記住我
ORIGINAL ARTICLE
Year : 2023 | Volume
: 13
| Issue : 1 | Page : 55-61
Clinical outcomes of prestripped, prestained, and preloaded Descemet's membrane endothelial keratoplasty (”P3 DMEK”)
Lena Juratli1, Sana Qureshi2, Nathan Liles3, Munira Hussain4, Christopher Hood3, Shahzad I Mian3
1 University of Michigan Medical School; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA
2 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan; Corneal Associates of New Jersey, Fairfield NJ, USA
3 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA
4 University of Michigan Medical School, Ann Arbor, Michigan, USA
Correspondence Address:
Dr. Shahzad I Mian
1000 Wall Street, Ann Arbor, Michigan 48105
USA
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/tjo.TJO-D-22-00155
PURPOSE: Despite faster healing and reduced risk of rejection, some surgeons are hesitant to adopt Descemet membrane endothelial keratoplasty (DMEK) due to difficult intraoperative tissue preparation. Use of eye bank prestripped, prestained, and preloaded (p3) DMEK tissue can reduce the learning curve and risk of complications.
MATERIALS AND METHODS: We conducted a prospective study including 167 eyes undergoing p3 DMEK and compared outcomes to a retrospective chart review of 201 eyes that underwent standard DMEK surgery. The primary outcomes were graft failure, detachment, and re-bubbling frequency. The secondary outcomes included baseline and postoperative visual acuity at months 1, 3, 6, and 12. Baseline and postoperative central corneal thickness (CCT) and endothelial cell counts (ECC) were collected.
RESULTS: ECC decrease for p3 DMEK at 3, 6, and 12 months were 15.0%, 18.0%, and 21.0%, respectively. Forty (24%) of p3 DMEK and 72 (35.8%) of standard DMEK eyes had at least a partial graft detachment. There was no difference in CCT, graft failures, or re-bubble frequency. At 6 months, mean visual acuity was 20/26 and 20/24 for standard and p3 DMEK, respectively. Mean case time for p3 DMEK with phaco or p3 DMEK alone was 33 and 24 min, respectively. Mean case time for eyes undergoing DMEK with phaco or DMEK alone was 59 and 45 min, respectively.
CONCLUSION: P3 DMEK tissue is safe and can provide excellent clinical outcomes that are comparable to standard DMEK tissue. Eyes undergoing p3 DMEK may have lower graft detachment and ECC loss.
Keywords: Descemet membrane endothelial keratoplasty, endothelial cell count, graft detachment, preloaded, rebubble
Endothelial keratoplasty (EK) has replaced penetrating keratoplasty (PKP) as the preferred surgical modality for the treatment of corneal endothelial disease. In 2021, PKP represented 33% of all transplants in the United States, a significant reduction from 95% in 2005. In contrast, EK rose from 3% in 2005 to 61% in the same time period. Descemet membrane endothelial keratoplasty (DMEK) has gained popularity over Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) as the preferred EK technique accounting for 47% of all EK cases.[1] Advancements in tissue preparation and safety may continue to increase the widespread adoption of DMEK.
DMEK affords several advantages over DSAEK. DMEK is a tissue neutral procedure that better mimics the physiological posterior corneal curvature thus resulting in not only better visual acuity but also lower higher order aberrations as well as reduced light scatter.[2] In addition, there is minimal change in topography, faster wound healing, and reduced risk of transplant rejection.[3],[4],[5],[6],[7],[8] A direct comparison between the two EK surgeries found that 6 months after surgery, 50% of DMEK eyes and 6% of DSAEK eyes reached a visual acuity of 20/25.[9]
On the other hand, there are several factors associated with the DMEK technique that may preclude surgeons from choosing it as their primary EK modality despite the proven benefits. These include a steeper learning curve that requires the surgeon to master a series of maneuvers to unfold the tissue intraoperatively, more difficult donor preparation, with the DMEK graft being substantially thinner, less forgiving than DSAEK tissue and more prone to endothelial cell loss, and increased surgical times due to graft preparation and graft folding.[10],[11],[12]
Recent studies have shown that as donor tissue preparation moves from the operating room to trained eye bank personnel, many of the above obstacles can be overcome without affecting clinical results.[13],[14] Eye bank prepared and preloaded tissue affords several advantages over surgeon-prepared tissue including decreased operating room time, instruments required in surgery, and reduced risk of endothelial damage.[15],[16] One method of tissue preparation that may overcome potential complications is via the use of a prestripped, prestained, and preloaded (p3) grafts prepared at the eye bank. Patient ready DMEK tissue is available in multiple types of injectors including Straiko-modified Jones tube, DORC tube, and Geuder cannula.
Continued assessment of the clinical safety and efficacy of preloaded DMEK is imperative to support its adoption nationwide. The extent to which long-term functional visual outcomes vary after p3 DMEK is unclear. Prior evidence for the safety of p3 DMEK is primarily focused on initial endothelial cell count (ECC) rather than ECC changes, long-term visual acuity, and primary outcomes and complications related to graft viability, detachment, and re-bubble frequency.[17],[18],[19],[20] No large studies of p3 DMEK have been conducted using patient-centered variables such as long-term visual acuity. In addition, there is limited published data that compares outcomes of standard and p3 DMEK tissue by the same surgeon or surgical group. Understanding how the use of p3 grafts affect long term visual acuity, pachymetry measurements, and ECC may encourage more corneal specialists to adopt p3 DMEK in their own practice and improve patient outcomes.
Herein, we report on the safety, related to primary outcomes and other complications, of a single center, two-surgeon case series of p3 DMEK tissue between 2017 and 2019. We examined the variations in baseline characteristics, including central corneal thickness (CCT) and donor ECC. We also examined variations in graft failure, graft detachment, re-bubble frequency, and other complications such as pupillary block, cystoid macular edema (CME), and retrobulbar hemorrhage postprocedure. In addition, we examined variations in visual acuity, ECC, and pachymetry at 3, 6, and 12 months postprocedure. Importantly, the purpose of this study is to compare the safety and cost of p3 DMEK with standard DMEK and to elucidate the advantages of using p3 DMEK for both the surgeon and operating facility.
Materials and MethodsWe conducted a prospective study of p3 DMEK at one institution and compared the outcomes to a retrospective review of cases performed in a time period immediately preceding by the same surgeons. Institutional review board approval was obtained (approval number: HUM00122967). The study adhered to the tenets of the Declaration of Helsinki and was conducted in compliance with the rules and regulations of the Health Insurance Portability and Accountability Act. All patients provided written informed consent before surgery.
Participants
Data from 167 eyes in 131 patients that underwent consecutive p3 DMEK surgery with or without combined cataract extraction (p3 DMEK Triple) from March 2017 to June 2019 were prospectively collected. Indications for DMEK included Fuchs' endothelial dystrophy (FECD), pseudophakic bullous keratopathy (PBK), and previously failed EK. Exclusion criteria were PKP and any ocular pathological conditions such as glaucoma, amblyopia, previous laser treatment, or any documented evidence of retinal or corneal disease that would limit the recovery of visual acuity after surgery. Data from the last consecutive 201 eyes in 151 patients that underwent surgeon-loaded, or standard, DMEK surgery with or without combined cataract extraction (DMEK triple) from October 2013 to March 2017 was retrospectively collected. The two surgeons began performing standard DMEK cases in early 2013, before data collection in October 2013.
Surgical protocol
All DMEK surgeries, standard and p3, were performed with tissue available through one eye bank (Eversight, Ann Arbor, Michigan). The tissue preparation and surgical techniques for performing standard and p3 DMEK are similar to what has been previously described.[13],[15] In summary, for standard DMEK, the graft arrived stripped and stamped by the eye bank with trephination, staining, and loading performed by the surgeon. All tissues, standard and p3 DMEK, were oriented in an endothelium-out configuration and 7.5 mm in size. Surgeries in both the p3 DMEK and standard cohorts were performed by two attending surgeons.
Data acquisition
The p3 DMEK surgeries were compared with the standard DMEK cases. Primary outcomes were rates of primary graft failure, graft detachment, and re-bubbling. Rate of complications including pupillary block, CME, and retrobulbar hemorrhage were also recorded. Secondary outcomes included baseline and postoperative visual acuity at months 1, 3, 6, and 12. Baseline and postoperative cylinder, sphere, pachymetry, and specular microscopy ECC were collected at months 3, 6, and 12. We also recorded and compared operative times for p3 DMEK, DMEK, p3 DMEK Triple, and DMEK Triple. ECC was measured by using a Konan noncontact specular microscope (Konan Medical Inc, Irvine, CA).
Statistical analysis
We calculated the 3-, 6-, and 12-month values for ECC change as the difference between preoperative and 3-, 6-, and 12-month postoperative ECC values, expressed as a percent of preoperative ECC. We also calculated the percent change in central corneal thickness (CCT) as the difference between preoperative and 3, 6, and 12-month postoperative CCT values, expressed as a percentage of preoperative CCT. The threshold for rebubbling of DMEK grafts included the presence of an edge lift or detachment that was 30% or greater of the total graft area, assessed at the slit lamp. Rebubbling was also performed for a smaller area of detachment that was associated with worsening edema involving the central cornea. Rebubbling was performed in the minor procedure room using an air bubble. For each characteristic, the mean and standard deviations were calculated, Student t-tests, Fisher exact t-test, binomial logistic regression, or Chi-square analysis were used for statistical comparisons, with significance defined as P < 0.05.
ResultsBaseline patient characteristics for standard DMEK and p3 DMEK are displayed in [Table 1]. Two hundred and one and one hundred and sixty-seven eyes were included in the analysis of standard DMEK and p3 DMEK, respectively. Mean follow-up for standard DMEK versus p3 DMEK was 331 and 312 days, respectively. There was no difference in mean age, sex, best Snellen-corrected visual acuity (BSCVA), and CCT between the two groups. Preloaded DMEK tissue had a significantly higher donor ECC compared with standard tissue, 2770 versus 2670 cells/mm2 (P < 0.001). DMEK only or p3 DMEK only was performed on 95/201 (47.3%) and 78/167 (46.7%) eyes. In the standard group, 10 patients had PBK, 8 had previously failed EK, and the remaining had FECD. In the p3 DMEK group, 2 patients had PBK, 3 had failed EK and the remaining had FECD.
Table 1: Baseline patient characteristics of standard descemet membrane endothelial keratoplasty versus P3 descemet membrane endothelial keratoplastyPrimary outcomes and complications are shown in [Table 2]. Primary graft failure occurred in 7 eyes (3.48%) and 4 eyes (2.40%) in the standard and p3 DMEK groups, respectively (P = 0.760). The higher rebubbling rate in the p3 DMEK group versus the standard DMEK group, 16.7% versus 10.9%, was not statistically significant (P = 0.071). However, the higher rate of partial graft detachment in the standard DMEK group, 35.8% versus 24.0%, was statistically significant (P = 0.017). [Table 3] shows that there were no differences in the incidences of additional recorded complications between the two groups.
Table 2: Primary outcomes in standard descemet membrane endothelial keratoplasty versus p3 descemet membrane endothelial keratoplasty
Table 3: Complications in standard descemet membrane endothelial keratoplasty versus p3 descemet membrane endothelial keratoplasty[Figure 1] shows operative times for standard and p3 DMEK alone as well as p3 DMEK Triple. For DMEK surgery, only mean (range) operative time for p3 DMEK versus standard was 24 (14–62) and 45 (23–111) min, respectively (P < 0.001). For DMEK triple mean (range) operative time for p3 DMEK versus standard was 33 (16–77) and 59 (40–125) min, respectively (P < 0.001).
Figure 1: Operative Times in Standard DMEK versus p3 DMEK for p3 DMEK alone and DMEK Triple. DMEK = Descemet membrane endothelial keratoplastyMean BSCVA and percentage of BSCVA >20/20 at 1, 3, 6, and 12 months are displayed in [Table 4]. There is no statistically significant difference in mean BSCVA or BSCVA >20/20 between standard and p3 DMEK groups at 1, 3, and 12 months. However, there was an improvement of mean BSCVA of 20/24 in the p3 DMEK group compared to the 20/26 in the standard group at 6 months (P = 0.008). There was a higher percentage of BSCVA 20/20 or better in the p3 DMEK of 51.8% compared to 39.3% in the standard DMEK group at 6 months (P = 0.016).
Table 4: Mean best Snellen-corrected visual acuity and percentage best Snellen-corrected visual acuity >20/20 as secondary outcomes of standard versus p3 descemet membrane endothelial keratoplasty patientsSpecular microscopy ECC, pachymetry CCT, mean sphere, and mean cylinder are displayed in [Table 5]. P3 DMEK tissue had a significantly higher donor ECC compared with standard tissue, 2770 versus 2670 cells/mm2 (P < 0.001). There is no statistically significant difference in pachymetry CCT, mean sphere, or mean cylinder initial, 3, 6, and 12 months.
Table 5: Endothelial cell count, central corneal thickness, sphere, and cylinder as secondary outcomes of standard versus p3 descemet membrane endothelial keratoplasty patients Discussion Patients undergoing p3 DMEK benefit from significantly decreased intraoperative times, long-term ECC loss, and risk of partial graft detachment. There is no difference in primary graft failure, rebubble frequency, or other complications such as pupillary block, CME, and retrobulbar hemorrhage. This study supports the safety and utilization of p3 DMEK tissue for improved outcomes for patients.
Our results demonstrate that p3 DMEK tissue had a significantly higher donor ECC, a baseline number prior to preparation, compared with standard tissue. It has been reported in previous studies that there is greater ECC loss in the initial phase and 4-year progression of standard tissue.[21][Table 5] showing our results of 21% ECC loss at 12 months for p3 DMEK, is significantly lower than reported in the literature for standard DMEK at 12 months being 29% ECC loss at 12 months for standard DMEK.[21] In addition, early cell loss is a strong predictor of further cell loss and graft failure.[22],[23] Given this, p3 DMEK is overall safer long-term because there is a higher initial ECC and improved cell health, likely due to less trauma immediately before and during surgery.
Previous literature in a multi-surgeon setting study has highlighted that there is a significantly higher detachment rate and rebubbling rate in the p3 DMEK compared to the surgeon-loaded DMEK tissue.[24] However, our data show that there is no difference in rebubbling rate between standard and p3 DMEK. In addition, our results show that there is lower risk for partial graft detachment in the p3 DMEK. The implementation of p3 DMEK bypasses the learning curve of graft preparation by surgeons with less experience, thus further supporting utilization of p3 DMEK for improved outcomes for patients.
The adoption of preloaded tissue for DMEK surgery, which has been fully prepared by an eye bank for surgeon use, has several proposed advantages over the standard tissue. A retrospective cost-effective analysis detailing that p3 DMEK was less costly and generated comparable utility values relative to surgeon-loaded DMEK was previously published.[25] Our results are consistent with previously published data that preloading DMEK grafts reduces cost by reducing surgical time. There are additional factors that are likely contributing to the reduced cost, including reducing tissue wastage, utility costs, and simplifying logistical requirements.[26] In addition to reducing the technical challenges in tissue preparation by surgeons, p3 DMEK is cost-effective for treating endothelial disease from a healthcare and societal perspective.
Our data shows a slight improvement in visual acuity among p3 DMEK compared to standard DMEK at 6 months postprocedure. This variation may be attributed to a few limitations of the study. First, the standard group is retrospective, and thus the data collected may be impacted by selection bias. For example, ECC of the standard DMEK group was not collected at the 3, 6, and 12-month follow-ups. Despite this, the two surgeons performing the procedures remained constant in both the retrospective and prospective groups, thus eliminating a potential confounder. In addition, there is an overall small sample size and limited follow-up, although 72 eyes were included this only presents 43% of the patients for the 12-month ECC measurements. Although these limitations could account for the slight improvement in visual acuity, this reassures that p3 DMEK does not result in long-term decrease in visual acuity.
In this study, we have shown equivalence of several primary outcomes and complications for patients having DMEK using standard or preloaded tissue. This is coupled with the reduced surgical time, risk of ECC loss, and risk of partial graft detachment. Although larger studies are needed to elucidate longer-term benefits for p3 DMEK, these results provide promising support for the use of preloaded DMEK tissue for surgery.
Financial support and sponsorship
Eversight Eyebank grant.
Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
Acknowledgments
All persons who have made substantial contributions to the work reported in the manuscript (e.g., technical help, writing and editing assistance, and general support), but who do not meet the criteria for authorship, are named in the Acknowledgments and have given us their written permission to be named. If we have not included an Acknowledgments in our manuscript, then that indicates that we have not received substantial contributions from nonauthors.
References
留言 (0)