Comparison of repeat penetrating keratoplasty, DSAEK and DMEK for the management of endothelial failure of previous PK.

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Harry Roberts, Laura de Benito-Llopis This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1918783/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jun, 2023 Read the published version in Eye → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: To compare the clinical outcomes of repeat penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (‘DSAEK-on-PK’) or Descemet membrane endothelial keratoplasty (‘DMEK-on-PK’) for the management of endothelial failure of previous penetrating keratoplasty Design: Retrospective, interventional consecutive case series. Participants: 104 consecutive eyes of 100 patients requiring a second keratoplasty for endothelial failure of their primary penetrating keratoplasty performed between September 2016 and December 2020 Intervention: Repeat keratoplasty Main Outcome Measures : Primary failure rate, 12 and 24 month survival, visual acuity at 12 and 24 months, rebubbling rate and complication profile. Results: Repeat PK was performed in 61/104 eyes (58.7%), DSAEK-on-PK was performed in 21/104 eyes (20.2%) and DMEK-on-PK was performed in 22/104 eyes (21.2%). 6.6% of repeat PKs failed in the first 12 months compared to 19% of DSAEK and 36.4% of DMEK. Chances of 2 year survival were 79.4% for repeat PK, 69.4% for DSAEK and 58.7% for DMEK. Visual acuity at one year was logMAR 0.53±0.51 in the redo PK group, 0.25±0.17 for DSAEK and 0.30±0.38 for DMEK. 24 month outcomes were 0.34± 0.28, 0.08 ± 0.16, and 0.36 ± 0.36 respectively. Conclusions: DMEK-on-PK and DSAEK-on-PK are known to have greater primary failure rates than redo PK but have faster rehabilitation times. DMEK-on-PK may offer the best clinical outcome when successful but also has the greatest primary failure rate. Penetrating keratoplasty Descemet membrane endothelial keratoplasty Descemet stripping endothelial keratoplasty endothelium cornea Introduction Despite the rise of lamellar keratoplasty techniques in the last two decades, penetrating keratoplasty (PK) is still commonly performed and remains the procedure of choice for selected indications by many surgeons. 1 Depending on the indication for surgery, a primary PK may have a median survival time of between 15–20 years. 2 Despite this apparent longevity, many PK recipients may ‘outlive’ their graft and require further keratoplasty. Repeat transplant is therefore one of the most common indications for transplant and in the United States is the second most common indication for PK and the fourth most common indication for endothelial keratoplasty (EK). 1 In the United Kingdom, regrafts represent 21.1% of all corneal transplants between 1999–2016. 3 As endothelial failure (whether primary failure, late decompensation, or irreversible rejection) of the PK represents the majority of indications for regraft, then surgical options for management of these cases include repeat PK, Descemet stripping (automated) endothelial keratoplasty (DSAEK/DSEK) or Descemet membrane endothelial keratoplasty (DMEK). 2 While many case series of outcomes for a single technique have been published, comparative studies have been relatively few and either compare DSAEK-on-PK vs. redo PK or DMEK-on-PK vs. DSAEK-on-PK. 4 – 7 To date we are not aware of any study comparing clinical outcomes of all three treatment modalities in one series. The aim of this study was to compare the 12- and 24-month outcomes of redo PK vs DSAEK-on-PK vs DMEK-on-PK for endothelial failure of first PK among multiple surgeons at Moorfields Eye Hospital, London, UK. Methods This study was approved as a clinical audit report by the Clinical Audit Committee at Moorfields Eye Hospital, London and was performed in accordance with the tenets of the Declaration of Helsinki. Informed consent to collect data for audit purposes was obtained before surgery as part of routine clinical practice. At Moorfields, all patients undergoing corneal graft surgery attend a follow-up appointment at 12 and 24 months after surgery at the Graft Outcome Clinic, where the status of the graft is recorded, in addition to visual acuity, complications and other clinical data. This is then introduced into the Moorfields Corneal Graft Database. This study was an institutional retrospective cohort study performed at Moorfields Eye Hospital, London, UK, with data extracted from the Moorfields Corneal Graft Database. We also reviewed case notes and electronic records from the Moorfields Electronic Healthcare Record System (OpenEyes, Apperta Foundation CIC, Sunderland, UK) to obtain information not available in the database. We included all eyes that underwent PK, DSAEK or DMEK between September 2016 and December 2020 with a past history of only one PK in the operated eye. Indication for surgery was endothelial failure of the primary PK from any cause (primary failure, immunological rejection, late endothelial failure). Eyes with previous lamellar graft surgery or more than one PK in the operated eye were not included i.e. this was the second keratoplasty for each eye in the study. Only cases with minimum 1-year follow-up and complete data available were included. We only included the initial graft performed during the audit period for each eye. Statistical Analysis All data collected in the study was entered into an electronic database via Microsoft Excel 2007 (Microsoft Corp., Redmond, WA), and statistical analyses were performed using SPSS Statistics Version 16 (IBM, Armonk, New York, USA). Descriptive statistics was used to calculate averages and standard deviation of the performances in each list. For normally distributed continuous data, 1-way analysis of variance (ANOVA) was used to determine significant differences between the means of the 3 groups P values less than 0.05 were considered statistically significant. A Kaplan-Meier survival analysis using log-rank test was conducted to compare the survival probabilities of the DMEK, DSAEK, and PK groups Results Overall, 104 eyes of 100 patients who underwent repeat PK, DSAEK or DMEK during the study period were included in the analysis. Demographics, indications for surgery and main baseline clinical data of the study population are described in Table 1 . The visual outcomes are reported in Table 2 . Eyes that developed graft failure (Table 3 ) were excluded from analysis of visual outcome but are included for the rest of the analysis. There was a statistically significant difference at baseline with eyes having repeat PK having worse pre-operative best-corrected visual acuity (BCVA) than those having DSAEK or DMEK. BCVA at 1 and 2 years postop did not show a statistically significant difference between the three groups. Table 3 demonstrates a Kaplan-Meier analysis of graft survival probability. 6.6% of repeat PKs failed in the first 12 months compared to 19% of DSAEK and 36.4% of DMEK. Chances of 2-year survival were 79.4% for repeat PK, 69.4% for DSAEK and 58.7% for DMEK. For those grafts surviving 12 months, the chances of surviving to 24 months were greatest for DMEK-on-PK at 92% vs 85% each for redo PK and DSAEK-on-PK. Postoperative complications are detailed in Table 4 . There was no difference between rebubbling rates for DSAEK (19.0%) and DMEK (18.2%). There was one case of endothelial rejection in each group (PK 1.63%, DSAEK 4.8%, DMEK 4.5%). Discussion Redo PK, DSAEK-on-PK and DMEK-on-PK are all viable treatment options for endothelial failure of PK although a direct comparison of the three techniques has yet to be published. Studies published to date have either compared DSAEK-on-PK with redo PK, DSAEK-on-PK with DMEK-on-PK or grouped all EK-on PK together. This is the first time to our knowledge that the three treatment options have been directly compared and demonstrates differences in survival rates between each procedure. The expected longevity of primary PK, DSAEK or DMEK in low risk recipients can be expected to exceed 5 years in 90% of recipients. 2 , 8 , 9 However, repeat grafts are known to have a greater failure rate than primary grafts so predicted longevity is of critical importance in offering second keratoplasty to patients. 3 The failure rates we report within the first 12 months of 6.6% (PK), 19% (DSAEK-on-PK) and 36.4% (DMEK-on-PK) are consistent with the literature with reported 12 month failure rates of 2–10% for redo PK, 11.7–36% for DSAEK-on-PK, and 7–37% for DMEK-on-PK. 4 , 6 , 7 , 10 , 11 . The greater rates of primary failure for the EK arms are likely to be partly as a result that EK-on-PK may be more technically challenging and are also known to have a higher rate of graft detachment than for primary EK with a concurrent increase in rebubbling rates. 7 EK rebubbling rates of 19% for DSAEK-on-PK are consistent with the reported rates in the literature (9–22%) and 18.2% for DMEK-on-PK is lower than the typically higher rate of rebubbling reported (28–56%). 7 Despite the 36.4% of DMEK-on-PK which fail in the first year, the 2-year survival rates in our series for those already surviving 12 months were greatest for DMEK-on-PK at 92% vs 85% each for redo PK and DSAEK-on-PK indicating that after the initial higher rate of failure for EK, the rates of late failure may plateau. There are conflicting reports in the literature on the long term differences in graft survival for EK-on-PK and redo PK. 5 , 12 Ang et al. found a three year survival rate of 66.8% for redo PK vs 86.4% for EK-on-PK in a study of 113 eyes 12 . In contrast, an Australian graft registry study including 335 redo PKs and 65 EK-on-PK demonstrated a statistically significant inferior graft survival for EK-on-PK 5 . A UK registry study found no difference in survival for EK-on-PK than redo PK for Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. 3 The discrepancy between registry study data and single centre outcomes may reflect the inclusion of learning curve cases within a registry study and outcomes from surgeons performing low volumes of keratoplasty compared with outcomes from a single centre and variations in thresholds for offering EK-on-PK vs redo PK. Advantages of EK-on-PK include that the previous astigmatic rehabilitation of the primary PK is preserved. This may be beneficial if this eye previously enjoyed a PK with low astigmatism and/or good visual acuity. An EK will offer faster visual rehabilitation than redo PK, and avoids the use of sutures to secure the graft with associated suture induced astigmatism, complications and the need for suture removal. 13 It also retains rather than resets the existing wound healing across the PK-host junction resulting in a tectonically stronger eye. 14 It is also more common to perform EK under local anaesthesia than PK thus avoiding potential disadvantages of general anesthesia. 15 Finally, it may be a better option in the setting of ocular surface disease in which a redo PK may be at high risk of surface failure. Despite the advantages of EK-on-PK, redo PK has its own advantages. It has the highest rate of 12-month survival in this series and avoids the need to posture post-operatively. Therefore, it is a good option in those who would find it difficult to tolerate post-operative posturing or those who would prefer to minimize the chance of needing further interventions such as rebubbling or regraft for primary failure. Redo PK is the most suitable option for combined endothelial failure with stromal opacity, or where the primary PK had intolerable astigmatism prior to failure. Stromal opacity may however be a relative indication for redo PK as it has been demonstrated that stromal opacity secondary to stromal edema may remodel for 12 months or longer after EK-on-PK. 16 Finally, it may often be the clinically most suitable option in complex anterior segment anatomy in which EK may be technically more challenging. It is well established that in primary keratoplasty PK has higher risk of rejection than DSAEK which in turn has higher risk of rejection than DMEK 17 . Regrafts do not have such low rates of rejection as primary low risk grafts, often due to vascularization of the primary PK. 18 While EK-on-PK may have a greater risk of rejection than primary EK, a meta-analysis of 4 studies did demonstrate that EK-on-PK had a lower risk of rejection than redo PK [OR = 0.43 (95% CI: 0.23–0.80, P = 0.007)]. 19 Our study had one case of immunological rejection in each group thus lacking sufficient numbers to make meaningful assertions. We did not find a statistically significant difference in the visual acuity at 1- or 2-years after surgery between the three techniques. The redo-PK group had significantly worse visual acuity at baseline than the DMEK-on-PK or DSAEK-on-PK groups (Table 2 ), which may indicate that this group were more likely to have concurrent endothelial failure with anterior scarring of the original PK, and the redo PK group were more likely to have a visually significant comorbidity recorded (72%) compared to DSAEK-on-PK (48%) and DMEK-on-PK (23%). As this was not a randomized controlled trial, there would have been heterogeneity between the groups and therefore this study was not designed to test for which treatment offered superior visual outcomes. Our findings were in keeping to the Australian Registry study which did not detect a visual difference between PK-PK and PK-EK. 5 Two single centre series reported better visual outcomes for DMEK-on-PK than DSAEK-on-PK although in both the DSAEK-on-PK group also had worse baseline visual acuity. 4 , 6 Without adequately powered randomised controlled trials it may be difficult to conclude which technique offers the best visual results and decision making will often come down to individual surgeon’s experience and factors such as graft astigmatism, degree of anterior stromal opacity and other risk factors for graft failure/challenging surgery. If we can extrapolate from studies on DMEK, DSAEK and PK in virgin eyes then we would assume that DMEK should be the technique most likely to optimise the visual acuity, however this needs to be balanced against the higher risk of failure within the first 12 months. 8 In summary, DMEK-on-PK had the highest 12 month failure rates followed by DSAEK-on-PK then redo PK but otherwise complication profiles were similar. There were no stastically significant differences in post-operative visual acuity although due to the nature of the study the groups were heterogenous..Surgeons should be prepared to offer any of these techniques depending on the merits of the clinical scenario and with careful attention to ocular or patient factors which may determine the choice of technique as well as the differences in failure rates compared to primary EK. Declarations ACKOWLEDGEMENTS/DISCLOSURE: No support, financial or otherwise was received for this study Harry Roberts has undertaken paid consultancy work for Alcon Inc (Fort Worth, TX, USA) in the past 36 months and has received honoraria from Thea Pharmaceuticals Ltd (Keele, UK). Laura De Benito-Llopis has no financial interest to disclose. No other acknowledgements are necessary References Eye Bank Association of America. 2019 Eye Banking Statistical Report. April 2020:1-110. Thompson RW, Price MO, Bowers PJ, Price FW. Long-term graft survival after penetrating keratoplasty. Ophthalmology. 2003;110(7):1396–1402. doi: 10.1016/S0161-6420(03)00463-9 . Aboshiha J, Jones MNA, Hopkinson CL, Larkin DFP. Differential Survival of Penetrating and Lamellar Transplants in Management of Failed Corneal Grafts. JAMA Ophthalmol. 2018;136(8):859–865. doi: 10.1001/jamaophthalmol.2018.1515 . Kiel M, Bu JB, Gericke A, et al. Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty. Cornea. 2021;40(9):1218–1224. doi: 10.1097/ICO.0000000000002786 . Keane MC, Galettis RA, Mills RAD, Coster DJ, Williams KA, for Contributors to the Australian Corneal Graft Registry. A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study. Br J Ophthalmol. 2016;100(11):1569–1575. doi: 10.1136/bjophthalmol-2015-307792 . Einan-Lifshitz A, Mednick Z, Belkin A, et al. Comparison of Descemet Stripping Automated Endothelial Keratoplasty and Descemet Membrane Endothelial Keratoplasty in the Treatment of Failed Penetrating Keratoplasty. Cornea. 2019;38(9):1077–1082. doi: 10.1097/ICO.0000000000001993 . Wu J, Wu T, Li J, Wang L, Huang Y. DSAEK or DMEK for failed penetrating keratoplasty: a systematic review and single-arm meta-analysis. Int Ophthalmol. June 2021:1–14. doi: 10.1007/s10792-021-01778-1 . Woo J-H, Ang M, Htoon HM, Tan D. Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty. Am J Ophthalmol. 2019;207:288–303. doi: 10.1016/j.ajo.2019.06.012 . Price MO, Fairchild KM, Price DA, Price FW. Descemet's stripping endothelial keratoplasty five-year graft survival and endothelial cell loss. Ophthalmology. 2011;118(4):725–729. doi: 10.1016/j.ophtha.2010.08.012 . Al-Mezaine H, Wagoner MD, King Khaled Eye Specialist Hospital Cornea Transplant Study Group. Repeat penetrating keratoplasty: indications, graft survival, and visual outcome. Br J Ophthalmol. 2006;90(3):324–327. doi: 10.1136/bjo.2005.079624 . Weisbrod DJ, Sit M, Naor J, Slomovic AR. Outcomes of repeat penetrating keratoplasty and risk factors for graft failure. Cornea. 2003;22(5):429–434. doi: 10.1097/00003226-200307000-00008 . Ang M, Ho H, Wong C, Htoon HM, Mehta JS, Tan D. Endothelial Keratoplasty After Failed Penetrating Keratoplasty: An Alternative to Repeat Penetrating Keratoplasty. 2014;158(6):1221–1227.e1221. doi: 10.1016/j.ajo.2014.08.024 . Droutsas K, Lazaridis A, Papaconstantinou D, et al. Visual Outcomes After Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty—Comparison of Specific Matched Pairs. Cornea. 2016;35(6):765. doi: 10.1097/ICO.0000000000000822 . Busin M, Bovone C, Scorcia V, et al. Ultrastructural Alterations of Grafted Corneal Buttons: The Anatomic Basis for Stromal Peeling along a Natural Plane of Separation. Am J Ophthalmol. June 2021. doi: 10.1016/j.ajo.2021.06.005 . Bizrah M, Ching G, Yusuf AM, et al. Local anaesthesia as a standard of care for penetrating keratoplasty? Eye. July 2021:1–8. doi: 10.1038/s41433-021-01618-7 . Pasari A, Price MO, Feng MT, Price FW. Descemet Membrane Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Visual Outcomes and Graft Survival. Cornea. 2019;38(2):151–156. doi: 10.1097/ICO.0000000000001763 . Anshu A, Price MO, Price FW. Risk of Corneal Transplant Rejection Significantly Reduced with Descemet's Membrane Endothelial Keratoplasty. Ophthalmology. 2012;119(3):536–540. doi: 10.1016/j.ophtha.2011.09.019 . Sibley D, Hopkinson CL, Tuft SJ, Kaye SB, Larkin DFP, National Health Service Blood and Transplant Ocular Tissue Advisory Group and contributing ophthalmologists (OTAG Study 26). Differential effects of primary disease and corneal vascularisation on corneal transplant rejection and survival. Br J Ophthalmol. 2020;104(5):729–734. doi: 10.1136/bjophthalmol-2019-314200 . Wang F, Zhang T, Kang YW, He JL, Li S-M, Li S-W. Endothelial keratoplasty versus repeat penetrating keratoplasty after failed penetrating keratoplasty: A systematic review and meta-analysis. PLoS ONE. 2017;12(7):e0180468. doi: 10.1371/journal.pone.0180468 . Tables Table 1. Baseline demographic and clinical characteristic of patients undergoing regraft and separated according the technique (PK vs DSAEK-on-PK vs DMEK-on-PK). PK N=61 DSAEK n=21 DMEK n=22 Total n=104 Age at surgery (Mean ± SD) 55.4 ± 19.5 60.3 ± 12.7 56.6 ± 14.3 56.6 ± 17.5 Laterality (% Right) 52.8% 38.8% 62.5% 51.7% Gender (%male) 60.7% 71.4% 63.6% 63.46% Indication for original PK Keratoconus BK FED Other dystrophies Bacterial Infection Fungal Infection Protozoal Infection Viral Infection Mechanical Injury Other/Unknown 19/61 11/61 0/61 3/61 1/61 3/61 2/61 2/61 2/61 18/61 7/21 3/21 1/21 1/21 1/21 0/21 1/21 0/21 0/21 7/21 13/22 1/22 2/22 2/22 0/22 0/22 0/22 1/22 1/22 2/22 39/104 15/104 3/104 6/104 2/104 3/104 3/104 3/104 3/104 27/104 Graft Diameter (mm) 8.02 ± 0.64 7.77 ± 0.35 7.52 ± 0.39 7.86 ± 0.62 Visually significant comorbidity Yes No 44/61 (72%) 17/61 10/21 (48%) 11/21 5/22 (23%) 17/22 59/104 45/104 Grade of Surgeon Consultant Fellow Other 57.4% 36.1% 6.6% 61.9% 28.6% 9.5% 50.0% 40.9% 9.1% 56.7% 35.6% 7.7% Secondary procedures at time of surgery None Phacoemulsification and IOL implantation IOL exchange Vitrectomy Glaucoma Surgery Others 67.2% 9.8% 8.2% 8.2% 3.3% 6.6% 76.2% 14.3% 0% 0% 0% 14.3% 77.3% 4.5% 0% 4.5% 0% 9.1% 71.2% 9.6% 4.8% 5.8% 1.9% 8.7% Abbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK), Bullous keratopathy (BK), Fuchs endothelial dystrophy (FED), Intraocular lens (IOL). Table 2: Best corrected visual acuity (BCVA) pre-operatively and at one and two years post-operatively for redo PK, DSAEK-on-PK and DMEK-on-PK Follow up duration (Years) Preop 1 2 BCVA LogMAR All Eyes PK 1.90 ± 0.97 1.19 ± 0.95 0.94 ± 0.93 DSAEK 1.24 ± 0.79 0.74 ± 0.78 0.75 ± 1.10 DMEK 1.17 ± 0.88 0.68 ± 0.78 0.77 ± 0.46 ANOVA F =6.49 p=0.002 F=2.47 p=0.092 F=0.17 p=0.846 Eyes with Visually significant comorbidities excluded PK 1.41 ± 0.89 0.53 ± 0.51 0.34 ± 0.28 DSAEK 0.72 ± 0.57 0.25 ± 0.17 0.08 ± 0.16 DMEK 1.23 ± 0.98 0.30 ± 0.38 0.36 ± 0.36 ANOVA F=1.79 p=0.179 F=1.35 p=0.278 F=1.84 p=0.18 Abbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK) Table 3. Kaplan-Meier analysis of graft survival probability (%) of redo PK, DSAEK-on-PK and DMEK-on-PK Redo-PK DSAEK DMEK Number of eyes at risk Kaplan-Meier survival probability estimate Number of eyes at risk Kaplan-Meier survival probability estimate Number of eyes at risk Kaplan-Meier survival probability estimate Year 1 61 93.4% 21 81.0% 22 63.6% Year 2 40 79.4% 14 69.4% 13 58.7% Abbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK) Table 4 : Post operative complication rates of redo PK, DSAEK-on-PK and DMEK-on-PK PK DSAEK DMEK Graft detachment requiring rebubbling 0 4/21 4/22 PK wound dehiscence 1/61 0 0 Endothelial rejection 1/61 1/21 1/22 Infection 0 1/21 0 Abbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK) Additional Declarations There is conflict of interest Cite Share Download PDF Status: Published Journal Publication published 02 Jun, 2023 Read the published version in Eye → Version 1 posted Editorial decision: revise 22 Sep, 2022 Review # 1 received at journal 14 Sep, 2022 Reviewer # 1 agreed at journal 23 Aug, 2022 Reviewers invited by journal 22 Aug, 2022 Editor assigned by journal 11 Aug, 2022 Submission checks completed at journal 04 Aug, 2022 First submitted to journal 01 Aug, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1918783","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":128249621,"identity":"a9d01911-24c6-46ea-833b-84a2a7034b66","order_by":0,"name":"Harry Roberts","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYBACA1RGBUMCSVoYGxjOQLUcIFoLYxsRWszZzz77zMNwT86cvff5w5/z7uTJN/AefPwBjxbLnnTj2TwMxcaWPccNm3m3PSs2OMCXbIDXYQfSmJl5GBISN9xIY2xm3HY4cQMDj5kEXi3nn0G13H/G2PhzzuHE+Q085j/warkBt4WNsYG34XBiwwEeM/whduMZM+McgwSgX9IYZ/McAzrsMI+xxBm8DktjZnhTkQAMsWMMH3/UAB3W3mP4oQKPFhBg4jFA5jITUA4CjD+IUDQKRsEoGAUjGAAAnrZOjEZs5P0AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3590-0856","institution":"Royal Devon University Healthcare NHS Foundation Trust","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Harry","middleName":"","lastName":"Roberts","suffix":""},{"id":128249622,"identity":"52e10bae-97af-48e9-b6aa-8aa2ff931a96","order_by":1,"name":"Laura de Benito-Llopis","email":"","orcid":"","institution":"Moorfields Eye Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"de Benito-Llopis","suffix":""}],"badges":[],"createdAt":"2022-08-01 18:10:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1918783/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1918783/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-023-02561-5","type":"published","date":"2023-06-02T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":37946323,"identity":"36e07f18-49e7-4cbd-a91d-cba4d341501a","added_by":"auto","created_at":"2023-06-03 07:06:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":398050,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1918783/v1/c43e1f03-2b8e-4ae5-a097-af03525792e5.pdf"}],"financialInterests":"There is conflict of interest","formattedTitle":"Comparison of repeat penetrating keratoplasty, DSAEK and DMEK for the management of endothelial failure of previous PK.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDespite the rise of lamellar keratoplasty techniques in the last two decades, penetrating keratoplasty (PK) is still commonly performed and remains the procedure of choice for selected indications by many surgeons. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Depending on the indication for surgery, a primary PK may have a median survival time of between 15\u0026ndash;20 years. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Despite this apparent longevity, many PK recipients may \u0026lsquo;outlive\u0026rsquo; their graft and require further keratoplasty. Repeat transplant is therefore one of the most common indications for transplant and in the United States is the second most common indication for PK and the fourth most common indication for endothelial keratoplasty (EK). \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In the United Kingdom, regrafts represent 21.1% of all corneal transplants between 1999\u0026ndash;2016. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAs endothelial failure (whether primary failure, late decompensation, or irreversible rejection) of the PK represents the majority of indications for regraft, then surgical options for management of these cases include repeat PK, Descemet stripping (automated) endothelial keratoplasty (DSAEK/DSEK) or Descemet membrane endothelial keratoplasty (DMEK). \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e While many case series of outcomes for a single technique have been published, comparative studies have been relatively few and either compare DSAEK-on-PK vs. redo PK or DMEK-on-PK vs. DSAEK-on-PK. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e To date we are not aware of any study comparing clinical outcomes of all three treatment modalities in one series.\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to compare the 12- and 24-month outcomes of redo PK vs DSAEK-on-PK vs DMEK-on-PK for endothelial failure of first PK among multiple surgeons at Moorfields Eye Hospital, London, UK.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was approved as a clinical audit report by the Clinical Audit Committee at Moorfields Eye Hospital, London and was performed in accordance with the tenets of the Declaration of Helsinki. Informed consent to collect data for audit purposes was obtained before surgery as part of routine clinical practice. At Moorfields, all patients undergoing corneal graft surgery attend a follow-up appointment at 12 and 24 months after surgery at the Graft Outcome Clinic, where the status of the graft is recorded, in addition to visual acuity, complications and other clinical data. This is then introduced into the Moorfields Corneal Graft Database.\u003c/p\u003e\n\u003cp\u003eThis study was an institutional retrospective cohort study performed at Moorfields Eye Hospital, London, UK, with data extracted from the Moorfields Corneal Graft Database. We also reviewed case notes and electronic records from the Moorfields Electronic Healthcare Record System (OpenEyes, Apperta Foundation CIC, Sunderland, UK) to obtain information not available in the database.\u003c/p\u003e\n\u003cp\u003eWe included all eyes that underwent PK, DSAEK or DMEK between September 2016 and December 2020 with a past history of only one PK in the operated eye. Indication for surgery was endothelial failure of the primary PK from any cause (primary failure, immunological rejection, late endothelial failure). Eyes with previous lamellar graft surgery or more than one PK in the operated eye were not included i.e. this was the second keratoplasty for each eye in the study. Only cases with minimum 1-year follow-up and complete data available were included. We only included the initial graft performed during the audit period for each eye.\u003c/p\u003e\n\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eAll data collected in the study was entered into an electronic database via Microsoft Excel 2007 (Microsoft Corp., Redmond, WA), and statistical analyses were performed using SPSS Statistics Version 16 (IBM, Armonk, New York, USA). Descriptive statistics was used to calculate averages and standard deviation of the performances in each list. For normally distributed continuous data, 1-way analysis of variance (ANOVA) was used to determine significant differences between the means of the 3 groups P values less than 0.05 were considered statistically significant. A Kaplan-Meier survival analysis using log-rank test was conducted to compare the survival probabilities of the DMEK, DSAEK, and PK groups\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOverall, 104 eyes of 100 patients who underwent repeat PK, DSAEK or DMEK during the study period were included in the analysis. Demographics, indications for surgery and main baseline clinical data of the study population are described in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eThe visual outcomes are reported in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Eyes that developed graft failure (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) were excluded from analysis of visual outcome but are included for the rest of the analysis. There was a statistically significant difference at baseline with eyes having repeat PK having worse pre-operative best-corrected visual acuity (BCVA) than those having DSAEK or DMEK. BCVA at 1 and 2 years postop did not show a statistically significant difference between the three groups.\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e demonstrates a Kaplan-Meier analysis of graft survival probability. 6.6% of repeat PKs failed in the first 12 months compared to 19% of DSAEK and 36.4% of DMEK. Chances of 2-year survival were 79.4% for repeat PK, 69.4% for DSAEK and 58.7% for DMEK. For those grafts surviving 12 months, the chances of surviving to 24 months were greatest for DMEK-on-PK at 92% vs 85% each for redo PK and DSAEK-on-PK.\u003c/p\u003e\n\u003cp\u003ePostoperative complications are detailed in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. There was no difference between rebubbling rates for DSAEK (19.0%) and DMEK (18.2%). There was one case of endothelial rejection in each group (PK 1.63%, DSAEK 4.8%, DMEK 4.5%).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRedo PK, DSAEK-on-PK and DMEK-on-PK are all viable treatment options for endothelial failure of PK although a direct comparison of the three techniques has yet to be published. Studies published to date have either compared DSAEK-on-PK with redo PK, DSAEK-on-PK with DMEK-on-PK or grouped all EK-on PK together. This is the first time to our knowledge that the three treatment options have been directly compared and demonstrates differences in survival rates between each procedure.\u003c/p\u003e\n\u003cp\u003eThe expected longevity of primary PK, DSAEK or DMEK in low risk recipients can be expected to exceed 5 years in 90% of recipients. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e However, repeat grafts are known to have a greater failure rate than primary grafts so predicted longevity is of critical importance in offering second keratoplasty to patients. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The failure rates we report within the first 12 months of 6.6% (PK), 19% (DSAEK-on-PK) and 36.4% (DMEK-on-PK) are consistent with the literature with reported 12 month failure rates of 2\u0026ndash;10% for redo PK, 11.7\u0026ndash;36% for DSAEK-on-PK, and 7\u0026ndash;37% for DMEK-on-PK.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. The greater rates of primary failure for the EK arms are likely to be partly as a result that EK-on-PK may be more technically challenging and are also known to have a higher rate of graft detachment than for primary EK with a concurrent increase in rebubbling rates.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e EK rebubbling rates of 19% for DSAEK-on-PK are consistent with the reported rates in the literature (9\u0026ndash;22%) and 18.2% for DMEK-on-PK is lower than the typically higher rate of rebubbling reported (28\u0026ndash;56%).\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eDespite the 36.4% of DMEK-on-PK which fail in the first year, the 2-year survival rates in our series for those already surviving 12 months were greatest for DMEK-on-PK at 92% vs 85% each for redo PK and DSAEK-on-PK indicating that after the initial higher rate of failure for EK, the rates of late failure may plateau. There are conflicting reports in the literature on the long term differences in graft survival for EK-on-PK and redo PK. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Ang et al. found a three year survival rate of 66.8% for redo PK vs 86.4% for EK-on-PK in a study of 113 eyes\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In contrast, an Australian graft registry study including 335 redo PKs and 65 EK-on-PK demonstrated a statistically significant inferior graft survival for EK-on-PK\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. A UK registry study found no difference in survival for EK-on-PK than redo PK for Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The discrepancy between registry study data and single centre outcomes may reflect the inclusion of learning curve cases within a registry study and outcomes from surgeons performing low volumes of keratoplasty compared with outcomes from a single centre and variations in thresholds for offering EK-on-PK vs redo PK.\u003c/p\u003e\n\u003cp\u003eAdvantages of EK-on-PK include that the previous astigmatic rehabilitation of the primary PK is preserved. This may be beneficial if this eye previously enjoyed a PK with low astigmatism and/or good visual acuity. An EK will offer faster visual rehabilitation than redo PK, and avoids the use of sutures to secure the graft with associated suture induced astigmatism, complications and the need for suture removal. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e It also retains rather than resets the existing wound healing across the PK-host junction resulting in a tectonically stronger eye.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e It is also more common to perform EK under local anaesthesia than PK thus avoiding potential disadvantages of general anesthesia. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Finally, it may be a better option in the setting of ocular surface disease in which a redo PK may be at high risk of surface failure.\u003c/p\u003e\n\u003cp\u003eDespite the advantages of EK-on-PK, redo PK has its own advantages. It has the highest rate of 12-month survival in this series and avoids the need to posture post-operatively. Therefore, it is a good option in those who would find it difficult to tolerate post-operative posturing or those who would prefer to minimize the chance of needing further interventions such as rebubbling or regraft for primary failure. Redo PK is the most suitable option for combined endothelial failure with stromal opacity, or where the primary PK had intolerable astigmatism prior to failure. Stromal opacity may however be a relative indication for redo PK as it has been demonstrated that stromal opacity secondary to stromal edema may remodel for 12 months or longer after EK-on-PK. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Finally, it may often be the clinically most suitable option in complex anterior segment anatomy in which EK may be technically more challenging.\u003c/p\u003e\n\u003cp\u003eIt is well established that in primary keratoplasty PK has higher risk of rejection than DSAEK which in turn has higher risk of rejection than DMEK\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Regrafts do not have such low rates of rejection as primary low risk grafts, often due to vascularization of the primary PK. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e While EK-on-PK may have a greater risk of rejection than primary EK, a meta-analysis of 4 studies did demonstrate that EK-on-PK had a lower risk of rejection than redo PK [OR\u0026thinsp;=\u0026thinsp;0.43 (95% CI: 0.23\u0026ndash;0.80, P\u0026thinsp;=\u0026thinsp;0.007)]. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Our study had one case of immunological rejection in each group thus lacking sufficient numbers to make meaningful assertions.\u003c/p\u003e\n\u003cp\u003eWe did not find a statistically significant difference in the visual acuity at 1- or 2-years after surgery between the three techniques. The redo-PK group had significantly worse visual acuity at baseline than the DMEK-on-PK or DSAEK-on-PK groups (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), which may indicate that this group were more likely to have concurrent endothelial failure with anterior scarring of the original PK, and the redo PK group were more likely to have a visually significant comorbidity recorded (72%) compared to DSAEK-on-PK (48%) and DMEK-on-PK (23%). As this was not a randomized controlled trial, there would have been heterogeneity between the groups and therefore this study was not designed to test for which treatment offered superior visual outcomes. Our findings were in keeping to the Australian Registry study which did not detect a visual difference between PK-PK and PK-EK. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Two single centre series reported better visual outcomes for DMEK-on-PK than DSAEK-on-PK although in both the DSAEK-on-PK group also had worse baseline visual acuity. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Without adequately powered randomised controlled trials it may be difficult to conclude which technique offers the best visual results and decision making will often come down to individual surgeon\u0026rsquo;s experience and factors such as graft astigmatism, degree of anterior stromal opacity and other risk factors for graft failure/challenging surgery. If we can extrapolate from studies on DMEK, DSAEK and PK in virgin eyes then we would assume that DMEK should be the technique most likely to optimise the visual acuity, however this needs to be balanced against the higher risk of failure within the first 12 months. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn summary, DMEK-on-PK had the highest 12 month failure rates followed by DSAEK-on-PK then redo PK but otherwise complication profiles were similar. There were no stastically significant differences in post-operative visual acuity although due to the nature of the study the groups were heterogenous..Surgeons should be prepared to offer any of these techniques depending on the merits of the clinical scenario and with careful attention to ocular or patient factors which may determine the choice of technique as well as the differences in failure rates compared to primary EK.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKOWLEDGEMENTS/DISCLOSURE:\u003c/strong\u003e\u003c/p\u003e\n\u003col style=\"list-style-type: lower-alpha;\"\u003e\n\u003cli\u003e\n\u003cp\u003eNo support, financial or otherwise was received for this study\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eHarry Roberts has undertaken paid consultancy work for Alcon Inc (Fort Worth, TX, USA) in the past 36 months and has received honoraria from Thea Pharmaceuticals Ltd (Keele, UK). Laura De Benito-Llopis has no financial interest to disclose.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eNo other acknowledgements are necessary\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eEye Bank Association of America. 2019 Eye Banking Statistical Report. April 2020:1-110.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eThompson RW, Price MO, Bowers PJ, Price FW. Long-term graft survival after penetrating keratoplasty. Ophthalmology. 2003;110(7):1396\u0026ndash;1402. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0161-6420(03)00463-9\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAboshiha J, Jones MNA, Hopkinson CL, Larkin DFP. Differential Survival of Penetrating and Lamellar Transplants in Management of Failed Corneal Grafts. JAMA Ophthalmol. 2018;136(8):859\u0026ndash;865. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaophthalmol.2018.1515\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKiel M, Bu JB, Gericke A, et al. Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty. Cornea. 2021;40(9):1218\u0026ndash;1224. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000002786\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKeane MC, Galettis RA, Mills RAD, Coster DJ, Williams KA, for Contributors to the Australian Corneal Graft Registry. A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study. 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Ophthalmology. 2011;118(4):725\u0026ndash;729. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ophtha.2010.08.012\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAl-Mezaine H, Wagoner MD, King Khaled Eye Specialist Hospital Cornea Transplant Study Group. Repeat penetrating keratoplasty: indications, graft survival, and visual outcome. Br J Ophthalmol. 2006;90(3):324\u0026ndash;327. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bjo.2005.079624\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWeisbrod DJ, Sit M, Naor J, Slomovic AR. Outcomes of repeat penetrating keratoplasty and risk factors for graft failure. Cornea. 2003;22(5):429\u0026ndash;434. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00003226-200307000-00008\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAng M, Ho H, Wong C, Htoon HM, Mehta JS, Tan D. Endothelial Keratoplasty After Failed Penetrating Keratoplasty: An Alternative to Repeat Penetrating Keratoplasty. 2014;158(6):1221\u0026ndash;1227.e1221. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajo.2014.08.024\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDroutsas K, Lazaridis A, Papaconstantinou D, et al. Visual Outcomes After Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty\u0026mdash;Comparison of Specific Matched Pairs. Cornea. 2016;35(6):765. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000000822\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBusin M, Bovone C, Scorcia V, et al. Ultrastructural Alterations of Grafted Corneal Buttons: The Anatomic Basis for Stromal Peeling along a Natural Plane of Separation. Am J Ophthalmol. June 2021. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajo.2021.06.005\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBizrah M, Ching G, Yusuf AM, et al. Local anaesthesia as a standard of care for penetrating keratoplasty? Eye. July 2021:1\u0026ndash;8. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41433-021-01618-7\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePasari A, Price MO, Feng MT, Price FW. Descemet Membrane Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Visual Outcomes and Graft Survival. Cornea. 2019;38(2):151\u0026ndash;156. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000001763\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAnshu A, Price MO, Price FW. Risk of Corneal Transplant Rejection Significantly Reduced with Descemet\u0026apos;s Membrane Endothelial Keratoplasty. Ophthalmology. 2012;119(3):536\u0026ndash;540. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ophtha.2011.09.019\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSibley D, Hopkinson CL, Tuft SJ, Kaye SB, Larkin DFP, National Health Service Blood and Transplant Ocular Tissue Advisory Group and contributing ophthalmologists (OTAG Study 26). Differential effects of primary disease and corneal vascularisation on corneal transplant rejection and survival. Br J Ophthalmol. 2020;104(5):729\u0026ndash;734. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bjophthalmol-2019-314200\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWang F, Zhang T, Kang YW, He JL, Li S-M, Li S-W. Endothelial keratoplasty versus repeat penetrating keratoplasty after failed penetrating keratoplasty: A systematic review and meta-analysis. PLoS ONE. 2017;12(7):e0180468. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0180468\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Baseline demographic and clinical characteristic of patients undergoing regraft and separated according the technique (PK vs DSAEK-on-PK vs DMEK-on-PK).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePK\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=61\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSAEK\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDMEK\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=104\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at surgery (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e55.4\u0026nbsp;\u0026plusmn;\u0026nbsp;19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e60.3\u0026nbsp;\u0026plusmn;\u0026nbsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e56.6\u0026nbsp;\u0026plusmn;\u0026nbsp;14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e56.6\u0026nbsp;\u0026plusmn;\u0026nbsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaterality (% Right)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e52.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e38.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e62.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e51.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender (%male)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e60.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e71.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e63.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e63.46%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication for original PK\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Keratoconus\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; BK\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; FED\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Other dystrophies\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Bacterial Infection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Fungal Infection\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Protozoal Infection\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Viral Infection\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Mechanical Injury\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Other/Unknown\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19/61\u003c/p\u003e\n \u003cp\u003e11/61\u003c/p\u003e\n \u003cp\u003e0/61\u003c/p\u003e\n \u003cp\u003e3/61\u003c/p\u003e\n \u003cp\u003e1/61\u003c/p\u003e\n \u003cp\u003e3/61\u003c/p\u003e\n \u003cp\u003e2/61\u003c/p\u003e\n \u003cp\u003e2/61\u003c/p\u003e\n \u003cp\u003e2/61\u003c/p\u003e\n \u003cp\u003e18/61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7/21\u003c/p\u003e\n \u003cp\u003e3/21\u003c/p\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003cp\u003e0/21\u003c/p\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003cp\u003e0/21\u003c/p\u003e\n \u003cp\u003e0/21\u003c/p\u003e\n \u003cp\u003e7/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13/22\u003c/p\u003e\n \u003cp\u003e1/22\u003c/p\u003e\n \u003cp\u003e2/22\u003c/p\u003e\n \u003cp\u003e2/22\u003c/p\u003e\n \u003cp\u003e0/22\u003c/p\u003e\n \u003cp\u003e0/22\u003c/p\u003e\n \u003cp\u003e0/22\u003c/p\u003e\n \u003cp\u003e1/22\u003c/p\u003e\n \u003cp\u003e1/22\u003c/p\u003e\n \u003cp\u003e2/22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39/104\u003c/p\u003e\n \u003cp\u003e15/104\u003c/p\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003cp\u003e6/104\u003c/p\u003e\n \u003cp\u003e2/104\u003c/p\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003cp\u003e27/104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGraft Diameter\u0026nbsp;\u003c/strong\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e8.02\u0026nbsp;\u0026plusmn;\u0026nbsp;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e7.77\u0026nbsp;\u0026plusmn;\u0026nbsp;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e7.52\u0026nbsp;\u0026plusmn;\u0026nbsp;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e7.86\u0026nbsp;\u0026plusmn;\u0026nbsp;0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisually significant comorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44/61\u0026nbsp;(72%)\u003c/p\u003e\n \u003cp\u003e17/61\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10/21\u0026nbsp;(48%)\u003c/p\u003e\n \u003cp\u003e11/21\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5/22 (23%)\u003c/p\u003e\n \u003cp\u003e17/22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59/104\u003c/p\u003e\n \u003cp\u003e45/104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade of Surgeon\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Consultant\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fellow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e57.4%\u003c/p\u003e\n \u003cp\u003e36.1%\u003c/p\u003e\n \u003cp\u003e6.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61.9%\u003c/p\u003e\n \u003cp\u003e28.6%\u003c/p\u003e\n \u003cp\u003e9.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50.0%\u003c/p\u003e\n \u003cp\u003e40.9%\u003c/p\u003e\n \u003cp\u003e9.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56.7%\u003c/p\u003e\n \u003cp\u003e35.6%\u003c/p\u003e\n \u003cp\u003e7.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.591836734693878%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary procedures at time of surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; None\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Phacoemulsification and IOL implantation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;IOL exchange\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Vitrectomy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Glaucoma Surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Others\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67.2%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.8%\u003c/p\u003e\n \u003cp\u003e8.2%\u003c/p\u003e\n \u003cp\u003e8.2%\u003c/p\u003e\n \u003cp\u003e3.3%\u003c/p\u003e\n \u003cp\u003e6.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e76.2%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14.3%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e14.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e77.3%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.5%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e4.5%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e9.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71.2%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.6%\u003c/p\u003e\n \u003cp\u003e4.8%\u003c/p\u003e\n \u003cp\u003e5.8%\u003c/p\u003e\n \u003cp\u003e1.9%\u003c/p\u003e\n \u003cp\u003e8.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK), Bullous keratopathy (BK), Fuchs endothelial dystrophy (FED), Intraocular lens (IOL).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Best corrected visual acuity (BCVA) pre-operatively and at one and two years post-operatively for redo PK, DSAEK-on-PK and DMEK-on-PK\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"11.224489795918368%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.346938775510203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"71.42857142857143%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow up duration (Years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"11.34020618556701%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.52577319587629%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.711340206185568%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreop\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.711340206185568%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.711340206185568%\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"10\" valign=\"top\" width=\"11.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBCVA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;LogMAR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"88.88888888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll Eyes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003ePK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.90\u0026nbsp;\u0026plusmn;\u0026nbsp;0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.19\u0026nbsp;\u0026plusmn;\u0026nbsp;0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.94\u0026nbsp;\u0026plusmn;\u0026nbsp;0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eDSAEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.24\u0026nbsp;\u0026plusmn;\u0026nbsp;0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.74\u0026nbsp;\u0026plusmn;\u0026nbsp;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.75\u0026nbsp;\u0026plusmn;\u0026nbsp;1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eDMEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.17\u0026nbsp;\u0026plusmn;\u0026nbsp;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.68\u0026nbsp;\u0026plusmn;\u0026nbsp;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.77\u0026nbsp;\u0026plusmn;\u0026nbsp;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eANOVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF =6.49 \u003cstrong\u003ep=0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF=2.47 p=0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF=0.17 p=0.846\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eEyes with Visually significant comorbidities excluded\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003ePK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.41 \u0026plusmn; 0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.53 \u0026plusmn; 0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.34 \u0026plusmn; 0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eDSAEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.72 \u0026plusmn; 0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.25 \u0026plusmn; 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.08 \u0026plusmn; 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eDMEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e1.23 \u0026plusmn; 0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.30 \u0026plusmn; 0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003e0.36 \u0026plusmn; 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.767441860465116%\"\u003e\n \u003cp\u003eANOVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF=1.79 p=0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF=1.35 p=0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.74418604651163%\"\u003e\n \u003cp\u003eF=1.84 p=0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Kaplan-Meier analysis of graft survival probability (%) of redo PK, DSAEK-on-PK and DMEK-on-PK\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.770609318996415%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"28.85304659498208%\"\u003e\n \u003cp\u003eRedo-PK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"29.39068100358423%\"\u003e\n \u003cp\u003eDSAEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.985663082437277%\"\u003e\n \u003cp\u003eDMEK\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.770609318996415%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003eNumber of eyes at risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.487455197132615%\"\u003e\n \u003cp\u003eKaplan-Meier survival probability estimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003eNumber of eyes at risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.025089605734767%\"\u003e\n \u003cp\u003eKaplan-Meier survival probability estimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.469534050179211%\"\u003e\n \u003cp\u003eNumber of eyes at risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.516129032258064%\"\u003e\n \u003cp\u003eKaplan-Meier survival probability estimate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.770609318996415%\"\u003e\n \u003cp\u003eYear 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.487455197132615%\"\u003e\n \u003cp\u003e93.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.025089605734767%\"\u003e\n \u003cp\u003e81.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.469534050179211%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.516129032258064%\"\u003e\n \u003cp\u003e63.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.770609318996415%\"\u003e\n \u003cp\u003eYear 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.487455197132615%\"\u003e\n \u003cp\u003e79.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.365591397849462%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.025089605734767%\"\u003e\n \u003cp\u003e69.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.469534050179211%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.516129032258064%\"\u003e\n \u003cp\u003e58.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK)\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 : Post operative complication rates of redo PK, DSAEK-on-PK and DMEK-on-PK\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003ePK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eDSAEK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eDMEK\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eGraft detachment requiring rebubbling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e4/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e4/22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003ePK wound dehiscence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1/61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eEndothelial rejection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1/61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1/22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: Penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK)\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, endothelium, cornea","lastPublishedDoi":"10.21203/rs.3.rs-1918783/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1918783/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To compare the clinical outcomes of repeat penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (‘DSAEK-on-PK’) or Descemet membrane endothelial keratoplasty (‘DMEK-on-PK’) for the management of endothelial failure of previous penetrating keratoplasty\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDesign:\u003c/strong\u003e Retrospective, interventional consecutive case series. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eParticipants:\u003c/strong\u003e 104 consecutive eyes of 100 patients requiring a second keratoplasty for endothelial failure of their primary penetrating keratoplasty performed between September 2016 and December 2020\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eIntervention:\u003c/strong\u003e Repeat keratoplasty\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMain Outcome Measures\u003c/strong\u003e: Primary failure rate, 12 and 24 month survival, visual acuity at 12 and 24 months, rebubbling rate and complication profile.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eRepeat PK was performed in 61/104 eyes (58.7%), DSAEK-on-PK was performed in 21/104 eyes (20.2%) and DMEK-on-PK was performed in 22/104 eyes (21.2%). 6.6% of repeat PKs failed in the first 12 months compared to 19% of DSAEK and 36.4% of DMEK. Chances of 2 year survival were 79.4% for repeat PK, 69.4% for DSAEK and 58.7% for DMEK. Visual acuity at one year was logMAR 0.53±0.51 in the redo PK group, 0.25±0.17 for DSAEK and 0.30±0.38 for DMEK. 24 month outcomes were 0.34± 0.28, 0.08 ± 0.16, and 0.36 ± 0.36 respectively.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e DMEK-on-PK and DSAEK-on-PK are known to have greater primary failure rates than redo PK but have faster rehabilitation times. DMEK-on-PK may offer the best clinical outcome when successful but also has the greatest primary failure rate.\u003c/p\u003e","manuscriptTitle":"Comparison of repeat penetrating keratoplasty, DSAEK and DMEK for the management of endothelial failure of previous PK.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-25 17:19:48","doi":"10.21203/rs.3.rs-1918783/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2022-09-22T09:16:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2022-09-14T12:26:30+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2022-08-23T21:25:08+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2022-08-22T15:58:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-08-11T14:18:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-08-04T14:33:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2022-08-01T18:09:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2437aeb3-32b5-4206-a562-c20b17f8ed91","owner":[],"postedDate":"August 25th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-06-03T07:06:51+00:00","versionOfRecord":{"articleIdentity":"rs-1918783","link":"https://doi.org/10.1038/s41433-023-02561-5","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2023-06-02 04:00:00","publishedOnDateReadable":"June 2nd, 2023"},"versionCreatedAt":"2022-08-25 17:19:48","video":"","vorDoi":"10.1038/s41433-023-02561-5","vorDoiUrl":"https://doi.org/10.1038/s41433-023-02561-5","workflowStages":[]},"version":"v1","identity":"rs-1918783","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1918783","identity":"rs-1918783","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}