Correspondence

1147

Conflict of interest keratoplasty (PK) because of lower refractive errors

The authors declare no conflict of interest. and a quicker visual rehabilitation,1,2 and notably
because of a lower incidence of graft-rejection episodes
compared with standard penetrating keratoplasties.3
Currently, there are only limited long-term data on
References
rejection rates following DSAEK and DMEK. Price et al2
confirmed immunologic graft rejections as the major
1 Siaudvytyte L, Januleviciene I, Daveckaite A, Ragauskas A, cause for graft failure in DSAEK and PK. The risk of
Bartusis L, Kucinoviene J et al. Literature review and meta- immune responses following DMEK is ~ 15 times
analysis of translaminar pressure difference in open-angle lower than in PK.4,5 For this reason, we hypothesize
glaucoma. Eye 2015; 29(10): 1242–1250. that the graft stroma is involved in triggering immune
2 Killer HE, Miller NR, Flammer J, Meyer P, Weinreb RN,
rejections. We herein examine whether graft diameter
Remonda L et al. Cerebrospinal fluid exchange in the optic
and in particular, the graft placement within the anterior
nerve in normal-tension glaucoma. Br J Ophthalmol 2012;
eye chamber, represent risk factors for graft rejections
96(4): 544–548.
following DSAEK.
3 Hayreh SS. Cerebrospinal fluid pressure and glaucomatous
Medical records of DSAEK patients with surgeries
optic disc cupping. Graefes Arch Clin Exp Ophthalmol 2009;
between 2008 and 2011 were reviewed for allograft
247(6): 721–724.
rejections. Graft rejection was diagnosed in case of:
4 Wostyn P, De Groot V, Van Dam D, Audenaert K, Killer HE,
De Deyn PP. Glaucoma considered as an imbalance between
production and clearance of neurotoxins. Invest Ophthalmol K presence of keratic leukocyte precipitates on the graft,
Vis Sci 2014; 55(8): 5351–5352. but not on the recipient cornea and/or
5 Wostyn P, De Groot V, Van Dam D, Audenaert K, K the presence of an endothelial rejection line on the
De Deyn PP. Senescent changes in cerebrospinal fluid
graft and/or
circulatory physiology and their role in the pathogenesis of
normal-tension glaucoma. Am J Ophthalmol 2013; 156(1): 5–14. K an increase of cells in the aqueous humour, and/or
K corneal edema not explained by rise of intraocular
P Wostyn1, V De Groot2, D Van Dam3, K Audenaert4 and pressure.
PP De Deyn3,5,6
1
Eyes with peripheral anterior synechiae or other anatomic
Department of Psychiatry, PC Sint-Amandus, anterior segment anomalies were excluded to reduce
Beernem, Belgium immunologic confounders as much as possible. For the
2
Department of Ophthalmology, Antwerp University same reason, we also excluded repeat keratoplasties and
Hospital, Antwerp, Belgium patients with a history of previous anterior chamber (AC)
3
Department of Biomedical Sciences, Laboratory of inflammation (eg, herpetic keratitis) from the start.
Neurochemistry and Behavior, Institute Born-Bunge, In 35 patients (18 females and 17 males) aged between
University of Antwerp, Antwerp, Belgium 39 and 89 years (median 71 years), a postoperative
4
Department of Psychiatry, Ghent University Hospital, anterior segment spectral OCT measurement (SS-1000
Ghent, Belgium Casia, Tomey, Japan) had been recorded (average
5
Department of Neurology and Memory Clinic, follow-up for 460 days, see Table 1).
Middelheim General Hospital (ZNA), Antwerp, The OCT images were used to define the central
Belgium and peripheral thickness and position of the graft. Graft
6
Department of Neurology and Alzheimer Research centering was determined as the averaged offset to the
Center, University of Groningen and University optical axis in 0°, 45°, and 90° sectional images. A single
Medical Center Groningen, Groningen, operator processed the images according to a planimetry
The Netherlands protocol (Figure 1). We extracted two spatial features
E-mail: wostyn.peter@skynet.be from each image: centration of the graft (absolute of
the difference between A and B, ‘de-center score’) and
Eye (2016) 30, 1146–1147; doi:10.1038/eye.2016.73; the maximal thickness of the graft (distance between
published online 15 April 2016 identification marks 3 vs 4 and 6 vs 7, respectively;
Figure 1c). We averaged these parameters from the three
OCT images of the 0°, 45°, and 90° degree meridians for
each patient separately. Data were analyzed using
Sir, the R platform (http://www.r-project.org/). A Cox
Graft decentering in DSAEK: a risk factor for immune proportional hazard model was fitted to predict the
reactions? rejection risk. The investigator was masked for the
rejection state to preclude any bias towards our
hypothesis. Ethics approval was provided by the
Lamellar keratoplasties have extended the range local Ethics Service Committee (Research Ethics
of corneal transplantation since the late 1990s. Committee of Albert-Ludwigs-University Freiburg;
Descemet's stripping (automated) endothelial Germany; reference: 71/11). Written informed consent
keratoplasty (DSAEK/DSEK) as well as Descemet was obtained from all patients involved in this study.
membrane endothelial keratoplasty (DMEK) are This study adheres to the tenets of the Declaration of
nowadays mostly preferred over penetrating Helsinki.

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1148

We observed a total of six immune reactions (Figure 2). peripheral graft section—the higher the risk for a
Cox regression revealed decentering of the corneal later graft rejection, whereas a thicker central graft
grafts as a highly statistically significant predictor of
graft rejections (Table 2, P = 0.007, hazard ratio 1.067). diameter is associated with decreased risk for later
The graft thickness seems also to be a predictor, immune rejections. The covariates ‘graft diameter’ and
albeit with contradictory correlation: the thicker the ‘age at time of surgery’ missed statistical significance.

Table 1 Study details

Median Minimum Maximum 1st quartile 3rd quartile

Follow-up (days) 460 90 1565 350 550

Age (years) 71 39 89 66 77
Central graft thickness (pixels) 26.04 17.14 40.06 21.94 28.36
Decentering (pixels) 80.33 22.00 188.00 52.00 124.50
Operation techniques K 1 femtosecondlaser-assisted operation and 34 microkeratome operations; thereof:
K 16 triple-operations and
K 19 standard DSAEK procedures
Transplant diameters Two 9.0 mm (one graft with a rejection episode)
Two 8.5 mm (one graft with a rejection episode)
31 × 8.0 mm (four rejection episodes)

c Optical axis
A
B
5

6
7

1 4

2 3
Decenter-Score = |A-B|

Host cornea - DS = 0 -> fully centred graft

Graft - the bigger the value of the DS -> the more decentered

Figure 1 Decenter score. Centering was determined as the average offset to the optical axis in three sectional images (0°, 45°, and 90°.
(a, b) Clinical examples of a slight (a) and a more decentered (b) DSAEK graft in two different patients; the second patient (b) developed
a later corneal graft rejection. Besides the centering of the graft (average offset in three axes; defined in each axis as the value of the
distances between a and b. (c) We also measured the central and peripheral transplant thickness (for the central graft thickness the
distance between identification marks 6 vs 7 was measured; for the peripheral thickness the distances between marks 1 vs 2, respectively
3 vs 4 were measured). (c) All measurements were calculated in pixels by using the R platform.

Eye
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1149

risk for graft rejection therefore needs to be confirmed in

a larger clinical setting.
Conflict of interest
The authors declare no conflict of interest.

References

1 Reid RA, Craig EA, Suleman H. Descemet’s membrane

endothelial keratoplasty (DMEK): first UK prospective study
of 1-year visual outcomes, graft survival and endothelial cell
count. Br J Ophthalmol 2015; 99(2): 166–169.
2 Price MO, Gorovoy M, Price FW, Benetz BA, Menegay HJ,
Lass JH. Descemet’s stripping automated endothelial
keratoplasty: three-year graft and endothelial cell survival
compared with penetrating keratoplasty. Ophthalmology 2013;
Figure 2 Kaplan–Meier plot. The plot shows the estimation of 120(2): 246–251.
rejection-free survival after DSAEK determined with the Kaplan– 3 Price MO, Price FW. Descemet’s stripping
Meier method (n = 35). All six rejections occurred within 1 year endothelial keratoplasty. Curr Opin Ophthalmol 2007; 18(4):
after transplantation. 290–294.
4 Anshu A, Price MO, Price FW Jr. Risk of corneal transplant
rejection significantly reduced with Descemet’s membrane
Table 2 Cox regression model with the end point graft rejection endothelial keratoplasty. Ophthalmology 2012; 119(3): 536–540.
5 Steven P, Hos D, Heindl LM, Bock F, Cursiefen C. Immune
Hazard ratio Standard error P reactions after DMEK, DSAEK and DALK. Klin Monbl
(HR) of the coefficient Augenheilkd 2013; 230(5): 494–499.
6 Lapp T, Zaher SS, Haas CT, Becker DL, Thrasivoulou C,
Decentering 1.067 0.0245 0.007 Chain BM et al. Identification of therapeutic targets of
Peripheral graft thickness 1.216 0.1002 0.051 inflammatory monocyte recruitment to modulate the
Central graft thickness 0.498 0.3143 0.027 allogeneic injury to donor cornea. Invest Ophthalmol Vis Sci
Age 1.018 0.0553 0.75 2015; 56(12): 7250–7259.
Graft diameter 0.273 1.3986 0.35
T Lapp, S Heinzelmann, WA Shanab, T Reinhard and
D Boehringer

Conclusions Eye Centre - University Hospital Freiburg,

Our data suggest that the DSAEK stroma may have Albert-Ludwigs-University of Freiburg, Freiburg,
a causative role in generating immune responses, that Germany
is, rejections seem to be favored by graft proximity E-mail: Daniel.Boehringer@uniklinik-freiburg.de
to the AC angle. It may contribute to the migration
of donor-derived antigen presenting cells (APCs) into
the recipient‘s lymphatics (direct pathway). Alternatively, Eye (2016) 30, 1147–1149; doi:10.1038/eye.2016.76;
access to the graft of recipient APCs may be promoted published online 15 April 2016
by decentered graft positioning (indirect pathway).
Interestingly, cells infiltrating the anterior chamber
(AC) belong to the innate immune system: the cellular Sir,
infiltrate contains mainly monocytes and cells Patient satisfaction in the Peterborough community
differentiating into APCs, that is, mainly macrophages.6 specialist optometrist in glaucoma shared-care scheme
These cells can also be found in the cornea—but as an
intact Descemet membrane does not allow any cellular We note with interest the results published by Levy and
transmigration, it is widely believed, that cells in AC Booth1 on 'Patient satisfaction with Peninsula Optometry
are recruited through iris vessels and ciliary body in the Community Glaucoma Scheme'. We have significant
context of a breakdown of the immune privilege. Cells experience with our own community optometrist
in the corneal stroma (eg, after DSAEK) or the exchange glaucoma scheme2 and have recently collected
of allo-antigens through APCs coming from the AC satisfaction data.
and/or the AC angle (especially after DMEK, where Questionnaires were sent to 120 patients attending
there are no donor stromal APCs present) consequently the community scheme and 120 patients in the hospital
must be crucial for the generation of an immune response. glaucoma service. Patients were questioned about the
In summary, the data may indicate an active role clinician they saw, and their satisfaction with the
of donor-derived immune cells in the rejection process. service overall (Table 1). Response rate was 57%.
Major limitation of our work is the size of the cohort; the Patients in the community scheme were asked whether
importance of graft centration in DSAEK to minimize the they would like to continue with the scheme, whereas

Eye