|
1
|
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; 14:1385-1409. [PMID: 40360962 PMCID: PMC12167220 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] [Download PDF] [Figures] [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.
Collapse
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
| |
Collapse
|
|
2
|
Parmar UPS, Surico PL, Scarabosio A, Barone V, Singh RB, D'Ancona F, Zeppieri M, Parodi PC, Mori T, Cutrupi F, Ma DHK, Di Zazzo A, Coassin M. Amniotic Membrane Transplantation for Wound Healing, Tissue Regeneration and Immune Modulation. Stem Cell Rev Rep 2025:10.1007/s12015-025-10892-x. [PMID: 40366553 DOI: 10.1007/s12015-025-10892-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2025] [Indexed: 05/15/2025]
Abstract
Amniotic membrane transplantation (AMT) has emerged as a versatile therapeutic modality with significant applications in wound healing, tissue regeneration, and ophthalmology. This review comprehensively evaluates AMT's efficacy in acute and chronic wound management, where it has been shown to alleviate pain, reduce infection risk, and facilitate epithelialization. In chronic wounds, AMT enhances healing through mechanisms such as re-epithelialization, angiogenesis, and immune modulation. Additionally, AMT exhibits promise in nerve regeneration, demonstrating potential in the repair of peripheral and central nervous system injuries by fostering neural recovery and minimizing scar formation. In ophthalmology, AMT is instrumental in corneal surface reconstruction, conjunctival repairs, and the management of dry eye syndrome and limbal stem cell deficiency. While the benefits of AMT are well-documented, this review also addresses significant challenges, including variability in success rates across different clinical conditions, ethical concerns regarding donor tissue usage, and regulatory hurdles impacting its broader clinical application. Furthermore, we integrate recent advances in the understanding of AMT's molecular mechanisms - such as its antioxidant effects via Nrf2/HO-1 pathway and immune modulation via P2X7 receptor pathways - and highlight innovative strategies including the incorporation of nanoceria nanoparticles, Vitamin D3 supplementation, and gene therapy approaches to enhance AMT outcomes. By exploring these dimensions, the review highlights not only the current state of AMT but also its potential future role in advancing regenerative medicine, including emerging applications in spinal cord repair, orthopaedics, and tissue engineering. This updated synthesis aims to inform clinicians and researchers about the multifaceted applications of AMT, promoting further investigation and optimization of this promising therapeutic approach.
Collapse
Affiliation(s)
| | - Pier Luigi Surico
- Department of Organs of Sense, University of Rome La Sapienza, Rome, 00185, Italy.
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan.
| | - Anna Scarabosio
- Department of Plastic Surgery, University Hospital of Udine, Udine, 33100, Italy
| | - Vincenzo Barone
- Department of Ophthalmology, Campus Bio-Medico University Hospital, Rome, 00128, Italy
| | - Rohan Bir Singh
- Discipline of Ophthalmology and Visual Science, Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, Australia
| | - Fabrizio D'Ancona
- Department of Ophthalmology, Royal Liverpool University Hospital, Liverpool, UK
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine, 33100, Italy
| | - Pier Camillo Parodi
- Department of Plastic Surgery, University Hospital of Udine, Udine, 33100, Italy
| | - Tommaso Mori
- Department of Ophthalmology, Campus Bio-Medico University Hospital, Rome, 00128, Italy
| | - Francesco Cutrupi
- Department of Ophthalmology, Campus Bio-Medico University Hospital, Rome, 00128, Italy
| | - David Hui-Kang Ma
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Ophthalmology, Xiamen Chang Gung Hospital, Xiamen, China
- Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Antonio Di Zazzo
- Department of Ophthalmology, Campus Bio-Medico University Hospital, Rome, 00128, Italy
| | - Marco Coassin
- Department of Ophthalmology, Campus Bio-Medico University Hospital, Rome, 00128, Italy
| |
Collapse
|
|
3
|
Tas MD, Gurdal M, Kocamanoglu M, Korkmaz I, Arici M, Yaman B, Palamar M, Yildirim N, Çalışır A, Gönen ES, Becerik IT, Barut Selver O. Topical application of amniotic membrane extract at a clinically correlated dose is effective in limiting complications in an experimental ocular alkaline burn model. Exp Eye Res 2025; 252:110259. [PMID: 39892153 DOI: 10.1016/j.exer.2025.110259] [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: 09/04/2024] [Revised: 01/22/2025] [Accepted: 01/28/2025] [Indexed: 02/03/2025]
Abstract
The purpose of this study is to investigate the clinical and histopathological effectiveness of topical amniotic membrane extract (AME) applied at a clinically relevant dose in an experimental corneal alkaline burn model and to compare the results with amniotic membrane transplantation (AMT) as one of the most frequently used biologically based treatment options. To create an alkaline burn model, NaOH-impregnated filter paper was applied to all rabbits for 30 s. Rabbits were divided into 3 groups: Group 1 (n = 6): AME eye drop; Group 2 (n = 6): AMT; Group 3 (n = 4): control group. AME eye drops were applied as 1 drop 4 times a day for 28 days. Clinical findings including corneal opacity, corneal vascularization, limbal stem cell deficiency (LSCD) was evaluated and graded in accordance with the updated literature. On day 28, corneas were histopathologically examined under the light microscope. Stromal inflammation, stromal fibrosis, intraepithelial edema, and corneal vascularization were scored in each group. When the groups were compared clinically, corneal opacity was significantly (p = 0.009) lower in the AME group. While lower LSCD grades were observed in the AME group, this difference was not significant (p > 0.05). Histopathologically; in the AME group, stromal inflammatory cell inflammation, corneal vascularization, intraepithelial edema, stromal fibrosis, and metaplastic epithelial layer thickness were significantly (p = 0.004; p = 0.022; p = 0.008; p = 0.002; p = 0.002, respectively) lower than the other groups.In this study, it was shown that AME eye drops were clinically and histopathologically more successful in providing corneal healing than the AMT and control groups in the ocular alkaline burn model. These findings are valuable as they show that AME eye drops may be an easy-to-apply biologically based treatment alternative to AMT in chemical burns.
Collapse
Affiliation(s)
- Muhammed Dara Tas
- Ege University, Faculty of Medicine, Department of Ophthalmology, Izmir, Turkey
| | - Mehmet Gurdal
- Ege University, Faculty of Medicine, Ocular Surface Research Laboratory, Izmir, Turkey; LimbuStem R&D Medical Products Ltd., Ege University Technopark, Izmir, Turkey
| | - Meltem Kocamanoglu
- Ege University, Faculty of Medicine, Ocular Surface Research Laboratory, Izmir, Turkey; Ege University, Faculty of Medicine, Department of Medical Biochemistry, Izmir, Turkey
| | - Ilayda Korkmaz
- Ege University, Faculty of Medicine, Department of Ophthalmology, Izmir, Turkey; Ege University, Faculty of Medicine, Ocular Surface Research Laboratory, Izmir, Turkey
| | - Mesut Arici
- Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Izmir, Turkey; Cord Blood Cell-Tissue Application and Research Center, Ege University, Izmir, Turkey
| | - Banu Yaman
- Ege University, Faculty of Medicine, Department of Medical Pathology, Izmir, Turkey
| | - Melis Palamar
- Ege University, Faculty of Medicine, Department of Ophthalmology, Izmir, Turkey
| | - Nuri Yildirim
- Ege University, Faculty of Medicine, Department of Gynecology and Obstetrics, Izmir, Turkey
| | - Ali Çalışır
- LimbuStem R&D Medical Products Ltd., Ege University Technopark, Izmir, Turkey
| | - Eda Seçil Gönen
- LimbuStem R&D Medical Products Ltd., Ege University Technopark, Izmir, Turkey
| | - Ilgin Timarci Becerik
- Izmir Katip Celebi University School of Medicine, Department of Public Health, Izmir, Turkey
| | - Ozlem Barut Selver
- Ege University, Faculty of Medicine, Department of Ophthalmology, Izmir, Turkey; Ege University, Faculty of Medicine, Ocular Surface Research Laboratory, Izmir, Turkey; LimbuStem R&D Medical Products Ltd., Ege University Technopark, Izmir, Turkey; Department of Stem Cell, Institute of Health Sciences, Ege University, Izmir, Turkey; Institute of Health Sciences, Department of Stem Cell, Ege University, Izmir, Turkey; Cord Blood Cell-Tissue Application and Research Center, Ege University, Izmir, Turkey.
| |
Collapse
|
|
4
|
Bachtalia K, Palioura S. Management of Diathermy-Induced Corneal Burn following Upper Eyelid Blepharoplasty with Multilayer Amniotic Membrane Transplantation: A Case Report and Review of the Literature. Case Rep Ophthalmol 2025; 16:133-142. [PMID: 39981542 PMCID: PMC11842102 DOI: 10.1159/000543760] [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: 12/02/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
Introduction Thermal injuries associated with cosmetic eyelid surgery can significantly impair corneal integrity, potentially leading to vision loss. Conventional management, including bandage contact lens use, topical steroids, lubrication, autologous serum tears, and vitamin C, plays a crucial role in preventing long-term complications. This case report explores the potential benefits of multilayer amniotic membrane transplantation (AMT) as an adjunct to standard therapy for treating diathermy-associated corneal burns. Review of the literature advocates the beneficial effects of supplementary AMT in managing thermal corneal trauma. Case Description A 75-year-old man presented with unilateral diathermy-associated corneal laceration superior to the visual axis following cosmetic blepharoplasty. Vision had deteriorated from his baseline 20/30 to 20/125 postoperatively. Intervention involved multilayer AMT alongside standard care, including topical steroids and antibiotics, oral doxycycline, and vitamin C. Postoperative course was monitored with anterior segment optical coherence tomography (AS-OCT) imaging. By 3 months, complete corneal healing and restoration of baseline visual acuity were achieved. Conclusion This is the first documented case of multilayer AMT as an effective supplement to conventional management of diathermy-associated corneal injury. While AMTs unique properties likely contributed to corneal healing and visual recovery, the results should be interpreted in the context of a multimodal therapeutic approach.
Collapse
Affiliation(s)
| | - Sotiria Palioura
- Department of Ophthalmology, University of Cyprus Medical School, Nicosia, Cyprus
| |
Collapse
|
|
5
|
Mazumdar S, Chauhan R, Chaudhary S. Autologous simple limbal stem cell transplantation with conjunctival autograft in chronic unilateral total LSCD with severe symblepharon due to severe alkali burn. BMJ Case Rep 2024; 17:e262267. [PMID: 39675809 PMCID: PMC11647074 DOI: 10.1136/bcr-2024-262267] [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: 07/16/2024] [Accepted: 11/21/2024] [Indexed: 12/17/2024] Open
Abstract
This report details the case of a middle-aged man with chronic unilateral total limbal stem cell deficiency with severe symblepharon in his left eye with upper lid mechanical ptosis, restricted ocular movements and visual acuity limited to counting fingers at 2 feet. 9 months prior to his first visit, he sustained an accidental unilateral alkali injury to the left eye. He underwent autologous simple limbal epithelial transplantation combined with conjunctival autograft in the left eye. Complete ocular surface epithelialisation was achieved within 24 days post surgery. After 24 months of follow-up, the patient exhibited a stable ocular surface, normal palpebral fissure and full range of eye movements, with a best-corrected visual acuity of 6/12p in the left eye.
Collapse
Affiliation(s)
- Shefali Mazumdar
- Department of Ophthalmology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
| | - Richa Chauhan
- Department of Ophthalmology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
| | - Shelly Chaudhary
- Department of Ophthalmology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
| |
Collapse
|
|
6
|
Bian Y, Jurkunas U. Ocular Chemical Injuries and Limbal Stem Cell Deficiency (LSCD): An Update on Management. Int Ophthalmol Clin 2024; 64:31-48. [PMID: 38525980 DOI: 10.1097/iio.0000000000000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
|
|
7
|
Chandran C, Santra M, Rubin E, Geary ML, Yam GHF. Regenerative Therapy for Corneal Scarring Disorders. Biomedicines 2024; 12:649. [PMID: 38540264 PMCID: PMC10967722 DOI: 10.3390/biomedicines12030649] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 03/08/2024] [Accepted: 03/12/2024] [Indexed: 05/09/2024] Open
Abstract
The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials. This review delves into the intricate composition of the cornea, the landscape of corneal regeneration, and the multifaceted repercussions of scar-related pathologies. It will elucidate the etiology and types of dysfunctions, assess current treatments and their limitations, and explore the potential of regenerative therapy that has emerged in both in vivo and clinical trials. This review will shed light on existing gaps in corneal disorder management and discuss the feasibility and challenges of advancing regenerative therapies for corneal stromal scarring.
Collapse
Affiliation(s)
- Christine Chandran
- Corneal Regeneration Laboratory, Department of Ophthalmology, Mercy Vision Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; (C.C.); (M.S.); (E.R.); (M.L.G.)
| | - Mithun Santra
- Corneal Regeneration Laboratory, Department of Ophthalmology, Mercy Vision Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; (C.C.); (M.S.); (E.R.); (M.L.G.)
| | - Elizabeth Rubin
- Corneal Regeneration Laboratory, Department of Ophthalmology, Mercy Vision Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; (C.C.); (M.S.); (E.R.); (M.L.G.)
| | - Moira L. Geary
- Corneal Regeneration Laboratory, Department of Ophthalmology, Mercy Vision Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; (C.C.); (M.S.); (E.R.); (M.L.G.)
| | - Gary Hin-Fai Yam
- Corneal Regeneration Laboratory, Department of Ophthalmology, Mercy Vision Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; (C.C.); (M.S.); (E.R.); (M.L.G.)
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| |
Collapse
|
|
8
|
Sanders FWB, Huang J, Alió Del Barrio JL, Hamada S, McAlinden C. Amniotic membrane transplantation: structural and biological properties, tissue preparation, application and clinical indications. Eye (Lond) 2024; 38:668-679. [PMID: 37875701 PMCID: PMC10920809 DOI: 10.1038/s41433-023-02777-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 07/20/2023] [Accepted: 09/25/2023] [Indexed: 10/26/2023] Open
Abstract
The amniotic membrane is a single epithelial layer of the placenta. It has anti-inflammatory, anti-scarring, anti-angiogenic and possibly bactericidal properties. The basement membrane of the amniotic membrane acts as a substrate to encourage healing and re-epithelialisation. It has been used in many ocular surface diseases including persistent epithelial defects (corneal or conjunctival), chemical or thermal burns, limbal stem cell deficiency, cicatrising conjunctivitis, ocular graft versus host disease, microbial keratitis, corneal perforation, bullous keratopathy, dry eye disease, corneal haze following refractive surgery and cross-linking, band keratopathy, ocular surface neoplasia, pterygium surgery, and ligneous conjunctivitis. This review provides an up-to-date overview of amniotic membrane transplantation including the structural and biological properties, preparation and application, clinical indications, and commercially available products.
Collapse
Affiliation(s)
- Francis W B Sanders
- Department of Ophthalmology, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK
| | - Jinhai Huang
- Eye and ENT Hospital, Fudan University, Shanghai, China
| | - Jorge L Alió Del Barrio
- Division of Ophthalmology, School of Medicine, Universidad Miguel Hernández, Alicante, Spain; and Cornea, Cataract and Refractive Surgery Department, VISSUM Corporation, Alicante, Spain
| | - Samer Hamada
- Corneo Plastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, UK
| | - Colm McAlinden
- Eye and ENT Hospital, Fudan University, Shanghai, China.
- Corneo Plastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, UK.
- School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, UK.
| |
Collapse
|
|
9
|
Lotfy NM, Al Rashidi S, Hagras SM. Clinical outcomes of vacuum-dehydrated amniotic membrane (Omnigen) mounted on contact lens (Omnilenz) in eyes with acute chemical eye injuries. Graefes Arch Clin Exp Ophthalmol 2023; 261:3541-3547. [PMID: 37358651 PMCID: PMC10667437 DOI: 10.1007/s00417-023-06151-9] [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: 03/10/2023] [Revised: 05/09/2023] [Accepted: 06/07/2023] [Indexed: 06/27/2023] Open
Abstract
BACKGROUND Omnigen is a vacuum-dehydrated amniotic membrane transplant. It can be delivered to the eye pre-mounted on a special bandage contact lens (Omnilenz) that enables its application without the need for sutures or glue; the aim of this study is to evaluate the short-term clinical outcomes of Omnilenz-Omnigen complex in eyes with acute chemical injury (CEI). METHODS A prospective interventional study included patients with different grades of acute CEI attending the casualty between July 2021 and November 2022. All patients received first aid measures followed by the application of Omnilenz-Omnigen within the first 2 days. Patients were followed up for at least 1 month. Primary outcomes include epithelial defect and limbal ischemia. Secondary outcomes include best-corrected visual acuity (BCVA) and tolerability. RESULTS The study included 23 eyes of 21 patients with acute CEI mostly due to alcohol (34.8%). After the 1st application, the size of the epithelial defect showed a statistically significant reduction (p = 0.016) with improvement in BCVA (p < 0.001). Restoration of the limbal vascularity was obtained in 56.5% of the eyes. Repeated application of Omnilenz was required in 5 eyes (21.7%). The size of the epithelial defect was reduced after the second application (p = 0.504) with improved BCVA (p = 0.185). After 1st month, complete epithelial healing was achieved in all the eyes. Mild limbal ischemia persists in 3 (13%) of the eyes. Final BCVA showed statistically significant improvement (p < 0.001). None of the patients develops any serious complications. CONCLUSION Omnilenz proved to be easy to apply and well tolerated by patients, with promising clinical outcomes.
Collapse
Affiliation(s)
- Nancy M Lotfy
- Department of Ophthalmology, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt.
| | | | | |
Collapse
|
|
10
|
Song L, Yang X, Cui H. Plasma fibrin membranes loaded with bone marrow mesenchymal stem cells and corneal epithelial cells promote corneal injury healing via attenuating inflammation and fibrosis after corneal burns. Biomater Sci 2023; 11:5970-5983. [PMID: 37486330 DOI: 10.1039/d3bm00713h] [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: 07/25/2023]
Abstract
The shortage of corneal donors has prompted the development of tissue-engineered corneal grafts as an alternative solution. Currently, amniotic membranes with good biocompatibility are widely used as scaffolds for loading stem cells in the treatment of corneal injury. However, this approach has its limitations. In this study, BMSCs were induced to differentiate into corneal epithelial cells via direct contact co-culture, and platelet-poor plasma was used to prepare fibrin gels, which were compressed to remove excess liquid and then lyophilized to obtain plasma fibrin membranes (PFMs). A tissue-engineered corneal implant with PFMs as a scaffold loaded with BMSCs and corneal epithelial cells was designed and obtained. Scanning electron microscopy showed that PFMs have a uniformly distributed microporous surface that facilitates cell attachment and nutrient transport. The rheological results showed that the freeze-dried and rehydrated PFMs were more rigid than fresh membranes, which makes it easier to use them for transplantation after cell loading. The experimental results of a rat alkali burn cornea injury model showed that PFMs effectively reduced the inflammatory reaction, inhibited fibrosis, and accelerated the healing of corneal wounds. It was also found that some of the BMSCs were successfully implanted into the corneal injury site in rats and differentiated into corneal epithelial cells. These results demonstrate the potential of tissue-engineered corneal implants using BMSCs and corneal epithelial cells and PFMs as scaffolds as a new treatment option for corneal injury.
Collapse
Affiliation(s)
- Liqun Song
- Key Laboratory of Chemical Biology, Ministry of Education, Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
| | - Xue Yang
- Key Laboratory of Chemical Biology, Ministry of Education, Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
| | - Huifei Cui
- Key Laboratory of Chemical Biology, Ministry of Education, Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
- National Glycoengineering Research Center, Cheeloo College of Medicine, Shandon University, Jinan, 250012, Shandong, China
- Shandong Provincial Key Laboratory of Carbohydrate Chemistry end Glycobiology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| |
Collapse
|
|
11
|
Wang L, Peng Y, Liu W, Ren L. Properties of Dual-Crosslinked Collagen-Based Membranes as Corneal Repair Material. J Funct Biomater 2023; 14:360. [PMID: 37504855 PMCID: PMC10381311 DOI: 10.3390/jfb14070360] [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: 05/16/2023] [Revised: 06/21/2023] [Accepted: 07/07/2023] [Indexed: 07/29/2023] Open
Abstract
Corneal disease has become the second leading cause of blindness in the world. Corneal transplantation is currently considered to be one of the common treatments for vision loss. This paper presents a novel approach utilizing dual-crosslinked membranes composed of polyrotaxane multiple aldehydes (PRAs), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS) in the development process. Collagen was crosslinked, respectively, by EDC/NHS and PRAs to form stable amide bonds and imine groups. Through the formation of a double interpenetrating network, dual-crosslinked (Col-EDC-PRA) membranes exhibited enhanced resistance to collagenase degradation and superior mechanical properties compared to membranes crosslinked with a single crosslinker. Furthermore, Col-EDC-PRA membranes display favorable light transmittance and water content characteristics. Cell experiments showed that Col-EDC-PRA membranes were noncytotoxic and were not significantly different from other membranes. In a rabbit keratoplasty model, corneal stromal repair occurred at 5 months, evidenced by the presence of stromal cells and neo-stroma, as depicted in hematoxylin-eosin-stained histologic sections and optical coherence tomography images of the anterior segment. Moreover, there was no inflammation and corneal neovascularization, as well as no corneal rejection reaction in the surgical area. Overall, the results demonstrated that the dual-crosslinked membranes served effectively for corneal tissue regeneration after corneal defect.
Collapse
Affiliation(s)
- Lulu Wang
- Henan Provincial People's Hospital, Henan Eye Hospital, Zhengzhou University People's Hospital, Zhengzhou 450003, China
| | - Yuehai Peng
- National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
- Guangzhou Proud Seeing Biotechnology Co., Ltd., Guangzhou 510623, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
| | - Wenfang Liu
- National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China
| | - Li Ren
- National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China
| |
Collapse
|
|
12
|
Lata S, Bari A, Agarwal T. Tectonic Deep Anterior Lamellar Keratoplasty in Severe Ocular Chuna Particle Injury in a Child. Cureus 2023; 15:e41712. [PMID: 37575863 PMCID: PMC10415958 DOI: 10.7759/cureus.41712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2023] [Indexed: 08/15/2023] Open
Abstract
A 10-year-old child presented to eye casualty with pain, watering and photophobia of the left eye for one month. Parents gave a history of chuna (lime) falling inside the eye one month back, following which the patient consulted at a primary health centre. However, there was no relief of symptoms and the patient was referred to a higher centre. On examination under anaesthesia, the eye was full of chuna particles. Removal of all visible chuna particles and the corneal chuna plaque was planned. Intra-operatively, the stromal melt was noted around the corneal chuna plaque extending up to Descemet's membrane. Microscope-integrated optical coherence tomography (Mi-OCT) guided removal of corneal chuna particles was done. A tectonic deep anterior lamellar keratoplasty (DALK) along with amniotic membrane graft (AMG) and symblepharon ring placement was done. Two weeks post-operatively, the patient was having a persistent epithelial defect. A repeat AMG with a symblepharon ring was done. On one month follow-up, the epithelial defect had healed. This case emphasises the fact that ocular chemical injuries are an emergency requiring urgent and apt management. In cases of severe ocular chuna injury with delayed presentation, removal of all particles, maintenance of globe integrity and ocular surface restoration is a challenging goal. Healing is slow and visual prognosis is generally guarded in such cases.
Collapse
Affiliation(s)
- Suman Lata
- Ophthalmology, All India Institute of Medical Sciences, New Delhi, IND
| | - Aafreen Bari
- Ophthalmology, All India Institute of Medical Sciences, New Delhi, IND
| | - Tushar Agarwal
- Ophthalmology, All India Institute of Medical Sciences, New Delhi, IND
| |
Collapse
|
|
13
|
Amniotic Membrane Biopolymer for Regenerative Medicine. Polymers (Basel) 2023; 15:polym15051213. [PMID: 36904453 PMCID: PMC10006864 DOI: 10.3390/polym15051213] [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: 01/14/2023] [Revised: 02/22/2023] [Accepted: 02/26/2023] [Indexed: 03/08/2023] Open
Abstract
Biopolymers based on the amniotic membrane compare favorably with synthetic materials in that, along with a specific 2D structure, they have biologically active properties. However, in recent years, there has been a tendency to perform decellularization of the biomaterial during the preparation of the scaffold. In this study, we studied the microstructure of 157 samples and identified individual biological components in the manufacture of a medical biopolymer from an amniotic membrane using various methods. Group 1 had 55 samples, and the amniotic membrane was impregnated with glycerol and dried over silica gel. Group 2 had 48 samples, and the decellularized amniotic membrane was impregnated with glycerol followed by lyophilization, Group 3 had 44 samples, and the decellularized amniotic membrane without pre-impregnation with glycerol was subjected to lyophilization. Decellularization was performed by treatment with a low-frequency ultrasound at a frequency of 24-40 kHz in an ultrasonic bath. A morphological study using a light microscope and a scanning electron microscope showed the preservation of the structure of the biomaterial and more complete decellularization in samples subjected to lyophilization without prior impregnation with glycerol. The study of the Raman spectroscopy lines of a biopolymer made from a lyophilized amniotic membrane without preliminary impregnation with glycerin showed significant differences in the intensity of the spectral lines of amides, glycogen, and proline. Additionally, in these samples, the spectral lines of Raman scattering the characteristic of glycerol were not visualized; therefore, only biological substances characteristic of the native amniotic membrane have been preserved.
Collapse
|
|
14
|
Borrelli M, Witt J, Roth M, Reichl S, Bradenbrink P, Schoppe M, Schrader S, Geerling G. Keratin films for ocular surface reconstruction: Wound healing in an in-vivo model. Exp Eye Res 2023; 227:109356. [PMID: 36563893 DOI: 10.1016/j.exer.2022.109356] [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: 09/12/2022] [Revised: 11/16/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022]
Abstract
The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane.
Collapse
Affiliation(s)
- M Borrelli
- Department of Ophthalmology, University of Duesseldorf, Germany.
| | - J Witt
- Department of Ophthalmology, University of Duesseldorf, Germany
| | - M Roth
- Department of Ophthalmology, University of Duesseldorf, Germany
| | - S Reichl
- Institute of Pharmaceutical Technology, Technical University of Braunschweig, Germany
| | - P Bradenbrink
- Department of Ophthalmology, University of Duesseldorf, Germany
| | - M Schoppe
- Department of Pathology, University of Duesseldorf, Germany
| | - S Schrader
- Department of Ophthalmology, Carl von Ossietzky University Oldenburg, Germany
| | - G Geerling
- Department of Ophthalmology, University of Duesseldorf, Germany
| |
Collapse
|
|
15
|
Sumioka T, Iwanishi H, Yasuda S, Ichikawa K, Miyazima M, Kokado M, Okada Y, Saika S. Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea. J Transl Med 2023; 103:100061. [PMID: 36801638 DOI: 10.1016/j.labinv.2022.100061] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/27/2022] [Accepted: 12/30/2022] [Indexed: 01/11/2023] Open
Abstract
Corneal injury-associated inflammation could induce inward-growing neovascularization from the periphery of the tissue. Such neovascularization could cause stromal opacification and curvature disturbance, and both potentially impair visual function. In this study, we determined the effects of the loss of transient receptor potential vanilloid 4 (TRPV4) expression on the development of neovascularization in the corneal stroma in mice by producing a cauterization injury in the central area of the cornea. New vessels were immunohistochemically labeled with anti-TRPV4 antibodies. TRPV4 gene knockout suppressed the growth of such CD31-labeled neovascularization in association with the suppression of infiltration of macrophages and tissue messenger RNA expression of the vascular endothelial cell growth factor A level. Treatment of cultured vascular endothelial cells with supplementation of HC-067047 (0.1 μM, 1 μM, or 10 μM), a TRPV4 antagonist, attenuated the formation of a tube-like structure with sulforaphane (15 μM, for positive control) that modeled the new vessel formation. Therefore, the TRPV4 signal is involved in injury-induced macrophagic inflammation and neovascularization activity by vascular endothelial cells in a mouse corneal stroma. TRPV4 could be a therapeutic target to prevent unfavorable postinjury neovascularization in the cornea.
Collapse
Affiliation(s)
- Takayoshi Sumioka
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan.
| | - Hiroki Iwanishi
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| | - Shingo Yasuda
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan; School of Optometry, Indiana University, Bloomington, Indiana
| | - Kana Ichikawa
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| | - Masayasu Miyazima
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| | - Masahide Kokado
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| | - Yuka Okada
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| | - Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan
| |
Collapse
|
|
16
|
Kaplan AT, Yalcin SO, Günaydın NT, Kaymak NZ, Gün RD. Ocular-periocular burns in a tertiary hospital: Epidemiologic characteristics. J Plast Reconstr Aesthet Surg 2023; 76:208-215. [PMID: 36527902 DOI: 10.1016/j.bjps.2022.10.049] [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: 05/14/2022] [Revised: 10/10/2022] [Accepted: 10/25/2022] [Indexed: 11/08/2022]
Abstract
PURPOSE Ocular burns are ophthalmic emergencies that can cause devastating injuries. This study aimed to analyze the epidemiology, complications, and management of ocular-periocular burns. METHODS A total of 193 patients with ocular-periocular burns were admitted to our tertiary hospital from January 2018 to December 2020. The demographic characteristics of the patients, injury variables, complications, and treatments were evaluated. RESULTS There were 142 male (73.6%) and 51 female (26.4%) patients with a mean age of 32.53±17.75 years. The average total body surface area was 12% (range, 1-80%). Injuries were most common at work (52.3%) and home (36.3%). Thermal burns were the most common injuries (74.6%), followed by chemical (14.5%) and electrical burns (10.9%). Alkaline agents (75.0%), mainly sodium hydroxide and lime, were common in chemical burns. Superficial lid burns were significantly higher in the thermal group (p < 0.001), and grade III-IV corneal burns were significantly higher in the chemical group (p < 0.001). Various complications were developed in 50 (13%) eyes. Medical treatment only was performed in 318 (82.4%) eyes, and additional surgical treatment was performed in 64 (17.6%) eyes; however, 54 (14.0%) underwent more than one surgery. The most common complications were corneal scars (7.3%), limbal deficiency (4.1%), and ectropion (3.9%). The most frequent procedures performed were amniotic membrane transplantation (AMT) (11.9%) and tarsorrhaphy (6.7%). CONCLUSION Chemical burns, limbal and conjunctival ischemia, and full-thickness eyelid defects had a poor prognosis. The degree of limbal deficiency and ınjury of intraocular structures were found to have a great influence on the outcome of their visual acuity.
Collapse
Affiliation(s)
- Aysin Tuba Kaplan
- Ophthalmology Department, SBU Kartal Dr. Lutfi Kırdar City Hospital, Kartal, Istanbul 34865, Turkey.
| | - Sibel Oskan Yalcin
- Ophthalmology Department, SBU Kartal Dr. Lutfi Kırdar City Hospital, Kartal, Istanbul 34865, Turkey
| | - Nesrin Tutas Günaydın
- Ophthalmology Department, SBU Kartal Dr. Lutfi Kırdar City Hospital, Kartal, Istanbul 34865, Turkey
| | - Nilüfer Zorlutuna Kaymak
- Ophthalmology Department, SBU Kartal Dr. Lutfi Kırdar City Hospital, Kartal, Istanbul 34865, Turkey
| | - Raziye Dönmez Gün
- Ophthalmology Department, SBU Kartal Dr. Lutfi Kırdar City Hospital, Kartal, Istanbul 34865, Turkey
| |
Collapse
|
|
17
|
Balla A, Tran B, Valtari A, Steven P, Scarpellini C, Augustyns K, Urtti A, Vellonen KS, Ruponen M. A Novel Ferroptosis Inhibitor UAMC-3203, a Potential Treatment for Corneal Epithelial Wound. Pharmaceutics 2022; 15:pharmaceutics15010118. [PMID: 36678747 PMCID: PMC9863691 DOI: 10.3390/pharmaceutics15010118] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/13/2022] [Accepted: 12/21/2022] [Indexed: 01/01/2023] Open
Abstract
Corneal wound, associated with pain, impaired vision, and even blindness, is the most common ocular injury. In this study, we investigated the effect of a novel ferroptosis inhibitor, UAMC-3203 (10 nM-50 µM), in corneal epithelial wound healing in vitro in human corneal epithelial (HCE) cells and ex vivo using alkali-induced corneal wounded mice eye model. We evaluated in vivo acute tolerability of the compound by visual inspection, optical coherence tomography (OCT), and stereomicroscope imaging in rats after its application (100 µM drug solution in phosphate buffer pH 7.4) twice a day for 5 days. In addition, we studied the partitioning of UAMC-3203 in corneal epithelium and corneal stroma using excised porcine cornea. Our study demonstrated that UAMC-3203 had a positive corneal epithelial wound healing effect at the optimal concentration of 10 nM (IC50 value for ferroptosis) in vitro and at 10 µM in the ex vivo study. UAMC-3203 solution (100 µM) was well tolerated after topical administration with no signs of toxicity and inflammation in rats. Ex-vivo distribution study revealed significantly higher concentration (~12-38-fold) and partition coefficient (Kp) (~52 times) in corneal epithelium than corneal stroma. The UAMC-3203 solution (100 µM) was stable for up to 30 days at 4 °C, 37 °C, and room temperature. Overall, UAMC-3203 provides a new prospect for safe and effective therapy for corneal wounds.
Collapse
Affiliation(s)
- Anusha Balla
- School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
- Correspondence:
| | - Bao Tran
- Division of Dry-Eye and Ocular GVHD, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 Cologne, Germany
| | - Annika Valtari
- School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
| | - Philipp Steven
- Division of Dry-Eye and Ocular GVHD, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 Cologne, Germany
| | - Camilla Scarpellini
- Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, B-2160 Antwerp, Belgium
| | - Koen Augustyns
- Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, B-2160 Antwerp, Belgium
| | - Arto Urtti
- School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
- Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
| | - Kati-Sisko Vellonen
- School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
| | - Marika Ruponen
- School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
| |
Collapse
|
|
18
|
Cognard S, Barnouin L, Bosc J, Gindraux F, Robin MC, Douet JY, Thuret G. New Devitalized Freeze-Dried Human Umbilical Cord Amniotic Membrane as an Innovative Treatment of Ocular Surface Defects: Preclinical Results. J Funct Biomater 2022; 13:jfb13030150. [PMID: 36135586 PMCID: PMC9502562 DOI: 10.3390/jfb13030150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/26/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022] Open
Abstract
A preclinical study was performed to investigate the efficacy and safety of a new viral inactivated, devitalized, freeze-dried and gamma-sterilized human umbilical cord amniotic membrane (lhUC-AM) for the treatment of deep scleral and corneal defects with or without perforation. Firstly, lhUC-AM was investigated on experimental deep sclerectomy in rabbit eyes (n = 12) and compared to autograft (n = 4) on cross section histology. Secondly, lhUC-AM was studied on a selected series of uncontrolled cases of corneal defects (n = 18) with or without perforation, in dogs and cats. lhUC-AM tolerance, reconstruction of the deep corneal lesion and recovery of the structural aspect of the tissue were followed post-surgery. In experimental deep sclerectomy, histology showed that the lhUC-AM was well tolerated and degraded completely in 45 days while allowing an overall quality and kinetic of scleral regeneration, similar to autograft. In the clinical situations, lhUC-AM was well tolerated, with ocular inflammatory signs quickly decreasing after surgery. Mean follow-up was 16.40 ± 11.43 months. In 15 out of 18 cases, lhUC-AM allowed ocular surface wound healing. The ocular surface was fully reconstructed three months after surgery. This study suggests a good safety and efficacy profile of lhUC-AM in the treatment of deep corneal or scleral defect in animals. This new tissue should now facilitate the treatment of severe ocular surface diseases in humans.
Collapse
Affiliation(s)
- Sophie Cognard
- Clinique Vétérinaire des Ducs de Bourgogne, 11 Ter Rue Paul Langevin, 21300 Chenove, France
| | - Laurence Barnouin
- Tissue Bank of France, 6 rue d’Italie, 69780 Mions, France
- Correspondence: ; Tel.: +33-4-72-68-69-09
| | - Justine Bosc
- Tissue Bank of France, 6 rue d’Italie, 69780 Mions, France
| | - Florelle Gindraux
- Service de Chirurgie Orthopédique, Traumatologique et Plastique, CHU Besançon, F-25000 Besançon, France
- Laboratoire de Nanomédecine, Imagerie, Thérapeutique EA 4662, Université Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Marie-Claire Robin
- Small Animal Clinic, Université de Toulouse, ENVT, 31300 Toulouse, France
| | - Jean-Yves Douet
- Small Animal Clinic, Université de Toulouse, ENVT, 31300 Toulouse, France
- IHAP, Université de Toulouse, INRAE, ENVT, 31300 Toulouse, France
| | - Gilles Thuret
- Biology, Engineering and IMAGING of Corneal Graft, BiiGC, Faculty of Medicine, Health Innovation Campus, 10 rue de la Marandière, 42270 Saint-Priest en Jarez, France
| |
Collapse
|
|
19
|
Abstract
BACKGROUND Ocular surface burns can be caused by chemicals (alkalis and acids) or direct heat. One effect of the burn is damage to the limbal epithelial stem cells of the ocular surface with delayed re-epithelialisation, stem cell failure, and conjunctivalisation of the cornea. Amniotic membrane transplantation (AMT) performed in the acute phase (day 0 to day 7) following an ocular surface burn is claimed to reduce pain and accelerate healing. The surgery involves securing a layer of amniotic membrane (AM) to the eyelid margins as a patch to cover the entire ocular surface. However, there is debate about the severity of an ocular burn that may benefit from AMT and uncertainty of whether AMT improves outcomes. OBJECTIVES To compare the effect of AMT with medical therapy in the first seven days after an ocular surface burn, compared to medical therapy alone. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 9); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 September 2021. SELECTION CRITERIA We included randomised trials that compared an AMT applied in the first seven days following an ocular surface burn in addition to medical therapy with medical therapy alone. The outcome measures were failure of re-epithelialisation by day 21 post injury, visual acuity at final follow-up, corneal neovascularisation, symblepharon, time to re-epithelialisation and adverse effects. DATA COLLECTION AND ANALYSIS Two review authors independently screened search results, assessed the included studies for risk of bias and extracted relevant data. We contacted trial investigators for missing information. We summarised data using risk ratios (RRs) and mean differences (MDs) as appropriate. MAIN RESULTS We analysed two RCTs, but excluded individual patients who had been treated outside the acute phase in one of the studies (data provided by study authors). In total, 36 moderate burns from one RCT and 92 severe burns from two RCTs were evaluated separately. For both categories, the certainty of the evidence was downgraded principally as a result of high risks of performance and detection biases, and because of imprecision indicated by very wide confidence intervals. In addition, follow-up was insufficiently frequent to calculate time-to-epithelialisation precisely. Moderate severity ocular burns (Roper-Hall classification II-III) The relative risk of AMT on failure of epithelialisation by day 21 was 0.18 (0.02 to 1.31), and LogMAR visual acuity was 0.32 lower (0.55 to 0.09 lower) in the treatment group (i.e. better), suggesting a possible benefit of AMT. The GRADE assessment for failure of epithelialisation by day 21 was downgraded to very low due to the risk of bias and imprecision (very wide confidence intervals including no effect). The GRADE assessment for visual acuity at final follow-up was downgraded to low due to the risk of bias and imprecision (optimal information size not met). The relative effects of AMT on corneal neovascularisation (RR 0.56; 0.21 to 1.48), symblepharon (RR 0.41; 0.02 to 9.48) and time-to-epithelialisation (13 days lower; 26.30 lower to 0.30 higher) suggest possible benefit of AMT, but the wide confidence intervals indicate that both harm and benefit are possible. GRADE assessments for these outcomes were once again downgraded to very low due to the risk of bias and imprecision. Since adverse effects are rare, the small sample would have fewer occurrences of rare but potentially important adverse effects. The GRADE assessment for adverse effects was therefore considered to be low. Severe ocular burns (Roper-Hall classification IV) The relative risk of AMT on failure of epithelialisation by day 21 was 1.03 (0.94 to 1.12), and LogMAR visual acuity was 0.01 higher (0.29 lower to 0.31 higher) in the treatment group (i.e, worse), indicating no benefit of AMT. GRADE assessments for failure of epithelialisation by day 21 and final outcomes were downgraded to low. The relative effects of AMT on corneal neovascularisation (RR 0.84; 0.66 to 1.06), symblepharon (RR 0.89; 0.56 to 1.42) and time-to-epithelialisation (1.66 days lower; 11.09 lower to 7.77 higher) may include both benefit and harm. GRADE assessments for corneal neovascularisation, symblepharon and time-to-epithelialisation were downgraded to low due to risk of bias and imprecision. For adverse effects, the GRADE assessment was downgraded to low, reflecting the small sample sizes in the RCTs. AUTHORS' CONCLUSIONS There is uncertain evidence to support the treatment of moderate acute ocular surface burns with AMT in addition to standard medical therapy as a means of preventing failure of epithelialisation by day 21, improving visual outcome and reducing corneal neovascularisation, symblepharon formation and time-to-epithelialisation. For severe burns, the available evidence does not indicate any significant benefit of treatment with AMT.
Collapse
Affiliation(s)
- Gerry Clare
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | | | - Stephen Tuft
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
| |
Collapse
|
|
20
|
Akgun Z, Palamar M, Egrilmez S, Yagci A, Selver OB. Clinical Characteristics and Severity Distribution of Tertiary Eye Center Attendance by Ocular Chemical Injury Patients. Eye Contact Lens 2022; 48:295-299. [PMID: 35580512 DOI: 10.1097/icl.0000000000000908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVES To report demographic characteristics, types and grades of injury, regional distribution of injury severity, clinical findings, and long-term results of acute ocular chemical burns. METHODS Medical records of patients with chemical burns between 2010 and 2020 who were admitted to Ege University less than 72 hr after the injury were reviewed. Age, gender, cause of the burn, injury severity, initial and final best-corrected visual acuity, surgical intervention, and complications were recorded. The injury severity was graded according to Dua classification. RESULTS A total of 104 patients (137 eyes) were included. The mean age was 42.69±17.39 (7-90) years with a male-to-female ratio of 86:18. The most common causes were home (32.6%) and industrial accidents (45.1%). The causative agent percentages for alkaline, acid, and neutral were 49.0%, 35.5%, and 5.7%, respectively. The percentages of eyes in each grade (1-6) were 16.0%, 16.0%, 15.3%, 16.7%, 17.5%, and 18.2%, respectively. Complications mostly occurred in eyes with grade 2 or higher injuries (83.7%). The relationship between injury grade and limbal stem-cell deficiency was statistically significant (P<0.001). Surgery was mostly needed in grade 4 or higher injuries (44 eyes). CONCLUSION The severity of the burn is one of the most important prognostic factors in chemical burns. It is important to determine the spreading of the regional injury severity beside the global one to predict complication risk of the injuries. In the present study, the injury distribution was homogeneous in all grades. Limbal stem-cell deficiency development took place mostly in grade 5 and 6 burns as expected.
Collapse
Affiliation(s)
- Zeynep Akgun
- Department of Ophthalmology, Ege University Hospital, Izmir, Turkey
| | | | | | | | | |
Collapse
|
|
21
|
Human Placental Mesenchymal Stem Cells for the Treatment of ARDS in Rat. Stem Cells Int 2022; 2022:8418509. [PMID: 35756754 PMCID: PMC9226970 DOI: 10.1155/2022/8418509] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 04/21/2022] [Accepted: 06/06/2022] [Indexed: 11/29/2022] Open
Abstract
The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. Unfortunately, until now, there are no effective treatments for ARDS caused by COVID-19. Many drugs are either ineffective or have a low effect. Currently, there have been reports of efficient use of mesenchymal stem cells (MSCs) for the treatment of ARDS caused by COVID-19. We investigated the influence of freeze-dried human placenta-derived mesenchymal stem cells (HPMSCs) in ARDS rat model. All animals have received intratracheal injection of 6 mg/kg of lipopolysaccharide (LPS). The rats were randomly divided into five groups: I: LPS, II: LPS+dexamethasone, III: LPS+HPMSCs, IV: HPMSC, and V: saline. ARDS observation time was short-term and amounted to 168 hours. The study has shown that HPMSCs are able to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space. Studies have also shown that the administration of HPMSCs in animals with ARDS model significantly reduced the levels of key cytokines such as IL-1β, IL-6, and TNF-α. Freeze-dried placental stem cell is a very promising biomaterial for the treatment of ARDS. The human placenta can be easily obtained because it is considered as a medical waste. At the same time, a huge number of MSCs can be obtained from the placental tissue, and there is no ethical controversy around their use. The freeze-dried MSCs from human placental tissue can be stored sterile at room temperature for a long time before use.
Collapse
|
|
22
|
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
|
|
23
|
Choi CM, Jeon HS. Clinical Outcomes of In-office Sutureless Amniotic Membrane Transplantation in Persistent Epithelial Defect. KOREAN JOURNAL OF OPHTHALMOLOGY 2021; 36:87-96. [PMID: 34823345 DOI: 10.3341/kjo.2021.0095] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 11/14/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose To investigate the efficacy of outpatient clinic-based sutureless amniotic membrane transplantation (AMT) along with therapeutic contact lens (T-lens) application in eyes with persistent epithelial defects (PED). Methods Nine eyes of nine patients (mean age: 71.7 ± 5.2 years) diagnosed with PED and treated with in-office sutureless AMT combined with T-lens application were retrospectively reviewed. Demographics, systemic diseases, PED etiology, corneal epithelial defect (ED) size, visual acuity, corneal scraping culture results, and clinical course were evaluated. Results Among nine eyes with PED, three had neurotrophic keratopathy, four had infectious keratitis (three with fungal keratitis, one with bacterial keratitis), one had limbal deficiency, and one had marginal keratitis. The mean ED size (calculated as an average of the horizontal and vertical diameters) was 3.13 ± 1.42 mm, and the mean duration from AMT to epithelial healing was 30.1 ± 10.5 days (range: 14-51 days) in successful trials. The success rates were 77.8% (7/9) per patient and 66.7% (8/12) per trial. The causes of failure in two patients were AMT displacement and uncontrolled infection. Conclusions Our results demonstrate that in-office sutureless AMT combined with T-lens application can be used in patients with PED who are refractory to medications. It will be especially helpful for elderly patients because of its easy-to-use method. To achieve successful outcomes with AMT, an appropriate periocular environment as well as infection control need to be considered.
Collapse
Affiliation(s)
- Choong Man Choi
- Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Hyun Sun Jeon
- Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul, Republic of Korea.,Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
24
|
Wang T, Shan F, Zhou Q, Shi W, Xie L. Allogeneic Cultivated Limbal Epithelial Sheet Transplantation in Reconstruction of Conjunctival Sac After Chemical and Thermal Burns. Front Med (Lausanne) 2021; 8:697264. [PMID: 34552942 PMCID: PMC8451903 DOI: 10.3389/fmed.2021.697264] [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: 04/19/2021] [Accepted: 08/16/2021] [Indexed: 11/13/2022] Open
Abstract
The study aims to evaluate the effect of allogeneic cultivated limbal epithelial cell sheet transplantation (CLET) in reconstructing conjunctival sac for severe symblepharon after chemical and thermal burns. A retrospective, non-comparative case series. Thirty-six eyes (36 patients) underwent CLET for severe symblepharon and conjunctival sac stenosis or atresia. Symblepharon was separated, and pseudopterygium was preserved to replace the palpebral conjunctiva. Allogeneic cultivated limbal epithelial cell sheet using human amniotic membrane as a carrier was transplanted into the recipient's eye to reconstruct the conjunctival sac. The effect of conjunctival sac reconstruction, eye and eyelid movement, ocular surface restitution, and symblepharon recurrence were analyzed after surgery. Symblepharon was completely relieved in 30 of the 36 eyes (83.3%) by a single surgical procedure, with fornix reconstruction, as well as free movement of eye globe and eyelids. Strip-like symblepharon remained in 6 eyes (16.7%) and was completely relieved after the second CLET. Twenty patients without visual function received prostheses 3 months after surgery and the other sixteen patients underwent different corneal transplantation for visual acuity improvement. During the follow-up period, no one had symblepharon recurrence. The transplantation of cultivated allogeneic limbal epithelial sheets offers an effective and safe alternative in the treatment of symblepharon and reconstruction of conjunctival sac in eyes with severe ocular burns, which lays the foundation for subsequent treatments.
Collapse
Affiliation(s)
- Ting Wang
- Department of Ophthalmology, Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Fengmei Shan
- Department of Ophthalmology, Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Qingjun Zhou
- Department of Ophthalmology, Qingdao Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Weiyun Shi
- Department of Ophthalmology, Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Lixin Xie
- Department of Ophthalmology, Qingdao Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| |
Collapse
|
|
25
|
Liang L, Luo X, Zhang J, Su W, Zhu W, Xie Y, Zhang N, Peng Y, Chen X, Xiang AP, Liu Y, Liang D. Safety and feasibility of subconjunctival injection of mesenchymal stem cells for acute severe ocular burns: A single-arm study. Ocul Surf 2021; 22:103-109. [PMID: 34333155 DOI: 10.1016/j.jtos.2021.07.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 06/06/2021] [Accepted: 07/28/2021] [Indexed: 01/27/2023]
Abstract
PURPOSE To investigate the safety and feasibility of topical injection of bone marrow derived mesenchymal stem cells (BM-MSCs) in acute severe ocular burns. METHODS In this open-label，single-arm study, subconjunctival injection of allogenic BM-MSCs combined with standard treatment was given to 16 patients with acute severe ocular burns (Dua's grade IV to VI) within 2 weeks after injury. The primary outcome was efficacy rate which referred to the proportion of complete corneal epithelialization patients without perforation. The secondary outcome was safety, visual acuity, the number of symblephara, and elevated intraocular pressure. RESULTS One patient was lost to follow-up. During the follow-up period, no corneal perforation was developed. Complete corneal epithelialization was noted 8 (ranged 4-10 weeks) weeks after treatment in 13 eyes (81.3%). The efficacy rate was 87.5% (95% confidence interval, CI: 61.7-98.4). Hypopyon was detected and later well controlled in 1 eye. Partial or total limbal stem cell deficiency (LSCD) was noted in all eyes. Improvement of visual acuity was achieved in 5 out of 16 eyes (31.3%). Seven eyes' visual acuity was reached 0.1. Symblepharon with varied severity was noted in 5 eyes. Two eyes had elevated intraocular pressure. CONCLUSIONS This study confirms the safety of subconjunctival injection of BM-MSCs as an innovative and convenient procedure in ocular burns. The overall result is promising considering the absence of perforation, the low severity of symblepharon and visual acuity improvement.
Collapse
Affiliation(s)
- Lingyi Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Xiaohui Luo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Jian Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Wenru Su
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Wenjie Zhu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Yanyan Xie
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Nuan Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China
| | - Yanwen Peng
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Xiaoyong Chen
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Andy Peng Xiang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Yizhi Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China.
| | - Dan Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Center, Sun Yat-sen University, 54S Xianlie Road, Guangzhou, 510060, China.
| |
Collapse
|
|
26
|
Sumioka T, Iwanishi H, Okada Y, Miyajima M, Ichikawa K, Reinach PS, Matsumoto KI, Saika S. Impairment of corneal epithelial wound healing is association with increased neutrophil infiltration and reactive oxygen species activation in tenascin X-deficient mice. J Transl Med 2021; 101:690-700. [PMID: 33782532 PMCID: PMC8137452 DOI: 10.1038/s41374-021-00576-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 01/28/2021] [Accepted: 02/01/2021] [Indexed: 01/14/2023] Open
Abstract
The purpose of the study was to uncover the role of tenascin X in modulation of healing in mouse corneas subjected to epithelium debridement. Healing in corneas with an epithelial defect was evaluated at the levels of gene and protein expression. Wound healing-related mediators and inflammatory cell infiltration were detected by histology, immunohistochemistry and real-time RT-PCR. Tenascin X protein was upregulated in the wounded wild-type (WT) corneal epithelium. The lack of tenascin X impaired closure of an epithelial defect and accelerated infiltration of neutrophils into the wound periphery as compared to the response in WT tissue. Expression of wound healing-related proinflammatory and reparative components, i.e., interleukin-6, transforming growth factor β, matrix metalloproteinases, were unaffected by the loss of tenascin X expression. Marked accumulation of malondialdehyde (a lipid peroxidation-derived product) was observed in KO healing epithelia as compared with its WT counterpart. Neutropenia induced by systemic administration of a specific antibody rescued the impairment of epithelial healing in KO corneas, with reduction of malondialdehyde levels in the epithelial cells. Finally, we showed that a chemical scavenging reactive oxygen species reversed the impairment of attenuation of epithelial repair with a reduction of tissue levels of malondialdehyde. In conclusion, loss of tenascin X prolonged corneal epithelial wound healing and increased neutrophilic inflammatory response to debridement in mice. Tenascin X contributes to the control of neutrophil infiltration needed to support the regenerative response to injury and prevent the oxidative stress mediators from rising to cytotoxic levels.
Collapse
Affiliation(s)
- Takayoshi Sumioka
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
| | - Hiroki Iwanishi
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Yuka Okada
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Masayasu Miyajima
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Kana Ichikawa
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Peter S Reinach
- Department of Ophthalmology, Wenzhou Medical University, Wenzhou, P. R. China
| | - Ken-Ichi Matsumoto
- Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Organization for Research and Academic Information, Shimane University, Izumo, Enya-cho, Japan
| | - Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| |
Collapse
|
|
27
|
Parmar DP, Bhole PK, Patel PN, Jadeja JN. Amniotic membrane transplant in acute ocular surface burns in Western India: A tertiary eye care center study. Indian J Ophthalmol 2021; 69:58-64. [PMID: 33323574 PMCID: PMC7926170 DOI: 10.4103/ijo.ijo_2252_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Purpose To evaluate the outcomes of early amniotic membrane transplant (AMT) in acute ocular surface burns using Dua's classification. Methods In this retrospective analysis conducted at a tertiary eye care center in Western India. We included 27 eyes of 24 patients from May 2014 to May 2019 who underwent AMT within 2 weeks post insult along with medical treatment for acute ocular surface burns using Dua's classification for grading on presentation. Post-operative assessment for ocular surface epithelization, corneal vascularization, symblepharon formation, and visual outcome at the time of complete epithelization was done. Results Eight, seven, three, and nine eyes with grade III, IV, V, and VI, respectively, were included in the study. The mean duration of the presentation was 5.5 ± 3.6 days, with the mean follow-up of 4.83 ± 2.2 months. Alkali burn (62.96%, 17/27 eyes) was the commonest. The mean epithelization time was 5.80 ± 2.92 weeks. Corneal vascularization for >6 clock hours was seen in 52.38% (11/21 eyes with vascularization). Symblepharon was seen in 55.55% (15/27 eyes). Vision improvement and corneal vascularization to a lesser extent (<6 clock hours) was observed in Group A (grades III and IV) as compared to group B (grades V and VI) and found to be significant (P-value = 0.031, P value = 0.007, respectively). Conclusion Amniotic membrane grafting is a useful aid in moderate grades of acute ocular surface burns with an important adjunct role in severe cases.
Collapse
Affiliation(s)
- Dipali P Parmar
- Cornea Department, M and J Institute of Ophthalmology (Government Eye Hospital), B.J. Medical College, Ahmedabad, Gujarat, India
| | - Pradnya K Bhole
- Cornea Department, M and J Institute of Ophthalmology (Government Eye Hospital), B.J. Medical College, Ahmedabad, Gujarat, India
| | - Parita N Patel
- PSM Department, GMERS Medical College, Sola, Ahmedabad, Gujarat, India
| | - Jagruti N Jadeja
- Cornea Department, M and J Institute of Ophthalmology (Government Eye Hospital), B.J. Medical College, Ahmedabad, Gujarat, India
| |
Collapse
|
|
28
|
Han SB, Ibrahim FNIM, Liu YC, Mehta JS. Efficacy of Modified Amnion-Assisted Conjunctival Epithelial Redirection (ACER) for Partial Limbal Stem Cell Deficiency. ACTA ACUST UNITED AC 2021; 57:medicina57040369. [PMID: 33920151 PMCID: PMC8069281 DOI: 10.3390/medicina57040369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/03/2021] [Accepted: 04/07/2021] [Indexed: 01/06/2023]
Abstract
Background and objectives: the aim of this study was to analyze the efficacy of a modified “amnion-assisted conjunctival epithelial redirection (ACER)” technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.
Collapse
Affiliation(s)
- Sang Beom Han
- Department of Ophthalmology, Kangwon National University School of Medicine, Kangwon National University Hospital, Chuncheon 24289, Korea;
| | - Farah Nur Ilyana Mohd Ibrahim
- Singapore National Eye Centre, Singapore 168751, Singapore; (F.N.I.M.I.); (Y.-C.L.)
- Singapore Eye Research Institute, Singapore 168751, Singapore
- Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Yu-Chi Liu
- Singapore National Eye Centre, Singapore 168751, Singapore; (F.N.I.M.I.); (Y.-C.L.)
- Singapore Eye Research Institute, Singapore 168751, Singapore
- Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Jodhbir S. Mehta
- Singapore National Eye Centre, Singapore 168751, Singapore; (F.N.I.M.I.); (Y.-C.L.)
- Singapore Eye Research Institute, Singapore 168751, Singapore
- Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Correspondence: ; Tel.: +65-91825146; Fax: +65-08701316622
| |
Collapse
|
|
29
|
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: 18] [Impact Index Per Article: 4.5] [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.
Collapse
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
| |
Collapse
|
|
30
|
Corneal reconstruction in chemically damaged cornea using temperature responsive surface assisted mesenchymal stem cell transplantation in rabbits. Graefes Arch Clin Exp Ophthalmol 2021; 259:1859-1870. [PMID: 33754210 DOI: 10.1007/s00417-021-05132-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/11/2021] [Accepted: 02/16/2021] [Indexed: 10/21/2022] Open
Abstract
PURPOSE Transplantation of autologous stem cells over damaged cornea seems to be a promising approach for corneal reconstruction. Use of a biocompatible carrier is still a challenge in bedside translation of transplantation. We investigated corneal reconstruction and tissue remodelling by transplantation of mesenchymal stem cells (MSCs) using temperature responsive membranes in chemically damaged rabbit cornea model. METHODS MSCs were cultured from rabbit's bone marrow and transplanted over alkali injured cornea, using either temperature responsive membrane or fibrin glue method. Endogenous levels of MSCs were assessed to decide the optimal time point for transplanting cells. MSC transplanted corneas were harvested at different time points post-transplantation. Corneal repair markers were evaluated using histopathology, immunohistochemistry (IHC) and real time qPCR. The quality of cornea reconstructed was evaluated and compared using corneal opacity scoring and immunohistochemistry (IHC). RESULTS Use of temperature responsive surface as carrier resulted in uniform and homogenous delivery of MSCs sheet over the damaged corneal surface. Corneal transparency improved day 7 onwards post-MSC transplantation in rabbit chemically injured cornea. Complete re-epithelialization of injured cornea was observed 15 days after MSC transplantation. Restoration of vimentin, α-smooth muscle actin and collagen levels in MSC transplanted cornea was observed post-transplantation. Further, differentiation of MSCs into mature corneal epithelial cells was also observed upon transplantation. CONCLUSIONS The extent of corneal repair was apparently better using temperature responsive surfaces. The surface provides biocompatible niche for MSCs and can be a method of choice in clinics for cell transplantation over the damaged ocular surfaces.
Collapse
|
|
31
|
Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases. Sci Rep 2021; 11:2351. [PMID: 33504908 PMCID: PMC7840674 DOI: 10.1038/s41598-021-81983-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/11/2021] [Indexed: 02/06/2023] Open
Abstract
Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.
Collapse
|
|
32
|
Figueiredo FC, Glanville JM, Arber M, Carr E, Rydevik G, Hogg J, Okonkwo A, Figueiredo G, Lako M, Whiter F, Wilson K. A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes. Ocul Surf 2021; 20:48-61. [PMID: 33412337 DOI: 10.1016/j.jtos.2020.12.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 12/15/2020] [Accepted: 12/28/2020] [Indexed: 01/18/2023]
Abstract
PURPOSE This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown. METHODS A protocol was registered with PROSPERO (CRD42017081117). Searches were conducted in 14 databases and 6 conference websites. Two reviewers independently selected studies, conducted data extraction and assessed risk of bias. One reviewer extracted individual patient data (IPD); a second checked extracted data. Data were assessed to determine the feasibility of statistical analysis, with Bayesian synthesis used to estimate improvement achieved by different treatments. RESULTS Fifty-two studies were eligible for inclusion (1113 eyes); 41 studies (716 eyes) reported IPD. No evidence was identified on cost-effectiveness. This SR was unable to confirm that any of the types of ex vivo cultured stem cell transplants identified for LSCD treatment were statistically superior when assessed against the outcomes of interest. CONCLUSIONS We believe this SR is the first to include IPD analysis of LSCD data. There is no evidence for the superiority of any method of limbal stem cell transplant. Confirmation of the safety and efficacy of this treatment modality is challenging due to heterogeneity within and between the studies identified. Therefore, recommendations for future research are proposed.
Collapse
Affiliation(s)
- F C Figueiredo
- Department of Ophthalmology, Royal Victoria Infirmary and University of Newcastle, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK.
| | - J M Glanville
- York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK
| | - M Arber
- York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK
| | - E Carr
- York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK
| | - G Rydevik
- Quantics Biostatistics, West End House, 28 Drumsheugh Gardens, Edinburgh, EH3 7RN, UK
| | - J Hogg
- Department of Ophthalmology, Royal Victoria Infirmary and University of Newcastle, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK
| | - A Okonkwo
- Department of Ophthalmology, Royal Victoria Infirmary and University of Newcastle, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK
| | - G Figueiredo
- Department of Ophthalmology, Royal Victoria Infirmary and University of Newcastle, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK
| | - M Lako
- Biosciences Institute, Newcastle University, International Centre for Life, Newcastle, NE1 3BZ, UK
| | - F Whiter
- York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK
| | - K Wilson
- York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK
| |
Collapse
|
|
33
|
Zhong Z, Deng X, Wang P, Yu C, Kiratitanaporn W, Wu X, Schimelman J, Tang M, Balayan A, Yao E, Tian J, Chen L, Zhang K, Chen S. Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection. Biomaterials 2021; 267:120462. [PMID: 33129190 PMCID: PMC7719077 DOI: 10.1016/j.biomaterials.2020.120462] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 09/28/2020] [Accepted: 10/18/2020] [Indexed: 12/19/2022]
Abstract
Ocular surface diseases including conjunctival disorders are multifactorial progressive conditions that can severely affect vision and quality of life. In recent years, stem cell therapies based on conjunctival stem cells (CjSCs) have become a potential solution for treating ocular surface diseases. However, neither an efficient culture of CjSCs nor the development of a minimally invasive ocular surface CjSC transplantation therapy has been reported. Here, we developed a robust in vitro expansion method for primary rabbit-derived CjSCs and applied digital light processing (DLP)-based bioprinting to produce CjSC-loaded hydrogel micro-constructs for injectable delivery. Expansion medium containing small molecule cocktail generated fast dividing and highly homogenous CjSCs for more than 10 passages in feeder-free culture. Bioprinted hydrogel micro-constructs with tunable mechanical properties enabled the 3D culture of CjSCs while supporting viability, stem cell phenotype, and differentiation potency into conjunctival goblet cells. These hydrogel micro-constructs were well-suited for scalable dynamic suspension culture of CjSCs and were successfully delivered to the bulbar conjunctival epithelium via minimally invasive subconjunctival injection. This work integrates novel cell culture strategies with bioprinting to develop a clinically relevant injectable-delivery approach for CjSCs towards the stem cell therapies for the treatment of ocular surface diseases.
Collapse
Affiliation(s)
- Zheng Zhong
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Xiaoqian Deng
- Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA
| | - Pengrui Wang
- Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA
| | - Claire Yu
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Wisarut Kiratitanaporn
- Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Xiaokang Wu
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Jacob Schimelman
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Min Tang
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Alis Balayan
- School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
| | - Emmie Yao
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Jing Tian
- Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Luwen Chen
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Kang Zhang
- Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA.
| | - Shaochen Chen
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA; Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.
| |
Collapse
|
|
34
|
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.
Collapse
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
| |
Collapse
|
|
35
|
A Human Amniotic Membrane Plug to Promote Retinal Breaks Repair and Recurrent Macular Hole Closure. Retina 2020; 39 Suppl 1:S95-S103. [PMID: 30312261 DOI: 10.1097/iae.0000000000002320] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
36
|
Yin HY, Cheng AMS, Tighe S, Kurochkin P, Nord J, Dhanireddy S, Swan R, Alpert S. Self-retained cryopreserved amniotic membrane for treating severe corneal ulcers: a comparative, retrospective control study. Sci Rep 2020; 10:17008. [PMID: 33046729 PMCID: PMC7550608 DOI: 10.1038/s41598-020-73672-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 08/07/2020] [Indexed: 02/07/2023] Open
Abstract
To compare the effectiveness of self- retained cryopreserved AM as an adjuvant therapy for infectious corneal ulcers. Retrospective, case–control study of 24 eyes of 24 consecutive patients with central and paracentral corneal infectious ulcers and initial visual acuity worse than 20/200. Among them, 11 eyes of 11 patients received additional placement of self-retained cryopreserved AM. Epithelialization and Best Corrected Snellen Visual Acuity (BCSVA) were compared between the two groups. At baseline, both groups had comparable age, gender, visual acuity (VA), size and location of corneal ulcer. Patients receiving additional placement of cryopreserved AM had significantly faster epithelialization within 3.56 ± 1.78 weeks vs 5.87 ± 2.20 weeks (p = 0.01) and achieved complete epithelialization in significantly more patients (72.7% vs 23.1% p = 0.04) despite overall larger baseline defect size (32.7 ± 19.5 mm2 vs 21.5 ± 10.7 mm2, p = 0.11). Consequently, the AM group had clinically significant BCSVA (> 3 lines) (81.8% vs 38.4%, p = 0.047) and total VA improvement (log MAR 0.7 ± 0.6 vs 1.6 ± 0.9, p = 0.016) compared to the control group at the time of complete epithelialization. In-office sutureless AM may be an effective adjuvant therapy in treating sight-threatening infectious corneal ulcers by promoting faster corneal epithelialization and overall better recovery of the VA.
Collapse
Affiliation(s)
- Han Y Yin
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA. .,Wake Forest Baptist Eye Center, Winston-Salem, NC, USA.
| | - Anny M S Cheng
- Florida International University College of Medicine, 11200 SW, 8th St, Miami, FL, 33199, USA.,Department of Surgery, Miller School of Medicine, University of Medicine, Miami, FL, USA
| | - Sean Tighe
- Florida International University College of Medicine, 11200 SW, 8th St, Miami, FL, 33199, USA.,Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA.,TissueTech, 7300 corporate Center Drive, Suite 700, Miami, FL, 33126, USA
| | - Philip Kurochkin
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA
| | - Jamie Nord
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA
| | - Swetha Dhanireddy
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA
| | - Robert Swan
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA
| | - Samuel Alpert
- Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Suit L 550 Harrison St, Syracuse, NY, 13202, USA.
| |
Collapse
|
|
37
|
Zhao M, Zhang H, Zhen D, Huang M, Li W, Li Z, Liu Y, Xie Y, Zeng B, Wang Z, Huang B. Corneal Recovery Following Rabbit Peripheral Blood Mononuclear Cell-Amniotic Membrane Transplantation with Antivascular Endothelial Growth Factor in Limbal Stem Cell Deficiency Rabbits. Tissue Eng Part C Methods 2020; 26:541-552. [PMID: 33019886 DOI: 10.1089/ten.tec.2020.0209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Limbal stem cell deficiency (LSCD) is a refractory ocular surface disorder characterized by progressive corneal epithelial degeneration, conjunctivalization, and neovascularization, potentially leading to blindness. There are currently no effective therapeutic options for patients experiencing routine symptomatic treatment failure. Transplantation of amniotic membrane (AM) with adherent stem cells (but not bare AM transplantation alone) has shown promise in preclinical studies for ocular surface restoration. A major limitation, however, is finding a reliable stem cell source. Stem cells can be isolated from the peripheral blood mononuclear cell (PBMC) population, and these PBMC-derived stem cells have numerous advantages over allogeneic and other autologous stem cell types for therapeutic application, including relative ease of acquisition, nonimmunogenicity, and the absence of ethical issues associated with embryonic stem cells. Experiment: We examined the efficacy of autologous PBMC-AM sheet cultures combined with postoperative antiangiogenesis treatment for corneal restoration in LSCD model rabbits. Rabbit PBMCs (rPBMCs) were isolated, labeled with EdU for in vivo tracing, and then cultured on AMs in conditioned medium before transplantation. Rabbits were transplanted with bare AMs (group 1), rPBMC-AM sheets (group 2), or rPBMC-AM sheets plus postoperative treatment with the vascular endothelial growth factor antagonist bevacizumab (group 3). Corneal opacity and neovascularization were monitored by slit-lamp imaging for 8 weeks and corneas were examined histologically at 1 and 2 months. Results: Corneal opacity decreased in all three groups over 8 weeks, but was significantly lower in group 2 and even lower in group 3. Corneal neovascularization was significantly higher in group 1 throughout the observation period, and significantly lower in group 3 than group 1 and 2 by 8 weeks post-transplant. At 4 weeks, the corneal surface completed epithelialization (although thinner than normal) in group 3 but still patchy in groups 1 and 2. By 8 weeks, the epithelium in group 3 was complete and smooth, resembling a normal epithelium. Integrin β1 as a progenitor marker was also generally higher in groups 2 and 3. Conclusions: Autologous rPBMC-AM sheets with post-transplant topical bevacizumab can effectively facilitate corneal epithelium recovery in a LSCD model, suggesting clinical utility for LSCD-related ocular surface diseases. Impact statement Limbal stem cell deficiency (LSCD) increases corneal opacity and vascularization, resulting in severe visual impairment or even blindness. Traditional surgical limbal transplant is currently the main treatment option for LSCD, but carries the risks of rejection and immunosuppressant side effects. Autologous stem cell-based therapy is a promising alternative approach, but a reliable stem cell source is a major limitation. We report that transplantation of autologous rabbit peripheral blood mononuclear cell-amniotic membrane sheets plus antivascular endothelial growth factor restored avascular transparent cornea in a rabbit LSCD model. These results demonstrate a potentially effective approach for ocular surface reconstruction in bilateral LSCD.
Collapse
Affiliation(s)
- Minglei Zhao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Hening Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Dongqin Zhen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | | | - Weihua Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Zhiquan Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Ying Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Yaojue Xie
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Baozhu Zeng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Zhichong Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| | - Bing Huang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, GuangZhou, China
| |
Collapse
|
|
38
|
Soleimani M, Naderan M. Management Strategies of Ocular Chemical Burns: Current Perspectives. Clin Ophthalmol 2020; 14:2687-2699. [PMID: 32982161 PMCID: PMC7501954 DOI: 10.2147/opth.s235873] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/20/2020] [Indexed: 11/25/2022] Open
Abstract
Ocular chemical burns are absolute ophthalmic emergencies and require immediate management to minimize devastating sequelae. Management of alkali and acid burns is started at the scene of the accident by copious irrigation. Treatment is directed at improving epithelial integrity and stromal stability, reduction of undue inflammation, and prevention or timely management of complications. To ascertain the best possible outcome, numerous biological medications and surgical interventions have been merged into conventional therapeutic regimens. These include autologous and umbilical cord serum preparations, platelet-rich plasma, amniotic membrane transplantation, limbal stem-cell transplantation, and anti-angiogenic agents.
Collapse
Affiliation(s)
- Mohammad Soleimani
- Ocular Trauma and Emergency Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Morteza Naderan
- Ocular Trauma and Emergency Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
39
|
Abouhussein MA, Elbaha SM, Aboushousha M. Human Amniotic Membrane Plug for Macular Holes Coexisting with Rhegmatogenous Retinal Detachment. Clin Ophthalmol 2020; 14:2411-2416. [PMID: 32904754 PMCID: PMC7457634 DOI: 10.2147/opth.s272060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 08/04/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose To evaluate the efficacy of human amniotic membrane in promoting closure of macular holes coexisting with rhegmatogenous retinal detachment. Methods This is a retrospective case series of 14 eyes (14 patients) with macula off retinal detachment. These patients had a macular hole coexistent with peripheral retinal breaks. A human amniotic membrane plug was used to close the macular hole during vitrectomy without ILM peeling. Results The mean preoperative BCVA (logMAR value) was 1.87 ± 0.31. At the 6-month follow-up visit, the mean LogMAR best-corrected visual acuity was 0.67 ± 0.17. At the 6-month follow-up, all patients showed complete retinal reattachment with macular hole closure. Conclusion The use of human amniotic membrane is a valid option in surgery for macular holes coexisting with rhegmatogenous retinal detachment.
Collapse
|
|
40
|
Tseng SCG, Chen SY, Mead OG, Tighe S. Niche regulation of limbal epithelial stem cells: HC-HA/PTX3 as surrogate matrix niche. Exp Eye Res 2020; 199:108181. [PMID: 32795525 DOI: 10.1016/j.exer.2020.108181] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 06/15/2020] [Accepted: 07/31/2020] [Indexed: 12/13/2022]
Abstract
Homeostasis of the corneal epithelium is ultimately maintained by stem cells that reside in a specialized microenvironment within the corneal limbus termed palisades of Vogt. This limbal niche nourishes, protects, and regulates quiescence, self-renewal, and fate decision of limbal epithelial stem/progenitor cells (LEPCs) toward corneal epithelial differentiation. This review focuses on our current understanding of the mechanism by which limbal (stromal) niche cells (LNCs) regulate the aforementioned functions of LEPCs. Based on our discovery and characterization of a unique extracellular matrix termed HC-HA/PTX3 (Heavy chain (HC1)-hyaluronan (HA)/pentraxin 3 (PTX3) complex, "-" denotes covalent linkage; "/" denotes non-covalent binding) in the birth tissue, i.e., amniotic membrane and umbilical cord, we put forth a new paradigm that HC-HA/PTX3 serves as a surrogate matrix niche by maintaining the in vivo nuclear Pax6+ neural crest progenitor phenotype to support quiescence and self-renewal but prevent corneal fate decision of LEPCs. This new paradigm helps explain how limbal stem cell deficiency (LSCD) develops in aniridia due to Pax6-haplotype deficiency and further explains why transplantation of HC-HA/PTX3-containing amniotic membrane prevents LSCD in acute chemical burns and Stevens Johnson syndrome, augments the success of autologous LEPCs transplantation in patients suffering from partial or total LSCD, and assists ex vivo expansion (engineering) of a graft containing LEPCs. We thus envisage that this new paradigm based on regenerative matrix HC-HA/PTX3 as a surrogate niche can set a new standard for regenerative medicine in and beyond ophthalmology.
Collapse
Affiliation(s)
- Scheffer C G Tseng
- Research & Development Department, TissueTech, Inc., Miami, FL, 33126, USA; Ocular Surface Center and Ocular Surface Research & Education Foundation, Miami, FL, 33126, USA.
| | - Szu-Yu Chen
- Research & Development Department, TissueTech, Inc., Miami, FL, 33126, USA
| | - Olivia G Mead
- Research & Development Department, TissueTech, Inc., Miami, FL, 33126, USA
| | - Sean Tighe
- Research & Development Department, TissueTech, Inc., Miami, FL, 33126, USA; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; Department of Ophthalmology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
| |
Collapse
|
|
41
|
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.
Collapse
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
| |
Collapse
|
|
42
|
Chen LB, Zhang SY, Yan CX, Yao QK, Shao CY, Fu Y. Evaluation of chronic ocular sequelae in patients with symblepharon caused by ocular burns. Int J Ophthalmol 2020; 13:1066-1073. [PMID: 32685393 DOI: 10.18240/ijo.2020.07.08] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 03/15/2020] [Indexed: 12/16/2022] Open
Abstract
AIM To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system. METHODS This was a retrospective, single-center clinical study. Patients with symblepharon caused by ocular burns at least six months later were assessed. Chronic ocular sequelae were classified into 3 categories (eyelid, conjunctiva, and cornea) and 9 chronic ocular sequelae [friction factors, exposure factors, conjunctival hyperemia, length of symblepharon, scope of adhesion, lacrimal area adhesion, loss of the palisades of Vogt (POV), corneal neovascularization, and corneal opacification]. Each ocular sequela was graded from 0 to 3, depending on the increasing severity. The 9 ocular sequelae were evaluated to obtain the total severity score for each eye. The total severity score was defined as Grade I (1-9), Grade II (10-18), and Grade III (19-27). Moreover, the correlation between the severity of chronic ocular sequelae and visual acuity, surgical strategy, and the prognosis was analyzed, respectively. RESULTS Cases of 79 eyes with symblepharon caused by ocular burns were included in this study. Of these, 20 (25.32%) were defined as Grade I, 43 (54.43%) as Grade II, and 16 (20.25%) as Grade III. Eyes with a high total severity score had reduced visual acuity, required complicated surgery strategies, and poor prognosis (P<0.001). Multivariate regression analysis showed that the scope of adhesion, corneal opacification, and corneal neovascularization significantly affected visual acuity, surgical strategy, and prognosis (all P<0.001). CONCLUSION The evaluation of chronic ocular sequelae enabled the development of an objective grading system for patients with symblepharon caused by ocular burns. This grading system can be applied to guide the treatment and predict the prognosis.
Collapse
Affiliation(s)
- Liang-Bo Chen
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Si-Yi Zhang
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Chen-Xi Yan
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Qin-Ke Yao
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Chun-Yi Shao
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Yao Fu
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| |
Collapse
|
|
43
|
Peng WY, He LW, Zeng P, Chen DC, Zhou SY. Tenonplasty Combined With Amniotic Membrane Transplantation for Patients With Severe Ocular Burns Induced Anterior Segment Necrosis. J Burn Care Res 2020; 41:668-673. [PMID: 32006003 PMCID: PMC7195555 DOI: 10.1093/jbcr/iraa016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
This article describes a novel surgical technique for successful repair of intractable corneoscleral necrosis caused by severe ocular burns. In this prospective case series, 19 eyes of 15 consecutive patients with sectional scleral necrosis and persistent corneal epithelial defects were treated with tenonplasty and amniotic membrane transplantation. The main outcome measure was the stability of the ocular surface after reepithelialization and repair of defects. All patients underwent successful combined surgery involving tenonplasty and amniotic membrane transplantation, in which the conjunctival and corneal surfaces were reconstructed. The interval from injury to surgery was 37.4 ± 24.5 days (3-91 days), and the ocular surfaces became stabilized in 82.2 ± 35.4 days (26-156 days, median 87 days). At the final visit, all cases presented with corneal opacity and neovascularization to various degrees. The best-corrected visual acuity decreased from 2.83 ± 1.02 LogMAR preoperatively to 2.87 ± 1.31 LogMAR postoperatively. The results imply that tenonplasty combined with amniotic membrane transplantation could provide vascular supply to the ischemic sclera, repair defects in the conjunctiva, and promote corneal reepithelialization, thus facilitating ocular surface stabilization after burns.
Collapse
Affiliation(s)
- Wen-Yan Peng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Li-Wen He
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Peng Zeng
- Department of Ophthalmology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and GeneRegulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dong-Cui Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shi-You Zhou
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
44
|
Anton-Sales I, D'Antin JC, Fernández-Engroba J, Charoenrook V, Laromaine A, Roig A, Michael R. Bacterial nanocellulose as a corneal bandage material: a comparison with amniotic membrane. Biomater Sci 2020; 8:2921-2930. [PMID: 32314754 DOI: 10.1039/d0bm00083c] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Corneal trauma and ulcerations are leading causes of corneal blindness around the world. These lesions require attentive medical monitoring since improper healing or infection has serious consequences in vision and quality of life. Amniotic membrane grafts represent the common solution to treat severe corneal wounds. However, amniotic membrane's availability remains limited by the dependency on donor tissues, its high price and short shelf life. Consequently, there is an active quest for biomaterials to treat injured corneal tissues. Nanocellulose synthetized by bacteria (BNC) is an emergent biopolymer with vast clinical potential for skin tissue regeneration. BNC also exhibits appealing characteristics to act as an alternative corneal bandage such as; high liquid holding capacity, biocompatibility, flexibility, natural - but animal free-origin and a myriad of functionalization opportunities. Here, we present an initial study aiming at testing the suitability of BNC as corneal bandage regarding preclinical requirements and using amniotic membrane as a benchmark. Bacterial nanocellulose exhibits higher mechanical resistance to sutures and slightly longer stability under in vitro and ex vivo simulated physiological conditions than amniotic membrane. Additionally, bacterial nanocellulose offers good conformability to the shape of the eye globe and easy manipulation in medical settings. These excellent attributes accompanied by the facts that bacterial nanocellulose is stable at room temperature for long periods, can be heat-sterilized and is easy to produce, reinforce the potential of bacterial nanocellulose as a more accessible ocular surface bandage.
Collapse
|
|
45
|
Abstract
Amniotic membrane transplantation is an established therapeutic and biological adjunct for several clinical situations, including treatment of diabetic foot ulcers and ocular surface disease. However, poorly standardized and validated clinical preparation and storage procedures can render the final product highly variable and an unpredictable biomaterial. We have therefore developed a novel, standardized method for processing and dry-preserving amniotic membrane, minimizing biochemical, compositional, and structure damage to produce a potentially superior membrane suitable for clinical use. The intellectual property associated with this methodology was patented by the University of Nottingham and licensed to NuVision® Biotherapies which formed the basis of the Tereo® manufacturing process which is used to manufacture Omnigen®.
Collapse
Affiliation(s)
- Andrew Hopkinson
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
- NuVision Biotherapies Ltd, MediCity, Nottingham, UK.
| | - Emily R Britchford
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
- NuVision Biotherapies Ltd, MediCity, Nottingham, UK
| | - Laura E Sidney
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
| |
Collapse
|
|
46
|
Li J, Zhou Z, Wen J, Jiang F, Xia Y. Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration. Front Endocrinol (Lausanne) 2020; 11:543623. [PMID: 33133012 PMCID: PMC7562979 DOI: 10.3389/fendo.2020.543623] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 08/27/2020] [Indexed: 12/13/2022] Open
Abstract
Bone regeneration has become a research hotspot and therapeutic target in the field of bone and joint medicine. Stem cell-based therapy aims to promote endogenous regeneration and improves therapeutic effects and side-effects of traditional reconstruction of significant bone defects and disorders. Human amniotic mesenchymal stem cells (hAMSCs) are seed cells with superior paracrine functions on immune-regulation, anti-inflammation, and vascularized tissue regeneration. The present review summarized the source and characteristics of hAMSCs and analyzed their roles in tissue regeneration. Next, the therapeutic effects and mechanisms of hAMSCs in promoting bone regeneration of joint diseases and bone defects. Finally, the clinical application of hAMSCs from current clinical trials was analyzed. Although more studies are needed to confirm that hAMSC-based therapy to treat bone diseases, the clinical application prospect of the approach is worth investigating.
Collapse
Affiliation(s)
- Jin Li
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Zhixuan Zhou
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
- Department of General Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Jin Wen
- Department of Prosthodontics, School of Medicine, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Fei Jiang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
- Department of General Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- *Correspondence: Fei Jiang
| | - Yang Xia
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
- Department of Prosthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Yang Xia
| |
Collapse
|
|
47
|
Diagnostik und Akuttherapie von Augenverletzungen durch Feuerwerkskörper. Ophthalmologe 2019; 116:1152-1161. [DOI: 10.1007/s00347-019-01000-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
48
|
Wang F, Cheng J, Zhai H, Dong Y, Li H, Xie L. Correlation analysis of the clinical features and prognosis of acute ocular burns-exploration of a new classification scheme. Graefes Arch Clin Exp Ophthalmol 2019; 258:147-155. [PMID: 31713750 DOI: 10.1007/s00417-019-04525-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/04/2019] [Accepted: 10/23/2019] [Indexed: 11/29/2022] Open
Abstract
PURPOSE To explore a new classification scheme for acute ocular burns. METHODS Medical records of 345 patients (450 eyes) with acute ocular burns treated at Shandong Eye Institute between January 2013 and January 2018 with a 12-month minimum follow-up were retrospectively reviewed. A total of 8 parameters in the acute phase were evaluated and graded on a scale from 0 to 3 according to their severity. RESULTS The key factors affecting the prognosis of acute ocular burns were conjunctival involvement (386 eyes, 85.8%), corneal epithelial defect (349 eyes, 77.6%), and limbal ischemia (244 eyes, 54.2%). Visual acuity in 181/450 eyes (40.2%) was worse than 6/60. The injury severity of the cornea, limbus, bulbar conjunctiva, eyelid, and fornix and intraocular signs in the acute phase was significantly correlated with the logarithm of the minimum angle of resolution (logMAR) visual acuity (correlation coefficient [R] 0.481-0.933, P < 0.0001) and corneal opacification, neovascularization, and symblepharon scores in the stable phase (R 0.513-0.855, P < 0.0001). The mean total score for the 8 parameters in the acute phase was 5.34 ± 4.04 (range 0-14); higher scores indicated worse visual acuity (R = 0.899, P < 0.0001). The total score for acute-phase parameters was significantly correlated with that for the stable-phase parameters (R = 0.872, P < 0.0001). CONCLUSIONS The severity of acute-phase parameters is significantly correlated with the final visual outcome and prognosis. The new grading scheme can help clinicians more accurately analyze the degree of ocular burns, determine a reasonable treatment protocol, and rationally evaluate the prognosis.
Collapse
Affiliation(s)
- Fuyan Wang
- Department of Ophthalmology, Clinical Medical College of Shandong University, Jinan, China.,State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Jun Cheng
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Hualei Zhai
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Yanling Dong
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Hua Li
- Department of Ophthalmology, Clinical Medical College of Shandong University, Jinan, China.,State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Lixin Xie
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
| |
Collapse
|
|
49
|
Eslani M, Baradaran-Rafii A, Cheung AY, Kurji KH, Hasani H, Djalilian AR, Holland EJ. Amniotic Membrane Transplantation in Acute Severe Ocular Chemical Injury: A Randomized Clinical Trial. Am J Ophthalmol 2019; 199:209-215. [PMID: 30419194 DOI: 10.1016/j.ajo.2018.11.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 10/28/2018] [Accepted: 11/01/2018] [Indexed: 11/28/2022]
Abstract
PURPOSE To compare the outcomes of conventional medical treatment vs combined medical treatment and amniotic membrane transplantation (AMT) in the management of patients with Roper-Hall grade IV ocular chemical injury. DESIGN Randomized, parallel-controlled clinical trial. METHODS Setting: Single tertiary referral hospital. PATIENTS Sixty eyes of 60 patients with Roper-Hall grade IV ocular chemical injury with a minimum follow-up of 12 months were enrolled in the study. INTERVENTION Patients were randomly assigned to 2 groups: Group 1 (30 eyes) received topical preservative-free lubricating gel and drops, chloramphenicol, betamethasone, homatropine, oral vitamin C, and doxycycline; Group 2 (30 eyes) received amniotic membrane transplant (AMT) on the entire ocular surface in addition to the medical treatment provided in Group 1. OUTCOME MEASURES The main outcome measure was time to complete corneal epithelialization. Secondary outcome measures were best-corrected visual acuity (BCVA) and neovascularization in the central 5 mm of the cornea. RESULTS Mean follow-up time was 20.3 ± 2.5 months (range 13-24 months). Corneal epithelial defects healed within 72.6 ± 30.4 (21-180) days in Group 1 vs 75.8 ± 29.8 (46-170) days in Group 2 (P = .610). Mean BCVA was 2.06 ± 0.67 (0.4-2.6) logMAR vs 2.06 ± 0.57 (1-2.9) logMAR in Groups 1 and 2, respectively (P = .85). Group 1 developed more central corneal neovascularization (22 eyes; 73.3%) compared to Group 2 (16 eyes; 53.3%); however, it was not statistically significant (P = .108). CONCLUSIONS In comparison to conventional medical therapy, combined amniotic membrane transplantation and medical therapy does not accelerate corneal epithelialization or affect final visual acuity in severe chemical injuries.
Collapse
Affiliation(s)
- Medi Eslani
- Cincinnati Eye Institute, Edgewood, Kentucky, USA; Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA; Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | | | - Albert Y Cheung
- Cincinnati Eye Institute, Edgewood, Kentucky, USA; Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA
| | - Khaliq H Kurji
- Cincinnati Eye Institute, Edgewood, Kentucky, USA; Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA
| | - Hamidreza Hasani
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali R Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
| | - Edward J Holland
- Cincinnati Eye Institute, Edgewood, Kentucky, USA; Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA.
| |
Collapse
|
|
50
|
Acute Chemical Eye Injury and Limbal Stem Cell Deficiency-A Prospective Study in the United Kingdom. Cornea 2019; 38:8-12. [PMID: 30199398 DOI: 10.1097/ico.0000000000001739] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To analyze the incidence, nature, outcomes, and complications of acute chemical eye injuries, including the incidence of limbal stem cell deficiency (LSCD) and to compare the 2 main classifications for ocular chemical injuries: Roper-Hall (RH) and Dua. METHODS This is a prospective, consecutive, interventional single-center study between April and October 2009 of all new patients with acute chemical eye injury presenting to the Royal Victoria Infirmary eye emergency department (EED). RESULTS Of 11,683 patients who attended the EED, 98 patients (110 eyes) presented with acute chemical eye injury (60% male). This represents an estimated annual incidence of 5.6 new cases per 100,000 population. Mean age was 36.5 years (1-78; SD 17.1 years), including 7 children (age <10 years). Fifty-one patients (52%) had work-related injuries. The most common chemical agent was alkali (78%). All 4 RH grade IV cases were unilateral, assault with ammonia, and required early amniotic membrane transplantation as per the protocol, but despite full treatment, they developed total LSCD in the affected eye. CONCLUSIONS Acute chemical eye injuries are rare. Male patients in the working age group are more prone to work-related chemical injuries, whereas young children tend to have domestic injuries. Grade I, II, and III RH and Dua chemical injuries had a very good prognosis with topical treatment only, whereas RH grade IV (Dua grade IV-VI), mainly assaults with ammonia, progressed to total/severe LSCD despite appropriate management including early amniotic membrane transplantation. The Dua classification includes conjunctival involvement, having a greater value in predicting the final clinical outcome when grading chemical eye injuries.
Collapse
|