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Price MO, Szczotka-Flynn LB, Bauza CE, Reed ZW, Benetz BA, Greiner MA, Verdier DD, Soper MC, Titus MS, Monnier VM, Arafah BM, Kollman C, Beck RW, Lass JH. Diabetes Endothelial Keratoplasty Study: Methods and Impact on the Use of Corneas From Donors With Diabetes for Descemet Membrane Endothelial Keratoplasty. Cornea 2025:00003226-990000000-00771. [PMID: 39808526 DOI: 10.1097/ico.0000000000003776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 11/05/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE Describe aims, methods, characteristics of donors, donor corneas and recipients, and potential impact of the Diabetes Endothelial Keratoplasty Study (DEKS). METHODS The DEKS is a randomized, clinical trial to assess graft success and endothelial cell density (ECD) 1 year after Descemet membrane endothelial keratoplasty (DMEK) using corneas from donors with versus without diabetes in a 1:2 minimization assignment. Diabetes severity in the donor is assessed by medical history, postmortem HbA1c, and donor skin advanced glycation end-products and oxidation markers. A central image analysis reading center assesses baseline donor, 1-month and 1-year postoperative ECD. RESULTS The DEKS used corneas from 1154 donors for 1421 DMEK procedures on 1097 participants (324 bilateral) at 28 clinical sites. Forty-eight tissue preparations failed (3%). Mean donor age was 65 years; mean eye bank-determined screening ECD was 2709 cells/mm2. Ultimately, 106 (9%) of 1154 donors without diabetes history were classified as diabetic based on postmortem HbA1c ≥6.5%, and 509 (36%) of 1421 donor lenticules were classified as coming from diabetic donors. Recipients were 58% female, 96% White, and 53% phakic. Study eyes were treated for Fuchs endothelial corneal dystrophy (96%), pseudophakic corneal edema (2%), and failed endothelial keratoplasty (2%). Mean recipient age was 70 years; 21% had diabetes history and 26 (2%) had central laboratory determined HbA1c ≥6.5% without diabetes history. CONCLUSIONS The DEKS will increase understanding of factors related to DMEK success while determining whether diabetes and/or diabetes severity in the donor and/or recipient adversely affects graft success and endothelial cell loss.
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Grants
- UG1 EY030030 NEI NIH HHS
- EY030030 and EY030039 National Eye Institute, Eye Bank Association of America, The Cornea Society, Cleveland Eye Bank Foundation, Beauty of Sight: A Lions Eye Bank, CorneaGen, Eversight, Eye Bank for Sight Restoration, Eye Bank of Kentucky, Lions Gift of Sight, Iowa Lions Eye Bank, Lions Eye Bank of Wisconsin, Kenneth Maverick, MD, Mayo Clinic, San Antonio Eye , San Diego Eye , Utah Lions Eye , VisionFirst, VisionGift
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Affiliation(s)
| | - Loretta B Szczotka-Flynn
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, University Hospitals Eye Institute, Cleveland, OH
| | | | | | - Beth Ann Benetz
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, University Hospitals Eye Institute, Cleveland, OH
| | - Mark A Greiner
- Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA
| | | | | | | | - Vincent M Monnier
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH; and
| | - Baha M Arafah
- Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, OH
| | | | - Roy W Beck
- Jaeb Center for Health Research, Tampa, FL
| | - Jonathan H Lass
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, University Hospitals Eye Institute, Cleveland, OH
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Greenwald MF, Sawant OB, Titus MS, Ballouz D, Hood CT, Mian SI. Suitability and Early Clinical Outcomes of Corneal Donor Tissue in the 76-80-Year-Old Age Group. Cornea 2025; 44:26-30. [PMID: 39630543 DOI: 10.1097/ico.0000000000003644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 06/23/2024] [Indexed: 08/10/2024]
Abstract
PURPOSE There is a significant global shortage of corneal donor tissue suitable for keratoplasty. One simple strategy for addressing this shortage is to increase the upper age limit for acceptable tissue over the current customary upper limit of age 75. We describe a pilot study completed at one eye bank procuring, processing, and distributing keratoplasty tissue from donors aged 76 to 80 years. METHODS This is a retrospective case series of donor tissues aged 76 to 80 years in comparison with donor tissues aged 71 to 75 years. Standard tissue parameters were evaluated for all tissues, including tissue suitability, mean endothelial cell density (ECD), death-to-procurement time, and cause of death. For the older tissues, clinical outcomes through 3 months were obtained from each surgeon, including intraoperative and postoperative complications. RESULTS Corneal tissues from donors aged 76 to 80 years had a similar suitability rate (57%) when compared with donors aged 71 to 75 years (59%) ( P = 0.635). Both groups had comparable ECDs ( P = 0.097). Early clinical outcomes of corneal grafts from donors older than 76 years were favorable, with no early graft failure or significant concerns for clinical safety or efficacy. CONCLUSIONS Our findings suggest that corneal tissues aged 76 to 80 years can be safely and efficiently transplanted in the United States. While additional study is needed, our results strengthen the case that expanding the upper age limit for donor age has the potential to help meet the global shortage for suitable keratoplasty tissue.
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Affiliation(s)
- Miles F Greenwald
- Kansas University Eye Center, Kansas University Medical Center, Prairie Village, KS
| | - Onkar B Sawant
- Eversight, Ann Arbor, MI
- Center for Vision and Eye Banking Research, Cleveland, OH; and
| | | | - Dena Ballouz
- Kellogg Eye Center, University of Michigan, Ann Arbor, MI
| | | | - Shahzad I Mian
- Eversight, Ann Arbor, MI
- Kellogg Eye Center, University of Michigan, Ann Arbor, MI
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Sneyers A, Daas L, Zemova E, Quintin A, Munteanu C, Seitz B. Impact of Donor, Host, and Surgical Parameters on High Endothelial Cell Density More Than 5 Years after Penetrating Keratoplasty. Klin Monbl Augenheilkd 2024; 241:1341-1348. [PMID: 39142340 DOI: 10.1055/a-2349-0770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
OBJECTIVES To investigate the correlation between postoperative endothelial cell loss (ECL) and donor, host, and surgical parameters, and to assess the clinical impact of maintaining a high endothelial cell density (ECD) of ≥ 1500 cells/mm2 5 years after penetrating keratoplasty (PKP). METHODS This retrospective cohort study included 216 eyes with 5 years of follow-up, of which 94 had annual visits, and who underwent normal-risk elective PKP for noninfectious indications by one corneal microsurgeon (B. S.) between 2009 and 2016. RESULTS Among the 216 eyes, ECL (39.1%) over 5 years postoperative exhibited weak positive correlations with storage solution time (p = 0.024) and postmortem time (p = 0.028), and moderately positively correlations with the preoperative ECD (p < 0.001). The 5-year postoperative ECL differed significantly between in domo-prepared (36.8%) and ex domo donor corneas (46.3%; p = 0.001). In the 94 eyes, no significant differences were found between the two groups for central pupil pachymetry (CCT) and BCVA (p > 0.074). However, CCT increased significantly between 1 and 4 years (p = 0.034) and 1 and 5 years postoperatively (p = 0.012), respectively. BCVA improved significantly at 1 year postoperatively and continued to improve until 2 years postoperatively (p < 0.001). CONCLUSION The Lions corneal bank Saar-Lor-Lux achieved a significantly reduced ECL (36.8%) over 5 years compared to ex domo donor corneas (46.3%). A weak positive correlation was found between ECL with the storage solution time and the postmortem time, as well as a moderate positive correlation with the preoperative ECD. Although CCT increased significantly over 5 years, BCVA improved significantly from the first to the second postoperative year and remained stable thereafter.
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Affiliation(s)
- Albéric Sneyers
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
| | - Loay Daas
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
| | - Elena Zemova
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
| | - Adrien Quintin
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
| | - Cristian Munteanu
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
| | - Berthold Seitz
- Department of Ophthalmology, Saarland University Medical Centre (UKS), Homburg/Saar, Germany
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Hatzfeld AS, Germain N, Maboudou P, Dhayer M, Marchetti P. Medical and economic impacts of managing corneas from older donors at the tissue bank-a single-center retrospective study spanning over 12 years. Front Med (Lausanne) 2024; 11:1415515. [PMID: 39512619 PMCID: PMC11540627 DOI: 10.3389/fmed.2024.1415515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 10/11/2024] [Indexed: 11/15/2024] Open
Abstract
Aim To evaluate the impact of corneas from donors over 80 years of age on the activity of the North of France Tissue Bank and to determine the potential cost implications for banks using corneas from older donors. Methods We analyzed data from a single-center retrospective cohort study of 6,023 corneas preserved at the Lille Tissue Bank between 2012 and 2023. Donors, unrestricted by age, were divided into two groups: younger (≤ 80 years) and older (> 80 years). Corneas were categorized based on endothelial cell density (ECD). Data were collected from patients who underwent corneal transplantation. A financial impact model was created to assess the effects of using corneas from different age groups on the overall benefits of corneal transplant procedures. Results The average donor age was 67.5 ± 14.5 years. The median age of donors gradually increased from 66 to 73 years over the 12-year study period, with donors over 80 years old representing more than 24% since 2021. Corneas from older donors had a higher discard rate (62.53% vs. 39.66%) due to poor endothelial quality and serological concerns (both p < 0.0001). Additionally, these corneas had lower ECD, with a larger proportion deemed unsuitable for grafting due to low ECD (30% vs. 8.2%). Corneas from younger donors were more often used for endothelial transplants, which require higher ECD. The mean economic benefit per cornea showed a moderate negative correlation with donor age. The net benefit of corneal transplants decreased as the proportion of donors aged over 80 years increased. It is predicted that a net benefit of zero would be attained when the proportion of donors over 80 years is 44.4%. Conclusion Using corneas from donors over 80 years of age can help alleviate the shortage of donor tissue and be effective if certain quality standards are met. However, additional costs incurred by eye banks must be factored into this equation.
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Affiliation(s)
| | - Nicolas Germain
- Tissue Bank of Lille, Biology Pathology Center, CHU Lille, Lille, France
- UMR 9020-U1277, CANTHER, University Lille, CNRS, Lille, France
| | - Patrice Maboudou
- Biochemistry Unit, Biology Pathology Center, CHU Lille, Lille, France
| | - Mélanie Dhayer
- UMR 9020-U1277, CANTHER, University Lille, CNRS, Lille, France
| | - Philippe Marchetti
- Tissue Bank of Lille, Biology Pathology Center, CHU Lille, Lille, France
- UMR 9020-U1277, CANTHER, University Lille, CNRS, Lille, France
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Yang Y, Zeng H, Gong L, Lin T. Risk Factors for Graft Failure After Penetrating Keratoplasty in Eastern China from 2018 to 2021. Ann Transplant 2024; 29:e945388. [PMID: 39434378 PMCID: PMC11512512 DOI: 10.12659/aot.945388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/02/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Penetrating keratoplasty (PK) remains the most common corneal transplant method in China. In this paper we aim to analyze the outcomes and the potential factors associated with graft failures of PKs in one of the largest keratoplasty centers in Eastern China during the past 4 years. MATERIAL AND METHODS A retrospective review was performed on 502 eyes from 481 recipients undergoing PKs from January 2018 to December 2021 at the Eye and ENT Hospital of Fudan University. Graft failures presenting between the first postoperative day and 8 weeks were defined as early graft failure and failures presenting between 8 weeks and the end of the 1-year follow-up as late failure. Cox proportional hazards regression models and logistic regression models were used to assess the association between factors and failures. RESULTS Of the 93 failed cases, 36 were classified as early failure and 57 as late failure. Risk factors, expressed as hazard ratio (HR) and confidence interval (CI), for the failures include the following: burns (HR: 12.56, 95% CI [2.4, 65.71]), nonsuppurative inflammation (HR: 11.06, 95% CI [2.49, 49.03]), suppurative inflammation (HR: 12.49, 95% CI [2.76, 56.37]), immune disease (HR: 1.70, 95% CI [0.64, 4.48]), low donor endothelial cell density (ECD) (HR: 0.92/100 cells, 95% CI [0.87, 0.98]), and surgical complications (HR: 1.83, 95% CI [1.06, 3.17]). Two social factors were strongly negatively associated with late failures: completion of compulsory education (HR: 0.45, 95% CI [0.21-0.94]) and marriage (HR: 0.27, 95% CI [0.09-0.81]). CONCLUSIONS Indications, surgical complications, immune disease of the recipient, and lower donor ECD were risk factors for failure. Social factors also affect the ocular health after PK in the long term.
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Affiliation(s)
- Yun Yang
- Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, PR China
- NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, PR China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, PR China
| | - HongYa Zeng
- Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, PR China
- NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, PR China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, PR China
| | - Lan Gong
- Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, PR China
- NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, PR China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, PR China
| | - Tong Lin
- Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, PR China
- NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, PR China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, PR China
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Chu X, Yin Y, Chen S, Chen F, Liu H, Zhao S. Suppressive Role of Pigment Epithelium-derived Factor in a Rat Model of Corneal Allograft Rejection. Transplantation 2024; 108:2072-2083. [PMID: 38644534 DOI: 10.1097/tp.0000000000005032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/23/2024]
Abstract
BACKGROUND Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis. METHODS The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot. RESULTS Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-β, emphasizing the suppressive role of PEDF on immune responses. CONCLUSIONS Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.
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Affiliation(s)
- Xiaoran Chu
- Department of Cornea and Refractive Surgery, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
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Nandzik M, Wylęgała A, Szkodny D, Wróblewska-Czajka E, Wylęgała E, Orzechowska-Wylęgała B. Risk Factors for Glaucoma and Ocular Hypertension and Post-Transplant Complications in Keratoconus: A Multivariable Analysis. J Clin Med 2024; 13:5407. [PMID: 39336894 PMCID: PMC11432017 DOI: 10.3390/jcm13185407] [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: 07/29/2024] [Revised: 09/05/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Background: The purpose of this study was to investigate the risk factors for glaucoma in patients with keratoconus following keratoplasty and to identify potential factors that could affect post-transplant complications. Methods: A retrospective analysis was conducted on the medical records of 192 keratoconus patients who underwent keratoplasty. Data on treatment history, perioperative information, tissue bank data, postoperative regimens, complications, and infections were collected and analyzed. Statistical analysis was performed to identify risk factors associated with glaucoma and transplant complications. Results: There was a 41.6% incidence of glaucoma (high IOP) (p < 0.001), with the median time to glaucoma development being 314 ± 67 days post-transplant. A significant number of patients required surgical intervention, accounting for 48.05%. Our analysis revealed a 14% graft failure rate. On univariable Cox proportional hazard analysis, the following factors demonstrated statistically significant associations with the risk of glaucoma after transplantation: donor endothelial cell density, the use of a single continuous suture type, and the surgeon (performing the surgery). For many variables, the only factor that remained significant was the surgeon. Among the factors analyzed for risks of failure post-transplantation, significant associations were observed for the donor age, the time from harvest to transplant, and the surgeon. In the multivariable analysis, donor age emerged as a significant predictor of post-transplant complications. Conclusions: Risk factors such as donor endothelial cell density, suture type, surgeon, host and donor size, and host gender were found to increase the risk of developing glaucoma post-keratoplasty. Surgeon type was identified as a significant risk factor, while donor age was predictive of post-transplant complications.
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Affiliation(s)
- Magdalena Nandzik
- Department of Ophthalmology, Faculty of Medical Sciences, Zabrze Medical University of Silesia, 40-760 Katowice, Poland
- Department of Ophthalmology, District Railway Hospital in Katowice, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland
| | - Adam Wylęgała
- Department of Ophthalmology, Faculty of Medical Sciences, Zabrze Medical University of Silesia, 40-760 Katowice, Poland
- Department of Ophthalmology, District Railway Hospital in Katowice, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland
| | - Dominika Szkodny
- Department of Ophthalmology, Faculty of Medical Sciences, Zabrze Medical University of Silesia, 40-760 Katowice, Poland
- Department of Ophthalmology, District Railway Hospital in Katowice, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland
| | - Ewa Wróblewska-Czajka
- Department of Ophthalmology, Faculty of Medical Sciences, Zabrze Medical University of Silesia, 40-760 Katowice, Poland
- Department of Ophthalmology, District Railway Hospital in Katowice, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland
| | - Edward Wylęgała
- Department of Ophthalmology, Faculty of Medical Sciences, Zabrze Medical University of Silesia, 40-760 Katowice, Poland
- Department of Ophthalmology, District Railway Hospital in Katowice, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland
| | - Bogusława Orzechowska-Wylęgała
- Department of Pediatric Otolaryngology, Head and Neck Surgery, Medical University of Silesia (SUM), 40-055 Katowice, Poland
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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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Romano V, Passaro ML, Ruzza A, Parekh M, Airaldi M, Levis HJ, Ferrari S, Costagliola C, Semeraro F, Ponzin D. Quality assurance in corneal transplants: Donor cornea assessment and oversight. Surv Ophthalmol 2024; 69:465-482. [PMID: 38199504 DOI: 10.1016/j.survophthal.2023.12.002] [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: 11/02/2023] [Revised: 12/12/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024]
Abstract
The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.
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Affiliation(s)
- Vito Romano
- Eye Clinic, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; Eye Clinic, ASST Spedali Civili di Brescia, Brescia, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy.
| | - Maria Laura Passaro
- Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples "Federico II", Naples, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Alessandro Ruzza
- International Center for Ocular Physiopathology, Fondazione Banca Degli Occhi del Veneto Onlus, Venice, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Mohit Parekh
- Schepens Eye Research Institute of Mass Eye and Ear, Dept. of Ophthalmology, Harvard Medical School, Boston, MA, USA; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Matteo Airaldi
- Eye Clinic, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; Eye Clinic, ASST Spedali Civili di Brescia, Brescia, Italy; Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples "Federico II", Naples, Italy; International Center for Ocular Physiopathology, Fondazione Banca Degli Occhi del Veneto Onlus, Venice, Italy; Schepens Eye Research Institute of Mass Eye and Ear, Dept. of Ophthalmology, Harvard Medical School, Boston, MA, USA; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy; Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Hannah J Levis
- Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy; Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Stefano Ferrari
- International Center for Ocular Physiopathology, Fondazione Banca Degli Occhi del Veneto Onlus, Venice, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Ciro Costagliola
- Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples "Federico II", Naples, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Francesco Semeraro
- Eye Clinic, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; Eye Clinic, ASST Spedali Civili di Brescia, Brescia, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
| | - Diego Ponzin
- International Center for Ocular Physiopathology, Fondazione Banca Degli Occhi del Veneto Onlus, Venice, Italy; Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy
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Blanco T, Musayeva A, Singh RB, Nakagawa H, Lee S, Alemi H, Gonzalez-Nolasco B, Ortiz G, Wang S, Kahale F, Dohlman TH, Chen Y, Dana R. The impact of donor diabetes on corneal transplant immunity. Am J Transplant 2023; 23:1345-1358. [PMID: 37245642 PMCID: PMC10527508 DOI: 10.1016/j.ajt.2023.05.027] [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: 03/03/2023] [Revised: 05/12/2023] [Accepted: 05/24/2023] [Indexed: 05/30/2023]
Abstract
Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lepob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.
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Affiliation(s)
- Tomás Blanco
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Aytan Musayeva
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Rohan Bir Singh
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Hayate Nakagawa
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Seokjoo Lee
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Hamid Alemi
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Bruno Gonzalez-Nolasco
- Transplant Research Center, Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Gustavo Ortiz
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Shudan Wang
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Francesca Kahale
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Thomas H Dohlman
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Yihe Chen
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Reza Dana
- Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
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Módis L, Lukács M, Makhoul S. [Corneal transplantation at the beginning of the 21th century]. Orv Hetil 2023; 164:1087-1093. [PMID: 37454331 DOI: 10.1556/650.2023.32822] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/23/2023] [Indexed: 07/18/2023]
Abstract
Corneal transplantation (keratoplasty) is necessary when various disorders result in corneal opacities with severe visual loss that cannot be treated conservatively, or the regular structure and curvature of the cornea is distorted, and its function is lost. Among human transplantation, keratoplasty is the most successful surgical procedure. In recent decades, penetrating keratoplasties have been increasingly replaced by lamellar techniques, where only the abnormal layer of the cornea is transplanted. The anterior form is deep anterior lamellar keratoplasty (DALK), recommended mainly for keratoconus. The main forms of posterior lamellar keratoplasty are Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). The indications are bullous keratopathy after cataract surgery with endothelial destruction and Fuchs endothelial dystrophy. Lamellar keratoplasty has several advantages over penetrating surgery. Postoperative visual acuity is better, wound healing, patient rehabilitation are faster and the course of any immune rejection is milder and can be better managed. Orv Hetil. 2023; 164(28): 1087-1093.
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Affiliation(s)
- László Módis
- 1 Debreceni Egyetem, Általános Orvostudományi Kar, Szemészeti Tanszék Debrecen, Nagyerdei krt. 98., 4032 Magyarország
| | - Miklós Lukács
- 1 Debreceni Egyetem, Általános Orvostudományi Kar, Szemészeti Tanszék Debrecen, Nagyerdei krt. 98., 4032 Magyarország
| | - Sára Makhoul
- 1 Debreceni Egyetem, Általános Orvostudományi Kar, Szemészeti Tanszék Debrecen, Nagyerdei krt. 98., 4032 Magyarország
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12
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Patel SV, Hodge DO, Winkler NS, Maguire LJ, Baratz KH. Graft Survival, Graft Rejection, and Glaucoma in a Consecutive Series of Descemet Stripping Endothelial Keratoplasty. Cornea 2023; 42:549-556. [PMID: 35543582 DOI: 10.1097/ico.0000000000003050] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/11/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE The goal of this study was to compare outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with glaucoma and abnormal anatomy to eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS In a retrospective interventional series of all cases of DSEK between April 1, 2006, and November 30, 2015, recipient diagnosis, preoperative glaucoma status, concurrent surgical procedures, and graft outcomes were recorded. Graft survival, risk of rejection, and subsequent glaucoma surgery were estimated by using Kaplan-Meier analysis with risk factors determined by proportional hazard models. RESULTS Of 703 DSEKs in 666 eyes (509 subjects), the main recipient diagnoses were FECD (n = 496), pseudophakic corneal edema (n = 112), and failed graft (n = 83). Glaucoma was present in 150 cases before DSEK. Overall graft survival was 85%, 75%, and 71% at 5, 10, and 12 years, respectively, and for FECD without glaucoma was 95%, 89%, and 87% at 5, 10, and 12 years, respectively. Independent risk factors for graft failure included recipient diagnoses of pseudophakic corneal edema (HR = 8.3, P < 0.001), failed graft (HR = 6.4, P < 0.001), and preoperative medical glaucoma (HR = 7.1, P < 0.001) or surgical glaucoma (HR = 12.3, P < 0.001). Preoperative glaucoma treated by previous surgery resulted in graft survival of 28% at 10 years. Preoperative glaucoma was associated with an increased risk of graft rejection (HR = 6.8, P < 0.001) and subsequent glaucoma surgery (HR > 17.4, P < 0.001). CONCLUSIONS Preoperative glaucoma increases the risk of graft failure, graft rejection, and needing subsequent glaucoma surgery in the first decade after DSEK. With previous glaucoma surgery, DSEK graft survival was more favorable compared with published reports of Descemet membrane endothelial keratoplasty.
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Affiliation(s)
- Sanjay V Patel
- Department of Ophthalmology, Mayo Clinic, Rochester, MN; and
| | - David O Hodge
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL
| | | | - Leo J Maguire
- Department of Ophthalmology, Mayo Clinic, Rochester, MN; and
| | - Keith H Baratz
- Department of Ophthalmology, Mayo Clinic, Rochester, MN; and
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Qureshi S, Dohlman TH. Penetrating Keratoplasty: Indications and Graft Survival by Geographic Region. Semin Ophthalmol 2023; 38:31-43. [PMID: 36527378 PMCID: PMC10084850 DOI: 10.1080/08820538.2022.2152710] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 02/02/2022] [Indexed: 12/23/2022]
Abstract
Corneal transplantation, or penetrating keratoplasty (PK), is the most common form of solid-organ transplantation performed worldwide. Here, we evaluated the indications for PK and rates of transplant survival around the world by geographic region. We conducted a literature search of PubMed, MEDLINE, and Google Scholar databases and identified 155 relevant studies from 41 countries published between 1987 and 2021. The most common indications for PK were keratoconus in Europe, Africa, the Middle East, Australia, New Zealand, and Central and South America, bullous keratopathy in North America, and corneal scarring in Asia. The overall global mean graft survival rates at 1-, 2-, 3-, 5-, and 10-years were 88.6%, 81.2%, 78.9%, 72.8%, and 61.2%, respectively. Through this systematic analysis of PK by region, we hope to bring a new perspective to the corneal transplantation literature and to potentially highlight global differences and unmet needs in patient care.
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Affiliation(s)
- Sana Qureshi
- Cornea Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
| | - Thomas H Dohlman
- Cornea Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA
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Comparison of Graft Outcomes Reusing Original Intermediate-Term Cold Storage Solution for Entire Corneal Donor Storage Period With Exchanged Fresh Storage Solution After Donor Preparation in the Cornea Preservation Time Study. Cornea 2022; 41:1539-1544. [PMID: 36036663 PMCID: PMC9640289 DOI: 10.1097/ico.0000000000003108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 06/12/2022] [Indexed: 11/26/2022]
Abstract
PURPOSE The purpose of this study was to evaluate outcomes of Descemet stripping automated endothelial keratoplasty comparing exchange with fresh intermediate-term cold storage solution after lenticule preparation versus reuse of the original solution in the Cornea Preservation Time Study. METHODS In the Cornea Preservation Time Study, 508 donor corneas had lenticules prepared by the eye bank with fresh solution exchange (Fresh group) and 283 with reuse of the original solution (Original group). Storage time for all donors was ≤11 days. Graft success rates, central endothelial cell loss at 3 years, and frequency of positive donor rim cultures were compared between the 2 groups. RESULTS The 3-year graft success rate (95% confidence interval) was 93.4% (90.7%-95.3%) in the Fresh group and 95.2% (91.8%-97.2%) in the Original group (adjusted hazard ratio for graft failure = 0.64, 95% confidence interval, 0.33-1.24, P = 0.19). The mean percentage endothelial cell loss was significantly greater in the Fresh group versus Original group (45% ± 22% vs. 38% ± 20%, respectively, P = 0.004). Cultures were positive in 4 (1.5%) of 267 donor rims (3 fungal and 1 bacterial) in the Fresh group and in 4 (2.5%) of 158 in the Original group (P = 0.57). There were 2 postoperative infections in the Original group and none in the Fresh group. CONCLUSIONS The use of the original intermediate-term cold storage solution did not reduce the 3-year graft success rate compared with exchanging with fresh solution after lenticule preparation for Descemet stripping automated endothelial keratoplasty, while the frequency of positive donor rim cultures did not significantly differ between groups.
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15
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Downward L, Ahmed M, Hopkinson C, Romano V, Curnow E, Kaye SB. Endothelial failure and rejection in recipients of corneas from the same donor. BMJ Open Ophthalmol 2022; 7:bmjophth-2021-000965. [PMID: 36161852 PMCID: PMC9389126 DOI: 10.1136/bmjophth-2021-000965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 04/08/2022] [Indexed: 11/12/2022] Open
Abstract
Objective To determine whether patients who receive corneas from the same donor have similar risks of endothelial failure and rejection. Methods and Analysis Patients with Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) who received their first corneal transplant between 1999 and 2016 were analysed. Patients receiving corneas from donors who donated both corneas for the same indication were defined as ‘paired’. Gray’s test was used to compare the cumulative incidence of endothelial failure and rejection within 5 years post-transplant for ‘paired’ and ‘unpaired’ groups. Cox regression models were fitted to determine whether there was an association between recorded donor characteristics (endothelial cell density (ECD), age and sex and endothelial graft failure and rejection. Results 10 838 patients were analysed of whom 1536 (14%) were paired. The unpaired group comprised 1837 (69%) recipients of single corneal donors and 7465 (69%) donors who donated both corneas for another indication. ECD was lower for unpaired single cornea donors (p<0.01). There was no significant difference in endothelial graft failure or rejection between paired and unpaired groups for FED (p=0.37, p=0.99) or PBK (p=0.88, p=0.28) nor for donor ECD, age, sex and paired donation after adjusting for transplant factors (across all models p>0.16 for ECD, p>0.32 for donor age, p>0.14 for sex match and p>0.17 for the donor effect). Conclusion The absence of a significant difference in graft outcome for corneal transplants for FED and PBK between paired and unpaired donors may reflect a homogeneous donor pool in the UK.
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Affiliation(s)
- Lewis Downward
- Statistics, NHS Blood and Transplant Organ Donation and Transplantation Directorate, Bristol, UK
| | - Mahmoud Ahmed
- Ophthalmology, Royal Liverpool University Hospital, Liverpool, UK
| | - Cathy Hopkinson
- Statistics, NHS Blood and Transplant Organ Donation and Transplantation Directorate, Bristol, UK
| | - Vito Romano
- Department of Eye and Vision Science, University of Liverpool, Liverpool, UK
| | - Elinor Curnow
- Statistics, NHS Blood and Transplant Organ Donation and Transplantation Directorate, Bristol, UK
| | - Stephen B Kaye
- Ophthalmology, Royal Liverpool University Hospital, Liverpool, UK
- Department of Eye and Vision Science, University of Liverpool, Liverpool, UK
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16
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Ang M, He F, Lang S, Sabanayagam C, Cheng CY, Arundhati A, Mehta JS. Machine Learning to Analyze Factors Associated With Ten-Year Graft Survival of Keratoplasty for Cornea Endothelial Disease. Front Med (Lausanne) 2022; 9:831352. [PMID: 35721073 PMCID: PMC9200960 DOI: 10.3389/fmed.2022.831352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 04/28/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose Machine learning analysis of factors associated with 10-year graft survival of Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. Methods Prospective study of donor characteristics, clinical outcomes and complications from consecutive patients (n = 1,335) who underwent DSAEK (946 eyes) or PK (389 eyes) for Fuchs’ endothelial dystrophy (FED) or bullous keratopathy (BK) were analyzed. Random survival forests (RSF) analysis using the highest variable importance (VIMP) factors were determined to develop the optimal Cox proportional hazards regression model. Main outcome measure was 10-year graft survival with RSF analysis of factors associated with graft failure. Results Mean age was 68 ± 11 years, 47.6% male, in our predominantly Chinese (76.6%) Asian cohort, with more BK compared to FED (62.2 vs. 37.8%, P < 0.001). Overall 10-year survival for DSAEK was superior to PK (73.6 vs. 50.9%, log-rank P < 0.001). RSF based on VIMP (best Harrell C statistic: 0.701) with multivariable modeling revealed that BK (HR:2.84, 95%CI:1.89–4.26; P < 0.001), PK (HR: 1.64, 95%CI:1.19–2.27; P = 0.002), male recipients (HR:1.75, 95%CI:1.31–2.34; P < 0.001) and poor pre-operative visual acuity (HR: 1.60, 95%CI:1.15–2.22, P = 0.005) were associated with graft failure. Ten-year cumulative incidence of complications such as immune-mediated graft rejection (P < 0.001), epitheliopathy (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK compared to the DSAEK group. Conclusion In our study, RSF combined with Cox regression was superior to traditional regression techniques alone in analyzing a large number of high-dimensional factors associated with 10-year corneal graft survival in Asian eyes with cornea endothelial disease.
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Affiliation(s)
- Marcus Ang
- Singapore National Eye Centre, Singapore, Singapore.,Singapore Eye Research Institute, Singapore, Singapore.,Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Singapore
| | - Feng He
- Singapore Eye Research Institute, Singapore, Singapore
| | | | - Charumathi Sabanayagam
- Singapore Eye Research Institute, Singapore, Singapore.,Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Singapore
| | - Ching-Yu Cheng
- Singapore Eye Research Institute, Singapore, Singapore.,Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Singapore
| | - Anshu Arundhati
- Singapore National Eye Centre, Singapore, Singapore.,Singapore Eye Research Institute, Singapore, Singapore.,Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Singapore
| | - Jodhbir S Mehta
- Singapore National Eye Centre, Singapore, Singapore.,Singapore Eye Research Institute, Singapore, Singapore.,Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Singapore, Singapore
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17
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Shehab A, Gram N, Ivarsen A, Hjortdal J. The importance of donor characteristics, post-mortem time and preservation time for use and efficacy of donated corneas for posterior lamellar keratoplasty. Acta Ophthalmol 2022; 100:269-276. [PMID: 34173345 DOI: 10.1111/aos.14943] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/20/2021] [Indexed: 11/30/2022]
Abstract
PURPOSE The aim of this study is to examine whether donor age, death-to-retrieval time (DRT) and death-to-preservation time (DPT) as well as total preservation time affect donor cornea suitability for endothelial keratoplasty (EK) or penetrating keratoplasty (PK). METHODS A registry-based study was performed identifying 3248 corneas donated between 2011 and 2017. Data regarding donated corneas were extracted from The Danish Cornea Bank and donor medical records and evaluated for missing information. The primary outcome was whether ECD at preservation (ECD-P) or at release (ECD-R) was >2000 cells/mm2 . RESULTS Logistic regression for ECD-P showed a significant negative effect of increasing age (OR: 1.07, 95%CI: 1.05;1.08, p < 0.001) on donor suitability. Higher ECD-P had a significant positive effect on graft eligibility (OR: 1.007 95%CI: 1.003;1.010, p < 0.001). No significant effect of donor sex (p = 0.547), DRT (p = 0.289) or DPT (p = 0.102) on donor suitability for EK or PK (Chi-squared test). CONCLUSION High donor age and low ECD-P negatively affect the suitability of donor corneas for EK/PK whereas DRT and DPT did not affect graft suitability.
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Affiliation(s)
- Anders Shehab
- Department of Ophthalmology Aarhus University Hospital Aarhus Denmark
- Department of Clinical Medicine Aarhus University Aarhus Denmark
| | - Niels Gram
- Department of Ophthalmology Aarhus University Hospital Aarhus Denmark
- Department of Clinical Medicine Aarhus University Aarhus Denmark
| | - Anders Ivarsen
- Department of Ophthalmology Aarhus University Hospital Aarhus Denmark
- Department of Clinical Medicine Aarhus University Aarhus Denmark
| | - Jesper Hjortdal
- Department of Ophthalmology Aarhus University Hospital Aarhus Denmark
- Department of Clinical Medicine Aarhus University Aarhus Denmark
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Liu S, Wong YL, Walkden A. Current Perspectives on Corneal Transplantation. Clin Ophthalmol 2022; 16:631-646. [PMID: 35282172 PMCID: PMC8904759 DOI: 10.2147/opth.s289359] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 01/20/2022] [Indexed: 12/18/2022] Open
Abstract
Disease of the cornea is the third leading cause of blindness worldwide. Corneal graft surgery is one of the most successful forms of solid organ transplantations in humans, with ever-increasing developments in surgical technique. To date, approximately 4504 corneal transplants are performed in the United Kingdom each year. While full thickness transplantation was the most commonly performed keratoplasty over the last few decades, selective lamellar transplantation of the diseased layers of the cornea has been universally adopted. This comprehensive review aims to provide an updated synthesis on different types of corneal transplantations, their treatment outcomes, and the associated complications of each procedure in both adult and paediatric population. In addition, we also present an up-to-date summary of the emerging therapeutic approaches that have the potential to reduce the demand for donor-dependent keratoplasty.
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Affiliation(s)
- Siyin Liu
- Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Yee Ling Wong
- Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - Andrew Walkden
- Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Correspondence: Andrew Walkden, Email
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19
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Chaussard D, Bloch F, Elnar AA, Zevering Y, Vermion JC, Moskwa R, Perone JM. Identification of the preoperative and perioperative factors that predict postoperative endothelial cell density after Descemet membrane endothelial keratoplasty: A retrospective cohort study. PLoS One 2022; 17:e0264401. [PMID: 35202443 PMCID: PMC8870504 DOI: 10.1371/journal.pone.0264401] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/09/2022] [Indexed: 11/19/2022] Open
Abstract
Low postoperative endothelial-cell density (ECD) plays a key role in graft failure after Descemet-membrane endothelial keratoplasty (DMEK). Identifying pre/perioperative factors that predict postoperative ECD could help improve DMEK outcomes. This retrospective study was conducted with consecutive adult patients with Fuchs-endothelial corneal dystrophy who underwent DMEK in 2015–2019 and were followed for 12 months. Patients underwent concomitant cataract surgery (triple-DMEK) or had previously undergone cataract surgery (pseudophakic-DMEK). Multivariate analyses assessed whether: patient age/sex; graft-donor age; preoperative ECD, mean keratometry, or visual acuity; triple DMEK; surgery duration; surgical difficulties; and need for rebubbling predicted 6- or 12-month ECD in the whole cohort or in subgroups with high/low ECD at 6 or 12 months. The subgroups were generated with the clinically relevant threshold of 1000 cells/mm2. Surgeries were defined as difficult if any part was not standard. In total, 103 eyes (95 patients; average age, 71 years; 62% women) were included. Eighteen eyes involved difficult surgery (14 difficult graft preparation or unfolding cases and four others). Regardless of how the study group was defined, the only pre/perioperative variable that associated significantly with 6- and 12-month ECD was difficult surgery (p = 0.01, 0.02, 0.05, and 0.0009). Difficult surgery also associated with longer surgery duration (p = 0.002). Difficult-surgery subgroup analysis showed that difficult graft dissection associated with lower postoperative ECD (p = 0.03). This association may reflect endothelial cell loss due to excessive graft handling and/or an intrinsic unhealthiness of the endothelial cells in the graft that conferred unwanted physical properties onto the graft that complicated its preparation/unfolding.
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Affiliation(s)
- Dimitri Chaussard
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
| | - Florian Bloch
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
| | - Arpiné Ardzivian Elnar
- Clinical Research Support Unit, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville Regional Hospital Center, Metz, France
| | - Yinka Zevering
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
| | - Jean-Charles Vermion
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
| | - Rémi Moskwa
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
| | - Jean-Marc Perone
- Ophthalmology Department, Mercy Hospital, Regional Hospital Center (CHR) of Metz-Thionville, Metz, France
- Institut Jean Lamour, Lorraine University, Nancy, France
- * E-mail:
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20
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Shah R, Hirwe S, Ashar J, Sengupta S. Utilization rate of corneal tissue obtained from donors over 75 years of age in Western India for keratoplasty. Indian J Ophthalmol 2022; 70:511-515. [PMID: 35086227 PMCID: PMC9023935 DOI: 10.4103/ijo.ijo_1329_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Purpose: To examine the utilization patterns of cornea procured from diseased individuals ≥75 years of age at an eye bank in western India. Methods: In this retrospective study, data from 1,217 eyes of 653 donors with age ≥75 years were reviewed from October 2008 to December 2019. Donor age, lens status, endothelial cell count (ECD), utilization of the tissue for transplantation or non-clinical purposes (e.g., research, training/discarded), and causes of non-utilization were noted. Results: The mean age of the donors was 80.9 ± 4.6 years and the tissue utilization rate was 36.5% (445 out of 1,217 eyes). The eyes used for keratoplasty procedures had a lower donor age (79.6 ± 5.7 vs. 81.5 ± 5.1; P < 0.001), a higher endothelial cell count (2493 ± 531 vs. 2034 ± 581; P < 0.001), and were more often phakic (61% vs. 36.6%) compared to the unused group. A multivariable logistic regression analysis showed that the likelihood of tissue utilization for keratoplasty was 13% higher with every 100-cell increment in donor ECD (odds ratio [OR] = 1.13, 95% CI = 1.10–1.16, P < 0.001) and 33% lower with having a pseudophakic status in the donor eye (OR = 0.67, 95% CI = 0.52–0.87, P = 0.03). Age was not a significant determinant of tissue utilization when used in the same multivariable model. Conclusion: More than one-third of the eyes (36.5%) can be utilized even when the donors are above 75 years of age. Eyes that were more likely to be utilized for keratoplasty were phakic and had a significantly higher ECD; age was not a determinant in tissue utilization.
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Affiliation(s)
- Rakesh Shah
- Swaraashi Netralaya, Mumbai, Maharashtra, India
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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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Epithelial cells removed in advanced surface ablation (ASA) surgery can be used as a source of corneal samples to perform in vitro studies. Exp Eye Res 2021; 214:108878. [PMID: 34871567 DOI: 10.1016/j.exer.2021.108878] [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: 07/30/2021] [Revised: 11/17/2021] [Accepted: 11/30/2021] [Indexed: 11/22/2022]
Abstract
Human corneal epithelial cells are needed to study corneal pathophysiology in vitro. Due to the limitations of cell lines, the use of primary cells is highly desirable, but the scarcity of human tissues, along with ethical issues, make it difficult to accomplish all required experiments. In advanced surface ablation (ASA), the central corneal epithelium is removed and discarded. We hypothesized that ASA samples could be used to perform in vitro assays. In this study, 29 samples from patients undergoing ASA were recovered in supplemented DMEM/F12 culture medium, RIPA buffer, or RLT lysis buffer. The first aim was to determine whether cells could be maintained in culture. Although with the explant technique, tissue pieces did not attach to the culture surface, after disaggregation, cells showed high viability (90.0 ± 6.0%), attached to plates, and remained viable for up to 14 days. The second aim was to elucidate if ASA samples could be used to study protein or gene expression. Cytokeratin-3, ZO-1, Ki67, and E-cadherin protein expression were confirmed by immunofluorescence. Total protein (485.8 ± 115.8 μg) was isolated from cells in RIPA buffer, and GAPDH was detected by Western blotting, indicating that samples are adequate for protein studies. RNA (9.0 ± 3.6 μg) was isolated from samples in RLT lysis buffer, and GAPDH gene expression was studied by PCR, confirming that samples were also suitable for gene expression studies. These results suggest that samples obtained from corneal surface ablation procedures may constitute a valuable source of human cells to accomplish in vitro studies.
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Sharma B, Soni D, Mohan RR, Sarkar D, Gupta R, Chauhan K, Karkhur S, Morya AK. Corticosteroids in the Management of Infectious Keratitis: A Concise Review. J Ocul Pharmacol Ther 2021; 37:452-463. [PMID: 34448619 DOI: 10.1089/jop.2021.0040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Microbial keratitis is devastating corneal morbidity with a variable spectrum of clinical manifestations depending on the infective etiology. Irrespective of the varied presentation delayed treatment can lead to severe visual impairment resulting from corneal ulceration, possible perforation, and subsequent scarring. Corticosteroids with a potent anti-inflammatory activity reduce host inflammation, thus minimizing resultant scarring while improving ocular symptoms. These potential effects of corticosteroids have been applied widely to treat various corneal diseases ranging from vernal keratoconjunctivitis to dry eye disease. However, antimicrobial therapy remains the mainstay of treatment in microbial keratitis, whereas the use of adjunctive topical corticosteroid therapy remains a matter of debate. Understandably, the use of topical corticosteroids is a double-edged sword with pros and cons in the treatment of microbial keratitis. Herein we review the rationale for and against the use and safety of topical corticosteroids in the treatment of infective keratitis. Important considerations, including type, dose, efficacy, the timing of initiation of corticosteroids, use of concomitant antimicrobial agents, and duration of corticosteroid therapy while prescribing corticosteroids for microbial keratitis, have been discussed. This review intends to provide new insights into the therapeutic utility of steroids as adjunctive treatment of corneal ulcer.
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Affiliation(s)
- Bhavana Sharma
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Deepak Soni
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Rajiv R Mohan
- Department of Ophthalmology, College of Veterinary Medicine and Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, USA
| | - Deepayan Sarkar
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Rituka Gupta
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Khushboo Chauhan
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Samendra Karkhur
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Arvind K Morya
- Department of Ophthalmology, All India Institute of Medical Sciences, Jodhpur, India
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Abstract
PURPOSE To investigate the key factors associated with eyes with an endothelial cell density (ECD) of ≥2000 cells/mm at 5 years after corneal transplantation. METHODS This retrospective cohort study included 174 eyes that underwent penetrating keratoplasty by 1 corneal specialist surgeon at the Baptist Eye Institute, Kyoto, Japan, from 1998 through 2011 and that were carefully followed for over 5 years postoperative. In all operated eyes, corneal ECD was measured at 1, 2, 3, 4, and 5 years postoperative. Multivariate analysis with adjustment for preoperative donor ECD was performed between eyes with an ECD of ≥2000 cells/mm and those with an ECD of <2000 cells/mm at 5 years postoperative. RESULTS Of the 174 eligible eyes, 16 eyes (9.2%) had an ECD of ≥2000 cells/mm at 5 years postoperative, and the annual rate of endothelial cell loss (mean ± SD) was 2.3% ± 3.7%. Multivariate analysis findings revealed that the donor-associated and surgery-related factors were not significant factors. Only the recipient diagnosis of bullous keratopathy was significantly associated with an ECD of <2000 cells/mm at 5 years postoperative. Of those 16 eyes, 6 (37.5%) had a recipient diagnosis of bullous keratopathy. CONCLUSIONS None of the donor- and surgery-related factors, previously recognized as associated with a lower endothelial cell loss after penetrating keratoplasty, were found to be significant in this study, thus suggesting that there are still unknown factors associated with maintaining a higher ECD over the long-term postoperative period.
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Moshirfar M, Odayar VS, McCabe SE, Ronquillo YC. Corneal Donation: Current Guidelines and Future Direction. Clin Ophthalmol 2021; 15:2963-2973. [PMID: 34285462 PMCID: PMC8285277 DOI: 10.2147/opth.s284617] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022] Open
Abstract
PURPOSE This review aims to outline current practices and guidelines of corneal donation and eye banking, describes the implications of COVID-19 and emerging diseases on the corneal donor pool, and discusses future trends to improve and increase the efficiency of the processes involved in corneal donation and eye banking. SUMMARY Corneal screening, preservation, corneal storage, and prevention of systemic disease transmission from donor to recipient have been crucial in shaping the policies of the FDA and eye banks across the world. Eye banks globally have developed varying guidelines and criteria for evaluating the viability of donor corneas. Variables such as the age of the donor, medical history, and potential disease transmission are important screening parameters. While known infectious diseases may be transmissible through the cornea, emerging infectious diseases that are not well studied may be more transmissible than other infections. In particular, coronavirus has impacted corneal transplantation as SARS-CoV-2 expression has been detected in corneal tissue and conjunctiva. In recent years, partial-thickness corneal transplantations have been introduced. Lamellar grafts and other corneal layers are now utilized for transplantation of the specific areas that are damaged.
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Affiliation(s)
- Majid Moshirfar
- Hoopes Vision Research Center, Draper, UT, 84020, USA
- John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA
- Utah Lions Eye Bank, Murray, UT, 84107, USA
| | - Varshini S Odayar
- Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA
| | - Shannon E McCabe
- Hoopes Vision Research Center, Draper, UT, 84020, USA
- Mission Hills Eye Center, Pleasant Hill, CA, 94523, USA
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26
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Català P, Thuret G, Skottman H, Mehta JS, Parekh M, Ní Dhubhghaill S, Collin RWJ, Nuijts RMMA, Ferrari S, LaPointe VLS, Dickman MM. Approaches for corneal endothelium regenerative medicine. Prog Retin Eye Res 2021; 87:100987. [PMID: 34237411 DOI: 10.1016/j.preteyeres.2021.100987] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/28/2021] [Accepted: 07/01/2021] [Indexed: 12/13/2022]
Abstract
The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.
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Affiliation(s)
- Pere Català
- University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands
| | - Gilles Thuret
- Laboratory of Biology, Engineering and Imaging of Corneal Graft, BiiGC, Faculty of Medicine, University of Saint Etienne, Saint Etienne, France; Institut Universitaire de France, Paris, France
| | - Heli Skottman
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jodhbir S Mehta
- Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-National University Singapore Medical School, Singapore; Singapore National Eye Centre, Singapore
| | - Mohit Parekh
- Institute of Ophthalmology, University College London, London, UK; The Veneto Eye Bank Foundation, Venice, Italy; Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Sorcha Ní Dhubhghaill
- Department of Ophthalmology, Antwerp University Hospital, Edegem, Belgium; Ophthalmology, Visual Optics and Visual Rehabilitation, Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium
| | - Rob W J Collin
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Rudy M M A Nuijts
- University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
| | | | - Vanessa L S LaPointe
- Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands
| | - Mor M Dickman
- University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands.
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Bicket AK, Mihailovic A, Zheng C, Kashaf MS, Nagarajan N, Huang AS, Chapagain S, Da J, Ramulu PY. Comparison of Patient-Reported Functional Recovery From Different Types of Ophthalmic Surgery. Am J Ophthalmol 2021; 227:201-210. [PMID: 33626362 DOI: 10.1016/j.ajo.2021.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/29/2021] [Accepted: 02/18/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To characterize and compare patient-reported recovery of function after cataract or glaucoma surgery using a novel visual analog scale. DESIGN Prospective observational cohort study. METHODS Daily for 2 weeks and weekly thereafter, patients recovering from trabeculectomy, tube shunt implantation, or cataract extraction (CE) completed a diary-style questionnaire including visual analog scales (VASs; scored 0-100) grading pain and global function. Clinical examination data and medical histories were collected. Generalized estimating equation models evaluated associations between VAS function scores and pain or visual acuity (VA) and compared scores between surgery types. RESULTS Among 51 participants followed for 12 weeks, tube shunt placement reduced postoperative day 1 (POD1) function by 47 of 100 points vs CE (P = .006), while trabeculectomy did not reduce POD1 function vs CE (P = .33). After CE, trabeculectomy, and tube shunt placement, average VAS function scores increased 13.94 per week for 2 weeks (P < .001), 4.18 per week for 4 weeks (P = .02), and 7.76 per week for 7 weeks (P < .001), respectively. After those timepoints, there was no further significant change. Beyond 2 weeks, pain levels plateaued, and VA returned to baseline across surgery types; function was inversely related to pain or VA only for the first 2 or 4 weeks, respectively. CONCLUSIONS Patients recovering from cataract and glaucoma surgery report reduced function in the postoperative period. Tube shunt implantation causes greater morbidity than trabeculectomy, and both are associated with slower improvement than CE. Early postoperative function is associated with VA and pain, but neither fully explains reported impairment. A VAS for function may efficiently capture postoperative recovery.
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28
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Kwon HY, Hyon JY, Jeon HS. Effect of Donor Age on Graft Survival in Primary Penetrating Keratoplasty with Imported Donor Corneas. KOREAN JOURNAL OF OPHTHALMOLOGY 2021; 34:35-45. [PMID: 32037748 PMCID: PMC7010478 DOI: 10.3341/kjo.2019.0086] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/23/2019] [Accepted: 10/04/2019] [Indexed: 11/25/2022] Open
Abstract
Purpose To investigate the influence of donor age on corneal graft survival following primary penetrating keratoplasty (PK) with imported donor corneas. Methods The eyes of patients who underwent primary PK with imported donor corneas were classified retrospectively into two groups according to a donor-age cutoff of 65 years. Primary outcome measures were rejection-free graft survival and graft survival. Cox proportional hazard regression analysis was used to assess the factors affecting graft survival. Survival analysis was performed using the Kaplan-Meier method, while differences between groups were examined using a log-rank test. A subgroup analysis of low- and high-risk eyes according to preoperative diagnosis was also performed. Results A total of 140 eyes from 138 patients (age, 58 ± 18 years) were enrolled. Cox regression analysis revealed that the donor age of 65 years or older group presented an increased risk of both graft rejection and failure. Survival analysis revealed that rejection-free graft survival and graft survival rates were higher in eyes in the donor age of less than 65 years group. Finally, in the subgroup analysis, both rejection-free graft survival and graft survival rates were significantly higher in the donor age of less than 65 years group than in the donor age of 65 years or older group, but only in the low-risk subgroup. Conclusions Donor age may correlate with graft survival in primary PK performed with imported donor corneas. Donor age could be a considerable factor in primary PK with imported donor corneas, especially in preoperatively low-risk patients.
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Affiliation(s)
- Hyeon Yoon Kwon
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
| | - Joon Young Hyon
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.,Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Sun Jeon
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.,Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
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29
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O'Brien RC, Ishwaran H, Szczotka-Flynn LB, Lass JH. Random Survival Forests Analysis of Intraoperative Complications as Predictors of Descemet Stripping Automated Endothelial Keratoplasty Graft Failure in the Cornea Preservation Time Study. JAMA Ophthalmol 2021; 139:191-197. [PMID: 33355637 DOI: 10.1001/jamaophthalmol.2020.5743] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance A new analytic method can evaluate factors of interest associated with graft failure after Descemet stripping automated endothelial keratoplasty (DSAEK) or more generally in any ophthalmic surgical setting with a time-to-event outcome. Objective To reanalyze types of intraoperative complications associated with DSAEK graft failure in the Cornea Preservation Time Study using random survival forests. Design, Setting, and Participants This cohort study, initially conceived in April 2019, used a prediction model to conduct a post hoc secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. The study included 1090 participants, representing 1330 eyes, undergoing DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic or aphakic corneal edema (75 eyes [5.6%]). Enrollment occurred between April 16, 2012, and February 20, 2014, and follow-up ended June 5, 2017. Statistical analysis was performed from July 10, 2019, to May 29, 2020. Intervention Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with preservation time of 7 days or less or 8 to 14 days. Main Outcomes and Measures Ranked variable importance for intraoperative complications among 50 donor, recipient, and eye bank variables and restricted mean survival time through 47 months (1434 days) after DSAEK were examined. Random survival forests, a nonparametric method (with less restrictive model assumptions) that is far more flexible in its ability to model nonlinear effects and interactions, was used to analyze the data. Results This study included 1090 participants (663 women [60.8%]; median age, 70 years [range, 42-90 years]), representing 1330 eyes. Random survival forests ranked a DSAEK intraoperative complication as the third most predictive factor of graft failure, after surgeon and eye bank, in the final model with 5 predictors. In the first 47 months after DSAEK, the estimated mean difference in restricted mean survival time for grafts that experienced a DSAEK intraoperative complication vs those that did not was -227 days (99% CI, -352 to -70 days) based on the final RSF model. Conclusions and Relevance These findings, while post hoc, support the hypothesis that random survival forests allow for an improved analytic approach for identifying factors predictive of graft failure and for obtaining adjusted graft survival estimates. Random survival forests offer the opportunity to guide the development of future population-based cohort ophthalmic surgical studies, establishing definitive factors for procedural success.
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Affiliation(s)
- Robert C O'Brien
- Department of Data Science, University of Mississippi Medical Center, Jackson
| | - Hemant Ishwaran
- Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami, Florida
| | - Loretta B Szczotka-Flynn
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio.,University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Jonathan H Lass
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio.,University Hospitals Cleveland Medical Center, Cleveland, Ohio
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Anshu A, Li L, Htoon HM, de Benito-Llopis L, Shuang LS, Singh MJ, Tiang Hwee TD. Long-Term Review of Penetrating Keratoplasty: A 20-Year Review in Asian Eyes. Am J Ophthalmol 2021; 224:254-266. [PMID: 33129808 DOI: 10.1016/j.ajo.2020.10.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/17/2020] [Accepted: 10/18/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To review the long-term outcomes of optical, therapeutic and tectonic forms of penetrating keratoplasty over a 20-year period in Asian eyes. DESIGN Prospective cohort study involving the Singapore Corneal Transplant Study (SCTS). METHODS All penetrating keratoplasties (PK) performed at the Singapore National Eye Centre (SNEC) from January 1991 to December 2010 were analyzed using records from the computerized database of the SCTS. This database includes preoperative, intraoperative, and postoperative patient data and donor cornea data. Only primary grafts were included. Patient demographics, donor cornea source, indications for grafting, complications, graft survival rate, and causes of graft failure were analyzed. RESULTS A total of 1,206 primary PKs were performed. The mean age of the patients was 55 years (range: <1-101 years). The overall corneal graft survival rates at 1, 5, 10, 15, and 20 years were 91%, 66.8%, 55.4%, 52%, and 44%, respectively. For optical grafts, pseudophakic bullous keratopathy, postinfectious corneal scarring and thinning and keratoconus were the most common diagnoses. Graft survival for optical grafts was significantly better than therapeutic and tectonic grafts at all time points. Multivariate analysis suggested that a younger donor cornea age and higher donor endothelial cell count are associated with better long-term graft survival for optical grafts. Irreversible allograft rejection and late endothelial failure accounted for more than 60% of graft failures. CONCLUSIONS Graft survival decreased over time from 91% at 1 year to 44% at 20 years' follow-up. Allograft rejection and late endothelial failure accounted for more than 60% of graft failures.
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31
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Arundhati A, Chew MC, Lim L, Mehta JS, Lang SS, Htoon HM, Tan DT. Comparative Study of Long-term Graft Survival Between Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty. Am J Ophthalmol 2021; 224:207-216. [PMID: 33253665 DOI: 10.1016/j.ajo.2020.11.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 11/08/2020] [Accepted: 11/13/2020] [Indexed: 11/18/2022]
Abstract
PURPOSE Endothelial failure and immunological graft rejection remain long-term complications leading to late graft failure in penetrating keratoplasty (PK). Deep anterior lamellar keratoplasty (DALK) has emerged as a viable alternative that enables preservation of the host's endothelial cells to eliminate risks of endothelial rejection and failure. The aim of this study was to compare long-term graft survival between PK and DALK. DESIGN Retrospective clinical cohort study. METHODS All consecutive primary grafts of DALKs (n = 362) and PKs (n = 307) performed for optical indications in a tertiary eye center from the ongoing, prospective Singapore Corneal Transplant Study. Ten-year graft survival outcomes were compared. Cases in which endothelial pathologies were diagnosed were excluded, as DALK was not performed for such cases. Main outcome measurements were mean graft survival rate. RESULTS The survival rate for PK was 94.4%, 80.4%, and 72.0% at 1, 5, and 10 years, respectively; and 95.8%, 93.9%, and 93.9% at 1, 5, and 10 years, respectively, for DALK (P = .001). Patients who underwent PK developed more complications of glaucoma (29.3% vs. 11.6%, respectively; P < .001), allograft rejection (16.6% vs. 1.7%, respectively; P < .001), epithelial problems (10.4% vs. 5.5%, respectively; P = .018), and nonimmunological failure (7.8% vs. 1.9%, respectively; P < .001), compared to DALK. Rates of graft failure attributable to rejection (36.7% vs. 5.9%, respectively; P = .015) and endothelial failure (36.7% vs. 5.9%, respectively; P = .015) were lower in DALK. CONCLUSIONS The 10-year graft survival for primary DALK was superior to that for PK for corneal pathologies with functional endothelium. Primary DALK resulted in fewer post-operative complications and lower rates of graft rejection and failure. This study strengthens the case in favor of performing DALK over PK when possible.
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Affiliation(s)
- Anshu Arundhati
- Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore
| | | | - Li Lim
- Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore
| | - Jodhbir Singh Mehta
- Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore
| | | | | | - Donald T Tan
- Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
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32
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Alió Del Barrio JL, Bhogal M, Ang M, Ziaei M, Robbie S, Montesel A, Gore DM, Mehta JS, Alió JL. Corneal transplantation after failed grafts: Options and outcomes. Surv Ophthalmol 2020; 66:20-40. [PMID: 33065176 DOI: 10.1016/j.survophthal.2020.10.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/30/2020] [Accepted: 10/05/2020] [Indexed: 12/27/2022]
Abstract
Corneal transplantation is the most commonly performed human tissue transplantation procedure worldwide. Because of the large number of transplants, corneal graft failure has become one of the most common indications for corneal transplantation. The relatively recently developed lamellar transplant techniques have brought about specific potential complications leading to graft failure that may require different approaches to repeat transplantation other than penetrating keratoplasty. On the other hand, these new lamellar techniques also provide novel ways of rescuing failed penetrating grafts, with potential advantages over successive penetrating keratoplasties, such as reduced intraoperative risks and faster visual rehabilitation. We summarize the incidence and risk factors of graft failure for penetrating and lamellar (stromal and endothelial) corneal transplants and discuss the various surgical alternatives currently available to rescue such failed grafts, with a focus on the reported outcomes and limitations.
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Affiliation(s)
- Jorge L Alió Del Barrio
- Cornea, Cataract and Refractive Surgery Unit, Vissum (Miranza Group), Alicante, Spain; Division of Ophthalmology, Universidad Miguel Hernández, Alicante, Spain.
| | | | - Marcus Ang
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology and Visual Science, Duke-NUS Graduate Medical School, Singapore
| | - Mohammed Ziaei
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Scott Robbie
- Cornea Unit, Guy's & St Thomas' Hospital, London, UK
| | - Andrea Montesel
- Cornea, Cataract and Refractive Surgery Unit, Vissum (Miranza Group), Alicante, Spain; Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
| | - Daniel M Gore
- External Disease Service, Moorfields Eye Hospital, London, UK
| | - Jodhbir S Mehta
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology and Visual Science, Duke-NUS Graduate Medical School, Singapore
| | - Jorge L Alió
- Cornea, Cataract and Refractive Surgery Unit, Vissum (Miranza Group), Alicante, Spain; Division of Ophthalmology, Universidad Miguel Hernández, Alicante, Spain
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Gender medicine in corneal transplantation: influence of sex mismatch on rejection episodes and graft survival in a prospective cohort of patients. Cell Tissue Bank 2020; 22:47-56. [PMID: 32935191 DOI: 10.1007/s10561-020-09864-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 09/07/2020] [Indexed: 10/23/2022]
Abstract
To evaluate the effect of donor-to-recipient sex mismatched (male donor corneas to female recipients) on the incidence of rejection episodes and failures up to 1 year after corneal transplantation. Prospective observational cohort study, with donor corneas randomly assigned and surgeons blind to the sex of donor. A unique eye bank retrieved and selected the donor corneas transplanted in 4 ophthalmic units in patients with clinical indication for primary or repeated keratoplasty for optical reasons, perforating or lamellar, either anterior or posterior. Rejection episode defined as any reversible or irreversible endothelial, epithelial or stromal sign, with or without development of corneal edema, and graft failure as a permanently cloudy graft or a regraft for any reason detected or acknowledged during a postoperative ophthalmic visit at any time up to 1 year after surgery were recorded.156 (28.6%) patients resulted donor-to-recipient gender mismatched for H-Y antigen (male donor to female recipient). During the 12 months follow-up, 83 (14.7%, 95% CI 12.0-17.9) grafts showed at least 1 rejection episode and 17 (3.2%, 95% CI 2.0-5.0) failed after immune rejection, among 54 (9.6%, 95% CI 7.4-12.3) grafts failed for all causes. No significant differences between matched and mismatched patients were found for cumulative incidence of both rejection episodes (15.2% and 13.5%) and graft failures following rejection (3.2% and 2.6%), respectively. Multivariable analyses showed that H-Y matching either is not a predictive factor for rejection or graft failure nor seems to influence incidence of failures on respect to patient's risk category. The lack of influence of donor-to-recipient mismatched on the rate of rejections and graft failures resulting from this study do not support the adoption of donor-recipient matching in the allocation of corneas for transplantation.
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Franco JJ, Reyes Luis JL, Rahim S, Greenstein S, Pineda R. Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo. Br J Ophthalmol 2020; 105:1076-1081. [PMID: 32859719 DOI: 10.1136/bjophthalmol-2020-316435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 07/05/2020] [Accepted: 07/19/2020] [Indexed: 11/04/2022]
Abstract
AIM To evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation. METHODS A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45 years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC). RESULTS Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76 months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm2 to 1436 cells/mm2 at the conclusion of postoperative follow-up. CONCLUSION Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely 'mature' corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.
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Affiliation(s)
| | | | - Salma Rahim
- Ophthalmology, Makkah Eye Complex, Khartoum, Sudan
| | | | - Roberto Pineda
- Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
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35
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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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36
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Montesel A, Alió Del Barrio JL, Yébana Rubio P, Alió JL. Corneal graft surgery: A monocentric long-term analysis. Eur J Ophthalmol 2020; 31:1700-1708. [PMID: 32757624 DOI: 10.1177/1120672120947592] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To investigate indications, outcomes and changes in clinical patterns of keratoplasty surgery in a Spanish tertiary eye center. SETTING Vissum Instituto Oftalmológico, Alicante, Spain. METHODS A retrospective review was performed on clinical records of patients that underwent any kind of corneal transplant from 2001 to 2017 in the study center. Inclusion criteria involved the presence of detailed preoperative examination, surgical report and at least 12 months follow-up after the surgery. A statistical analysis was performed on the indications for keratoplasty, survival rates, type of graft failures, and visual outcomes. RESULTS A total of 907 keratoplasties procedures were identified. About 432 penetrating keratoplasty (PK), 148 deep anterior lamellar keratoplasty (DALK), and 134 endothelial keratoplasty (EK) met the inclusion criteria. Cumulative survival rate ranged from 94% to 69% in a 1-year period and from 85% to 45% in a 5-years period according to the different graft types. The main cause for failure was immunological rejection for PK, surface diseases for DALK and primary graft failure for EK. Postoperative visual function improved for all the surgical techniques. CONCLUSION Corneal transplant is a challenging surgery still complicated by a relevant risk of failure. Our study offers a useful opinion of the current trends on keratoplasty in our country, where the outcomes of the grafts differ considerably in relation to the indications and the different surgical techniques, with lamellar procedures that showed higher rates of success and better visual outcomes than full-thickness grafts.
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Affiliation(s)
- Andrea Montesel
- Cornea, Cataract and Refractive Surgery Unit, Vissum Corporación, Alicante, Spain
| | - Jorge L Alió Del Barrio
- Cornea, Cataract and Refractive Surgery Unit, Vissum Corporación, Alicante, Spain.,Division of Ophthalmology, School of Medicine, Universidad Miguel Hernández, Alicante, Spain
| | - Pilar Yébana Rubio
- Cornea, Cataract and Refractive Surgery Unit, Vissum Corporación, Alicante, Spain
| | - Jorge L Alió
- Cornea, Cataract and Refractive Surgery Unit, Vissum Corporación, Alicante, Spain.,Division of Ophthalmology, School of Medicine, Universidad Miguel Hernández, Alicante, Spain
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Corneal donation for research versus for transplantation: A-year prospective study of acceptance rates in a French University Hospital. PLoS One 2020; 15:e0233392. [PMID: 32437464 PMCID: PMC7241724 DOI: 10.1371/journal.pone.0233392] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 05/04/2020] [Indexed: 11/20/2022] Open
Abstract
Fresh corneal donation is essential for basic and preclinical research, but more unknown to public and the medical teams than donation for transplantation: it may raise concerns. We prospectively compared the acceptance rates and the characteristics of targeted corneal donation for research versus donation for transplantation during one year. The Agence de la Biomédecine authorized us to procure fresh corneas targeted for research, only from the donors with medical contraindications for transplantation, in order not to increase grafts shortage. Three nurses from the hospital coordination team of Saint-Etienne University Hospital, obtained consent for research and transplantation in parallel, screening all intra-hospital deaths cases, following standard protocol to check no refusal from families, despite the French opt-out system. They contacted 127 families for research and 244 for transplantation, in 71% of cases by telephone. Consent was obtained in 62% of cases for research and 54% for transplantation (P = 0.135). The main contraindication for transplantation was the cognitive disorders (66%) followed by the blood cancers (8%). This new specific activity, providing new source of fresh corneas for research immediately usable without any eyebank storage steps, didn't reduce the number of corneas procured for transplantation versus previous years (P = 0.998). Donors in the research group were 10 years older (P<0.001) without difference regarding endothelial cell quality (P = 0.071), allowing maximal clinical relevance for protocols using these fresh human scientific corneas provided by targeted donation.
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Schaub F, Collmer M, Schrittenlocher S, Bachmann BO, Cursiefen C, Hos D. Outcome of Descemet Membrane Endothelial Keratoplasty Using Corneas from Donors ≥80 Years of Age. Am J Ophthalmol 2020; 211:200-206. [PMID: 31837315 DOI: 10.1016/j.ajo.2019.12.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 10/20/2019] [Accepted: 12/01/2019] [Indexed: 12/26/2022]
Abstract
PURPOSE The purpose of this study was to investigate whether corneas from donors ≥80 years old are suitable for Descemet membrane endothelial keratoplasty (DMEK). DESIGN Retrospective, comparative, interventional case series. METHODS Records of 1,765 consecutive DMEKs were reviewed and matched with corresponding donor tissue data. Older donors (≥80 years of age) were compared to younger donors (<80 years). Outcome measurements in DMEK recipients included best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), central corneal thickness (CCT) at 3 and 6 months and at 1, 2, and 3 years' follow-up and re-bubbling rates. RESULTS Of 1,748 DMEKs, 284 (16.2%) were performed with older donor lamellae (mean donor age, 83.96 ± 3.19 years; range, 80-94 years) and 1,464 (83.7%) with younger donor tissue (mean donor age, 65.27 ± 9.57 years; range, 17-79). BSCVA results were comparable for all postoperative time points. CCT results for younger donors were more favorable in the early postoperative course (P < 0.001 at 6 months; and P < 0.001 at 1 year), whereas mid-term results were comparable in both groups. ECD values were significantly higher in donors <80 years of age preoperatively and during the first 2 postoperative years (P ≤ 0.024). Overall re-bubbling rates were comparable in both groups. CONCLUSIONS Older donors, ≥80 to 94 years of age, seem to produce comparable mid-term functional results following DMEK surgery compared to younger donors. The use of corneas from donors aged ≥80 for DMEK surgery may therefore be a promising approach to counteract global donor shortage.
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Affiliation(s)
- Friederike Schaub
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
| | - Maurice Collmer
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Silvia Schrittenlocher
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Björn O Bachmann
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Claus Cursiefen
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Germany
| | - Deniz Hos
- Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Germany
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Kanavi MR, Javadi MA, Chamani T, Rahmanian M, Kanavi MR, Kheiri B. Proposed risk factors for failure of transplanted eye bank-prepared descemet stripping automated endothelial keratoplasty tissues. Cell Tissue Bank 2020; 21:151-158. [PMID: 31907690 DOI: 10.1007/s10561-020-09808-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 01/01/2020] [Indexed: 11/30/2022]
Abstract
To investigate the possible risk factors for failure of transplanted eye bank-prepared Descemet stripping automated endothelial keratoplasty (DSAEK) tissues. In a retrospective study between March 2011 and March 2019, all the failed DSAEK cases (131 cases) reported to the Central Eye Bank of Iran were compared with a surgeon-matched successful DSAEK group (control, 126 cases) in terms of the donor, DSAEK tissue, and recipient characteristics. Univariate analysis indicated that the DSAEK tissue preparation from excised corneoscleral tissues (OR 2.17; P = 0.026) and donor conjunctival hyperemia (OR 1.62; P = 0.042) were more common in the re-DSAEK group than in the controls. Other donor and recipient characteristics as well as other DSAEK tissue criteria were not significantly different between the re-DSAEK and control groups. DSAEK lenticules in both re-DSAEK and control groups demonstrated symmetric contours. Subgroup analyses in the re-DSAEK group revealed a higher rate of surgeons' low to moderate experience in comparison to those of high experience (P < 0.001). Additionally, failed DSAEK was observed more commonly in donors aged over 50 years than among those under 30 years (P < 0.001). Our study showed that DSAEK tissues prepared from excised corneoscleral tissues and from donors with conjunctival hyperemia were associated with higher rates of re-DSAEK due to failed DSAEK. An increasing trend of re-DSAEK was observed with shorter surgeons' experience and more advanced donor's age.
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Affiliation(s)
- Mozhgan Rezaei Kanavi
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, No 23, Paydarfard-9th Boostan St., Pasdaran Ave, Tehran, 1666673111, Iran.
| | - Mohammad Ali Javadi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Central Eye Bank of Iran, Tehran, Iran
| | | | | | | | - Bahareh Kheiri
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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40
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Pessoa JLE, Schirmer J, Freitas DD, Knihs NDS, Roza BDA. Ocular tissue distribution in the State of São Paulo: analysis on corneal discarding reasons. Rev Lat Am Enfermagem 2019; 27:e3196. [PMID: 31618389 PMCID: PMC6792342 DOI: 10.1590/1518-8345.3041.3196] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 06/18/2019] [Indexed: 11/22/2022] Open
Abstract
Objective to identify the reasons for refusal of corneas. Method this was a cross-sectional, retrospective, descriptive and correlational
study composed of 5,560 optical corneas. The information was taken from the
notification, organ procurement and distribution centers database as well as
donor records. Descriptive statistics were used for the analysis of
categorical variables and specific tests with a significance level of 5% for
assessing the associations between variables. This study met the ethical
aspects of scientific research. Results 60% of the donors were male and 40% died by circulatory problems. The main
reason for refusal as informed by transplant teams is the donor’s age and
the endothelial cell count. For each year added to the donor’s age, there is
a 1% decrease in the chance that this cornea will be used for
transplantation, and the increase of 100 cells per mm2 increases the chances
that this cornea will be used by 9%. Conclusion the main cause of refusal in the acceptance of corneal tissue is related to
the age and the endothelial cell count.
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Affiliation(s)
- João Luis Erbs Pessoa
- Secretaria de Saúde do Estado de São Paulo, Central de Transplantes, São Paulo, SP, Brasil
| | - Janine Schirmer
- Universidade Federal de São Paulo, Escola Paulista de Enfermagem, São Paulo, SP, Brasil
| | - Denise de Freitas
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brasil
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Aldave AJ, Terry MA, Szczotka-Flynn LB, Liang W, Ayala AR, Maguire MG, O'Brien RC, Benetz BA, Bokosky JE, Dunn SP, Gillette TE, Hammersmith KM, Hardten DR, Jeng BH, Jones MF, Lindstrom RL, Maverick KJ, Nirankari VS, Oliva MS, Raber IM, Rapuano CJ, Rosenwasser GO, Ross KW, Seedor JW, Shamie N, Stoeger CG, Tauber S, Van Meter WS, Verdier DD, Lass JH. Effect of Graft Attachment Status and Intraocular Pressure on Descemet Stripping Automated Endothelial Keratoplasty Outcomes in the Cornea Preservation Time Study. Am J Ophthalmol 2019; 203:78-88. [PMID: 30849341 DOI: 10.1016/j.ajo.2019.02.029] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 01/25/2019] [Accepted: 02/22/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS 1090 individuals (1330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N = 675) or 8-14 days (N = 655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and (99% confidence intervals). RESULTS Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio [OR]: 2.29 [1.30, 4.02]), increased pre-lamellar dissection central corneal thickness (OR: 1.13 [1.01, 1.27] per 25µ increase), and operative complications (OR: 2.97 [1.24, 7.11]). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; P < .001) and 29 (2.4%; P = .04), respectively, of 1226 eyes without GD. 24 (2%) of 1330 study eyes had early acutely elevated postoperative IOP that was associated with a higher risk of graft failure through 3 years (hazard ratio: 3.42 [1.01, 11.53]), but not with a lower mean 3-year ECD (mean difference 61 (-479, 601) cells/mm2, P = .77). History of elevated postoperative IOP beyond 1 month was not significantly associated with 3-year graft success or ECD. CONCLUSIONS Donor diabetes, increased donor corneal thickness, and intraoperative complications were associated with an increased risk of GD. Early acutely elevated postoperative IOP and GD significantly increased the risk for graft failure following DSAEK.
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Lass J, Benetz BA, Verdier DD, Szczotka-Flynn LB, Ayala AR, Liang W, Aldave AJ, Dunn SP, McCall T, Mian SI, Navarro LC, Patel SV, Pramanik S, Rosenwasser GO, Ross KW, Terry MA, Kollman C, Gal RL, Beck RW. Corneal Endothelial Cell Loss 3 Years After Successful Descemet Stripping Automated Endothelial Keratoplasty in the Cornea Preservation Time Study: A Randomized Clinical Trial. JAMA Ophthalmol 2019; 135:1394-1400. [PMID: 29127432 DOI: 10.1001/jamaophthalmol.2017.4970] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Importance Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty. Objective To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT. Design, Setting, and Participants A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 945 eyes of 769 participants were included in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK, performed primarily for Fuchs endothelial corneal dystrophy (96% of the cohort). The study was conducted from April 16, 2012, to June 5, 2017. Interventions DSAEK with random assignment of a donor cornea with PT of 0 to 7 days (0-7d PT) or 8 to 14 days (8-14d PT). Main Outcomes and Measures Endothelial cell density (ECD) at 3 years determined by a central image analysis reading center from clinical specular or confocal central endothelial images. Results Nine hundred forty-five eyes of 769 participants (median age, 70 years [range, 42-90 years], 60.8% women, 93.0% white) in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK were included. At the initial eye bank tissue screening, mean (SD) central ECD was 2746 (297) cells/mm2 in the 0-7d PT group (n = 485) and 2723 (284) cells/mm2 in the 8-14d PT group (n = 460). At 3 years, the mean (SD) ECD decreased from baseline by 37% (21%) in the 0-7d PT group and 40% (22%) in the 8-14d PT group to 1722 (626) cells/mm2 and 1642 (631) cells/mm2, respectively (mean difference, 73 cells/mm2; 95% CI, 8-138 cells/mm2; P = .03). When analyzed as a continuous variable (days), longer PT was associated with lower ECD (mean difference by days, 15 cells/mm2; 95% CI, 4-26 cells/mm2; P = .006). Endothelial cell loss (ECL) was comparable from 4 to 13 days’ PT (n = 878; 36%-43% when tabulated by day). Available extension study ECD results at 4 years mirrored those at 3 years in the 203 eyes in the 0-7d PT group (mean [SD] ECD, 1620 [673] cells/mm2 and mean [SD] ECL, 41% [23%]) and 209 eyes in the 8-14d PT group (mean [SD] ECD, 1537 [683] cells/mm2 and mean [SD] ECL, 44% [23%]) (mean difference, 112 cells/mm2; 95% CI, 5-219 cells/mm2; P = .04). Conclusions and Relevance Although ECL 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer PT, the effect of PT on ECL is comparable from 4 to 13 days’ PT.
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Affiliation(s)
- Jonathan Lass
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio,University Hospitals Cleveland Medical Center, Cleveland, Ohio,Cornea Image Analysis Reading Center, Cleveland, Ohio
| | - Beth Ann Benetz
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio,University Hospitals Cleveland Medical Center, Cleveland, Ohio,Cornea Image Analysis Reading Center, Cleveland, Ohio
| | | | - Loretta B Szczotka-Flynn
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio,University Hospitals Cleveland Medical Center, Cleveland, Ohio,Cornea Image Analysis Reading Center, Cleveland, Ohio
| | | | - Wendi Liang
- Jaeb Center for Health Research, Tampa, Florida
| | - Anthony J Aldave
- Stein Eye Institute, UCLA (University of California, Los Angeles)
| | | | | | | | | | - Sanjay V Patel
- Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
| | | | | | | | | | | | - Robin L Gal
- Jaeb Center for Health Research, Tampa, Florida
| | - Roy W Beck
- Jaeb Center for Health Research, Tampa, Florida
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Patel SV, Lass JH, Benetz BA, Szczotka-Flynn LB, Cohen NJ, Ayala AR, Maguire MG, Drury DC, Dunn SP, Jeng BH, Jones MF, Menegay HJ, Oliva MS, Rosenwasser GOD, Seedor JA, Terry MA, Verdier DD. Postoperative Endothelial Cell Density Is Associated with Late Endothelial Graft Failure after Descemet Stripping Automated Endothelial Keratoplasty. Ophthalmology 2019; 126:1076-1083. [PMID: 30790587 DOI: 10.1016/j.ophtha.2019.02.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 01/17/2019] [Accepted: 02/11/2019] [Indexed: 01/21/2023] Open
Abstract
PURPOSE To determine whether preoperative endothelial cell density (ECD) and postoperative ECD after Descemet stripping automated endothelial keratoplasty (DSAEK) are associated with late endothelial graft failure (LEGF) in the Cornea Preservation Time Study (CPTS). DESIGN Cohort study within a multicenter, randomized clinical trial. PARTICIPANTS A total of 1007 individuals (1223 study eyes), mean age 70 years, undergoing DSAEK for Fuchs' dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE) (6% of eyes) and followed for up to 5 years. METHODS Central ECD was determined by a central image analysis reading center. Preoperative ECD was determined for 1209 eyes that did not fail and 14 eyes that experienced LEGF. The ECD at 6 and 12 months after DSAEK, the change in ECD from preoperative to 6 and 12 months, surgeon-reported operative complications, and postoperative graft dislocation were investigated for an association with LEGFs unrelated to other postoperative events. Univariable and multivariable Cox proportional hazards regression models were used to assess associations. MAIN OUTCOME MEASURES Late endothelial graft failure and its associations with pre- and postoperative ECD and operative complications. RESULTS The cumulative probability of LEGF was 1.3% (95% confidence interval [CI], 0.8%-2.4%). Median (interquartile range [IQR]) preoperative ECDs were similar for eyes with LEGF (2523; 2367-3161) cells/mm2) and eyes without failure (2727; 2508-2973) cells/mm2) (P = 0.34). The ECD at 6 months was associated with LEGF (P < 0.001) in time-to-event analyses, whereas preoperative ECD was not (P = 0.55). The cumulative incidence (95% CI) of LEGF was 6.5% (3.0%, 14.0%) for 97 grafts with a 6-month ECD less than 1200 cells/mm2, 0.3% (0.0%, 2.4%) for 310 grafts with a 6-month ECD between 1200 and 2000 cells/mm2, and 0.6% (0.1%, 2.7%) for 589 grafts with a 6-month ECD greater than 2000 cells/mm2. In multivariable analyses, ECD at 6 months and operative complications were both associated with LEGF (P = 0.002 and P = 0.01, respectively), whereas graft dislocation was not (P = 0.61). CONCLUSIONS In eyes undergoing DSAEK, preoperative ECD is unrelated to LEGF, whereas lower ECD at 6 months is associated with LEGF. Early endothelial cell loss after DSAEK and intraoperative complications should be minimized to improve graft survival.
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Affiliation(s)
- Sanjay V Patel
- Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
| | - Jonathan H Lass
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio.
| | - Beth Ann Benetz
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio
| | - Loretta B Szczotka-Flynn
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio
| | | | | | - Maureen G Maguire
- Center for Preventive Ophthalmology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Steven P Dunn
- Michigan Cornea Consultants, P.C., Southfield, Michigan
| | - Bennie H Jeng
- University of California-San Francisco, San Francisco, California (now the University of Maryland, Baltimore, Maryland)
| | | | - Harry J Menegay
- Case Western Reserve University Department of Ophthalmology and Visual Sciences and University Hospitals Eye Institute, Cleveland, Ohio
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Lass JH, Benetz BA, Patel SV, Szczotka-Flynn LB, O’Brien R, Ayala AR, Maguire MG, Daoud YJ, Greiner MA, Hannush SB, Lee WB, Mauger TF, Menegay HJ, Mifflin MD, Raizman MB, Rose-Nussbaumer J, Schultze RL, Schmidt GA, Sugar A, Terry MA, Verdier DD. Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study. JAMA Ophthalmol 2019; 137:185-193. [PMID: 30422157 PMCID: PMC6439830 DOI: 10.1001/jamaophthalmol.2018.5669] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 09/26/2018] [Indexed: 12/19/2022]
Abstract
Importance Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.
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Affiliation(s)
- Jonathan H. Lass
- Cornea Image Analysis Reading Center, Department of Ophthalmology and Visual Sciences, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio
| | - Beth Ann Benetz
- Cornea Image Analysis Reading Center, Department of Ophthalmology and Visual Sciences, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio
| | - Sanjay V. Patel
- Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
| | - Loretta B. Szczotka-Flynn
- Cornea Image Analysis Reading Center, Department of Ophthalmology and Visual Sciences, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio
| | | | | | - Maureen G. Maguire
- Center for Preventive Ophthalmology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Yassine J. Daoud
- The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
| | | | | | | | - Thomas F. Mauger
- The Ohio State University Wexner Medical Center-Havener Eye Institute, Columbus
| | - Harry J. Menegay
- Cornea Image Analysis Reading Center, Department of Ophthalmology and Visual Sciences, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio
| | | | | | | | | | | | - Alan Sugar
- Kellogg Eye Center, University of Michigan, Ann Arbor
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Abstract
PURPOSE To report long-term visual and astigmatism outcomes in cases of zig-zag femtosecond laser-enabled penetrating keratoplasty (FLEK). METHODS Retrospective review. Three hundred thirty-five eyes of 287 patients underwent (FLEK) with a zig-zag incision pattern. Patients were assessed preoperatively and underwent postoperative comprehensive examinations at standard intervals of 1, 3, 6, 9, and 12 months, and 6 months thereafter. Postoperative uncorrected distance visual acuity and spectacle-corrected distance visual acuity and manifest and topographical (Mrx cyl and Topo cyl) astigmatism were compared with preoperative values. RESULTS Three hundred thirty-five eyes received FLEK with zig-zag configuration. Data are presented for the last recorded visit before any refractive procedure. Sutures were removed in 202 of 335 eyes at an average time to removal of 1.3 ± 1.1 years, and a mean follow-up period of 2.9 ± 2.1 years (range 0-10 years). After full suture removal, mean uncorrected distance visual acuity and spectacle-corrected distance visual acuity were logarithm of the minimum angle of resolution 0.84 (Snellen 20/138) ± 0.55 and 0.33 (Snellen 20/42) ± 0.33, respectively. Mean Mrx cyl and Topo cyl of these groups were 3.38 ± 2.22 and 4.77 ± 3.15, respectively. Of the total number of grafts, the rate of graft rejections was 14.0%, and the failure rate was 5.6%. CONCLUSIONS The femtosecond laser-generated zig-zag-shaped incision results in lower manifest and topographical astigmatism than the reported average for conventional penetrating keratoplasty. Graft rejection and failure rates are similar to published data for conventional penetrating keratoplasty.
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Gediz F, Yüksel B, Küsbeci T, Akmaz O, Kartı Ö. The Effect of Donor- and Recipient-Related Factors on Corneal Graft Survival in Penetrating Keratoplasty. Semin Ophthalmol 2018; 34:11-18. [PMID: 30496015 DOI: 10.1080/08820538.2018.1549681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Purpose: To investigate the impact of donor and recipient factors on graft survival in penetrating keratoplasty (PK).Material and Methods: This retrospective study included 365 eyes that underwent PK using corneas from 231 donors between June 2010 and June 2015. Patients were divided into three groups (group 1: primary endothelial diseases; group 2: iatrogenic endothelial disorders; and group 3: other pathologies with a healthy endothelium) according to PK indications. The primary outcome measure was corneal graft survival at the last visit (clear or opaque). Graft clarity was assessed using Kaplan-Meier survival analysis.Results: The most frequent PK indication was keratoconus (KC) (20.5%) followed by pseudophakic bullous keratopathy (PBK) (18.9%). Donor age had a negative impact on endothelial cell density (ECD) measured by an eye bank specular microscope (p < 0.001). Median best-corrected visual acuity in logarithm of the minimum angle of resolution units increased from 2.1 to 0.8 at 1 year after PK (p < 0.001). The clear graft rate was 96.7% at year 1, 88.8% at year 2, and 85.5% at year 3. Overall graft survival was 84.9% during a median of 39 months (range: 24-79 months) of follow-up. A higher graft survival rate (67.2%) was observed in KC compared to PBK during 6 years (p < 0.001). Recipients younger than 50 years of age showed a better graft survival rate than those older than 70 years of age (p = 0.037). Donor ECD, time between excision and death, and preservation time had no significant effect on graft survival. Frequent graft rejection episodes (GREs) and additional procedures during surgery had a negative impact on graft survival (p < 0.001 and p = 0.014, respectively). A worse graft survival was observed in group 2 compared to groups 1 and 3 (p = 0.042).Conclusions: Young recipient age and KC were associated with a better graft survival. Graft endothelial density and preservation time had no impact on graft survival. PBK, low vision at baseline and year 1, frequent GREs, and additional interventions during surgery had a negative impact on graft survivals.
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Affiliation(s)
- Feyza Gediz
- Department of Ophthalmology, Bozyaka Training and Research Hospital, İzmir, Turkey
| | - Bora Yüksel
- Department of Ophthalmology, Bozyaka Training and Research Hospital, İzmir, Turkey
| | - Tuncay Küsbeci
- Department of Ophthalmology, Bozyaka Training and Research Hospital, İzmir, Turkey
| | - Okan Akmaz
- Department of Ophthalmology, Merkezefendi State Hospital, Manisa, Turkey
| | - Ömer Kartı
- Department of Ophthalmology, Bozyaka Training and Research Hospital, İzmir, Turkey
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Terry MA, Aldave AJ, Szczotka-Flynn LB, Liang W, Ayala AR, Maguire MG, Croasdale C, Daoud YJ, Dunn SP, Hoover CK, Macsai MS, Mauger TF, Pramanik S, Rosenwasser GOD, Rose-Nussbaumer J, Stulting RD, Sugar A, Tu EY, Verdier DD, Yoo SH, Lass JH. Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study. Ophthalmology 2018; 125:1700-1709. [PMID: 30098353 PMCID: PMC6196643 DOI: 10.1016/j.ophtha.2018.08.002] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 07/27/2018] [Accepted: 08/03/2018] [Indexed: 01/08/2023] Open
Abstract
PURPOSE To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES Graft success at 3 years. RESULTS One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.
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Affiliation(s)
| | - Anthony J Aldave
- Stein Eye Institute, University of California, Los Angeles, Los Angeles, California
| | - Loretta B Szczotka-Flynn
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, Ohio
| | - Wendi Liang
- Jaeb Center for Health Research, Tampa, Florida
| | | | - Maureen G Maguire
- Center for Preventive Ophthalmology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Yassine J Daoud
- The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
| | - Steven P Dunn
- Michigan Cornea Consultants, PC, Southfield, Michigan
| | | | | | - Thomas F Mauger
- The Ohio State University Wexner Medical Center, Havener Eye Institute, Columbus, Ohio
| | | | | | - Jennifer Rose-Nussbaumer
- Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California
| | | | - Alan Sugar
- University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan
| | - Elmer Y Tu
- University of Illinois Chicago Eye and Ear Infirmary, Chicago, Illinois
| | | | - Sonia H Yoo
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
| | - Jonathan H Lass
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, Ohio.
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Comparison of Hospital Cornea Retrieval and Voluntary Eye Donation Program in Eye Banking. Eye Contact Lens 2018; 44 Suppl 1:S54-S58. [PMID: 28060143 DOI: 10.1097/icl.0000000000000320] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Comparison of demographic, clinical, microbiological, and utility profile of the corneas obtained through hospital corneal retrieval program (HCRP) and voluntary eye donation (VED) program. METHODS Donor corneas retrieved during a 14 months period at National eye bank, India were included in the study. The donor cornea grading was done according to the cornea donor study. The corneal swabs were taken from the donor eyes and were sent for microbiological evaluation. The quality of the donor corneas and their utility was assessed. RESULTS Out of 1,014 donor corneas collected (700 through HCRP, 314 through VED), 455 were of optical grade (91.2% [415/455] through the HCRP and 8.7% [40/455] through the VED). HCRP had a higher proportion of donors in younger age (81.6% vs. 21%, P<0.0001), clear lens (78.6% vs. 66.2%, P<0.0001), and endothelial cell counts of more than2,000 cells per squared millimeter (64.9% vs. 28%, P<0.0001). Higher proportions of corneas in HCRP were used for optical indications (Penetrating keratoplasty, 24.5% vs. 13.3%, P<0.0001 and endothelial keratoplasty, 18.14% vs. 4.14%, P<0.0001). VED had a greater number of corneas found unsuitable for keratoplasty (37.4% vs. 6.4%, P<0.001). Most of the donors in the HCRP belonged to lower socioeconomic status (59.4% vs. 17.9%, P<0.0001). No significant difference was found in the microbial contamination between the two groups. CONCLUSIONS Most corneas retrieved through HCRP were of optical grade quality and efforts should be focused on HCRP to reduce the demand-supply deficit in cornea transplantation.
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Dayoub JC, Cortese F, Anžič A, Grum T, de Magalhães JP. The effects of donor age on organ transplants: A review and implications for aging research. Exp Gerontol 2018; 110:230-240. [PMID: 29935294 PMCID: PMC6123500 DOI: 10.1016/j.exger.2018.06.019] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 06/15/2018] [Accepted: 06/18/2018] [Indexed: 12/21/2022]
Abstract
Despite the considerable amount of data available on the effect of donor age upon the outcomes of organ transplantation, these still represent an underutilized resource in aging research. In this review, we have compiled relevant studies that analyze the effect of donor age in graft and patient survival following liver, kidney, pancreas, heart, lung and cornea transplantation, with the aim of deriving insights into possible differential aging rates between the different organs. Overall, older donor age is associated with worse outcomes for all the organs studied. Nonetheless, the donor age from which the negative effects upon graft or patient survival starts to be significant varies between organs. In kidney transplantation, this age is within the third decade of life while the data for heart transplantation suggest a significant effect starting from donors over age 40. This threshold was less defined in liver transplantation where it ranges between 30 and 50 years. The results for the pancreas are also suggestive of a detrimental effect starting at a donor age of around 40, although these are mainly derived from simultaneous pancreas-kidney transplantation data. In lung transplantation, a clear effect was only seen for donors over 65, with negative effects of donor age upon transplantation outcomes likely beginning after age 50. Corneal transplants appear to be less affected by donor age as the majority of studies were unable to find any effect of donor age during the first few years posttransplantation. Overall, patterns of the effect of donor age in patient and graft survival were observed for several organ types and placed in the context of knowledge on aging.
Data on the effects of donor age upon the outcomes of organ transplantation are an underutilized resource in biogerontology We compiled data on the effect of donor age following liver, kidney, pancreas, heart, lung and cornea transplantation Older donor age is associated with worse outcomes for all the organs studied The donor age from which the negative effects upon survival starts to be significant varies between organs
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Affiliation(s)
- Jose Carlos Dayoub
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, Room 281, 6 West Derby Street, Liverpool L7 8TX, United Kingdom
| | - Franco Cortese
- Biogerontology Research Foundation, Research Department, Oxford, United Kingdom
| | - Andreja Anžič
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, Room 281, 6 West Derby Street, Liverpool L7 8TX, United Kingdom
| | - Tjaša Grum
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, Room 281, 6 West Derby Street, Liverpool L7 8TX, United Kingdom
| | - João Pedro de Magalhães
- Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, Room 281, 6 West Derby Street, Liverpool L7 8TX, United Kingdom; Biogerontology Research Foundation, Research Department, Oxford, United Kingdom.
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Ramirez-Garcia MA, Khalifa YM, Buckley MR. Vulnerability of corneal endothelial cells to mechanical trauma from indentation forces assessed using contact mechanics and fluorescence microscopy. Exp Eye Res 2018; 175:73-82. [PMID: 29883637 DOI: 10.1016/j.exer.2018.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/17/2018] [Accepted: 06/04/2018] [Indexed: 11/25/2022]
Abstract
Corneal endothelial cell (CEC) loss occurs from tissue manipulation during anterior segment surgery and corneal transplantation as well as from contact with synthetic materials like intraocular lenses and tube shunts. While several studies have quantified CEC loss for specific surgical steps, the vulnerability of CECs to isolated, controllable and measurable mechanical forces has not been assessed previously. The purpose of this study was to develop an experimental testing platform where the susceptibility of CECs to controlled mechanical trauma could be measured. The corneal endothelial surfaces of freshly dissected porcine corneas were subjected to a range of indentation forces via a spherical stainless steel bead. A cell viability assay in combination with high-resolution fluorescence microscopy was used to visualize and quantify injured/dead CEC densities before and after mechanical loading. In specimens subjected to an indentation force of 9 mN, the mean ± SD peak contact pressure P0 was 18.64 ± 3.59 kPa (139.81 ± 26.93 mmHg) in the center of indentation and decreased radially outward. Injured/dead CEC densities were significantly greater (p ≤ 0.001) after mechanical indentation of 9 mN (167 ± 97 cells/mm2) compared to before indentation (39 ± 52 cells/mm2) and compared to the sham group (34 ± 31 cells/mm2). In specimens subjected to "contact only" - defined as an applied indentation force of 0.65 mN - the peak contact pressure P0 was 7.31 ± 1.5 kPa (54.83 ± 11.25 mmHg). In regions where the contact pressures was below 78% of P0 (<5.7 kPa or 42.75 mmHg), injured/dead CEC densities were within the range of CEC loss observed in the sham group, suggesting negligible cell death. These findings indicate that CECs are highly susceptible to mechanical trauma via indentation, supporting the established "no-touch" policy for ophthalmological procedures. While CECs can potentially remain viable below contact pressures of 5.7 kPa (42.75 mmHg), this low threshold suggests that prevention of indentation-associated CEC loss may be challenging.
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Affiliation(s)
| | | | - Mark R Buckley
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA
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