Purpose
To investigate whether the impression held by Descemet membrane endothelial keratoplasty (DMEK) surgeons that young donors are less suitable for DMEK is reflected in 1-year postoperative results.
Design
Retrospective, comparative, interventional case series.
Methods
Records of 1084 consecutive DMEKs were reviewed and matched with corresponding donor tissue data. Young donors (aged ≤55 years; subgroups: 10–40, 41–55) were compared with old donors (>55 years; subgroups: 56–65, >65). Outcome measures in DMEK recipients included best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), central corneal thickness (CCT) at 6 and 12 months, and rebubbling rate.
Results
Out of 529 included DMEKs, 94 (17.8%) were performed with young donor lamellae (mean donor age 49.31 ± 6.35 years; range: 17–55 years) and 435 (82.2%) with older donor tissue (mean age 70.68 ± 7.77 years; range: 56–90 years). Postoperative BSCVA, ECD, and CCT results were comparable in both groups at 6 and 12 months without statistically significant differences. Overall rebubbling rate in the young donor group was 42.6% and in the old donors was 53.3% ( P = .058). Complication rates also did not differ significantly.
Conclusion
Younger donor age seems not to affect the clinical outcome of DMEK surgery negatively within the first postoperative year, suggesting donor corneas with donor age down to 17 years as safe donor tissue for DMEK surgery.
Different techniques for posterior lamellar keratoplasty have been developed for the replacement of diseased corneal endothelium. In most cases of endothelial pathologies requiring keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK) or Descemet membrane endothelial keratoplasty (DMEK) is applied. To date, DSAEK is still the method of choice in most countries, whereas DMEK, which is more challenging, has achieved growing attention and has already replaced DSAEK as the standard procedure for posterior lamellar keratoplasty in some areas in Europe and within the United States. Since the graft prepared for DMEK comprises corneal endothelium and Descemet membrane only and lacks, in contrast to DSAEK, any adhering corneal stroma, DMEK provides faster and more complete visual rehabilitation as well as reduced rates of immune reactions compared with DSAEK. However, donor preparation, implantation, and intracameral unfolding of the graft are more challenging in DMEK. Especially graft preparation and intracameral unfolding are only little standardized, but at the same time represent the most critical steps with the need of mechanical manipulations of the donor lamella. Up to now, many surgeons have preferred donor corneas from older donors (eg, above 55 years of age) for DMEK, since free-floating DMEK grafts spontaneously form a roll that is tighter in young donors, and therefore unfolding is suggested to be more challenging. Several eye banks and surgeons exclude young donors from becoming DMEK tissue donors owing to the suggested rolling behavior. Since DMEK is related with a high endothelial cell loss of about 35% owing to graft preparation and transplantation, grafts with a high endothelial cell density (ECD) are desirable to improve the success rate of DMEK surgery. Therefore, some eye banks already started to accept eye donations from older donors above the age of 80 years with correspondingly high ECD. Because DMEK’s popularity in many countries is growing and therefore corneas offering the presumed ideal combination of high donor age and high ECD become scarce, there is a rationale for questioning whether high donor age is associated with fewer complications and better clinical outcomes owing to shorter and easier preparation and safer transplantation, in contrast to young donors, where the intraoperative endothelial cell loss may be higher because surgery may eventually be more challenging, especially during the surgeon’s learning curve. However, so far there is only limited evidence for a possible relation between donor age and outcome parameters in DMEK surgery.
We therefore investigated whether young donor age (≤55 years) may influence the clinical outcome and postoperative complication rates of DMEK surgery. This may have an impact on tissue allocation in the growing field of posterior lamellar transplant surgery.
Methods
In this retrospective study, we reviewed clinical records of 1084 consecutively performed DMEKs for endothelial pathologies between July 1, 2011 and November 30, 2015 at the Department of Ophthalmology, University of Cologne, Cologne, Germany. The data have been prospectively compiled within the Cologne DMEK database, using REDCap electronic data capture tools. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies. Furthermore, the database of the local eye bank was reviewed for corresponding corneal donor tissue parameters.
The study was approved by the local Institutional Review Board (14-373) and was conducted in adherence to the tenets of the Declaration of Helsinki.
Collection of Donor Graft Data
Prior to donor graft distribution and transplantation, the following data were assessed: age (years) and sex of donor (male/female), ECD (cells/mm 2 ), preservation technique (organ culture vs 4°C preservation), and preservation time until grafting (days).
Endothelial cell density was measured by phase-contrast microscopy (Axiovert 25; Zeiss, Oberkochen, Germany).
Clinical Information and Collected Data of Recipients
Prior to surgery, 6-month and 12-month postoperative standardized eye examinations, including best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP), central corneal thickness (CCT; Orbscan; Bausch & Lomb, Rochester, New York, USA), ECD (Tomey EM-3000 specular microscope; Tomey, Erlangen, Germany), slit-lamp biomicroscopy, and funduscopy were performed. Intraoperative rates of preparation failures and rates of postoperative Descemet membrane detachments requiring air reinjection into the anterior chamber (rebubbling) were documented. Furthermore, occurrence of relevant complications during the first postoperative year were collected, including primary graft failure, immune reaction, graft rejection, need for regrafting, cystoid macular edema, epiretinal membrane formation, presence of persistent epithelial disorders (erosions, keratitis, or corneal ulcers), secondary glaucoma, and retinal detachment. In cases that underwent DMEK combined with phacoemulsification and posterior chamber lens implantation, occurrence of capsular fibrosis or posterior chamber lens dislocation postoperatively was recorded.
Inclusion and Exclusion Criteria
All DMEK surgeries between July 1, 2011 and November 30, 2015 were reviewed. Only cases in which preoperative and postoperative clinical data at 6 and/or 12 months were available, as well as corresponding donor tissue parameters, were included into the study. A total of 509 cases had to be excluded for different reasons:
- (1)
Sufficient follow-up data at 6 and/or 12 months were not available. Thereby in 208 cases DMEK surgery was carried out <6 months ago, and 255 cases had to be excluded because follow-up data were insufficient owing to lost to follow-up or to not having perceived examinations after 6 and 12 months postoperatively.
- (2)
Recipient eyes with complex pathologies of the anterior or posterior segment (uncontrolled glaucoma, presence of drainage implants, active vascular retinal diseases, manifest uveitis, high myopia >−6 diopters, history of nonperforating or perforating trauma, previous penetrating keratoplasty, pre-existing anterior chamber lens) that underwent DMEK surgery were excluded as well. Only eyes in which these exclusion criteria were present preoperatively were excluded from the analysis. Eighteen eyes had to be excluded because of history of previous penetrating keratoplasty; a further 28 eyes were excluded owing to complex anterior or posterior segment pathologies.
DMEK surgery alone in phakic or pseudophakic eyes, as well as triple procedures (DMEK combined with phacoemulsification and posterior chamber lens implantation for coexistent cataract) were included.
For statistical evaluation of donor age related to clinical outcome after DMEK, all included datasets were divided into 2 groups: (1) young corneal donors (donor age ≤55 years) and (2) old donors (>55 years). In decision upon group sets, we ensured that the number of evaluable cases was representative enough for evaluation and statistical analysis.
Forty cases received donor tissue of donors aged ≤40 years and a further 21 cases received tissue of donors aged 41–50 years. Therefore, we decided to set the limit at 55 years for young vs old donors to include a sufficient number of cases into each group (94 vs 435 cases).
Furthermore, for evaluation of clinical outcome parameters and complication rates, the following subgroups were defined: donor age 17–40, 41–55, 56–65, and >65 years.
For statistical analysis concerning BSCVA, eyes with extracorneal visual acuity limiting factors such as age-related macular degeneration, amblyopia, or advanced stage of glaucoma were excluded.
Donor Preparation and Surgical Technique
All patients underwent surgery under full anesthesia and under steady-state conditions at the Department of Ophthalmology from the University Hospital of Cologne.
DMEK was performed in a standardized fashion by 2 experienced surgeons (C.C. and B.B.) with some variations to methods described previously. In short: corneoscleral buttons were mounted onto a suction block (Moria SA, Antony, France) and marked with an 8-mm trephine. Trypan blue staining was performed for 5-15 seconds to allow visualization of the mark. The peripheral Descemet membrane was peeled off with a razor blade, and the central margin was lifted with a round blade and then peeled off using 2 forceps. The Descemet membrane was cut with an 8.0 mm trephine. Stripping of the graft was performed using forceps. Afterwards the DMEK graft was transferred into an injector cartridge (AT. Smart Cartridge; Zeiss Meditec, Jena, Germany) commonly used for lens implantation during cataract surgery. In eyes showing coexistent cataract formation, a combined procedure (triple DMEK) with phacoemulsification and posterior chamber lens implantation was performed directly before DMEK. For removal of the endothelium–Descemet membrane layer, the anterior chamber was filled with air. The descemetorrhexis was performed within an area of 9.0 mm using a Price hook. Following descemetorrhexis, the injector cartridge, in combination with the injector AT Shooter A2-2000 (Zeiss Meditec, Jena, Germany), was used to insert the graft into the anterior chamber. To maintain the anterior chamber depth during graft implantation a bimanual technique was used, stabilizing the anterior chamber with an irrigation handpiece (0.8 mm; Geuder GmbH, Heidelberg, Germany). Then unfolding of the graft lamella was performed either by insertion of an air bubble into the inner lumen of the roll, by gentle tapping of the cornea with the tip of a cannula, or by the combination of both. After centering of the graft, an air bubble was placed underneath the donor lamella and the anterior chamber was then filled completely with air or sulfur hexafluoride 20% (SF 6 20%) to secure the graft at the recipient’s posterior corneal surface.
The decision for each anterior chamber tamponade was independent of patient-related factors. One of the 2 surgeons used SF 6 20% routinely in all consecutive cases since July 2014.
Prior to surgery, an iridotomy at 6 o’clock was performed with a neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser to avoid postoperative angle block with intraocular pressure decompensation. In cases in which the laser iridotomy was inadequate in size owing to poor visualization of the iris, the iridotomy was surgically extended during DMEK surgery.
Postoperative Treatment
All patients were hospitalized after DMEK surgery for approximately 1 week and received routine postoperative management in the form of topical prednisolone acetate 1% in tapering doses over 12 months and topical antibiotic eye drops for 1–2 weeks as well as lubricant eye drops (5 times a day) as long as needed. Pilocarpine 1% eye drops were applied 3 times a day as long as the anterior chamber was filled with air or gas covering the pupil’s bottom margin. Patients were instructed to keep a strict supine position postoperatively (for at least 3 days, with only bathroom privileges) under continuous monitoring of intraocular pressure (IOP). IOP was measured at least 4 times a day. In exceptional cases of postoperative IOP decompensation owing to approximately complete air or gas filling of the anterior chamber with covering of the 6 o’clock iridotomy, temporary alternation to upright position was recommended to achieve permeability of the iridotomy.
In case of clinically significant Descemet membrane detachment in the postoperative course, a rebubbling was performed. Descemet membrane detachments were defined as either partial or complete dehiscence of DMEK lamella detected by slit-lamp biomicroscopy or by optical coherence tomography of the anterior segment. They were considered clinically significant based on the surgeons’ experience, taking into account the size of the graft detachment and the distance of the graft detachment from the recipient’s cornea. Curling edges of the detached graft and corneal edema were a strong indicator for the need for an additional rebubbling. Therefore, air was reinjected into the anterior chamber (approximately 90% of the anterior chamber was filled with air) to reattach the DMEK graft. Patients were again instructed to maintain a supine position and pilocarpine eye drops 1% were applied 3 times a day as long as the anterior chamber was filled with air covering the pupil’s bottom margin. Single or circumscribed edge lifts without curling tendency and without corneal edema were clinically observed only.
Statistical Analyses
Descriptive data for donor tissue and recipients were collected in REDCap and analyzed by SPSS (version 22.0 for Windows; SPSS, Inc, Chicago, Illinois, USA). The BSCVA was converted to logMAR. For statistical significance testing for interval scale parameters Student t test (CCT and BSCVA) as well as Mann-Whitney U test (ECD), and χ 2 test was used for ordinal scale parameters (rebubbling rate) for the young and older donor group. Donor age subgroup analysis regarding clinical outcome parameters (BSCVA, ECD, and CCT) and postoperative complication rates was performed by Kruskal-Wallis test. The level of significance was defined as P < .05. The Holm-Bonferroni procedure was performed to correct P values for multiple testing.
Results
Clinical records of 1084 consecutively performed DMEKs in eyes with endothelial pathologies were reviewed; 529 cases (48.8%) met all inclusion and no exclusion criteria and were available for further analyses. Out of these 529 cases, 94 (17.8%) could be assigned to the young donor group (donor age ≤55 years), whereas 435 (82.2%) could be assigned to the old donor group (>55 years).
Donor Details
Young donors
Donors (n = 94) had a mean ± SD age of 49.31 ± 6.35 years (range, 17–55 years) and a female-to-male ratio of 0.6:1. Mean ± SD overall preservation time was 14.35 ± 6.10 days (range, 5–35 days), and mean ± SD preoperative ECD of donor lenticule was counted as 2783.98 ± 283.06 cells/mm 2 (range, 2280–3600 cells/mm 2 ).
Thirty-three donor corneas (35.1%) were stored at 2–8 C in Optisol GS (Bausch & Lomb Surgical, Inc, Rochester, New York, USA) or Life 4°C (Chiron Vision, Irvine, California, USA), and 61 donor corneas (64.9%) were organ cultured (Biochrom, Berlin, Germany) at 31 ± 1 C.
Old donors
Donors (n = 435) had a mean ± SD age of 70.68 ± 7.77 years (range, 56–90 years) and a female-to-male ratio of 166:289. Mean ± SD overall preservation time was 15.72 ± 5.91 days (range, 3–35 days), and mean ± SD preoperative ECD measured 2683.23 ± 213.69 cells/mm 2 (range, 2200–3691 cells/mm 2 ).
A total of 131 donor corneas (30.1%) were stored at 2–8 C in Optisol GS (Bausch & Lomb Surgical, Inc) or Life 4°C (Chiron Vision), and 304 donor corneas (69.9%) were organ cultured (Biochrom) at 31 ± 1 C.
Differences Between Both Groups Regarding Donor Tissue Parameters
By Student t test, significant differences for donor tissue parameters could be revealed for donor age, as expected ( P < .001), as well as donor ECD ( P = .006), but no difference was seen in preservation time ( P = .176) or preservation technique ( P = .343).
Demographic Data of Descemet Membrane Endothelial Keratoplasty Recipient Eyes
Recipients of young donor corneal tissue
DMEK surgery was performed in 94 eyes (female-to-male ratio: 1.29:1; mean age ± SD 67.51 ± 12.78 years [range, 44–89 years]). Indications for DMEK included Fuchs endothelial dystrophy in 81 eyes (86.2%), pseudophakic bullous keratopathy in 6 eyes (6.4%), further endothelial dystrophies (including congenital hereditary endothelial dystrophy [CHED] and posterior polymorphous corneal dystrophy [PPCD]) in 4 eyes (4.3%), pseudoexfoliation (PEX)-related bullous keratopathy in 1 eye (1.1%), and graft failure or graft rejection following previously performed DMEK in 2 eyes (2.1%).
Of 94 DMEKs, 10 DMEKs (10.6%) were performed as a single procedure in phakic eyes, 39 DMEKs (41.5%) were performed as a single procedure in pseudophakic eyes, and in 45 eyes (47.9%) a triple procedure was conducted. In 92 eyes (97.9%) air was used as tamponade in the anterior chamber, whereas in 2 eyes (2.1%) SF 6 20% was used.
Recipients of old donor corneal tissue
In 435 eyes (female-to-male ratio: 1.74:1; mean age ± SD 69.88 ± 10.49 years [range, 33–92 years]) DMEK surgery was performed. Indications for DMEK included Fuchs endothelial dystrophy in 370 eyes (85.1%), pseudophakic bullous keratopathy in 26 eyes (6.0%), further endothelial dystrophies (including CHED and PPCD) in 28 eyes (6.4%), PEX-related bullous keratopathy in 1 eye (0.2%), graft failure or graft rejection following previously performed DMEK in 8 eyes (1.8%), and graft failure or graft rejection following previously performed DSAEK in 2 eyes (0.5%).
Of 435 DMEKs, 52 DMEKs (12.0%) were performed as a single procedure in phakic eyes, 201 DMEKs (46.2%) were performed as a single procedure in pseudophakic eyes, and in 182 eyes (41.8%) a triple procedure was performed. In 411 eyes (94.5%) air was used as tamponade in the anterior chamber, whereas in 24 eyes (5.5%) SF 6 20% was used.
Clinical Outcome Parameters
Recipients of young donor corneal tissue
At 6 months follow-up mean BSCVA was 0.24 ± 0.15 logMAR (range, 0–0.6), ECD was 1799.98 ± 421.86 cells/mm 2 (range, 850–3000 cells/mm 2 ), and CCT was 554.92 ± 63.32 (range, 428.0–750.0 μm).
At 12 months mean BSCVA was 0.22 ± 0.19 logMAR (range, 0–0.80), ECD measured 1796.47 ± 352.41 cells/mm 2 (range, 692–2441 cells/mm 2 ), and CCT was 552.94 ± 60.73 μm (range, 412–684 μm).
Endothelial cell loss was 34.7% ± 15.0% after 6 months and 36.0% ± 12.7% after 12 months, compared with corresponding donor ECD.
Recipients of old donor corneal tissue
At 6 months follow-up mean BSCVA was 0.26 ± 0.17 logMAR (range, −0.10 to 1.00), ECD was 1706.43 ± 378.80 cells/mm 2 (range, 711–2677 cells/mm 2 ), and CCT was 570.79 ± 62.94 (range, 415–805.00 μm).
At 12 months mean BSCVA was 0.22 ± 0.18 logMAR (range, 0–1.00), ECD measured 1674.78 ± 401.46 cells/mm 2 (range, 703–2967 cells/mm 2 ), and CCT was 569.95 ± 66.13 μm (range, 387–862 μm).
Endothelial cell loss was 36.3% ± 14.4% after 6 months and 37.1% ± 15.1% after 12 months, compared with corresponding donor ECD.
Clinical outcome parameters for subgroups are condensed in Table 1 .
| Clinical Outcome Parameter | Subgroups Defined by Donor Age (y) | P Value | |||
|---|---|---|---|---|---|
| 17–40 (n = 6) | 41–55 (n = 88) | 56–65 (n = 125) | 66–90 (n = 310) | ||
| BSCVA at 6 months (logMAR) | 0.40 (± 1.4) | 0.24 (± 1.4) | 0.26 (± 1.7) | 0.25 (± 1.7) | .503 |
| BSCVA at 12 months (logMAR) | 0.5 a | 0.19 (± 1.8) | 0.20 (± 1.7) | 0.22 (± 1.9) | .339 |
| ECD at 6 months (cells/mm 2 ) | 1586.2 (± 531.7) | 1825.1 (± 406.1) | 1756.2 (± 373.7) | 1683.5 (± 379.9) | .084 |
| ECD at 12 months (cells/mm 2 ) | 1917.7 b (± 230.6) | 1788.2 (± 359.6) | 1712.2 (± 379.4) | 1661.4 (± 409.3) | .176 |
| CCT at 6 months (μm) | 539.32 (± 63.4) | 556.9 (± 63.7) | 562.5 (± 64.0) | 574.6 (± 62.3) | .225 |
| CCT at 12 months (μm) | 569.7 (± 109.4) | 551.3 (± 56.8) | 554.5 (± 75.4) | 575.3 (± 62.0) | .057 |
a Reduced sample size (n = 1); no standard deviation available.
Rebubbling Rate
Recipients of young donor corneal tissue
Rebubblings were performed in 40 eyes (39 eyes following initial air tamponade and 1 eye following SF 6 20%). Overall rebubbling rate was at 42.6%. Of these 40 eyes, 37 eyes (92.5%) needed only 1 rebubbling, and 3 eyes (7.5%) had a second rebubbling.
Recipients of old donor corneal tissue
Rebubblings were performed in 232 eyes (229 eyes following initial air tamponade and 3 eyes following SF 6 20%). Overall rebubbling rate was at 53.3%. Of these, 199 eyes (85.8%) needed only 1 rebubbling, 26 eyes (6.0%) had a second rebubbling, and in 7 eyes (1.6%) a third rebubbling was performed.
Postoperative Complication Rate
Recipients of young donor corneal tissue
No cases of primary graft failure, immune reaction, or graft rejection could be observed. Three of 94 eyes (3.2%) needed regrafting within the first postoperative year. In all cases a re-DMEK was performed. Six eyes (6.4%) developed secondary glaucoma and 4 eyes (4.3%) cystoid macular edema. Further details are condensed in Table 2 .
