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Descemet membrane endothelial keratoplasty after penetrating keratoplasty
Journal of EuCornea 2 (2019) 10–13
Contents lists available at ScienceDirect
Journal of EuCornea journal homepage: www.elsevier.com/locate/xjec
Descemet membrane endothelial keratoplasty after penetrating keratoplasty a,b,c,d,⁎
Jose L. Güell , Merce Morral Felicidad Maneroa
a,b
a
a
, Miriam Barbany , Oscar Gris , Daniel Elies
a,b
T
,
a
Institut de Microcirurgia Ocular (IMO), Barcelona, Spain European School for Advanced Studies in Ophthalmology (ESASO), Switzerland Universitat Autonoma de Barcelona (UAB), Barcelona, Spain d Cornea and Refractive Surgery Unit, Institut de Microcirurgia Ocular, Barcelona, Spain b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Keratoplasty DMEK PK Corneal transplant Corneal endothelium Graft failure Fuchs dystrophy Descemetorhexis Penetrating keratoplasty
Purpose: To describe visual and clinical outcomes of descemet membrane endothelial keratoplasty (DMEK) for late endothelial failure after penetrating keratoplasty (PK). Methods: Retrospective, observational study of patients who consecutively received DMEK to treat PK graft failure. Intraoperative complications were recorded. Our previously described DMEK surgical technique was used except that host descemet membrane was not stripped in any of the eyes. Corrected distance visual acuity (CDVA), and endothelial cell density (ECD) were evaluated before surgery and at regular intervals up to 24 months after the surgery. Results: Twenty-six eyes of 26 patients were included. Mean host age was 58.50 ± 12.50 years old. Mean donor age was 65.30 ± 10.49. Mean follow up after DMEK was 23.08 ± 10.27 (range 6 months–48 months). Seventeen (65.38%) eyes reached at least the 24-month follow up time point. At last follow up, 24 eyes (92.31%) presented with clear corneas. Twenty-four months postoperatively, mean Snellen CDVA in decimal fraction was 0.75 ± 0.03 (range 0.6–0.80) and mean central endothelial cell density was 1480.41 ± 320.56 cells/mm2 (range, 591–1950 cells/mm2). Mean cell loss at 6 months was 27.67 ± 16.03%. Three (11.53%) eyes had significant graft detachment that required re-bubbling. No episodes of immunological graft rejection were documented. Conclusions: Our experience shows that DMEK is a useful technique to treat endothelial graft failure following PK. Compared to repeat PK, DMEK-specific surgical complications and postsurgical management should be expected.
1. Introduction Late endothelial failure is one of the commonest causes for re-intervention after full-thickness corneal transplantation worldwide. Endothelial keratoplasty (EK), either in the form of Descemet stripping automated endothelial keratoplasty (DSEK/DSAEK) or descemet membrane endothelial keratoplasty (DMEK), has become the preferred treatment for graft failure over a repeat penetrating keratoplasty (PK) during these last few years [1,2]. The main advantages of EK seem to be better visual outcomes in most cases, lower risk of rejection and to escape from intraoperative and postoperative risks associated with an “open-sky” technique such as expulsive hemorrhage [3–7] and secondary astigmatism. Additionally, several studies have suggested that DMEK grafts fit better over the irregular posterior corneal surface of a full thickness graft [8–10].
⁎
The aim of this study is to describe our clinical experience with DMEK for late endothelial failure after PK. 2. Material and methods Data collected prospectively at a single center was reviewed retrospectively to identify patients who underwent DMEK after failed primary PK between April 2012 and January 2018 and with at least 3 months of follow-up and potential CDVA of 0.8 or better. Patients with concurrent, non-corneal ocular pathology that limited visual potential such as macular disease, advanced glaucoma and/or aniridia were excluded. All surgeries were performed by a single surgeon (J.L.G.) at the Institut de Microcirurgia Ocular, Barcelona, Spain. The study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients for the research as well as for the
Corresponding author at: Institut de Microcirurgria Ocular (IMO), c/Josep Maria Llado 3, 08035 Barcelona, Spain. E-mail address: [email protected] (J.L. Güell).
https://doi.org/10.1016/j.xjec.2019.03.003 Received 18 October 2018; Received in revised form 26 March 2019; Accepted 31 March 2019 Available online 02 April 2019 2452-4034/ © 2019 The Authors. Published by Elsevier Inc. on behalf of European Society of Cornea & Ocular Surface Disease Specialists. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of EuCornea 2 (2019) 10–13
J.L. Güell, et al.
USA). Endothelial cell loss was calculated by subtracting the 6-months postoperative ECD from the baseline donor ECD, dividing by the baseline donor ECD, and multiplying by 100. Postoperatively, central endothelial cell count (cECC) was measured with the TOPCON SP3000p (Topcon Corporation, Tokyo, Japan) [9,10]. Imaging of the anterior segment (AS) was obtained using the Cirrus OCT (Carl Zeiss Meditec, Jena, Germany). After surgery, all eyes were checked for graft attachment at the slitlamp and with AS OCT, regardless of the transparency of the cornea. Postoperative complications, including the need for air re-injection, immunologic rejection, IOP elevation, and graft failure, were documented. All data was analyzed preoperatively, and 6, 12 and 24 months postoperatively. Because the aim of this study was purely descriptive, and the sample size was low, no statistical analysis was performed other than descriptive statistics. Continuous variables were described with mean, standard deviation (SD), and range.
surgical procedures. 2.1. Surgical technique Donor corneas were stored in organ culture medium as detailed in our previous publication [11]. The preparation of the lenticule was performed by the surgeon immediately before each surgery and a standardized DMEK technique was followed, as previously described [11]. Some modifications were adopted for this particular group of eyes, which include: (1) the 2.4 mm wide posterior corneal incision and the two paracentesis were precisely located to avoid any interference with the old penetrating wound; (2) no descemetorhexis was performed because no penetrating grafts had significant posterior fibrosis, to avoid any change in the posterior corneal profile and any reopening of the existing penetrating wound; (3) membraneblue-dual® (D.O.R.C., Rotterdam, The Netherlands) was used in order to maintain good visualization longer than with other dyes. Graft diameter was 8.0 mm in 19/ 26 (73.07%) eyes and 7.5 mm in 7/26 (26.93%) eyes. All DMEK grafts were 0.5-mm smaller than the first PK surgery. Endothelium-Descemet (DMEK) grafts were cautiously centered at the center of the previous full-thickness graft. In all cases, sulfur hexafluoride (SF6) at a non-expansible concentration of 20% was used for tamponade, leaving a bubble occupying 80% of the anterior chamber [11,12]. Normal eye pressure was left at the end of surgery. Intracameral injection of cefuroxime (1.0 mg in 0.1 mL normal saline) was given to all patients. Additionally, 80 mg of subconjunctival methylprednisolone and 1 mg/kg of intravenous methylprednisolone were administered.
3. Results Twenty-six consecutive eyes of 16 patients (14 males and 2 females) were identified. Mean host age was 58.50 ± 12.50 years old. Mean donor age was 65.30 ± 10.49. Mean follow up duration after DMEK was 23.08 ± 10.27 months (range, 6 months–48 months). Seventeen (65.38%) eyes reached at least the 24-month follow up time point. At last follow up, 24 eyes (92.31%) presented with clear corneas. Twelve eyes (46.15%) had a previous history of one or more episodes of graft rejection. All eyes had a CDVA of 0.8 or better. Original indications for PK were: advanced keratoconus (n = 7), pseudophakic bullous keratopathy (n = 11), aphakic bullous keratopathy (n = 1), post infectious keratitis (non-herpetic) scar (n = 4), Fuchs’ endothelial dystrophy (n = 1; phakic eye), and posttraumatic corneal scar (n = 2).
2.2. Postoperative management Postoperative treatment consisted of: topical tobramycin 0.3% and dexamethasone 0.1% (Tobradex, Alcon Cusi, El Mas Nou, Barcelona, Spain) 4 times daily for three weeks, and 2 times daily for the following 8 weeks; timolol 0.5% (Cusimolol, Alcon Cusi, El Mas Nou, Barcelona, Spain) 2 times daily for 12 weeks; and dexamethasone 0.05% and chloramphenicol 1% ointment (DeIcol, Alcon Cusi) at bedtime for 6 months, and then stopped in the absence of any inflammatory signs or signs of rejection. Additional ocular hypotensive medications were prescribed if needed. Oral methylprednisolone (Urbason, Sanofi Aventis Pharma S.A., Barcelona, Spain) was also prescribed and slowly tapered off for the first three weeks: 40 mg/day for three days; 20 mg/day for three more days; 10 mg/day for 1 week; and 10 mg every 48 h for 1 week. To ensure graft attachment with the aid of SF6 20% bubble, patients were also instructed on different positioning regimens as previously described [11].
3.1. Visual acuity and endothelial cell density Table 1 summarizes mean CDVA and endothelial cell density at each timepoint. A significant improvement in CDVA was observed (p = 0.047). Six months postoperatively there was a significant decrease in ECD (p = 0.039), which remained stable between 6 and 12 months and decreased again between 12 and 24 months. However, only one eye had less than 600 cells/mm2 24 months postoperatively. Mean cell loss at 6 months was 27.67 ± 16%. 3.2. Intraoperative and postoperative complications All surgeries were uneventful with complete attachment of the DMEK graft in all eyes at the first postoperative day. Three eyes (11.53%) had significant graft detachment during the first three postoperative weeks. Two of them were immediately treated by SF6 20% re-
2.3. Re-bubbling In case of a significant graft detachment that affected more than 30% of the graft surface (with or without visual axis involvement), a rebubbling procedure was scheduled. All re-bubbling procedures were performed in the operating room under topical anaesthesia using an automated irrigation-aspiration system.
Table 1 Visual acuity, refraction and endothelial cell density. Data is shown with mean (standard deviation). Preoperative
Postop
(n = 26)
6 months (n = 26)
12 months (n = 24)
24 months (n = 17)
CDVA (decimal Snellen) SE (D) Cylinder (D)
0.29 (0.20)
0.67 (0.06)
0.71 (0.04)
0.75 (0.03)
1.91 (3.29) −1.44 (0.53)
1.91 (3.01) −1.47 (0.59)
1.60 (2.89) −1.38 (0.53)
ECD (cells/mm2)
2612 (296)*
1.75 (2.75) −1.50 (0.52) 1889 (575)
1712 (303)
1480 (320)
2.4. Outcome analysis Microsoft Excel (Redmond, WA, USA) was used for data collection and to perform descriptive statistics. Corrected distance visual acuity (CDVA) was measured using Snellen projector charts. Intraocular pressure was measured using the Goldman applanation tonometer and the Icare (Icare USA, Raleigh, NC). The baseline donor endothelial cell density (ECD) was measured by the Barcelona Tissue Eye Bank (Banc de Sang i Teixits “BST”) using specular microscopy (Cellcheck plus, Konan Medical Inc, Fair Lawn, NJ,
CDVA: corrected distance visual acuity; SE: Spherical Equivalent; ECD: endothelial cell density; n: number of eyes. * ECD of the donor cornea measured at eye bank. 11
Journal of EuCornea 2 (2019) 10–13
J.L. Güell, et al.
Fig. 1. (A, B) Intraoperative view of gas rebubbling of DMEK after failed PK four weeks after surgery. (A) First, corneal epithelium is removed to achieve a better view. (B) Sulfur hexafluoride 20% bubble almost fully occupying the anterior chamber. (C) Complete reposition of the graft could not be achieved and a significant tension of the graft was observed. (D) Nd:YAG laser membranotomy was successfully performed and complete graft reattachment was achieved. An inferior horizontal rupture line in the graft that did not affect adequate endothelial function can be seen. (F) Optical Coherence Tomography (OCT) image of the detached DMEK graft. (G) OCT image shows complete graft attachment.
group of eyes with a visual potential equal or greater than 0.8. Specifically, key advantages include avoiding a new full thickness graft and open sky surgery. This results in greater safety. Additionally, visual rehabilitation is faster because no significant changes in the refractive status of the eye are induced. However, given the limited follow-up, no conclusion can be drawn with reference to the rate of endothelial graft rejection and chronic endothelial cell loss. Compared to repeat PK, we do not expect any significant differences. Complications in this study of DMEK after failed PK were consistent with those reported with primary DMEK, postoperative graft detachment being the most frequently encountered. Both the rate and characteristics of graft detachment are similar to our experience with primary DMEK [12]. In line with other studies, graft detachments occur in the first few weeks after the surgery. In our opinion, tamponade with SF6 20%, together with careful positioning of the membrane over the ‘host’ stroma and the postoperative head positioning during the first few postoperative days are the key factors that explain our low rebubbling rate in primary DMEK of 6.6%, even lower than the current series (11.53%) [11]. One eye had to undergo Nd:YAG membranotomy after re-bubbling with SF6 20% to achieve complete attachment of the graft, which adhered to the inferior edge of the posterior penetrating wound. The endothelial graft may have been damaged during the surgical maneuvers, when the inferior iridectomy was performed. Regarding ECD loss, our results are in line with other series of primary DMEK and repeat DMEK after failed DMEK [11,12,16]. Only the
bubbling as previously described and the graft successfully reattached. In the third case, as the graft detachment was closer to the host, we decided to wait for spontaneous resolution. Four weeks after surgery, gas reinjection was performed but complete apposition of the graft could not be achieved, and significant tension on the graft was observed (Fig. 1). In an attempt to achieve complete re-attachment, Nd:YAG laser membranotomy was successfully performed. Despite an inferior horizontal rupture line in the graft, this did not affect adequate endothelial function. Although all eyes maintained normal IOP values, 22/26 (84.61%) eyes required at least one topical medication (beta blocker in the majority of cases). No episodes of immunological graft rejection were documented during the study period. Eight months after DMEK surgery, Artisan IOL implantation was performed in the aphakic eye to correct a residual refractive error. Another eye had Sulcoflex add-on explantation because of a secondary central IOL opacification (Fig. 2). Surgery was uneventful but, as expected, significant residual ametropia resulted. 4. Discussion The findings of this study are consistent with previous reports on DMEK to treat endothelial graft failure after PK, DSAEK and DMEK [13–16]. In our experience, excellent visual outcomes were achieved in a 12
Journal of EuCornea 2 (2019) 10–13
J.L. Güell, et al.
Fig. 2. Opacification of a Sulcoflex add-on intraocular lens (IOL). Explantation of the IOL was required. (A) Preoperative image. (B) Postoperative image once Sulcoflex IOL was removed.
material or method mentioned.
eye that received Nd:YAG membranotomy had ECD below 600 cells/ mm2 (Fig. 1). While some authors have suggested that, in the absence of significant fibrosis, leaving the ‘host’ Descemet’s membrane in place has no negative impact in relation to detachment rate or postoperative ECD decay [8], other authors prefer to perform a descemetorhexis [10,17]. In our opinion, in the context of DMEK after failed PK, leaving the host Descemet better preserves the posterior corneal profile. Despite our encouraging results with leaving the ‘host’ Descemet’s membrane intact, we are currently exploring performing a 4–5 mm central descemetorhexis to both avoid any manipulation of the posterior penetrating wound and possibly restoring ‘normal’ anatomy to the central cornea. This may allow the achievement of better visual and optical postoperative results. Moreover, we would theoretically diminish the load of donor antigenic cells. None of the 16 pseudophakic eyes had clinically significant IOL opacification. The only eye that experienced IOL opacification had a Sulcoflex “add-on” IOL for the correction of a significant refractive error. Study limitations included its retrospective nature, the inclusion of a small number of eyes with an excellent visual prognosis, the fact that it is a single surgeon and single center experience, and the relatively short follow-up especially in terms of risk for graft rejection. Nevertheless, in our experience, this study reinforces the idea of considering endothelial keratoplasty and, particularly DMEK, as the surgical technique of choice for the management of failed PK grafts. In conclusion, this study showed that DMEK after failed PK is a safe and effective method for management of failed PK grafts and probably superior to repeat PK. The complication rates with DMEK after failed PK were comparable with the rates reported with primary DMEK. Although longer-term follow-up studies are needed, endothelial keratoplasty appears to be the surgical technique of choice for the management of failed PK grafts.
References [1] F.W. Price Jr., M.O. Price, Endothelial keratoplasty to restore clarity to a failed penetrating graft, Cornea 5 (2006) 895–899. [2] M. Ang, H. Ho, C. Wong, et al., Endothelial keratoplasty after failed penetrating keratoplasty: an alternative to repeat penetrating keratoplasty, Am. J. Ophthalmol. 158 (2014) 1221–1227. [3] A. Panda, M. Vanathi, A. Kumar, et al., Corneal graft rejection, Surv. Ophthalmol. 52 (2007) 375–396. [4] M. Claesson, W.J. Armitage, Clinical outcome of repeat penetrating keratoplasty, Cornea 32 (2013) 1026–1030. [5] I. Dapena, L. Ham, M. Netukova, et al., Incidence of early allograft rejection after descemet membrane endothelial keratoplasty, Cornea 30 (2011) 1341–1345. [6] A. Anshu, M.O. Price, F.W. Price Jr., Risk of corneal transplant rejection significantly reduced with descemet’s membrane endothelial keratoplasty, Ophthalmology 119 (2012) 536–540. [7] A.S. Kitzmann, G.R. Wandling, J.E. Sutphin, Comparison of outcomes of penetrating keratoplasty versus Descemet’s stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure due to corneal edema, Int. Ophthalmol. 32 (2012) 15–23. [8] A. Ahshu, M.O. Price, F.W. Price Jr., descemet membrane endothelial keratoplasty and hybrid techniques for managing failed penetrating grafts, Cornea 32 (2013) 1–4. [9] M.C. Keane, R.A. Galettis, R.A. Mills, et al., A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study, Br. J. Ophthalmol. (2016), https://doi.org/10.0036/bjophthalmol2015-307792. [10] I. Lavy, R.M. Verdijk, M. Bruinsma, et al., Sex-chromosome analysis of post mortem endothelium in corneas after Descemet membrane endothelial keratoplasty, Cornea 36 (2017) 11–16. [11] J.L. Güell, M. Morral, O. Gris, et al., Bimanual technique for insertion and positioning of endotheliaum-Descemet membrane graft in Descemet membrane endothelial keratoplasty, Cornea 32 (2013) 1521–1526. [12] J.L. Güell, M. Morral, O. Gris, et al., Comparison of sulfur hexafluoride 20% versus air tampnade in Descemet membrane endothelial keratoplasty, Ophthalmology 122 (9) (2015 Sep) 1757–1764. [13] M.D. Straiko, M.A. Terry, N. Shamie, Descemet stripping automated endothelial keratoplasty under failed penetrating keratoplasty: a surgical strategy to minimize complications, Am. J. Ophthalmol. 151 (2011) 233–237. [14] A. Einan-Lifshitz, A. Belkin, N. Sorkin, et al., Descemet membrane endothelial keratoplasty after penetrating keratoplasty: features for success, Cornea 37 (2018) 1093–1097. [15] J.M. Weller, T. Tourtas, F.E. Kruse, et al., Descemet membrane endothelial keratoplasty as treatment for graft failure after descemet stripping automated endothelial keratoplasty, Am. J. Ophthalmol. 159 (6) (2015) 1050–1057. [16] M.O. Price, M.T. Feng, Y. McKee, F.W. Price Jr., Repeat descemet membrane endothelial keratoplasty secondary grafts with early intervention are comparable with fellow-eye primary grafts, Ophthalmology 122 (2015) 1639–1644. [17] S. Heinzelmann, D. Böhringer, P. Eberwein, et al., Outcomes of Descemet membrane endothelial keratoplasty. Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study, Graefes Arch. Clin. Exp. Ophthalmol. 254 (2016) 515–522.
Meeting presentation Presented in part at the European Society of Cataract and Refractive Surgeons Winter Meeting 2015. Financial support None. Conflict of interest None of the authors have no financial or proprietary interest in any
13
Contents lists available at ScienceDirect
Journal of EuCornea journal homepage: www.elsevier.com/locate/xjec
Descemet membrane endothelial keratoplasty after penetrating keratoplasty a,b,c,d,⁎
Jose L. Güell , Merce Morral Felicidad Maneroa
a,b
a
a
, Miriam Barbany , Oscar Gris , Daniel Elies
a,b
T
,
a
Institut de Microcirurgia Ocular (IMO), Barcelona, Spain European School for Advanced Studies in Ophthalmology (ESASO), Switzerland Universitat Autonoma de Barcelona (UAB), Barcelona, Spain d Cornea and Refractive Surgery Unit, Institut de Microcirurgia Ocular, Barcelona, Spain b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Keratoplasty DMEK PK Corneal transplant Corneal endothelium Graft failure Fuchs dystrophy Descemetorhexis Penetrating keratoplasty
Purpose: To describe visual and clinical outcomes of descemet membrane endothelial keratoplasty (DMEK) for late endothelial failure after penetrating keratoplasty (PK). Methods: Retrospective, observational study of patients who consecutively received DMEK to treat PK graft failure. Intraoperative complications were recorded. Our previously described DMEK surgical technique was used except that host descemet membrane was not stripped in any of the eyes. Corrected distance visual acuity (CDVA), and endothelial cell density (ECD) were evaluated before surgery and at regular intervals up to 24 months after the surgery. Results: Twenty-six eyes of 26 patients were included. Mean host age was 58.50 ± 12.50 years old. Mean donor age was 65.30 ± 10.49. Mean follow up after DMEK was 23.08 ± 10.27 (range 6 months–48 months). Seventeen (65.38%) eyes reached at least the 24-month follow up time point. At last follow up, 24 eyes (92.31%) presented with clear corneas. Twenty-four months postoperatively, mean Snellen CDVA in decimal fraction was 0.75 ± 0.03 (range 0.6–0.80) and mean central endothelial cell density was 1480.41 ± 320.56 cells/mm2 (range, 591–1950 cells/mm2). Mean cell loss at 6 months was 27.67 ± 16.03%. Three (11.53%) eyes had significant graft detachment that required re-bubbling. No episodes of immunological graft rejection were documented. Conclusions: Our experience shows that DMEK is a useful technique to treat endothelial graft failure following PK. Compared to repeat PK, DMEK-specific surgical complications and postsurgical management should be expected.
1. Introduction Late endothelial failure is one of the commonest causes for re-intervention after full-thickness corneal transplantation worldwide. Endothelial keratoplasty (EK), either in the form of Descemet stripping automated endothelial keratoplasty (DSEK/DSAEK) or descemet membrane endothelial keratoplasty (DMEK), has become the preferred treatment for graft failure over a repeat penetrating keratoplasty (PK) during these last few years [1,2]. The main advantages of EK seem to be better visual outcomes in most cases, lower risk of rejection and to escape from intraoperative and postoperative risks associated with an “open-sky” technique such as expulsive hemorrhage [3–7] and secondary astigmatism. Additionally, several studies have suggested that DMEK grafts fit better over the irregular posterior corneal surface of a full thickness graft [8–10].
⁎
The aim of this study is to describe our clinical experience with DMEK for late endothelial failure after PK. 2. Material and methods Data collected prospectively at a single center was reviewed retrospectively to identify patients who underwent DMEK after failed primary PK between April 2012 and January 2018 and with at least 3 months of follow-up and potential CDVA of 0.8 or better. Patients with concurrent, non-corneal ocular pathology that limited visual potential such as macular disease, advanced glaucoma and/or aniridia were excluded. All surgeries were performed by a single surgeon (J.L.G.) at the Institut de Microcirurgia Ocular, Barcelona, Spain. The study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients for the research as well as for the
Corresponding author at: Institut de Microcirurgria Ocular (IMO), c/Josep Maria Llado 3, 08035 Barcelona, Spain. E-mail address: [email protected] (J.L. Güell).
https://doi.org/10.1016/j.xjec.2019.03.003 Received 18 October 2018; Received in revised form 26 March 2019; Accepted 31 March 2019 Available online 02 April 2019 2452-4034/ © 2019 The Authors. Published by Elsevier Inc. on behalf of European Society of Cornea & Ocular Surface Disease Specialists. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of EuCornea 2 (2019) 10–13
J.L. Güell, et al.
USA). Endothelial cell loss was calculated by subtracting the 6-months postoperative ECD from the baseline donor ECD, dividing by the baseline donor ECD, and multiplying by 100. Postoperatively, central endothelial cell count (cECC) was measured with the TOPCON SP3000p (Topcon Corporation, Tokyo, Japan) [9,10]. Imaging of the anterior segment (AS) was obtained using the Cirrus OCT (Carl Zeiss Meditec, Jena, Germany). After surgery, all eyes were checked for graft attachment at the slitlamp and with AS OCT, regardless of the transparency of the cornea. Postoperative complications, including the need for air re-injection, immunologic rejection, IOP elevation, and graft failure, were documented. All data was analyzed preoperatively, and 6, 12 and 24 months postoperatively. Because the aim of this study was purely descriptive, and the sample size was low, no statistical analysis was performed other than descriptive statistics. Continuous variables were described with mean, standard deviation (SD), and range.
surgical procedures. 2.1. Surgical technique Donor corneas were stored in organ culture medium as detailed in our previous publication [11]. The preparation of the lenticule was performed by the surgeon immediately before each surgery and a standardized DMEK technique was followed, as previously described [11]. Some modifications were adopted for this particular group of eyes, which include: (1) the 2.4 mm wide posterior corneal incision and the two paracentesis were precisely located to avoid any interference with the old penetrating wound; (2) no descemetorhexis was performed because no penetrating grafts had significant posterior fibrosis, to avoid any change in the posterior corneal profile and any reopening of the existing penetrating wound; (3) membraneblue-dual® (D.O.R.C., Rotterdam, The Netherlands) was used in order to maintain good visualization longer than with other dyes. Graft diameter was 8.0 mm in 19/ 26 (73.07%) eyes and 7.5 mm in 7/26 (26.93%) eyes. All DMEK grafts were 0.5-mm smaller than the first PK surgery. Endothelium-Descemet (DMEK) grafts were cautiously centered at the center of the previous full-thickness graft. In all cases, sulfur hexafluoride (SF6) at a non-expansible concentration of 20% was used for tamponade, leaving a bubble occupying 80% of the anterior chamber [11,12]. Normal eye pressure was left at the end of surgery. Intracameral injection of cefuroxime (1.0 mg in 0.1 mL normal saline) was given to all patients. Additionally, 80 mg of subconjunctival methylprednisolone and 1 mg/kg of intravenous methylprednisolone were administered.
3. Results Twenty-six consecutive eyes of 16 patients (14 males and 2 females) were identified. Mean host age was 58.50 ± 12.50 years old. Mean donor age was 65.30 ± 10.49. Mean follow up duration after DMEK was 23.08 ± 10.27 months (range, 6 months–48 months). Seventeen (65.38%) eyes reached at least the 24-month follow up time point. At last follow up, 24 eyes (92.31%) presented with clear corneas. Twelve eyes (46.15%) had a previous history of one or more episodes of graft rejection. All eyes had a CDVA of 0.8 or better. Original indications for PK were: advanced keratoconus (n = 7), pseudophakic bullous keratopathy (n = 11), aphakic bullous keratopathy (n = 1), post infectious keratitis (non-herpetic) scar (n = 4), Fuchs’ endothelial dystrophy (n = 1; phakic eye), and posttraumatic corneal scar (n = 2).
2.2. Postoperative management Postoperative treatment consisted of: topical tobramycin 0.3% and dexamethasone 0.1% (Tobradex, Alcon Cusi, El Mas Nou, Barcelona, Spain) 4 times daily for three weeks, and 2 times daily for the following 8 weeks; timolol 0.5% (Cusimolol, Alcon Cusi, El Mas Nou, Barcelona, Spain) 2 times daily for 12 weeks; and dexamethasone 0.05% and chloramphenicol 1% ointment (DeIcol, Alcon Cusi) at bedtime for 6 months, and then stopped in the absence of any inflammatory signs or signs of rejection. Additional ocular hypotensive medications were prescribed if needed. Oral methylprednisolone (Urbason, Sanofi Aventis Pharma S.A., Barcelona, Spain) was also prescribed and slowly tapered off for the first three weeks: 40 mg/day for three days; 20 mg/day for three more days; 10 mg/day for 1 week; and 10 mg every 48 h for 1 week. To ensure graft attachment with the aid of SF6 20% bubble, patients were also instructed on different positioning regimens as previously described [11].
3.1. Visual acuity and endothelial cell density Table 1 summarizes mean CDVA and endothelial cell density at each timepoint. A significant improvement in CDVA was observed (p = 0.047). Six months postoperatively there was a significant decrease in ECD (p = 0.039), which remained stable between 6 and 12 months and decreased again between 12 and 24 months. However, only one eye had less than 600 cells/mm2 24 months postoperatively. Mean cell loss at 6 months was 27.67 ± 16%. 3.2. Intraoperative and postoperative complications All surgeries were uneventful with complete attachment of the DMEK graft in all eyes at the first postoperative day. Three eyes (11.53%) had significant graft detachment during the first three postoperative weeks. Two of them were immediately treated by SF6 20% re-
2.3. Re-bubbling In case of a significant graft detachment that affected more than 30% of the graft surface (with or without visual axis involvement), a rebubbling procedure was scheduled. All re-bubbling procedures were performed in the operating room under topical anaesthesia using an automated irrigation-aspiration system.
Table 1 Visual acuity, refraction and endothelial cell density. Data is shown with mean (standard deviation). Preoperative
Postop
(n = 26)
6 months (n = 26)
12 months (n = 24)
24 months (n = 17)
CDVA (decimal Snellen) SE (D) Cylinder (D)
0.29 (0.20)
0.67 (0.06)
0.71 (0.04)
0.75 (0.03)
1.91 (3.29) −1.44 (0.53)
1.91 (3.01) −1.47 (0.59)
1.60 (2.89) −1.38 (0.53)
ECD (cells/mm2)
2612 (296)*
1.75 (2.75) −1.50 (0.52) 1889 (575)
1712 (303)
1480 (320)
2.4. Outcome analysis Microsoft Excel (Redmond, WA, USA) was used for data collection and to perform descriptive statistics. Corrected distance visual acuity (CDVA) was measured using Snellen projector charts. Intraocular pressure was measured using the Goldman applanation tonometer and the Icare (Icare USA, Raleigh, NC). The baseline donor endothelial cell density (ECD) was measured by the Barcelona Tissue Eye Bank (Banc de Sang i Teixits “BST”) using specular microscopy (Cellcheck plus, Konan Medical Inc, Fair Lawn, NJ,
CDVA: corrected distance visual acuity; SE: Spherical Equivalent; ECD: endothelial cell density; n: number of eyes. * ECD of the donor cornea measured at eye bank. 11
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Fig. 1. (A, B) Intraoperative view of gas rebubbling of DMEK after failed PK four weeks after surgery. (A) First, corneal epithelium is removed to achieve a better view. (B) Sulfur hexafluoride 20% bubble almost fully occupying the anterior chamber. (C) Complete reposition of the graft could not be achieved and a significant tension of the graft was observed. (D) Nd:YAG laser membranotomy was successfully performed and complete graft reattachment was achieved. An inferior horizontal rupture line in the graft that did not affect adequate endothelial function can be seen. (F) Optical Coherence Tomography (OCT) image of the detached DMEK graft. (G) OCT image shows complete graft attachment.
group of eyes with a visual potential equal or greater than 0.8. Specifically, key advantages include avoiding a new full thickness graft and open sky surgery. This results in greater safety. Additionally, visual rehabilitation is faster because no significant changes in the refractive status of the eye are induced. However, given the limited follow-up, no conclusion can be drawn with reference to the rate of endothelial graft rejection and chronic endothelial cell loss. Compared to repeat PK, we do not expect any significant differences. Complications in this study of DMEK after failed PK were consistent with those reported with primary DMEK, postoperative graft detachment being the most frequently encountered. Both the rate and characteristics of graft detachment are similar to our experience with primary DMEK [12]. In line with other studies, graft detachments occur in the first few weeks after the surgery. In our opinion, tamponade with SF6 20%, together with careful positioning of the membrane over the ‘host’ stroma and the postoperative head positioning during the first few postoperative days are the key factors that explain our low rebubbling rate in primary DMEK of 6.6%, even lower than the current series (11.53%) [11]. One eye had to undergo Nd:YAG membranotomy after re-bubbling with SF6 20% to achieve complete attachment of the graft, which adhered to the inferior edge of the posterior penetrating wound. The endothelial graft may have been damaged during the surgical maneuvers, when the inferior iridectomy was performed. Regarding ECD loss, our results are in line with other series of primary DMEK and repeat DMEK after failed DMEK [11,12,16]. Only the
bubbling as previously described and the graft successfully reattached. In the third case, as the graft detachment was closer to the host, we decided to wait for spontaneous resolution. Four weeks after surgery, gas reinjection was performed but complete apposition of the graft could not be achieved, and significant tension on the graft was observed (Fig. 1). In an attempt to achieve complete re-attachment, Nd:YAG laser membranotomy was successfully performed. Despite an inferior horizontal rupture line in the graft, this did not affect adequate endothelial function. Although all eyes maintained normal IOP values, 22/26 (84.61%) eyes required at least one topical medication (beta blocker in the majority of cases). No episodes of immunological graft rejection were documented during the study period. Eight months after DMEK surgery, Artisan IOL implantation was performed in the aphakic eye to correct a residual refractive error. Another eye had Sulcoflex add-on explantation because of a secondary central IOL opacification (Fig. 2). Surgery was uneventful but, as expected, significant residual ametropia resulted. 4. Discussion The findings of this study are consistent with previous reports on DMEK to treat endothelial graft failure after PK, DSAEK and DMEK [13–16]. In our experience, excellent visual outcomes were achieved in a 12
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Fig. 2. Opacification of a Sulcoflex add-on intraocular lens (IOL). Explantation of the IOL was required. (A) Preoperative image. (B) Postoperative image once Sulcoflex IOL was removed.
material or method mentioned.
eye that received Nd:YAG membranotomy had ECD below 600 cells/ mm2 (Fig. 1). While some authors have suggested that, in the absence of significant fibrosis, leaving the ‘host’ Descemet’s membrane in place has no negative impact in relation to detachment rate or postoperative ECD decay [8], other authors prefer to perform a descemetorhexis [10,17]. In our opinion, in the context of DMEK after failed PK, leaving the host Descemet better preserves the posterior corneal profile. Despite our encouraging results with leaving the ‘host’ Descemet’s membrane intact, we are currently exploring performing a 4–5 mm central descemetorhexis to both avoid any manipulation of the posterior penetrating wound and possibly restoring ‘normal’ anatomy to the central cornea. This may allow the achievement of better visual and optical postoperative results. Moreover, we would theoretically diminish the load of donor antigenic cells. None of the 16 pseudophakic eyes had clinically significant IOL opacification. The only eye that experienced IOL opacification had a Sulcoflex “add-on” IOL for the correction of a significant refractive error. Study limitations included its retrospective nature, the inclusion of a small number of eyes with an excellent visual prognosis, the fact that it is a single surgeon and single center experience, and the relatively short follow-up especially in terms of risk for graft rejection. Nevertheless, in our experience, this study reinforces the idea of considering endothelial keratoplasty and, particularly DMEK, as the surgical technique of choice for the management of failed PK grafts. In conclusion, this study showed that DMEK after failed PK is a safe and effective method for management of failed PK grafts and probably superior to repeat PK. The complication rates with DMEK after failed PK were comparable with the rates reported with primary DMEK. Although longer-term follow-up studies are needed, endothelial keratoplasty appears to be the surgical technique of choice for the management of failed PK grafts.
References [1] F.W. Price Jr., M.O. Price, Endothelial keratoplasty to restore clarity to a failed penetrating graft, Cornea 5 (2006) 895–899. [2] M. Ang, H. Ho, C. Wong, et al., Endothelial keratoplasty after failed penetrating keratoplasty: an alternative to repeat penetrating keratoplasty, Am. J. Ophthalmol. 158 (2014) 1221–1227. [3] A. Panda, M. Vanathi, A. Kumar, et al., Corneal graft rejection, Surv. Ophthalmol. 52 (2007) 375–396. [4] M. Claesson, W.J. Armitage, Clinical outcome of repeat penetrating keratoplasty, Cornea 32 (2013) 1026–1030. [5] I. Dapena, L. Ham, M. Netukova, et al., Incidence of early allograft rejection after descemet membrane endothelial keratoplasty, Cornea 30 (2011) 1341–1345. [6] A. Anshu, M.O. Price, F.W. Price Jr., Risk of corneal transplant rejection significantly reduced with descemet’s membrane endothelial keratoplasty, Ophthalmology 119 (2012) 536–540. [7] A.S. Kitzmann, G.R. Wandling, J.E. Sutphin, Comparison of outcomes of penetrating keratoplasty versus Descemet’s stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure due to corneal edema, Int. Ophthalmol. 32 (2012) 15–23. [8] A. Ahshu, M.O. Price, F.W. Price Jr., descemet membrane endothelial keratoplasty and hybrid techniques for managing failed penetrating grafts, Cornea 32 (2013) 1–4. [9] M.C. Keane, R.A. Galettis, R.A. Mills, et al., A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study, Br. J. Ophthalmol. (2016), https://doi.org/10.0036/bjophthalmol2015-307792. [10] I. Lavy, R.M. Verdijk, M. Bruinsma, et al., Sex-chromosome analysis of post mortem endothelium in corneas after Descemet membrane endothelial keratoplasty, Cornea 36 (2017) 11–16. [11] J.L. Güell, M. Morral, O. Gris, et al., Bimanual technique for insertion and positioning of endotheliaum-Descemet membrane graft in Descemet membrane endothelial keratoplasty, Cornea 32 (2013) 1521–1526. [12] J.L. Güell, M. Morral, O. Gris, et al., Comparison of sulfur hexafluoride 20% versus air tampnade in Descemet membrane endothelial keratoplasty, Ophthalmology 122 (9) (2015 Sep) 1757–1764. [13] M.D. Straiko, M.A. Terry, N. Shamie, Descemet stripping automated endothelial keratoplasty under failed penetrating keratoplasty: a surgical strategy to minimize complications, Am. J. Ophthalmol. 151 (2011) 233–237. [14] A. Einan-Lifshitz, A. Belkin, N. Sorkin, et al., Descemet membrane endothelial keratoplasty after penetrating keratoplasty: features for success, Cornea 37 (2018) 1093–1097. [15] J.M. Weller, T. Tourtas, F.E. Kruse, et al., Descemet membrane endothelial keratoplasty as treatment for graft failure after descemet stripping automated endothelial keratoplasty, Am. J. Ophthalmol. 159 (6) (2015) 1050–1057. [16] M.O. Price, M.T. Feng, Y. McKee, F.W. Price Jr., Repeat descemet membrane endothelial keratoplasty secondary grafts with early intervention are comparable with fellow-eye primary grafts, Ophthalmology 122 (2015) 1639–1644. [17] S. Heinzelmann, D. Böhringer, P. Eberwein, et al., Outcomes of Descemet membrane endothelial keratoplasty. Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study, Graefes Arch. Clin. Exp. Ophthalmol. 254 (2016) 515–522.
Meeting presentation Presented in part at the European Society of Cataract and Refractive Surgeons Winter Meeting 2015. Financial support None. Conflict of interest None of the authors have no financial or proprietary interest in any
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