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Sandwich Infectious Keratitis (“SIK” Syndrome) – A New Clinical Entity Following Lamellar Keratoplasty (DLEK, DSAEK, DALK, ALK)
T. John1,2, C. Karp3, E. Malbran4, L. Wiley5, M. John2, T. O’Brien3, J. Kieval3, R.K. Forster3, M. Gorovoy6, TE Gillette7, A. Panda8 /
Loyola University Medical Center, Maywood, Illinois; 2Thomas John Vision Institute, Tinley Park & Oak Lawn, IL; 3Bascom Palmer Eye Institute, Miami, FL; 4Clinica
Oftalmologica Malbran, Buenos Aires, Argentina; 5West Virginia University, Morgantown, WV; 6Gorovoy Eye Center, Fort Meyers, FL; 7Eye Associates NW, Seattle, WA;
8All India Institute of Medical Sciences, New Delhi, India
1
Purpose
To report sandwich
infectious keratitis
(“SIK” syndrome) a new
clinical entity of corneal
interface infections after
deep lamellar
endothelial keratoplasty
(DLEK), Descemet’s
stripping automated
endothelial keratoplasty
(DSAEK), preDescemetic deep
anterior lamellar
keratoplasty (DALK),
and anterior lamellar
keratoplasty (ALK).
Results
•Surgical
Procedures:
• Interface Infection
DLEK = 1
=9
DSAEK = 2
DALK = 2
• Eye disproptionately
ALK
=4
quiet
=9
• Organisms:
Fungus
Figure 2. SIK following DSAEK
=4
Figure 4. SIK following DALK
Conclusion
• SIK is a new clinical
entity, that was first
described by John T et al in
2003
(Candida glabrata,
Candida, Aureobacidium
pullulans, Rhodotorula)
Bacteria = 4
• Unlike a corneal ulcer,
•SIK has atypical symptoms
and signs & is challenging
to treat surgically
(Coag. Neg. Staph.,
Staph. aureus, Strep.
pneumonia,
Pseudomonas
aeruginosa)
• Patients with SIK after
DLEK, DSAEK, DALK, &
ALK may be asymptomatic
& clinicians should be
aware of this new entity
Methods
References
Nine cases of SIK were
identified and
retrospectively reviewed.
• John, T, Delany C, John ME: Sandwich keratitis: New clinical entity following
deep lamellar endothelial keratoplasty. Presented at the Annual Meeting of the
American Society of Cataract and Refractive Surgery, San Francisco, CA,
April 12 - 16, 2003.
Sharma N, Gupta V, Vanathi M, Agarwal T, Vajpayee RB, Satpathy G: Microbial
keratitis following lamellar keratoplasty. Cornea 2004; 23:472-478.
Kanavi MR, Foroutan AR, Kamel MR, Afsar N, Javadi MA: Candida interface
keratitis after deep anterior lamellar keratoplasty: clinical, microbiologic,
histopathologic, and confocal microscopic reports. Cornea 2007; 26:913-916.
Fontana L, Parente G, Di Pede B, Tassinari G: Candida albicans interface infection
after deep anterior lamellar keratoplasty. Cornea 2007; 26:883-885.
Figure 1. SIK following DSAEK
Figure 3. SIK following DLEK
Research supported by the Richard A. Perritt Charitable
foundation
SIK: A New Clinical Entity Following Lamellar Keratoplasty (DLEK,
DSAEK, DALK, ALK)
Purpose:
To report SIK a new clinical
entity of interface infectious
keratitis after DLEK, DSAEK,
pre-Descemetic DALK, and ALK
Light and Electron Microscopic Analysis of Excised Human Descemet's Membrane
Following Descemetorhexis with Endokeratoplasty
E. B. Price1, T. John1, K.R. Kenyon2,3
University Medical Center, Maywood, Illinois; 2Harvard Medical School, Boston, Massachusetts
thickness (4-6 excrescences per
hpf)
4 = severe variability in sample
To
evaluate
the
efficacy
of thickness
(>6 excrescences per hpf)
descemetorhexis and Descemet’s
stripping at producing a smooth
recipient stromal surface in the
context of descemetorhexis with
endokeratoplasty.
Figure 1. Excised tissue samples
Objective
Methods
Twenty-eight
posterior
lamellar
recipient corneal samples were
obtained from 27 DXEK patients
through
descemetorhexis
and
Descemet’s stripping with the John
dexatome. Two samples from
normal human donor eyes were also
obtained as controls. All samples
were
examined
using
light
microscopy and a representative
sample
was
examined
with
transmission electron microscopy.
All samples were evaluated for the
presence of residual corneal stroma
and the thickness of Descemet’s
membrane (DM). Patient samples
were also scored for the number of
DM excrescences (guttata) per high
power field.
Light
and
electron
microscopic
examination of all samples revealed no
residual corneal stroma. The mean (SD)
thickness of the DM was 18.09 (6.99) µm in
the patient group and 11.27 (2.90) µm in the
normal controls, with no statistical
difference between groups (P = 0.19).
Patient samples with smooth DM had a
mean (SD) thickness of 14.27 (2.70) µm,
while those with DM excrescences
averaged 21.40 (7.93) µm thick. This
difference was statistically significant (P <
0.01). When the level of excrescences on
the visual rating scale was compared
between the two groups,
Table 1. Tissue characteristics
Experimental ID
Number
Patient Patient Descemet's Membrane,
Age Sex
mean (μm)
SD (μm)
758M (Control #1)
Insert Photo
of
Lenticules
Photo of all excised samples on light
microscopy
758N (Control #2)
758P
758V
758O
758Z
758T
758U
758AA
758I
758L
758G
758CC
758S
758Y
758J
758H
758W
758X
758D
758R
758B
758C
758K
758BB
758F
758E
758DD
758Q
758A
53
74
41
77
85
81
78
86
90
77
83
91
73
77
79
77
77
98
58
84
70
80
77
67
76
73
88
64
F
F
M
M
F
F
M
F
M
F
F
F
M
M
M
M
F
F
F
F
M
F
F
F
F
F
F
F
9.22
1.06
13.32
11.53
11.67
11.95
12.27
12.37
12.94
13.20
13.42
13.47
13.78
14.43
15.38
16.88
17.57
17.61
17.79
17.90
18.84
19.06
19.38
19.87
20.18
20.31
20.80
23.72
24.15
30.62
45.46
1.00
1.02
1.04
1.44
1.18
0.71
1.61
0.78
1.33
2.96
1.10
1.06
1.89
2.32
1.17
3.77
4.55
4.52
1.97
2.42
0.76
1.37
4.77
3.61
5.37
2.57
5.22
5.94
4.38
the ranked mean (SD) of the
excrescences samples (n = 15) was
3.33 (0.82), versus 1 (0) for the
smooth samples (n = 13). This
difference was also statistically
significant (P < 0.01).
Figure 2. DM thickness in patients and controls
30
25
20
15
5
Control
s
Patient
s
Mean thickness of Descemet’s membrane
(DM) in excised posterior lamellar tissue in
patients (n = 28) and controls (n = 2). Bars
indicate standard deviation.
Figure 3. DM thickness in smooth and
excrescences samples
35
30
25
20
3
2
1
0
Smoot
h
Excrescence
s
Conclusion
Descemetorhexis and Descemet’s
stripping, performed in the present
study with the John dexatome,
produce a smooth separation of DM
from the posterior stroma. As there
was no recipient stromal loss, we
presume the posterior stromal
surface to be smooth. This
information is encouraging because it
reinforces that tissue separation
occurs at the plane that we intend it
to.
References
15
10
5
0
4
Mean visual excrescences score in excised
posterior lamellar tissue in smooth DM
patient samples (n = 13) and sawtooth DM
patient samples (n = 15). Bars indicate
standard deviation.
10
0
Figure 4. Visual excrescences score in smooth
and excrescences samples
Mean Visual Excrescences Score, (1-4)
Results
Thickness of Descemet's Membrane, mean
(SD), μm
To measure the thickness of the
DM, five photos were taken of each
sample at 40x magnification and 10
Descemetorhexis
with thickness measurements were made
endokeratoplasty (DXEK, Descemet’s on each photo using Scion Image
stripping
automated
endothelial software (Scion Corp., Frederick, MD).
keratoplasty, DSAEK) has become
the treatment of choice for many Visual excrescences scores were
types of corneal endothelial disease. assigned as follows:
A better understanding of the plane at
1 = smooth surface
which tissue separation occurs will
2 = mild variability in sample
promote the advancement of the best thickness (1-3 excrescences per highpossible
posterior
lamellar power-field [hpf])
keratoplasty technique.
3 = moderate variability in sample
Introduction
Thickness of Descemet's Membrane, mean
(SD), μm
1Loyola
Smoot
Excrescence
h
s
Mean thickness of Descemet’s
membrane
(DM) in excised posterior lamellar tissue in
smooth DM patient samples (n = 13) and
excrescences DM patient samples (n = 15).
Bars indicate standard deviation.
Melles GRJ, Eggink FAGJ, Lander F, et al. A surgical technique for posterior lamellar keratoplasty.
Cornea 1998;17:618.26.
Melles GRJ, Wijdh RHJ, Nieuwendaal CP. A technique to excise the Descemet membrane from a
recipient cornea
(descemetorhexis). Cornea 2004;23:286.288.
Melles GRJ, San Ong T, Ververs B, et al. Descemet membrane endothelial keratoplasty (DMEK). Cornea
2006;25:987.990.
Tappin M. A method for true endothelial cell (Tencell) transplantation using a custom made cannula for
the treatment of endothelial
cell failure. Eye 2007;21:775.779.
Melles GRJ, San Ong T, Ververs B, et al. Preliminary clinical results of Descemet membrane endothelial
keratoplasty. Am J
Ophthalmol 2008;145:222.227.
Shimmura S, Miyashita H, Konomi K, et al. Transplantation of corneal endothelium with Descemet's
membrane using a hyroxyethyl
methacrylate polymer as a carrier. Br J Ophthalmol 2005;89:134.137.
Ignacio TS, Nguyen TTB, Sarayba MA, et al. A technique to harvest Descemet's membrane with viable
endothelial cells for selective
transplantation. Am J Ophthalmol 2005;139:325.330.
Terry MA, Hoar KL, Wall J, et al. Histology of dislocations in endothelial keratoplasty (DSEK and DLEK):
a laboratory based, surgical
solution to dislocation in 100 consecutive DSEK cases. 2006;25:926.932.
Heindl LM, Hofmann-Rummelt C, Schlötzer-Schrehardt et al. Histologic analysis of Descemet stripping
in posterior lamellar
keratoplasty. Arch Ophthalmol. 2008;126:461.464.
Tillet CW. Posterior lamellar keratoplasty. Am J Ophthalmol. 1956;41:530.533.
Research supported by the Richard A. Perritt
Charitable foundation
Light and Electron Microscopic Analysis of Excised Human Descemet's Membrane
Following Descemetorhexis with Endokeratoplasty
Objective
To evaluate the efficacy of
descemetorhexis and Descemet’s
stripping at producing a smooth
recipient stromal surface in the
context of descemetorhexis with
endokeratoplasty.
Visual excrescences scores were
assigned as follows:
1 = smooth surface
2 = mild variability in sample
thickness (1-3 excrescences per
high-power-field [hpf])
3 = moderate variability in sample
thickness (4-6 excrescences per
hpf)
4 = severe variability in sample
thickness
(>6 excrescences per
hpf)
Figure 1. Excised tissue samples
Light and electron microscopic
examination of all samples revealed
no residual corneal stroma. The mean
(SD) thickness of the DM was 18.09
(6.99) mm in the patient group and
11.27 (2.90) mm in the normal
controls, with no statistical difference
between groups (P = 0.19). Patient
samples with smooth DM had a mean
(SD) thickness of 14.27 (2.70) mm,
while those with DM excrescences
averaged 21.40 (7.93) mm thick. This
difference was statistically significant
(P < 0.01). When the level of
excrescences on the visual rating
scale was compared between the two
groups,
Table 1. Tissue characteristics
Experimental ID
Number
Methods
Twenty-eight posterior lamellar
recipient corneal samples were
obtained from 27 DXEK patients
through descemetorhexis and
Descemet’s stripping with the John
dexatome. Two samples from
normal human donor eyes were also
obtained as controls. All samples
were examined using light
microscopy and a representative
sample was examined with
transmission electron microscopy.
All samples were evaluated for the
presence of residual corneal stroma
and the thickness of Descemet’s
membrane (DM). Patient samples
were also scored for the number of
DM excrescences (guttata) per high
power field.
Results
Insert Photo
of
Lenticules
Photo of all excised samples on light
microscopy
Patient Patient Descemet's Membrane,
Age Sex
mean (μm)
SD (μm)
758M (Control #1)
9.22
1.06
758N (Control #2)
758P
758V
758O
758Z
758T
758U
758AA
758I
758L
758G
758CC
758S
758Y
758J
758H
758W
758X
758D
758R
758B
758C
758K
758BB
758F
758E
758DD
758Q
758A
13.32
11.53
11.67
11.95
12.27
12.37
12.94
13.20
13.42
13.47
13.78
14.43
15.38
16.88
17.57
17.61
17.79
17.90
18.84
19.06
19.38
19.87
20.18
20.31
20.80
23.72
24.15
30.62
45.46
1.00
1.02
1.04
1.44
1.18
0.71
1.61
0.78
1.33
2.96
1.10
1.06
1.89
2.32
1.17
3.77
4.55
4.52
1.97
2.42
0.76
1.37
4.77
3.61
5.37
2.57
5.22
5.94
4.38
53
74
41
77
85
81
78
86
90
77
83
91
73
77
79
77
77
98
58
84
70
80
77
67
76
73
88
64
F
F
M
M
F
F
M
F
M
F
F
F
M
M
M
M
F
F
F
F
M
F
F
F
F
F
F
F
the ranked mean (SD) of the
excrescences samples (n = 15) was
3.33 (0.82), versus 1 (0) for the
smooth samples (n = 13). This
difference was also statistically
significant (P < 0.01).
Figure 2. DM thickness in patients and controls
30
25
20
15
4
3
2
1
0
Smoot
h
Excrescence
s
Mean visual excrescences score in excised
posterior lamellar tissue in smooth DM
patient samples (n = 13) and sawtooth DM
patient samples (n = 15). Bars indicate
standard deviation.
10
5
0
Figure 4. Visual excrescences score in smooth
and excrescences samples
Mean Visual Excrescences Score, (1-4)
Descemetorhexis with
endokeratoplasty (DXEK, Descemet’s
stripping automated endothelial
keratoplasty, DSAEK) has become
the treatment of choice for many
types of corneal endothelial disease.
A better understanding of the plane at
which tissue separation occurs will
promote the advancement of the best
possible posterior lamellar
keratoplasty technique.
To measure the thickness of the
DM, Five photos were taken of each
sample at 40x magnification and 10
thickness measurements were made
on each photo using Scion Image
software (Scion Corp., Frederick, MD).
Thickness of Descemet's Membrane, mean
(SD), μm
Introduction
E. B. Price1, T. John1, K.R. Kenyon2,3
University Medical Center, Maywood, Illinois; 2Harvard Medical School, Boston, Massachusetts
Control
s
Patient
s
Mean thickness of Descemet’s membrane
(DM) in excised posterior lamellar tissue in
patients (n = 28) and controls (n = 2). Bars
indicate standard deviation.
Figure 3. DM thickness in smooth and
excrescences samples
Thickness of Descemet's Membrane, mean
(SD), μm
1Loyola
35
30
25
Conclusion
Descemetorhexis and Descemet’s
stripping, performed in the present
study with the John dexatome,
produce a smooth separation of DM
from the posterior stroma. As there
was no recipient stromal loss, we
presume the posterior stromal
surface to be smooth. This
information is encouraging because it
reinforces that tissue separation
occurs at the plane that we intend it
to.
20
References
15
10
5
0
Smoot
Excrescence
h
s
Mean thickness of Descemet’s
membrane
(DM) in excised posterior lamellar tissue in
smooth DM patient samples (n = 13) and
excrescences DM patient samples (n = 15).
Bars indicate standard deviation.
Melles GRJ, Eggink FAGJ, Lander F, et al. A surgical technique for posterior lamellar keratoplasty.
Cornea 1998;17:618.26.
Melles GRJ, Wijdh RHJ, Nieuwendaal CP. A technique to excise the Descemet membrane from a
recipient cornea
(descemetorhexis). Cornea 2004;23:286.288.
Melles GRJ, San Ong T, Ververs B, et al. Descemet membrane endothelial keratoplasty (DMEK). Cornea
2006;25:987.990.
Tappin M. A method for true endothelial cell (Tencell) transplantation using a custom made cannula for
the treatment of endothelial
cell failure. Eye 2007;21:775.779.
Melles GRJ, San Ong T, Ververs B, et al. Preliminary clinical results of Descemet membrane endothelial
keratoplasty. Am J
Ophthalmol 2008;145:222.227.
Shimmura S, Miyashita H, Konomi K, et al. Transplantation of corneal endothelium with Descemet's
membrane using a hyroxyethyl
methacrylate polymer as a carrier. Br J Ophthalmol 2005;89:134.137.
Ignacio TS, Nguyen TTB, Sarayba MA, et al. A technique to harvest Descemet's membrane with viable
endothelial cells for selective
transplantation. Am J Ophthalmol 2005;139:325.330.
Terry MA, Hoar KL, Wall J, et al. Histology of dislocations in endothelial keratoplasty (DSEK and DLEK):
a laboratory based, surgical
solution to dislocation in 100 consecutive DSEK cases. 2006;25:926.932.
Heindl LM, Hofmann-Rummelt C, Schlötzer-Schrehardt et al. Histologic analysis of Descemet stripping
in posterior lamellar
keratoplasty. Arch Ophthalmol. 2008;126:461.464.
Tillet CW. Posterior lamellar keratoplasty. Am J Ophthalmol. 1956;41:530.533.
Research supported by the Richard A. Perritt
Charitable foundation