Hindawi Publishing Corporation
Journal of Ophthalmology
Volume 2013, Article ID 686587, 5 pages
Low-Cost and Readily Available Tissue Carriers for the Boston
Keratoprosthesis: A Review of Possibilities
Andrea Cruzat, Allyson Tauber, Anita Shukla, Eleftherios I. Paschalis,
Roberto Pineda, and Claes H. Dohlman
Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School,
243 Charles Street, Boston, MA 02114, USA
Correspondence should be addressed to Andrea Cruzat; firstname.lastname@example.org
Received 1 August 2013; Accepted 8 October 2013
Academic Editor: Shivalingappa K. Swamynathan
Copyright © 2013 Andrea Cruzat et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual
autografts, xenografts, noncorneal autologous tissues, and laboratory-made tissue constructs, as well as modifications to corneal
allografts, such as deep-freezing, glycerol-dehydration, gamma irradiation, and cross-linking. These alternative tissue carriers for
the B-KPro are discussed with special regard to safety, practicality, and cost for the developing world.
The Boston keratoprosthesis (B-KPro) is an artificial cornea
that offers a viable solution for corneal transplant candidates
history of graft rejection, dry eyes, and severe neurotrophic
out astigmatism and rapid visual recovery postoperatively.
It is the most widely used corneal prosthesis in the United
States and in the rest of the world . The B-KPro has a
collar-button design with a front plate, stem, and back plate
of poly[methyl methacrylate] (PMMA) or titanium . The
device is implanted into a corneal graft and then sutured into
the patient’s cornea as in standard penetrating keratoplasty
adequate tear secretion, whereas the type II B-KPro (with an
added anterior nub) is reserved for near-hopeless cases with
eye conditions and cicatricial diseases .
From a global perspective, the need for human corneas
in many regions of the developed world with established eye
bank systems, this is not the case for other populations. In
many developing countries, cultural and religious concerns
limit organ donations [4, 5]. Furthermore, healthcare and
financial restrictions can be a major barrier: for example,
a donor cornea from an eye bank in the United States can
cost about $3,000 due to the need for microbial testing,
administration, and transport alone . Thus, the lack of
human donor tissue at a reasonable cost is one of the largest
barriers to reducing blindness through either standard PK
or KPro implantation . A long-term, safe, and inexpensive
alternative is clearly needed for the developing world.
Why is it necessary to use a corneal graft as a vehicle
for the B-KPro? After all, several other artificial corneas,
proposed from other centers throughout history, have been
experience that a double-plated (collar-button) keratopros-
thesis design has advantages over designs where the optical
stem is anchored by a horizontal haptic (plastic, metal, tooth,
etc.) placed within or in front of the patient’s cornea. Accord-
ing to our results, positioning of the B-KPro’s back plate
entirely behind the corneal tissue, with its intact Descemet’s
2 Journal of Ophthalmology
membrane, provides better long-term retention than other
arrangements. Accepting this principle of positioning, we
have in the past tried to work out practical techniques for
direct insertion into the patient’s cornea without using a
graft but without success. Such approaches have been too
we have used a corneal graft as a vehicle for the device since
the mid-1960s, with improved retention.
We are therefore exploring alternatives to fresh corneal
tissue for use as a keratoprosthesis carrier. This includes
physical alterations to increase storage time, such as deep-
freezing, glycerol-dehydration, gamma irradiation, or cross-
linking of tissue. Other substitutes may include corneal
autografts, xenografts, skin, cartilage, and tissue constructs.
This review identifies alternative tissue carriers suitable for
the developing world in terms of safety, practicality, and cost
2. Carriers for the Boston Keratoprosthesis
In the developed world with high levels of health expen-
ditures and established eye banks, standard fresh corneal
allografts (preserved from 1 to 14 days) are preferred. Addi-
tionally, allografts allow assembly with the B-KPro on a
side table before opening the patient’s eye. This minimizes
the time the eye is open and risk of vitreous protrusion or
choroidal hemorrhage. But, in the developing world, issues
with cost, logistics, and administration of the donor graft are
One alternative is to modify the donor tissue in order
to lengthen storage time prior to use. It is known that an
allograft can be stored deep-frozen (thus nonviable) and
still be usable as a lamellar graft . As a carrier for the
B-KPro, there was no demonstrable difference in clinical
outcomes between fresh and frozen donor materials in a
and should theoretically be less antigenic. Storing human
allogenic corneas in a hospital freezer is practical for the B-
KPro surgery locally, but transport remains a problem.
frozen corneal tissue, where shipment in a small vial is easy
and practical see Table 1. Dehydration is performed simply
by replacing corneal water with glycerol and has long been
a standard technique in biology . Glycerol-preservation
of donor corneal tissue has for many decades been used in
lamellar keratoplasty with satisfactory outcomes . This
method extends the time that a cornea can be stored and can
thereby allow the use of tissue that would otherwise be dis-
carded on the basis of prolonged death-to-preservation time.
In 2008, the Eye Bank Association of America estimated that
the United States harvested over 92,000 corneas, including
30,000 that were deemed unsuitable for optical grafting. Of
these, approximately 25% could have been preserved with
glycerol and eventually used, increasing the cornea donor
but the corneas need to be rehydrated in saline for 30–
60 minutes before use; otherwise their leathery consistence
makes suturing difficult. Corneas dehydrated by freeze-
drying, rather than by glycerol, would be expected to have
similar qualities, but preparation and shipment would be
Corneal allografts can be modified in other ways. After
B-KPro implantation, graft necrosis, melt, and subsequent
leak can occur postoperatively, particularly in autoimmune
diseases, leading to calamities like retinal detachment or
infection. Pretreatment aimed at increasing resistance to
enzymatic digestion might help reduce the incidence. Cross-
linking corneas with the help of riboflavin plus UV-A light
has been shown to reduce corneal susceptibility to digestion
with collagenases . Whether such modified corneal grafts
show increased long-term stability is presently the subject of
a clinical study.
Gamma irradiated human corneas, such as Visiongraft
Sterile Cornea, available from Tissue Banks International,
have recently been used in place of fresh donor corneas for
lamellar patch grafts . They have also been used success-
fully as carriers for the B-KPro . In our experience, these
grafts are thinner than a fresh graft but are still functional.
In addition, these corneas can be easily transported in a
vial at room temperature. However, as long as testing for
residual viruses is required, the cost remains high, and it
is questionable whether gamma irradiated corneas have any
advantage over glycerol-dehydrated tissue.
For countries with limited resources and no eye bank
ters will, by necessity, be the same. The B-KPro assembly will
Journal of Ophthalmology3
Table 1: Possible tissue carriers for the Boston keratoprosthesis and predicted qualities.
UnevenNone No issueStandardLow NoneLow
BetterNone No issue No issueComplexVery lowNone Very low
Allograft, dehydratedGoodHigh Good
Low Very lowLow
Complex Standard LowLow Low
(tested for viruses)
GoodHigh?Good StandardLow Very lowLow
훾-radiationGood Standard Low??
(untested for viruses)
GoodLowGood Complex?Low Very low?
have to take place on a side table with the patient’s eye open,
which should take a maximum of five minutes. In spite of
such relatively minor disadvantages, the benefits of low cost
and easy logistics are often overriding, and this approach is
in use in several countries. A recent pilot keratoprosthesis
used patients’ own corneas as carriers for the B-KPro .
While these results are promising, widespread adoption is
limited by the health of the presurgical cornea which must
not have any stromal melt, perforation, or infection. Often,
between the B-KPro plates, compounded by a heightened
sensitivity to necrosis and melt in corneas severely damaged
from disease. Therefore, we recommend the patient’s own
is not too scarred, inflamed, or thin .
A thin and scarred cornea can be used as an autograft,
however, if covered by a large conjunctival flap . Such a
flap should be mobilized vertically, from the temporal sclera,
with intact bases above and below. It should be moderately
thick and wide enough to fit loosely over the entire cornea. It
is important that all corneal epithelium be removed before
the flap is sutured down (with 10-0 nylon) to the limbus,
so that a pure connective tissue interface is created. Leaving
patches of epithelium behind would later result in epithelial
cysts. A small central opening can be made in the flap at
the end of surgery and will result in gradual retraction of
the conjunctival edge to the edge of the B-KPro front plate.
Such a flap is an effective way of covering the carrier cornea
with a much needed barrier of conjunctival epithelium and
soft contact lens wear unnecessary. The downside of such a
vertical conjunctival flap is that it makes the procedure more
complex by adding surgery time. Also, there are situations
where the conjunctiva is too thin and scarred down to be
A hypothetical carrier possibility would be to use an
extracorneal autologous tissue, such as skin. Thin, hairless
dermis can be harvested from behind the ears or elsewhere.
and the back plate will be needed in order to block cells and
large proteins from entering the eye through the plate holes.
Such studies are presently being conducted in animals. Also,
various forms of cartilage in the body are being explored as
carrier graft substitutes shaped into suitable diameter and
thickness as either autografts, allografts, or xenografts .
In prior studies, cartilage from sternum or ears has been
implanted in animal corneas [18, 19].
It is important to acknowledge that not only availability
and safety but also low cost is a requirement for B-KPro
carrier tissue in the developing world. For many patients,
4 Journal of Ophthalmology
beyond those possibilities. One such possibility is xenografts
bovine heart valves, pericardium, and so forth have been
successfully used in humans for years. If corneas from such
animals, ubiquitous in barnyards all over the world, could
be tolerated in human eyes, the search for a suitable carrier
material would be over. The biological questions regarding
xenografts would be transplantation immunity and sterility.
Gamma irradiation reduces antigenicity and sterilizes the
tissue, making xenografts a real possibility for humans.
Xenotransplantation from pigs is appealing with respect
to the cornea, as there are many similarities to humans with
regards to refractive power, size, and tensile strength .
Recent genetic manipulation of pigs has led to the prospect
that the remaining immunological barriers will be overcome
. Though there is less risk of rejection from genetically
manipulated pigs, the cost is still high and availability is
complex. The question of sterility is also of high importance
bacteria but also all viruses that can pose a potential threat
to the new host. If the surface of such a xenograft would
still be vulnerable to necrosis and melt, a conjunctival flap as
described above, should be protective. These hypotheses are
presently being tested by our group in animal experiments
Finally, laboratory-synthesized tissue constructs may be
an alternative carrier tissue. Sheets of collagen fibrils, mod-
erately cross-linked, have been successfully used as lamellar
grafts in humans with keratoconus [23, 24]. Recent studies
on the safety and functionality of a biosynthetic cornea
found that it supported the ingrowth of endogenous cells
and nerves, as well as functions such as touch sensation,
development of tear film, and normal eye pressure [23, 25].
Theoretically, the use of such constructs would be very
attractive as costly microbiological testing would not be
difficulty seems to be making the constructs biocompatible,
thick, and cohesive enough for suturing into a recipient
In addition to expanding available options for B-KPro
carrier tissue, efforts are under way to make the B-KPro
device more readily available for the developing world and
the postoperative care less expensive. New designs of the B-
KPro that are more cost-effective are under current develop-
ment. Low-cost bandage contact lenses of variable diameters
are recommended to be used with the B-KPro. Although
antibiotic prophylaxis is needed for life in a patient with a
B-KPro, simple and affordable antibiotic combinations are
suggested such as Polymyxin B + Trimethoprim sulfate daily
to diminish the financial burden of this approach.
blindness needing surgical rehabilitation, at least 80% live in
the developing world [5, 26]. For this underserved popula-
tion, the B-KPro is expected to play an increasing role. The
present surgical technique of implantation requires corneal
tissue as a carrier for the device—however, the high cost
and lack of availability constitute a severe hurdle in many
carrier tissues that must be inexpensive, readily available,
and safe. In this review, we have presented a number of
alternative options and their advantages and disadvantages
Conflict of Interests
The authors have no financial/conflicting interests to dis-
 M. A. Klufas and K. A. Colby, “The boston keratoprosthesis,”
International Ophthalmology Clinics, vol. 50, no. 3, pp. 161–175,
 K. A. Colby and E. B. Koo, “Expanding indications for the
Boston keratoprosthesis,” Current Opinion in Ophthalmology,
vol. 22, no. 4, pp. 267–273, 2011.
 S. Pujari, S. S. Siddique, C. H. Dohlman, and J. Chodosh, “The
boston keratoprosthesis type II: the massachusetts eye and ear
infirmary experience,” Cornea, vol. 30, no. 12, pp. 1298–1303,
Medical Journal of Australia, vol. 157, no. 6, pp. 405–408, 1992.
 D. Pascolini and S. P. Mariotti, “Global estimates of visual
5, pp. 614–618, 2012.
 T. D. Miller, A. J. Maxwell, T. D. Lindquist, and J. Requard
3rd, “Validation of cooling effect of insulated containers for the
Cornea, vol. 32, no. 1, pp. 63–69, 2013.
of glycerol-preserved corneas in the developing world,” Middle
East African Journal of Ophthalmology, vol. 17, no. 1, pp. 38–43,
 E. C. Sweebe and C. H. Dohlman, “Nonviable donor material
 M.-C. Robert, K. Biernacki, and M. Harissi-Dagher, “Boston
keratoprosthesis type 1 surgery: use of frozen versus fresh
 M. C. Banker, J. R. Layne Jr., G. L. Hicks Jr., and T. Wang,
“Freezing preservation of the mammalian cardiac explant. II.
Comparing the protective effect of glycerol and polyethylene
glycol,” Cryobiology, vol. 29, no. 1, pp. 87–94, 1992.
 J. H. King Jr. and W. M. Townsend, “The prolonged storage of
donor corneas by glycerine dehydration,” Transactions of the
American Ophthalmological Society, vol. 82, pp. 106–110, 1984.
 S. Arafat, A. Shukla, C. Dohlman, J. Chodosh, and J. B. Ciolino,
method of increasing resistance to collagenolytic degradation,”
Investigative Ophthalmology & Visual Science, vol. 53, p. 6072,
 C. A. Utine, J. H. Tzu, and E. K. Akpek, “Lamellar keratoplasty
using gamma-irradiated corneal lenticules,” American Journal
of Ophthalmology, vol. 151, no. 1, pp. 170–e1, 2011.
Journal of Ophthalmology5 Download full-text
gamma-irradiated corneal lenticules in Boston type 1 kerato-
prosthesis implantation,” American Journal of Ophthalmology,
vol. 154, no. 3, pp. 495–498, 2012.
 J. D. Ament, Y. Tilahun, E. Mudawi, and R. Pineda, “Role for
prosthesis: the Africa experience,” Archives of Ophthalmology,
vol. 128, no. 6, pp. 795–797, 2010.
 J. Al-Merjan, N. Sadeq, and C. H. Dohlman, “Temporary tissue
coverage of keratoprosthesis,” Middle East African Journal of
Ophthalmology, vol. 8, pp. 12–18, 2000.
 D. Myung, C.Ta, E. Yung, and C. Frank, “Chondro-ocular graft
transfer: an alternative to allograft transplantation?” Investiga-
tive Ophthalmology & Visual Science, vol. 54, p. 3477, 2013.
 J. M. Rohrbach, T.-M. Wohlrab, B. Sadowski, and H.-J. Thiel,
“Biological corneal replacement—alternative to keratoplasty
and keratoprosthesis? A pilot study with heterologous hyaline
cartilage in the rabbit model,” Klinische Monatsblatter fur
Augenheilkunde, vol. 207, no. 3, pp. 191–196, 1995.
 T.-M. Wohlrab, K. K¨ uper, and J. M. Rohrbach, “Allogen hetero-
topic cartilage transplantation for primarycorneal replacement
in rabbit model,” Klinische Monatsblatter fur Augenheilkunde,
vol. 214, no. 3, pp. 142–146, 1999.
 P. Zhiqiang, S. Cun, J. Ying, W. Ningli, and W. Li, “WZS-pig
is a potential donor alternative in corneal xenotransplantation,”
Xenotransplantation, vol. 14, no. 6, pp. 603–611, 2007.
 H. Hara and D. K. C. Cooper, “Xenotransplantation-the future
of corneal transplantation?” Cornea, vol. 30, no. 4, pp. 371–378,
 A. Cruzat, A. Shukla, E. I. Paschalis, F. Cade, and C. Dohlman,
“Corneal Xenografts: carrier for the Boston Keratoprosthesis?”
Investigative Ophthalmology & Visual Science, vol. 53, p. 4126,
 M. Griffith, N. Polisetti, L. Kuffova et al., “Regenerative
approaches as alternatives to donor allografting for restoration
of corneal function,” The Ocular Surface, vol. 10, no. 3, pp. 170–
 P. Fagerholm, N. S. Lagali, K. Merrett et al., “A biosynthetic
alternative to human donor tissue for inducing corneal regen-
eration: 24-month follow-up of a phase 1 clinical study,” Science
Translational Medicine, vol. 2, no. 46, Article ID 46ra61, 2010.
 S. Proulx and I. Brunette, “Methods being developed for
corneal endothelium,” Experimental Eye Research, vol. 95, no. 1,
pp. 68–75, 2012.
 P. Garg, P. V. Krishna, A. K. Stratis, and U. Gopinathan, “The
19, no. 10, pp. 1106–1114, 2005.