Download Corneal Transplant, Endothelial Keratoplasty

MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
Original Issue Date (Created):
7/9/2002
Most Recent Review Date (Revised):
7/26/2016
Effective Date:
3/1/2017
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Corneal Transplant
Corneal transplantation may be considered medically necessary for patients with the following
conditions:
 Aphakic corneal edema
 Chemical injuries
 Complications of transplanted organ
 Congenital opacities
 Corneal degenerations
 Ectasias/thinnings
 Keratoconus
 Mechanical complication of corneal graft
 Mechanical trauma, non-surgical
 Microbial /post-microbial keratitis
 Non-infectious ulcerative keratitis or perforation
 Other causes of corneal opacification/distortion
 Primary corneal endotheliopathies
 Pseudophakic corneal edema
 Regraft related to allograft rejection
 Regraft unrelated to allograft rejection
 Stromal corneal dystrophies
 Viral/post-viral keratitis
Corneal transplantation for indications other than those listed in this policy (e.g., astigmatism,
correction of refractive errors) is considered not medically necessary.
Endothelial Keratoplasty
Endothelial keratoplasty (Descemet’s stripping endothelial keratoplasty [DSEK] or Descemet’s
stripping automated endothelial keratoplasty [DSAEK], Descemet’s membrane endothelial
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
keratoplasty [DMEK] or Descemet’s membrane automated endothelial keratoplasty [DMAEK])
may be considered medically necessary for the treatment of endothelial dysfunction, including
but not limited to the following conditions:
 ruptures in Descemet’s membrane
 endothelial dystrophy
 aphakic and pseudophakic bullous keratopathy
 iridocorneal endothelial (ICE) syndrome
 corneal edema attributed to endothelial failure
 failure or rejection of a previous corneal transplant
Femtosecond laser-assisted corneal endothelial keratoplasty (FLEK) or femtosecond and excimer
lasers-assisted endothelial keratoplasty (FELEK) are considered investigational. There is
insufficient evidence to support a conclusion concerning the health outcomes or benefits
associated with this procedure.
Endothelial keratoplasty is not medically necessary when endothelial dysfunction is not the
primary cause of decreased corneal clarity.
Policy guidelines
Endothelial keratoplasty should not be used in place of penetrating keratoplasty for conditions
with concurrent endothelial disease and anterior corneal disease. These situations would include
concurrent anterior corneal dystrophies, anterior corneal scars from trauma or prior infection, and
ectasia after previous laser vision correction surgery. Clinical input suggested that there may be
cases where anterior corneal disease should not be an exclusion, particularly if endothelial
disease is the primary cause of the decrease in vision. EK should be performed by surgeons who
are adequately trained and experienced in the specific techniques and devices used.
Keratoprostheses
The Boston (Dohlman-Doane) Keratoprosthesis (Boston KPro) may be considered medically
necessary for the surgical treatment of severe corneal opacification under the following
conditions:
 The cornea is severely opaque and vascularized; AND
 Best-corrected vision is ≤20/400 in the affected eye and ≤20/40 in the contralateral eye;
AND
 No end-stage glaucoma or retinal detachment is present; AND
 The patient has one of the following indications:
o History of 1 or more corneal transplant graft failures
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
o Stevens-Johnson syndrome
o Ocular cicatricial pemphigoid
o Autoimmune conditions with rare ocular involvement
o Ocular chemical burns
o An ocular condition unlikely to respond favorably to primary corneal transplant
surgery (e.g., limbal stem cell compromise or post herpetic anesthesia)
Note that patients should be expected to be able to be compliant with postoperative care.
Note: Implantation of a keratoprosthesis is considered a high-risk procedure associated with
numerous complications and probable need for additional surgery. Therefore, the
likelihood of regaining vision and the patient’s visual acuity in the contralateral eye
should be taken into account when considering the appropriateness of this procedure.
Treatment should be restricted to centers experienced in treating this condition and
staffed by surgeons adequately trained in techniques addressing implantation of this
device.
A permanent keratoprosthesis for all other conditions is considered investigational.
All other types of permanent keratoprostheses are considered investigational. There is
insufficient evidence to support a conclusion concerning the health outcomes or benefits
associated with these procedures.
Cross-references:
MP-1.044 Corneal Surgery to Correct Refractive Errors and Phototherapeutic
Keratoplasty
MP-6.031 Gas Permeable Scleral Contact Lens and Therapeutic Soft Contact Lens
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
FEP PPO*
* Refer to FEP Medical Policy Manual MP-9.03.22 Endothelial Keratoplasty and MP 9.03.01
Keratoprosthesis. The FEP Medical Policy manual can be found at: www.fepblue.org
Page 3
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
III. DESCRIPTION/BACKGROUND
TOP
Corneal Transplant
Corneal transplants are also referred to as keratoplasty. This surgical procedure is usually
performed under local anesthesia in an outpatient setting and involves implantation of a cornea
from a donor eye. This is the most common organ transplant procedure in the United States.
There are two major types of corneal transplants, lamellar keratoplasty and penetrating
keratoplasty (PK).
Endothelial Keratoplasty
Endothelial keratoplasty (EK), also referred to as posterior lamellar keratoplasty, is a form of
corneal transplantation in which the diseased inner layer of the cornea, the endothelium, is
replaced with healthy donor tissue. Specific techniques include Descemet’s stripping
endothelial keratoplasty, Descemet’s stripping automated endothelial keratoplasty, or
Descemet’s membrane endothelial keratoplasty.
The cornea, a clear, dome-shaped membrane that covers the front of the eye, is a key refractive
element of the eye. Layers of the cornea consist of the epithelium (outermost layer); Bowman’s
layer; the stroma, which comprises approximately 90% of the cornea; Descemet’s membrane;
and the endothelium. The endothelium removes fluid from the stroma and limits entry of fluid
as well, thereby maintaining the ordered arrangement of collagen and preserving the cornea’s
transparency. Diseases that affect the endothelial layer include Fuchs’ endothelial dystrophy,
aphakic and pseudophakic bullous keratopathy (corneal edema following cataract extraction),
and failure or rejection of a previous corneal transplant.
The established surgical treatment for corneal disease is penetrating keratoplasty (PK), which
involves the creation of a large central opening through the cornea and then filling the opening
with full-thickness donor cornea that is sutured in place. Visual recovery after PK may take 1
year or more due to slow wound healing of the avascular full-thickness incision, and the
procedure frequently results in irregular astigmatism due to the sutures and the full-thickness
vertical corneal wound. PK is associated with an increased risk of wound dehiscence,
endophthalmitis, and total visual loss after relatively minor trauma for years after the index
procedure. There is also risk of severe, sight-threatening complications such as expulsive
suprachoroidal hemorrhage, in which the ocular contents are expelled during the operative
procedure, as well as postoperative catastrophic wound failure.
A number of related techniques have been, or are being, developed to selectively replace the
diseased endothelial layer. One of the first endothelial keratoplasty (EK) techniques was termed
deep lamellar endothelial keratoplasty (DLEK), which used a smaller incision than PK, allowed
more rapid visual rehabilitation, and reduced postoperative irregular astigmatism and suture
complications. Modified EK techniques include endothelial lamellar keratoplasty,
endokeratoplasty, posterior corneal grafting, and microkeratome-assisted posterior keratoplasty.
Most frequently used at this time are Descemet’s stripping endothelial keratoplasty (DSEK),
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
which uses hand-dissected donor tissue, and Descemet’s stripping automated endothelial
keratoplasty (DSAEK), which uses an automated microkeratome to assist in donor tissue
dissection. A laser may also be utilized for stripping in a procedure called femtosecond laserassisted corneal endothelial keratoplasty (FLEK) or femtosecond and excimer lasers-assisted
endothelial keratoplasty (FELEK). These techniques include some donor stroma along with the
endothelium and Descemet’s membrane, which results in a thickened stromal layer after
transplantation. If the donor tissue comprises Descemet’s membrane and endothelium alone, the
technique is known as Descemet’s membrane endothelial keratoplasty (DMEK). By eliminating
the stroma on the donor tissue and possibly reducing stromal interface haze, DMEK is
considered to be a potential improvement over DSEK/DSAEK. A variation of DMEK is
Descemet’s membrane automated EK (DMAEK). DMAEK contains a stromal rim of tissue at
the periphery of the DMEK graft to improve adherence and increase ease of handling of the
donor tissue. A laser may also be used for stripping in a procedure called femtosecond laserassisted endothelial keratoplasty (FLEK) and femtosecond and excimer lasers‒assisted
endothelial keratoplasty (FELEK).
EK involves removal of the diseased host endothelium and Descemet’s membrane with special
instruments through a small peripheral incision. A donor tissue button is prepared from
corneoscleral tissue after removing the anterior donor corneal stroma by hand (e.g., DSEK) or
with the assistance of an automated microkeratome (e.g., DSAEK) or laser (FLEK or FELEK).
Several microkeratomes have received clearance for marketing through the U.S. Food and Drug
Administration (FDA) 510(k) process. Donor tissue preparation may be performed by the
surgeon in the operating room, or by the eye bank and then transported to the operating room
for final punch out of the donor tissue button. To minimize endothelial damage, the donor tissue
must be carefully positioned in the anterior chamber. An air bubble is frequently used to center
the donor tissue and facilitate adhesion between the stromal side of the donor lenticule and the
host posterior corneal stroma. Repositioning of the donor tissue with application of another air
bubble may be required in the first week if the donor tissue dislocates. The small corneal
incision is closed with one or more sutures, and steroids or immunosuppressants may be
provided either topically or orally to reduce the potential for graft rejection. Visual recovery
following EK is typically achieved in 4-8 weeks.
Eye Bank Association of America (EBAA) statistics show the number of EK cases in the
United States increased from 1,429 in 2005 to 23,409 in 2012. The EBAA report estimates that
approximately 1/2 of corneal transplants performed in the U.S. were endothelial grafts. As with
any new surgical technique, questions have been posed about long-term efficacy and the risk of
complications. EK-specific complications include graft dislocations, endothelial cell loss, and
rate of failed grafts. Long-term complications include increased intraocular pressure, graft
rejection, and late endothelial failure. Also of interest is the impact of the surgeon’s learning
curve on the risk of complications.
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
Regulatory Status
Endothelial keratoplasty is a surgical procedure and, as such, is not subject to regulation by the
U.S. Food and Drug Administration (FDA). Several microkeratomes have been cleared for
marketing by FDA through the 510(k) process.
Keratoprostheses
A keratoprosthesis is an artificial cornea that is intended to restore vision to patients with severe
bilateral corneal disease (such as prior failed corneal transplants, chemical injuries, or certain
immunologic conditions) for whom a corneal transplant is not an option.
The cornea, a clear, dome-shaped membrane that covers the front of the eye, is a key refractive
element of the eye. Layers of the cornea consist of the epithelium (outermost layer); Bowman’s
layer; the stroma, which comprises approximately 90% of the cornea; Descemet’s membrane;
and the endothelium. The established surgical treatment for corneal disease is penetrating
keratoplasty (PK), which involves making a large central opening through the cornea and then
filling the opening with full-thickness donor cornea. In certain conditions, such as StevensJohnson syndrome; cicatricial pemphigoid; chemical injury; or prior failed corneal transplant,
survival of transplanted cornea is poor. The keratoprosthesis has been developed to restore
vision in patients for whom a corneal transplant is not an option.
Keratoprosthetic devices consist of a central optic held in a cylindrical frame. The
keratoprosthesis replaces the section of cornea that has been removed, and, along with being
held in place by the surrounding tissue, may be covered by a membrane to further anchor the
prosthesis. A variety of biologic materials are being investigated to improve the integration of
prosthetic corneal implants into the stroma and other corneal layers.
The Dohlman-Doane keratoprosthesis, most commonly referred to as the Boston
Keratoprosthesis (KPro), is manufactured under the auspices of the Harvard Medical School‒
affiliated Massachusetts Eye and Ear Infirmary. The Boston type 1 KPro uses a donor cornea
between a central stem and a back plate. The Boston type 2 prosthesis is a modification of the
type 1 prosthesis and is designed with an anterior extension to allow implantation through
surgically closed eyelids. The AlphaCor, previously known as the Chirila keratoprosthesis
(Chirila KPro), consists of a polymethylmethacrylate (PMMA) device with a central optic region
fused to a surrounding sponge skirt; the device is inserted in a 2-stage surgical procedure.
Autologous keratoprostheses use a central PMMA optic supported by a skirt of either tibia bone
or the root of a tooth with its surrounding alveolar bone. The most common is the OOKP, which
uses osteodental lamina derived from an extracted tooth root and attached alveolar bone that has
been removed from the patient’s jaw. Insertion of the OOKP device requires a complex staged
procedure, in which the cornea is first covered with buccal mucosa. The prosthesis itself consists
of a PMMA optical cylinder, which replaces the cornea, and is held in place by a biological
support made from a canine tooth extracted from the recipient. A hole is drilled through the
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
dental root and alveolar bone, and the PMMA prosthesis is placed within. This entire unit is
placed into a subcutaneous ocular pocket and is then retrieved 6 to 12 months later for final
insertion.
Hydroxyapatite, with a similar mineral composition to both bone and teeth (phosphate and
calcium), may also be used as a bone substitute and as a bioactive prosthesis with the orbit.
Collagen coating and scaffolds have also been investigated to improve growth and
biocompatibility with the cornea epithelial cells, which form the protective layer of the eye.
Many of these materials and devices are currently being tested in vitro or in animal models.
Regulatory Status
A keratoprosthesis is considered a class II device by the U.S. Food and Drug Administration
(FDA) and is intended to provide a transparent optical pathway through an opacified cornea, in
an eye that is not a reasonable candidate for a corneal transplant. Two permanent
keratoprostheses, the Boston KPro (Dohlman-Doane keratoprosthesis) and the AlphaCor®
(Chirila keratoprosthesis), have been cleared for marketing by FDA through the 510(k) process.
Both devices are indicated as permanent implantable keratoprostheses for eyes that are not
corneal transplant candidates and are made of materials that have been proven to be
biocompatible. FDA determined that the AlphaCor keratoprosthesis was substantially
equivalent to the Dohlman-Doane type 1 keratoprosthesis. FDA product code: HQM
IV. RATIONALE
TOP
Endothelial Keratoplasty
Descemet Stripping Endothelial Keratoplasty and
Descemet Stripping Automated Endothelial Keratoplasty
A 2009 review, performed by the American Academy of Ophthalmology’s (AAO) Ophthalmic
Technology Assessment Committee, of the safety and efficacy of Descemet stripping automated
endothelial keratoplasty (DSAEK) identified 1 level I study (randomized controlled trial of
precut vs surgeon dissected) along with 9 level II (well-designed observational studies) and 21
level III studies (mostly retrospective case series).1 Although more than 2000 eyes treated with
DSAEK were reported in different publications, most were reported by 1 research group with
some overlap in patients. The main results from this review are as follows:
DSAEK-induced hyperopia ranged from 0.7 to 1.5 diopters (D), with minimal induction of
astigmatism (range, -0.4 to 0.6 D).
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
The reporting of visual acuity was not standardized in studies reviewed. The average bestcorrected visual acuity (BCVA) ranged from 20/34 to 20/66, and the percentage of
patients seeing 20/40 or better ranged from 38% to 100%.
The most common complication from DSAEK was posterior graft dislocation (mean, 14%;
range, 0%-82%), with a lack of adherence of the donor posterior lenticule to the recipient
stroma, typically occurring within the first week. It was noted that this percentage might
be skewed by multiple publications from 1 research group with low complication rates.
Graft dislocation required additional surgical procedures (rebubble procedures), but did
not lead to sight-threatening vision loss in the articles reviewed.
Endothelial graft rejection occurred in a mean of 10% of patients (range, 0%-45%); most
were reversed with topical or oral immunosuppression, with some cases progressing to
graft failure. Primary graft failure, defined as unhealthy tissue that has not cleared within
2 months, occurred in a mean of 5% of patients (range, 0%-29%). Iatrogenic glaucoma
occurred in mean of 3% of patients (range, 0%-15%) due to a pupil block induced from
the air bubble in the immediate postoperative period or delayed glaucoma from topical
corticosteroid adverse effects.
Endothelial cell loss, which provides an estimate of long-term graft survival, was on mean
37% at 6 months and 41% at 12 months. These percentages of cell loss were reported to
be similar to those observed with penetrating keratoplasty (PK).
The review concluded that DSAEK appeared to be at least equivalent to PK in terms of safety,
efficacy, surgical risks, and complication rates, although long-term results were not yet available.
The evidence also indicated that endothelial keratoplasty (EK) is superior to PK in terms of
refractive stability, postoperative refractive outcomes, wound- and suture-related complications,
and risk of intraoperative choroidal hemorrhage. The reduction in serious and occasionally
catastrophic adverse events associated with PK has led to the rapid adoption of EK for treatment
of corneal endothelial failure.
More recently, in 2016, Heinzelmann et al reported on outcomes in patients who underwent EK
or PK for Fuchs endothelial dystrophy or bullous keratopathy.2 The study included 89 eyes
undergoing DSAEK and 329 eyes undergoing PK. Postoperative visual improvement was faster
after EK than after PK. For example, among patients with Fuchs endothelial dystrophy, 50% of
patients achieved a BCVA of Snellen 6/12 or more 18 months after DSAEK versus more than 24
months after PK. Endothelial cell loss was similar after EK or PK in the early postoperative
period. However, after an early decrease, endothelial cell loss stabilized in patients who received
EK whereas the decrease continued in those who had PK. Among patients with Fuchs
endothelial dystrophy, there was a slightly increased risk of late endothelial failure in the first 2
years with EK than with PK. Graft failure was lower after bullous keratopathy than after Fuchs
endothelial dystrophy (numbers not reported).
Longer term outcomes were reported in several studies. Five-year outcomes from a prospective
study conducted at the Mayo Clinic were published in 2016 by Wacker et al.3 The study included
45 participants (52 eyes) with Fuchs endothelial corneal dystrophy who underwent Descemet
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
stripping endothelial keratoplasty (DSEK). Five-year follow-up was available for 34 (65%) eyes.
Mean high-contrast BCVA was 20/56 Snellen equivalent presurgery, and decreased to 20/25
Snellen equivalent at 60 months. The difference in high-contrast BCVA at 5 years versus
presurgery was statistically significant (p<0.001). Similarly, the proportion of those with BCVA
of 20/25 Snellen equivalent or better increased from 26% at 1 year postsurgery to 56% at 5 years
(p<0.001). There were 6 graft failures during the study period (4 failed to clear after surgery, 2
failed during follow-up). All patients with graft failures were regrafted.
Previously, in 2012, 3-year outcomes after DSAEK were reported by the Devers Eye Institute.4
This retrospective analysis included 108 patients who underwent DSAEK for Fuchs endothelial
dystrophy or pseudophakic bullous keratopathy and had no other ocular comorbidities. BCVA
was measured at 6 months and 1, 2, and 3 years. BCVA after DSAEK improved over the 3 years
of the study. For example, the percentage of patients who reached a BCVA of 20/20 or greater
was 0.9% at baseline, 11.1% at 6 months, 13.9% at 1 year, 34.3% at 2 years, and 47.2% at 3
years. Ninety-eight percent of patients reached a BCVA of 20/40 or greater by 3 years.
Descemet Membrane Endothelial Keratoplasty and
Descemet Membrane Automated Endothelial Keratoplasty
It has been suggested that by eliminating the stroma on the donor tissue, Descemet membrane
endothelial keratoplasty (DMEK) and Descemet membrane automated endothelial keratoplasty
(DMAEK) may reduce stromal interface haze and provide better visual acuity outcomes than
DSEK or DSAEK.5,6 Tourtas et al reported a retrospective comparison of 38 consecutive
patients/eyes that underwent DMEK versus 35 consecutive patients (35 eyes) who had
undergone DSAEK.7 Only patients with Fuchs endothelial dystrophy or pseudophakic bullous
keratopathy were included. After DMEK, 82% of eyes required rebubbling. After DSAEK, 20%
of eyes required rebubbling. BCVA in the 2 groups was comparable at baseline (DMEK=0.70
logMAR; DSAEK=0.75 logMAR). At 6-month follow-up, mean visual acuity improved to 0.17
logMAR after DMEK and 0.36 logMAR after DSAEK. This difference was statistically
significant. At 6 months following surgery, 95% of DMEK-treated eyes reached a visual acuity
of 20/40 or better and 43% of DSAEK-treated eyes reached a visual acuity of 20/40 or better.
Endothelial cell density decreased by a similar amount after the 2 procedures (41% after DMEK,
39% after DSAEK).
In 2013, van Dijk et al reported outcomes of their first 300 consecutive eyes treated with
DMEK.8 Indications for DMEK were Fuchs dystrophy, pseudophakic bullous keratopathy, failed
PK, or failed EK. Of the 142 eyes evaluated for visual outcome at 6 months, 79% reached a
BCVA of 20/25 or more and 46% reached a BCVA of 20/20 or more. Endothelial cell density
measurements at 6 months were available in 251 eyes. An average cell density was 1674
cells/mm2, representing a decrease of 34.6% from preoperative donor cell density. The major
postoperative complication in this series was graft detachment requiring rebubbling or regraft,
which occurred in 10.3% of eyes. Allograft rejection occurred in 3 eyes (1%) and intraocular
pressure (IOP) was increased in 20 (6.7%) eyes. Except for 3 early cases that may have been
prematurely regrafted, all but 1 eye with an attached graft cleared in 1 to 12 weeks.
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
A review of cases from another group in Europe suggested that a greater number of patients
achieve 20/25 vision or better with DMEK.9 Of the first 50 consecutive eyes, 10 (20%) required
a secondary DSEK for failed DMEK. For the remaining 40 eyes, 95% had a BCVA of 20/40 or
better, and 75% had a BCVA of 20/25 or better. Donor detachments and primary graft failure
with DMEK were problematic. In 2011, this group reported on the surgical learning curve for
DMEK, with their first 135 consecutive cases retrospectively divided into 3 subgroups of 45
eyes.10 Graft detachment was the most common complication, and decreased with experience. In
their first 45 cases, a complete or partial graft detachment occurred in 20% of cases, compared
with 13.3% in the second group and 4.4% in the third group. Clinical outcomes in eyes with
normal visual potential and a functional graft (n=110) were similar across the 3 groups, with an
average endothelial cell density of 1747 cells and 73% of cases achieving a BCVA of 20/25 or
better at 6 months.
A North American group reported 3-month outcomes from a prospective consecutive series of 60
cases of DMEK in 2009, and in 2011, they reported 1-year outcomes from these 60 cases plus an
additional 76 cases of DMEK.11,12 Preoperative BCVA averaged 20/65 (range of 20/20 to
counting fingers). Sixteen eyes were lost to follow-up and 12 (8.8%) grafts had failed. For the
108 grafts examined and found to be clear at 1 year, 98% achieved BCVA of 20/30 or better.
Endothelial cell loss was 31% at 3 months and 36% at 1 year. Although visual acuity outcomes
appeared to be improved over a DSAEK series from the same investigators, preparation of the
donor tissue and attachment of the endothelial graft were more challenging. A 2012 cohort study
by this group found reduced transplant rejection with DMEK.13 One (0.7%) of 141 patients in the
DMEK group had a documented episode of rejection compared with 54 (9%) of 598 in the
DSEK group and 5 (17%) of 30 in the PK group.
The same group also reported a prospective consecutive series of their initial 40 cases (36
patients) of DMAEK (microkeratome dissection and a stromal ring) in 2011.14 Indications for
EK were Fuchs endothelial dystrophy (87.5%), pseudophakic bullous keratopathy (7.5%), and
failed EK (5%). Air was reinjected in 10 (25%) eyes to promote graft attachment; 2 (5%) grafts
failed to clear and were successfully regrafted. Compared with a median BCVA of 20/40 at
baseline (range, 20/25 to 20/400), median BCVA at 1 month was 20/30 (range, 20/15 to 20/50).
At 6 months, 48% of eyes had 20/20 vision or better and 100% were 20/40 or better. Mean
endothelial cell loss at 6 months relative to baseline donor cell density was 31%.
Femtosecond Laser-Assisted Endothelial Keratoplasty
In 2009, Cheng et al reported a multicenter randomized trial from Europe that compared
femtosecond laser-assisted endothelial keratoplasty (FLEK) with PK.15 Eighty patients with
Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or posterior polymorphous
dystrophy, and a BCVA less than 20/50 were included in the study. In the FLEK group, 4 of the
40 eyes did not receive treatment due to significant preoperative events and were excluded from
the analysis. Eight (22%) of 36 eyes failed, and 2 patients were lost to follow-up due to death in
the FLEK group. One patient was lost to follow-up in the PK group due to health issues. At 12
months postoperatively, refractive astigmatism was lower in the FLEK group than in the PK
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
group (86% vs 51%, respectively, with astigmatism of 3 oculus dexter), but there was greater
hyperopic shift. Mean BCVA was better following PK than FLEK at 3-, 6-, and 12-month
follow-ups. There was greater endothelial cell loss in the FLEK group (65%) than in the PK
group (23%). With the exception of dislocation and need to reposition the FLEK grafts in 28% of
eyes, the percentage of complications was similar between groups. Complications in the FLEK
group were due to pupillary block, graft failure, epithelial ingrowth, and elevated IOP, whereas
complications in the PK group were related to the sutures and elevated IOP.
A small retrospective cohort study from 2013 found a reduction in visual acuity when the
endothelial transplant was prepared with laser (FLEK=0.48 logMAR; n=8) compared with
microtome (DSAEK=0.33 logMAR; n=14).16 There was also greater surface irregularity with
FLEK.
Ongoing and Unpublished Clinical Trials
Currently unpublished trials that might influence this review are listed in Table 1.
Table 1. Summary of Key Trials
NCT No.
Trial Name
Ongoing
NCT00800111
Study of Endothelial Keratoplasty Outcomes
NCT02470793
Technique and Results In Endothelial Keratoplasty (TREK)
NCT: national clinical trial.
Planned
Enrollment
Completion
Date
4000
100
Feb 2020
Dec 2025
Summary of Evidence
Endothelial keratoplasty (EK), also referred to as posterior lamellar keratoplasty, is a form of
corneal transplantation in which the diseased inner layer of the cornea, the endothelium, is
replaced with healthy donor tissue. Specific techniques include Descemet stripping endothelial
keratoplasty (DSEK), Descemet stripping automated endothelial keratoplasty (DSAEK),
Descemet membrane endothelial keratoplasty (DMEK), and Descemet membrane automated
endothelial keratoplasty (DMAEK). EK, and particularly DSEK, DSAEK, DMEK, and
DMAEK, are becoming standard procedures. Femtosecond laser-assisted corneal endothelial
keratoplasty (FLEK) and femtosecond and excimer lasers‒assisted endothelial keratoplasty
(FELEK) have also been reported as alternatives to prepare the donor endothelium.
The evidence for Descemet stripping endothelial keratoplasty, Descemet stripping automated
endothelial keratoplasty, Descemet membrane endothelial keratoplasty, and Descemet membrane
automated endothelial keratoplasty in individuals who have endothelial disease of the cornea
includes a number of cohort studies and a systematic review. Relevant outcomes are change in
disease status, morbid events, and functional outcomes. The available literature indicates that
these procedures improve visual outcomes and reduce serious complications associated with
penetrating keratoplasty (PK). Specifically, visual recovery occurs much earlier, and because
endothelial keratoplasty maintains an intact globe without a sutured donor cornea, astigmatism,
or the risk of severe, sight-threatening complications such as expulsive suprachoroidal
hemorrhage and postoperative catastrophic wound failure are eliminated. The evidence is
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sufficient to determine qualitatively that the technology results in a meaningful improvement in
the net health outcome.
The evidence for .femtosecond laser-assisted corneal endothelial keratoplasty (FLEK) and
femtosecond and excimer lasers‒assisted endothelial keratoplasty (FELEK) in individuals who
have endothelial disease of the cornea includes a multicenter randomized trial that compared
FLEK with PK. Relevant outcomes are change in disease status, morbid events, and functional
outcomes. Mean best-corrected visual acuity was worse after FLEK than after PK, and
endothelial cell loss was higher. With the exception of dislocation and need for repositioning of
the FLEK, the percentage of complications was similar between groups. Complications in the
FLEK group were due to pupillary block, graft failure, epithelial ingrowth, and elevated
intraocular pressure (IOP), whereas complications in the PK group were related to sutures and
elevated IOP. The evidence is insufficient to determine the effects of the technology on health
outcomes.
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process, through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
2013 Vetting
In response to requests, input was received through 3 physician specialty societies (2 reviewers)
and 3 academic medical centers while this policy was under review in 2013. Clinical input
uniformly considered DMEK and DMAEK to be medically necessary procedures, while most
input considered FLEK and FELEK to be investigational. Input was mixed on the exclusion of
patients with anterior corneal disease. Additional indications suggested by the reviewers were
added as medically necessary.
2009 Vetting
In response to requests, input was received through physician specialty societies (3 reviewers
representing 3 associated organizations) and 2 academic medical centers while this policy was
under review in 2009. Clinical input supported DSEK and DSAEK as the standard of care for
endothelial failure, due to improved outcomes compared to PK.
Practice Guidelines and Position Statements
American Academy of Ophthalmology
In 2009, the Health Policy Committee of the American Academy of Ophthalmology (AAO)
published a position paper on EK, stating that the optical advantages, speed of visual
rehabilitation, and lower risk of catastrophic wound failure have driven the adoption of EK as the
standard of care for patients with endothelial failure and otherwise healthy corneas. The AAO
position paper was based in large part on a comprehensive review of the literature on DSAEK by
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AAO’s Ophthalmic Technology Assessment Committee.1 This committee concluded that “the
evidence reviewed suggests DSAEK appears safe and efficacious for the treatment of endothelial
diseases of the cornea. Evidence from retrospective and prospective DSAEK reports described a
variety of complications from the procedure, but these complications do not appear to be
permanently sight threatening or detrimental to the ultimate vision recovery in the majority of
cases. Long-term data on endothelial cell survival and the risk of late endothelial rejection cannot
be determined with this review.” “DSAEK should not be used in lieu of PK for conditions with
concurrent endothelial disease and anterior corneal disease. These situations would include
concurrent anterior corneal dystrophies, anterior corneal scars from trauma or prior infection, and
ectasia after previous laser vision correction surgery.”
National Institute for Health and Clinical Excellence
The U.K.’s National Institute for Health and Clinical Excellence released guidance on corneal
endothelial transplantation in 2009.17 Additional data reviewed from the U.K. Transplant
Register showed lower graft survival rates after EK than after PK; however, the difference in
graft survival between the 2 procedures was noted to be narrowing with increased experience in
EK use. The guidance concluded that “current evidence on the safety and efficacy of corneal
endothelial transplantation (also known as endothelial keratoplasty [EK]) is adequate to support
the use of this procedure provided that normal arrangements are in place for clinical governance
and consent.” The guideline committee noted that techniques for this procedure continue to
evolve, and thorough data collection should continue to allow future review of outcomes.
U.S. Preventive Services Task Force Recommendations
Not applicable.
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage
decisions are left to the discretion of local Medicare carriers.
Keratoprosthesis
The most recent literature review was performed through February 8, 2016.
Assessment of efficacy for therapeutic interventions involves a determination of whether the
intervention improves health outcomes. The optimal study design for a therapeutic intervention
is a randomized controlled trial (RCT) that includes clinically relevant measures of health
outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also
be adequate if there is an established link between the intermediate outcome and true health
outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide
useful information on health outcomes, but are prone to biases such as noncomparability of
treatment groups, the placebo effect, and variable natural history of the condition.
The keratoprosthesis is intended for the relatively small number of patients with severe corneal
damage who have lost vision and for whom a corneal transplant is not expected to result in
satisfactory outcomes. These criteria generally refer to the population of patients who have failed
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1 or more corneal transplants and who therefore have very few options to prevent blindness.
Because this surgery is considered a salvage procedure with no acceptable alternative treatments,
comparative studies are limited and/or lacking. The available literature primarily consists of
retrospective case series. This evidence review examines the types of devices currently being
tested in humans, focusing on reports that allow assessment of integration within the eye,
durability, visual outcomes, and adverse events following implantation.
Boston (Dohlman-Doane) Keratoprosthesis (KPro)
A 2015 systematic review from the American Academy of Ophthalmology identified 22 studies
on the efficacy and safety of the Boston (Dohlman-Doane) Keratoprosthesis (Boston KPro).1
Studies were published in English and retrospective series needed to include at least 25 eyes. No
RCTs were identified. The proportion of patients with visual acuity of 20/200 after surgery
ranged from 54% to 84% in the 10 studies reporting this outcome. Five articles reported that
11% to 39% of treated eyes attained visual acuities of 20/40 or better. The review authors noted
that published data were skewed toward visual improvement. Fourteen articles reported retention
rates (eyes retaining the KPro device without loss, extrusion or dehiscence of the device), and
these rates ranged from 65% to 100% (mean, 88%). The most common reasons for KPro loss
were corneal melts with device exposure or extrusion, endophthalmitis, infectious keratitis, or
corneal ulceration. The most common complication was retroprosthetic membrane formation,
which ranged from 1% to 65% (mean, 30%) in the 13 studies reporting complications.
Representative larger series are described below.
A 2013 report from the Boston Type 1 Keratoprosthesis Study Group assessed retention of the
device in 300 eyes of 300 patients.2 At a mean follow-up duration of 17.1 months (range, 1 week
to 6 years), 93% of the keratoprostheses were retained. The probability of retention was 94% at 1
year and 89% at 2 years. Mean device durability was 3.8 years. Risk factors for keratoprosthesis
loss were autoimmune disease, ocular surface exposure, and number of prior failed penetrating
keratoplasties (PKs). Additional data on this cohort were published in 2016.3 Preoperative visual
acuity, available for 47% of eyes was 20/1205. During a mean follow-up of 17 months (range, 1
week to 6 years), visual acuity improved significantly for 85% of eyes to a final mean of 20/150.
Median time to achieve visual acuity of 20/200 was 1 month, and this level of acuity lasted for a
mean of 48 months among patients with sufficient follow-up.
In 2014, Srikumaran et al reported mean follow-up of 46.7 months (range, 6 weeks to 8.7 years)
on 139 eyes of 133 patients who had received a Boston KPro at 1 of 5 tertiary referral centers in
the United States.4 Twenty-seven percent of eyes underwent a primary KPro procedure while
73% had a prior donor graft failure. Postoperatively, visual acuity improved to at least 20/200 in
70% of eyes. The probability of maintaining visual acuity of at least 20/200 was 50%, and device
retention was estimated at 67% at 7 years. The 7-year cumulative incidence of complications was
49.7% for retroprosthetic membrane formation, 21.6% for glaucoma surgery, 18.6% for retinal
detachment, and 15.5% for endophthalmitis.
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In 2010, Dunlap et al reported a retrospective analysis of 122 patients (126 eyes) at 2 centers
who received a Boston type 1 keratoprosthesis between 2004 and 2007.5 For most patients, the
affected eye had a visual acuity of less than 20/400, and the contralateral eye did not have better
vision. Of the 126 eyes, 112 had a history of multiple failed corneal grafts, and 14 had received
the keratoprosthesis as a primary procedure due to the presence of limbal stem cell deficiency or
significant ocular surface diseases. Following implantation, 96 (76%) eyes had improved vision,
22 (17.4%) eyes did not improve, and 8 (6.3%) eyes lost vision. At 3-month follow-up, 54% of
eyes had 20/200 vision or better, with 18% achieving 20/40 or better. In approximately 45% of
the eyes, visual acuity remained less than 20/400. The percentage of patients with improved
visual outcomes was lower than in other published studies, due in part to the presence of
comorbid conditions (e.g., glaucoma, retinal detachment).
Indications
A 2009 study reported expanding indications and outcomes from a consecutive series of 50 eyes
of 49 patients implanted with the Boston type 1 keratoprosthesis and a donor cornea.6 Thirty-one
percent of patients had good preoperative vision (visual acuity of 20/40 or better) in the
contralateral eye. Study inclusion criteria for keratoprosthesis implantation were: visually
significant corneal opacification (best-corrected visual acuity [BCVA] ≤20/200); poor candidacy
for repeat corneal transplantation because of a history of 2 or more failed transplantations,
extensive corneal limbal stem cell failure with or without corneal vascularization and scarring, or
both; and adequate visual potential for meaningful visual restoration. Exclusion criteria were:
adequate potential for a successful outcome after PK; the presence of a comorbid ocular
condition associated with a minimal chance of recovering meaningful vision (e.g., chronic retinal
detachment, near end-stage glaucoma); the presence of comorbid ocular conditions associated
with an unacceptably high risk of postoperative complications (e.g., inadequate eyelid function,
severe ocular surface desiccation, ocular surface keratinization, recalcitrant intraocular
inflammation, patient inability or unwillingness to comply with the routine postoperative
regimen, combination thereof). Of the 50 eyes implanted with the Boston KPro, 42 had a history
of prior corneal transplantation, varying between 1 and 5 prior transplantations (mean, 2.3).
Preoperative visual acuity was 20/200 or worse in all eyes, with vision of counting fingers, hand
movements, or light perception in 42 (88%) eyes. Glaucoma was present in 38 (76%) eyes, and
tube shunt implantation was performed simultaneously with keratoprosthesis implantation in
45% of the eyes with glaucoma. A total of 57 Boston type 1 KPro devices were implanted in 50
eyes. Two eyes were excluded (1 patient died, 1 replacement of a type 1 KPro with a type 2
KPro). Nine of the 57 keratoprostheses implanted were removed, resulting in a retention rate of
84% during an average follow-up of 17 months (range, 3-49 months). Three of the 9 were
removed in the first 6 months after surgery, and 5 were removed between 1 and 2 years after
surgery. Final postoperative vision was improved over preoperative vision in 38 (79%) eyes, was
unchanged in 9 (9%) eyes, and decreased in 1 (2%) eye (from counting fingers preoperatively to
light perception postoperatively). The percentage of eyes with postoperative visual acuity of
20/100 or better was 75% of 28 eyes followed up to 1 year, 69% of 13 eyes at 2 years, and all of
the 7 eyes followed up for at least 3 years. In 38 (76%) eyes, 1 or more postoperative
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complications developed. The most common postoperative complications were retroprosthetic
membrane formation (44% of eyes) and persistent epithelial defects (38% of eyes). This detailed
report provides information on visual outcomes and complications in a well-described patient
population. The major limitation of this study is the small number of subjects who were followed
beyond 6 months.
Use of the Boston KPro has been reported in patients with herpetic keratitis, autoimmune
disease, aniridia, atopic keratoconjunctivitis, medication toxicity, and other corneal dystrophies.7
Use has also been reported in children. The device has a lower retention rate (i.e., eyes retaining
the device without loss, extrusion or dehiscence) when used to treat highly inflammatory,
cicatricial, and autoimmune ocular disorders. Other studies have also reported success in patients
with severe ocular trauma (e.g., mechanical trauma, chemical burns, thermal burns).8
Also reported is use of the KPro as a primary treatment in eyes with little or no chance of success
with PK.9-11 For example, in a study by Kang et al, the most common preoperative diagnosis was
primary or secondary limbal stem cell disease (71.4%), including chemical/thermal injury
(28.6%), aniridia (23.8%), and Stevens-Johnson syndrome (4.8%).9 Retention rate of the
keratoprosthesis was 90.5% at a mean follow-up of 14.6 months (range, 6-36.3 months). In
another series reporting on KPro as primary treatment in patients at high risk of failing PK, 37
(86%) of 43 eyes had corneal scarring with vascularization, and the most common underlying
etiology was aniridic keratopathy (11/37 [27%] eyes).10
A 2016 systematic review by Ahmad et al examined 26 studies on repeat PK versus Boston KPro
implantation after failed PK.12 Studies included focused on patients with corneal opacity who
had failed 1 or more PKs. Studies were excluded if only selected patients with ocular surface
disease. The primary outcome of interest was the proportion of patients with visual acuity of
20/200 or better at 2 or more years postsurgery. In a meta-analysis of 9 studies, the likelihood of
20/200 vision or better at least 2 years after repeat PK surgery was 42% (95% confidence
interval [CI], 30% to 56%). A total of 104 eyes from 98 patients underwent KPro after failed PK
surgery; 31 patients had only 1 previous PK. In a meta-analysis of data on KPro implantation
after failed PK surgery, the probability of maintaining visual acuity of 20/200 or better at 2 years
was 80% (95% CI, 68% to 88%). Among patients with a history of 1 failed PK, the probability
of maintaining a visual acuity of 20/200 or better at 2 years was 74% (95% CI, 45% to 89%).
(The authors did not specify the number of patients receiving KPro who were included in the
analysis of 20/200 vision at 2 years.) In terms of complications after KPro following failed PK,
at 2 years 29% of patients had elevated intraocular pressure (IOP) and 8% needed surgery for
glaucoma. In an analysis limited to patients undergoing KPro after 1 failed KP, complication
rates were 29% and 10%, respectively (which did not differ significantly from patients with
KPro after >1 failed KPs). The authors did not report the number of patients included in the
complication analyses.
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Complications
In 2015, Odorcic et al published a literature review on fungal infections after Boston type 1
KPro.13 The authors identified 15 relevant publications, primarily retrospective case series. Rates
of fungal infections reported in these studies ranged from 0.009 to 0.02 per patient-year of
follow-up. The largest case series assessed 291 eyes, and the incidence of fungal endophthalmitis
was 2.4% over 10 years.
Longer term vision outcomes and complications with the Boston type 1 KPro were reported by
Greiner et al in 2011.14 Included in the series were 40 eyes of 35 patients who received a Boston
KPro between 2004 and 2010 at the authors’ institution. Preoperative diagnoses included failed
corneal transplants (47.5%), chemical injury (25%), and aniridia (12.5%). Preoperative visual
acuity ranged from 20/150 to light perception and was 20/400 or less in 38 eyes (95%). Followup evaluations were performed at 1, 3, 6, 9, and 12 months and then annually, with a mean
follow-up duration of 33.6 months (range, 5-72 months). Of 36 eyes followed for at least 1 year,
32 (89%) achieved postoperative BCVA of 20/200 or more. The percentage of eyes that retained
BCVA of 20/200 or more was 59% (19/32) at 1 year, 59% (16/27) at 2 years, 50% (7/14) at 3
years, and 29% (2/7) at 4 years or longer. The most common reason for vision loss (54% [7/13]
eyes when BCVA ≥20/200 was not retained) was end-stage glaucoma. Other complications
included glaucoma drainage device erosion (22.5%), retroprosthetic membrane formation (55%),
endophthalmitis (12.5%), and corneal melt (15%).
In a separate publication, this group of investigators reported that in 25 eyes implanted with both
the Boston type 1 KPro and glaucoma drainage devices, conjunctival breakdown occurred in 10
implants in 9 eyes.15 The authors noted that glaucoma is one of the most difficult postoperative
management challenges in patients with a Boston type 1 keratoprosthesis.
A prospective series of 265 eyes (265 patients) from 18 medical centers, published by the Boston
Type 1 Keratoprosthesis Study Group in 2012, focused on the time to development of
retroprosthetic membranes.16 Most eyes (85.4%) had undergone an average of 2.2 (range, 1-8)
PKs before keratoprosthesis implantation. The remaining eyes (14.6%) were considered at high
risk for PK failure and had received a primary keratoprosthesis. At a mean follow-up of 17.8
months, retroprosthetic membranes had formed in 31.7% of eyes. The mean time to development
of retroprosthetic membranes was 216.7 days (range, 7 days to 4 years). Risk factors were the
indication for the keratoprosthesis; specifically, infectious keratitis had a hazard ratio of 3.20 and
aniridia had a hazard ratio of 3.13.
Posterior segment complications were reported by Goldman et al in 2013.17 Of 83 eyes (93
procedures) with follow-up of at least 6 months (range, 6-84 months), 38 (40.9%) eyes had at
least 1 postoperative posterior segment complication, which included retinal detachment
(16.9%), choroidal detachment (16.9%), and sterile vitritis (14.5%). Visual acuity was worse in
eyes that experienced posterior segment complications than in eyes that did not. Pujari et al
reported outcomes from 29 eyes of 26 patients who received the Boston type 2 keratoprosthesis
between 2000 and 2009 at the Massachusetts Eye and Ear Infirmary.18 Preoperative diagnoses
were mucous membrane pemphigoid (51.7%), Stevens-Johnson syndrome and toxic epidermal
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necrolysis (41.4%), and other ocular surface disease (6.9%). In patients who had more than 1
year of follow-up (mean, 3.7 years), loss of visual acuity occurred due to retinal detachment
(17.4%), end-stage glaucoma (8.7%), choroidal detachment (8.7%), endophthalmitis (4.3%), and
unknown cause (21.7%). Fourteen (48.3%) eyes required treatment for retroprosthetic
membranes. Of the 29 eyes, 12 (41.4%) either underwent reimplantation of the device or
experienced partial or total extrusion of the keratoprosthesis during follow-up (hazard ratio, 0.11
per person-year).
Keratoprosthesis Other Than the Boston KPro
Osteo-Odonto-Keratoprosthesis
A 2012 systematic review by Tan et al included 8 case series describing surgical outcomes and
complication rates of the osteo-odonto-keratoprosthesis (OOKP).19 Sample sizes ranged from 4
to 181 eyes. At 5 years, the pooled anatomic survival rate was 87.8% (range, 67%-100%) and, at
20 years, based on pooled data from 3 series, the anatomic survival rate was 81.0% (range, 65%98%). About half of the patients obtained visual acuity better than 6/18. Visual acuity in the
other patients was not described.
The largest case series (included in Tan) is by Falcinelli et al who reported on OOKP in 181
patients.20 At a median follow-up of 12 years, survival analysis estimated that the probability of
retaining an anatomically intact OOKP 18 years after surgery with reasonable visual acuity was
85%.
In 2008, investigators from Spain published a retrospective review (also in Tan) of 227 patients
who underwent OOKP (n=145), or osteokeratoprosthesis (OKP; n=82) using tibial bone in
patients who lacked canine teeth to assemble the prosthesis.21 A second publication in 2011 from
the same study examined the impact of clinical factors on long-term functional and anatomic
outcomes.22 The primary diagnosis was chemical or thermal burn (48%), Steven-Johnson
syndrome and Lyell syndrome (13%), cicatricial pemphigoid (11%), trachoma (11%), and 17%
other or not assignable. Mean preoperative decimal BCVA was 0.00062 (range, light perception
to 0.10). (On the decimal visual acuity scale, 0 = no light perception, 0.00001 = light perception,
0.0001 = light projection, and 0.001 = counting fingers.) Functional survival was defined as
BCVA of 0.05 or more, and anatomic survival as retention of the keratoprosthesis lamina. Mean
follow-up was 8.4 years for OOKP and 3.5 years for OKP. Anatomic success at 10 years was
estimated to be 66% for OOKP and 47% for OKP. Functional success at 10 years was estimated
to be 38% for OOKP and 17% for OKP. The best functional survival was in the Stevens-Johnson
group, followed by chemical burn and trachoma. The least favorable prognosis was thermal burn.
Complications included extrusion of the keratoprosthesis (28%), retinal detachment (16%),
uncontrolled glaucoma (11%), infection (9%), retroprosthetic membrane (5%), and vitreous
hemorrhage (3%). In cases without complications, functional survival was 57% at 5 years and
42% at 10 years.
Hughes et al reported vitreoretinal complications of the OOKP in a retrospective review of 35
patients performed at 1 hospital in England between 1996 and 2005.23 Diagnoses were StevensPage 18
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Johnson syndrome in 15 patients, chemical injury in 5, mucous membrane pemphigoid in 3, and
topical medication toxicity in 3. Follow-up at a mean 57 months (range, 13-105 months) revealed
9 vitreoretinal complications in 8 (23%) patients, which included vitreous hemorrhage, retinal
detachment, and intraoperative choroidal hemorrhage. A 2008 publication of 36 patients treated
at the same hospital between 1996 and 2006 (likely to have reported patients assessed by
Hughes23) estimated that the probability of retaining visual acuity was 53% at 5 years and 44% at
9 years.24 In addition to the vitreoretinal complications causing loss of vision, resorption of the
bony lamina led to visual or anatomic compromise in 7 (19%) cases.
AlphaCor Device
Studies have suggested that, with the AlphaCor device, thinning or “melting” of the anterior
corneal surface can lead to loss of biointegration.25,26 This complication appears most prevalent
in patients with ocular herpes, hence, the AlphaCor device is contraindicated in these patients. In
a 2003 case series, 42% of eyes had a visual acuity better than 20/200 at an average 30-month
follow-up.25 An additional case series, evaluating the AlphaCor device implanted in 12 patients
was published in 2015.27 At a mean follow-up of 25 months, 8 (67%) of devices were retained
and patients had a mean gain in BCVA of 2.5 lines. The most common complication was corneal
necrosis, observed in 7 (59%) patients, 2 of whom had a history of ocular herpes.
BIOKOP Device
The BIOKOP device is similar to the AlphaCor device in that it uses a microporous polymer to
promote host tissue integration. However, follow-up results for this device have been
disappointing. In 1 case series of 11 patients with 5-year follow-up, the authors concluded that
the BIOKOP keratoprosthesis was only able to restore vision for a short postoperative period.28
Limited success was due to device instability and postoperative complications.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 1.
Table 1. Summary of Key Trials
NCT No.
Trial Name
Planned
Enrollment
Completion
Date
60
Mar
2017
Ongoing
NCT02084745
Timing of Glaucoma Drainage Device With
Boston KPro Surgery (GDD-KPro)
NCT: national clinical trial.
Summary of Evidence
The evidence for Boston Keratoprosthesis in individuals who have corneal blindness and failed
or are not candidates for corneal transplantation includes case series and systematic reviews.
Relevant outcomes are change in disease status, morbid events, quality of life, and treatmentrelated morbidity. Systematic reviews and case series with longer follow-up (i.e., at least 2 years)
have shown improvement in visual outcomes in a substantial percentage of patients with Boston
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KPro. This procedure is high risk and is associated with numerous complications (e.g., growth of
retro prosthetic membranes) and a probable need for additional surgery, thus careful patient
selection is important. The evidence is sufficient to determine qualitatively that the technology
results in a meaningful improvement in the net health outcome.
The evidence for a keratoprosthesis other than the Boston KPro in individuals who have corneal
blindness and failed or are not candidates for corneal transplantation includes case series and
systematic reviews. Relevant outcomes are change in disease status, morbid events, quality of
life, and treatment-related morbidity. The data are more limited for devices other than the Boston
KPro. Available evidence suggests that complications with other keratoprosthesis designs are
worse than those associated with the Boston KPro. The evidence is insufficient to determine the
effects of the technology on health outcome.
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process, through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
In response to requests, input was received from 1 specialty society and 4 academic medical
centers while this policy was under review in 2009. Reviewers generally supported a limited role
for the Boston KPro in selected patients. Some reviewers recommended use without first
attempting a transplant under specific conditions that have a poor prognosis for corneal
transplant; however, other input found this controversial. Some reviewers recommended use only
in patients with limited visual acuity in the contralateral eye. Overall, input indicated that the
Boston KPro should be reserved for cases in which no other alternative (i.e., corneal
transplantation) is available for treatment of corneal opacification.
Practice Guidelines and Position Statements
In 2004, the U.K.’s National Institute for Health and Care Excellence (NICE) concluded that
“Current evidence on the safety and efficacy of insertion of hydrogel keratoprosthesis does not
appear adequate for this procedure to be used without special arrangements for consent and for
audit or research.”29 NICE has not updated this guidance.
U.S. Preventive Services Task Force Recommendations
Not applicable.
Medicare National Coverage
There is no Medicare national coverage policy. In 2006, Medicare has established an
Ambulatory Payment Classification 0293 for level V anterior segment eye procedures that
includes CPT code 65770 (keratoprosthesis) and a HCPCS code for the prosthesis (C1818 integrated keratoprosthesis OR L8609 - artificial cornea).30
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V. DEFINITIONS
TOP
APHAKIA is a condition in which part or all of the crystalline lens of the eye is absent, due to
a congenital defect or because it has been surgically removed, as in the treatment of cataracts.
CORNEA is the transparent anterior portion of the sclera (the fibrous outer layer of the eyeball);
it is a key refractive element of the eye. Layers of the cornea consist of the epithelium
(outermost layer); Bowman’s layer; the stroma, which comprises approximately 90% of the
cornea; Descemet’s membrane; and the endothelium.
MYOPIA is an error in refraction in which light rays are focused in front of the retina, enabling
the person to see distinctly for only a short distance.
STROMA refers to the supporting tissue or the matrix of an organ.
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under
the member's contract. Benefit determinations should be based in all cases on the applicable
contract language. Medical policies do not constitute a description of benefits. A member’s
individual or group customer benefits govern which services are covered, which are excluded,
and which are subject to benefit limits and which require preauthorization. Members and
providers should consult the member’s benefit information or contact Capital for benefit
information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider
and consult their benefit information to determine if the service is covered. If there is a discrepancy between this
medical policy and a member’s benefit information, the benefit information will govern. Capital considers the
information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by the
terms of member benefit information. In addition, not all covered services are eligible for separate
reimbursement.
Page 21
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
Investigational; therefore not covered:
HCPCS
Code
L8609
Description
Artificial cornea
Investigational; therefore not covered:
CPT Codes®
0290T
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
Covered when medically necessary:
CPT Codes®
65710
65730
65750
65755
65756
65757
65770
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
HCPCS
Code
C1818
Description
Integrated keratoprosthesis
ICD-10-CM
Diagnosis
Codes*
A18.52
A18.59
A54.33
B00.52
B02.33
B05.81
B30.0
B60.13
H16.001
H16.002
H16.003
H16.011
H16.012
H16.013
H16.021
H16.022
H16.023
Description
Tuberculous keratitis
Other tuberculosis of eye
Gonococcal keratitis
Herpes viral keratitis
Zoster keratitis
Measles keratitis and keratoconjunctivitis
Keratoconjunctivitis due to adenovirus
Keratoconjunctivitis due to Acanthamoeba
Unspecified corneal ulcer, right eye
Unspecified corneal ulcer, left eye
Unspecified corneal ulcer, bilateral
Central corneal ulcer, right eye
Central corneal ulcer, left eye
Central corneal ulcer, bilateral
Ring corneal ulcer, right eye
Ring corneal ulcer, left eye
Ring corneal ulcer, bilateral
Page 22
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
H16.031
H16.032
H16.033
H16.041
H16.042
H16.043
H16.051
H16.052
H16.053
H16.061
H16.062
H16.063
H16.071
H16.072
H16.073
H16.301
H16.302
H16.303
H16.311
H16.312
H16.313
H16.321
H16.322
H16.323
H16.331
H16.332
H16.333
H16.391
H16.392
H16.393
H16.401
H16.402
H16.403
H16.411
H16.412
H16.413
H16.421
H16.422
H16.423
Description
Corneal ulcer with hypopyon, right eye
Corneal ulcer with hypopyon, left eye
Corneal ulcer with hypopyon, bilateral
Marginal corneal ulcer, right eye
Marginal corneal ulcer, left eye
Marginal corneal ulcer, bilateral
Mooren's corneal ulcer, right eye
Mooren's corneal ulcer, left eye
Mooren's corneal ulcer, bilateral
Mycotic corneal ulcer, right eye
Mycotic corneal ulcer, left eye
Mycotic corneal ulcer, bilateral
Perforated corneal ulcer, right eye
Perforated corneal ulcer, left eye
Perforated corneal ulcer, bilateral
Unspecified interstitial keratitis, right eye
Unspecified interstitial keratitis, left eye
Unspecified interstitial keratitis, bilateral
Corneal abscess, right eye
Corneal abscess, left eye
Corneal abscess, bilateral
Diffuse interstitial keratitis, right eye
Diffuse interstitial keratitis, left eye
Diffuse interstitial keratitis, bilateral
Sclerosing keratitis, right eye
Sclerosing keratitis, left eye
Sclerosing keratitis, bilateral
Other interstitial and deep keratitis, right eye
Other interstitial and deep keratitis, left eye
Other interstitial and deep keratitis, bilateral
Unspecified corneal neovascularization, right eye
Unspecified corneal neovascularization, left eye
Unspecified corneal neovascularization, bilateral
Ghost vessels (corneal), right eye
Ghost vessels (corneal), left eye
Ghost vessels (corneal), bilateral
Pannus (corneal), right eye
Pannus (corneal), left eye
Pannus (corneal), bilateral
Page 23
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
H16.431
H16.432
H16.433
H16.441
H16.442
H16.443
H16.8
H16.9
H17.01
H17.02
H17.03
H17.11
H17.12
H17.13
H17.811
H17.812
H17.813
H17.821
H17.822
H17.823
H17.89
H17.9
H18.001
H18.002
H18.003
H18.011
H18.012
H18.013
H18.021
H18.022
H18.023
H18.031
H18.032
H18.033
H18.041
H18.042
H18.043
H18.051
H18.052
Description
Localized vascularization of cornea, right eye
Localized vascularization of cornea, left eye
Localized vascularization of cornea, bilateral
Deep vascularization of cornea, right eye
Deep vascularization of cornea, left eye
Deep vascularization of cornea, bilateral
Other keratitis
Unspecified keratitis
Adherent leukoma, right eye
Adherent leukoma, left eye
Adherent leukoma, bilateral
Central corneal opacity, right eye
Central corneal opacity, left eye
Central corneal opacity, bilateral
Minor opacity of cornea, right eye
Minor opacity of cornea, left eye
Minor opacity of cornea, bilateral
Peripheral opacity of cornea, right eye
Peripheral opacity of cornea, left eye
Peripheral opacity of cornea, bilateral
Other corneal scars and opacities
Unspecified corneal scar and opacity
Unspecified corneal deposit, right eye
Unspecified corneal deposit, left eye
Unspecified corneal deposit, bilateral
Anterior corneal pigmentations, right eye
Anterior corneal pigmentations, left eye
Anterior corneal pigmentations, bilateral
Argentous corneal deposits, right eye
Argentous corneal deposits, left eye
Argentous corneal deposits, bilateral
Corneal deposits in metabolic disorders, right eye
Corneal deposits in metabolic disorders, left eye
Corneal deposits in metabolic disorders, bilateral
Kayser-Fleischer ring, right eye
Kayser-Fleischer ring, left eye
Kayser-Fleischer ring, bilateral
Posterior corneal pigmentations, right eye
Posterior corneal pigmentations, left eye
Page 24
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
H18.053
H18.061
H18.062
H18.063
H18.11
H18.12
H18.13
H18.20
H18.211
H18.212
H18.213
H18.221
H18.222
H18.223
H18.231
H18.232
H18.233
H18.30
H18.311
H18.312
H18.313
H18.321
H18.322
H18.323
H18.331
H18.332
H18.333
H18.40
H18.411
H18.412
H18.413
H18.421
H18.422
H18.423
H18.43
H18.441
H18.442
H18.443
H18.451
Description
Posterior corneal pigmentations, bilateral
Stromal corneal pigmentations, right eye
Stromal corneal pigmentations, left eye
Stromal corneal pigmentations, bilateral
Bullous keratopathy, right eye
Bullous keratopathy, left eye
Bullous keratopathy, bilateral
Unspecified corneal edema
Corneal edema secondary to contact lens, right eye
Corneal edema secondary to contact lens, left eye
Corneal edema secondary to contact lens, bilateral
Idiopathic corneal edema, right eye
Idiopathic corneal edema, left eye
Idiopathic corneal edema, bilateral
Secondary corneal edema, right eye
Secondary corneal edema, left eye
Secondary corneal edema, bilateral
Unspecified corneal membrane change
Folds and rupture in Bowman's membrane, right eye
Folds and rupture in Bowman's membrane, left eye
Folds and rupture in Bowman's membrane, bilateral
Folds in Descemet's membrane, right eye
Folds in Descemet's membrane, left eye
Folds in Descemet's membrane, bilateral
Rupture in Descemet's membrane, right eye
Rupture in Descemet's membrane, left eye
Rupture in Descemet's membrane, bilateral
Unspecified corneal degeneration
Arcus senilis, right eye
Arcus senilis, left eye
Arcus senilis, bilateral
Band keratopathy, right eye
Band keratopathy, left eye
Band keratopathy, bilateral
Other calcerous corneal degeneration
Keratomalacia, right eye
Keratomalacia, left eye
Keratomalacia, bilateral
Nodular corneal degeneration, right eye
Page 25
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
H18.452
H18.453
H18.461
H18.462
H18.463
H18.49
H18.50
H18.51
H18.52
H18.53
H18.54
H18.55
H18.59
H18.601
H18.602
H18.603
H18.611
H18.612
H18.613
H18.621
H18.622
H18.623
H18.70
H18.711
H18.712
H18.713
H18.721
H18.722
H18.723
H18.731
H18.732
H18.733
H18.791
H18.792
H18.793
H18.831
H18.832
H18.833
Q13.3
Description
Nodular corneal degeneration, left eye
Nodular corneal degeneration, bilateral
Peripheral corneal degeneration, right eye
Peripheral corneal degeneration, left eye
Peripheral corneal degeneration, bilateral
Other corneal degeneration
Unspecified hereditary corneal dystrophies
Endothelial corneal dystrophy
Epithelial (juvenile) corneal dystrophy
Granular corneal dystrophy
Lattice corneal dystrophy
Macular corneal dystrophy
Other hereditary corneal dystrophies
Keratoconus, unspecified, right eye
Keratoconus, unspecified, left eye
Keratoconus, unspecified, bilateral
Keratoconus, stable, right eye
Keratoconus, stable, left eye
Keratoconus, stable, bilateral
Keratoconus, unstable, right eye
Keratoconus, unstable, left eye
Keratoconus,
Unspecified corneal deformity
Corneal ectasia, right eye
Corneal ectasia, left eye
Corneal ectasia, bilateral
Corneal staphyloma, right eye
Corneal staphyloma, left eye
Corneal staphyloma, bilateral
Descemetocele, right eye
Descemetocele, left eye
Descemetocele, bilateral
Other corneal deformities, right eye
Other corneal deformities, left eye
Other corneal deformities, bilateral
Recurrent erosion of cornea, right eye
Recurrent erosion of cornea, left eye
Recurrent erosion of cornea, bilateral
Congenital corneal opacity
Page 26
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
Q13.4
S05.10XA
S05.10XD
S05.11XA
S05.11XD
S05.12XA
S05.12XD
T26.11XA
T26.11XD
T26.12XA
T26.12XD
T85.318A
T85.318D
T85.328A
T85.328D
T85.398A
T85.398D
T85.72XA
T85.79XA
T85.79XD
T85.848A
T85.848D
T85.848S
T85.890A
T85.890D
T85.898A
T85.898D
T86.840
Description
Other congenital corneal malformations
Contusion of eyeball and orbital tissues, unspecified eye, initial encounter
Contusion of eyeball and orbital tissues, unspecified eye, subsequent encounter
Contusion of eyeball and orbital tissues, right eye, initial encounter
Contusion of eyeball and orbital tissues, right eye, subsequent encounter
Contusion of eyeball and orbital tissues, left eye, initial encounter
Contusion of eyeball and orbital tissues, left eye, subsequent encounter
Burn of cornea and conjunctival sac, right eye, initial encounter
Burn of cornea and conjunctival sac, right eye, subsequent encounter
Burn of cornea and conjunctival sac, left eye, initial encounter
Breakdown (mechanical) of other ocular prosthetic devices, implants and grafts,
subsequent encounter
Breakdown (mechanical) of other ocular prosthetic devices, implants and grafts, initial
encounter
Breakdown (mechanical) of other ocular prosthetic devices, implants and grafts,
subsequent encounter
Displacement of other ocular prosthetic devices, implants and grafts, initial encounter
Displacement of other ocular prosthetic devices, implants and grafts, subsequent
encounter
Other mechanical complication of other ocular prosthetic devices, implants and grafts,
initial encounter
Other mechanical complication of other ocular prosthetic devices, implants and grafts,
subsequent encounter
Infection and inflammatory reaction due to insulin pump, initial encounter
Infection and inflammatory reaction due to other internal prosthetic devices, implants and
grafts, initial
Infection and inflammatory reaction due to other internal prosthetic devices, implants and
grafts, subsequent encounter
Pain due to other internal prosthetic devices, implants and grafts, initial encounter
Pain due to other internal prosthetic devices, implants and grafts, subsequent encounter
Pain due to other internal prosthetic devices, implants and grafts, sequela
Other specified complication of nervous system prosthetic devices, implants and grafts,
initial encounter
Other specified complication of nervous system prosthetic devices, implants and grafts,
subsequent encounter
Other specified complication of other internal prosthetic devices, implants and grafts,
initial encounter
Other specified complication of other internal prosthetic devices, implants and grafts,
subsequent encounter
Corneal transplant rejection
Page 27
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
ICD-10-CM
Diagnosis
Codes*
T86.841
T86.842
T86.90
T86.91
T86.92
T86.93
T86.99
Z94.7
Description
Corneal transplant failure
Corneal transplant infection
Unspecified complication of unspecified transplanted organ and tissue
Unspecified transplanted organ and tissue rejection
Unspecified transplanted organ and tissue failure
Unspecified transplanted organ and tissue infection
Other complications of unspecified transplanted organ and tissue
Corneal transplant status
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
IX. REFERENCES
TOP
Endothelial Keratoplasty
1. Lee WB, Jacobs DS, Musch DC, et al. Descemet's stripping endothelial keratoplasty: safety
and outcomes: a report by the American Academy of Ophthalmology. Ophthalmology. Sep
2009;116(9):1818-1830. PMID 19643492
2. Heinzelmann S, Bohringer D, Eberwein P, et al. Outcomes of Descemet membrane
endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and
penetrating keratoplasty from a single centre study. Graefes Arch Clin Exp Ophthalmol. Jan
7 2016. PMID 26743748
3. Wacker K, Baratz KH, Maguire LJ, et al. Descemet stripping endothelial keratoplasty for
fuchs' endothelial corneal dystrophy: five-year results of a prospective study.
Ophthalmology. Jan 2016;123(1):154-160. PMID 26481820
4. Li JY, Terry MA, Goshe J, et al. Three-year visual acuity outcomes after Descemet's
stripping automated endothelial keratoplasty. Ophthalmology. Jun 2012;119(6):1126-1129.
PMID 22364863
5. Dapena I, Ham L, Melles GR. Endothelial keratoplasty: DSEK/DSAEK or DMEK--the
thinner the better? Curr Opin Ophthalmol. Jul 2009;20(4):299-307. PMID 19417653
6. Rose L, Kelliher C, Jun AS. Endothelial keratoplasty: historical perspectives, current
techniques, future directions. Can J Ophthalmol. Aug 2009;44(4):401-405. PMID 19606160
7. Tourtas T, Laaser K, Bachmann BO, et al. Descemet membrane endothelial keratoplasty
versus descemet stripping automated endothelial keratoplasty. Am J Ophthalmol. Jun
2012;153(6):1082-1090 e1082. PMID 22397955
Page 28
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
8. van Dijk K, Ham L, Tse WH, et al. Near complete visual recovery and refractive stability in
modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
Cont Lens Anterior Eye. Feb 2013;36(1):13-21. PMID 23108011
9. Ham L, Dapena I, van Luijk C, et al. Descemet membrane endothelial keratoplasty (DMEK)
for Fuchs endothelial dystrophy: review of the first 50 consecutive cases. Eye (Lond). Oct
2009;23(10):1990-1998. PMID 19182768
10. Dapena I, Ham L, Droutsas K, et al. Learning curve in Descemet's membrane endothelial
keratoplasty: first series of 135 consecutive cases. Ophthalmology. Nov 2011;118(11):21472154. PMID 21777980
11. Price MO, Giebel AW, Fairchild KM, et al. Descemet's membrane endothelial keratoplasty:
prospective multicenter study of visual and refractive outcomes and endothelial survival.
Ophthalmology. Dec 2009;116(12):2361-2368. PMID 19875170
12. Guerra FP, Anshu A, Price MO, et al. Descemet's membrane endothelial keratoplasty:
prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
Ophthalmology. Dec 2011;118(12):2368-2373. PMID 21872938
13. Anshu A, Price MO, Price FW, Jr. Risk of corneal transplant rejection significantly reduced
with Descemet's membrane endothelial keratoplasty. Ophthalmology. Mar 2012;119(3):536540. PMID 22218143
14. McCauley MB, Price MO, Fairchild KM, et al. Prospective study of visual outcomes and
endothelial survival with Descemet membrane automated endothelial keratoplasty. Cornea.
Mar 2011;30(3):315-319. PMID 21099412
15. Cheng YY, Schouten JS, Tahzib NG, et al. Efficacy and safety of femtosecond laser-assisted
corneal endothelial keratoplasty: a randomized multicenter clinical trial. Transplantation.
Dec 15 2009;88(11):1294-1302. PMID 19996929
16. Vetter JM, Butsch C, Faust M, et al. Irregularity of the posterior corneal surface after curved
interface femtosecond laser-assisted versus microkeratome-assisted descemet stripping
automated endothelial keratoplasty. Cornea. Feb 2013;32(2):118-124. PMID 23132446
17. National Institute for Health and Clinical Excellence. IPG 304 Corneal endothelial
transplantation. 2009; http://www.nice.org.uk/nicemedia/pdf/IPG304Guidance.pdf. Accessed
May 11, 2016.
Keratoprosthesis
1. Lee WB, Shtein RM, Kaufman SC, et al. Boston Keratoprosthesis: outcomes and
complications: a report by the American Academy of Ophthalmology. Ophthalmology. Jul
2015;122(7):1504-1511. PMID 25934510
2. Ciolino JB, Belin MW, Todani A, et al. Retention of the Boston keratoprosthesis type 1:
multicenter study results. Ophthalmology. Jun 2013;120(6):1195-1200. PMID 23499061
3. Rudnisky CJ, Belin MW, Guo R, et al. Visual acuity outcomes of the Boston Keratoprosthesis
Type 1: multicenter study results. Am J Ophthalmol. Feb 2016;162:89-98 e81. PMID
26550696
Page 29
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
4. Srikumaran D, Munoz B, Aldave AJ, et al. Long-term outcomes of boston type 1
keratoprosthesis implantation: a retrospective multicenter cohort. Ophthalmology. Nov
2014;121(11):2159-2164. PMID 25017414
5. Dunlap K, Chak G, Aquavella JV, et al. Short-term visual outcomes of Boston type 1
keratoprosthesis implantation. Ophthalmology. Apr 2010;117(4):687-692. PMID 20096462
6. Aldave AJ, Kamal KM, Vo RC, et al. The Boston type I keratoprosthesis: improving outcomes
and expanding indications. Ophthalmology. Apr 2009;116(4):640-651. PMID 19243830
7. Colby KA, Koo EB. Expanding indications for the Boston keratoprosthesis. Curr Opin
Ophthalmol. Jul 2011;22(4):267-273. PMID 21537184
8. Harissi-Dagher M, Dohlman CH. The Boston Keratoprosthesis in severe ocular trauma. Can
J Ophthalmol. Apr 2008;43(2):165-169. PMID 18347618
9. Kang JJ, de la Cruz J, Cortina MS. Visual outcomes of Boston keratoprosthesis implantation
as the primary penetrating corneal procedure. Cornea. Dec 2012;31(12):1436-1440. PMID
22367042
10. Chang HY, Luo ZK, Chodosh J, et al. Primary implantation of type I Boston keratoprosthesis
in nonautoimmune corneal diseases. Cornea. Mar 2015;34(3):264-270. PMID 25611395
11. Fadous R, Levallois-Gignac S, Vaillancourt L, et al. The Boston Keratoprosthesis type 1 as
primary penetrating corneal procedure. Br J Ophthalmol. Dec 2015;99(12):1664-1668.
PMID 26034079
12. Ahmad S, Mathews PM, Lindsley K, et al. Boston Type 1 Keratoprosthesis versus repeat
donor keratoplasty for corneal graft failure: a systematic review and meta-analysis.
Ophthalmology. Jan 2016;123(1):165-177. PMID 26545318
13. Odorcic S, Haas W, Gilmore MS, et al. Fungal infections after Boston Type 1
Keratoprosthesis Implantation: literature review and in vitro antifungal activity of
hypochlorous acid. Cornea. Dec 2015;34(12):1599-1605. PMID 26488624
14. Greiner MA, Li JY, Mannis MJ. Longer-term vision outcomes and complications with the
Boston type 1 keratoprosthesis at the University of California, Davis. Ophthalmology. Aug
2011;118(8):1543-1550. PMID 21397948
15. Li JY, Greiner MA, Brandt JD, et al. Long-term complications associated with glaucoma
drainage devices and Boston keratoprosthesis. Am J Ophthalmol. Aug 2011;152(2):209-218.
PMID 21636070
16. Rudnisky CJ, Belin MW, Todani A, et al. Risk factors for the development of retroprosthetic
membranes with Boston keratoprosthesis type 1: multicenter study results. Ophthalmology.
May 2012;119(5):951-955. PMID 22361316
17. Goldman DR, Hubschman JP, Aldave AJ, et al. Postoperative posterior segment
complications in eyes treated with the Boston type I keratoprosthesis. Retina. Mar
2013;33(3):532-541. PMID 23073339
18. Pujari S, Siddique SS, Dohlman CH, et al. The Boston keratoprosthesis type II: the
Massachusetts Eye and Ear Infirmary experience. Cornea. Dec 2011;30(12):1298-1303.
PMID 21963861
Page 30
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
19. Tan A, Tan DT, Tan XW, et al. Osteo-odonto keratoprosthesis: systematic review of surgical
outcomes and complication rates. Ocul Surf. Jan 2012;10(1):15-25. PMID 22330056
20. Falcinelli G, Falsini B, Taloni M, et al. Modified osteo-odonto-keratoprosthesis for
treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases.
Arch Ophthalmol. Oct 2005;123(10):1319-1329. PMID 16219722
21. Michael R, Charoenrook V, de la Paz MF, et al. Long-term functional and anatomical results
of osteo- and osteoodonto-keratoprosthesis. Graefes Arch Clin Exp Ophthalmol. Aug
2008;246(8):1133-1137. PMID 18491123
22. De La Paz MF, De Toledo JA, Charoenrook V, et al. Impact of clinical factors on the longterm functional and anatomic outcomes of osteo-odonto-keratoprosthesis and tibial bone
keratoprosthesis. Am J Ophthalmol. May 2011;151(5):829-839. PMID 21310387
23. Hughes EH, Mokete B, Ainsworth G, et al. Vitreoretinal complications of
osteoodontokeratoprosthesis surgery. Retina. Oct 2008;28(8):1138-1145. PMID 18779721
24. Liu C, Okera S, Tandon R, et al. Visual rehabilitation in end-stage inflammatory ocular
surface disease with the osteo-odonto-keratoprosthesis: results from the UK. Br J
Ophthalmol. Sep 2008;92(9):1211-1217. PMID 18511541
25. Hicks CR, Crawford GJ, Lou X, et al. Corneal replacement using a synthetic hydrogel
cornea, AlphaCor: device, preliminary outcomes and complications. Eye (Lond). Apr
2003;17(3):385-392. PMID 12724702
26. Crawford GJ, Hicks CR, Lou X, et al. The Chirila Keratoprosthesis: phase I human clinical
trial. Ophthalmology. May 2002;109(5):883-889. PMID 11986092
27. Hoffart L, Carles G, Matonti F. Lamellar corneal lenticule graft to treat keratolysis after
AlphaCor keratoprosthesis implantation. Eur J Ophthalmol. Jan-Feb 2015;25(1):1-7. PMID
25198171
28. Alio JL, Mulet ME, Haroun H, et al. Five year follow up of biocolonisable microporous
fluorocarbon haptic (BIOKOP) keratoprosthesis implantation in patients with high risk of
corneal graft failure. Br J Ophthalmol. Dec 2004;88(12):1585-1589. PMID 15550368
29. National Institute for Health and Clinical Excellence (NICE). IPG69: Insertion of hydrogel
keratoprosthesis. 2004; http://guidance.nice.org.uk/IPG69/guidance/pdf/English. Accessed
June 2, 2016.
30. Medicare Program—Revisions to Hospital Outpatient Prospective Payment System and
Calendar Year 2007 Payment Rates; Final Rule. Federal Register. 2006;71(226):6805268054.
Other sources
Novitas Solutions. Local Coverage Determination (LCD) L35094 Services that are not
Reasonable and Necessary. Effective 05/12/16. [Website]:
https://www.novitas-solutions.com/policy/mac-ab/l31481-r1.html Accessed June 2, 2016.
Page 31
MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
X. POLICY HISTORY
MP
9.011
TOP
CAC 5/25/04
CAC 11/30/04
CAC 6/28/05
CAC 8/30/05
CAC 7/25/06
CAC 6/26/07
CAC 11/27/07
CAC 9/29/09 Policy retitled. Endothelial keratoplasty added to policy as medically
necessary for treatment of endothelial dysfunction.
CAC 5/25/10 Policy retitled. Policy criteria for keratoprostheses revised from
investigational to medically necessary.
CAC 4/26/11 Consensus
CAC 6/26/12 Consensus review; no changes, references updated.
7/9/12- FEP variation revised to refer to the FEP medical policy manual.
CAC 9/24/13 Consensus review. References updated but no changes to the
policy statements. FEP variation revised to refer to FEP Keratoprosthesis medical
policy. No coding changes.
CAC 7/22/14 Minor. BCBSA adopted for endothelial prosthesis and
keratoprosthesis.
For endothelial keratoplasty DMEK [Descemet’s membrane endothelial
keratoplasty] and DMAEK [Descemet’s membrane automated endothelial
keratoplasty] added to the MN policy statement.
Added the following as medically necessary;
 ruptures in Descemet’s membrane
 iridocorneal endothelia (ICE) syndrome
 corneal edema attributed to endothelial failure
Investigational statement added for Femtosecond laser-assisted corneal
endothelial keratoplasty (FLEK) and femtosecond and excimer lasers-assisted
endothelial keratoplasty (FELEK).
No change to policy statements related to keratoprosthesis or corneal transplant.
References updated. Rationale section added.
CAC 7/21/15 Minor revision. For keratoprosthesis, conditions that are likely to
have poor outcomes with a corneal transplant were added to the medically
necessary policy statement. No changes to the policy statements for endothelial
keratoplasty or corneal transplant. Reference and rationale update. Coding
reviewed.
Admin update 11/23/16: Variation section reformatted.
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MEDICAL POLICY
POLICY TITLE
CORNEAL TRANSPLANT, ENDOTHELIAL KERATOPLASTY AND
KERATOPROSTHESES
POLICY NUMBER
MP-9.011
Admin Update 1/1/17: New diagnosis codes added effective 10/1/16. Removed
end dated code 0289T; effective 1/1/17.
CAC 7/26/16 Minor For keratoprosthesis. In the medically necessary policy
statement. “Multiple graft failure” changed to “history of 1 or more” graft
failures. Other wording changes did not alter intent of the policy.
Background/Description, rationale and references updated. Coding reviewed.
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Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company®,
Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the BlueCross BlueShield Association.
Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies.
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