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Bonacci E, Kilian R, Rizzo C, De Gregorio A, Bosello F, Fasolo A, Ponzin D, Marchini G, Pedrotti E. Microscopic corneal epithelial changes and clinical outcomes in simple limbal epithelial transplantation surgery after treatment with amniotic membrane eye drops (AMED): A case report. Am J Ophthalmol Case Rep 2023; 29:101763. [PMID: 36483519 PMCID: PMC9723931 DOI: 10.1016/j.ajoc.2022.101763] [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: 09/05/2022] [Revised: 11/15/2022] [Accepted: 11/26/2022] [Indexed: 12/03/2022] Open
Abstract
Purpose To describe the microscopic epithelial changes and the clinical outcomes of a patient treated with amniotic membrane eye drops (AMED) because of a persistent epithelial defect (PED) and a partial limbal stem cell deficiency (LSCD) after simple limbal epithelial transplantation (SLET) and deep anterior lamellar keratoplasty (DALK). Observations A 72-year-old patient, who had previously undergone SLET and DALK due to a total LSCD, presented with a PED related to a partial LSCD, and was treated with AMED for one month. We evaluated the patient's visual acuity, the Oxford grading scale, the Wong-Baker Pain Rating Scale, and in vivo confocal microscopy, both at baseline and 3 months after the end of treatment. Visual acuity improved from 0.5 to 0.4 LogMAR, the Oxford grading scale changed from grade III to grade I and the Wong-Baker Pain Rating Scale from grade 4 to grade 1. The corneal surface, which initially showed conjunctival characteristics over approximately 50% of the whole area, consisted mainly (75%) of mature corneal epithelium 3 months after the end of treatment. Conclusions and importance While improving symptoms and clinical characteristics, AMED was also able to restore the normal corneal epithelium's morphology in a case of partial LSCD after SLET and DALK.
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Affiliation(s)
- Erika Bonacci
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | - Raphael Kilian
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | - Clara Rizzo
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | | | - Francesca Bosello
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | - Adriano Fasolo
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
- The Veneto Eye Bank Foundation, Venice, Italy
| | | | - Giorgio Marchini
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | - Emilio Pedrotti
- Ophthalmic Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
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Kate A, Basu S. Amniotic Membrane Granuloma in a Case of Ocular Chemical Injury: Clinical Features, Histopathology, and Outcomes. Cureus 2021; 13:e19171. [PMID: 34873514 PMCID: PMC8632734 DOI: 10.7759/cureus.19171] [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] [Accepted: 10/31/2021] [Indexed: 11/17/2022] Open
Abstract
This report describes the clinical features of a granuloma within the layers of amniotic membranes (AM) along with its surgical management and outcome. An eight-year-old boy underwent an AM graft in the right eye for an acute chemical injury. As there was slow healing of the ocular surface, the eye was subjected to a simple limbal epithelial transplantation (SLET). Although the corneal surface was well epithelialized, a superior symblepharon was noted six weeks following SLET. Excision of the fibrotic tissue with an AM graft was carried out. Growth of a grayish-white fibrotic lesion in the visual axis of the cornea was noted eight months after the second AM graft. The optical coherence tomography line scan revealed the location of the lesion to be anterior to the retained SLET AM. This lesion progressively increased in size, so an excision biopsy was carried out. The lesion excised in toto with the AM, and an optically clear plane was noted. Histopathology of the tissue revealed the presence of myofibroblasts, which possibly originated from the AM fibroblasts. At the three-year follow-up period, there was no recurrence of the growth, and the final visual acuity was 20/40. This is a rare report of a granuloma case arising within the layers of an AM. The underlying etiopathogenesis could be due to the multiple AM grafts that the patient underwent. These repeated grafts can incite an immune response and lead to the formation of a granuloma. The special staining and the restoration of the corneal clarity with a stable ocular surface suggest the AM origin of the mass lesion. Removal of the layer of the AM with the granuloma has good outcomes, with no recurrence on long-term follow-up.
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Affiliation(s)
- Anahita Kate
- Cornea, L V Prasad Eye Institute, Vijayawada, IND
| | - Sayan Basu
- Cornea, L V Prasad Eye Institute, Hyderabad, IND
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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.
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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
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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.
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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
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Trinh T, Mimouni M, Santaella G, Cohen E, Chan CC. Surgical Management of the Ocular Surface in Neurotrophic Keratopathy: Amniotic Membrane, Conjunctival Grafts, Lid Surgery, and Neurotization. Eye Contact Lens 2021; 47:149-153. [PMID: 33196502 DOI: 10.1097/icl.0000000000000753] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2020] [Indexed: 11/27/2022]
Abstract
PURPOSE To review the surgical modalities available to treat Mackie stage 2 and stage 3 neurotrophic keratopathy. METHODS Literature review and technique descriptions. RESULTS The following procedures are described in detail with accompanying videos: temporary, permanent, and botox-assisted tarsorrhaphy; amniotic membrane transplant; keratoplasty with amniotic membrane and tarsorrhaphy augmentation; Gunderson and conjunctival pedicle flaps; buccal graft transplantation; and neurotization. CONCLUSION A variety of surgical options exist to manage neurotrophic keratopathy when medical treatments alone fail to resolve epitheliopathy. Ongoing protection and optimization of the ocular surface health remains crucial to prevent recurrent epithelial breakdown.
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Affiliation(s)
- Tanya Trinh
- Department of Ophthalmology and Vision Sciences, the University of Toronto, Toronto, ON, Canada
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Zhao X, Zuo X, Zhong J, Wang B, Li S, Xiao Y, Yuan J. Heparin-Modified Amniotic Membrane Combined With Growth Factors for Promoting Corneal Wound Healing After Alkali Burn. Front Bioeng Biotechnol 2020; 8:599800. [PMID: 33330430 PMCID: PMC7719686 DOI: 10.3389/fbioe.2020.599800] [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: 08/28/2020] [Accepted: 10/27/2020] [Indexed: 12/13/2022] Open
Abstract
Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.
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Affiliation(s)
| | | | | | | | | | | | - Jin Yuan
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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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.
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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
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Singh SR, Yangzes S, Ram J. Saving the melting eye-alkali burns. QJM 2019; 112:621-622. [PMID: 30690637 DOI: 10.1093/qjmed/hcz013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- S R Singh
- Advanced Eye Centre, Department of Ophthalmology, Post graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - S Yangzes
- Advanced Eye Centre, Department of Ophthalmology, Post graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - J Ram
- Advanced Eye Centre, Department of Ophthalmology, Post graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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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.
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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.
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Stereologic and ultrastructural comparison of human and rat amniotic membrane wrapping for rat sciatic nerve repair. J Clin Neurosci 2018; 57:157-161. [DOI: 10.1016/j.jocn.2018.08.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 06/13/2018] [Accepted: 08/08/2018] [Indexed: 01/28/2023]
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Marton E, Giordan E, Gioffrè G, Canova G, Paolin A, Mazzucco MG, Longatti P. Homologous cryopreserved amniotic membrane in the repair of myelomeningocele: preliminary experience. Acta Neurochir (Wien) 2018; 160:1625-1631. [PMID: 29858946 DOI: 10.1007/s00701-018-3577-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 05/23/2018] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Surgical management of spinal dysraphism often requires the use of dural substitutes. Amniotic membrane (AM) has drawn the interest of clinicians for its valuable concentration of cytokines and factors capable of promoting wound healing, re-epithelialization, inhibiting fibrosis and regulating angiogenesis. These beneficial qualities could make AM an interesting dural substitute for spina bifida repair. In this study, we describe the use of banked homologous AM as a dural substitute for the repair of spinal dysraphism in newborns. Our purpose is to test the mechanical characteristics, as well as the safety and effectiveness of AM in preventing postoperative complications and re-tethering. METHODS The AM patch was carefully detached from the chorion of donors undergoing caesarean section, rinsed in saline solution, and cryopreserved in liquid nitrogen. Five newborns were treated using AM: three affected by open spinal dysraphism and two by spina bifida occulta. The AM patch was used as a dural substitute with two different positions and purposes: the amnion-side down covering the placode to prevent adhesions or placed extradurally facing the dura to avoid scarring and facilitating the sliding of the dural sac itself under the extradural tissue layers. RESULTS No adverse events occurred, and the surgical wounds healed without complications. MRI scans taken at 3 and 6 months after surgery showed a satisfying de-tethering of the spinal cord with no obvious evidence of new adherence formation. CONCLUSIONS We present a multimodal interposition technique using AM as a reconstructive and anti-adhesive tissue for the treatment of open myelomeningocele (MMC) and lipomeningocele (LMC) treatment. In our experience, AM proved its efficacy in restoring the dural sac integrity without complications. We support the use of AM as a promising dural substitute, speculating on how the use of AM could potentially change reconstructive strategies for spinal dysraphism.
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Affiliation(s)
- Elisabetta Marton
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy
| | - Enrico Giordan
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy.
| | - Giorgio Gioffrè
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy
| | - Giuseppe Canova
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy
| | | | - Marina Grazia Mazzucco
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy
| | - Pierluigi Longatti
- Department of Neurosurgery, Treviso Hospital, University of Padova, Via Piazzale 1, 31100, Padova, Treviso, Italy
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12
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Lobo Gajiwala A. Regulatory aspects of tissue donation, banking and transplantation in India. Cell Tissue Bank 2018; 19:241-248. [DOI: 10.1007/s10561-018-9689-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 02/19/2018] [Indexed: 10/17/2022]
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Jie J, Yang J, He H, Zheng J, Wang W, Zhang L, Li Z, Chen J, Vimalin Jeyalatha M, Dong N, Wu H, Liu Z, Li W. Tissue remodeling after ocular surface reconstruction with denuded amniotic membrane. Sci Rep 2018; 8:6400. [PMID: 29686390 PMCID: PMC5913251 DOI: 10.1038/s41598-018-24694-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 04/05/2018] [Indexed: 12/16/2022] Open
Abstract
Amniotic membrane (AM) has been widely used as a temporary or permanent graft in the treatment of various ocular surface diseases. In this study, we compared the epithelial wound healing and tissue remodeling after ocular surface reconstruction with intact amniotic membrane (iAM) or denuded amniotic membrane (dAM). Partial limbal and bulbar conjunctival removal was performed on New Zealand rabbits followed by transplantation of cryo-preserved human iAM or dAM. In vivo observation showed that the epithelial ingrowth was faster on dAM compared to iAM after AM transplantation. Histological observation showed prominent epithelial stratification and increased goblet cell number on dAM after 2 weeks of follow up. Collagen VII degraded in dAM within 2 weeks, while remained in iAM even after 3 weeks. The number of macrophages and α-SMA positive cells in the stroma of remodelized conjunctiva in the dAM transplantation group was considerably less. In conclusion, dAM facilitates epithelial repopulation and goblet cell differentiation, further reduces inflammation and scar formation during conjunctival and corneal limbal reconstruction.
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Affiliation(s)
- Jing Jie
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
- Guilin Women and Children's Hospital, Guilin, Guangxi, China
| | - Jie Yang
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
- Zhengzhou Second Hospital, Zhengzhou, Henan, China
| | - Hui He
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
| | - Jianlan Zheng
- Xiamen University affiliated Chenggong Hospital, Xiamen, Fujian, China
| | - Wenyan Wang
- Xiamen University affiliated Chenggong Hospital, Xiamen, Fujian, China
| | - Liying Zhang
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
- Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China
| | - Zhiyuan Li
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
| | - Jingyao Chen
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
| | - M Vimalin Jeyalatha
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
| | - Nuo Dong
- Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China
| | - Huping Wu
- Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China
| | - Zuguo Liu
- Eye Institute of Xiamen University, Xiamen, Fujian, China
- Medical College of Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China
- Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China
| | - Wei Li
- Eye Institute of Xiamen University, Xiamen, Fujian, China.
- Medical College of Xiamen University, Xiamen, Fujian, China.
- Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
- The Affiliated Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
- Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China.
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Singh G, Singh Bhinder H. Evaluation of Therapeutic Deep Anterior Lamellar Keratoplasty in Acute Ocular Chemical Burns. Eur J Ophthalmol 2018; 18:517-28. [DOI: 10.1177/112067210801800403] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- G. Singh
- Guru Gobind Singh International, Eye Research and Cure Centre, New Delhi - India
- Ex Prof. M.A.M. College and Associated Guru Nanak Eye Centre, New Delhi - India
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Treatment of acute ocular chemical burns. Surv Ophthalmol 2017; 63:214-235. [PMID: 28935121 DOI: 10.1016/j.survophthal.2017.09.005] [Citation(s) in RCA: 132] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 09/08/2017] [Accepted: 09/11/2017] [Indexed: 01/15/2023]
Abstract
Ocular chemical burns are an ophthalmic emergency and are responsible for 11.5%-22.1% of ocular injuries. Immediate copious irrigation is universally recommended in acute ocular burns to remove the offending agent and minimize damage. Conventional medical therapy consists of the use of agents that promote epithelialization, minimize inflammation, and prevent cicatricial complications. Biological fluids such as autologous serum, umbilical cord blood serum, platelet-rich plasma, and amniotic membrane suspension are a rich source of growth factors and promote healing when used as adjuncts to conventional therapy. Surgical treatment of acute ocular burns includes the debridement of the necrotic tissue, application of tissue adhesives, tenoplasty, and tectonic keratoplasty. Amniotic membrane transplantation is a novel surgical treatment that is increasingly being used as an adjunct to conventional treatment to promote epithelial healing, minimize pain, and restore visual acuity. Various experimental treatments that aim to promote wound healing and minimize inflammation are being evaluated such as human mesenchymal and adipose stem cells, beta-1,3 glucan, angiotensin-converting enzyme inhibitors, cultivated fibroblasts, zinc desferrioxamine, antifibrinolytic agents, antioxidants, collagen cross-linking, and inhibitors of corneal neovascularization.
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Palioura S, Kymionis G. Corneal neovascularization in childhood keratitis. EXPERT REVIEW OF OPHTHALMOLOGY 2017. [DOI: 10.1080/17469899.2017.1379900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Sotiria Palioura
- Athens Vision Eye Institute, Cornea Service, Athens, Greece
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - George Kymionis
- Jules Gonin Eye Hospital, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Ophthalmology, ‘Gennimatas Hospital’, National and Kapoditrian University of Athens, Athens, Greece
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17
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Amniotic membrane use for management of corneal limbal stem cell deficiency. Curr Opin Ophthalmol 2017; 28:363-369. [DOI: 10.1097/icu.0000000000000386] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Tabatabaei SA, Soleimani M, Behrouz MJ, Torkashvand A, Anvari P, Yaseri M. A randomized clinical trial to evaluate the usefulness of amniotic membrane transplantation in bacterial keratitis healing. Ocul Surf 2017; 15:218-226. [DOI: 10.1016/j.jtos.2017.01.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 01/21/2017] [Accepted: 01/21/2017] [Indexed: 11/15/2022]
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Tsompos C, Panoulis C, Toutouzas K, Zografos G, Papalois A. The effect of erythropoietin on endometrial edema during ischemia–reperfusion injury in rats. J Histotechnol 2016. [DOI: 10.1080/01478885.2016.1202406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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20
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Sharma N, Singh D, Maharana PK, Kriplani A, Velpandian T, Pandey RM, Vajpayee RB. Comparison of Amniotic Membrane Transplantation and Umbilical Cord Serum in Acute Ocular Chemical Burns: A Randomized Controlled Trial. Am J Ophthalmol 2016; 168:157-163. [PMID: 27210276 DOI: 10.1016/j.ajo.2016.05.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 05/09/2016] [Accepted: 05/11/2016] [Indexed: 10/21/2022]
Abstract
PURPOSE To compare the efficacy of topical umbilical cord serum drops (UCS) and amniotic membrane transplantation (AMT) in acute ocular chemical burns. DESIGN Randomized controlled trial. METHODS setting: Tertiary care hospital. STUDY POPULATION Forty-five eyes with acute chemical burns of grade III, IV, and V (Dua's classification) presenting within the first week of injury were randomized into 3 groups (15 each). Patients with perforation/impending corneal perforation were excluded from the study. INTERVENTION Groups 1, 2, and 3 received UCS with medical therapy (MT), AMT with MT, and MT alone, respectively. MAIN OUTCOME MEASURE Time to complete epithelialization. RESULTS The mean time to complete epithelialization was 56.7 ± 14.9, 22.0 ± 10.2, and 22.9 ± 10.1 days in MT, AMT, and UCS groups, respectively, with a significant difference between MT and AMT (P = .001) and between MT and UCS (P = .001), but not between UCS and AMT (P = .9). Improvement in pain score was better with UCS than AMT (P value: .012, .002, and .012 on days 7, 14, and 21, respectively). Corneal clarity was better in the UCS group at 21 (P = .008) and 30 days (P = .002), but not at 3 months (P = .9). By month 3, visual outcome, symblepharon, tear film status, and lid abnormalities were comparable between the 3 groups. CONCLUSIONS UCS and AMT, as an adjuvant to standard medical therapy in acute chemical injury, are equally efficacious. UCS has the advantage of faster improvement in corneal clarity, better pain control, and avoidance of surgery in an inflamed eye.
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Uhlig CE, Frings C, Rohloff N, Harmsen-Aasman C, Schmitz R, Kiesel L, Eter N, Busse H, Alex AF. Long-term efficacy of glycerine-processed amniotic membrane transplantation in patients with corneal ulcer. Acta Ophthalmol 2015; 93:e481-7. [PMID: 25773445 DOI: 10.1111/aos.12671] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 01/01/2015] [Indexed: 12/27/2022]
Abstract
PURPOSE The aim of this study was to determine the long-term treatment efficacy of glycerine-preserved human amniotic membrane transplantation in patients suffering from corneal ulcers. METHODS This was a retrospective, non-controlled, monocentric analysis. Included were patients with corneal ulcers that were non-responsive to ointment or contact lenses and had been treated by amniotic membrane transplantation with either the overlay or sandwich procedure. Analysis parameters were visual acuity before and following treatment, recurrence rate and subjective comfort at the last follow-up. RESULTS Of the 371 amniotic membrane transplantations that were conducted, 135 surgical treatments in 108 patients (51.9% male, 48.1% female; mean age 63.7 years) met the inclusion criteria. In total, 99 overlay and 36 multilayer amniotic membrane transplantations were performed. The follow-up period was 47.5 ± 66.7 weeks (mean ± SD). The recurrence rate at the last follow-up was 47.8% with overlay membranes and 51.8% with the sandwich technique. There was no significant change in best-corrected visual acuity following treatment with overlays (p = 0.219) or sandwich procedure (p = 0.703). At the last follow-up, 72.1% (overlay) and 78.3% (sandwich) of the patients reported either no pain or increased comfort. CONCLUSION The recurrence rates and changes in visual acuity following overlay or sandwich amniotic membrane transplantation in patients suffering from corneal ulcer were lower than reported elsewhere in the literature. More than half of the patients profited from each of the amniotic membrane transplantation techniques with respect to recurrence and postoperative comfort.
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Affiliation(s)
| | - Charlotte Frings
- Department of Ophthalmology; University Medical Center; Muenster Germany
| | - Nadine Rohloff
- Department of Ophthalmology; University Medical Center; Muenster Germany
| | | | - Ralf Schmitz
- Department of Gynecology and Obstetrics; University Medical Center; Muenster Germany
| | - Ludwig Kiesel
- Department of Gynecology and Obstetrics; University Medical Center; Muenster Germany
| | - Nicole Eter
- Department of Ophthalmology; University Medical Center; Muenster Germany
| | - Holger Busse
- Department of Ophthalmology; University Medical Center; Muenster Germany
| | - Anne F. Alex
- Department of Ophthalmology; University Medical Center; Muenster Germany
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22
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de Araujo AL, Gomes JP. Corneal stem cells and tissue engineering: Current advances and future perspectives. World J Stem Cells 2015; 7:806-814. [PMID: 26131311 PMCID: PMC4478627 DOI: 10.4252/wjsc.v7.i5.806] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 01/05/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.
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Sharma N, Lathi SS, Sehra SV, Agarwal T, Sinha R, Titiyal JS, Velpandian T, Tandon R, Vajpayee RB. Comparison of umbilical cord serum and amniotic membrane transplantation in acute ocular chemical burns. Br J Ophthalmol 2014; 99:669-73. [PMID: 25370084 DOI: 10.1136/bjophthalmol-2014-305760] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 10/19/2014] [Indexed: 11/04/2022]
Abstract
PURPOSE To compare the efficacy of umbilical cord serum (UCS) with amniotic membrane transplantation (AMT) in cases of acute ocular chemical burns. METHODS In a retrospective, interventional, comparative case series, 55 eyes with grades III, IV and V chemical burns (Dua's classification) who presented within 3 weeks of injury were evaluated. Patients were treated with conventional medical (CM group, 20 eyes) management alone or combined with either UCS (UCS group, 17 eyes) or AMT (AMT group, 18 eyes). The parameters evaluated were time to epithelialisation, epithelial defect diameter, epithelial defect area, corneal clarity, tear break-up time (TBUT), Schirmer test and best-corrected vision. RESULTS UCS and AMT groups showed early epithelialisation as compared with the CM group (Kaplan-Meier analysis=0.01). Mean time for healing of epithelial defect was 57.7±29.3, 27.4±19.0, 41.1±28.9 days in the CM, UCS and AMT groups, respectively (p=0.02). Mean TBUT at the last follow-up was 8.6±0.7, 10.3±1.1, 9.4±1.2 s in the CM, UCS and AMT groups, respectively (p=0.02). The mean Schirmer value at the last follow-up was 13.7±1.0, 16.9±3.0 and 13.2±1.5 mm in the CM, UCS and AMT groups, respectively (p=0.01). The visual outcomes and the occurrence of corneal vascularisation, symblepheron, ectropion and entropion were comparable in between the groups. CONCLUSIONS Our study suggests that the UCS therapy may be a better alternative to AMT in acute moderate to severe (grades III, IV and V) ocular chemical burns, as it avoids surgical manoeuvre in already inflamed eyes.
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Affiliation(s)
- Namrata Sharma
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Shiv Shankar Lathi
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Sri Vatsa Sehra
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Tushar Agarwal
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Sinha
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Jeewan S Titiyal
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Thirumurthy Velpandian
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Radhika Tandon
- Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Rasik B Vajpayee
- Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
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Ramachandran C, Basu S, Sangwan VS, Balasubramanian D. Concise review: the coming of age of stem cell treatment for corneal surface damage. Stem Cells Transl Med 2014; 3:1160-8. [PMID: 25205842 PMCID: PMC4181400 DOI: 10.5966/sctm.2014-0064] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Accepted: 07/21/2014] [Indexed: 12/13/2022] Open
Abstract
The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,000 CLET procedures have been reported from around the world, with varying degrees of success. In this paper, we compare the methods of cultivation and the outcomes and discuss some problem areas, use of other cells as substitutes for limbal epithelium, and various carrier materials used in transplantation. Our analysis suggests that CLET as a treatment for corneal surface damage has come of age. We also highlight a simpler procedure (simple limbal epithelial transplantation) that involves cultivation of limbal tissue in situ on the surface of the cornea in vivo and that has outcomes comparable to CLET.
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Affiliation(s)
- Charanya Ramachandran
- Centre for Ocular Regeneration, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India
| | - Sayan Basu
- Centre for Ocular Regeneration, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India
| | - Virender S Sangwan
- Centre for Ocular Regeneration, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India
| | - Dorairajan Balasubramanian
- Centre for Ocular Regeneration, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India
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Okada Y, Shirai K, Reinach PS, Kitano-Izutani A, Miyajima M, Flanders KC, Jester JV, Tominaga M, Saika S. TRPA1 is required for TGF-β signaling and its loss blocks inflammatory fibrosis in mouse corneal stroma. J Transl Med 2014; 94:1030-41. [PMID: 25068659 PMCID: PMC5919187 DOI: 10.1038/labinvest.2014.85] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 05/28/2014] [Accepted: 05/29/2014] [Indexed: 12/19/2022] Open
Abstract
We examined whether the loss of transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing ion channel, or TRPA1 antagonist treatment affects the severity inflammation and scarring during tissue wound healing in a mouse cornea injury model. In addition, the effects of the absence of TRPA1 on transforming growth factor β1 (TGF-β1)-signaling activation were studied in cell culture. The lack of TRPA1 in cultured ocular fibroblasts attenuated expression of TGF-β1, interleukin-6, and α-smooth muscle actin, a myofibroblast the marker, but suppressed the activation of Smad3, p38 MAPK, ERK, and JNK. Stroma of the healing corneas of TRPA1(-/-) knockout (KO) mice appeared more transparent compared with those of wild-type mice post-alkali burn. Eye globe diameters were measured from photographs. An examination of the corneal surface and eye globes suggested the loss of TRPA1 suppressed post-alkali burn inflammation and fibrosis/scarring, which was confirmed by histology, immunohistochemistry, and gene expression analysis. Reciprocal bone marrow transplantation between mice showed that KO corneal tissue resident cells, but not KO bone marrow-derived cells, are responsible for KO mouse wound healing with reduced inflammation and fibrosis. Systemic TRPA1 antagonists reproduced the KO phenotype of healing. In conclusion, a loss or blocking of TRPA1 in mice reduces inflammation and fibrosis/scarring in the corneal stroma during wound healing following an alkali burn. The responsible mechanism may include the inhibition of TGF-β1-signaling cascades in fibroblasts by attenuated TRPA1 signaling. Inflammatory cells are considered to have a minimum involvement in the exhibition of the KO phenotype after injury.
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Affiliation(s)
- Yuka Okada
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
| | - Kumi Shirai
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
| | - Peter S Reinach
- Wenzhou Medical University School of Ophthalmology and Optometry, Wenzhou, China
| | - Ai Kitano-Izutani
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
| | - Masayasu Miyajima
- Laboratory Animal Center, Wakayama Medical University, Wakayama, Japan
| | - Kathleen C Flanders
- Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | | | - Makoto Tominaga
- Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute of Natural Science, Okazaki, Aichi, Japan
| | - Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
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Alió JL, Abad M, Scorsetti DH. Preparation, indications and results of human amniotic membrane transplantation for ocular surface disorders. Expert Rev Med Devices 2014; 2:153-60. [PMID: 16293052 DOI: 10.1586/17434440.2.2.153] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
In comparison with other biologic tissues used as reconstructive grafts, the amniotic membrane has the advantage that it is thinner and better tolerated by the patient. Amniotic membrane, when appropriately preserved, can be used as a substrate replacement, such that host cells can migrate into the membrane to form new and healthy tissue. The amniotic membrane is the deeper layer of the fetal membrane; it is avascular, multilayered tissue with antiangiogenic, antiscarring and anti-inflammatory properties. Since it does not express antigens of histocompatibility, the membrane is never rejected by the receiving tissues. In addition, the beneficial effects of reducing inflammation and neovascularization persist for a long time, if properly cryopreserved.
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Affiliation(s)
- Jorge L Alió
- Vissum, Instituto Oftalmológico de Alicante, Research, Development and Innovation Department, Miguel Hernandez University, Alicante, Spain.
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28
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Deshpande P, Ramachandran C, Sefat F, Mariappan I, Johnson C, McKean R, Hannah M, Sangwan VS, Claeyssens F, Ryan AJ, MacNeil S. Simplifying corneal surface regeneration using a biodegradable synthetic membrane and limbal tissue explants. Biomaterials 2013; 34:5088-106. [DOI: 10.1016/j.biomaterials.2013.03.064] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 03/25/2013] [Indexed: 10/27/2022]
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Deshpande P, Ramachandran C, Sangwan VS, Macneil S. Cultivation of limbal epithelial cells on electrospun poly (lactide-co-glycolide) scaffolds for delivery to the cornea. Methods Mol Biol 2013; 1014:179-85. [PMID: 23690013 DOI: 10.1007/978-1-62703-432-6_12] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
In delivering tissues to the body, both natural and synthetic materials have been used. Currently, a natural membrane, the human amniotic membrane (AM), is used to deliver limbal epithelial cells (LEC) to the cornea. AM presents inherent problems with structural variation and requires extensive serological screening before use. Therefore alternatives are required to improve the predictability in clinical outcomes and economic costs associated with the use of this biological substrate. In this chapter, we describe the development of an alternative, structurally simple, synthetic biodegradable electrospun scaffold based on poly(lactide-co-glycolide) (PLGA: materials used in dissolvable sutures) to replace AM.
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Affiliation(s)
- Pallavi Deshpande
- The Kroto Research Institute, University of Sheffield, Sheffield, UK
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Abstract
BACKGROUND Ocular surface burns can be caused by chemicals (alkalis and acids) or by direct heat. Amniotic membrane transplantation (AMT) performed in the acute phase (day 0 to day 7) of an ocular surface burn is reported to relieve pain, accelerate healing and reduce scarring and blood vessel formation. The surgery involves applying a patch of amniotic membrane (AM) over the entire ocular surface up to the eyelid margins. OBJECTIVES To assess the effects of AMT on the eyes of people having suffered acute ocular surface burns. SEARCH METHODS We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 June 2012. SELECTION CRITERIA We included randomised trials of medical therapy and AMT applied in the first seven days after an ocular surface burn compared to medical therapy alone. DATA COLLECTION AND ANALYSIS Two authors independently assessed the risk of bias of included studies 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 included one RCT of 100 participants with ocular burns that were randomised to treatment with AMT and medical therapy or medical therapy alone. A subset of patients (n = 68) who were treated within the first seven days of the injury met the inclusion criteria and were included in the analysis. The remaining 32 eyes were excluded. The included subset consisted of 36 moderate (Dua classification II-III) and 32 severe (Dua classification IV-VI) ocular burns from alkali, acid and thermal injuries. In the moderate category, 13/20 control eyes and 14/16 treatment eyes had complete epithelialisation by 21 days. The RR of failure of epithelialisation by day 21 was 0.18 in the treatment group (95% confidence interval (CI) 0.02 to 1.31; P = 0.09). Mean LogMAR final visual acuities were 0.06 (standard deviation (SD) 0.10) in the treatment group and 0.38 (SD 0.52) in the control group, representing a MD of -0.32 (95% CI -0.05 to -0.59). In the severe category, 1/17 treatment and 1/15 control eyes were epithelialised by day 21. The RR of failure of epithelialisation in the treatment group was 1.01 (95% CI 0.84 to 1.21; P = 0.93). Final visual acuity was 1.77 (SD 1.31) in the treated eyes and 1.64 (SD 1.48) in the control group (MD 0.13; 95% CI -0.88 to 1.14). The risks of performance and detection biases were high, because treating personnel and outcome assessors could not be masked to treatment. There was also a high risk of bias in the visual outcomes of the moderate category, since mean visual acuity was significantly worse at presentation in the control eyes. This reduced confidence in the study findings. AUTHORS' CONCLUSIONS Conclusive evidence supporting the treatment of acute ocular surface burns with AMT is lacking. Heterogeneity of disease presentation, variations in treatment, undefined criteria for treatment success and failure, and non-uniform outcome measures are some of the factors complicating the search for clear evidence regarding this treatment.
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Affiliation(s)
- Gerry Clare
- Ophthalmology and Visual Sciences, University of Nottingham, Nottingham, UK.
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Clare G, Suleman H, Bunce C, Dua H. Amniotic membrane transplantation for acute ocular burns. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2011. [DOI: 10.1002/14651858.cd009379] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Okada Y, Reinach PS, Shirai K, Kitano A, Kao WWY, Flanders KC, Miyajima M, Liu H, Zhang J, Saika S. TRPV1 involvement in inflammatory tissue fibrosis in mice. THE AMERICAN JOURNAL OF PATHOLOGY 2011; 178:2654-64. [PMID: 21641388 DOI: 10.1016/j.ajpath.2011.02.043] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2010] [Revised: 02/06/2011] [Accepted: 02/10/2011] [Indexed: 10/18/2022]
Abstract
We examined whether absence or blocking of transient receptor potential vanilloid subtype 1 (TRPV1) affects the level of inflammation and fibrosis/scarring during healing of injured tissue using an alkali burn model of cornea in mice. A cornea burn was produced with 1 N NaOH instilled into one eye of TRPV1-/- (KO) (n = 88) or TRPV1+/+ (n = 94) mice. Examinations of the corneal surface and eye globe size suggested that the loss of TRPV1 suppressed inflammation and fibrosis/scarring after alkali burn, and this was confirmed by histology, IHC, and gene expression analysis. The loss of TRPV1 inhibited inflammatory cell invasion and myofibroblast generation in association with reduction of expression of proinflammatory and profibrogenic components. Experiments of bone marrow transplantation between either genotype of mice showed that KO corneal tissue resident cells, but not KO bone marrow-derived cells, are responsible for KO-type wound healing with reduced inflammation and fibrosis. The absence of TRPV1 attenuated expression of transforming growth factor β 1 (TGFβ1) and other proinflammatory gene expression in cultured ocular fibroblasts, but did not affect TGFβ1 expression in macrophages. Loss of TRPV1 inhibited myofibroblast transdifferentiation in cultured fibroblasts. Systemic TRPV1 antagonists reproduced the KO type of healing. In conclusion, absence or blocking of TRPV1 suppressed inflammation and fibrosis/scarring during healing of alkali-burned mouse cornea. TRPV1 is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing.
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Affiliation(s)
- Yuka Okada
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
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Abstract
PURPOSE To analyze the short- and intermediate-term results of simultaneous transplantation of amniotic membrane with high-risk keratoplasty. METHODS Between January 2002 and February 2004, a simultaneous amniotic membrane patch was transplanted with penetrating keratoplasty in 16 eyes of 16 patients. In 13 eyes, a soft contact lens was applied afterward. Corneal perforation was present in 10 of 14 eyes with emergency keratoplasty. Five patients received systemic immunosuppressive medication for 4-6 months after penetrating keratoplasty. RESULTS The amniotic membrane patch fell off after 8 ± 3 (range: 4-14) days without residual tissue except in 1 case. In 15 of 16 eyes, the epithelium was completely closed after 10 ± 8 (range: 4-30) days. In 3 eyes, recurrence of the epithelial defect occurred after 3-6 months. During a follow-up period of 18 ± 6 months, 13 of 16 corneal grafts were clear. CONCLUSIONS Simultaneous amniotic membrane transplantation and penetrating keratoplasty may improve the prognosis of corneal graft in eyes with risk of epithelial healing problems.
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Abstract
OBJECTIVE Eye burns can cause significant ocular morbidity and miss early detection if unsuspected. The objective was to ascertain the reported causes of burns to the eyes in children. METHODS Published literature on eye burns in children was searched from 1950 to July 2008 in MEDLINE and from 1982 to July 2008 in CINAHL (Cumulative Index to Nursing and Allied Health Literature) to identify all reported cases. RESULTS Forty-two articles from MEDLINE, 5 from CINAHL database, and 6 from the reference lists were included in the analysis. Eye burns in children were caused by thermal, electrical, microwaved food and drinks, and solar hazards. Chemical agents included household cleaning agents, industrial chemicals, certain medications, agricultural chemicals, and some miscellaneous agents. Biological agents reported were millipedes, snake venom, vesicatory insects, and Manchineel tree sap. CONCLUSIONS This article shows that children experience eye burns due to many preventable causes. Public education strategies should be implemented to prevent eye burns in children.
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Liang L, Li W, Ling S, Sheha H, Qiu W, Li C, Liu Z. Amniotic membrane extraction solution for ocular chemical burns. Clin Exp Ophthalmol 2009; 37:855-63. [DOI: 10.1111/j.1442-9071.2009.02159.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Shay E, Kheirkhah A, Liang L, Sheha H, Gregory DG, Tseng SC. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol 2009; 54:686-96. [PMID: 19699503 PMCID: PMC2853888 DOI: 10.1016/j.survophthal.2009.03.004] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2009] [Accepted: 03/31/2009] [Indexed: 01/13/2023]
Abstract
Stevens-Johnson syndrome and its more severe variant, toxic epidermal necrolysis, have relatively low overall incidence; however, this disease presents with high morbidity and mortality. The majority of patients develop ocular inflammation and ulceration at the acute stage. Due to the hidden nature of these ocular lesions and the concentration of effort toward life-threatening issues, current acute management has not devised a strategy to preclude blinding cicatricial complications. This review summarizes recent literature data, showing how sight-threatening corneal complications can progressively develop from cicatricial pathologies of lid margin, tarsus, and fornix at the chronic stage. It illustrates how such pathologies can be prevented with the early intervention of cryopreserved amniotic membrane transplantation to suppress inflammation and promote epithelial healing at the acute stage. Significant dry eye problems and photophobia can also be avoided with this intervention. This new therapeutic strategy can avert the catastrophic ophthalmic sequelae of this rare but devastating disease.
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Affiliation(s)
| | - Ahmad Kheirkhah
- Ocular Surface Center and Ocular Surface Research and Education Foundation, Miami, Florida, USA
| | - Lingyi Liang
- Ocular Surface Center and Ocular Surface Research and Education Foundation, Miami, Florida, USA
| | - Hossam Sheha
- Ocular Surface Center and Ocular Surface Research and Education Foundation, Miami, Florida, USA
| | - Darren G. Gregory
- Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, Colorado, USA
| | - Scheffer C.G. Tseng
- TissueTech Inc., Miami, Florida, USA
- Ocular Surface Center and Ocular Surface Research and Education Foundation, Miami, Florida, USA
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Abstract
Patients with limbal stem cell deficiency (LSCD) suffer from photophobia and a severe loss of vision uncorrectable by conventional PKP. This literature review shows that new strategies can be formulated for treating LSCD. Early cryopreserved amniotic membrane transplantation (AMT) as a temporary biological bandage with sutures or with sutureless ProKera in the acute stage of chemical burn and Stevens-Johnson syndrome prevents the occurrence of LSCD by preserving and expanding the remaining limbal epithelial stem cells. Similarly, remaining limbal stem cells can also be expanded in corneal surfaces with partial or nearly total LSCD if corneal pannus is removed and AMT is performed as a graft with or without sutures by the use of fibrin glue. Moreover, AMT as a temporary bandage and a graft using fibrin glue can also facilitate corneal surface reconstruction by reducing the size of a conjunctival limbal autograft (CLAU) to one 60 degrees graft for unilateral total LSCD as well as promote the success of a keratolimbal allograft (KLAL) for bilateral total LSCD. The latter success is further dictated by effective systemic immunosuppression and by measures to restore the ocular surface defenses, suppress conjunctival inflammation, and correct cicatricial complications so that a stable tear film can be maintained before surgery. This review also summarizes recent findings and outlines future challenges that we need to overcome in squamous metaplasia, that is, another major type of ocular surface failure.
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Affiliation(s)
- L Liang
- Department of Tissue Tech., Ocular Surface Center, Ocular Surface Research and Education Foundation, Miami, FL, USA
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Ocular Surface Disease Center, Sun Yat-sen University, Guangzhou, China
| | - H Sheha
- Department of Tissue Tech., Ocular Surface Center, Ocular Surface Research and Education Foundation, Miami, FL, USA
- Research Institute of Ophthalmology, Cairo, Egypt
| | - J Li
- Department of Tissue Tech., Ocular Surface Center, Ocular Surface Research and Education Foundation, Miami, FL, USA
- Department of Ophthalmology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
| | - SCG Tseng
- Department of Tissue Tech., Ocular Surface Center, Ocular Surface Research and Education Foundation, Miami, FL, USA
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Preservation, sterilization and de-epithelialization of human amniotic membrane for use in ocular surface reconstruction. Biomaterials 2009; 31:216-25. [PMID: 19781769 DOI: 10.1016/j.biomaterials.2009.09.034] [Citation(s) in RCA: 170] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2009] [Accepted: 09/10/2009] [Indexed: 01/22/2023]
Abstract
In the past 20 years, human amniotic membrane (AM) has become widely used as an ophthalmic surgical patch as well as a substrate for stem cell tissue equivalents for ocular surface reconstruction. AM reduces ocular surface scarring and inflammation, and enhances epithelialization. In addition, it shows limited immunogenicity and some anti-microbial properties. Before being applied clinically, the donor of AM is required to undergo a thorough health screening and the membrane has to undergo an accepted processing routine, which includes preservation, sterilization and de-epithelialization. There have been various articles describing methods in preserving, sterilizing and de-epithelializing AM. Each preparation technique has been reported to have differential effects on the physical and biological properties of the AM. Therefore, it is difficult to establish a standardized procedure. In this review, we discuss the present techniques and several novel, new approaches in the preparation of AM for use in ocular surface reconstruction, and their impact on AM structure and biological activity.
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Abstract
Diseases that affect the limbal stem cells are multifactorial and present with different stages of severity. The most important features to be considered in evaluating these patients include the degree of limbal stem cell loss, the extent of conjunctival disease, and the presence and etiology of ocular surface inflammation. Other important factors are tear film and eyelid abnormalities, keratinization of the ocular surface, laterality of the disease process, health and age of the patient. Careful consideration of all of these factors help tremendously in tailoring the most suitable method of treatment for each patient. The management of severe ocular surface disease has benefited from numerous advances in recent years. At one time, available techniques for visual rehabilitation consisted of superficial keratectomy, use of artificial tears, tarsorraphy as well as lamellar and penetrating keratoplasty. A lamellar or penetrating keratoplasty procedure resulted in a stable surface only for as long as the donor epithelium was present and once the epithelium sloughed off, the ocular surface failed due to conjunctivalization. The last few decades enjoyed the development and, especially, progress of new ocular surface reconstruction techniques such as amniotic membrane transplantation, limbal stem cell transplant procedures, transplantation of cultivated oral mucosal or limbal stem cell sheets. This review will briefly focus on the indications and methodology of each procedure and the currently available clinical data on the results of these procedures.
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Yoon KC, Im SK, Kim JC, Yoon KW, Choi SK. Prognosis of Paraquat-Induced Ocular Surface Injury: Therapeutic Effect of Amniotic Membrane Transplantation. Cornea 2009; 28:520-3. [DOI: 10.1097/ico.0b013e3181914316] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye (Lond) 2009; 23:1442-50. [PMID: 19373264 DOI: 10.1038/eye.2009.60] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
PURPOSE To access the feasibility of using cultivated oral mucosal epithelial cell transplantation (COMET) for the management of severe corneal burn. METHODS COMET was performed to promote re-epithelialization in two eyes with acute alkaline burn and one eye with chronic alkaline burn, and to reconstruct the ocular surface in two eyes with chronic thermal burn. Autologous oral mucosal epithelial cells obtained from biopsy were cultivated on amniotic membrane. Immunoconfocal microscopy for keratins and progenitor cell markers was performed to characterize the cultivated epithelial sheet. Following transplantation, the clinical outcome and possible complications were documented. The patients were followed for an averaged 29.6+/-3.6 (range: 26-34) months. RESULTS Cultivated oral mucosal epithelial sheet expressed keratin 3, 13, and progenitor cell markers p63, p75, and ABCG2. After COMET, all the corneas became less inflamed, and the corneal surface was completely re-epithelialized in 6.0+/-3.2 (range: 3-10) days in all but one patients. Microperforation occurred in one patient, and a small persistent epithelial defect developed in another. Both were solved uneventfully. In all patients, superficial corneal blood vessels invariably developed, and to further improve vision, conjunctivo-limbal autografting (N=3) and/or penetrating keratoplasty (N=3) were performed subsequently. The vision of all patients showed substantial improvement after additional surgeries. CONCLUSIONS This study showed the potential of COMET to promote re-epithelialization and reduce inflammation in acute corneal burn, and to reconstruct the corneal surface in chronic burn. COMET may, therefore, be considered an alternative treatment for severe corneal burn.
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Limbal stem cell transplantation: new progresses and challenges. EYE (LONDON, ENGLAND) 2008. [PMID: 19098704 DOI: 10.1038/eye] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients with limbal stem cell deficiency (LSCD) suffer from photophobia and a severe loss of vision uncorrectable by conventional PKP. This literature review shows that new strategies can be formulated for treating LSCD. Early cryopreserved amniotic membrane transplantation (AMT) as a temporary biological bandage with sutures or with sutureless ProKera in the acute stage of chemical burn and Stevens-Johnson syndrome prevents the occurrence of LSCD by preserving and expanding the remaining limbal epithelial stem cells. Similarly, remaining limbal stem cells can also be expanded in corneal surfaces with partial or nearly total LSCD if corneal pannus is removed and AMT is performed as a graft with or without sutures by the use of fibrin glue. Moreover, AMT as a temporary bandage and a graft using fibrin glue can also facilitate corneal surface reconstruction by reducing the size of a conjunctival limbal autograft (CLAU) to one 60 degrees graft for unilateral total LSCD as well as promote the success of a keratolimbal allograft (KLAL) for bilateral total LSCD. The latter success is further dictated by effective systemic immunosuppression and by measures to restore the ocular surface defenses, suppress conjunctival inflammation, and correct cicatricial complications so that a stable tear film can be maintained before surgery. This review also summarizes recent findings and outlines future challenges that we need to overcome in squamous metaplasia, that is, another major type of ocular surface failure.
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Yildiz EH, Nurozler AB, Ozkan Aksoy N, Altiparmak UE, Onat M, Karaguzel H. Amniotic membrane transplantation: indications and results. Eur J Ophthalmol 2008; 18:685-90. [PMID: 18850543 DOI: 10.1177/112067210801800504] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To describe amniotic membrane transplantation indications and results at the authors' institution. METHODS In this study, chart review of 108 patients who underwent amniotic membrane transplantation between January 2002 and April 2006 was performed. The survival rate of corneal integrity was compared, using Kaplan-Meier survival analysis, as a measure of success rate. RESULTS The mean age of the patients was 55.2+/-20.1 (6-87 years, 75 female, 51 male). The patients underwent amniotic membrane transplantation for six different diagnoses: nontraumatic corneal perforation (32 eyes, Group 1), persistent epithelial defect (29 eyes, Group 2), aphakic/pseudophakic bullous keratopathy (18 eyes, Group 3), infectious ulcer resistant to treatment (14 eyes, Group 4), necrotizing keratitis secondary to endophthalmitis (10 eyes, Group 5), and caustic injury (5 eyes, Group 6). The mean survival of corneal integrity was similar in all groups (p=0.156). CONCLUSIONS Amniotic membrane transplantation is a successful adjunctive method in achieving corneal epithelization in the study indications.
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Affiliation(s)
- E H Yildiz
- Department of Ophthalmology, Ankara Education and Research Hospital, Ankara - Turkey.
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Kheirkhah A, Johnson DA, Paranjpe DR, Raju V, Casas V, Tseng SCG. Temporary sutureless amniotic membrane patch for acute alkaline burns. ARCHIVES OF OPHTHALMOLOGY (CHICAGO, ILL. : 1960) 2008; 126:1059-66. [PMID: 18695099 PMCID: PMC2849136 DOI: 10.1001/archopht.126.8.1059] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate the clinical outcome of a new sutureless approach for a temporary amniotic membrane patch (ProKera; Bio-Tissue, Inc, Miami, Florida) in eyes with acute burns. METHODS Retrospective review of 5 eyes of 5 patients with grades I to III acute alkaline burns, receiving ProKera insertion within 8 days of injury. RESULTS These eyes had either total (2 cases) or extensive (60%-75%, 3 cases) corneal epithelial defects with limbal (120 degrees -360 degrees ) and conjunctival (30%-60%) epithelial defects. ProKera was inserted within a mean (SD) of 3.7 (3.1) days after burn and repeated 1 to 3 times for 3 cases. Conjunctival defects reepithelialized in 8.2 (5) days (range, 5-17 days), while limbal and corneal defects healed in 13.6 (8.3) days (range, 5-25 days). The latter was completed with circumferential closure of limbal defects followed by centripetal healing of corneal defects. In 3 eyes, early peripheral corneal neovascularization was followed by marked regression on completion of healing. During 16.8 (10.8) months of follow-up, all eyes retained a stable surface with improved corneal clarity, and without limbal deficiency or symblepharon. CONCLUSION This sutureless application of an amniotic membrane patch allows for early delivery of its biologic actions, which may help preserve remaining limbal stem cells for rapid expansion and prevent late cicatricial complications in eyes with mild and moderate acute alkaline burns.
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Affiliation(s)
- Ahmad Kheirkhah
- Ocular Surface Center, Miami, Florida
- Ocular Surface Research and Education Foundation, Miami, Florida
| | - Daniel A. Johnson
- Department of Ophthalmology, University of Texas Health Science Center at San Antonio
| | - Deval R. Paranjpe
- Department of Ophthalmology, Allegheny General Hospital, Pittsburgh, Pennsylvania
| | - V.K. Raju
- Ocular Surface Center, Miami, Florida
- Ocular Surface Research and Education Foundation, Miami, Florida
| | | | - Scheffer C. G. Tseng
- Ocular Surface Center, Miami, Florida
- Ocular Surface Research and Education Foundation, Miami, Florida
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Tsuzuki K, Yamashita K, Izumisawa Y, Kotani T. Microstructure and glycosaminoglycan ratio of canine cornea after reconstructive transplantation with glycerin-preserved porcine amniotic membranes. Vet Ophthalmol 2008; 11:222-7. [DOI: 10.1111/j.1463-5224.2008.00629.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
PURPOSE To report the results of one 60 degrees conjunctival limbal autograft (CLAU) combined with amniotic membrane (AM) transplantation for an eye with total limbal stem cell deficiency (LSCD). METHODS One eye of a patient with chronic total LSCD and symblepharon caused by chemical burn was subjected to symblepharon lysis, removal of pannus from corneal surface, AM transplantation to cover the conjunctival and corneal surfaces as a permanent graft, one 60 degrees CLAU to the superior limbal area, and insertion of ProKera as a temporary AM patch to cover the CLAU. RESULTS After surgery, corneal epithelialization over the AM was evident adjacent to the CLAU on day 6, progressed to pass the horizontal midline by day 11, and was completed by day 18. During a follow-up of 1 year, the corneal surface remained stable and smooth, and the stroma considerably regained clarity with regression of midstromal vascularization. The best-corrected visual acuity improved from 20/400 to 20/50. The conjunctival inflammation completely resolved, and the fornices were deep. CONCLUSIONS One 60 degrees CLAU combined with AM transplantation as both a permanent graft and a temporary patch can restore the entire corneal surface in an eye with total LSCD caused by chemical burn.
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48
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The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in India. Cell Tissue Bank 2008; 10:93-101. [DOI: 10.1007/s10561-008-9086-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2008] [Revised: 06/02/2008] [Accepted: 06/02/2008] [Indexed: 10/21/2022]
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López-García JS, Rivas Jara L, García-Lozano I, Murube J. Histopathologic Limbus Evolution After Alkaline Burns. Cornea 2007; 26:1043-8. [PMID: 17893531 DOI: 10.1097/ico.0b013e31812375fd] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To study the histopathologic evolution of the corneal limbus after alkaline burns according to the clinical severity and therapy used. METHODS A prospective study of 15 eyes from 12 patients (9 men and 3 women) with moderate and severe alkaline burns was performed. All patients were divided into 2 groups in accordance with the clinical ocular severity and the therapy that was used: medical therapy, amniotic membrane transplantation (AMT), autologous limbal transplantation (ALT), and ALT combined with AMT (ALT + AMT). Biopsies were obtained from affected limbal areas immediately after the ocular burn and 9 months later. RESULTS Limbal regeneration was limited to small areas in patients with moderate burns treated with medical therapy; in contrast, the limbal structure showed significant stromal and epithelial regeneration in patients with moderate burns treated with AMT. There was an important stromal regeneration with an incomplete reepithelialization in patients with severe burns treated with AMT. Patients treated with ALT showed a good reepithelialization with a defective stromal regeneration. Epithelial and stromal regeneration was notable in patients with severe burns treated with ALT + AMT. CONCLUSIONS In patients with moderate alkaline burns, AMT improved both limbal stromal and epithelial regeneration more effectively than medical therapy. In patients with severe burns, the best reepithelialization and stromal regeneration were obtained with ALT + AMT.
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Saika S, Yamanaka O, Okada Y, Miyamoto T, Kitano A, Flanders KC, Ohnishi Y, Nakajima Y, Kao WWY, Ikeda K. Effect of overexpression of PPARgamma on the healing process of corneal alkali burn in mice. Am J Physiol Cell Physiol 2007; 293:C75-86. [PMID: 17625041 DOI: 10.1152/ajpcell.00332.2006] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Wound healing involves both local cells and inflammatory cells. Alkali burn of ocular surface tissue is a serious clinical problem often leading to permanent visual impairment resulting from ulceration, scarring and neovascularization during healing. Behaviors of corneal cells and inflammatory cells are orchestrated by growth factor signaling networks that have not been fully uncovered. Here we showed that adenoviral gene introduction of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibits activation of ocular fibroblasts and macrophages in vitro and also induced anti-inflammatory and anti-fibrogenic responses in an alkali-burned mouse cornea. PPARgamma overexpression suppressed upregulation of inflammation/scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages. It also suppressed expression of such growth factors and collagen Ialpha2 and myofibroblast generation upon exposure to TGFbeta1. Exogenous PPARgamma did not alter phosphorylation of Smad2, but inhibited its nuclear translocation. PPARgamma overexpression enhanced proliferation of corneal epithelial cells, but not of fibroblasts in vitro. Epithelial cell expression of MMP-2/-9 and TGFbeta1 and its migration were suppressed by PPARgamma overexpression. In vivo experiments showed that PPARgamma gene introduction suppressed monocytes/macrophages invasion and suppressed the generation of myofibroblasts, as well as upregulation of cytokines/growth factors and MMPs in a healing cornea. In vivo re-epitheliazation with basement membrane reconstruction in the healing, burned, cornea was accelerated by PPARgamma-Ad expression, although PPARgamma overexpression was considered to be unfavorable for cell migration. Together, these data suggest that overexpression of PPARgamma may represent an effective new strategy for treatment of ocular surface burns.
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MESH Headings
- Adenoviridae/genetics
- Animals
- Basement Membrane/metabolism
- Burns, Chemical/etiology
- Burns, Chemical/genetics
- Burns, Chemical/metabolism
- Burns, Chemical/physiopathology
- Burns, Chemical/therapy
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Cicatrix/genetics
- Cicatrix/metabolism
- Cicatrix/physiopathology
- Cicatrix/therapy
- Cornea/metabolism
- Cornea/pathology
- Cornea/physiopathology
- Corneal Diseases/chemically induced
- Corneal Diseases/genetics
- Corneal Diseases/metabolism
- Corneal Diseases/physiopathology
- Corneal Diseases/therapy
- Disease Models, Animal
- Epithelium, Corneal/metabolism
- Epithelium, Corneal/pathology
- Eye Burns/chemically induced
- Eye Burns/genetics
- Eye Burns/metabolism
- Eye Burns/physiopathology
- Eye Burns/therapy
- Fibroblasts/metabolism
- Fibroblasts/pathology
- Fibrosis
- Gelatinases/metabolism
- Genetic Therapy/methods
- Genetic Vectors
- Inflammation/genetics
- Inflammation/metabolism
- Inflammation/physiopathology
- Inflammation/therapy
- Intercellular Signaling Peptides and Proteins/metabolism
- Macrophages/metabolism
- Macrophages/pathology
- Mice
- Mice, Inbred C57BL
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/physiopathology
- Neovascularization, Pathologic/therapy
- PPAR gamma/genetics
- PPAR gamma/metabolism
- RNA, Messenger/metabolism
- Signal Transduction
- Smad Proteins/metabolism
- Sodium Hydroxide
- Transfection
- Up-Regulation
- Wound Healing
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Affiliation(s)
- Shizuya Saika
- Dept. of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan.
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