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Wang C, Xie H, Sun B, Tang K, Wang H, Zhao Z, Zheng Q, Wu J, Zhang Q, Chen B, Dong H, Yang J, Liu H, Wen F, Sun T, Xue J, Zhao S, Chen L, Liu Z, Yang Y, Sheng X, Wu P, Han Y, Qiang W, Xie Q, Xu Y, Liu H, Yu M, Huang L, Li H, Wei R, Wang M, Chen G, Cheng Y, Chen W. Clinical characteristics and risk factors for readmission after deep anterior lamellar keratoplasty: a nationwide, cross-sectional, multicenter study. BMC Ophthalmol 2025; 25:193. [PMID: 40205532 PMCID: PMC11984012 DOI: 10.1186/s12886-025-04010-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND To assess the incidence, cause and risk factors for unplanned readmission within 90 days after deep anterior lamellar keratoplasty (DALK). METHODS A multicentre cross-sectional study of 3603 eyes of 3588 patients after keratoplasty between January 1st, 2019, and September 30th, 2021 in 16 hospitals across China was performed. The demographic and clinical features between patients after DALK with 90-day unplanned readmission and those who did not have been compared. The risk factors of unplanned readmission were identified by a multivariable Cox regression model. RESULTS Among 873 patients (878 eyes) after DALK, and the primary indications for DALK were keratitis (391 eyes, 44.53%) and keratoconus (275 eyes, 31.32%). The rates of unplanned readmission within 30 days, 60 days, and 90 days were 1.95%, 4.01%, and 5.15%. The main reason of 90-day readmission was infectious keratitis (18 eyes, 40.00%), followed by corneal epithelial defects (11 eyes, 24.44%) and immune-related keratitis (10 eyes, 22.22%). Patients readmitted within 90 days exhibit a more advanced age (p = 0.013). It is also more concentrated in patients with corneal ulcers or perforations (p = 0.029) or blindness (p = 0.02). Compared with patients with keratoconus, patients with keratitis (HR = 3.545, 95% CI 1.104-11.386, p = 0.034) and corneal degeneration or malnutrition (HR = 6.470, 95% CI 1.942-21.560, p = 0.002) are more likely to have an unplanned readmission risk within 90 days. CONCLUSION The main causes of unplanned readmission within 90 days after DALK were infectious keratitis, corneal epithelial defects, and immune-related keratitis. The indications for DALK were associated with 90-day readmissions. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Chenxi Wang
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Center of Ophthalmology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China
| | - He Xie
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Binjia Sun
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Kexin Tang
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Haiou Wang
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zelin Zhao
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qinxiang Zheng
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Department of Ophthalmology, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China
| | - Jie Wu
- Department of Ophthalmology, Xi'an No. 1 Hospital, No. 30, Fen Alley, South Street, Xi'an, Shaanxi, China
| | - Qi Zhang
- Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Baihua Chen
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - He Dong
- Department of Ophthalmology, The Third People's Hospital of Dalian & Dalian Municipal Eye Hospital, Dalian, Liaoning, China
| | - Jizhong Yang
- Department of Cornea, Shanxi Eye Hospital, Taiyuan, Shanxi, China
| | - Hai Liu
- Department of Ophthalmology, Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, China
| | - Feng Wen
- Department of Ophthalmology, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China
| | - Tao Sun
- Department of Ophthalmology, Jiangxi Province Division of National Clinical Research Center of Ocular Disease, The Affiliated eye hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jinsong Xue
- Department of Ophthalmology, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shaozhen Zhao
- Corneal & Refractive surgery center, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute, School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Limin Chen
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Zhirong Liu
- Department of Ophthalmology, Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yanning Yang
- Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xunlun Sheng
- Department of Ophthalmology, Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Third Clinical Medical College of Ningxia Medical University, Ningxia Hui Autonomous Region, Yinchuan, China
| | - Pengcheng Wu
- Department of Ophthalmology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Yuping Han
- Department of Cornea, Shanxi Eye Hospital, Taiyuan, Shanxi, China
| | - Wei Qiang
- Department of Ophthalmology, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China
| | - Qi Xie
- Department of Ophthalmology, Jiangxi Province Division of National Clinical Research Center of Ocular Disease, The Affiliated eye hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yingnan Xu
- Department of Ophthalmology, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hui Liu
- Corneal & Refractive surgery center, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute, School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Man Yu
- Department of Ophthalmology, Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Linying Huang
- Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Huiping Li
- Department of Ophthalmology, Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Third Clinical Medical College of Ningxia Medical University, Ningxia Hui Autonomous Region, Yinchuan, China
| | - Ruifen Wei
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Minye Wang
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Gang Chen
- First People's Hospital of Aksu, Aksu, Xinjiang, China
| | - Yan Cheng
- Department of Ophthalmology, Xi'an No. 1 Hospital, No. 30, Fen Alley, South Street, Xi'an, Shaanxi, China.
| | - Wei Chen
- Department of Ophthalmology, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Department of Ophthalmology, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China.
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Shalaby WS, Shiuey EJ, Patel TM, Rapuano CJ, Syed ZA. Risk Factors for Progression of Graft Rejection to Graft Failure Following Penetrating Keratoplasty. Ocul Immunol Inflamm 2025:1-9. [PMID: 40035781 DOI: 10.1080/09273948.2025.2470883] [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: 08/15/2024] [Revised: 02/05/2025] [Accepted: 02/18/2025] [Indexed: 03/06/2025]
Abstract
PURPOSE To analyze the risk factors for graft failure in eyes with endothelial graft rejection following penetrating keratoplasty (PK). METHODS Single-center, retrospective study that included patients who underwent PK at Wills Eye Hospital (2007-2018) who later presented with endothelial graft rejection, defined as clinical appearance of keratic precipitates or anterior chamber reaction. Among patients with rejection across multiple grafts, only the first PK of the first eye with documented rejection was included. The primary outcome measures were progression to graft failure, defined as irreversible and visually significant stromal edema, haze, or scarring, and acute graft failure, defined as failure within 6 months of rejection. RESULTS 296 eyes from 296 patients were included with mean age of 54.4 ± 21.3 years. Average follow-up duration was 4.5 ± 2.9 years and rejection occurred 16.2 ± 18.7 months after transplantation. The rate of graft failure was 45.9% and the rate of acute failure was 31.4%. Predictors of failure after rejection included history of systemic autoimmune disorders (OR = 8.99, 95% CI = 2.03-39.77, p = 0.004), prior glaucoma surgery (OR = 2.73, 95% CI = 1.05-7.11, p = 0.039), and postoperative lens status as aphakia (OR = 7.59, 95% CI = 1.00-57.52, p = 0.0497). Predictors of acute graft failure after rejection included history of systemic autoimmune disorders (OR = 4.69, 95% CI = 1.20-18.33, p = 0.026), active microbial infection (OR = 3.52, 95% CI = 1.69-7.31, p = 0.001), and prior glaucoma surgery (OR = 3.50, 95% CI = 1.42-8.62, p = 0.006). CONCLUSION Systemic autoimmune disorders and prior glaucoma surgery predicted both overall and acute graft failure, suggesting more aggressive rejection episodes in these cohorts.
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Affiliation(s)
- Wesam Shamseldin Shalaby
- Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Tanta Medical School, Tanta University, Tanta, Egypt
| | - Eric J Shiuey
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Tejal M Patel
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Christopher J Rapuano
- Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Zeba A Syed
- Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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Feizi S, Javadi MA, Bayat K, Arzaghi M, Rahdar A, Ahmadi MJ. Machine learning methods to identify risk factors for corneal graft rejection in keratoconus. Sci Rep 2024; 14:29131. [PMID: 39587303 PMCID: PMC11589830 DOI: 10.1038/s41598-024-80967-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/22/2024] [Indexed: 11/27/2024] Open
Abstract
Machine learning can be used to identify risk factors associated with graft rejection after corneal transplantation for keratoconus. The study included all keratoconus eyes that underwent primary corneal transplantation from 1994 to 2021. Data relating to the recipient, donor, surgery, and postoperative course that might be associated with the occurrence of a graft rejection reaction were compiled. This study used five supervised learning algorithms including artificial neural network, support vector machine, gradient boosting, extra trees classifier, and random survival forests to select the most predictive factors for graft rejection. A total of 1214 consecutive eyes of 985 keratoconus patients were included in the study, and the technique of keratoplasty included penetrating keratoplasty in 574 eyes (47.3%) and deep anterior lamellar keratoplasty in 640 eyes (52.7%). The overall prevalence of first graft rejection was 28.1%. All five models had similar ability in identifying predictive factors for corneal graft rejection. Technique of keratoplasty was associated with an increased risk of graft rejection in all models. Other identified risk factors included patient age, keratoplasty in the fellow eye, donor age, graft endothelial cell density, duration of corticosteroid application, time from keratoplasty to complete suture removal, and suture-associated complications. It is advisable that in the absence of any contraindication, post-transplant keratoconus eyes receive a low dose topical corticosteroid until all sutures are removed.
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Affiliation(s)
- Sepehr Feizi
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Ophthalmic Research Center, Labbafinejad Medical Center, Boostan 9 St., Pasdaran Ave, Tehran, 16666, Iran.
| | - Mohammad Ali Javadi
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kia Bayat
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Arzaghi
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ali M, Dun C, Yenokyan G, Soiberman U, Jeng BH, Makary MA, Woreta F, Srikumaran D. Corneal Transplant Rejection Postvaccination Among Medicare Beneficiaries. Cornea 2024; 43:1392-1396. [PMID: 38456658 DOI: 10.1097/ico.0000000000003524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 01/23/2024] [Indexed: 03/09/2024]
Abstract
PURPOSE The purpose of this study was to describe the incidence of corneal graft rejection after COVID and influenza vaccination. METHODS Patients 65 years or older undergoing penetrating keratoplasty or endothelial keratoplasty any time between 2016 and 2021 followed by COVID or influenza vaccination in 2021 among the 100% Medicare Fee-For-Service database were included. Demographic and ocular history characteristics of patients with (cases) and without graft rejection (controls) were compared using the χ 2 test. RESULTS After COVID (n = 31,398) and influenza (n = 24,290) vaccination, 0.45% (n = 140) and 0.17% (n = 41) patients developed rejection within 90 days, respectively. There was no difference in the rate of graft rejection within 90 days relative to 90 to 180 days after vaccination after both COVID (90 days: 0.45% vs. 180 days: 0.61%, P = 0.37) and influenza (90 days: 0.17% vs. 180 days: 0.29%, P = 0.11) vaccines. For COVID vaccination, patients who underwent penetrating keratoplasty (n = 51, 0.97%; vs. endothelial keratoplasty = 89; 0.34%, P < 0.001), history of rejection up to 1 year before vaccination (n = 13; 1.30% vs. no history = 127, 0.42%; P < 0.001), and having an ocular comorbidity (n = 110, 0.54% vs. no ocular comorbidity = 30, 0.27%; P = 0.001) had higher rates of graft rejections, and most rejections were after 1 year postkeratoplasty (87.14%, n = 122). CONCLUSIONS The incidence of graft rejection postvaccination is low compared with the overall rates of rejection in the published literature. Most post-COVID vaccination graft rejections were after 1 year postkeratoplasty when corticosteroids are expected to have been tapered to lower doses. Surgeons may counsel patients regarding graft rejection symptoms, but overall low rates may not warrant pretreatment in low-risk keratoplasty patients.
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Affiliation(s)
- Muhammad Ali
- Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD
| | - Chen Dun
- Department of Surgery, Johns Hopkins University, Baltimore, MD
- Department of Biomedical Informatics and Data Science, Johns Hopkins University, Baltimore, MD
| | - Gayane Yenokyan
- Johns Hopkins Biostatistics Center, Johns Hopkins University, Baltimore, MD; and
| | - Uri Soiberman
- Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD
| | - Bennie H Jeng
- Department of Ophthalmology and Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Martin A Makary
- Department of Surgery, Johns Hopkins University, Baltimore, MD
| | - Fasika Woreta
- Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD
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Boroumand S, Rahmani M, Sigaroodi F, Ganjoury C, Parandakh A, Bonakdar A, Khani MM, Soleimani M. The landscape of clinical trials in corneal regeneration: A systematic review of tissue engineering approaches in corneal disease. J Biomed Mater Res B Appl Biomater 2024; 112:e35449. [PMID: 39032135 DOI: 10.1002/jbm.b.35449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 04/27/2024] [Accepted: 06/19/2024] [Indexed: 07/22/2024]
Abstract
The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.
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Affiliation(s)
- Safieh Boroumand
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahya Rahmani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faraz Sigaroodi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Camellia Ganjoury
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azim Parandakh
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Bonakdar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad-Mehdi Khani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoud Soleimani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Xiao Y, Zhong J, Yang J, Fu Z, Wang B, Peng L, Zuo X, Zhao X, He D, Yuan J. Myeloid-derived suppressor cells ameliorate corneal alkali burn through IL-10-dependent anti-inflammatory properties. Transl Res 2023; 262:25-34. [PMID: 37543286 DOI: 10.1016/j.trsl.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 06/03/2023] [Accepted: 07/23/2023] [Indexed: 08/07/2023]
Abstract
This study aims to investigate the efficiency and the underlying mechanism of myeloid-derived suppressor cells (MDSCs) in corneal alkali burns (CAB). In the study, CD11b+ Gr-1+ cells from C57BL/6J mice bone marrow were cultured and induced. Cell activity and immunoregulatory function were assessed by flow cytometry in vitro. The optimal strategy of MDSCs therapy was assessed by slit-lamp microscopy, and flow cytometry in vivo. The therapeutic effects of MDSCs and the critical signaling pathway were investigated by hematoxylin-eosin (HE) staining, slit-lamp microscopy, flow cytometry, and immunofluorescence. The expression level of the NLRP3 inflammasome pathway was examined. The crucial biochemical parameters of MDSCs were examined by RNA-seq and qPCR to screen out the key regulators. The mechanism of MDSCs' therapeutic effects was explored using MDSCs with IL-10 knockout/rescue by slit-lamp microscopy, HE staining, and qPCR evaluation. The cell frequencies of macrophages and neutrophils in the cornea were examined by flow cytometry in vivo. The results demonstrated that the induced MDSCs meet the standard of phenotypic and functional characteristics. The treatment of 5 × 105 MDSCs conjunctival injection on alternate days significantly ameliorated the disease development, downregulated the NLRP3 inflammasome pathway, and decreased the cell frequencies of macrophages and neutrophils in vivo significantly. IL-10 was screened out to be the critical factor for MDSCs therapy. The therapeutic effects of MDSCs were impaired largely by IL-10 knock-out and saved by the IL-10 supplement. In conclusion, MDSCs therapy is a promising therapeutic solution for CAB. MDSCs fulfilled immunoregulatory roles for CAB by IL-10-dependent anti-inflammatory properties.
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Affiliation(s)
- Yichen Xiao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Jing Zhong
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Jiahui Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Zhenyuan Fu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Bowen Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Lulu Peng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Xin Zuo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Xuan Zhao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Dalian He
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China
| | - Jin Yuan
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong, China.
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Mandal S, Maharana PK, Kaweri L, Asif MI, Nagpal R, Sharma N. Management and prevention of corneal graft rejection. Indian J Ophthalmol 2023; 71:3149-3159. [PMID: 37602601 PMCID: PMC10565940 DOI: 10.4103/ijo.ijo_228_23] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/03/2023] [Accepted: 04/04/2023] [Indexed: 08/22/2023] Open
Abstract
The management of an episode of corneal graft rejection (CGR) is primarily by corticosteroids. Immunomodulators are useful for long-term immunosuppression and in dealing with cases of high-risk (HR) corneal grafts. The classical signs of CGR following penetrating keratoplasty (PKP) include rejection line, anterior chamber (AC) reaction, and graft edema. However, these signs may be absent or subtle in cases of endothelial keratoplasty (EK). Prevention of an episode of graft rejection is of utmost importance as it can reduce the need for donor cornea significantly. In our previous article (IJO_2866_22), we had discussed about the immunopathogenesis of CGR. In this review article, we aim to discuss the various clinical aspects and management of CGR.
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Affiliation(s)
- Sohini Mandal
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Prafulla K Maharana
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Luci Kaweri
- Consultant, Narayana Nethralaya, Bengaluru, Karnataka, India
| | | | - Ritu Nagpal
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Namrata Sharma
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
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Tian Y, Zhang T, Li J, Tao Y. Advances in development of exosomes for ophthalmic therapeutics. Adv Drug Deliv Rev 2023; 199:114899. [PMID: 37236425 DOI: 10.1016/j.addr.2023.114899] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 04/18/2023] [Accepted: 05/21/2023] [Indexed: 05/28/2023]
Abstract
Exosomes contain multiple bioactive molecules and maintain the connection between cells. Recent advances in exosome-based therapeutics have witnessed unprecedented opportunities in treating ophthalmic diseases, including traumatic diseases, autoimmune diseases, chorioretinal diseases and others. Utilization of exosomes as delivery vectors to encapsulate both drugs and therapeutic genes could yield higher efficacy and avoid the unnecessary immune responses. However, exosome-based therapies also come with some potential ocular risks. In this review, we first present a general introduction to exosomes. Then we provide an overview of available applications and discuss their potential risks. Moreover, we review recently reported exosomes as delivery vectors for ophthalmic diseases. Finally, we put forward future perspectives to grapple with its translation and underlying issues.
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Affiliation(s)
- Ying Tian
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Tao Zhang
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Jing Li
- Beijing Key Laboratory of DNA Damage Response, College of Life Sciences, Capital Normal University, Beijing 100048, PR China
| | - Yong Tao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China.
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Kumar R, Sinha NR, Mohan RR. Corneal gene therapy: Structural and mechanistic understanding. Ocul Surf 2023; 29:279-297. [PMID: 37244594 PMCID: PMC11926995 DOI: 10.1016/j.jtos.2023.05.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 05/29/2023]
Abstract
Cornea, a dome-shaped and transparent front part of the eye, affords 2/3rd refraction and barrier functions. Globally, corneal diseases are the leading cause of vision impairment. Loss of corneal function including opacification involve the complex crosstalk and perturbation between a variety of cytokines, chemokines and growth factors generated by corneal keratocytes, epithelial cells, lacrimal tissues, nerves, and immune cells. Conventional small-molecule drugs can treat mild-to-moderate traumatic corneal pathology but requires frequent application and often fails to treat severe pathologies. The corneal transplant surgery is a standard of care to restore vision in patients. However, declining availability and rising demand of donor corneas are major concerns to maintain ophthalmic care. Thus, the development of efficient and safe nonsurgical methods to cure corneal disorders and restore vision in vivo is highly desired. Gene-based therapy has huge potential to cure corneal blindness. To achieve a nonimmunogenic, safe and sustained therapeutic response, the selection of a relevant genes, gene editing methods and suitable delivery vectors are vital. This article describes corneal structural and functional features, mechanistic understanding of gene therapy vectors, gene editing methods, gene delivery tools, and status of gene therapy for treating corneal disorders, diseases, and genetic dystrophies.
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Affiliation(s)
- Rajnish Kumar
- Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, 65201, USA; One-health One-medicine Vision Research Program, Departments of Veterinary Medicine and Surgery & Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow campus, UP, 226028, India
| | - Nishant R Sinha
- Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, 65201, USA; One-health One-medicine Vision Research Program, Departments of Veterinary Medicine and Surgery & Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA
| | - Rajiv R Mohan
- Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, 65201, USA; One-health One-medicine Vision Research Program, Departments of Veterinary Medicine and Surgery & Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, 65212, USA.
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10
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Lyu Y, Liu Y, He H, Wang H. Application of Silk-Fibroin-Based Hydrogels in Tissue Engineering. Gels 2023; 9:gels9050431. [PMID: 37233022 DOI: 10.3390/gels9050431] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/12/2023] [Accepted: 05/17/2023] [Indexed: 05/27/2023] Open
Abstract
Silk fibroin (SF) is an excellent protein-based biomaterial produced by the degumming and purification of silk from cocoons of the Bombyx mori through alkali or enzymatic treatments. SF exhibits excellent biological properties, such as mechanical properties, biocompatibility, biodegradability, bioabsorbability, low immunogenicity, and tunability, making it a versatile material widely applied in biological fields, particularly in tissue engineering. In tissue engineering, SF is often fabricated into hydrogel form, with the advantages of added materials. SF hydrogels have mostly been studied for their use in tissue regeneration by enhancing cell activity at the tissue defect site or counteracting tissue-damage-related factors. This review focuses on SF hydrogels, firstly summarizing the fabrication and properties of SF and SF hydrogels and then detailing the regenerative effects of SF hydrogels as scaffolds in cartilage, bone, skin, cornea, teeth, and eardrum in recent years.
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Affiliation(s)
- Yihan Lyu
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Yusheng Liu
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Houzhe He
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Hongmei Wang
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
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11
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Shiuey EJ, Zhang Q, Rapuano CJ, Ayres BD, Hammersmith KM, Nagra PK, Syed ZA. Prior Contralateral Penetrating Keratoplasty Is a Risk Factor for Second Eye Graft Rejection. Ocul Immunol Inflamm 2023; 31:257-262. [PMID: 35050842 DOI: 10.1080/09273948.2021.2024860] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
AIMS To determine whether prior penetrating keratoplasty (PK) in the contralateral eye increases risk of second eye PK graft rejection. METHODS Cohort study of 593 consecutive PKs in transplant-naïve eyes (500 unilateral cases, 93 second eyes). Outcomes were compared between PKs performed in eyes with versus without a history of prior contralateral eye PK. Risks of rejection and failure were estimated using Cox proportional hazards models. RESULTS Mean age was 53.7 ± 23.3 years; average follow-up was 4.00 ± 2.87 years. Rejection occurred in 211 (35.6%) grafts. The incidence of rejection was 34.0% in unilateral cases and 44.1% in second eyes with PK in the contralateral eye. Prior contralateral PK was a significant risk factor for graft rejection (HR = 1.42, 95% CI 1.01-2.01, p = .045). CONCLUSION Contralateral PK is associated with increased risk of second eye graft rejection. Loss of ocular immune privilege is a possible mechanism.
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Affiliation(s)
- Eric J Shiuey
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Qiang Zhang
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Biostatistics Consulting Core, Vickie and Jack Farber Vision Research Center, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
| | - Christopher J Rapuano
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
| | - Brandon D Ayres
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
| | - Kristin M Hammersmith
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
| | - Parveen K Nagra
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
| | - Zeba A Syed
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.,Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
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12
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Jia S, Bu Y, Lau DSA, Lin Z, Sun T, Lu WW, Lu S, Ruan C, Chan CHJ. Advances in 3D bioprinting technology for functional corneal reconstruction and regeneration. Front Bioeng Biotechnol 2023; 10:1065460. [PMID: 36686254 PMCID: PMC9852906 DOI: 10.3389/fbioe.2022.1065460] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 12/19/2022] [Indexed: 01/09/2023] Open
Abstract
Corneal transplantation constitutes one of the major treatments in severe cases of corneal diseases. The lack of cornea donors as well as other limitations of corneal transplantation necessitate the development of artificial corneal substitutes. Biosynthetic cornea model using 3D printing technique is promising to generate artificial corneal structure that can resemble the structure of the native human cornea and is applicable for regenerative medicine. Research on bioprinting artificial cornea has raised interest into the wide range of materials and cells that can be utilized as bioinks for optimal clarity, biocompatibility, and tectonic strength. With continued advances in biomaterials science and printing technology, it is believed that bioprinted cornea will eventually achieve a level of clinical functionality and practicality as to replace donated corneal tissues, with their associated limitations such as limited or unsteady supply, and possible infectious disease transmission. Here, we review the literature on bioprinting strategies, 3D corneal modelling, material options, and cellularization strategies in relation to keratoprosthesis design. The progress, limitations and expectations of recent cases of 3D bioprinting of artifial cornea are discussed. An outlook on the rise of 3D bioprinting in corneal reconstruction and regeneration is provided.
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Affiliation(s)
- Shuo Jia
- Department of Ophthalmology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yashan Bu
- Department of Ophthalmology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Dzi-Shing Aaron Lau
- Department of Orthopedic and Traumatology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Zhizhen Lin
- Department of Ophthalmology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Tianhao Sun
- Department of Orthopedic and Traumatology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Shenzhen Gangqing Biomedical Technology Co. Ltd, Shenzhen, China
| | - Weijia William Lu
- Department of Orthopedic and Traumatology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Research Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Sheng Lu
- Department of Orthopedic Surgery, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Changshun Ruan
- Research Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Cheuk-Hung Jonathan Chan
- Department of Ophthalmology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
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13
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Cruz GKP, Júnior MAF, Goldiano JAS, Fernandes GHDP, Flores VGT, Jarcem KG. Donation Process and Evaluation of Corneal Tissue in a Slit Lamp. Transplant Proc 2022; 54:1190-1196. [PMID: 35811151 DOI: 10.1016/j.transproceed.2022.03.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/13/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND The process of capturing and classifying the viability of corneal tissue for corneal transplantation is complex. The biomicroscopic examination is one of the techniques used to evaluate the quality of corneal tissues. The aim of this study was to analyze the relationship between the evaluation criteria used in biomicroscopic examination using a slit lamp and the classification of the quality of corneal tissue. METHODS This is a longitudinal, retrospective cohort study, performed at the Human Ocular Tissue Bank in the state of Rio Grande do Norte, Brazil. The sample consisted of 419 corneas donated between 2005 to 2016. RESULTS After the evaluation, the 419 corneas were classified as excellent (8 -1.91%), good (217 - 51.79%), regular (85 - 20.29%), and bad (109 - 26.01%). The classification of corneal quality attributed by ophthalmologists considered 13 criteria: senile arch, scars, epithelial defect, epithelial exposure, stromal infiltrate, subepithelial opacity, pterygium, Descemet's folds, stromal edema, stromal streak, cornea guttata, specular reflex, and cell loss endothelial. The quality of the cornea classified as excellent and good showed a statistically significant association (P value < .05) with senile arch, scar, epithelial defect, epithelial exposure, Descemet's folds, stromal edema, stromal streak, cornea guttata, specular reflex, and losses of endothelial cells; they had evaluated criteria that were absent or slightly present. CONCLUSIONS The evaluation of the corneal quality for corneal transplantation should involve the implementation of reliable techniques and trained, qualified professionals. There is a need to create evaluation instruments that consider the criteria according to their degree of interference in the quality of corneal tissue.
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Affiliation(s)
| | | | | | | | | | - Karine Gomes Jarcem
- Department of Nursing, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
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14
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Abstract
PURPOSE OF REVIEW Corneal graft rejection has been reported after coronavirus disease 2019 (COVID-19) vaccination. The purpose of this review is to evaluate the literature regarding corneal graft rejection after vaccination, including rejection rates and risk factors. We aim to create a framework to identify patients who are at higher risk for graft rejection and may warrant consideration of prophylactic interventions. RECENT FINDINGS Graft rejection has been reported following administration of mRNA, viral vector, and inactivated whole-virion COVID-19 vaccines. Most cases had additional risk factors associated with rejection. Vaccination increases circulation of proinflammatory cytokines, CD4+ and CD8+ T-cell responses, and antispike neutralizing antibody, all of which may contribute to graft rejection. Two prospective studies have found no relationship between recent vaccination and rejection but 20% of cornea specialists report to have seen a vaccine-associated rejection and 22% recommend delaying vaccination in certain circumstances. Many specialists recommend prophylactic topical corticosteroids before and after vaccination to mitigate rejection risk but there is no evidence to support this practice on a wider scale. SUMMARY Our framework identified 96.8% of penetrating keratoplasty patients with vaccine-associated rejection as higher risk. Further research is needed in order to develop evidence-based guidelines.
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Affiliation(s)
- Sarah P Dugan
- Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA
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15
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Risk factors of rejection after penetrating keratoplasty: a retrospective monocentric study. Graefes Arch Clin Exp Ophthalmol 2022; 260:3627-3638. [PMID: 35546638 DOI: 10.1007/s00417-022-05691-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/15/2022] [Accepted: 04/27/2022] [Indexed: 11/04/2022] Open
Abstract
PURPOSE To assess risk factors of rejection after penetrating keratoplasty (PKP). METHODS This retrospective monocentric study assessed risk factors for rejection in patients who underwent PKP at Montpellier University Hospital between June 2005 and September 2018. Graft and donor data were obtained from our tissue bank in Montpellier. Clinical data of recipients were recorded from medical files. Survival was estimated by the Kaplan-Meir method. Potential risk factors of rejection were assessed by multivariate Cox proportional hazards analysis, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS Among the 316 consecutive patients (59% male, mean SD] age 52 [17]), 360 eyes underwent PKP. Indications for PKP were bullous keratopathy (27%), infectious keratitis (20%), and keratoconus (15%). The median follow-up was 44 months (IQR 22-73). The overall graft survival and irreversible rejection rate at 5 years were 70% and 29%, respectively. Factors associated with risk of rejection were prior indication for graft rejection (SHR [CI 95%] = 7.8 [2.6-23.1]), trauma (SHR [CI 95%] = 3.6 [1.1-11.7]), and infectious keratitis (SHR [CI 95%] = 2.7 [1.2-11.1]), history of corneal neovascularization (SHR [CI 95%] = 2.1 [1.2-3.8]), hypertonia (SHR [CI 95%] = 2.8 [1.8-4.3]), and mixed sex matching (SHR [CI 95%] = 2.0 [1.01-4.0]). CONCLUSION The significant risk factors of graft rejection after PKP found in this study agree with those from major international cohorts: prior indication for graft rejection, history of neovascularization and high intraocular pressure. Sex matching donor-recipient is a most recent parameter in the literature confirmed by the present analysis. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04791696.
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16
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Ong HS, Chiam N, Htoon HM, Kumar A, Arundhati A, Mehta JS. The Effects of Donor-Recipient Age and Sex Compatibility in the Outcomes of Deep Anterior Lamellar Keratoplasties. Front Med (Lausanne) 2022; 8:801472. [PMID: 35155480 PMCID: PMC8828935 DOI: 10.3389/fmed.2021.801472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
PurposeCorneal transplantations are the commonest allogenic transplant surgeries performed worldwide. Transplantable grade donor cornea is a finite resource. There is thus an impetus for eye banks to optimize the use of each harvested cornea, and clinicians to minimize the risks of graft rejection and failure. With better survival and lower rejection rates, anterior lamellar keratoplasty has gained popularity as an alternative technique to full-thickness penetrating keratoplasty, for the treatment of corneal stromal diseases. This study evaluated the effects of donor-recipient age- and sex-matching on the outcomes of eyes that had undergone deep anterior lamellar keratoplasty (DALK) surgeries.DesignObservational cross-sectional study (national corneal graft registry data).SubjectsAll DALK surgeries performed in a tertiary ophthalmic hospital over an 11-year period.MethodsTo analyse the effects of donor-recipient sex-matching, transplantations were classified as “presumed H-Y incompatible” (male donor to female recipient) or “presumed H-Y compatible” (all other donor-recipient sex combinations). For age-matching, differences in donor and recipient ages were calculated. Cox proportional hazards regressions were used to evaluate the influence of donor-recipient sex-matching and age-matching on graft failure and rejection.Main Outcome MeasuresRates of graft failure and rejection within each group.Results401 eyes were included. 271 (67.6%) transplants were presumed H-Y compatible. 29 (7.2%) grafts failed and 9 (2.2%) grafts rejected. There were trends of lower hazard ratios (HRs) in graft failure and rejection in the presumed H-Y compatible group [HRs: 0.59 (95% CI 0.20–1.77, p = 0.34) and 0.93 (95% CI 0.22–3.89, p = 0.926), respectively]. Median difference in age between recipients and donors was 15.0 years (IQR −2.8–34.3). The HRs of graft failure and rejection were not influenced by donor-recipient age [HRs per 1-year increase in age difference: 0.995 (95% CI 0.98–1.01, p = 0.483) and 1.01 (95% CI 0.99–1.03, p = 0.394), respectively].ConclusionIn eyes that had undergone DALK surgeries, no significant influence of donor-recipient sex- or age-matching on graft rejection and failure was observed. Without strong evidence and the limitations of obtaining sample sizes required for an adequately powered study, the benefits of sex- and age-matching of donors and recipients during graft allocation for DALK surgeries is currently inconclusive.
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Affiliation(s)
- Hon Shing Ong
- Corneal and External Diseases Department, Singapore National Eye Centre, Singapore, Singapore
- Singapore Eye Research Institute, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Hon Shing Ong
| | - Nathalie Chiam
- Corneal and External Diseases Department, Singapore National Eye Centre, Singapore, Singapore
| | - Hla Myint Htoon
- Singapore Eye Research Institute, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Ashish Kumar
- Corneal and External Diseases Department, Singapore National Eye Centre, Singapore, Singapore
| | - Anshu Arundhati
- Corneal and External Diseases Department, Singapore National Eye Centre, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Jodhbir S. Mehta
- Corneal and External Diseases Department, Singapore National Eye Centre, Singapore, Singapore
- Singapore Eye Research Institute, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- School of Material Science and Engineering, Nanyang Technological University, Singapore, Singapore
- *Correspondence: Jodhbir S. Mehta
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17
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Corneal Allografts: Factors for and against Acceptance. J Immunol Res 2021; 2021:5372090. [PMID: 34642632 PMCID: PMC8502534 DOI: 10.1155/2021/5372090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 08/26/2021] [Accepted: 09/21/2021] [Indexed: 12/21/2022] Open
Abstract
Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.
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Pereira Cruz GK, Ferreira Júnior MA, Pereira Frota O, Ferraz Teston E, Pereira Santos VE, Fortes Vitor A, Penza Cardoso M, Rodrigues Leocates de Moraes FR. Cornea donation process and tissue quality for transplantation. PLoS One 2021; 16:e0249927. [PMID: 33878135 PMCID: PMC8057599 DOI: 10.1371/journal.pone.0249927] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/27/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction The quality of the corneal tissue can be influenced by several factors inherent to the recipient, donor, and to the donation and transplantation process. The donated corneal tissue can be classified by its quality as excellent, good, regular, bad, or unacceptable for transplantation, evaluating it in a slit lamp. Objective To analyze the relationship between the clinical and sociodemographic variables of the donors and the donation process and the classification of the quality of the corneal tissue collected for transplantation. Methods This is an epidemiologic study, retrospective cohort type, which addressed the process of cornea donation by the Human Eye Tissue Bank in a reference service in Northeast Brazil. The sample consisted of corneas processed by the Human Eye Tissue Bank of Rio Grande do Norte (n = 419). For descriptive and inferential analysis, the study used the Statistical Package for the Social Sciences (SPSS) software, version 25.0, and considered a significance level of 0.05. Logistic regression analysis was used for the adjustment of the final model. Results It was verified that the epidemiological profile showed a prevalence of individuals with a mean age of 42.54 years old, male (73.99%), and living in the metropolitan region of the state capital (75.66%). When analyzing the relationship between the clinical and sociodemographic variables of the donors, it was identified that those aged 45 years old or less had better quality corneas (excellent and good), while the chronological variables were predictive factors for corneas of regular and bad qualities. Conclusion The identification of the factors inherent to the donation process and predictors of corneal tissue quality contribute to minimizing the risk of transplantation and to a better ocular prognosis.
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Affiliation(s)
| | - Marcos Antonio Ferreira Júnior
- Nursing Department, Health and Development in The Midwest Region, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Oleci Pereira Frota
- Nursing Department, Health and Development in The Midwest Region, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Elen Ferraz Teston
- Nursing Department, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | | | - Allyne Fortes Vitor
- Nursing Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
| | - Mayk Penza Cardoso
- Nursing Department, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
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Zafar S, Wang P, Woreta FA, Aziz K, Makary M, Srikumaran D. Risk Factors for Repeat Keratoplasty after Endothelial Keratoplasty in the Medicare Population. Am J Ophthalmol 2021; 221:287-298. [PMID: 32791066 DOI: 10.1016/j.ajo.2020.08.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/03/2020] [Accepted: 08/03/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To evaluate long-term rates of repeated keratoplasty after endothelial keratoplasty (EK), and to explore risk factors associated with graft failure. DESIGN Retrospective, cohort study. METHODS Population-based using 2010-2019 Medicare carrier claims. STUDY POPULATION Medicare beneficiaries aged ≥65 years who underwent endothelial keratoplasty (EK) procedures. Main outcome measures were 1) occurrence of repeated keratoplasty for the overall cohort as well as stratified by clinical indication, and 2), risk factors associated with repeated keratoplasty. The probability of undergoing repeated keratoplasty for different indications was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was constructed to determine patient and physician factors associated with the risk of repeated keratoplasty. RESULTS A total of 94,829 Medicare EK procedures (N = 71,040 unique patients) were included in the analysis. Over the study period, 11,013 of 94,829 EK procedures were followed by repeated keratoplasty. The overall probability of receiving a repeated keratoplasty was 6.1% at 6 months, 7.6% at 1 year, 14.3% at 5 years and 16.9% at 8 years. The probability of repeated keratoplasty was highest for procedures performed for prior failed grafts: 10.2% at 1 year, 29.9% at 8 years. Whereas 6.4% and 11.4% of grafts performed for Fuchs' endothelial dystrophy (FED) required repeated keratoplasty at 1 and 8 years of follow-up, respectively. For bullous keratoplasty and/or corneal edema, 8.6% and 22% of grafts underwent repeated keratoplasty at 1 and 8 years, respectively. In a multivariate analysis, patient factors associated with increased risk of repeated keratoplasty were black (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.20-1.38) or Asians (HR: 1.26; 95% CI: 1.10-1.45) having a glaucoma diagnosis (HR: 1.53; 95% CI: 1.46-1.60), prior glaucoma surgery (HR: 1.26; 95% CI: 1.18-1.35), and concurrent glaucoma surgery (HR: 1.31; 95% CI: 1.20-1.44). Surgeons with higher EK volumes had a decreased risk of repeated keratoplasty. Physicians who graduated medical school >30 years previously had increased risk of repeated keratoplasty compared to those who graduated within 10 years (HR: 1.16; 95% CI: 1.10-1.23). CONCLUSIONS Blacks or Asians, comorbid glaucoma, concurrent or prior glaucoma surgery, and lower volumes of surgery are associated with increased risk of repeated keratoplasty. Racial disparities identified in this study warrant further investigation.
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20
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Alio JL, Montesel A, El Sayyad F, Barraquer RI, Arnalich-Montiel F, Alio Del Barrio JL. Corneal graft failure: an update. Br J Ophthalmol 2020; 105:1049-1058. [DOI: 10.1136/bjophthalmol-2020-316705] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/29/2020] [Accepted: 07/03/2020] [Indexed: 11/04/2022]
Abstract
Corneal graft surgery is one of the most successful forms of human solid-tissue transplantation, and nowadays, there is a worldwide expansion of the surgical volume of corneal grafts. This surgery is continuously evolving, with new surgical techniques and postoperative treatments that have considerably increased the chance of survival for the grafts. Despite the high rate of success, corneal transplantation is still complicated by a relevant risk of graft failure. This study investigates the causes that lead to the failure of the different corneal graft surgical techniques and provides an updated synthesis on this topic. A comprehensive review of the main pathological pathways that determine the failure of corneal grafts is provided, analysing the main risk factors and disclosing the survival rates of the principal form of corneal grafts. Our results revealed that penetrating keratoplasty has higher failure rates than lamellar keratoplasty, with immunological rejection being the leading cause of graft failure, followed by late endothelial failure (LEF) and ocular surface disorders. Postoperative glaucoma and dehiscence of the surgical wound represent other important causes of failure. Endothelial keratoplasty showed the lowest rates of failure in the mid-term, with LEF, detachment of the graft and primary graft failure representing the most common pathological reasons for failure.
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21
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Barraquer RI, Pareja-Aricò L, Gómez-Benlloch A, Michael R. Risk factors for graft failure after penetrating keratoplasty. Medicine (Baltimore) 2019; 98:e15274. [PMID: 31027083 PMCID: PMC6831321 DOI: 10.1097/md.0000000000015274] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 03/04/2019] [Accepted: 03/25/2019] [Indexed: 11/30/2022] Open
Abstract
The objective of our study was to define principal risk factors for graft failure in patients who underwent penetrating keratoplasty (PK).Retrospective data obtained from a cohort of 895 penetrating keratoplasties performed between 2001 and 2006 were analysed. Recipient related factors, graft characteristics, and surgical technique were assessed in a univariate analysis and with a multivariate proportional hazard model to detect principal risk factors for definitive graft failure.Multivariate analysis showed clear significance for diagnosis and number of previous grafts and border line significance for the oldest donor age group. Patients with keratoconus had the best 10-year survival estimate (95%), followed by endothelial and stromal dystrophies (both 55%), infectious leukomas (49%), trauma (33%) and chemical burns (14%). Primary PK grafts had a survival rate of 81%, second grafts of 33% and third or more grafts of 16%. Overall 10-year survival estimate based on univariate analysis was found to be 65%.In conclusion, we found that primary diagnosis and previous graft failures in the recipient are the most important risk factors of graft failure after a PK.
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Affiliation(s)
- Rafael Ignacio Barraquer
- Institut Universitari Barraquer, Universitat Autònoma de Barcelona
- Centro de Oftalmología Barraquer
- Universitat Internacional de Catalunya, Barcelona
| | - Luis Pareja-Aricò
- Institut Universitari Barraquer, Universitat Autònoma de Barcelona
- Hospital Clinico Universitario Valladolid, Universidad de Valladolid, Valladolid, Spain
| | - Alba Gómez-Benlloch
- Institut Universitari Barraquer, Universitat Autònoma de Barcelona
- Centro de Oftalmología Barraquer
| | - Ralph Michael
- Institut Universitari Barraquer, Universitat Autònoma de Barcelona
- Centro de Oftalmología Barraquer
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Stulting RD, Lass JH, Terry MA, Benetz BA, Cohen NJ, Ayala AR, Maguire MG, Croasdale C, Daoud YJ, Dunn SP, Goins KM, Gupta PC, Macsai MS, Mian SI, Pramanik S, Rose-Nussbaumer J, Song JC, Stark WJ, Sugar A, Verdier DD, Szczotka-Flynn LB. Factors Associated With Graft Rejection in the Cornea Preservation Time Study. Am J Ophthalmol 2018; 196:197-207. [PMID: 30308200 DOI: 10.1016/j.ajo.2018.10.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 09/25/2018] [Accepted: 10/02/2018] [Indexed: 01/03/2023]
Abstract
PURPOSE To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN Cohort study within a multicenter randomized clinical trial. METHODS A total of 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0-7 days (n = 675) or 8-14 days (n = 655) and followed for 3 years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection. RESULTS Cumulative probability of definite graft rejection was 3.6% (99% confidence interval 2.5%-5.3%). Younger recipient age was associated with graft rejection (P < .001; hazard ratio: 0.53 [0.33, 0.83] per decade). PT, donor-recipient sex mismatch, recipient diagnosis, recipient race, graft size, discontinuation of topical corticosteroids and immune-modulators, prior immunizations within 3 months, and prior glaucoma surgery were not associated with rejection (P > .01). Among clear grafts with an ECD measurement at baseline and 3 years (n = 913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (n = 27) than in those that did not (n = 886) (48% vs 38%, P = .03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS. CONCLUSIONS Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure.
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Affiliation(s)
| | - Jonathan H Lass
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio, USA.
| | | | - Beth Ann Benetz
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio, USA
| | | | | | - Maureen G Maguire
- Center for Preventive Ophthalmology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Yassine J Daoud
- The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA
| | - Steven P Dunn
- Michigan Cornea Consultants, P.C., Southfield, Michigan, USA
| | - Kenneth M Goins
- University of Iowa Department of Ophthalmology and Visual Sciences, Iowa City, Iowa, USA
| | - Pankaj C Gupta
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio, USA
| | - Marian S Macsai
- Northshore University Health System, Glenview, Illinois, USA
| | - Shahzad I Mian
- Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Jennifer Rose-Nussbaumer
- University of California - San Francisco, and Francis I Proctor Foundation, San Francisco, California, USA
| | - Jonathan C Song
- University of Southern California Roski Eye Institute, Los Angeles, California, USA
| | - Walter J Stark
- The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA
| | - Alan Sugar
- Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Loretta B Szczotka-Flynn
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio, USA
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Ludwig PE, Huff TJ, Zuniga JM. The potential role of bioengineering and three-dimensional printing in curing global corneal blindness. J Tissue Eng 2018; 9:2041731418769863. [PMID: 29686829 PMCID: PMC5900811 DOI: 10.1177/2041731418769863] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023] Open
Abstract
An insufficiency of accessible allograft tissue for corneal transplantation leaves many impaired by untreated corneal disease. There is promise in the field of regenerative medicine for the development of autologous corneal tissue grafts or collagen-based scaffolds. Another approach is to create a suitable corneal implant that meets the refractive needs of the cornea and is integrated into the surrounding tissue but does not attempt to perfectly mimic the native cornea on a cellular level. Materials that have been investigated for use in the latter concept include natural polymers such as gelatin, semisynthetic polymers like gelatin methacrylate, and synthetic polymers. There are advantages and disadvantages inherent in natural and synthetic polymers: natural polymers are generally more biodegradable and biocompatible, while synthetic polymers typically provide greater control over the characteristics or property adjustment of the materials. Additive manufacturing could aid in the precision production of keratoprostheses and the personalization of implants.
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Affiliation(s)
| | - Trevor J Huff
- Creighton University School of Medicine, Omaha, NE, USA
| | - Jorge M Zuniga
- Department of Biomechanics, University of Nebraska Omaha, Omaha, NE, USA.,Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile
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24
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Chen Z, You J, Liu X, Cooper S, Hodge C, Sutton G, Crook JM, Wallace GG. Biomaterials for corneal bioengineering. ACTA ACUST UNITED AC 2018; 13:032002. [PMID: 29021411 DOI: 10.1088/1748-605x/aa92d2] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Corneal transplantation is an important surgical treatment for many common corneal diseases. However, a worldwide shortage of tissue from suitable corneal donors has meant that many people are not able to receive sight-restoring operations. In addition, rejection is a major cause of corneal transplant failure. Bioengineering corneal tissue has recently gained widespread attention. In order to facilitate corneal regeneration, a range of materials is currently being investigated. The ideal substrate requires sufficient tectonic durability, biocompatibility with cultured cellular elements, transparency, and perhaps biodegradability and clinical compliance. This review considers the anatomy and function of the native cornea as a precursor to evaluating a variety of biomaterials for corneal regeneration including key characteristics for optimal material form and function. The integration of appropriate cells with the most appropriate biomaterials is also discussed. Taken together, the information provided offers insight into the requirements for fabricating synthetic and semisynthetic corneas for in vitro modeling of tissue development and disease, pharmaceutical screening, and in vivo application for regenerative medicine.
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Affiliation(s)
- Zhi Chen
- ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales 2519, Australia
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Gulias-Cañizo R, Gonzalez-Salinas R, Hernandez-Zimbron LF, Hernandez-Quintela E, Sanchez-Huerta V. Indications and outcomes of pediatric keratoplasty in a tertiary eye care center: A retrospective review. Medicine (Baltimore) 2017; 96:e8587. [PMID: 29137083 PMCID: PMC5690776 DOI: 10.1097/md.0000000000008587] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
To evaluate indications and outcomes of pediatric keratoplasty in a tertiary eye center, and identify factors that affect visual outcomes.We performed a retrospective review of penetrating keratoplasty in children aged 0 to 18 years between 1995 and 2011 in the Asociación para Evitar la Ceguera en México IAP, Hospital "Dr. Luis Sánchez Bulnes".A total of 574 penetrating keratoplasties were performed during the study interval. Median follow-up was 5.0 years. Main indications included keratoconus (55.58%), postherpetic scarring (9.58%), traumatic opacities (7.49%), and bullous keratopathy (6.09%). Rejection rates at 5 years were 27% overall, and among indications, keratoconus showed the best graft survival at 60-months follow-up (85%). The percentage of patients with best corrected visual acuity (BCVA) posttransplant >20/400 at 5 years in the nonrejection group was 81.25% and 82.74% in < and > 10 years of age (YOA) groups, respectively, versus a BCVA posttransplant > 20/400 at 5 years in the rejection group of 53.68% and 51.72% in < and > 10 YOA groups, respectively. There was a statistically significant reduced rejection rate between genders at 18 months of follow-up, favoring males.Despite being considered a high-risk procedure in children, penetrating keratoplasty can achieve good results, especially in patients with keratoconus. It can achieve significative improvements of visual acuity, provided there is an adequate follow-up and treatment adherence.
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Affiliation(s)
- Rosario Gulias-Cañizo
- Research Department, Association to Prevent Blindness in Mexico IAP, “Dr. Luis Sanchez Bulnes Hospital”
- Cell Biology Department, Center for Advanced Research and Studies of the IPN, CINVESTAV-IPN
| | - Roberto Gonzalez-Salinas
- Research Department, Association to Prevent Blindness in Mexico IAP, “Dr. Luis Sanchez Bulnes Hospital”
| | | | - Everardo Hernandez-Quintela
- Cornea Department, Association to Prevent Blindness in Mexico IAP, “Dr. Luis Sanchez Bulnes Hospital”, Mexico City, Mexico
| | - Valeria Sanchez-Huerta
- Cornea Department, Association to Prevent Blindness in Mexico IAP, “Dr. Luis Sanchez Bulnes Hospital”, Mexico City, Mexico
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State of the Art and Beyond: Anterior Segment Diagnostics Genetic Diagnostics in Corneal Disease. Int Ophthalmol Clin 2017; 57:13-26. [PMID: 28590278 DOI: 10.1097/iio.0000000000000178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Purpose The aim of the study was to evaluate the various donor and recipient factors associated with short-term prevalence of surface epithelial keratopathy after optical penetrating keratoplasty (OPK). Methods Preoperative and postoperative data of 91 eyes of 91 patients were reviewed retrospectively who had undergone OPK from March 2013 to February 2016. Donor and recipient data were analyzed for age and sex of the donor, cause of death, death to enucleation time (DET), death to preservation time (DPT), enucleation to utilisation time (EUT) and total time (TT), age and sex of recipient, indications of penetrating keratoplasty (PK), associated glaucoma and recipient size (RS). The presence of various epitheliopathies were recorded at various postoperative visits. Results The range of age of recipient in this study was 10–83 yrs (mean 49.19 ± 19.35 yrs). The donor age ranged in between 17 and 95 years (70.27 ± 15.11 years). Age and preoperative diagnosis of host showed significant influence on epitheliopathy till two weeks and one month post-PK (P = 0.032 and 0.05), respectively. Donor's age and gender showed significant impact on surface keratopathy (SK) till two weeks follow-up with P value of 0.04 and 0.004, respectively. DET, DPT, EUT, and TT affected the surface epithelium significantly with P value of 0.007, 0.001, 0.05, and 0.03, respectively. On first postoperative day 33 (36.26%) eyes developed epithelial defect involving >1/2 of cornea. Conclusion Various donor and recipient factors showed influence on various epithelial abnormalities of surface epithelium in early postoperative period.
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Jabbehdari S, Rafii AB, Yazdanpanah G, Hamrah P, Holland EJ, Djalilian AR. Update on the Management of High-Risk Penetrating Keratoplasty. CURRENT OPHTHALMOLOGY REPORTS 2017; 5:38-48. [PMID: 28959505 DOI: 10.1007/s40135-017-0119-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW In this article, we review the indications and latest management of high-risk penetrating keratoplasty. RECENT FINDINGS Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. SUMMARY Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.
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Affiliation(s)
- Sayena Jabbehdari
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
| | - Alireza Baradaran Rafii
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghasem Yazdanpanah
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
| | - Pedram Hamrah
- Department of Ophthalmology, Tufts University Medical School, Boston, MA
| | - Edward J Holland
- Cincinnati Eye Institute, University of Cincinnati, Cincinnati, Ohio
| | - Ali R Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
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30
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Sayegh RR, Lass JH. Predicting long-term graft survival after keratoplasty. EXPERT REVIEW OF OPHTHALMOLOGY 2016. [DOI: 10.1080/17469899.2016.1226802] [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: 10/21/2022]
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Feizi S, Javadi MA, Ghasemi H, Javadi F. Effect of Donor Graft Quality on Clinical Outcomes After Penetrating Keratoplasty for Keratoconus. J Ophthalmic Vis Res 2016; 10:364-9. [PMID: 27051479 PMCID: PMC4795384 DOI: 10.4103/2008-322x.176912] [Citation(s) in RCA: 7] [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 effect of donor and eye bank characteristics on graft rating and clinical outcomes after penetrating keratoplasty (PK) for keratoconus. METHODS This retrospective interventional case series included 252 keratoconic eyes which underwent PK. Donor data included age and sex, cause of death, death-to-preservation time, preservation-to-surgery time, epithelial and stromal status, endothelial cell density (ECD) and morphology, and graft rating. Postoperative outcomes included visual acuity, refractive error, epithelial problems, suture-related complications, graft rejection, and graft transparency. Multivariate regression analysis assessed correlations between donor and eye bank characteristics and graft quality, and postoperative outcomes. RESULTS Mean recipient and donor age was 29.7 ± 10.0 and 26.2 ± 8.8 years, respectively and mean follow-up period was 66.7 ± 38.5 months. Death-to-preservation time was significantly associated with the presence of graft epithelial sloughing (P = 0.005) and stromal cloudiness (P < 0.001). Donor age significantly influenced ECD (P = 0.02), mean cell area (P = 0.04), and hexagonality (P = 0.01). The presence of epithelial defects on postoperative day 1 correlated significantly with death-to-preservation time (P = 0.004). Graft stromal edema on postoperative day 1 was significantly associated with graft epithelial sloughing (P < 0.001). Postoperative visual and refractive outcomes, complications, and graft survival were not correlated with any donor or eye bank factors. CONCLUSION Donor and eye bank variables affected the quality of donor corneas and early postoperative course. However, their long term effect on clinical outcomes, complications, and graft survival were insignificant.
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Affiliation(s)
- Sepehr Feizi
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Javadi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Department of Ophthalmology, Shahed University, Tehran, Iran
| | - Fatemeh Javadi
- Department of Ophthalmology, Shahed University, Tehran, Iran
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Yu T, Rajendran V, Griffith M, Forrester JV, Kuffová L. High-risk corneal allografts: A therapeutic challenge. World J Transplant 2016; 6:10-27. [PMID: 27011902 PMCID: PMC4801785 DOI: 10.5500/wjt.v6.i1.10] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 10/03/2015] [Accepted: 12/04/2015] [Indexed: 02/05/2023] Open
Abstract
Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in “low-risk” settings. Furthermore, although corneal graft survival in “low-risk” recipients is favourable, the prognosis in “high-risk” recipients for corneal graft is poor. In “high-risk” grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of “high-risk” recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in “high-risk” recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicine may be able to solve both important short comings of allotransplantation: (1) graft rejection and ultimate graft failure; and (2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide problem of corneal blindness in both “low-risk” and “high-risk” hosts.
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Risk Factors Predicting the Need for Graft Exchange After Descemet Stripping Automated Endothelial Keratoplasty. Cornea 2016; 34:876-9. [PMID: 26020823 DOI: 10.1097/ico.0000000000000455] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To identify the risk factors predicting the need for graft exchange after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS This is a retrospective cohort study. The study group included all 117 eyes that underwent or necessitated repeat DSAEK performed between January 2005 and June 2014 at Villa Serena-Villa Igea private hospitals (Forlì, Italy). The control group consisted of 1033 eyes that underwent only primary DSAEK during the same period. Demographic details, indications for primary surgery, ocular preoperative status and comorbidities, donor endothelial cell density (ECD), and postoperative complications were compared between the groups using univariate and multivariate analyses. RESULTS The prevalence of graft failure necessitating graft exchange was 10.2% (117 of 1150 eyes). In univariate analysis, a diagnosis of Fuchs endothelial dystrophy was a protective factor against the risk of repeat DSAEK. Prior trabeculectomy or aqueous shunt implantation, postoperative graft detachment, lower donor ECD, and a rejection episode were all associated with a significantly higher risk of requiring repeat DSAEK. The presence of buphthalmos, anterior chamber intraocular lens, aphakia, or prior penetrating keratoplasty were not risk factors for the failure of DSAEK. Of these variables, multivariate analysis showed that only prior aqueous shunt implantation [odds ratio (OR) = 5.5, 95% confidence interval (CI), 1.4-22.2], lower donor ECD (OR = 0.99, 95% CI, 0.997-0.999), and a documented postoperative rejection episode (OR = 18.2, 95% CI, 7.9-45.0) predicted the need for repeat DSAEK. CONCLUSIONS DSAEK grafts have similarly good long-term survival regardless of the indication for surgery, lens status, or ocular comorbidities, with the only exception being the presence of an aqueous shunt.
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Lass JH, Szczotka-Flynn LB, Ayala AR, Benetz BA, Gal RL, Aldave AJ, Corrigan MM, Dunn SP, McCall TL, Pramanik S, Rosenwasser GO, Ross KW, Terry MA, Verdier DD, Writing Committee for the Cornea Preservation Time Study Group. Cornea preservation time study: methods and potential impact on the cornea donor pool in the United States. Cornea 2015; 34:601-8. [PMID: 25850706 PMCID: PMC4426012 DOI: 10.1097/ico.0000000000000417] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 01/14/2015] [Accepted: 01/28/2015] [Indexed: 01/27/2023]
Abstract
PURPOSE The aim of this study was to describe the aims, methods, donor and recipient cohort characteristics, and potential impact of the Cornea Preservation Time Study (CPTS). METHODS The CPTS is a randomized clinical trial conducted at 40 clinical sites (70 surgeons) designed to assess the effect of donor cornea preservation time (PT) on graft survival 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were randomized to receive donor corneas stored ≤7 days or 8 to 14 days. Donor and patient characteristics, tissue preparation and surgical parameters, recipient and donor corneal stroma clarity, central corneal thickness, intraocular pressure, complications, and a reading center-determined central endothelial cell density were collected. Surveys were conducted to evaluate pre-CPTS PT practices. RESULTS The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median eye bank-determined screening endothelial cell density of 2688 cells/mm, and 74% eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240 bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18% diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for DSAEK in 2010 to 2011; 96% were preserved ≤7 days. Of 305 American Academy of Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their maximum PT preference at 8 days or less. CONCLUSIONS The CPTS will increase understanding of factors related to DSAEK success and, if noninferiority of longer PT is shown, will have great potential to extend the available pool of endothelial keratoplasty donors.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01537393.
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Affiliation(s)
- Jonathan H. Lass
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH
| | - Loretta B. Szczotka-Flynn
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH
| | | | - Beth A. Benetz
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH
| | | | - Anthony J. Aldave
- Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA
| | | | | | | | | | | | | | | | | | - Writing Committee for the Cornea Preservation Time Study Group
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH
- Jaeb Center for Health Research, Tampa, FL
- Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA
- Eye Associates Northwest, Seattle, WA
- Michigan Cornea Consultants, PC, Southfield, MI
- Cornea Associates of Texas, Dallas, TX
- Mid Atlantic Cornea Consultants, Baltimore, MD
- Central Pennsylvania Eye Center, Hershey, PA
- Midwest Eye-Banks, Ann Arbor, MI
- Devers Eye Institute, Portland, OR; and
- Verdier Eye Center, Grand Rapids, MI
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Cryopreservation of extracted corneal lenticules after small incision lenticule extraction for potential use in human subjects. Cornea 2015; 33:1355-62. [PMID: 25343698 PMCID: PMC4218759 DOI: 10.1097/ico.0000000000000276] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Purpose: To describe the technique of cryopreservation of corneal lenticules extracted after small incision refractive lenticule extraction (ReLEx SMILE) and initial results of femtosecond laser intrastromal lenticular implantation for hyperopia. Methods: Lenticules were collected from patients undergoing ReLEx SMILE for the correction of myopia and subjected to a tissue processing technique and cryopreservation. These lenticules were subsequently used to treat 8 hyperopic eyes and 1 aphakic eye. A femtosecond laser was used to create a pocket into each patient's cornea, followed by implantation of a cryopreserved lenticule. The patients were monitored through follow-up examinations for a mean 155.4 days (38–310 days). Results: The mean interval from storage of lenticules to removal from liquid nitrogen was 96 days (range, 19–178 days). Mean spherical equivalent of hyperopic eyes treated was +4.50 ± 1.1 diopter (D). Mean keratometry and pachymetry changed from preoperative 43.9 D and 531.6 μm to 47.4 D and 605.2 μm, respectively, postoperatively. Mean residual spherical equivalent for hyperopic eyes was +0.6 D and +4.1 D for the aphakic eye. None of the eyes showed evidence of rejection or loss of best-corrected visual acuity at the end of the follow-up period. Conclusions: The cryopreservation technique seems to be a safe method of long-term storage of refractive lenticules extracted after ReLEx SMILE for use in allogeneic human subjects. It may potentially be a safe and effective alternative to excimer laser ablation for hyperopia because of the low risks of regression, haze, flap-related complications, postoperative dry eye, and higher-order aberrations. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: CTRI/2014/01/004331.
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Abstract
PURPOSE The aim of this study was to assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure. METHODS One thousand ninety subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models. RESULTS Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (±99% confidence interval) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least 1 probable, but no definite rejection event, and 22% ± 20% in eyes with at least 1 definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when previous glaucoma surgery had been performed and glaucoma medications were being used at the time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, P = 0.008). CONCLUSIONS Patients who experienced a definite rejection event frequently developed graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that previous use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event.
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Wu W, Yu S, Feng S, Yang J, Lu X. Effect of the TLR2/MyD88/NF-κB axis on corneal allograft rejection after penetrating keratoplasty. J Recept Signal Transduct Res 2015; 36:45-52. [PMID: 25800037 DOI: 10.3109/10799893.2015.1016578] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
PURPOSE To evaluate the effect of the TLR2 (Toll-like receptor 2)/MyD88/NF-κB axis on the allograft rejection after penetrating keratoplasty (PK). METHODS The PK rat models were randomly divided into four groups: allograft group, dexamethasone group, PDTC group and isograft group. The mean survival time (MST) and rejection index of corneal grafts were observed. The immunohistochemical staining of TGF-α was performed on day 15. The messenger RNA (mRNA) and protein expression of TLR2, MyD88 and NF-κB p65 in corneal grafts were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. RESULTS On days 5, 7, 9, 11, 13 and 15, the rejection index in the allograft group was higher than in the other three groups (p < 0.05). The MST in the PDTC group (MST, 23.30 ± 0.42 days, n = 10) and in the dexamethasone group (MST, 24.40 ± 0.50 days, n = 10) were higher than in the allograft group (MST, 14.7 ± 0.70 days, n = 10) (χ(2) = 18.02, p < 0.01; χ(2) = 21.47, p < 0.01). The expression of TNF-α in the PDTC group and in the dexamethasone group decreased compared with the allograft group by immunohistochemistry. On day 15, the mRNA and protein expression of TLR2, MyD88 and NF-κB p65 in the PDTC group and the dexamethasone group were less than in the allograft group (p < 0.05). CONCLUSIONS Expression of TLR2, MyD88 and NF-κB p65 in rat corneal graft increased significantly and concurred with the allograft rejection, but were effectively inhibited by the treatment with dexamethasone and PDTC after PK. Dexamethasone could improve corneal allograft survival by the TLR2/MyD88/NF-κB axis. PDTC could suppress corneal graft rejection by inhibiting the activity of NF-κB. The TLR2/MyD88/NF-κB axis maybe a potential therapeutic target for corneal allograft rejection.
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Affiliation(s)
- Wei Wu
- a Department of Ophthalmology , ZhuJiang Hospital of Southern Medical University , Guangzhou 510282 , Guangdong Province , China and
| | - Shengyou Yu
- b Department of pediatrics , Guangzhou first people's Hospital , Guangzhou 510282 , Guangdong Province , China
| | - Songfu Feng
- a Department of Ophthalmology , ZhuJiang Hospital of Southern Medical University , Guangzhou 510282 , Guangdong Province , China and
| | - Jize Yang
- a Department of Ophthalmology , ZhuJiang Hospital of Southern Medical University , Guangzhou 510282 , Guangdong Province , China and
| | - Xiaohe Lu
- a Department of Ophthalmology , ZhuJiang Hospital of Southern Medical University , Guangzhou 510282 , Guangdong Province , China and
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van Essen TH, Roelen DL, Williams KA, Jager MJ. Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - to do or not to do. Prog Retin Eye Res 2015; 46:84-110. [PMID: 25601193 DOI: 10.1016/j.preteyeres.2015.01.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 01/05/2015] [Accepted: 01/07/2015] [Indexed: 12/15/2022]
Abstract
As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts.
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Affiliation(s)
- T H van Essen
- Department of Ophthalmology, J3-S, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
| | - D L Roelen
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - K A Williams
- Department of Ophthalmology, Flinders University, Adelaide, Australia
| | - M J Jager
- Department of Ophthalmology, J3-S, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary and Harvard Medical School, Boston, USA; Peking University Eye Center, Peking University Health Science Center, Beijing, China.
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Vora GK, Ciolino JB. Corneal allograft reaction associated with nonocular inflammation. Digit J Ophthalmol 2014; 20:29-31. [PMID: 25097462 DOI: 10.5693/djo.02.2013.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Corneal allograft rejection is known to have many risk factors, including ocular infection and inflammation. Although not reported in the literature, local nonocular inflammation may also have the ability to incite a graft reaction. We report 2 cases, one with dental inflammation and the other with a facial abscess, with simultaneous corneal transplant rejection. Possible pathophysiology and a review of the literature are given.
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Affiliation(s)
- Gargi Khare Vora
- Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary
| | - Joseph B Ciolino
- Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary
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40
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Chew ACY, Mehta JS, Tan DTH. One Year of Cornea Research in Review-2012. Asia Pac J Ophthalmol (Phila) 2013; 2:401-13. [PMID: 26107152 DOI: 10.1097/apo.0000000000000022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
PURPOSE The purpose of this study was to provide an update of significant cornea literature published in the past 1 year. DESIGN This was a literature review. METHODS The authors conducted a 1-year English-language literature search on PubMed, from January 1, 2012, to December 31, 2012, using the following terms: corneal transplantation, anterior lamellar keratoplasty, penetrating keratoplasty, endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, Descemet membrane endothelial keratoplasty, Descemet membrane endothelial transfer, ocular surface epithelial transplantation, limbal epithelial transplantation, cultivated oral mucosal epithelial transplantation, keratoprosthesis, infectious keratitis, cross-linking, keratoconus, corneal neovascularization, corneal imaging, optical coherence tomography, Pentacam Scheimpflug imaging, and in vivo confocal microscopy. RESULTS This review includes original articles and review articles that contain significant updates and novel aspects in the field of cornea from the following journals: American Journal of Ophthalmology, British Journal of Ophthalmology, Ophthalmology, Investigative Ophthalmology and Visual Science, and Cornea. Letters to the editor, unpublished work, manuscripts not in English, and abstracts were not included. CONCLUSIONS This review highlights significant literature that is applicable to the practicing ophthalmologist.
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Affiliation(s)
- Annabel C Y Chew
- From the *Singapore National Eye Centre, †Singapore Eye Research Institute, ‡Duke-NUS Graduate Medical School, and §Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Abstract
PURPOSE To assess corneal thickness (CT) and correlation with graft outcome after penetrating keratoplasty in the Cornea Donor Study. METHODS A total of 887 subjects with a corneal transplant for a moderate-risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) had postoperative CT measurements throughout a 5-year follow-up time. Relationships between baseline (recipient, donor, and operative) factors and CT were explored. Proportional hazards models were used to assess the association between CT and graft failure. Relationship between CT and cell density was assessed with a longitudinal repeated measures model and Spearman correlation estimates. RESULTS Higher longitudinal CT measurements were associated with the following: diagnosis of pseudophakic or aphakic corneal edema (P < 0.001), intraocular pressure >25 mm Hg during the first postoperative month (P = 0.003), white (non-Hispanic) donor race (P = 0.002), and respiratory causes of donor death (P < 0.001). Among those without graft failure within the first postoperative year, the 5-year cumulative incidence (± 95% confidence interval) of graft failure was 5% ± 5% in those with a 1-year CT ≤ 500 μm, 5% ± 3% for CT 501 to 550 μm, 7% ± 4% for CT 551 to 600 μm, and 20% ± 11% for CT >600 μm. In a multivariate analysis, both 1-year CT and cell density were associated with subsequent graft failure (P = 0.002 and 0.009). CT increase was modestly associated with endothelial cell loss during follow-up (r = -0.29). CONCLUSIONS During the first 5 years after penetrating keratoplasty, CT can serve as a predictor of graft survival. However, CT is not a substitute for cell density measurement because both measures were independently predictive of graft failure.
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Duman F, Kosker M, Suri K, Reddy JC, Ma JF, Hammersmith KM, Nagra PK, Rapuano CJ. Indications and outcomes of corneal transplantation in geriatric patients. Am J Ophthalmol 2013; 156:600-607.e2. [PMID: 23769195 DOI: 10.1016/j.ajo.2013.04.034] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2012] [Revised: 04/26/2013] [Accepted: 04/27/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE To identify the most common corneal transplant procedures, indications, coexisting ocular diseases, and outcomes in elderly patients, and to compare younger geriatric patients with super-geriatric patients. DESIGN Retrospective case series. METHODS Data of all patients 65 years old and older who underwent corneal transplantation at Wills Eye Institute from April 2007 to January 2013, and were followed up for at least 1 year, were collected. Two hundred seventy-one eyes of 253 patients were divided into 2 groups according to the age of the patient. RESULTS Group I (65-79 years old) included 181 eyes and Group II (80 years and older) included 90 eyes. The most common indication was Fuchs endothelial dystrophy, with 78 eyes (43%) in Group I and 34 eyes (38%) in Group II. In Group I, 93 Descemet stripping endothelial keratoplasty (DSEK) (51%), 84 penetrating keratoplasty (PK) (46%), and 4 keratoprosthesis procedures(2%) were performed; in Group II, 37 DSEK (41%), 51 PK (57%), and 2 keratoprosthesis procedures (2%) were performed. Graft survival rate at last visit was 90% for Group I and 88% for Group II. Rejection occurred in 18 Group I eyes (10%) and 7 Group II eyes (8%) (P = .562). CONCLUSION Endothelial abnormalities were more common indications and keratoconus was a less common indication for surgery in the elderly. Fuchs dystrophy was the leading indication for surgery in both super-geriatric and younger geriatric patients. Graft survival rate was slightly higher in the younger geriatric age group but was not statistically significant. In the elderly, there is an increased prevalence of both glaucoma and retinal diseases that can affect the visual outcomes after corneal transplantation.
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Descemet Stripping Automated Endothelial Keratoplasty for Bullous Keratopathy With an Irregular Posterior Surface. Cornea 2013; 32:1183-8. [DOI: 10.1097/ico.0b013e31829623d6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Descemet's membrane endothelial keratoplasty surgery: update on the evidence and hurdles to acceptance. Curr Opin Ophthalmol 2013; 24:329-35. [PMID: 23680758 DOI: 10.1097/icu.0b013e32836229ab] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
PURPOSE OF REVIEW Descemet's stripping endothelial keratoplasty (DSEK) is the most popular treatment for endothelial dysfunction, but Descemet's membrane endothelial keratoplasty (DMEK) now provides better vision with lower risk of immunologic rejection. Although DMEK is more challenging, advances in instrumentation and techniques are reducing the learning curve. RECENT FINDINGS In contrast to DSEK, which includes posterior donor stroma, DMEK consists merely of donor endothelium and Descemet's membrane, so DMEK does not create a stromal interface and induces significantly less posterior surface aberrations, resulting in better vision. Furthermore, multiple centers report remarkably low (<1%) cumulative probability of immunologic graft rejection episodes through 2 years after DMEK. Initially, the biggest challenges were tissue loss in preparation and ensuring attachment. Subsequent improvements have reduced complication rates to levels experienced with DSEK. DMEK/DSEK hybrids and 'thin' DSEK also can provide better vision than standard DSEK; randomized controlled comparisons with DMEK are needed. SUMMARY DMEK provides an anatomically exact replacement of dysfunctional host endothelium and has set new benchmarks for rejection risk and visual outcomes following endothelial replacement. DMEK is providing new insights into how different corneal layers contribute to immunogenicity and immune tolerance and into the key factors that limit vision after endothelial keratoplasty.
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Price MO, Gorovoy M, Price FW, Benetz BA, Menegay HJ, Lass JH. Descemet's stripping automated endothelial keratoplasty: three-year graft and endothelial cell survival compared with penetrating keratoplasty. Ophthalmology 2012; 120:246-51. [PMID: 23107581 DOI: 10.1016/j.ophtha.2012.08.007] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 08/02/2012] [Accepted: 08/03/2012] [Indexed: 01/18/2023] Open
Abstract
PURPOSE To assess 3-year outcomes of Descemet's stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Cornea Donor Study (CDS). DESIGN Prospective, multicenter, nonrandomized clinical trial. PARTICIPANTS A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema) compared with 1101 subjects undergoing PKP from the CDS. METHODS The DSAEK procedures were performed by 2 experienced surgeons using the same donor and similar recipient criteria as for the CDS PKP procedures, performed by 68 surgeons. Graft success was assessed by Kaplan-Meier survival analysis. Central endothelial cell density (ECD) was determined from baseline donor and postoperative central endothelial images by the reading center used in the CDS Specular Microscopy Ancillary Study. MAIN OUTCOME MEASURES Graft clarity and ECD. RESULTS The donor and recipient demographics were comparable in the DSAEK and PKP groups, except that the proportion of Fuchs' dystrophy cases was higher in the DSAEK cohort. The 3-year survival rate did not differ significantly between DSAEK and PKP procedures performed for either Fuchs' dystrophy (96% for both; P = 0.81) or non-Fuchs' cases (86% vs. 84%, respectively; P = 0.41). Principal causes of graft failure or regraft within 3 years after DSAEK and PKP were immunologic graft rejection (0.6% vs. 3.1%), endothelial decompensation in the absence of documented rejection (1.7% vs 2.1%), unsatisfactory visual or refractive outcome (1.7% vs. 0.5%), and infection (0% vs. 1.1%), respectively. The 3-year predicted probability of a rejection episode was 9% with DSAEK versus 20% with PKP (P = 0.0005). The median 3-year cell loss for DSAEK and PKP was 46% and 51%, respectively (P = 0.33), in Fuchs' dystrophy cases and 59% and 61%, respectively (P = 0.70), in the non-Fuchs' cases. At 3 years, use of a smaller DSAEK insertion incision was associated with significantly higher cell loss (60% vs. 33% for 3.2- and 5.0-mm incisions, respectively; P = 0.0007), but not with a significant difference in graft survival (P = 0.45). CONCLUSIONS The graft success rate and endothelial cell loss were comparable at 3 years for DSAEK and PKP procedures. A 5-mm DSAEK incision width was associated with significantly less cell loss than a 3.2-mm incision.
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Affiliation(s)
- Marianne O Price
- Cornea Research Foundation of America, Indianapolis, Indiana 46260, USA.
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