Refractive surgery after corneal transplantation
Daniel H. Changa,b,c and David R. Hardtena,c,d
Purpose of review
Many patients who have undergone corneal transplantation
are unable to achieve satisfactory visual acuity with
spectacle and contact lens correction alone. For these
patients, refractive surgery becomes a viable option to
reduce the post-keratoplasty ametropia. With the many
recent advances in refractive surgery for naturally occurring
refractive error, new possibilities arise for application to this
complicated set of patients. This review discusses key
recent developments in refractive surgery after corneal
transplantation.
Recent findings
The biomechanical effects of incisional keratotomy on post-
keratoplasty corneas continue to be studied, and these
techniques remain a common and simple method of
reducing astigmatism. Photorefractive keratectomy,
previously problematic for regression and haze formation, is
gaining new prominence as early experience with the
adjunctive use of mitomycin C has demonstrated good
results. Long-term studies with laser in-situ keratomileusis
(LASIK) have continued to show good safety and efficacy.
Modern developments in cataract surgery appear to have
lower incidences of graft rejection and failure.
Developments in lens implantation technology continue to
offer expanding options for intraocular refractive surgery.
Summary
Although visual rehabilitation after corneal transplantation
remains a formidable challenge, developments in refractive
surgery for naturally occurring ametropias directly translate
into an improved ability to help these most challenging
refractive cases. Continued research will bring about
improved efficacy while maintaining a high level of safety.
Keywords
corneal transplantation, keratoplasty, laser in-situ
keratomileusis, photorefractive keratectomy,
refractive surgery
—255. ª 2005 Lippincott Williams & Wilkins.
Curr Opin Ophthalmol 16:251—
a
Minnesota Eye Consultants, Minneapolis, Minnesota; bParadise Valley Eye
Specialists, Scottsdale, Arizona; cRegions Medical Center, St Paul, Minnesota; and
d
University of Minnesota, Minneapolis, Minnesota, USA
Correspondence to David R Hardten, MD, 710 E 24th Street, Suite 106,
Minneapolis, MN 55404, USA
Tel: 612 813 3632; fax: 612 813 3658; e-mail: drhardten@mneye.com
Current Opinion in Ophthalmology 2005, 16:251—
—255
Abbreviation
LASIK laser in-situ keratomileusis
ª 2005 Lippincott Williams & Wilkins.
1040-8738
Introduction
Visual rehabilitation following corneal transplantation re-
mains a formidable challenge. High degrees of regular and
irregular astigmatism, frequently associated with signif-
icant myopia, hyperopia, and anisometropia can lead to
poor functional vision despite a clear corneal graft.
Although spectacles are the simplest method of address-
ing postoperative refractive error, contact lenses often pro-
vide superior visual acuity and are frequently required in
eyes with moderate and severe ametropia. Unfortunately,
contact lenses are often difficult to fit, and they may in-
duce peripheral corneal neovascularization, leading to graft
rejection and failure. Furthermore, many patients (the el-
derly in particular) are unable to handle or to maintain con-
tact lenses [1].
When these conservative methods fail to provide satisfac-
tory vision, surgical correction of the post-keratoplasty am-
etropia may be an option. This review discusses the use of
incisional keratotomies, photorefractive keratectomy, laser
in-situ keratomileusis (LASIK), lens implants, and other
modalities for the reduction of refractive error after pen-
etrating keratoplasty.
General considerations
The etiology of refractive error after anatomically success-
ful corneal transplantation is multifactorial, and it includes
preoperative corneal irregularity (of the host and the do-
nor), intraoperative surgical tissue alignment, and postop-
erative wound healing variability [1].
Prior to attempting refractive surgery after penetrating
keratoplasty, there must be adequate tectonic, refractive,
and immunogenic stability. This exact timing of surgery
will depend on the anticipated trauma of the planned pro-
cedure, but it should generally be at least 12 months after
keratoplasty and 3 months after suture removal. Early su-
ture removal should be avoided because problems in wound
apposition may develop due to tectonic instability. Prior
rejection episodes should be noted, and the patient should
be stable on minimal immunosuppressive agents [2].
Astigmatism should be evaluated through a combination
of refraction, keratometry, keratoscopy, corneal topography,
and wavefront analysis. Slit-lamp biomicroscopy should be
used to evaluate graft centration, size, and clarity, with at-
tention to areas of haze or neovascularization. The graft-
host interface should be assessed for quality of apposition,
override or underride, asymmetry, and edema. Pachymetry
measurements should be performed centrally and on either
251
252 Refractive surgery
side of the graft-host interface. Specular microscopy is
helpful in determining the status of the endothelial cell
layer [2].
Incisional keratotomy
The biomechanical response to contraction or relaxation
of corneal tissue forms the basis of incisional keratotomy.
Using the same principles as selective suture removal,
radial and astigmatic keratotomies are rapid and may be
performed in the office, but their refractive effects can be
highly variable. Relaxing incisions and compression sutures
can correct an average of 4–5 D of astigmatism [1]. In a
recent study evaluating the refractive effect of a standard-
ized incision (paired 600 mm depth, 60
arc, 6.0 mm apart
keratotomies), the astigmatic effect was found to be
proportional to the magnitude of the preoperative cylin-
der. This suggests that nomograms for congenital astigma-
tism do not apply to the correction of post-keratoplasty
astigmatism [3••].
Photorefractive keratotomy
Photorefractive keratectomy has been used after corneal
transplantation since the early 1990s [4]. Unfortunately,
these studies demonstrated substantial regression [4,5],
haze [4,5], and even severe scarring [6].
The adjunctive use of mitomycin C 0.02% (0.2 mg/ml) is
a promising new method of scar prevention in high-risk
eyes undergoing photorefractive keratectomy. Initially used
to prevent recurrence of subepithelial fibrosis after ra-
dial keratotomy and photorefractive keratectomy [7], mi-
tomycin C has also been studied for the prevention of haze
in patients with moderate myopia [8], high myopia [9••],
and in patients who have had LASIK flap complications
[10–12]. In a fellow-eye head-to-head comparison of sin-
gle 2-minute application of mitomycin C to a 3-month
steroid taper in highly myopic eyes, mitomycin C yielded
significantly better uncorrected visual acuity at the
12-month, 24-month, and 36-month time points, with sig-
nificantly less corneal haze as measured by slit-lamp bio-
microscopy and by confocal microscopy. Additionally,
confocal microscopy demonstrated progressive normali-
zation of the corneal stroma to the preoperative state with
no morphologic change to the cornea epithelium or
endothelium [9••].
Early reports of photorefractive keratectomy with mito-
mycin C after penetrating keratoplasty have been very
positive. The first reported case was in a patient with a
buttonhole from attempted LASIK. Subsequent photore-
fractive keratectomy with a 1-min application of 0.02%
mitomycin C resulted in a clear graft with uncorrected vi-
sual acuity of 20/40 [13••]. In another report, photorefrac-
tive keratectomy with mitomycin C was used to treat
post-keratoplasty hyperopic astigmatism. With larger abla-
tion zones and deeper peripheral ablation than myopic
treatments, hyperopic treatments may particularly com-
promise the integrity of the graft-host junction. In this
case, the preoperative refraction was +7.00 ÿ 4.75 3 125.
A single 2-min application of 0.02% mitomycin C was used
during photorefractive keratectomy. Six months post-
operative uncorrected visual acuity was 20/30, and best
spectacle-corrected visual acuity was 20/20 with a refrac-
tion of ÿ0.25 ÿ 0.25 3 164 [14].
No complications have been reported with the adjunctive
one-time use of mitomycin C at the time of photorefrac-
tive keratectomy, although there has been a case of corneal
edema from the topical use of mitomycin C as drops for
1 week after phototherapeutic keratectomy [15].
Laser in-situ keratomileusis
Because of early difficulties with regression, haze, and
scarring after photorefractive keratectomy, LASIK has be-
come a popular modality for correcting refractive error af-
ter corneal transplantation. This can be combined with
arcuate keratotomies and wedge resections for optimal as-
tigmatic control [16••,17].
Most authors wait at least 1 year after keratoplasty and
3 months after last suture removal or other refractive pro-
cedure prior to performing LASIK [16••,17–19]. Good wound
apposition with minimal graft override and underride is
important. Adequate endothelial cell counts for flap ap-
position should also be assessed [2].
Several recent studies with up to 5 years of follow-up have
demonstrated good outcomes [16••,17–19]. Uncorrected
visual acuity was 20/40 or better in 32% to 86% of eyes.
Best-corrected visual acuity was 20/40 or better in 86%–
98% of eyes. Fifty percent to 86% of eyes were within
1 D of intended correction, and only 0%–7% of eyes
lost two or more lines of best-corrected visual acuity
[16••,17,18]. Endothelial cell loss after LASIK is no higher
than the normal post-keratoplasty decline [16••,18],
Because the creation of a lamellar corneal flap alone can
induce significant corneal flattening, some authors have
suggested performing a microkeratome cut without laser
ablation and retreating several months later [19,20]. In
a prospective observational study, patients had LASIK
performed either as a one-step or a two-step procedure.
Although patients who had their LASIK as a two-step
procedure had significantly better vector analysis of re-
fractive cylinder, there was no difference in postoperative
uncorrected or best-corrected visual acuity, spherical
equivalent, or cylinder [19]. Based on these results, and
the fact that a two-step procedure is essentially LASIK
with a planned enhancement, performing a one-step LASIK
with flap-lift enhancement only when needed seems to be
the logical approach. In most recent series of ‘one-step’

LASIK, enhancements were performed in only 9%–39% of
cases [16••,17,18].
Typical LASIK complications such as buttonholes, flap
dislocation, sterile interface inflammation, striae, and epi-
thelial ingrowth can occur in LASIK after corneal trans-
plantation [13••,18]. Typical post-keratoplasty complications,
such as graft rejection [16••] and failure [18], can also oc-
cur. Corneal edema may manifest as fluid in the lamellar
interface due to the preferential collection of fluid in this
potential space. Endothelial failure should be suspected
in this setting, particularly with normal intraocular pres-
sures [18,21].
Dehiscence of the graft-host junction is rare but has been
reported in an eye that had LASIK 3 years after penetrat-
ing keratoplasty. Interestingly, the dehiscence did not oc-
cur with high suction at the time of LASIK but was caused
by moderate eye rubbing 2 weeks later. Because the lamel-
lar flap was larger than the corneal graft, the authors spec-
ulate that the thinned residual stromal bed did not provide
adequate appositional strength to sustain the forces of eye
rubbing [22].
Retraction of the lamellar flap has also been reported. Three
days after LASIK in a patient who had had keratoplasty
11 months previously, the inferior edge of a superior-
hinged flap became raised and 1–2 mm retracted. There
was marked edema, but the subjacent tissue appeared
normal. In the absence of flap striae, it was postulated that
the poor apposition of the peripheral flap edge allowed for
direct stromal hydration and subsequent retraction [23].
New laser technologies
The severe irregular astigmatism present in many patients
after penetrating keratoplasty is more difficult to treat than
most naturally occurring refractive error. New solid-state
lasers with a small flying spot [24] and unique ablation algo-
rithms incorporating corneal topography data [24–26] are
being evaluated to improve the clinical outcomes of laser
keratectomy in these patients.
Conductive keratoplasty
Conductive keratoplasty is a radiofrequency-based tech-
nique that denatures and shrinks corneal stromal collagen
from the heat generated secondary to tissue resistance to
current flow. Although conductive keratoplasty is most of-
ten used for the reduction of low to moderate levels of
hyperopia [27], some have applied this technique to treat
post-LASIK hyperopia [28]. Because tissue contraction
flattens the area of treatment, zonal application of conduc-
tive keratoplasty, as guided by corneal topography, can cor-
rect asymmetric corneal astigmatism after penetrating
keratoplasty. Although we have treated several patients
with good results, the long-term stability of this modality
remains unknown.
Corneal transplantation Chang and Hardten 253
Cataract extraction and intraocular
lens implantation
The treatment of patients with both a cataract and corneal
disease is controversial. Some advocate an initial triple pro-
cedure (combined penetrating keratoplasty, cataract ex-
traction, and intraocular lens implantation) [29], whereas
others recommend initial penetrating keratoplasty followed
by later cataract extraction and intraocular lens implan-
tation [30,31]. In the latter case, the function of cataract sur-
gery is frequently refractive.
Surprisingly, there are few studies on post-keratoplasty
cataract surgery by phacoemulsification. A recent review
of studies of graft failure after secondary intraocular sur-
gery found rejection rates between 0 and 66%, but many
studies were taken from the 1970s, with one study from as
early as 1960 [32]. Another study of 14 eyes found no sig-
nificant endothelial cell loss from extracapsular cataract
extraction [32].
In a recent study of 30 eyes undergoing phacoemulsifica-
tion after therapeutic penetrating keratoplasty for bacte-
rial or fungal ulcers, 47% of eyes were 20/40 or better, with
mean postoperative astigmatism of 2.7 D at 1 year. Three
eyes (10%) developed graft failure [33]. In another study
of 29 eyes, phacoemulsification was performed in 23 eyes
and extracapsular cataract extraction was performed in six
eyes. Although the outcomes were not stratified by tech-
nique, 97% of corneas remained clear during the postop-
erative mean follow-up of 44.5 months. Specifically, grafts
as old as 432 months, with endothelial cell count as low
as 576, and with corneal thickness as high as 684 mm, re-
mained clear. The one case of graft failure was in an eye
with three previous rejection episodes. Fifty-two percent
of eyes with clear corneas achieved best-corrected visual
acuity of 20/30 or better. Absolute mean spherical refrac-
tive error decreased from 6.60 to 2.47 D, but mean cylin-
der only decreased from 3.18 to 2.77 D because spherical
intraocular lens implants were used [34••]. In an interest-
ing case report of a patient with 16.5 D of manifest astig-
matism and 22.5 D of corneal astigmatism with a small and
decentered graft, a custom intraocular lens with 30 D of
cylindrical power was implanted, resulting in a final refrac-
tive cylinder of 4.0 D [35].
Pseudophakic post-keratoplasty patients with high levels
of refractive error may benefit from piggyback intraocular
lens implantation. Less invasive than an intraocular lens
exchange, this technique can be effective in correcting
pseudophakic refractive error. Because lens position is fairly
predictable, the lens power calculation can be based solely
on the preoperative refractive error, which is amenable
in the post-keratoplasty situation with irregular keratom-
etry. In a study of six myopic patients, mean spherical
254 Refractive surgery
equivalent decreased from ÿ8.08 D to ÿ0.94 D, with all
patients improving in uncorrected visual acuity [36].
Other lens implants
Iris-fixated intraocular lens implants have been used for
the surgical correction of aphakia and have recently been
approved in the United States for use in moderate and
high myopes. A toric Artisan, or Verisyse, iris-fixated intra-
ocular lens (Ophtec BV, Groningen, The Netherlands) has
been used to correct spherocylindrical refractive error af-
ter penetrating keratoplasty. Mean time from keratoplasty
to lens implantation was 48.9 months, with a mean 21.3
months after suture removal. After implantation, mean re-
fractive spherical equivalent decreased from ÿ4.09 D to
ÿ0.96 D, and mean cylinder decreased from ÿ6.66 D to
ÿ1.42 D. Eight eyes (50%) had a postoperative uncor-
rected visual acuity of 20/40 or better, and 94% of eyes
were 20/80 or better. No eyes lost lines of best-corrected
visual acuity, and eight eyes (50%) gained two or more
lines. Although the endothelial loss rate was 7.6% at 3
months and 21.7% at 6 months, there were no cases of
graft failure during the study period [37••].
Conclusion
At a time when advancements in refractive surgery are
providing an unprecedented ability to correct refractive er-
ror, an increasing number of options are available to help
patients with challenging post-keratoplasty ametropia.
As the understanding of post-keratoplasty biomechanics
improves, the ability to apply incisional techniques can be
refined with more accurate nomograms. The use of mito-
mycin C has brought about a resurgence of photorefractive
keratectomy, which may eventually prove to be advanta-
geous over LASIK by avoiding the creation of a lamellar
incision. More efficient methods of phacoemulsification
are less traumatic to the cornea and warrant further study
in this setting. New lens implants allow for the correction
of high degrees of ametropia and even astigmatism. With
the proliferation of new technologies, our ability to im-
prove visual acuity and quality of life through refractive
surgery after corneal transplantation continues to be a chal-
lenging and promising endeavor.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
• of special interest
•• of outstanding interest
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Corneal transplantation Chang and Hardten 255
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An excellent study using the Artisan iris-fixated intraocular lens in post-keratoplasty
patients.