Purpose
To describe corneal clearance after re-endothelialization of the recipient posterior stroma through Descemet membrane endothelial transfer (DMET) (ie, a “free-floating” donor Descemet graft in the recipient anterior chamber after descemetorhexis), in managing corneal endothelial disorders.
Design
Nonrandomized prospective study at a tertiary referral center.
Methods
Twelve eyes enrolled in our study, 7 suffering from Fuchs endothelial dystrophy and 5 with bullous keratopathy. The clinical outcome was monitored by biomicroscopy, optical coherence tomography, confocal microscopy, endothelial cell density, and pachymetry measurements.
Results
All eyes operated on for Fuchs endothelial dystrophy showed corneal clearance, with pachymetry values returning to normal (533 ±47 μm). The denuded recipient stroma re-endothelialized with an average endothelial cell density of 797 (± 743) cells/mm 2 at 6 months after surgery. In contrast, none of the bullous keratopathy eyes showed any improvement throughout the follow-up period.
Conclusion
DMET may be effective in the management of Fuchs endothelial dystrophy (primarily a Descemet membrane disorder), but not in bullous keratopathy (primarily an endothelial depletion). Apparently, the indication for surgery (ie, a “dystrophy” vs a “depletion” of recipient endothelial cells) relates to the capacity of the cornea to clear. This suggests that the remaining rim of recipient endothelium (after descemetorhexis) is involved in the re-endothelialization of the recipient posterior stroma after DMET.
From 1998, we have introduced various concepts for endothelial keratoplasty, which include both Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). It is generally believed that these techniques are effective in restoring corneal transparency by complete donor-to-host apposition with the transplanted endothelium in its anatomic position. This paradigm relates to the clinical observation that corneal clearance does not occur if an endothelial transplant is “detached.”
However, we recently reported on several DMEK eyes that showed corneal clearance with visual recoveries improving up to 20/20, despite subtotal graft detachment. A similar observation after DSAEK has been reported by Zafirakis and associates. Since specular and confocal microscopy showed repopulation of the recipient posterior stroma with endothelial cells, it may be speculated that endothelial migration occurs by donor or host cells, or both. If so, a simplified surgical technique, tentatively named “Free-DMEK” or “Descemet membrane endothelial transfer” (DMET), in which donor tissue is merely injected into the recipient anterior chamber after descemetorhexis, could potentially be effective in the management of corneal endothelial disease.
However, the main question in the further development of DMET or any related technique would be whether it is the host or the donor endothelium that contributes primarily to the restoration of corneal clarity. Hence, the purpose of the current study was to further investigate the mechanism through which DMET is effective, by analyzing the clinical outcome of a “free-floating” Descemet graft in a series of 12 eyes.
Methods
Twelve eyes of 12 patients, averaging 67 (± 16) years of age, 7 male and 5 female, were enrolled in our study. All of these eyes underwent surgical intervention for Fuchs endothelial dystrophy or bullous keratopathy. Eight eyes had a DMEK procedure, complicated by subtotal detachment of the Descemet graft, so that the larger portion of the graft was “free-floating” in the recipient anterior chamber. In the remaining 4 eyes, with nanophthalmos and/or a history of advanced glaucoma, multiple posterior segment surgeries, an instable or subluxated intraocular lens, or a combination thereof, a lack of adequate air-bubble support of the graft at termination of the surgery was anticipated. Hence, during the DMEK procedure, the upper edge of the graft was fixated within the corneal tunnel incision to secure a contact area between the graft and the host posterior stroma, as has been found to be a prerequisite for “spontaneous corneal clearance” in eyes with Descemet graft detachment. For purpose of clarity in nomenclature (ie, to distinguish the clinical outcome of these “free-floating” Descemet grafts from uncomplicated, attached Descemet grafts after routine DMEK), the procedure is referred to below as DMET. For DMET the observed clinical effects cannot have resulted from “keratoplasty” (ie, no corneal reconstruction was obtained) but only from transferal of donor endothelium instead.
Donor Tissue
From a donor globe obtained less than 24 hours postmortem, a corneoscleral button was excised less than 36 hours postmortem and stored by organ culture in modified minimum essential medium (EMEM) at 31 C. After 1 week of culture, endothelial cell morphology and viability were evaluated and the corneoscleral button was mounted endothelial side up on a custom-made holder with a suction cup. Descemet membrane was stripped from the posterior stroma, so that a 8.0- to 12.0-mm-diameter flap of Descemet membrane with its endothelial monolayer was obtained. Because of the elastic properties of the membrane, a “Descemet roll” formed spontaneously, with the endothelium at the outer side. The Descemet roll was then stored in organ culture medium for 1 to 3 weeks (depending on tissue harvesting, surgical planning, and other logistical parameters) until the time of transplantation. In the eye bank, donor endothelial cell density and viability were evaluated in vitro with an inverted light microscope (Axiovert 40; Zeiss, Göttingen, Germany), and digital photographs were made (PixeLINK PL-A662; Zeiss, Göttingen, Germany).
At surgery, a 9.0-mm descemetorhexis was made and a 8.0- to 12.0-mm Descemet graft was injected into the anterior chamber. Cases 1 through 8 were completed as a DMEK procedure, as well as Cases 9 through 12, except for additional fixation of the Descemet graft at the interior lip of the clear corneal tunnel by positioning the outer, proximal edge of the donor tissue inside the incision. Postoperative medication included chloramphenicol 6 times daily, dexamethasone 0.1% 4 times daily, changed to fluorometholone 0.1% 4 times daily at 1 month and 3 times daily at 6 months; after that period it is further reduced to twice daily at 9 months and once daily at 1 year). Each surgical procedure was recorded on DVD (Pioneer DVR-RT601H-S, Tokyo, Japan).
All 12 eyes were examined at 1, 3, and 6 months after surgery. The clinical outcome was evaluated by comparing the preoperative to postoperative best-corrected visual acuity (BCVA), noncontact specular microscopy (SP3000; Topcon Medical Europe BV, Capelle a/d IJssel, The Netherlands), anterior segment optical coherence tomography (Heidelberg Engineering GmbH, Heidelberg, Germany), confocal microscopy (Confoscan 4; Nidek Technologies, Padova, Italy), Scheimpflug imaging (Pentacam HR; Oculus, Wetzlar, Germany), and photo-slit-lamp biomicroscopy (Topcon Medical Europe BV). Throughout the 6-month follow-up period, the “free-floating” position of the Descemet graft within the recipient anterior chamber remained unchanged in all eyes.
Statistical analysis was performed with SPSS version 15.0 for Windows (SPSS Inc, Chicago, Illinois, USA). Because of the relatively small number of cases, a nonparametric test (Mann-Whitney U ) was used to compare the pachymetry (at the thinnest point) between Fuchs endothelial dystrophy and bullous keratopathy cases at different time points. Analysis of variance (1-way ANOVA) was used to evaluate the thinnest point pachymetry changes over time in both groups. Statistical significance was determined as P < .05.
Results
All of the 12 DMET eyes (ie, eyes with a largely “free-floating” Descemet graft in the recipient anterior chamber) showed corneal decompensation at 1 month after surgery ( Figures 1 and 2 ) . However, at the 3- to 6-months-postoperative time interval, all eyes operated on for Fuchs endothelial dystrophy showed progressive “corneal clearance,” while no improvement could be detected in any of the eyes operated on for (aphakic or pseudophakic) bullous keratopathy ( Table ).
| Patient Data | Preoperative | 6 Months Postoperative | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient # | Age (y) | Sex | OD/OS | Indication Surgery | Concomitant Eye Disease | BCVA | Donor Age (y) | ECD on DM Graft Before Transplantation (Cells/mm 2 ) | DM Graft Diameter (mm) | BCVA | ECD Recipient Posterior Stroma (Cells/mm 2 ) | Thinnest Point Pachymetry | Remarks |
| Fuchs endothelial dystrophy | |||||||||||||
| 1 | 47 | F | OS | FED | None (phakic) | 20/50 (0.40) | 75 | 2560 | 9.5 | 20/20 (1.00) | 380 | 548 | |
| 2 | 70 | F | OD | FED | None (pseudophakic: PC IOL) | 20/125 (0.15) | 44 | 2370 | 9.5 | 20/28 (0.70) | 340 | 533 | |
| 3 | 75 | M | OD | FED | Amblyopia (phakic) | 20/50 (0.40) | 60 | 2200 | 9.5 | 20/100 (0.20) | 530 | 517 | |
| 4 | 61 | M | OD | FED | None (pseudophakic: PC IOL) | CF (1/60) | 38 | 2425 | 9.5 | CF (1/60) | n.a. | n.a. | 4-months-postoperative data, because DSEK at 4 months after initial DMEK |
| 5 | 75 | M | OS | FED | ARMD (pseudophakic: PC IOL) | CF (1/60) | 60 | 2840 | 9.5 | CF (1/60) | 2270 | 492 | |
| 6 | 80 | F | OS | FED | ARMD (pseudophakic: PC IOL) | CF (1/60) | 48 | 2680 | 9.5 | 20/200 (0.10) | 830 | 476 | |
| 7 | 60 | M | OD | FED | None (phakic) | 20/25 (0.80) | 60 | 2565 | 9.5 | CF (1/60) | 430 | 602 | |
| Bullous keratopathy | |||||||||||||
| 8 | 75 | M | OS | PPBK | PK for KC; Artisan iris claw after complicated cataract surgery | CF (1/60) | 72 | 2655 | 9.5 | CF (1/60) | n.m. | 603 | Postoperative hypotonia |
| 9 | 31 | F | OS | ABK | Nanophthalmos; glaucoma; aphakia; partial aniridia, glaucoma tube | CF (1/60) | 52 | 2450 | 8.0 | CF (1/60) | n.m. | 755 | Postoperative hypotonia |
| 10 | 83 | F | OS | PPBK | Complicated cataract surgery (pseudophakic: PC IOL) | CF (1/60) | 58 | 2495 | 9.5 | CF (1/60) | n.m. | 741 | |
| 11 | 66 | M | OD | PPBK | Retinal detachment; iris clip lens; FED in contralateral eye | 20/100 (0.20) | 57 | 2500 | 12.0 | CF (1/60) | n.m. | 970 | |
| 12 | 82 | M | OD | PPBK | Retinal detachment; subluxated IOL | HM (1/300) | 57 | 2500 | 11.0 | HM (1/300) | n.m. | 817 | |
In eyes operated on for Fuchs endothelial dystrophy, thinnest point pachymetry values averaged 636 (± 89) μm before surgery, 718 (± 95) μm at 1 month after surgery, 548 (± 51) μm at 3 months after surgery, and 533 (± 47) μm at 6 months after surgery ( Figure 3 ; Table ). In eyes operated on for bullous keratopathy, pachymetry values averaged 768 (± 104) μm before surgery, 826 (± 103) μm at 1 month after surgery, 792 (± 76) μm at 3 months after surgery, and 777 (± 133) μm at 6 months after surgery ( Figure 3 ; Table ).
