthalmol Ther 2025:10.1007/s40123-025-01143-w. [PMID: 40360962 DOI: 10.1007/s40123-025-01143-w] [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: 12/14/2024] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
This narrative review explores the pathophysiology of ocular surface inflammation and highlights the therapeutic potential of patch amniotic membrane transplantation (patch-AMT) in ocular surface repair. Disruptions in ocular surface homeostasis caused by trauma, disease, or immune dysregulation trigger an inflammatory cascade that, if unresolved, can impair epithelial healing, lead to fibrosis, corneal haze, and vision loss. Patch-AMT provides a biological intervention with epitheliotropic, anti-inflammatory, anti-fibrotic, anti-angiogenic, and neuroprotective effects that support wound healing, regulate inflammation, and reduce pain. The review examines patch-AMT's role in acute conditions (chemical burns, Stevens-Johnson Syndrome) and chronic disease (persistent epithelial defects, dry eye disease), focusing on its ability to entrap immune cells, regulate cytokine signaling, and prevent fibrotic remodeling while releasing trophic proteins. Additionally, this review explores how preservation methods, application orientation, and intervention timing influences patch-AMT's efficacy. Recent advancements in non-surgical application methods have expanded accessibility, enabling earlier intervention and outpatient use. However, variability in clinical protocols emphasize the need for standardized guidelines. The review concludes by highlighting the need for further research to refine treatment timing, optimize repeat application strategies, and evaluate cost-effectiveness. While patch-AMT remains underutilized, growing evidence underscores its potential to improve clinical outcomes, particularly when applied early in disease progression.
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Affiliation(s)
- Andrew Hopkinson
- Academic Ophthalmology, Division of Clinical Neuroscience, Queen's Medical Centre (QMC), University of Nottingham, Queen's Medical Centre Campus, Nottingham, NG7 2UH, UK.
- NuVision Biotherapies, MediCity Nottingham, Nottingham, NG90 6BH, UK.
| | - Francisco C Figueiredo
- Department of Ophthalmology, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
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Tutas Günaydın N, Barut Selver O. Pediatric limbal stem cell deficiency: An overview of a rarely studied pathology. Eur J Ophthalmol 2025; 35:821-833. [PMID: 39473431 DOI: 10.1177/11206721241291995] [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] [Indexed: 04/22/2025]
Abstract
The cornea is the outermost transparent layer of the eye, and the continuous renewal of the corneal epithelium is important for its transparency. This process is primarily facilitated by corneal stem cells, most of which are found at the limbus. However, any deterioration or damage in this region leads to corneal conjunctivalization and consequent limbal stem cell deficiency (LSCD), which compromises corneal transparency. LSCD is an important condition, especially in the pediatric population, as it can lead to corneal vascularization, opacity and ultimately loss of vision and subsequent amblyopia, unlike adults. Although pediatric LSCD is often due to chemical injuries, as in adults, it is also caused by conditions such as congenital aniridia, Steven Johnson Syndrome and various other immunological disorders. Appropriate and timely treatment in pediatric LSCD is of particular importance in preventing progression to amblyopia, unlike adults. Accurate staging of the disease is essential for the necessary medical and surgical treatment decision. While medical approaches are at the forefront to eliminate the causative agent and improve the ocular surface in reversible cases, it is essential to replace the limbal stem cells lost in advanced disease. For these replacement procedures, it is noteworthy that there is a tendency for minimally invasive methods compared to adults to avoid possible complications due to long life expectancy in children. In conclusion, although there are various reviews on limbal stem cell deficiency (LSCD) in adults, we believe that this review for childhood LSCD will make an important contribution to the literature, since the relevant literature currently reported for the pediatric population is limited.
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Affiliation(s)
- Nesrin Tutas Günaydın
- Department of Ophtalmology, Istanbul Arel University, Bahçelievler Memorial Hospital, Istanbul, Turkey
| | - Ozlem Barut Selver
- Department of Ophthalmology, School of Medicine, Ege University, Izmir, Turkey
- Stem Cell Department, Graduate School of Health Sciences, Ege University, Izmir, Turkey
- Limbustem R&D Medical Products Ltd & Ocular Surface Research Laboratory, Ege University, Izmir, Turkey
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Singh P, Palit A, Gupta A, Niyogi SG, Loganathan S, Chattopadhyay M, Meshram S, Verma A, Tripathy PK. Amniotic membrane grafting for acute ocular involvement in Stevens-Johnson syndrome: Review of perioperative considerations, surgical techniques, and outcomes. Indian J Ophthalmol 2025; 73:553-562. [PMID: 40146142 PMCID: PMC12097413 DOI: 10.4103/ijo.ijo_1238_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 10/11/2024] [Accepted: 10/26/2024] [Indexed: 03/28/2025] Open
Abstract
To review the perioperative considerations, surgical techniques, and outcomes of amniotic membrane grafting for acute ocular manifestations in Stevens-Johnson syndrome (SJS) and discuss a novel amniotic membrane grafting method. An online literature search of published articles on amniotic membrane grafting in acute SJS was performed using appropriate keywords on March 1, 2024. The relevant articles were included and analyzed. The review summarizes the relevance of amniotic membrane grafting in the current scenario. It also compares different techniques of amniotic membrane grafting and the ocular surface coverage each procedure provides. A novel technique of amniotic membrane grafting has been discussed with a schematic explanation. It also summarizes the complications of amniotic membrane grafting and their management, and the long-term outcomes of amniotic membrane grafting in preventing chronic sequelae. One should have a lower threshold for doing amniotic membrane grafting in cases with ocular involvement. This prevents the development of long-term sequelae and subsequent corneal blindness.
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Affiliation(s)
- Prabhakar Singh
- Department of Ophthalmology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Aparna Palit
- Department of Dermatology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Abhishek Gupta
- Department of Ophthalmology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Subhrashis G Niyogi
- Department of Anesthesiology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Sekar Loganathan
- Department of Anesthesiology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Mahuya Chattopadhyay
- Department of Ophthalmology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Sheel Meshram
- Department of Ophthalmology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Abhishek Verma
- Department of Ophthalmology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Peeyush K Tripathy
- Department of Dermatology, All India Institute of Medical Sciences, Kalyani, West Bengal, India
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Rashad R, Kwan JT, Shanbhag SS, Ngowyutagon P, Saeed M, Tahboub MA, Haseeb A, Chodosh J, Saeed HN. Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study. Br J Ophthalmol 2024; 108:1508-1513. [PMID: 38490716 DOI: 10.1136/bjo-2023-324076] [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: 06/13/2023] [Accepted: 03/03/2024] [Indexed: 03/17/2024]
Abstract
PURPOSE To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.
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Affiliation(s)
- Ramy Rashad
- Department of Ophthalmology, Boston Medical Center, Boston, Massachusetts, USA
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
| | - James T Kwan
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
- Department of Ophthalmology, New England Eye Center, Boston, Massachusetts, USA
| | - Swapna S Shanbhag
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
- The Cornea Institute, L.V. Prasad Eye Institute, Hyderabad, Telangana, India
| | - Panotsom Ngowyutagon
- Department of Ophthalmology, Mahidol University, Salaya, Thailand
- Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois, USA
| | - Musa Saeed
- Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois, USA
| | - Mohammad A Tahboub
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
| | - Abid Haseeb
- Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois, USA
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
- Division of Ophthalmology, University of New Mexico, Albuquerque, New Mexico, USA
| | - Hajirah N Saeed
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
- Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois, USA
- Department of Ophthalmology, Loyola University Medical Center, Maywood, IL, USA
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Hu S, Chen J, Jin J, Liu Y, Xu GT, Ou Q. Construction of living-cell tissue engineered amniotic membrane for ocular surface disease. BMC Ophthalmol 2024; 24:409. [PMID: 39300402 PMCID: PMC11412061 DOI: 10.1186/s12886-024-03680-7] [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: 07/08/2023] [Accepted: 09/12/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. METHODS AND RESULTS In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs' tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. CONCLUSIONS In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.
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Affiliation(s)
- Shuqin Hu
- Department of Ophthalmology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jie Chen
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiahui Jin
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yifan Liu
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guo-Tong Xu
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Qingjian Ou
- Department of Ophthalmology and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
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Boroumand S, Rahmani M, Sigaroodi F, Ganjoury C, Parandakh A, Bonakdar A, Khani MM, Soleimani M. The landscape of clinical trials in corneal regeneration: A systematic review of tissue engineering approaches in corneal disease. J Biomed Mater Res B Appl Biomater 2024; 112:e35449. [PMID: 39032135 DOI: 10.1002/jbm.b.35449] [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: 11/20/2023] [Revised: 04/27/2024] [Accepted: 06/19/2024] [Indexed: 07/22/2024]
Abstract
The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.
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Affiliation(s)
- Safieh Boroumand
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahya Rahmani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faraz Sigaroodi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Camellia Ganjoury
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azim Parandakh
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Bonakdar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad-Mehdi Khani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoud Soleimani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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7
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Sahay P, Behbehani M, Filippini P, Bruti G, Townsend M, McKean R, Dua HS. A Biosynthetic Alternative to Human Amniotic Membrane for Use in Ocular Surface Surgery. Transl Vis Sci Technol 2024; 13:3. [PMID: 38696180 PMCID: PMC11077906 DOI: 10.1167/tvst.13.5.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/06/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose The biosynthetic Symatix membrane (SM) was developed to replace fresh human amniotic membrane (hAM) in ocular surgical applications. The purpose of this study was to test the biocompatibility of the SM with human limbus-derived epithelial cells with regard to their physical and biological properties. Methods Different physical properties of SM were tested ex vivo by simulation on human corneas. In vitro, primary limbal epithelial cells from limbal explants were used to test biological properties such as cell migration, proliferation, metabolic activity, and limbal epithelial cell markers on the SM, hAM, and freeze-dried amniotic membrane (FDAM). Results The surgical handleability of the SM was equivalent to that of the hAM. Ultrastructural and histological studies demonstrated that epithelial cells on the SM had the typical tightly apposed, polygonal, corneal epithelial cell morphology. The epithelial cells were well stratified on the SM, unlike on the hAM and FDAM. Rapid wound healing occurred on the SM within 3 days. Immunofluorescence studies showed positive expression of CK-19, Col-1, laminin, ZO-1, FN, and p-63 on the SM, plastic, and FDAM compared to positive expression of ZO-1, Col-1, laminin, FN, and p63 and negative expression of CK-19 in the hAM. Conclusions These results indicate that the SM is a better substrate for limbal epithelial cell migration, proliferation, and tight junction formation. Altogether, the SM can provide a suitable alternative to the hAM for surgical application in sight-restoring operations. Translational Relevance The hAM, currently widely used in ocular surface surgery, has numerous variations and limitations. The biocompatibility of corneal epithelial cells with the SM demonstrated in this study suggests that it can be a viable substitute for the hAM.
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Affiliation(s)
- Prity Sahay
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, UK
| | | | - Perla Filippini
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, UK
| | | | | | - Rob McKean
- The Electrospinning Company, Oxfordshire, UK
| | - Harminder S. Dua
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, UK
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Chen YL, Tsai TY, Pan LY, Tsai YJ, Chen SY, Hsiao CH, Yeh LK, Tan HY, Chen HC, Hung KH, Quan W, Chen CB, Chung WH, Ma DHK. Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients. Am J Ophthalmol 2023; 256:108-117. [PMID: 37633318 DOI: 10.1016/j.ajo.2023.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 07/16/2023] [Accepted: 08/17/2023] [Indexed: 08/28/2023]
Abstract
PURPOSE To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN Retrospective comparative case series. METHODS This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used. RESULTS Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications. CONCLUSIONS Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.
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Affiliation(s)
- Yueh-Ling Chen
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Tsung-Ying Tsai
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Li-Yen Pan
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yueh-Ju Tsai
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shin-Yi Chen
- Department of Ophthalmology (S.-Y.C.), Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Hsi Hsiao
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Lung-Kun Yeh
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Yuan Tan
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hung-Chi Chen
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Hsuan Hung
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wuyong Quan
- Department of Ophthalmology (W.Q., D.H.-K.M.), Xiamen Chang Gung Hospital, Xiamen, China
| | - Chun-Bing Chen
- Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Drug Hypersensitivity Clinical and Research Center (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences (C.-B.C., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology (C.-B.C., W.-H.C.), Xiamen Chang Gung Hospital, Xiamen, China
| | - Wen-Hung Chung
- Department of Medicine (Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H., C.-BC., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Drug Hypersensitivity Clinical and Research Center (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences (C.-B.C., W.-H.C.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory (C.-B.C., W.-H.C.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology (C.-B.C., W.-H.C.), Xiamen Chang Gung Hospital, Xiamen, China
| | - David Hui-Kang Ma
- From the Department of Ophthalmology (Y.L.-C, T.-Y.T., L.-Y.P., Y.-J.T., C.-H.H., L.-K.Y., H-Y.T., H.-C.C., K.-S.H.), Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Ophthalmology (W.Q., D.H.-K.M.), Xiamen Chang Gung Hospital, Xiamen, China; Department of Chinese Medicine (D.H.-K.M.), College of Medicine, Chang Gung University, Taoyuan, Taiwan; Center for Tissue Engineering (D.H.-K.M.), Chang Gung Memorial Hospital, Linkou, Taiwan.
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Xu L, Wang G, Shi R, Zeng B, Zhang Y, Liu Z, Dong N, Wang S, Li C. A cocktail of small molecules maintains the stemness and differentiation potential of conjunctival epithelial cells. Ocul Surf 2023; 30:107-118. [PMID: 37634570 DOI: 10.1016/j.jtos.2023.08.005] [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: 03/29/2023] [Revised: 07/19/2023] [Accepted: 08/18/2023] [Indexed: 08/29/2023]
Abstract
PURPOSE The conjunctival epithelial cells cultured with bovine serum or feeder cells were not suitable for clinical application. Therefore, we developed a novel serum-free and feeder cell-free culture system containing only a cocktail of three chemicals (3C) to expand the conjunctival epithelial cells. METHODS The cell proliferative ability was evaluated by counting, crystal violet staining and Ki67 immunostaining. Co-staining of K7 and MUC5AC was performed to identify goblet cells. PAS staining was used to assess the ability of cells to synthesis and secrete glycoproteins. In vivo, eye drops containing 3C was administered to verify the role of 3C in the mouse conjunctival injury model. PAS, HE and immunofluorescence staining were performed to show conjunctival epithelial repair. RESULTS Compared with other small molecule groups and the serum group, the cells in 3C group showed superior morphology and proliferative ability. Meanwhile, 3C maintained the well-proliferative capacity of cells even after fifth passage. The 3C group also exhibited more K7 and MUC5AC double positive cells, and the PAS staining positive areas were present in both the cytoplasm and extracellular matrix. The cell sheets treated with 3C in air-lifted culture were obviously stratified. In vivo, more goblet cells in the conjunctival epithelium were observed in the 3C group. CONCLUSION Overall, our culture system can expand the conjunctival epithelial cells and retain their potential to differentiate into mature goblet cells, which provided a promising source of seed cells for conjunctival reconstruction. Furthermore, this system provides new insights for the clinical treatment of ocular surface diseases.
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Affiliation(s)
- Lina Xu
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Guoliang Wang
- Huaxia Eye Hospital of Quanzhou, Quanzhou, Fujian, 362000, China; School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, 361102, China
| | - Ruize Shi
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Baihui Zeng
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Yan Zhang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Zhen Liu
- Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China
| | - Nuo Dong
- Huaxia Eye Hospital of Quanzhou, Quanzhou, Fujian, 362000, China; Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.
| | - Shurong Wang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
| | - Cheng Li
- Huaxia Eye Hospital of Quanzhou, Quanzhou, Fujian, 362000, China; Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China; Department of Ophthalmology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, China.
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10
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Zhang N, Geng X, Liu R, Liu X, Cui H, Dou R, Hou S, Li J, Zhu L, Li Z. Novel technique for amniotic membrane transplantation for acute Stevens-Johnson syndrome/toxic epidermal necrolysis patients. Heliyon 2023; 9:e18853. [PMID: 37600383 PMCID: PMC10432697 DOI: 10.1016/j.heliyon.2023.e18853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 07/27/2023] [Accepted: 07/31/2023] [Indexed: 08/22/2023] Open
Abstract
Purpose To report a novel technique to facilitate amniotic membrane transplantation (AMT) for acute stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Design Laboratory investigation and retrospective, single-center case series. Methods The polylactic acid (PLA) amniotic fornical ring (AFR) have been successfully manufactured by three-dimensional (3D) printing technology for AMT. This study retrospectively analyzed the medical records of 5 SJS/TEN patients at the acute stage between 2019 and 2023. Patients were surgically treated with AFR or sutured amniotic membrane transplant (SAMT). Epidemiology, best-corrected visual acuity (BCVA), acute ocular severity score, operative duration, epithelial healing time, amniotic dissolution and follow-up time were evaluated. Results Of all five patients, three patients (6 eyes) received AFR/AMT (Group A), and 2 patients (4 eyes) received SAMT (Group B). There were no significant differences between two groups in the mean preoperative days and vision changes. The mean operation duration was 11.7 ± 3.8 mins in group A. Compared with the SAMT (48.8 ± 5.3 mins), the operation duration was reduced by 76.02%. The mean times for epithelial healing were 32.5 ± 29.2 days in group A and 12.0 ± 0.0 days in group B. In addition, there were no significant side effects of 3D-printed sterile AFR on the eyes. Conclusions 3D-printed PLA scaffolds could be used as an AFR device for acute SJS/TEN. In addition, personalized 3D-printed AFR is superior to conventional SAMT in operation duration.
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Affiliation(s)
| | | | - Ruixing Liu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Xiaowu Liu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Haohao Cui
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Runan Dou
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Songlin Hou
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Lei Zhu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
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11
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Liu Y, Feng J, Ren Y, Shi W, Kang H, Peng Y, Tan Y, Wu R, Zhang G, He Y. Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study. BMC Ophthalmol 2023; 23:297. [PMID: 37400766 DOI: 10.1186/s12886-023-03052-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 06/19/2023] [Indexed: 07/05/2023] Open
Abstract
BACKGROUND Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. METHODS Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. RESULTS Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. CONCLUSIONS Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.
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Affiliation(s)
- Yingyi Liu
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Jianing Feng
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
- Xi'an People's Hospital (Xi'an Fourth Hospital), Shaanxi Eye Hospital, Northwest University Affiliated People's Hospital, Xi'an, Shaanxi Province, China
| | - Yuerong Ren
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Wen Shi
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Huanmin Kang
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Yingqian Peng
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Yixin Tan
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ruifang Wu
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guiying Zhang
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yan He
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
- Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China.
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12
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Ceylan A, Mergen B, Aydin FO, Avci E, Yildirim Y. Sutureless Amniotic Membrane Transplantation Using Pediatric Nasogastric Tube for Patients With Acute Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. Eye Contact Lens 2023; 49:199-203. [PMID: 36943174 DOI: 10.1097/icl.0000000000000986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
PURPOSE Evaluation of the results of sutureless amniotic membrane transplantation (AMT) using a pediatric nasogastric tube (NGT) for patients with acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) was aimed. METHODS Twenty-six eyes of 13 patients with SJS/TEN with ocular involvement at a single tertiary care hospital between May 2020 and January 2022 were included in the study. An amniotic membrane was implanted to the ocular surface and conjunctival fornix using a modified symblepharon ring (MR) created by inserting NGT end-to-end. Patients were followed for at least 6 months. The mean duration of the surgery was recorded. The presence of corneal epithelial defect and vascularization, meibomian gland dysfunction (MGD) grade, conjunctival scarring, eyelid margin keratinization, symblepharon, and trichiasis were recorded. RESULTS The mean age of the patients was 38.4±17.6 years. Amniotic membrane transplantation was performed only once for eight patients and twice for five patients. The mean duration of the surgery was 3.2±0.4 min. The modified symblepharon ring was removed 28 days after its application. At the first examination, 20 eyes (76.9%) had a corneal epithelial defect and 6 (23.1%) had early symblepharon. At the postoperative 6 months, although seven eyes (26.9%) had conjunctival scarring and 5 (19.2%) had eyelid margin keratinization, all patients were without any corneal defect, corneal vascularization, or symblepharon. Only 11 eyes (42.3%) showed MGD, and 1 eye (3.8%) showed trichiasis. CONCLUSIONS This study showed that sutureless AMT using pediatric NGT could be a potentially fast and inexpensive treatment option for the treatment of SJS/TEN with ocular involvement at the bedside without the need for general anesthesia.
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Affiliation(s)
- Ali Ceylan
- Department of Ophthalmology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
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13
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Sharma R, Nappi V, Empeslidis T. The developments in amniotic membrane transplantation in glaucoma and vitreoretinal procedures. Int Ophthalmol 2023; 43:1771-1783. [PMID: 36715957 PMCID: PMC10149474 DOI: 10.1007/s10792-022-02570-5] [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: 05/01/2022] [Accepted: 11/12/2022] [Indexed: 01/31/2023]
Abstract
The main reasons why Amniotic Membrane (AM) is transplanted in Ophthalmology are: to provide a substrate for cellular growth and to provide tectonic support or as a biological bandage and barrier that protects the wound to facilitate an environment for wound healing. The application of AM is well-documented in corneal disorders of various aetiologies [1], however, research within the field has highlighted how it can be used in conjunctival disorders and most recently, in glaucoma and vitreoretinal procedures. This review explores the preservation modalities of AM and summarises the current literature regarding AM transplantation in Glaucoma and Vitreoretinal conditions. AM transplantation in conjunction with trabeculectomy was reported to be used in two different surgical techniques. They differ in relation to the position of the implant: below the scleral flap or over the entire exposed sclera. The results of these studies suggest that AM transplant is a safe procedure that helps in the improvement of the intraocular pressure when associated with trabeculectomies. Moreover, it enhances trabeculectomies success rates when used along with mitomycin C [2]. The use of AM is also described for managing leaking blebs. It is mentioned to be a suitable alternative to conjunctival advancement. Regarding AM transplantation in glaucoma shunt or valve surgeries, the current literature is relatively limited. However, AM has been described as a good tectonic support for shunt procedures [3]. Successful results are described in the literature for surgical treatments using AM plug for vitreoretinal procedures. In particular macular hole closure and rhegmatogenous retinal detachment. In conclusion, AM transplant is a very promising and versatile adjutant therapy. However, further studies are also required for a better understanding and refinement of surgical techniques.
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Affiliation(s)
- Rohit Sharma
- Eye Department, University Hospitals Derby & Burton NHS trust, Burton, UK. .,School of Medicine, University of Nottingham, Nottingham, UK.
| | - Vivian Nappi
- Ophthalmology Department, Nottingham University Hospital NHS Trust, Nottingham, UK
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14
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Ying PX, Fu M, Huang C, Li ZH, Mao QY, Fu S, Jia XH, Cao YC, Hong LB, Cai LY, Guo X, Liu RB, Meng FK, Yi GG. Profile of biological characterizations and clinical application of corneal stem/progenitor cells. World J Stem Cells 2022; 14:777-797. [PMID: 36483848 PMCID: PMC9724387 DOI: 10.4252/wjsc.v14.i11.777] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 11/08/2022] [Accepted: 11/23/2022] [Indexed: 12/13/2022] Open
Abstract
Corneal stem/progenitor cells are typical adult stem/progenitor cells. The human cornea covers the front of the eyeball, which protects the eye from the outside environment while allowing vision. The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role. Corneal stem/progenitor cells include mainly corneal epithelial stem cells, corneal endothelial cell progenitors and corneal stromal stem cells. Since the discovery of corneal epithelial stem cells (also known as limbal stem cells) in 1971, an increasing number of markers for corneal stem/progenitor cells have been proposed, but there is no consensus regarding the definitive markers for them. Therefore, the identification, isolation and cultivation of these cells remain challenging without a unified approach. In this review, we systematically introduce the profile of biological characterizations, such as anatomy, characteristics, isolation, cultivation and molecular markers, and clinical applications of the three categories of corneal stem/progenitor cells.
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Affiliation(s)
- Pei-Xi Ying
- Department of Ophthalmology, Zhujiang Hospital, The Second Clinical School, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Min Fu
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Chang Huang
- Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200030, China
- NHC Key Laboratory of Myopia, Fudan University, Shanghai 200030, China
- Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200030, China
| | - Zhi-Hong Li
- Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Lab of Shock and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou 510550, Guangdong Province, China
| | - Qing-Yi Mao
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Sheng Fu
- Hengyang Medical School, The University of South China, Hengyang 421001, Hunan Province, China
| | - Xu-Hui Jia
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Yu-Chen Cao
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Li-Bing Hong
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Li-Yang Cai
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xi Guo
- Medical College of Rehabilitation, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Ru-Bing Liu
- The Second Clinical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Fan-ke Meng
- Emergency Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Guo-Guo Yi
- Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
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15
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Shanbhag SS, Tahboub MA, Chodosh J, Saeed HN. Visual function and quality of life in patients with Stevens-Johnson syndrome who received acute protocol-based ocular care. FRONTIERS IN TOXICOLOGY 2022; 4:992696. [PMID: 36408350 PMCID: PMC9666488 DOI: 10.3389/ftox.2022.992696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/14/2022] [Indexed: 12/05/2022] Open
Abstract
Purpose: To report visual function and quality of life (VF/QOL) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the ocular surface disease index (OSDI) in patients in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: The NEI-VFQ-25 questionnaire was administered to 15 patients who received protocol-based care in the form of topical medications with or without amniotic membrane transplantation (AMT) for acute SJS/TEN. The scores obtained were compared with scores from a healthy population. The associations between the NEI-VFQ-25 and dry eye symptoms as measured by OSDI questionnaire were also studied. Results: Patients were surveyed at a mean of 4.47 ± 2.22 years after acute SJS/TEN. Eleven patients received AMT in the acute phase. The median best corrected visual acuity at the time of administration of the questionnaire was 20/20. The mean composite NEI-VFQ-25 score was 86.48 ± 12. Patients who received protocol-based treatment in the acute phase of SJS/TEN had comparable NEI-VFQ-25 scores with healthy subjects on all subscales except ocular pain (p = 0.027) and mental health (p = 0.014), which were significantly reduced. The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.75, p = 0.001). Conclusion: A protocol-based management strategy composed of early ophthalmic evaluation, grading based on severity, the use of topical corticosteroids and AMT in the acute phase of SJS/TEN in patients with ocular complications helped preserve the VF/QOL. This study highlights the impact of appropriate management of the ocular complications in the acute phase of SJS/TEN.
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Affiliation(s)
- Swapna S. Shanbhag
- The Cornea Institute, L. V. Prasad Eye Institute, Hyderabad, India,Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - Mohammad A. Tahboub
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - Hajirah N. Saeed
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States,Department of Ophthalmology, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, IL, United States,Department of Ophthalmology, Loyola University Medical Center, Chicago, IL, United States,*Correspondence: Hajirah N. Saeed,
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16
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Modified technique for sutureless amniotic membrane transplantation in acute Stevens-Johnson syndrome using fibrin sealant. Ocul Surf 2022; 25:89-91. [DOI: 10.1016/j.jtos.2022.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 04/09/2022] [Accepted: 05/23/2022] [Indexed: 11/19/2022]
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17
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Magone MT, Maiberger M, Clayton J, Pasieka H. Vulvovaginal and ocular involvement and treatment in female patients with Stevens-Johnson syndrome and toxic epidermal necrolysis: A review. Int J Womens Dermatol 2022; 7:520-528. [PMID: 35024409 PMCID: PMC8721055 DOI: 10.1016/j.ijwd.2021.08.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/25/2021] [Accepted: 08/26/2021] [Indexed: 10/31/2022] Open
Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.
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Affiliation(s)
- M Teresa Magone
- Ophthalmology Consult Services Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland
| | - Mary Maiberger
- Department of Dermatology, Veterans Affairs Medical Center, Washington, DC
| | - Janine Clayton
- Ophthalmology Consult Services Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland.,Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland
| | - Helena Pasieka
- Uniformed Services University of Health Sciences, Bethesda, Maryland
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18
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Rapuano C, Lam S, Sklar B, Schoen M. Severe ocular alkali injury managed with an externally sutured amniotic membrane and customized symblepharon ring. Taiwan J Ophthalmol 2022; 13:101-105. [DOI: 10.4103/2211-5056.362597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 09/29/2022] [Indexed: 12/05/2022] Open
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19
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Ogawa M, Mukudai S, Sugiyama Y, Matsushita H, Kinoshita S, Ozawa S, Hashimoto K, Fuse S, Kaneko M, Nakanishi Y, Yoshizaki T, Sotozono C, Hirano S. The Effects of Amniotic Membrane Transplantation on Vocal Fold Regeneration. Laryngoscope 2021; 132:2017-2025. [PMID: 34951490 DOI: 10.1002/lary.29997] [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: 09/10/2021] [Revised: 12/05/2021] [Accepted: 12/10/2021] [Indexed: 11/08/2022]
Abstract
OBJECTIVES/HYPOTHESIS Vocal fold (VF) scar and sulcus cause severe vocal problems, but optimal methods have not been established. Total replacement of the mucosa is required particularly for cases in which the whole lamina propria is occupied by severe fibrosis and vibratory function is totally lost. The amniotic membrane (AM) has been proven to have regenerative potential, as it contains stem cells and growth factors. The current study investigated the biocompatibility and effects of AM for regeneration of the VF mucosa. STUDY DESIGN In vitro and in vivo studies. METHODS Vocal fold fibroblasts (VFFs) from 13 Sprague-Dawley rats were seeded on AM and subjected to histology and immunohistochemistry, and gene expressions in the VFFs on AM were examined in in vitro study. Twelve New Zealand White rabbits were used in in vivo study. VFs were stripped down and were reconstructed with AM. The regenerative effects were examined 3 months later by histological examination. RESULTS In vitro study indicated VFFs survived on AM and stained positively for Ki67, vimentin, and fibronectin. Gene expressions of Has1, Has2, and Hgf were significantly increased in the VFFs on AM compared with the other groups. The in vivo study indicated AM-transplanted VFs showed a significantly higher density of hyaluronic acid and lower density of collagen compared with sham VFs. CONCLUSIONS The current preliminary study suggests biocompatibility and possible regenerative effects of AM for VFs. LEVEL OF EVIDENCE NA Laryngoscope, 2021.
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Affiliation(s)
- Machiko Ogawa
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.,Department of Otolaryngology Head and Neck Surgery, Kanazawa University, Kanazawa, Japan
| | - Shigeyuki Mukudai
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoichiro Sugiyama
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroki Matsushita
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shota Kinoshita
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satomi Ozawa
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Keiko Hashimoto
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shinya Fuse
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mami Kaneko
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yosuke Nakanishi
- Department of Otolaryngology Head and Neck Surgery, Kanazawa University, Kanazawa, Japan
| | - Tomokazu Yoshizaki
- Department of Otolaryngology Head and Neck Surgery, Kanazawa University, Kanazawa, Japan
| | - Chie Sotozono
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shigeru Hirano
- Department of Otolaryngology Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
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20
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Loureiro RR, Cristovam PC, da Rosa LR, Nova L, Gasparetto G, Gil CD, Gomes JÁP. Analysis of different conditioned media secreted by limbal progenitor cells in the modulation of corneal healing. Exp Eye Res 2021; 215:108907. [PMID: 34954203 DOI: 10.1016/j.exer.2021.108907] [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: 09/15/2021] [Revised: 12/16/2021] [Accepted: 12/20/2021] [Indexed: 11/18/2022]
Abstract
Ex vivo cultivation and transplantation of limbal epithelial cells has been reported as an alternative source for ocular surface reconstruction. However, until now, the functional improvement of these patients is limited due to the low survival rate of the transplanted cells. Consequently, the clinical benefits of this therapeutic strategy are only temporary and can assign them to paracrine effects associated with the transplanted cells. With this background in mind, we aimed to analyze the effect of different conditioned media containing growth factors secreted by limbal progenitor cells on corneal epithelial healing, both in vitro and in vivo. Limbal tissue was used to obtain different conditioned media (CM). For the in vitro assay, corneal epithelial cells were treated with CM and the epithelial migration was analyzed. Growth factors in the CM were identified with ELISA and multiplex. For the in vivo assay in rats, total limbal stem cell deficiency (LSCD) was induced with an abrasive injury to the ocular surface, and the animals were treated with different CM. Clinical and histological analyses were performed. In the in vitro assay, treatment with limbal fibroblast (LF CM) was more effective compared to the other CM, and analysis revealed high concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF). In the in vivo assay, animals treated with LF CM showed epithelial defect improvement, maintenance of thickness, and decreased opacity and neovascularization. This treatment also allowed better ocular surface tissue organization when compared to the other treatments. The in vitro and in vivo experiments showed better outcomes in the corneal wound healing for the LF CM treatment. The high concentrations of KGF and HGF, linked to epithelial cell migration and proliferation, may correlate to the best results found in this treatment.
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Affiliation(s)
- Renata Ruoco Loureiro
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
| | - Priscila Cardoso Cristovam
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Larissa Rigobeli da Rosa
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Lucimeire Nova
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Gustavo Gasparetto
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Cristiane Damas Gil
- Department of Morphology and Genetics, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - José Álvaro Pereira Gomes
- Advanced Center of Ocular Surface (CASO), Department of Ophthalmology and Visual Science, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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21
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Mahmood AH, Alharbi AS, Almanea BA, Alsaati AF. Sutureless Amniotic Membrane (ProKera®) and Intravenous Immunoglobulin in the Management of Ocular Complications of Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis Overlap. Cureus 2021; 13:e16989. [PMID: 34540392 PMCID: PMC8422256 DOI: 10.7759/cureus.16989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2021] [Indexed: 11/05/2022] Open
Abstract
PURPOSE To report a case of Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, with severe acute ocular manifestations successfully managed with sutureless Amniotic Membrane device ProKera® (Bio-Tissue, Inc., Miami, FL) and topical steroids, followed by late complications that were successfully managed with intravenous immunoglobulin (IVIG) therapy. OBSERVATIONS A 24-year-old lady, known case of epilepsy, admitted to the burn unit with SJS-TEN overlap attributed to a recent change of her anti-convulsant therapy, with severe ocular manifestations, inability to open both eyes, and poor visual acuity. Early management included intensive topical steroids and lubrication, in addition to the application of a ProKera® device. Despite achieving full epithelialization within two weeks with the improvement of ocular manifestations, the patient presented three weeks later with recurrence of conjunctival epithelial defects, partial ankyloblepharon, and severely dry corneas. These late sequelae were managed with bandage contact lens (BCL) application, intensive topical steroid, and lubrication in addition to IVIG therapy. After six cycles of IVIG therapy, ocular manifestations improved significantly and the patient achieved uncorrected visual acuity of 6/9 in both eyes. Conclusion and importance: Existing evidence suggests that the use of IVIG in combination with systemic steroids in the early phase of SJS-TEN can reduce mortality, without affecting the final visual outcome in patients with ocular manifestations. This case highlights the possible role of IVIG therapy alone - without systemic steroids - in managing and preventing long-term ocular complications of SJS-TEN.
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Affiliation(s)
- Abdulhameed H Mahmood
- Ophthalmology, Salmaniya Medical Complex, Manama, BHR
- Ophthalmology, Anterior Segment Division, Prince Sultan Military Medical City, Riyadh, SAU
| | | | | | - Anoud F Alsaati
- Ophthalmology, Anterior Segment Division, Prince Sultan Military Medical City, Riyadh, SAU
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22
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Metcalfe D, Iqbal O, Chodosh J, Bouchard CS, Saeed HN. Acute and Chronic Management of Ocular Disease in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in the USA. Front Med (Lausanne) 2021; 8:662897. [PMID: 34322500 PMCID: PMC8311126 DOI: 10.3389/fmed.2021.662897] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/31/2021] [Indexed: 11/25/2022] Open
Abstract
Stevens Johnson syndrome and toxic epidermal necrolysis are on a spectrum of a severe, immune-mediated, mucocutaneous disease. Ocular involvement occurs in the vast majority of cases and severe involvement can lead to corneal blindness. Treatment in the acute phase is imperative in mitigating the severity of chronic disease. Advances in acute treatment such as amniotic membrane transplantation have shown to significantly reduce the severity of chronic disease. However, AMT is not a panacea and severe chronic ocular disease can and does still occur even with aggressive acute treatment. Management of chronic disease is equally critical as timely intervention can prevent worsening of disease and preserve vision. This mini-review describes the acute and chronic findings in SJS/TEN and discusses medical and surgical management strategies.
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Affiliation(s)
- Derek Metcalfe
- Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA, United States
| | - Omer Iqbal
- Loyola University Medical Center, Maywood, IL, United States
| | - James Chodosh
- Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA, United States
| | | | - Hajirah N Saeed
- Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA, United States
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23
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Gregory DG. USA: Ophthalmologic Evaluation and Management of Acute Stevens-Johnson Syndrome. Front Med (Lausanne) 2021; 8:670643. [PMID: 34307405 PMCID: PMC8292721 DOI: 10.3389/fmed.2021.670643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/21/2021] [Indexed: 11/13/2022] Open
Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can cause significant damage to the ocular surface and eyelids. The sloughing and inflammation of the ocular mucosal epithelium during the acute phase may lead to scarring sequelae of the eyelids and ocular surface, resulting in pain and vision loss. Amniotic membrane transplantation (AMT) to the eyes and eyelids during the initial 1–2 weeks of the disease can decrease the chronic sequelae. The main development in the ophthalmologic treatment of SJS/TEN in the USA over the last 15 years has been the use of AMT on the ocular surface and eyelids during the acute phase. The evolution of AMT techniques, refinement of the evaluation of the eyes in acute SJS, and the efforts to increase the use of AMT in the USA are discussed.
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Affiliation(s)
- Darren G Gregory
- Sue Anschutz-Rodgers Eye Center, University of Colorado, Aurora, CO, United States
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24
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Ogawa Y, Kawakami Y, Tsubota K. Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease. Int J Mol Sci 2021; 22:ijms22116114. [PMID: 34204098 PMCID: PMC8201206 DOI: 10.3390/ijms22116114] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/30/2021] [Accepted: 05/31/2021] [Indexed: 01/12/2023] Open
Abstract
Ocular graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Ocular GVHD affects recipients' visual function and quality of life. Recent advanced research in this area has gradually attracted attention from a wide range of physicians and ophthalmologists. This review highlights the mechanism of immune processes and the molecular mechanism, including several inflammation cascades, pathogenic fibrosis, and stress-induced senescence related to ocular GVHD, in basic spectrum topics in this area. How the disease develops and what kinds of cells participate in ocular GVHD are discussed. Although the classical immune process is a main pathological pathway in this disease, senescence-associated changes in immune cells and stem cells may also drive this disease. The DNA damage response, p16/p21, and the expression of markers associated with the senescence-associated secretory phenotype (SASP) are seen in ocular tissue in GVHD. Macrophages, T cells, and mesenchymal cells from donors or recipients that increasingly infiltrate the ocular surface serve as the source of increased secretion of IL-6, which is a major SASP driver. Agents capable of reversing the changes, including senolytic reagents or those that can suppress the SASP seen in GVHD, provide new potential targets for the treatment of GVHD. Creating innovative therapies for ocular GVHD is necessary to treat this intractable ocular disease.
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Affiliation(s)
- Yoko Ogawa
- Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan;
- Correspondence: ; Tel.: +81-3-3353-1211
| | - Yutaka Kawakami
- Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan;
- Department of Immunology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan
| | - Kazuo Tsubota
- Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan;
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25
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Ma DHK, Tsai TY, Pan LY, Chen SY, Hsiao CH, Yeh LK, Tan HY, Lu CW, Chen CB, Chung WH. Clinical Aspects of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications in Taiwan. Front Med (Lausanne) 2021; 8:661891. [PMID: 34055837 PMCID: PMC8149748 DOI: 10.3389/fmed.2021.661891] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/08/2021] [Indexed: 12/17/2022] Open
Abstract
Purpose: Over the last decade, there has been tremendous progress in the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To understand whether this has resulted in better ophthalmic outcomes, we aimed to study the incidence of severe ocular complications (SOCs) in the acute and chronic stage among SJS/TEN patients, major causative medications, and therapeutic effect of medical and surgical treatment. Methods: Using electronic medical records review of patients of Chang Gung Memorial Hospital Linkou Branch from 2010 to 2020, 119 patients (236 eyes) received ophthalmic consultation during the acute stage and were retrospectively studied. Sotozono's grading score systems for acute and chronic SJS/TEN were employed for accessing correlation between acute and chronic presentations, the therapeutic effect of systemic etanercept treatment, and outcome of early amniotic membrane transplantation (AMT) performed in patients with severe acute SOCs. Results: There were 46 male and 73 female patients with a mean age of 45.6 ± 22.7 years old (2–90 years), and follow-up time of 408.3 ± 351.0 (116–1,336) days. The numbers of patients with SJS, overlap syndrome, and TEN were 87, 9, and 23, respectively. In total, 109 eyes (55 patients) had acute SOCs, which comprised 46.2% of patients who underwent ophthalmic examination. Antiepileptics were the most common category of culprit drugs causing SOCs in the acute stage. At the end of follow-up, there were 14 eyes (9 patients) with chronic SOCs (5.9%), and non-steroidal anti-inflammatory drugs and cold medicine were the most common causative medications that were associated with severe chronic sequela. The correlation between Sotozono's acute and chronic grading score showed a positive relationship [Spearman's rank correlation coefficient (r) = 0.52, p < 0.001]. The average chronic grading scores in patients receiving systemic corticosteroid combined with etanercept treatment were significantly lower than those receiving corticosteroid only, Finally, the average chronic grading scores in patients receiving AMT <7 days after onset were significantly lower than those performed beyond 7 days. Conclusion: Our study implies that acute manifestation can be an indicator for chronic sequelae. Additional early etanercept treatment and early AMT showed beneficial effect in reducing chronic ocular sequela.
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Affiliation(s)
- David Hui-Kang Ma
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Ophthalmology, Xiamen Chang Gung Hospital, Xiamen, China
| | - Tsung-Ying Tsai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Li-Yen Pan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Shin-Yi Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Hsi Hsiao
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Lung-Kun Yeh
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Yuan Tan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Wei Lu
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chun-Bing Chen
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
| | - Wen-Hung Chung
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
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26
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Chen Z, Lao HY, Liang L. Update on the application of amniotic membrane in immune-related ocular surface diseases. Taiwan J Ophthalmol 2021; 11:132-140. [PMID: 34295618 PMCID: PMC8259520 DOI: 10.4103/tjo.tjo_16_21] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 04/23/2021] [Indexed: 12/18/2022] Open
Abstract
Immune-related ocular surface diseases, a group of diseases in which immune dysregulation damages the ocular surface, can induce uncontrolled inflammation and persistent epithelial defect, thus leading to the most severe forms of acute keratoconjunctivitis, dry eye disease, epithelial keratitis, stromal ulceration, and corneal perforation. As these diseases are often refractory to treatments, they have a threatening impact on the vision and life quality of patients. This review summarizes the current literature regarding the clinical application of sutured and self-retained cryopreserved amniotic membrane (AM) in treating Stevens-Johnson syndrome/toxic epidermal necrolysis, ocular graft-versus-host disease, Sjögren's syndrome, Mooren's ulcer, and peripheral ulcerative keratitis. Current evidence supports the safety and effectiveness of AM, especially self-retained cryopreserved AM, in decreasing ocular surface inflammation, promoting corneal epithelial and stromal healing, improving visual acuity, and preventing sight-threatening complications. Future studies are still required to validate the above findings and explore the varied application methods of AM to improve the clinical efficacy in maintaining ocular surface health.
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Affiliation(s)
- Ziyan Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Hubert Yuenhei Lao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Lingyi Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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27
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Bonnet C, Roberts JS, Deng SX. Limbal stem cell diseases. Exp Eye Res 2021; 205:108437. [PMID: 33571530 PMCID: PMC8044031 DOI: 10.1016/j.exer.2021.108437] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/14/2020] [Accepted: 01/02/2021] [Indexed: 12/13/2022]
Abstract
The function of limbal stem/progenitor cells (LSCs) is critical to maintain corneal epithelial homeostasis. Many external insults and intrinsic defects can be deleterious to LSCs and their niche microenvironment, resulting in limbal stem cell dysfunction or deficiency (LSCD). Ocular comorbidities, frequent in eyes with LSCD, can exacerbate the dysfunction of residual LSCs, and limit the survival of transplanted LSCs. Clinical presentation and disease evolution vary among different etiologies of LSCD. New ocular imaging modalities and molecular markers are now available to standardize the diagnosis criteria and stage the severity of the disease. Medical therapies may be sufficient to reverse the disease if residual LSCs are present. A stepwise approach should be followed to optimize the ocular surface, eliminate the causative factors and treat comorbid conditions, before considering surgical interventions. Furthermore, surgical options are selected depending on the severity and laterality of the disease. The standardized diagnostic criteria to stage the disease is necessary to objectively evaluate and compare the efficacy of the emerging customized therapies.
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Affiliation(s)
- Clémence Bonnet
- Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA; Cornea Department, Paris University, Cochin Hospital, AP-HP, F-75014, Paris, France.
| | - JoAnn S Roberts
- Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
| | - Sophie X Deng
- Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
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28
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Abstract
PURPOSE To characterize the clinical presentation of limbal stem cell deficiency (LSCD) associated with glaucoma surgeries. METHODS This is a retrospective cross-sectional study of patients with LSCD and glaucoma who presented to the Stein Eye Institute at the University of California, Los Angeles, between 2009 and 2018. Patients who underwent trabeculectomy and/or aqueous shunt surgery were included. The severity of LSCD was staged using global consensus guidelines and a clinical scoring system, and basal epithelial cell density was measured by in vivo confocal microscopy. Anatomic locations of glaucoma and non-glaucoma surgeries, locations of LSCD, and severity of LSCD were compared. RESULTS Fifty-one eyes of 41 patients with LSCD associated with glaucoma surgery were included in this study. LSCD in these patients uniquely featured sectoral replacement of corneal epithelium by conjunctival epithelium, without corneal neovascularization or pannus. The sites of glaucoma surgery strongly correlated with the locations of LSCD (P = 0.002). There was a trend toward increased severity of LSCD in eyes with 2 or more glaucoma surgeries as compared to eyes with 1 glaucoma surgery, although the difference did not reach statistical significance (P = 0.3). Use of topical glaucoma medications correlated with LSCD severity, while the impact of antimetabolites did not reach statistical significance. The location of glaucoma drainage surgery is correlated with the location of LSCD. CONCLUSIONS LSCD associated with glaucoma surgery has clinical features distinct from LSCD resulting from other etiologies. Further study is required to delineate the full impact of glaucoma surgery on limbal stem cell function and survival.
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29
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Kim MK, Yoon KC, Yoon SH, Seo KY. Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in South Korea. Front Med (Lausanne) 2021; 8:640360. [PMID: 33693020 PMCID: PMC7937613 DOI: 10.3389/fmed.2021.640360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/22/2021] [Indexed: 12/22/2022] Open
Abstract
This review describes the current knowledge regarding genetic susceptibilities and treatment strategies for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with ocular complications, in Korea. In a case-control study, the gene frequencies of both HLA-A*0206 (20.0%) and HLA-Cw*0304 (15.0%) increased but the gene frequency of HLA-Cw*0303 (1.3%) decreased with cold medicine (CM)-SJS/TEN with severe ocular complications (SOCs). In a case-series, positive genotyping of HLA-B*5801 was 80.0% in allopurinol-induced SJS/TEN without SOCs. In a genome-wide association study, HLA-A*0206 was substantially related to CM-SJS/TEN with SOCs. Both HLA-A*0206 and prostaglandin-E receptor 3 (PTGER3) single nucleotide polymorphism (SNP) rs1327464 exert a synergistic effect on SOCs in CM-SJS/TEN. In the acute stage, conventional procedures, amniotic membrane transplantation or suture-less amniotic contact lenses are applied. Applications of intravenous Immunoglobulin (IVIG) or mega-dose steroids are attempted in patients with high acute ocular and systemic involvement scores. In the chronic stage, keratolimbal transplantation and penetrating keratoplasty are the standard procedures. Either autologous nasal or oral mucosal grafts, or biomaterial-free cultured oral mucosal epithelial cell sheets are transplanted as alternative therapies. Deep anterior lamellar keratoplasty is attempted. Combined photodynamic therapy with intrastromal bevacizumab injection or intense pulse laser are used to resolve chronic ocular complication. Corneoscleral contact lenses are available for a visual rehabilitation. As a last resort, Seoul-type keratoprosthesis had been transplanted. There are unmet needs to standardize nationwide ocular grading system and to correct tarsal scarring using mucosal grafting. This review provides a perspective on the current practices to treat ocular complications in SJS/TEN.
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Affiliation(s)
- Mee Kum Kim
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea.,Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, South Korea
| | - Kyung Chul Yoon
- Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju, South Korea
| | - Sook Hyun Yoon
- Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyoung Yul Seo
- Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea
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30
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Gise R, Elhusseiny AM, Scelfo C, Mantagos IS. Ocular involvement in recurrent infectious mucocutaneous eruption (RIME): a variation on a theme. J AAPOS 2021; 25:62-64. [PMID: 33348041 DOI: 10.1016/j.jaapos.2020.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/29/2020] [Accepted: 10/25/2020] [Indexed: 11/30/2022]
Abstract
We present 2 cases of pediatric patients with reactive infectious mucocutaneous eruption with ophthalmic involvement. In both cases, the disease processes behaved similarly to that seen in patients with Mycoplasma pneumoniae-induced rash and mucositis. Visual outcomes were good.
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Affiliation(s)
- Ryan Gise
- Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
| | - Abdelrahman M Elhusseiny
- Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Christina Scelfo
- Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Iason S Mantagos
- Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
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31
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Elhusseiny AM, Gise R, Scelfo C, Mantagos IS. Amniotic membrane transplantation in a 2-month-old infant with toxic epidermal necrolysis. Am J Ophthalmol Case Rep 2021; 21:101017. [PMID: 33521381 PMCID: PMC7820027 DOI: 10.1016/j.ajoc.2021.101017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 10/05/2020] [Accepted: 01/11/2021] [Indexed: 02/07/2023] Open
Abstract
Purpose To report a case of 2-month-old boy with Stevens-Johnson syndrome (SJS)/Toxic epidermal necrolysis (TEN) and ocular involvement that was successfully treated with cryopreserved amniotic membrane transplantation (AMT). Observation A 2-month-old otherwise healthy boy was referred to Boston Children's Hospital with extensive rash and desquamation concerning for SJS/TEN. A skin biopsy was performed which showed full-thickness epidermal necrosis. AMT was performed at the bedside under general anesthesia. A combination of tobramycin and dexamethasone ointment was prescribed four times per day. On reassessment two weeks following AMT, the entire ocular surface had healed with no signs of conjunctival and/or corneal inflammation or ulceration. Conclusion and importance To the best of our knowledge, our case represents the youngest patient with SJS/TEN to be managed by AMT and one of very few cases where acetaminophen is suspected to be the offending agent. This case highlights the efficacy of AMT at such a young age and feasibility of performing the procedure at bedside in these patients It also highlights that SJS/TEN can develop at such young age.
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Affiliation(s)
- Abdelrahman M Elhusseiny
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ryan Gise
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Christina Scelfo
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Iason S Mantagos
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
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32
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Amniotic Membrane-Covered Conformer and Fibrin Glue for Toxic Epidermal Necrolysis. Cornea 2021; 40:525-528. [PMID: 33881813 DOI: 10.1097/ico.0000000000002591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Stevens-Johnson syndrome and its more severe form, toxic epidermal necrolysis, are immunologic disorders that cause widespread blistering of the skin and mucous membranes. Its incidence is higher in children and can lead to long-term disabling ocular surface complications that can be averted with amniotic membrane transplantation early in the disease. To introduce an amniotic membrane treatment technique that is time efficient and minimally invasive but still allows for extensive coverage of the ocular mucosal surfaces to prevent and lessen the severity of the complications from ocular surface sequelae. METHODS The procedure was undertaken in the operating room under general anesthesia. Symblephara were divided before an amniotic membrane-covered conformer was placed into the fornices. Fibrin glue was used to secure the conformer and to keep the palpebral aperture closed. Topical chloramphenicol 0.5% and prednisolone 0.5% were prescribed 4 times a day. RESULTS After 7 days, the conformers were removed and new amniotic membrane-covered conformers were reapplied in both eyes for a further week. After the second round of treatment, the conformers were left out for 3 days. Inferior symblephara reformed in the left lower fornix, and therefore, a third round of treatment was undertaken in the left eye only, which was then removed after 7 days. A follow-up at 8 weeks revealed 20/20 vision with minimal symblephara in either eye. CONCLUSIONS This novel technique, using an amniotic membrane-covered conformer in combination with fibrin glue, allows for the coverage of the entire ocular surface and protection of the lid margins while requiring minimal preparation and surgical time. This technique could also be used in patients with other cicatrizing ocular surface conditions, such as chemical or thermal injuries or postreconstructive surgery of the fornices.
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Wu N, Yan C, Chen J, Yao Q, Lu Y, Yu F, Sun H, Fu Y. Conjunctival reconstruction via enrichment of human conjunctival epithelial stem cells by p75 through the NGF-p75-SALL2 signaling axis. Stem Cells Transl Med 2020; 9:1448-1461. [PMID: 32602639 PMCID: PMC7581450 DOI: 10.1002/sctm.19-0449] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 05/03/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022] Open
Abstract
Severe conjunctival diseases can cause significant conjunctival scarring, which seriously limits eye movement and affects patients' vision. Conjunctival reconstruction remains challenging due to the lack of efficient methods for stem cells enrichment. This study indicated that p75 positive conjunctival epithelial cells (CjECs) were mainly located in the basal layer of human conjunctival epithelium and showed an immature differentiation state in vivo. The p75 strongly positive (p75++) CjECs enriched by immuno-magnetic beads exhibited high expression of stem cell markers and low expression of differentiated keratins. During continuous cell passage cultivation, p75++ CjECs showed the strongest proliferation potential and were able to reconstruct the conjunctiva in vivo with the most complete structure and function. Exogenous addition of NGF promoted the differentiation of CjECs by increasing nuclear localization of SALL2 in p75++ CjECs while proNGF played an opposite role. Altogether, p75++ CjECs present stem cell characteristics and exhibit the strongest proliferation potential so can be used as seed cells for conjunctival reconstruction, and NGF-p75-SALL2 signaling pathway was involved in regulating the differentiation of CjECs.
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Affiliation(s)
- Nianxuan Wu
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Chenxi Yan
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Junzhao Chen
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Qinke Yao
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Yang Lu
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Fei Yu
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Hao Sun
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
| | - Yao Fu
- Department of OphthalmologyShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiPeople's Republic of China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghaiPeople's Republic of China
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Baş Z, Uçakhan Gündüz Ö. Sutureless Amniotic Membrane Transplantation in a Pediatric Patient with Acute Toxic Epidermal Necrolysis. Turk J Ophthalmol 2020; 49:356-360. [PMID: 31893592 PMCID: PMC6961079 DOI: 10.4274/tjo.galenos.2019.13333] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
The purpose of this case report is to describe a new surgical method for sutureless placement of the amniotic membrane with a symblepharon ring in a pediatric patient with acute toxic epidermal necrolysis (TEN). A 1-year-old girl developed severe ocular surface inflammation with large corneal and conjunctival epithelial defects secondary to TEN. She was treated by applying a large (4 cm x 4 cm) amniotic membrane graft and non-sterile symblepharon ring under sedoanalgesia at bedside in the intensive care unit. The ocular surface was completely epithelized by post-treatment week 6 in the right and week 8 in the left eye. Two years after amniotic membrane transplantation, both eyes were quiet with no symblepharon, scar formation, or limbal stem cell deficiency. Performing bilateral amniotic membrane transplantation under a symblepharon ring at bedside provided sufficient acute coverage of the ocular surface and led to excellent clinical outcomes by reducing inflammation and protecting the ocular surface.
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Affiliation(s)
- Zeynep Baş
- Ankara University, Faculty of Medicine, Department of Ophthalmology, Ankara, Turkey
| | - Ömür Uçakhan Gündüz
- Ankara University, Faculty of Medicine, Department of Ophthalmology, Ankara, Turkey
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Galvis V, Tello A, Carreño NI, Niño CA, García NA, Otoya V, Arana R. Severe corneal burn due to the accidental application of salicylic acid packed in a plastic dropper bottle. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2020; 40:456-463. [PMID: 33030823 PMCID: PMC7666852 DOI: 10.7705/biomedica.5284] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/03/2020] [Indexed: 11/21/2022]
Abstract
Eye burns due to the accidental application of pharmacological or nonpharmacological substances packaged in plastic dropper bottles have been described for more than three decades and continue to occur. These burns can cause potentially serious corneal injuries. We report the case of a patient who mistakenly applied salicylic acid to the right eye after confusing it with an eye lubricant, which caused him a severe corneal burn. Fortunately, after aggressive medical and surgical management (including oxygen therapy and amniotic membrane grafting), the visual results were good. We suggest conducting educational campaigns and taking legislative measures in our country to avoid packaging corrosive substances in this type of dropper bottle to reduce the risk of accidental burns.
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Affiliation(s)
- Virgilio Galvis
- Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Floridablanca, Colombia; Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Departamento de Oftalmología, Fundación Oftalmológica de Santander, FOSCAL, Floridablanca, Colombia.
| | - Alejandro Tello
- Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Floridablanca, Colombia; Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Departamento de Oftalmología, Fundación Oftalmológica de Santander, FOSCAL, Floridablanca, Colombia.
| | - Néstor I Carreño
- Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Floridablanca, Colombia; Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Departamento de Oftalmología, Fundación Oftalmológica de Santander, FOSCAL, Floridablanca, Colombia.
| | - Camilo A Niño
- Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Floridablanca, Colombia; Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Departamento de Oftalmología, Fundación Oftalmológica de Santander, FOSCAL, Floridablanca, Colombia.
| | - Natalia A García
- Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Facultad de Ciencias de la Salud, Universidad del Rosario, Bogotá, D.C., Colombia.
| | - Valeria Otoya
- Departamento de Oftalmología, Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Floridablanca, Colombia.
| | - Rodrigo Arana
- Departamento de Oftalmología, Centro Oftalmológico Virgilio Galvis, Floridablanca, Colombia; Departamento de Oftalmología, Fundación Oftalmológica de Santander, FOSCAL, Floridablanca, Colombia.
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Walkden A. Amniotic Membrane Transplantation in Ophthalmology: An Updated Perspective. Clin Ophthalmol 2020; 14:2057-2072. [PMID: 32801614 PMCID: PMC7383023 DOI: 10.2147/opth.s208008] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 06/22/2020] [Indexed: 01/23/2023] Open
Abstract
Aim The aim of this paper is to provide a succinct literature review of the different clinical applications for AMT usage in an ophthalmic setting, ranging from commonly used applications to less mainstream approaches. The hope is that this review enables the reader to have a better understanding of the biological properties of amnion as well as the indications and scenarios in which AMT can be used, whilst presenting relevant evidence from within the literature which may be of interest. We also provide an update on the methods of preservation of amniotic membrane and the application methodologies. Methods Literature search. A PubMed search was performed using the search terms “amniotic membrane transplant”, “amnion AND cornea”, amnion AND ophthalmology”, “amnion AND ocular surface” and “Amnion AND eye”. A full review of the literature using the PubMed database was conducted up until 01/05/20. The articles used were written in English, with all articles accessed in full. Both review articles and original articles were used for this review. All full publications related to ophthalmology were considered.
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Affiliation(s)
- Andrew Walkden
- Manchester Royal Eye Hospital, Manchester University Foundation Trust, Manchester, UK.,University of Manchester Faculty of Medical and Human Sciences, Manchester, Greater Manchester, UK
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Treatment of Oculoplastic and Ocular Surface Disease in Eyes Implanted with a Type I Boston Keratoprosthesis in Southern China: A Retrospective Study. Adv Ther 2020; 37:3206-3222. [PMID: 32436025 DOI: 10.1007/s12325-020-01381-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION This study aimed to describe the clinical features, surgical management of the eyelid and ocular surface, and outcomes of 16 patients implanted with a Boston type I keratoprosthesis (KPro). METHODS A retrospective, single-center, consecutive case series of 16 patients with Stevens-Johnson syndrome (1), ocular chemical burns (12), and ocular thermal burns (3) implanted with KPro was studied. All subjects were men aged 27-51 years. Surgical treatment and outcomes for eyelid malposition, symblepharon, and glaucoma were assessed. RESULTS From September 2010 to February 2019, 29 patients were admitted to Zhongshan Ophthalmic Center for KPro implantation, of whom 16 (55%) required eyelid or ocular surface surgeries to maintain hydration and protect the corneal tissue, which is vulnerable to epithelial defects. Forty-one adnexal surgical procedures were performed. The most common indication for surgery was symblepharon, and the most frequent procedures were symblepharon lysis with ocular mucous membrane grafts and amniotic membranes (7) and full-thickness skin grafts to the eyelids (7). Preoperative conjunctival injection and corneal staining were documented in 9 (56%) and 8 (50%) eyes, respectively, and at up to 4 months postoperative follow-up (the last adnexal surgery before KPro) were recorded in 3 (19%, p = 0.03) and 2 (12%, p = 0.02) eyes, respectively. Glaucoma drainage devices were inserted in six patients. One patient with Stevens-Johnson syndrome underwent FP7 Ahmed glaucoma valve (AGV) implantation inferotemporally and developed plate exposure 2 months postoperatively. Five patients underwent FP8 AGV implantation with tube insertion into the vitreous cavity due to the scarred conjunctiva and limited subconjunctival space. In the study period, intraocular pressure (IOP) was in the normal range, and no tube or plate exposure was observed. CONCLUSION The ocular environment is critical for successful KPro surgery. A multidisciplinary approach for any lid and ocular surface abnormality in ocular burns or Stevens-Johnson syndrome is important to improve the quality of the ocular surface and accommodate KPro and AGV, which is vital for maintaining vision after KPro surgery. FP8 AGV may be feasible for IOP control in adult KPro cases with restricted subconjunctival space.
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A Systematic Review of Emerging Therapeutic Strategies in the Management of Chemical Injuries of the Ocular Surface. Eye Contact Lens 2020; 46:329-340. [PMID: 32452924 DOI: 10.1097/icl.0000000000000715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To evaluate recent in vivo studies on emerging therapies for managing corneal epithelial injuries. METHODS The search was conducted on PubMed for articles published between January 2015 and September 2019 and in English language. RESULTS Thirty studies were identified for evaluation, including those on mesenchymal stem cells, amniotic membrane-derived therapies, endogenous peptides and their inhibitors, as well as hydrogel therapies. Intermediate to strong levels of evidence are presented regarding the use of these strategies on chemically injured cornea, including their effects on healing of corneal epithelial defect, anti-inflammatory properties, prevention of corneal neovascularization, as well as restoration of anatomy and functions of the anterior eye, although clinical trials are needed to determine the safety and efficacy of these strategies on humans. CONCLUSION Recent advances and understanding in various novel therapeutic methods for corneal epithelial chemical injuries should provide potential alternatives to current standard treatment regimens and help reduce risks of complications, hence improve patient outcomes.
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Shanbhag SS, Chodosh J, Fathy C, Goverman J, Mitchell C, Saeed HN. Multidisciplinary care in Stevens-Johnson syndrome. Ther Adv Chronic Dis 2020; 11:2040622319894469. [PMID: 32523661 PMCID: PMC7236394 DOI: 10.1177/2040622319894469] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 11/12/2019] [Indexed: 12/17/2022] Open
Abstract
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are potentially fatal mucocutaneous diseases that can involve many organ systems. Manifestations of SJS/TEN outside of the skin, eyes, and oral mucosa are not well defined or well recognized, and, therefore, are often not addressed clinically. As supportive care improves and mortality from SJS/TEN decreases, chronic complications in affected organ systems are becoming more prevalent. Recognition of the manifestations of SJS/TEN in the acute phase is critical to optimal care. In this review, we review the organ systems that may be involved in SJS/TEN, provide an overview of their management, and propose a list of items that should be communicated to the patient and family upon discharge. The organ systems discussed include the pulmonary, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynecologic, genitourinary, and renal systems. In addition, the significant psychosocial, nutritional, and pain consequences and management of SJS/TEN are discussed.
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Affiliation(s)
- Swapna S Shanbhag
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
| | - Cherie Fathy
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Jeremy Goverman
- Department of Surgery, Massachusetts General Hospital, Sumner Redstone Burn Center, Boston, MA, USA
| | - Caroline Mitchell
- Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA
| | - Hajirah N Saeed
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, USA
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Shanbhag SS, Hall L, Chodosh J, Saeed HN. Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2020; 18:517-522. [PMID: 32200005 DOI: 10.1016/j.jtos.2020.03.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/21/2020] [Accepted: 03/11/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera® device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up ≥ 3 months after discharge were included. RESULTS Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was ≥20/40 in 87% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78% of eyes (43/55) and 58% of eyes (32/55) respectively. CONCLUSIONS Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM.
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Affiliation(s)
- Swapna S Shanbhag
- Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA, USA; The Cornea Institute, L.V. Prasad Eye Institute, Hyderabad, India
| | - Leangelo Hall
- Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA, USA
| | - Hajirah N Saeed
- Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA, USA.
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Seminario-Vidal L, Kroshinsky D, Malachowski SJ, Sun J, Markova A, Beachkofsky TM, Kaffenberger BH, Ergen EN, Mauskar M, Bridges A, Calhoun C, Cardones AR, Chen ST, Chodosh J, Cotliar J, Davis MDP, DeNiro KL, Dominguez AR, Eljure-Téllez J, Femia A, Fox LP, Guda A, Mitchell C, Mostaghimi A, Ortega-Loayza AG, Owen C, Pasieka H, Rahnama-Moghadam S, Saeed HN, Saunderson RB, Shanbhag S, Sharon VR, Strowd L, Venkatesh S, Wanat KA, Wetter DA, Worswick S, Micheletti RG. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol 2020; 82:1553-1567. [PMID: 32151629 DOI: 10.1016/j.jaad.2020.02.066] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/04/2020] [Accepted: 02/26/2020] [Indexed: 12/14/2022]
Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.
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Affiliation(s)
- Lucia Seminario-Vidal
- Department of Dermatology, University of South Florida, Morsani College of Medicine, Tampa, Florida; Cutaneous Oncology Program, H. Lee Moffitt Cancer Center, Tampa, Florida.
| | - Daniela Kroshinsky
- Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Stephen J Malachowski
- Department of Internal Medicine, Medical College of Wisconsin Affiliated Hospitals, St. Joseph's Hospital, Milwaukee, Wisconsin
| | - James Sun
- Cutaneous Oncology Program, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Alina Markova
- Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | | | - Elizabeth N Ergen
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Melissa Mauskar
- Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Alina Bridges
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | - Cody Calhoun
- Department of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Adela R Cardones
- Department of Dermatology, Duke University, Durham, North Carolina
| | - Steven T Chen
- Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - James Chodosh
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
| | - Jonathan Cotliar
- Division of Dermatology, Harbor-University of California, Los Angeles Medical Center, Los Angeles, California
| | - Mark D P Davis
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | | | - Arturo R Dominguez
- Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Juliana Eljure-Téllez
- Department of Dermatology, "Dr. Manuel Gea González" General Hospital, Mexico City, Mexico
| | - Alisa Femia
- Ronald O. Perelman Department of Dermatology, New York University Langone Health, New York, New York
| | - Lindy P Fox
- Department of Dermatology, University of California, San Francisco, California
| | - Anisha Guda
- University of Texas Health San Antonio Long School of Medicine, San Antonio, Texas
| | - Caroline Mitchell
- Vincent Center for Reproductive Biology, Department of Obstetrics, Gynecology & Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts
| | - Arash Mostaghimi
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alex G Ortega-Loayza
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon
| | - Cindy Owen
- Division of Dermatology, Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Helena Pasieka
- Department of Dermatology, MedStar Washington Hospital Center, Washington, DC
| | | | - Hajirah N Saeed
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
| | - Rebecca B Saunderson
- Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Swapna Shanbhag
- Tej Kohli Cornea Institute, L.V. Prasad Eye Institute, Hyderabad, India
| | - Victoria R Sharon
- Department of Dermatology, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York
| | - Lindsay Strowd
- Department of Dermatology, Wake Forest University School of Medicine, Wake Forest, North Carolina
| | - Samantha Venkatesh
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Karolyn A Wanat
- Department of Dermatology, University of Southern California, Los Angeles, California
| | - David A Wetter
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | - Scott Worswick
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Robert G Micheletti
- Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania
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Klama-Baryła A, Rojczyk E, Kitala D, Łabuś W, Smętek W, Wilemska-Kucharzewska K, Kucharzewski M. Preparation of placental tissue transplants and their application in skin wound healing and chosen skin bullous diseases - Stevens-Johnson syndrome and toxic epidermal necrolysis treatment. Int Wound J 2020; 17:491-507. [PMID: 31943788 DOI: 10.1111/iwj.13305] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022] Open
Abstract
Unique properties of amniotic membrane make it a promising source for tissue engineering and a clinically useful alternative for patients suffering from chronic wounds including, for example, ulcers, burns, ocular surface damages and wounds occurring in the course of bullous diseases like stevens-johnson syndrome and toxic epidermal necrolysis. Its use has many advantages over standard wound care, as it contains pluripotent cells, nutrients, anti-fibrotic and anti-inflammatory cytokines, growth factors and extracellular matrix (ECM) proteins. Placental tissues can be prepared as a medical component, an advanced therapy medicinal product or a tissue graft. In addition to basic preparation procedures such as washing, rinsing, cutting, drying and sterilisation, there are many optional steps such as perforation, crosslinking and decellularisation. Finally, transplants should be properly stored-in cryopreserved or dehydrated form. In recent years, many studies including basic science and clinical trials have proven the potential to expand the use of amniotic membrane and amnion-derived cells to the fields of orthopaedics, dentistry, surgery, urology, vascular tissue engineering and even oncology. In this review, we discuss the role of placental tissues in skin wound healing and in the treatment of various diseases, with particular emphasis on bullous diseases. We also describe some patented procedures for placental tissue grafts preparation.
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Affiliation(s)
- Agnieszka Klama-Baryła
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Ewa Rojczyk
- Department of Descriptive and Topographic Anatomy, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Zabrze, Poland
| | - Diana Kitala
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Wojciech Łabuś
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Wojciech Smętek
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | | | - Marek Kucharzewski
- Department of Descriptive and Topographic Anatomy, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Zabrze, Poland
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Shanbhag SS, Rashad R, Chodosh J, Saeed HN. Long-Term Effect of a Treatment Protocol for Acute Ocular Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. Am J Ophthalmol 2019; 208:331-341. [PMID: 31326519 PMCID: PMC7935472 DOI: 10.1016/j.ajo.2019.07.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/16/2019] [Accepted: 07/12/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE To describe the long-term effect of a treatment protocol for ocular involvement in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), including focused ocular examination and pathology-appropriate use of lubrication, topical corticosteroids, topical antibiotics, and amniotic membrane transplantation (AMT). DESIGN Retrospective, comparative case series. METHODS A total of 48 patients (96 eyes) were included in this study. Nine of 48 patients (18 eyes) had acute SJS/TEN from 2000 to 2007 and did not receive protocol care (Group I). Thirty-nine of 48 patients (78 eyes) had acute SJS/TEN from 2008 to 2017 and received protocol care (Group II). The main outcome measures were best-corrected visual acuity (BCVA) at final follow-up visit and incidence of complications in the chronic phase. RESULTS No eyes in Group I received AMT for SJS/TEN, compared to 87% of qualifying eyes in Group II (P < .0001) There was a significant difference in the proportion of eyes with BCVA ≥20/40 at last follow-up between Group I and Group II (33% vs 92%, P < .001). The proportion of eyes with vision-threatening complications in the chronic phase was significantly higher in Group I versus Group II (67% vs 17%, P = .002), with most complications occurring in the first 2 years after disease onset in both groups. CONCLUSIONS A specific protocol for acute ocular care in SJS/TEN, including aggressive use of AMT, was highly successful in reducing corneal blindness and severe vision-threatening complications of the disorder.
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Affiliation(s)
- Swapna S Shanbhag
- Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA; Tej Kohli Cornea Institute, L.V. Prasad Eye Institute, Hyderabad, India
| | - Ramy Rashad
- Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA; Tufts University School of Medicine, Boston, Massachusetts, USA
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA
| | - Hajirah N Saeed
- Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
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Shanbhag SS, Chodosh J, Saeed HN. Sutureless amniotic membrane transplantation with cyanoacrylate glue for acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2019; 17:560-564. [PMID: 30872140 DOI: 10.1016/j.jtos.2019.03.001] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/05/2019] [Accepted: 03/05/2019] [Indexed: 12/01/2022]
Abstract
Amniotic membrane (AM) transplantation, when performed in the acute phase in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) for patients with ocular complications, is known to reduce the morbidity of ocular complications in the chronic phase. In conditions such as SJS/TEN, AM needs to be secured to the ocular surface as well as the eyelids. Previously, techniques of securing a large sheet of AM with fibrin glue to the ocular surface and with sutures and bolsters to the eyelids have been described in the acute phase of SJS/TEN. These techniques often necessitate the use of an operating room in acutely ill patients. We describe a bedside technique that uses cyanoacrylate glue to secure the AM to the eyelids, as well as long-term outcomes in 4 patients with acute SJS/TEN. The combination of a custom symblepharon ring to secure AM over the entire ocular surface and cyanoacrylate glue to secure AM to the eyelid margins is quick, painless, does not require local or general anesthesia, and might prove useful in other conditions previously shown to benefit from AMT, such as ocular chemical injuries.
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Affiliation(s)
- Swapna S Shanbhag
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
| | - James Chodosh
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
| | - Hajirah N Saeed
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
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Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, Pellegrini G, Shimmura S, Kruse FE. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea 2019; 38:364-375. [PMID: 30614902 PMCID: PMC6363877 DOI: 10.1097/ico.0000000000001820] [Citation(s) in RCA: 215] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis, and staging of LSCD. METHODS A Limbal Stem Cell Working Group was first established by The Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all participants after a comprehensive literature search, and final agreement was reached on the definition, classification, diagnosis, and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group. RESULTS A consensus was reached on the definition, classification, diagnosis, and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established. CONCLUSIONS This global consensus provides a comprehensive framework for the definition, classification, diagnosis, and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD, which will facilitate a better understanding of the condition and help with clinical management, research, and clinical trials in this area.
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Affiliation(s)
- Sophie X. Deng
- Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles
| | - Vincent Borderie
- Quinze-Vingts National Eye Hospital, Faculté de Médecine Sorbonne Université, Paris, France
| | - Clara C. Chan
- University of Toronto Department of Ophthalmology & Vision Sciences Toronto, Ontario
| | - Reza Dana
- Massachusetts Eye and Ear Infirmary, Harvard Medical School
| | - Francisco C. Figueiredo
- Department of Ophthalmology, Royal Victoria Infirmary and Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK
| | - José A. P. Gomes
- Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina/Universidade Federal de São Paulo (EPM/UNIFESP), Brazil
| | - Graziella Pellegrini
- Centre for Regenerative Medicine, University of Modena and Reggio Emilia; Holostem Terapie Avanzate, Modena, Italy
| | - Shigeto Shimmura
- Department of Ophthalmology, Keio University School of Medicine, Japan
| | - Friedrich E. Kruse
- Department of Ophthalmology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
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Update on the Surgical Reconstruction of Ocular Surface in Eyes with Limbal Stem Cell Deficiency. CURRENT OPHTHALMOLOGY REPORTS 2018. [DOI: 10.1007/s40135-018-0187-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Efficacy of fixation of the amniotic membrane on a symblepharon ring with continuous suturing in acute ocular chemical burn patients. Int Ophthalmol 2018; 39:2103-2109. [DOI: 10.1007/s10792-018-1049-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 11/12/2018] [Indexed: 10/27/2022]
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Talebi R, Saki N, Raeisi Shahraki H, Owji SH. An Epidemiological Study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis during 2010-2015 at Shahid Faghihi Hospital, Shiraz, Iran. IRANIAN JOURNAL OF MEDICAL SCIENCES 2018; 43:421-425. [PMID: 30046212 PMCID: PMC6055217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two ends of the spectrum of severe immunobullous state characterized by keratinocyte apoptosis. The present study aimed to draw attention to various epidemiological features of SJS and TEN diseases such as causative drugs, underlying diseases, duration of hospitalization, and types of treatment. The records of all patients with the diagnosis of SJS, TEN, and SJS/TEN overlap during 2010-2015 were retrospectively reviewed. The records belonged to patients who were admitted to the Dermatology Tertiary Referral Center of Shahid Faghihi Hospital affiliated to the Shiraz University of Medical Sciences, Shiraz, Iran. From a total of 97 patients with such skin disorders, we identified SJS in 89 (91.8 %), TEN in 5 (5.1%), and SJS/TEN overlap in 3 (3.1%) patients. The most commonly consumed drug was Lamotrigine (21.6%) and the most common drug category was anticonvulsants (46.4%). In line with many studies, especially in Iran, Lamotrigine and anticonvulsant drugs were the most common causative drug and epilepsy was the most common underlying disease. Patients with SJS/TEN overlap or TEN were treated with combination therapy, whereas SJS patients received systemic corticosteroids.
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Affiliation(s)
- Roghayeh Talebi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Saki
- Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hadi Raeisi Shahraki
- Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Hossein Owji
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Chronic Ocular Sequelae of Stevens-Johnson Syndrome in Children: Long-term Impact of Appropriate Therapy on Natural History of Disease. Am J Ophthalmol 2018; 189:17-28. [PMID: 29421293 DOI: 10.1016/j.ajo.2018.01.028] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 01/20/2018] [Accepted: 01/22/2018] [Indexed: 11/24/2022]
Abstract
PURPOSE To describe the long-term ocular and visual morbidity in children with chronic sequelae of Stevens-Johnson syndrome (SJS) and visual outcomes of various management strategies. DESIGN Retrospective comparative case series. METHODS This study included 568 eyes of 284 children with SJS who presented between 1990 and 2015. Affected eyes received either conservative therapy (n = 440) or definitive management (n = 128), including lid margin mucous membrane grafting (MMG), prosthetic replacement of the ocular surface ecosystem (PROSE) contact lenses, allogeneic limbal transplantation, or keratoprosthesis using an algorithmic approach based on the severity of dryness and cause and extent of corneal damage. The primary outcome measure was best-corrected visual acuity (BCVA). RESULTS Two thirds of patients presented more than a year after acute SJS, 99% without prior amniotic membrane grafting, with low vision or blindness in 60% of eyes. Children 8 years or younger in age had significantly worse ocular and visual morbidity (P ≤ .037). At 5 years of follow-up, definitive therapy significantly altered the natural history of the disease by improving BCVA and preventing the development or progression of keratopathy, as compared to conservative therapy (P ≤ .002). In eyes with lid-related keratopathy, MMG was significantly more effective than PROSE, although both were significantly better than conservative therapy and the combination of MMG followed by PROSE provided the best results (P < .0001). CONCLUSION Children receiving suboptimal care during acute SJS presented later with severe ocular and visual morbidity. Timely therapy, particularly with PROSE and MMG in eyes with lid-related keratopathy, changed the natural course and helped in preserving and improving vision.
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Avinash A, Amberkar VM, Kunder SK, Madhyastha S, Meenakumari K. Carbamazepine-induced Life-threatening Stevens-Johnson Syndrome and Agranulocytosis: The Maiden Case. J Clin Diagn Res 2017; 10:FD01-FD03. [PMID: 28208879 DOI: 10.7860/jcdr/2016/23748.9065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 09/26/2016] [Indexed: 11/24/2022]
Abstract
Stevens-Johnson syndrome is one of the few dermatological emergencies in clinical practice. The syndrome is often secondary to the usage of drugs, of which allopurinol, penicillins, sulfa drugs, ibuprofen, sodium valproate, phenytoin, lamotrigine and carbamazepine are commonly implicated. Agranulocytosis is the existence of a clinically significant reduction in neutrophil count. This condition is a serious threat to the patient, as he/she is at a greater risk of contracting bacterial or fungal infections, which may prove to be fatal. The co-existence of Stevens-Johnson syndrome and agranulocytosis in the same patient further increases the risk of morbidity and mortality. To the best of our knowledge, there are no reports available in the existing literature, of cases that were reported with both these life-threatening conditions in a single patient, at the same point of time. This is a case narrative of a patient who presented with both Stevens-Johnson syndrome and agranulocytosis, following the administration of carbamazepine The patient's differential leucocyte count revealed a neutrophil proportion of 2.33%. A causality assessment done using Naranjo's algorithm showed that carbamazepine "definitely" caused Agranulocytosis and "probably" caused Stevens-Johnson syndrome.
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Affiliation(s)
- A Avinash
- Postgraduate, Department of Pharmacology, Kasturba Medical College, Manipal University , Manipal, Karnataka, India
| | - V Mohanbabu Amberkar
- Associate Professor, Department of Pharmacology, Kasturba Medical College, Manipal University , Manipal, Karnataka, India
| | - Sushil Kiran Kunder
- Postgraduate, Department of Pharmacology, Kasturba Medical College, Manipal University , Manipal, Karnataka, India
| | - Sharath Madhyastha
- Assistant Professor, Department of Medicine, Kasturba Medical College, Manipal University , Manipal, Karnataka, India
| | - K Meenakumari
- Associate Professor, Department of Pharmacology, Kasturba Medical College, Manipal University , Manipal, Karnataka, India
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