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Causes of Glaucoma After Descemet Membrane Endothelial Keratoplasty
Causes of Glaucoma After Descemet Membrane Endothelial Keratoplasty MIGUEL NAVEIRAS, MARTIN DIRISAMER, JACK PARKER, LISANNE HAM, KORINE VAN DIJK, ISABEL DAPENA, AND GERRIT R.J. MELLES ● PURPOSE:
To describe the incidence and causes of glaucoma after Descemet membrane endothelial keratoplasty (DMEK). ● DESIGN: Nonrandomized prospective cohort study at a tertiary referral center. ● METHODS: The incidence of glaucoma was evaluated in the first 275 consecutive eyes that underwent DMEK for Fuchs endothelial dystrophy (260 eyes) or bullous keratopathy (15 eyes). Glaucoma was defined as a postoperative intraocular pressure (IOP) elevation of >24 mm Hg, or >10 mm Hg from the preoperative baseline. If possible, the cause of glaucoma was identified, and best-corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative course were documented, with a mean follow-up of 22 (ⴞ 13) months. ● RESULTS: Overall, 18 eyes (6.5%) showed postoperative glaucoma after DMEK. Seven eyes (2.5%) had an exacerbation of a pre-existing glaucoma. Eleven eyes (4%) presented with a de novo IOP elevation, associated with air bubble–induced mechanical angle closure (2%), steroid response (0.7%), or peripheral anterior synechiae (0.4%), or without detectable cause (0.7%). Two eyes (0.7%) required glaucoma surgery after DMEK. At 6 months, all eyes had a BCVA of >20/40 (>0.5), and 81% reached >20/25 (>0.8) (n ⴝ 16); mean ECD was 1660 (ⴞ 554) cells/mm2 (n ⴝ 15) (P > .1). ● CONCLUSION: Glaucoma after DMEK may be a relatively frequent complication that could be avoided by reducing the residual postoperative air bubble to 30% in phakic eyes, applying a population-specific steroid regime, and avoiding decentration of the Descemet graft. Eyes with a history of glaucoma may need close IOP monitoring in the first postoperative months, especially in eyes with an angle-supported phakic intraocular lens. (Am J Ophthalmol 2012;153:958 –966. © 2012 by Elsevier Inc. All rights reserved.)
I
N THE PAST DECADE, WE HAVE INTRODUCED VARIOUS
techniques for endothelial keratoplasty, later popularized as deep lamellar endothelial keratoplasty (DLEK) and Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK).1,2 More recently, we described a technique for the selective transplantation of a donor Descemet membrane, now referred to as Descemet membrane endothelial keratoplasty (DMEK).3⫺6 With the advent of endothelial keratoplasty, the type of complications and their incidence have shifted compared to those encountered after penetrating keratoplasty. Astigmatism, suture-related problems, and wound dehiscence have been virtually eliminated and the risk of allograft rejection may have been reduced, while graft detachment as a “new” complication has surfaced.1,5,6 However, endothelial keratoplasty may also be associated with a shift in intraocular complications, particularly specific types of glaucoma induced by the presence of an intraocular air bubble in the immediate postoperative phase.7 Overall, glaucoma has been described to occur in about 30% of cases after endothelial or penetrating keratoplasty, so that it may be one of few severe complications after keratoplasty today, affecting the clinical outcome and/or graft survival in the long term.7,8 Since DMEK grafts may require a longer air bubble support to obtain graft adherence to the recipient posterior stroma,1,4 the risk of glaucoma after DMEK could be higher than after DSEK/ DSAEK, so a better understanding of the various mechanisms may aid in preventing glaucoma, thereby improving the overall success rate of the procedure. In the present study, we prospectively documented all glaucoma episodes associated with the first 275 DMEK surgeries performed at our center, to determine the causes and incidence of postoperative intraocular pressure (IOP) elevations and to possibly define precautions to minimize the risk of glaucoma after DMEK.
MATERIALS AND METHODS Accepted for publication Oct 4, 2011. From the Netherlands Institute for Innovative Ocular Surgery (M.N., M.D., J.P., L.H., K.v.D., I.D., G.R.J.M.), Melles Cornea Clinic Rotterdam (M.N., M.D., J.P., L.H., K.v.D., I.D., G.R.J.M.), and Amnitrans EyeBank (G.R.J.M.), Rotterdam, The Netherlands; and AKh Linz (M.D.), Linz, Austria. Inquiries to Gerrit R.J. Melles, Netherlands Institute for Innovative Ocular Surgery, Rotterdam, The Netherlands; e-mail: [email protected]
958
©
2012 BY
THIS STUDY WAS A NONRANDOMIZED PROSPECTIVE CO-
hort study at a tertiary referral center. For the first consecutive 275 eyes of 229 patients that underwent DMEK for Fuchs endothelial dystrophy (n ⫽ 260) or bullous keratopathy (n ⫽ 15), the perioperative IOP was documented, with a mean postoperative follow-up time of
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22 (⫾ 13) months. Significant IOP elevation was defined as an IOP of ⱖ24 mm Hg or an elevation of ⱖ10 mm Hg compared to the preoperative IOP, as measured by Goldmann applanation tonometry. No eyes were excluded from analysis, and none of the eyes had preoperative angle abnormalities, a history of trauma, uveitis, or other relevant comorbidities, other than the pre-existing lens status or the presence of a phakic intraocular lens. ● SURGICAL PROCEDURE:
From donor globes obtained less than 24 hours postmortem, corneoscleral buttons were excised and stored by organ culture in modified minimum essential medium (EMEM) at 31 C.9 After 1 week of culture, endothelial cell morphology and viability were evaluated and the corneoscleral buttons were mounted endothelial side up on a custom-made holder with a suction cup. The Descemet membrane (DM) was stripped from the posterior stroma so that a 9.5-mm-diameter flap of posterior DM with its endothelial monolayer was obtained.9 Because of the elastic properties of the membrane, a “Descemet roll” formed spontaneously, with the endothelium at the outer side. Each Descemet roll was then stored in organ culture medium until the time of transplantation. In recipient eyes, a 3.0-mm tunnel incision was made just within the limbus, entering the anterior chamber just at the mark. With an inverted Sinskey hook (D.O.R.C. International, Zuidland, The Netherlands), a circular portion of DM was scored and stripped from the posterior stroma, so that a 9.0-mmdiameter “descemetorrhexis” was created, and the central portion of DM was removed from the eye.3,4 The donor Descemet roll was stained with a 0.06% trypan blue solution (VisionBlue, D.O.R.C. International) and sucked into a custom-made injector (D.O.R.C. International). Using the injector, the donor Descemet roll was inserted into the anterior chamber and the graft was oriented endothelial side down (donor DM facing recipient posterior stroma) by careful, indirect manipulation of the tissue with air and fluid. While maintaining the anterior chamber with fluid and air, the graft was gently spread out over the iris. Then, an air bubble was injected underneath the donor DM to position the tissue onto the recipient posterior stroma.3,4 The anterior chamber was completely filled and pressurized with air for 45 to 60 minutes followed by a 50% air-liquid exchange to pressurize the eye. Thus, at termination of the surgery, a 50% air bubble, which did not cover the inferior pupillary margin with the patient in an upright position, was left in the anterior chamber. Two weeks before surgery, a peripheral yttrium-aluminum-garnet (YAG) iridotomy was routinely made at the 12-o’clock position (because patients were requested to lie flat for several hours, Bell’s phenomenon could render an iridotomy at the 6-o’clock position ineffective). Postoperative medication included 0.5% chloramVOL. 153, NO. 5
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TABLE 1. Topical Steroid Regime After Descemet Membrane Endothelial Keratoplasty Postoperative Time Interval
Steroid Prescribed
1st month 2nd⫺3rd month 4th⫺6th month 7th⫺9th month 10th⫺12th month ⬎12 months
Dexamethasone 0.1%, 4 times daily Fluorometholone 0.1%, 4 times daily Fluorometholone 0.1%, 3 times daily Fluorometholone 0.1%, 2 times daily Fluorometholone 0.1%, 1 time daily Fluorometholone 0.1%, every other day
phenicol for 2 weeks and a routine steroid regime of 0.1% dexamethasone 4 times daily for 4 weeks, followed by fluorometholone 4 times daily, tapered to 1 time daily over a period of 1 year (Table 1). Patients were evaluated at 1 day, 1 week, and 1, 3, 6, 9, and 12 months after the surgery, and at 6-month time intervals thereafter. Best-corrected visual acuity (BCVA), endothelial cell density by specular microscopy (Topcon SP3000P; Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands), Scheimpflug imaging (Oculus Pentacam HR 70900, Wetzlar, Germany), anterior segment optical coherence tomography (SL-OCT B01; Heidelberg Engineering, Heidelberg, Germany), and slit-lamp photography were performed. All intraoperative and postoperative complications were documented in an SQL database. ● STATISTICAL ANALYSIS:
Statistical analysis (SPSS 12.0 statistical package, SPSS, Inc, Chicago, Illinois, USA) was used to compare BCVA (t test for independent samples [Levine test significance: P ⬎ .05]) and endothelial cell density (Mann-Whitney U test) outcomes at 6 months after DMEK between the glaucoma (n ⫽ 18) and the normal visual potential group (n ⫽ 176). P value less than .05 was considered statistically significant.
RESULTS IOP ELEVATION WAS FOUND IN 18 DMEK EYES (18/275; 6.5%)
of 18 patients, 14 male and 4 female, 9 phakic and 9 pseudophakic, aged 33 to 81 years (Table 2). Seven of 275 eyes (2.5%) had an exacerbation of a pre-existing glaucoma and 11 eyes (4.0%) presented with a de novo IOP elevation (Figures 1 and 2). The incidence of IOP elevation after DMEK was 25% (7/28) in the group with a history of glaucoma and 4.5% (11/247) in the group without a glaucoma history. One of the eyes in our study had undergone glaucoma surgery prior to DMEK but did not develop an IOP elevation after DMEK. Two of 275 eyes (0.7%; Cases 7 and 16; Table 2) required glaucoma surgery after DMEK.
GLAUCOMA AFTER DESCEMET MEMBRANE ENDOTHELIAL KERATOPLASTY
959
960 TABLE 2. Glaucoma After Descemet Membrane Endothelial Keratoplasty: Patient Data
Patient # (Case #)
Age (y), Sex
OD/OS
Indication for Surgery
ACD (mm)
Glaucoma Type
Onset
IOP (mm Hg)
Initial Treatment
Clinical Course
BCVA at 6 Months
⌬ ECD (%) at 6 Months (Absolute ECD in Cells/mm2)
Eventual Status and Remarks
Patients With History of Glaucoma
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60, M
OS
Fuchs ED (pseudophakic)
n/a
Pre-existing glaucoma; POAG exacerbation
6th mo postop
24
Topical medication
Controlled with topical medication
20/20 (1.0)
8% (2270)
Clear transplant
2 (33)
81, M
OD
Fuchs ED (pseudophakic)
4.1
Pre-existing glaucoma; steroid response
3rd mo postop.
25
Steroid tapering; topical medication
Controlled with topical medication
20/25 (0.8)
16% (2350)
Clear transplant
3 (75)
76, M
OD
Fuchs ED (pseudophakic)
4.4
Pre-existing glaucoma; POAG exacerbation
6th mo postop
40
Topical and oral medication
Controlled with topical medication
20/25 (0.8)
16% (2590)
Clear transplant (DMEK after DSEK)
4 (188)
74, M
OS
Bullous keratopathy (pseudophakic)
4.0
Pre-existing glaucoma; POAG exacerbation
1st wk postop
40
Topical and oral medication
Controlled with topical medication
20/25 (0.8)a
32% (2020)
Clear transplant
5 (193)
78, M
OS
Fuchs ED (pseudophakic)
4.4
Pre-existing glaucoma; POAG exacerbation
3rd mo postop
25
Topical medication
Controlled with topical medication
20/28 (0.7)
21% (1890)
Clear transplant
6 (271)
46, F
OD
Bullous keratopathy (phakic)
2.8
Pre-existing glaucoma; angle-supported phakic IOL-induced glaucoma
1st wk postop
26
Topical medication
Controlled with topical medication
[20/130 (0.15)]b
26% (1650)b
Clear transplant, CME
7 (272)
42, M
OD
Bullous keratopathy (phakic)
2.9
Pre-existing glaucoma; angle-supported phakic IOL-induced glaucoma
1st wk postop
40
Topical and oral medication
Filtering surgery 4 months after DMEK
20/40 (0.5)
67% (760)b
Clear transplant, anterior synechiae, gonio synechiae, cataract
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1 (6)
OPHTHALMOLOGY
Patients Without History of Glaucoma
MAY
8 (30)
45, M
OS
Fuchs ED (phakic)
2.3
Mechanical angle closure due to air bubble dislocation behind iris
1st day postop
30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
47% (1430)
Clear transplant (unrelated mild allograft rejection 18 months after DMEK)
9 (40)
48, M
OD
Fuchs ED (phakic)
2.5
Mechanical angle closure due to air bubble dislocation behind iris
1st day postop
36
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
48% (1270)
Clear transplant
10 (131)
33, M
OS
Fuchs ED (phakic)
3.0
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
11 (138)
54, M
OS
Fuchs ED (phakic)
2.0
Mechanical angle closure due to air bubble–induced crystalline lens tilting
1st day postop
32
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/22 (0.9)
57% (970)
Clear transplant
12 (228)
50, F
OS
Fuchs ED (phakic)
2.9
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
⬎30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/28 (0.7)
65% (840)
Clear transplant
2% (2510)b
Clear transplant
Continued on next page
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VOL. 153, NO. 5 CAUSES
TABLE 2. Glaucoma After Descemet Membrane Endothelial Keratoplasty: Patient Data (Continued)
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GLAUCOMA AFTER DESCEMET MEMBRANE ENDOTHELIAL KERATOPLASTY
Patient # (Case #)
Age (y), Sex
13 (251)
Initial Treatment
Clinical Course
BCVA at 6 Months
⌬ ECD (%) at 6 Months (Absolute ECD in Cells/mm2)
36
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/18 (1.2)
16% (2020)
Clear transplant
6th mo postop
26
Steroid tapering
No current treatment
20/20 (1.0)
67% (810)
Clear transplant
Steroid response
1st mo postop
28
Steroid tapering; topical medication
No current treatment
20/18 (1.2)
47% (1390)
Clear transplant
3.0
Peripheral anterior synechiae formation
3rd mo postop
36
Topical and oral medication
Filtering surgery 5 months after DMEK
20/20 (1.0)c
23% (1870)
Clear transplant, peripheral anterior synechiae
Fuchs ED (pseudophakic)
4.2
Unknown
3rd mo postop
25
Topical medication
Controlled with topical medication
20/25 (0.8)
36% (1780)
Clear transplant
Fuchs ED (pseudophakic)
2.8
Unknown
1st wk postop
22
No treatment
No current treatment
20/21 (0.95)
40% (1400)
Clear transplant
OD/OS
Indication for Surgery
ACD (mm)
Glaucoma Type
Onset
IOP (mm Hg)
50, F
OD
Fuchs ED (phakic)
2.5
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
14 (87)
66, M
OD
Fuchs ED (pseudophakic)
3.4
Steroid response
15 (154)
66, M
OD
Fuchs ED (pseudophakic)
4.3
16 (163)
62, M
OD
Fuchs ED (phakic)
17 (143)
72, M
OS
18 (166)
79, F
OD
Average at 6 months after DMEK Compared to 257 (275 ⴚ 18) DMEK eyes without glaucoma complication
100% (16/16) ⱖ20/40 (0.5) 81.3% (13/16) ⱖ20/25 (0.8) P ⬎ .1
Eventual Status and Remarks
36% ⫾19% (1660 ⫾ 554) P ⬎ .1
ACD ⫽ anterior chamber depth; BCVA ⫽ best-corrected visual acuity; CME ⫽ cystoid macular edema; DMEK ⫽ Descemet membrane endothelial keratoplasty; ECD ⫽ endothelial cell density; ED ⫽ endothelial dystrophy; IOL ⫽ intraocular lens; IOP ⫽ intraocular pressure; POAG ⫽ primary open-angle glaucoma; postop ⫽ postoperative. a Best spectacle-corrected visual acuity 20/40 (0.5) due to Salzmann nodulus; 20/25 (0.8) with contact lens 8 months after surgery. b 3-month data are shown because 6-month data unavailable. c Best spectacle-corrected visual acuity 20/20 (1.0) after secondary filtering surgery and cataract extraction; 20/30 (0.6) at 6 months, before cataract extraction.
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FIGURE 1. Graph displaying the incidence of the various causes of glaucoma in the first 275 consecutive Descemet membrane endothelial keratoplasty surgeries.
FIGURE 2. Graph displaying the postoperative time interval at which different types of glaucoma presented in the first 275 consecutive Descemet membrane endothelial keratoplasty surgeries.
● EYES WITH HISTORY OF GLAUCOMA:
● EYES WITH DE NOVO GLAUCOMA – IMMEDIATE POSTOPERATIVE MECHANICAL ANGLE CLOSURE: In the 11
In eyes with a history of glaucoma (Cases 1⫺7; Table 2), IOP elevation was attributed to an exacerbation of primary open-angle glaucoma in 4 eyes, to secondary glaucoma in the presence of an angle-supported “phakic intraocular lens” in 2 eyes, and to steroid response in 1 eye. In 6 of these 7 eyes, the IOP normalized with intensified medication and steroid tapering. One of these eyes (Case 7; Table 2) with an angle-supported phakic IOL showed progressive, uncontrolled IOP elevations from 3 months after DMEK onwards, and was scheduled for glaucoma surgery.
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eyes with a de novo glaucoma (Cases 8⫺18; Table 2), treatment varied with the assumed mechanism inducing the IOP elevation. In 6 phakic eyes (Cases 8⫺13; Figure 1; Table 2), the IOP elevation was attributed to an “air bubble–induced mechanical angle-closure glaucoma.” In 2 of these eyes, the air bubble had moved behind the iris (Figure 3). In all 6 eyes, the situation could be resolved by pupillary dilation, topical 1% apraclonidine and 250 mg acetazolamide orally, and laying the patient down in a supine position for 1 to 2 hours. With the antiglaucoma OF
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did not differ from that of the whole DMEK series (P ⬎ .1) (Table 2). At 6 months, the endothelial cell density in the eyes with postoperative glaucoma averaged 1660 (⫾ 554) cells/mm2 and did not differ from that of the whole DMEK series (1708 [⫾ 526] cells/mm2; P ⬎ .1) (Table 2). No secondary graft failures were seen in the 18 eyes with postoperative glaucoma after DMEK.
DISCUSSION GLAUCOMA MAY BE ONE OF THE MOST SERIOUS, BUT LEAST
FIGURE 3. Schematic diagram illustrating the hypothesized mechanism of air bubble–induced angle-closure glaucoma attributable to a tilt of the crystalline lens, either by an air bubble (Left) in front of or (Right) behind the iris. Since the mechanism is different from a pupillary block glaucoma (ie, not induced by aqueous, but air), note that the peripheral iridotomy (gray arrow) is not effective in closure of the chamber angle because of the crystalline lens tilt.
medication continued for 1 to 2 days, no recurrences were seen. ● EYES WITH DE NOVO GLAUCOMA – DELAYED POSTOPERATIVE OCULAR HYPERTENSION: In 2 eyes (Cases 14
and 15; Figure 1; Table 2), a response to topical steroid medication was managed by tapering the steroids and/or prescribing additional antiglaucoma medication. One eye (Case 16; Table 2) developed intermittent IOP elevations in the third month after surgery, apparently caused by peripheral anterior synechiae formation that eventually required filtering surgery with a Baerveldt tube. In 2 eyes (Cases 17 and 18; Figure 1; Table 2), the cause could not be determined. Of the 18 eyes with glaucoma after DMEK, 16 eyes allowed for BCVA measurements at the 6-month follow-up interval. All of these eyes reached a BCVA of ⱖ20/40 (ⱖ0.5), 13 eyes (81%) reached ⱖ20/25 (ⱖ0.8), and 7 eyes (44%) reached ⱖ20/20 (ⱖ1.0). In the 2 remaining eyes, both referred for corneal decompensation after angle-supported phakic intraocular lens implantation, the BCVA was impaired by concomitant pathology. One eye (Case 6) had pre-existing cystoid macular edema and the other eye (Case 7) developed a mature cataract after filtering surgery. Overall, BCVA in the 18 glaucoma cases VOL. 153, NO. 5
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tangible, complications after keratoplasty, potentially affecting long-term graft survival, as well as the overall condition of the eye. Published reports have described an incidence of glaucoma after penetrating keratoplasty or earlier types of endothelial keratoplasty (ie, DLEK and DSEK/DSAEK) ranging from 15% to 35%, or even higher (Table 3).8,10⫺15 Overall, the postkeratoplasty IOP elevations may be categorized in 2 groups for the glaucoma’s etiology: exacerbation of pre-existing glaucoma and surgically induced ocular hypertension. The first group of eyes may be recognized before surgery to be “at risk,” whereas the second group may unexpectedly present with glaucoma because of more specific causes related to the surgical technique or the change in corneal anatomy. Although we expected a higher incidence of glaucoma, given the literature and because of the prolonged air bubble time in DMEK, only 18 eyes out of the 275 DMEK eyes (6.5%) presented with an episode of glaucoma. This relatively low percentage could primarily be explained by our topical steroid regime (Table 1), as well as by the study population which was predominantly white. Because the incidence of steroid-induced glaucoma may be as high as 60% after PK11 and 35% after DSEK (Table 3),10 our routine medication schedule included topical 0.1% dexamethasone for just the first postoperative month and switching to fluorometholone thereafter (Table 1), because the risk of allograft rejection in DMEK may be relatively low.16 It may be important to note that Asian and African-American patients may be more prone to allograft rejection, therefore requiring stronger steroid regimes, obviously increasing the risk of a steroid response. ● EYES WITH HISTORY OF GLAUCOMA: In our study, 28 eyes had a history of glaucoma before surgery, and 7 of these eyes (25%) showed an exacerbation within the first 3 months after DMEK, up to 40 mm Hg. In all eyes, the IOP initially normalized after switching from dexamethasone to fluorometholone and/or adjustments of the (additional) topical medication (Table 1). One patient showed a similar IOP elevation in both eyes after bilateral DMEK (Cases 3 and 5; Table 2). Thus, although eyes with a history of glaucoma may need to be closely monitored over an extended time,15,17 our findings did not reveal any
GLAUCOMA AFTER DESCEMET MEMBRANE ENDOTHELIAL KERATOPLASTY
963
964 TABLE 3. Review of Glaucoma After Endothelial Keratoplasty and Penetrating Keratoplasty
Number of Eyes
Follow-up, Months
Postoperative IOP Elevation
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Preoperative History of Glaucoma
Overall
Glaucoma Exacerbation
ⱖ24 mm Hg or ⱖ10 over baseline
10%
6.5%
2.5%
4%
n.a.
n.a.
0%
n.a.
n.a.
⬎21 mm Hg
n.a.
54%
28%
27%
ⱖ24 mm Hg or ⱖ10 over baseline
21%
37%
9.5%
28
Author, Year
Procedure
DMEK Naveiras, Current study
DMEK
275
Price, 200912 DSEK/DSAEK Allen, 200919
DMEK
60
DSAEK
68
11 ⫾ 8
Vajaranant, 200910
DSEK
400
ⱖ12
Lee, 200920
DSEK
100
6
ⱖ30 mm Hg
n.a.
13%
6%
7%
Espana, 200921
DSEK
45
12
ⱖ21 mm Hg
29%
22%
9%
13%
Terry, 200922
DSAEK
200
ⱖ4
n.a.
n.a.
n.a.
Suh, 200823
DSAEK
118
n.a.
n.a.
n.a.
No pupillary block 2% pupillary block
80 44
27 n.a.
n.a. n.a.
18% n.a.
8219 1090 13 350
36 ⱕ60 n.a.
24% 15% n.a.
22 ⫾ 13
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DLEK Wandling, 201016 Hyams, 200624 PK Stewart, 201117 Sugar, 200925 Williams, 200826
DLEK DLEK PKP PKP PKP
Glaucoma Definition
n.a. ⬎25 mm Hg n.a.
De Novo
Mechanisms Identified
Secondary Glaucoma Surgery
Glaucoma-Induced Secondary Graft Failure
⫺ Air bubble–induced mechanical angle closure - Steroid-induced - PAS - No pupillary block n.a.
0.7%
0%
n.a.
n.a.
9%
n.a.
2%
0%
3%
n.a.
n.a.
n.a.
n.a.
⫺ Steroid induced - Pupillary block - No angle closure - No PAS ⫺ Steroid induced - No pupillary block - No PAS - No angle closure ⫺ Air bubble–induced mechanical angle closure & PAS - Pupillary block ⫺ Angle closure/pupillary block - Steroid response ⫺ Pupillary block
n.a.
n.a.
n.a.
n.a.
⫺ Pupillary block
n.a.
n.a.
16% n.a.
7.5% 70%
9% 7%
⫺ Steroid induced n.a.
5% 5%
n.a. n.a.
20% 12% 15%
10% n.a. n.a.
19% n.a. n.a.
n.a. n.a. n.a.
n.a. n.a. 20%
n.a. n.a. n.a.
MAY 2012
DLEK ⫽ deep lamellar endothelial keratoplasty; DMEK ⫽ Descemet membrane endothelial keratoplasty; DS(A)EK ⫽ Descemet stripping (automated) endothelial keratoplasty; IOP ⫽ intraocular pressure; n.a. ⫽ not applicable; PAS ⫽ peripheral anterior synechiae; PKP ⫽ penetrating keratoplasty.
mandatory changes in our surgical protocol or medication schedule, to avoid postoperative pressure spikes in eyes with pre-existing glaucoma. It may be of interest that the 2 most difficult eyes to manage (Cases 6 and 7; Table 2) were both referred for corneal decompensation after anglesupported phakic intraocular lens implantation. One of these eyes suffered from chronic cystoid macular edema, whereas the other eye eventually required filtering surgery.
may better balance the risk of graft detachment with that of air bubble–induced angle-closure glaucoma. It may also be important to note that reducing the air bubble size may be the only effective precaution, since secondary glaucoma attributable to mechanical forward displacement of the iris diaphragm is caused by a different mechanism than a true pupillary block glaucoma, for which the peripheral YAG iridotomy made before the surgery is not effective.
● EYES WITH DE NOVO GLAUCOMA – IMMEDIATE POSTOPERATIVE MECHANICAL ANGLE CLOSURE: In the re-
● EYES WITH DE NOVO GLAUCOMA – DELAYED POSTOPERATIVE OCULAR HYPERTENSION: Of the other 5 eyes
maining 11 eyes without a history of glaucoma (11/275; 4%), the ocular hypertension was caused by clearly different mechanisms.18,19 Six of these eyes developed a mechanical angleclosure glaucoma within the first 24 hours after surgery (Cases 8⫺13; Figures 1 and 2; Table 2). All of these eyes were phakic, and in each case the presence of the crystalline lens seemed to be part of the mechanism causing the glaucoma (Figure 3). In all 6 eyes, the 50% air bubble left in situ in the recipient anterior chamber at termination of the surgery apparently caused a “backward” tilt of the crystalline lens, displacing the inferior part of the iris diaphragm forward, resulting in a mechanical closure of the anterior chamber angle. In all of these eyes, the glaucomatous crisis could be reversed by pupillary dilation, topical 1% apraclonidine and 250 mg acetazolamide orally, and laying the patient down in a supine position for 1 to 2 hours. With the antiglaucoma medication continued for 1 to 2 days, no recurrences were seen, while the air bubble diminished in size within days. From the total of 275 eyes in our study, 55 (20%) were phakic, so air bubble–induced secondary angle-closure glaucoma may have occurred in a relatively high incidence of cases, that is, in 11% (6/55). Hence, it may be advocated to pressurize the anterior chamber with a complete air fill for about 1 hour at termination of a DMEK surgery, but then to reduce the air fill to only 20% to 30% (instead of 50%) in phakic eyes. Since phakic eyes represent a younger age group, and a Descemet graft may adhere more easily in younger patients, this change in protocol
without a history of glaucoma, 1 eye (Case 16; Table 2) underwent uncomplicated DMEK surgery but presented with IOP spikes not responsive to topical medication at 1 month postoperatively, in the absence of inflammation and while the visual acuity had improved to 20/28 (0.7). Gonioscopy revealed iridocorneal adhesions in the inferior quadrants, possibly caused by adherence of the peripheral flange of the Descemet graft to the recipient peripheral iris (ie, peripheral anterior synechiae). After cataract extraction and filtering surgery, the IOP normalized and the BCVA improved to 20/20 (1.0). Although peripheral anterior synechiae formation was rare in our series (0.4%; 1/275), this complication may be avoided by proper centration of the Descemet graft. In conclusion, our study indicated that eyes with pre-existing glaucoma undergoing DMEK may require close monitoring of the postoperative IOP to detect postoperative glaucoma episodes. In eyes without a history of glaucoma, this complication may be avoided in most cases by adjustments of the air bubble management in phakic eyes, a steroid regime titrated to the patient population, and proper graft positioning. Compared to the literature on penetrating keratoplasty and DSEK/DSAEK, our study suggests that DMEK does not come with an increased risk of uncontrolled glaucoma. Incidental cases may be related to the presence of an angle-supported (phakic) intraocular lens, or peripheral anterior synechiae formation in eyes with a decentered graft causing adhesions between the donor tissue and the iris.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. The authors indicate no funding support. Dr Melles is a consultant for D.O.R.C./Dutch Ophthalmic USA. Involved in design of the study (M.N., G.M.); conduct of the study (M.N., M.D., L.H., K.v.D., I.D., G.M.); collection, management, analysis, and interpretation of the data (M.N., M.D., J.P., L.H., K.v.D., I.D., G.M.); and preparation, review, or approval of the manuscript (M.N., I.D., M.D., L.H., K.v.D., G.M.). The study was conducted in compliance with Institutional Review Board and informed consent requirements, in adherence to the tenets of the Declaration of Helsinki, at the Netherlands Institute for Innovative Ocular Surgery (Study registration no N.05.14). The study was submitted to http://www.clinicaltrals.gov (study registration no NCT00521898).
REFERENCES 1. Dapena I, Ham L, Melles GR. Endothelial keratoplasty: DSEK/DSAEK or DMEK-the thinner the better? Curr Opin Ophthalmol 2009;20(4):299 –307. 2. Melles GR. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea 2006;25(8):879 – 881. 3. Melles GR, Ong TS, Ververs B, Van der Wees J. Descemet membrane endothelial keratoplasty (DMEK). Cornea 2006;25(8): 987–990.
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4. Ham L, Dapena I, van Luijk C, Van der Wees J, Melles GRJ. Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: Review of the first 50 consecutive cases. Eye (Lond) 2009;23(10):1990 –1998. 5. Dapena I, Ham L, van Luijk C, Van der Wees J, Melles GRJ. Back-up procedure for graft failure in Descemet membrane endothelial keratoplasty (DMEK). Br J Ophthalmol 2010; 94(2):241–244. 6. Balachandran C, Ham L, Verschoor CA, Ong TS, Van der Wees J, Melles GRJ. Spontaneous corneal clearance despite
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17. Stewart RM, Jones MN, Batterbury M, Tole D, Larkin DFP, Kaye SB. Effect of glaucoma on corneal graft survival according to indication for penetrating keratoplasty. Am J Ophthalmol 2011;151(2):257–262. 18. Greenlee EC, Kwon YH. Graft failure: III. glaucoma escalation after penetrating keratoplasty. Int Ophthalmol 2008(3); 28:191-207. 19. Allen MB, Lieu P, Mootha VV, Bowman RW, et al. Risk factors for intraocular pressure elevation after Descemet stripping automated endothelial keratoplasty. Eye Contact Lens 2010;36(4):223–227. 20. Lee JS, Desai NR, Schmidt GW, et al. Secondary angle closure caused by air migrating behind the pupil in Descemet stripping endothelial keratoplasty. Cornea 2009;28(6):652–656. 21. Espana EM, Robertson ZM, Huang B. Intraocular pressure changes following Descemet’s stripping with endothelial keratoplasty. Graefes Arch Clin Exp Ophthalmol 2010; 248(2):237–242. 22. Terry MA. Endothelial keratoplasty: A comparison of complication rates and endothelial survival between precut tissue and surgeon-cut tissue by a single DSAEK surgeon. Trans Am Ophthalmol Soc 2009;107:184 –191. 23. Suh LH, Yoo SH, Deobhakta A,et al. Complications of Descemet’s stripping with automated endothelial keratoplasty: Survey of 118 eyes at one institute. Ophthalmology 2008;115(9):1517–1524. 24. Hyams M, Segev F, Yepes N, Slomovic AR, Rootman DS. Early postoperative complications of deep lamellar endothelial keratoplasty. Cornea 2007;26(6):650 – 653. 25. Sugar A, Tanner JP, Dontchev M, et al. Recipient risk factors for graft failure in the cornea donor study. Ophthalmology 2009;116(6):1023–1028. 26. Williams KA, Lowe M, Bartlett C, Kelly TL, Douglas J. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation 2008;86(12):1720 – 1724.
graft detachment in Descemet membrane endothelial keratoplasty. Am J Ophthalmol 2009;148(2):227–234. Banitt MR, Chopra V. Descemet’s stripping with automated endothelial keratoplasty and glaucoma. Curr Opin Ophthalmol 2010;21(2):144 –149. Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein RM. Descemet’s stripping endothelial keratoplasty: Safety and outcomes: A report by the American Academy of Ophthalmology. Ophthalmology 2009;116(9):1818 –1830. Lie JT, Birbal R, Ham L, Van der Wees J, Melles GRJ. Donor tissue preparation for Descemet membrane endothelial keratoplasty. J Cataract Refract Surg 2008;34(9):1578 –1583. Vajaranant TS, Price MO, Price FW. Visual acuity and intraocular pressure after Descemet’s stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. Ophthalmology 2009;116(9):1644 –1650. Erdurmus M, Cohen EJ, Yildiz EH, et al. Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy. Cornea 2009;28(7):759 –764. Price MO, Giebel AW, Fairchild KM, Price FW. Descemet’s membrane endothelial keratoplasty: Prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology 2009;116(12):2361–2368. Chen ES, Terry MA, Shamie N, Hoar KL, Friend DJ. Descemet-stripping automated endothelial keratoplasty: Sixmonth results in a prospective study of 100 eyes. Cornea 2008;27(5):514 –520. Frost NA, Wu J, Lai TF, Coster DJ. A review of randomized controlled trials of penetrating keratoplasty techniques. Ophthalmology 2006;113(6):942–949. Dapena I, Ham L, Netukova M, Van der Wees J, Melles GRJ. Incidence of early allograft rejection following Descemet membrane endothelial keratoplasty (DMEK). Cornea. Forthcoming. Wandling GR Jr, Parikh M, Robinson C, et al. Escalation of glaucoma therapy after deep lamellar endothelial keratoplasty. Cornea 2010;29(9):991–995.
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Biosketch Miguel Naveiras, MD, and PhD candidate by the Autonomous University of Madrid, graduated from the Hospital Central de Asturias, Spain, as a specialist ophthalmologist in 2010. In addition, he has undergone extra training at Massachusetts Eye and Ear Infirmary (Harvard Medical School, Boston, Massachusetts), Bascom Palmer Institute (University of Miami, Miami, Florida), Moorfields eye Hospital (London, United Kingdom) and Mermoud Clinic (Switzerland). He is currently a clinical fellow at Melles Cornea Clinic Rotterdam, and transplant coordinator at Amnitrans Eyebank Rotterdam. Both organizations are part of the Netherlands Institute for Innovative Ocular Surgery (www.niios.com), Rotterdam, The Netherlands.
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To describe the incidence and causes of glaucoma after Descemet membrane endothelial keratoplasty (DMEK). ● DESIGN: Nonrandomized prospective cohort study at a tertiary referral center. ● METHODS: The incidence of glaucoma was evaluated in the first 275 consecutive eyes that underwent DMEK for Fuchs endothelial dystrophy (260 eyes) or bullous keratopathy (15 eyes). Glaucoma was defined as a postoperative intraocular pressure (IOP) elevation of >24 mm Hg, or >10 mm Hg from the preoperative baseline. If possible, the cause of glaucoma was identified, and best-corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative course were documented, with a mean follow-up of 22 (ⴞ 13) months. ● RESULTS: Overall, 18 eyes (6.5%) showed postoperative glaucoma after DMEK. Seven eyes (2.5%) had an exacerbation of a pre-existing glaucoma. Eleven eyes (4%) presented with a de novo IOP elevation, associated with air bubble–induced mechanical angle closure (2%), steroid response (0.7%), or peripheral anterior synechiae (0.4%), or without detectable cause (0.7%). Two eyes (0.7%) required glaucoma surgery after DMEK. At 6 months, all eyes had a BCVA of >20/40 (>0.5), and 81% reached >20/25 (>0.8) (n ⴝ 16); mean ECD was 1660 (ⴞ 554) cells/mm2 (n ⴝ 15) (P > .1). ● CONCLUSION: Glaucoma after DMEK may be a relatively frequent complication that could be avoided by reducing the residual postoperative air bubble to 30% in phakic eyes, applying a population-specific steroid regime, and avoiding decentration of the Descemet graft. Eyes with a history of glaucoma may need close IOP monitoring in the first postoperative months, especially in eyes with an angle-supported phakic intraocular lens. (Am J Ophthalmol 2012;153:958 –966. © 2012 by Elsevier Inc. All rights reserved.)
I
N THE PAST DECADE, WE HAVE INTRODUCED VARIOUS
techniques for endothelial keratoplasty, later popularized as deep lamellar endothelial keratoplasty (DLEK) and Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK).1,2 More recently, we described a technique for the selective transplantation of a donor Descemet membrane, now referred to as Descemet membrane endothelial keratoplasty (DMEK).3⫺6 With the advent of endothelial keratoplasty, the type of complications and their incidence have shifted compared to those encountered after penetrating keratoplasty. Astigmatism, suture-related problems, and wound dehiscence have been virtually eliminated and the risk of allograft rejection may have been reduced, while graft detachment as a “new” complication has surfaced.1,5,6 However, endothelial keratoplasty may also be associated with a shift in intraocular complications, particularly specific types of glaucoma induced by the presence of an intraocular air bubble in the immediate postoperative phase.7 Overall, glaucoma has been described to occur in about 30% of cases after endothelial or penetrating keratoplasty, so that it may be one of few severe complications after keratoplasty today, affecting the clinical outcome and/or graft survival in the long term.7,8 Since DMEK grafts may require a longer air bubble support to obtain graft adherence to the recipient posterior stroma,1,4 the risk of glaucoma after DMEK could be higher than after DSEK/ DSAEK, so a better understanding of the various mechanisms may aid in preventing glaucoma, thereby improving the overall success rate of the procedure. In the present study, we prospectively documented all glaucoma episodes associated with the first 275 DMEK surgeries performed at our center, to determine the causes and incidence of postoperative intraocular pressure (IOP) elevations and to possibly define precautions to minimize the risk of glaucoma after DMEK.
MATERIALS AND METHODS Accepted for publication Oct 4, 2011. From the Netherlands Institute for Innovative Ocular Surgery (M.N., M.D., J.P., L.H., K.v.D., I.D., G.R.J.M.), Melles Cornea Clinic Rotterdam (M.N., M.D., J.P., L.H., K.v.D., I.D., G.R.J.M.), and Amnitrans EyeBank (G.R.J.M.), Rotterdam, The Netherlands; and AKh Linz (M.D.), Linz, Austria. Inquiries to Gerrit R.J. Melles, Netherlands Institute for Innovative Ocular Surgery, Rotterdam, The Netherlands; e-mail: [email protected]
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2012 BY
THIS STUDY WAS A NONRANDOMIZED PROSPECTIVE CO-
hort study at a tertiary referral center. For the first consecutive 275 eyes of 229 patients that underwent DMEK for Fuchs endothelial dystrophy (n ⫽ 260) or bullous keratopathy (n ⫽ 15), the perioperative IOP was documented, with a mean postoperative follow-up time of
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/$36.00 doi:10.1016/j.ajo.2011.10.003
22 (⫾ 13) months. Significant IOP elevation was defined as an IOP of ⱖ24 mm Hg or an elevation of ⱖ10 mm Hg compared to the preoperative IOP, as measured by Goldmann applanation tonometry. No eyes were excluded from analysis, and none of the eyes had preoperative angle abnormalities, a history of trauma, uveitis, or other relevant comorbidities, other than the pre-existing lens status or the presence of a phakic intraocular lens. ● SURGICAL PROCEDURE:
From donor globes obtained less than 24 hours postmortem, corneoscleral buttons were excised and stored by organ culture in modified minimum essential medium (EMEM) at 31 C.9 After 1 week of culture, endothelial cell morphology and viability were evaluated and the corneoscleral buttons were mounted endothelial side up on a custom-made holder with a suction cup. The Descemet membrane (DM) was stripped from the posterior stroma so that a 9.5-mm-diameter flap of posterior DM with its endothelial monolayer was obtained.9 Because of the elastic properties of the membrane, a “Descemet roll” formed spontaneously, with the endothelium at the outer side. Each Descemet roll was then stored in organ culture medium until the time of transplantation. In recipient eyes, a 3.0-mm tunnel incision was made just within the limbus, entering the anterior chamber just at the mark. With an inverted Sinskey hook (D.O.R.C. International, Zuidland, The Netherlands), a circular portion of DM was scored and stripped from the posterior stroma, so that a 9.0-mmdiameter “descemetorrhexis” was created, and the central portion of DM was removed from the eye.3,4 The donor Descemet roll was stained with a 0.06% trypan blue solution (VisionBlue, D.O.R.C. International) and sucked into a custom-made injector (D.O.R.C. International). Using the injector, the donor Descemet roll was inserted into the anterior chamber and the graft was oriented endothelial side down (donor DM facing recipient posterior stroma) by careful, indirect manipulation of the tissue with air and fluid. While maintaining the anterior chamber with fluid and air, the graft was gently spread out over the iris. Then, an air bubble was injected underneath the donor DM to position the tissue onto the recipient posterior stroma.3,4 The anterior chamber was completely filled and pressurized with air for 45 to 60 minutes followed by a 50% air-liquid exchange to pressurize the eye. Thus, at termination of the surgery, a 50% air bubble, which did not cover the inferior pupillary margin with the patient in an upright position, was left in the anterior chamber. Two weeks before surgery, a peripheral yttrium-aluminum-garnet (YAG) iridotomy was routinely made at the 12-o’clock position (because patients were requested to lie flat for several hours, Bell’s phenomenon could render an iridotomy at the 6-o’clock position ineffective). Postoperative medication included 0.5% chloramVOL. 153, NO. 5
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TABLE 1. Topical Steroid Regime After Descemet Membrane Endothelial Keratoplasty Postoperative Time Interval
Steroid Prescribed
1st month 2nd⫺3rd month 4th⫺6th month 7th⫺9th month 10th⫺12th month ⬎12 months
Dexamethasone 0.1%, 4 times daily Fluorometholone 0.1%, 4 times daily Fluorometholone 0.1%, 3 times daily Fluorometholone 0.1%, 2 times daily Fluorometholone 0.1%, 1 time daily Fluorometholone 0.1%, every other day
phenicol for 2 weeks and a routine steroid regime of 0.1% dexamethasone 4 times daily for 4 weeks, followed by fluorometholone 4 times daily, tapered to 1 time daily over a period of 1 year (Table 1). Patients were evaluated at 1 day, 1 week, and 1, 3, 6, 9, and 12 months after the surgery, and at 6-month time intervals thereafter. Best-corrected visual acuity (BCVA), endothelial cell density by specular microscopy (Topcon SP3000P; Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands), Scheimpflug imaging (Oculus Pentacam HR 70900, Wetzlar, Germany), anterior segment optical coherence tomography (SL-OCT B01; Heidelberg Engineering, Heidelberg, Germany), and slit-lamp photography were performed. All intraoperative and postoperative complications were documented in an SQL database. ● STATISTICAL ANALYSIS:
Statistical analysis (SPSS 12.0 statistical package, SPSS, Inc, Chicago, Illinois, USA) was used to compare BCVA (t test for independent samples [Levine test significance: P ⬎ .05]) and endothelial cell density (Mann-Whitney U test) outcomes at 6 months after DMEK between the glaucoma (n ⫽ 18) and the normal visual potential group (n ⫽ 176). P value less than .05 was considered statistically significant.
RESULTS IOP ELEVATION WAS FOUND IN 18 DMEK EYES (18/275; 6.5%)
of 18 patients, 14 male and 4 female, 9 phakic and 9 pseudophakic, aged 33 to 81 years (Table 2). Seven of 275 eyes (2.5%) had an exacerbation of a pre-existing glaucoma and 11 eyes (4.0%) presented with a de novo IOP elevation (Figures 1 and 2). The incidence of IOP elevation after DMEK was 25% (7/28) in the group with a history of glaucoma and 4.5% (11/247) in the group without a glaucoma history. One of the eyes in our study had undergone glaucoma surgery prior to DMEK but did not develop an IOP elevation after DMEK. Two of 275 eyes (0.7%; Cases 7 and 16; Table 2) required glaucoma surgery after DMEK.
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960 TABLE 2. Glaucoma After Descemet Membrane Endothelial Keratoplasty: Patient Data
Patient # (Case #)
Age (y), Sex
OD/OS
Indication for Surgery
ACD (mm)
Glaucoma Type
Onset
IOP (mm Hg)
Initial Treatment
Clinical Course
BCVA at 6 Months
⌬ ECD (%) at 6 Months (Absolute ECD in Cells/mm2)
Eventual Status and Remarks
Patients With History of Glaucoma
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60, M
OS
Fuchs ED (pseudophakic)
n/a
Pre-existing glaucoma; POAG exacerbation
6th mo postop
24
Topical medication
Controlled with topical medication
20/20 (1.0)
8% (2270)
Clear transplant
2 (33)
81, M
OD
Fuchs ED (pseudophakic)
4.1
Pre-existing glaucoma; steroid response
3rd mo postop.
25
Steroid tapering; topical medication
Controlled with topical medication
20/25 (0.8)
16% (2350)
Clear transplant
3 (75)
76, M
OD
Fuchs ED (pseudophakic)
4.4
Pre-existing glaucoma; POAG exacerbation
6th mo postop
40
Topical and oral medication
Controlled with topical medication
20/25 (0.8)
16% (2590)
Clear transplant (DMEK after DSEK)
4 (188)
74, M
OS
Bullous keratopathy (pseudophakic)
4.0
Pre-existing glaucoma; POAG exacerbation
1st wk postop
40
Topical and oral medication
Controlled with topical medication
20/25 (0.8)a
32% (2020)
Clear transplant
5 (193)
78, M
OS
Fuchs ED (pseudophakic)
4.4
Pre-existing glaucoma; POAG exacerbation
3rd mo postop
25
Topical medication
Controlled with topical medication
20/28 (0.7)
21% (1890)
Clear transplant
6 (271)
46, F
OD
Bullous keratopathy (phakic)
2.8
Pre-existing glaucoma; angle-supported phakic IOL-induced glaucoma
1st wk postop
26
Topical medication
Controlled with topical medication
[20/130 (0.15)]b
26% (1650)b
Clear transplant, CME
7 (272)
42, M
OD
Bullous keratopathy (phakic)
2.9
Pre-existing glaucoma; angle-supported phakic IOL-induced glaucoma
1st wk postop
40
Topical and oral medication
Filtering surgery 4 months after DMEK
20/40 (0.5)
67% (760)b
Clear transplant, anterior synechiae, gonio synechiae, cataract
OF
1 (6)
OPHTHALMOLOGY
Patients Without History of Glaucoma
MAY
8 (30)
45, M
OS
Fuchs ED (phakic)
2.3
Mechanical angle closure due to air bubble dislocation behind iris
1st day postop
30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
47% (1430)
Clear transplant (unrelated mild allograft rejection 18 months after DMEK)
9 (40)
48, M
OD
Fuchs ED (phakic)
2.5
Mechanical angle closure due to air bubble dislocation behind iris
1st day postop
36
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
48% (1270)
Clear transplant
10 (131)
33, M
OS
Fuchs ED (phakic)
3.0
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/20 (1.0)
11 (138)
54, M
OS
Fuchs ED (phakic)
2.0
Mechanical angle closure due to air bubble–induced crystalline lens tilting
1st day postop
32
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/22 (0.9)
57% (970)
Clear transplant
12 (228)
50, F
OS
Fuchs ED (phakic)
2.9
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
⬎30
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/28 (0.7)
65% (840)
Clear transplant
2% (2510)b
Clear transplant
Continued on next page
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Patient # (Case #)
Age (y), Sex
13 (251)
Initial Treatment
Clinical Course
BCVA at 6 Months
⌬ ECD (%) at 6 Months (Absolute ECD in Cells/mm2)
36
Pupillary dilation, topical and oral medication, supine position
No current treatment
20/18 (1.2)
16% (2020)
Clear transplant
6th mo postop
26
Steroid tapering
No current treatment
20/20 (1.0)
67% (810)
Clear transplant
Steroid response
1st mo postop
28
Steroid tapering; topical medication
No current treatment
20/18 (1.2)
47% (1390)
Clear transplant
3.0
Peripheral anterior synechiae formation
3rd mo postop
36
Topical and oral medication
Filtering surgery 5 months after DMEK
20/20 (1.0)c
23% (1870)
Clear transplant, peripheral anterior synechiae
Fuchs ED (pseudophakic)
4.2
Unknown
3rd mo postop
25
Topical medication
Controlled with topical medication
20/25 (0.8)
36% (1780)
Clear transplant
Fuchs ED (pseudophakic)
2.8
Unknown
1st wk postop
22
No treatment
No current treatment
20/21 (0.95)
40% (1400)
Clear transplant
OD/OS
Indication for Surgery
ACD (mm)
Glaucoma Type
Onset
IOP (mm Hg)
50, F
OD
Fuchs ED (phakic)
2.5
Mechanical angle closure due to air bubble–induced crystalline lens tilting
Hrs after surgery
14 (87)
66, M
OD
Fuchs ED (pseudophakic)
3.4
Steroid response
15 (154)
66, M
OD
Fuchs ED (pseudophakic)
4.3
16 (163)
62, M
OD
Fuchs ED (phakic)
17 (143)
72, M
OS
18 (166)
79, F
OD
Average at 6 months after DMEK Compared to 257 (275 ⴚ 18) DMEK eyes without glaucoma complication
100% (16/16) ⱖ20/40 (0.5) 81.3% (13/16) ⱖ20/25 (0.8) P ⬎ .1
Eventual Status and Remarks
36% ⫾19% (1660 ⫾ 554) P ⬎ .1
ACD ⫽ anterior chamber depth; BCVA ⫽ best-corrected visual acuity; CME ⫽ cystoid macular edema; DMEK ⫽ Descemet membrane endothelial keratoplasty; ECD ⫽ endothelial cell density; ED ⫽ endothelial dystrophy; IOL ⫽ intraocular lens; IOP ⫽ intraocular pressure; POAG ⫽ primary open-angle glaucoma; postop ⫽ postoperative. a Best spectacle-corrected visual acuity 20/40 (0.5) due to Salzmann nodulus; 20/25 (0.8) with contact lens 8 months after surgery. b 3-month data are shown because 6-month data unavailable. c Best spectacle-corrected visual acuity 20/20 (1.0) after secondary filtering surgery and cataract extraction; 20/30 (0.6) at 6 months, before cataract extraction.
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FIGURE 1. Graph displaying the incidence of the various causes of glaucoma in the first 275 consecutive Descemet membrane endothelial keratoplasty surgeries.
FIGURE 2. Graph displaying the postoperative time interval at which different types of glaucoma presented in the first 275 consecutive Descemet membrane endothelial keratoplasty surgeries.
● EYES WITH HISTORY OF GLAUCOMA:
● EYES WITH DE NOVO GLAUCOMA – IMMEDIATE POSTOPERATIVE MECHANICAL ANGLE CLOSURE: In the 11
In eyes with a history of glaucoma (Cases 1⫺7; Table 2), IOP elevation was attributed to an exacerbation of primary open-angle glaucoma in 4 eyes, to secondary glaucoma in the presence of an angle-supported “phakic intraocular lens” in 2 eyes, and to steroid response in 1 eye. In 6 of these 7 eyes, the IOP normalized with intensified medication and steroid tapering. One of these eyes (Case 7; Table 2) with an angle-supported phakic IOL showed progressive, uncontrolled IOP elevations from 3 months after DMEK onwards, and was scheduled for glaucoma surgery.
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eyes with a de novo glaucoma (Cases 8⫺18; Table 2), treatment varied with the assumed mechanism inducing the IOP elevation. In 6 phakic eyes (Cases 8⫺13; Figure 1; Table 2), the IOP elevation was attributed to an “air bubble–induced mechanical angle-closure glaucoma.” In 2 of these eyes, the air bubble had moved behind the iris (Figure 3). In all 6 eyes, the situation could be resolved by pupillary dilation, topical 1% apraclonidine and 250 mg acetazolamide orally, and laying the patient down in a supine position for 1 to 2 hours. With the antiglaucoma OF
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did not differ from that of the whole DMEK series (P ⬎ .1) (Table 2). At 6 months, the endothelial cell density in the eyes with postoperative glaucoma averaged 1660 (⫾ 554) cells/mm2 and did not differ from that of the whole DMEK series (1708 [⫾ 526] cells/mm2; P ⬎ .1) (Table 2). No secondary graft failures were seen in the 18 eyes with postoperative glaucoma after DMEK.
DISCUSSION GLAUCOMA MAY BE ONE OF THE MOST SERIOUS, BUT LEAST
FIGURE 3. Schematic diagram illustrating the hypothesized mechanism of air bubble–induced angle-closure glaucoma attributable to a tilt of the crystalline lens, either by an air bubble (Left) in front of or (Right) behind the iris. Since the mechanism is different from a pupillary block glaucoma (ie, not induced by aqueous, but air), note that the peripheral iridotomy (gray arrow) is not effective in closure of the chamber angle because of the crystalline lens tilt.
medication continued for 1 to 2 days, no recurrences were seen. ● EYES WITH DE NOVO GLAUCOMA – DELAYED POSTOPERATIVE OCULAR HYPERTENSION: In 2 eyes (Cases 14
and 15; Figure 1; Table 2), a response to topical steroid medication was managed by tapering the steroids and/or prescribing additional antiglaucoma medication. One eye (Case 16; Table 2) developed intermittent IOP elevations in the third month after surgery, apparently caused by peripheral anterior synechiae formation that eventually required filtering surgery with a Baerveldt tube. In 2 eyes (Cases 17 and 18; Figure 1; Table 2), the cause could not be determined. Of the 18 eyes with glaucoma after DMEK, 16 eyes allowed for BCVA measurements at the 6-month follow-up interval. All of these eyes reached a BCVA of ⱖ20/40 (ⱖ0.5), 13 eyes (81%) reached ⱖ20/25 (ⱖ0.8), and 7 eyes (44%) reached ⱖ20/20 (ⱖ1.0). In the 2 remaining eyes, both referred for corneal decompensation after angle-supported phakic intraocular lens implantation, the BCVA was impaired by concomitant pathology. One eye (Case 6) had pre-existing cystoid macular edema and the other eye (Case 7) developed a mature cataract after filtering surgery. Overall, BCVA in the 18 glaucoma cases VOL. 153, NO. 5
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tangible, complications after keratoplasty, potentially affecting long-term graft survival, as well as the overall condition of the eye. Published reports have described an incidence of glaucoma after penetrating keratoplasty or earlier types of endothelial keratoplasty (ie, DLEK and DSEK/DSAEK) ranging from 15% to 35%, or even higher (Table 3).8,10⫺15 Overall, the postkeratoplasty IOP elevations may be categorized in 2 groups for the glaucoma’s etiology: exacerbation of pre-existing glaucoma and surgically induced ocular hypertension. The first group of eyes may be recognized before surgery to be “at risk,” whereas the second group may unexpectedly present with glaucoma because of more specific causes related to the surgical technique or the change in corneal anatomy. Although we expected a higher incidence of glaucoma, given the literature and because of the prolonged air bubble time in DMEK, only 18 eyes out of the 275 DMEK eyes (6.5%) presented with an episode of glaucoma. This relatively low percentage could primarily be explained by our topical steroid regime (Table 1), as well as by the study population which was predominantly white. Because the incidence of steroid-induced glaucoma may be as high as 60% after PK11 and 35% after DSEK (Table 3),10 our routine medication schedule included topical 0.1% dexamethasone for just the first postoperative month and switching to fluorometholone thereafter (Table 1), because the risk of allograft rejection in DMEK may be relatively low.16 It may be important to note that Asian and African-American patients may be more prone to allograft rejection, therefore requiring stronger steroid regimes, obviously increasing the risk of a steroid response. ● EYES WITH HISTORY OF GLAUCOMA: In our study, 28 eyes had a history of glaucoma before surgery, and 7 of these eyes (25%) showed an exacerbation within the first 3 months after DMEK, up to 40 mm Hg. In all eyes, the IOP initially normalized after switching from dexamethasone to fluorometholone and/or adjustments of the (additional) topical medication (Table 1). One patient showed a similar IOP elevation in both eyes after bilateral DMEK (Cases 3 and 5; Table 2). Thus, although eyes with a history of glaucoma may need to be closely monitored over an extended time,15,17 our findings did not reveal any
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964 TABLE 3. Review of Glaucoma After Endothelial Keratoplasty and Penetrating Keratoplasty
Number of Eyes
Follow-up, Months
Postoperative IOP Elevation
AMERICAN JOURNAL
Preoperative History of Glaucoma
Overall
Glaucoma Exacerbation
ⱖ24 mm Hg or ⱖ10 over baseline
10%
6.5%
2.5%
4%
n.a.
n.a.
0%
n.a.
n.a.
⬎21 mm Hg
n.a.
54%
28%
27%
ⱖ24 mm Hg or ⱖ10 over baseline
21%
37%
9.5%
28
Author, Year
Procedure
DMEK Naveiras, Current study
DMEK
275
Price, 200912 DSEK/DSAEK Allen, 200919
DMEK
60
DSAEK
68
11 ⫾ 8
Vajaranant, 200910
DSEK
400
ⱖ12
Lee, 200920
DSEK
100
6
ⱖ30 mm Hg
n.a.
13%
6%
7%
Espana, 200921
DSEK
45
12
ⱖ21 mm Hg
29%
22%
9%
13%
Terry, 200922
DSAEK
200
ⱖ4
n.a.
n.a.
n.a.
Suh, 200823
DSAEK
118
n.a.
n.a.
n.a.
No pupillary block 2% pupillary block
80 44
27 n.a.
n.a. n.a.
18% n.a.
8219 1090 13 350
36 ⱕ60 n.a.
24% 15% n.a.
22 ⫾ 13
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DLEK Wandling, 201016 Hyams, 200624 PK Stewart, 201117 Sugar, 200925 Williams, 200826
DLEK DLEK PKP PKP PKP
Glaucoma Definition
n.a. ⬎25 mm Hg n.a.
De Novo
Mechanisms Identified
Secondary Glaucoma Surgery
Glaucoma-Induced Secondary Graft Failure
⫺ Air bubble–induced mechanical angle closure - Steroid-induced - PAS - No pupillary block n.a.
0.7%
0%
n.a.
n.a.
9%
n.a.
2%
0%
3%
n.a.
n.a.
n.a.
n.a.
⫺ Steroid induced - Pupillary block - No angle closure - No PAS ⫺ Steroid induced - No pupillary block - No PAS - No angle closure ⫺ Air bubble–induced mechanical angle closure & PAS - Pupillary block ⫺ Angle closure/pupillary block - Steroid response ⫺ Pupillary block
n.a.
n.a.
n.a.
n.a.
⫺ Pupillary block
n.a.
n.a.
16% n.a.
7.5% 70%
9% 7%
⫺ Steroid induced n.a.
5% 5%
n.a. n.a.
20% 12% 15%
10% n.a. n.a.
19% n.a. n.a.
n.a. n.a. n.a.
n.a. n.a. 20%
n.a. n.a. n.a.
MAY 2012
DLEK ⫽ deep lamellar endothelial keratoplasty; DMEK ⫽ Descemet membrane endothelial keratoplasty; DS(A)EK ⫽ Descemet stripping (automated) endothelial keratoplasty; IOP ⫽ intraocular pressure; n.a. ⫽ not applicable; PAS ⫽ peripheral anterior synechiae; PKP ⫽ penetrating keratoplasty.
mandatory changes in our surgical protocol or medication schedule, to avoid postoperative pressure spikes in eyes with pre-existing glaucoma. It may be of interest that the 2 most difficult eyes to manage (Cases 6 and 7; Table 2) were both referred for corneal decompensation after anglesupported phakic intraocular lens implantation. One of these eyes suffered from chronic cystoid macular edema, whereas the other eye eventually required filtering surgery.
may better balance the risk of graft detachment with that of air bubble–induced angle-closure glaucoma. It may also be important to note that reducing the air bubble size may be the only effective precaution, since secondary glaucoma attributable to mechanical forward displacement of the iris diaphragm is caused by a different mechanism than a true pupillary block glaucoma, for which the peripheral YAG iridotomy made before the surgery is not effective.
● EYES WITH DE NOVO GLAUCOMA – IMMEDIATE POSTOPERATIVE MECHANICAL ANGLE CLOSURE: In the re-
● EYES WITH DE NOVO GLAUCOMA – DELAYED POSTOPERATIVE OCULAR HYPERTENSION: Of the other 5 eyes
maining 11 eyes without a history of glaucoma (11/275; 4%), the ocular hypertension was caused by clearly different mechanisms.18,19 Six of these eyes developed a mechanical angleclosure glaucoma within the first 24 hours after surgery (Cases 8⫺13; Figures 1 and 2; Table 2). All of these eyes were phakic, and in each case the presence of the crystalline lens seemed to be part of the mechanism causing the glaucoma (Figure 3). In all 6 eyes, the 50% air bubble left in situ in the recipient anterior chamber at termination of the surgery apparently caused a “backward” tilt of the crystalline lens, displacing the inferior part of the iris diaphragm forward, resulting in a mechanical closure of the anterior chamber angle. In all of these eyes, the glaucomatous crisis could be reversed by pupillary dilation, topical 1% apraclonidine and 250 mg acetazolamide orally, and laying the patient down in a supine position for 1 to 2 hours. With the antiglaucoma medication continued for 1 to 2 days, no recurrences were seen, while the air bubble diminished in size within days. From the total of 275 eyes in our study, 55 (20%) were phakic, so air bubble–induced secondary angle-closure glaucoma may have occurred in a relatively high incidence of cases, that is, in 11% (6/55). Hence, it may be advocated to pressurize the anterior chamber with a complete air fill for about 1 hour at termination of a DMEK surgery, but then to reduce the air fill to only 20% to 30% (instead of 50%) in phakic eyes. Since phakic eyes represent a younger age group, and a Descemet graft may adhere more easily in younger patients, this change in protocol
without a history of glaucoma, 1 eye (Case 16; Table 2) underwent uncomplicated DMEK surgery but presented with IOP spikes not responsive to topical medication at 1 month postoperatively, in the absence of inflammation and while the visual acuity had improved to 20/28 (0.7). Gonioscopy revealed iridocorneal adhesions in the inferior quadrants, possibly caused by adherence of the peripheral flange of the Descemet graft to the recipient peripheral iris (ie, peripheral anterior synechiae). After cataract extraction and filtering surgery, the IOP normalized and the BCVA improved to 20/20 (1.0). Although peripheral anterior synechiae formation was rare in our series (0.4%; 1/275), this complication may be avoided by proper centration of the Descemet graft. In conclusion, our study indicated that eyes with pre-existing glaucoma undergoing DMEK may require close monitoring of the postoperative IOP to detect postoperative glaucoma episodes. In eyes without a history of glaucoma, this complication may be avoided in most cases by adjustments of the air bubble management in phakic eyes, a steroid regime titrated to the patient population, and proper graft positioning. Compared to the literature on penetrating keratoplasty and DSEK/DSAEK, our study suggests that DMEK does not come with an increased risk of uncontrolled glaucoma. Incidental cases may be related to the presence of an angle-supported (phakic) intraocular lens, or peripheral anterior synechiae formation in eyes with a decentered graft causing adhesions between the donor tissue and the iris.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. The authors indicate no funding support. Dr Melles is a consultant for D.O.R.C./Dutch Ophthalmic USA. Involved in design of the study (M.N., G.M.); conduct of the study (M.N., M.D., L.H., K.v.D., I.D., G.M.); collection, management, analysis, and interpretation of the data (M.N., M.D., J.P., L.H., K.v.D., I.D., G.M.); and preparation, review, or approval of the manuscript (M.N., I.D., M.D., L.H., K.v.D., G.M.). The study was conducted in compliance with Institutional Review Board and informed consent requirements, in adherence to the tenets of the Declaration of Helsinki, at the Netherlands Institute for Innovative Ocular Surgery (Study registration no N.05.14). The study was submitted to http://www.clinicaltrals.gov (study registration no NCT00521898).
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4. Ham L, Dapena I, van Luijk C, Van der Wees J, Melles GRJ. Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: Review of the first 50 consecutive cases. Eye (Lond) 2009;23(10):1990 –1998. 5. Dapena I, Ham L, van Luijk C, Van der Wees J, Melles GRJ. Back-up procedure for graft failure in Descemet membrane endothelial keratoplasty (DMEK). Br J Ophthalmol 2010; 94(2):241–244. 6. Balachandran C, Ham L, Verschoor CA, Ong TS, Van der Wees J, Melles GRJ. Spontaneous corneal clearance despite
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graft detachment in Descemet membrane endothelial keratoplasty. Am J Ophthalmol 2009;148(2):227–234. Banitt MR, Chopra V. Descemet’s stripping with automated endothelial keratoplasty and glaucoma. Curr Opin Ophthalmol 2010;21(2):144 –149. Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein RM. Descemet’s stripping endothelial keratoplasty: Safety and outcomes: A report by the American Academy of Ophthalmology. Ophthalmology 2009;116(9):1818 –1830. Lie JT, Birbal R, Ham L, Van der Wees J, Melles GRJ. Donor tissue preparation for Descemet membrane endothelial keratoplasty. J Cataract Refract Surg 2008;34(9):1578 –1583. Vajaranant TS, Price MO, Price FW. Visual acuity and intraocular pressure after Descemet’s stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. Ophthalmology 2009;116(9):1644 –1650. Erdurmus M, Cohen EJ, Yildiz EH, et al. Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy. Cornea 2009;28(7):759 –764. Price MO, Giebel AW, Fairchild KM, Price FW. Descemet’s membrane endothelial keratoplasty: Prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology 2009;116(12):2361–2368. Chen ES, Terry MA, Shamie N, Hoar KL, Friend DJ. Descemet-stripping automated endothelial keratoplasty: Sixmonth results in a prospective study of 100 eyes. Cornea 2008;27(5):514 –520. Frost NA, Wu J, Lai TF, Coster DJ. A review of randomized controlled trials of penetrating keratoplasty techniques. Ophthalmology 2006;113(6):942–949. Dapena I, Ham L, Netukova M, Van der Wees J, Melles GRJ. Incidence of early allograft rejection following Descemet membrane endothelial keratoplasty (DMEK). Cornea. Forthcoming. Wandling GR Jr, Parikh M, Robinson C, et al. Escalation of glaucoma therapy after deep lamellar endothelial keratoplasty. Cornea 2010;29(9):991–995.
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Biosketch Miguel Naveiras, MD, and PhD candidate by the Autonomous University of Madrid, graduated from the Hospital Central de Asturias, Spain, as a specialist ophthalmologist in 2010. In addition, he has undergone extra training at Massachusetts Eye and Ear Infirmary (Harvard Medical School, Boston, Massachusetts), Bascom Palmer Institute (University of Miami, Miami, Florida), Moorfields eye Hospital (London, United Kingdom) and Mermoud Clinic (Switzerland). He is currently a clinical fellow at Melles Cornea Clinic Rotterdam, and transplant coordinator at Amnitrans Eyebank Rotterdam. Both organizations are part of the Netherlands Institute for Innovative Ocular Surgery (www.niios.com), Rotterdam, The Netherlands.
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