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Seoul-Type Keratoprosthesis
Preliminary Results of the First 7 Human Cases
Mee Kum Kim, MD;
Jae Lim Lee, MD;
Won Ryang Wee, MD;
Jin Hak Lee, MD
Arch Ophthalmol. 2002;120:761-766.
ABSTRACT
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Objective To evaluate the clinical efficacy of a newly designed Seoul-type keratoprosthesis
(S-KPro).
Methods The S-KPro, which consists of a polymethyl methacrylate optic, a skirt
(polyurethane or polypropylene), and polypropylene haptics, was developed
and implanted into 2 unsighted and 5 sighted eyes of 7 patients. One patient
had a chemical burn, another had an ocular pemphigoid, and the remainder were
diagnosed as having Stevens-Johnson syndrome. The preoperative visual acuities
ranged from light perception to hand motions. The average follow-up time was
25.6 months.
Main Outcome Measures We evaluated anatomical stability, visual acuity, retinal status, and
the visual field.
Results At the last follow-up visit, the S-KPro was well placed in 6 patients.
The best-corrected visual acuities of the sighted patients ranged from 20/100
to 20/60 in the affected eye. One patient each experienced retinal detachment
or endophthalmitis. Partial extrusion was found in the patient with glaucoma.
A retroprosthetic membrane was detected in 1 patient and was treated with
an Nd:YAG laser. No glaucomatous visual field defects were found in any of
the sighted patients.
Conclusions Anatomical success was achieved in 6 of 7 eyes. In 3 of the 5 sighted
eyes, the S-KPro could rehabilitate corneal blindness not correctable with
keratoplasty.
INTRODUCTION
THE TREATMENT of corneal blindness is a major area in the field of ophthalmology.
Because corneal blindness cannot be treated with keratoplasty or limbal cell
transplantation, a keratoprosthesis (KPro) is required. Although researchers
have designed prostheses1-4
and made improvements for a more acceptable artificial cornea,5-9
many ideas regarding prosthetic design, surgical technique, and treatment
of complications remain to be proved.
The type of KPro commonly used consists of an optical stem with an anchoring
skirt. Tissue breakdown around the prosthesis and extrusion of the KPro is
the major cause of its failure. Therefore, a newly designed Seoul-type keratoprosthesis
(S-KPro) was introduced. The prosthesis consists of an optic made of polymethyl
methacrylate, a skirt of polyurethane or polypropylene, and haptics of monofilament
polypropylene(Prolene; Ethicon Ltd, Edinburgh, Scotland).10
The main characteristic of the S-KPro is the double-fixed design, which includes
anchoring sutures between the cornea and skirt and ab internal scleral fixation
of the haptics, synergistically improving the mechanical biostability. The
clinical effects of the double fixation on the S-KPro's biostability were
investigated in 7 human subjects.
PATIENTS, MATERIALS, AND METHODS
DEMOGRAPHICS OF THE PATIENTS
We confirm that the research followed the tenets of the Declaration
of Helsinki. Seven patients who provided written informed consent, including
2 unsighted ones, were enrolled in this study (Table 1). They consisted of 2 women and 5 men, and the mean age
was 42.6 years. Five of them were diagnosed as having Stevens-Johnson syndrome
(SJS), 1 had a chemical burn, and 1 had an ocular cicatricial pemphigoid (OCP).
The preoperative visual acuities ranged from light perception to hand motions.
In all study patients, repeated penetrating keratoplasty with amniotic membrane
implantation was unsuccessful. The prognosis of all patients was very poor,
not only for penetrating keratoplasty but also for keratoprosthesis implantation.
One of the unsighted patients had amblyopia, and the other had uncontrolled
glaucoma. These 2 patients were engaged to evaluate the anatomical stability
of the implanted S-KPro. The mean follow-up time was 25.6 months.
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Demographics of Patients and Outcomes of Eyes That Underwent S-KPro
Implantation*
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S-KPRO DESIGN AND SURGICAL TECHNIQUE
The design and characteristics of the S-KPro were introduced previously
(Figure 1).10
The optic was made of surface-modified polymethyl methacrylate. Polyethylene
glycol was used for surface modification to reduce cell adhesion.11 Three of the S-KPros had a polyurethane skirt (thickness,
0.3 mm; porosity, 60%-80%; pore diameter, 40 µm), and the others had
a nonwoven polypropylene skirt (Q 2030 NW; Seon-Kyoung Co, Seoul, Korea; fiber
diameter, 15-20 µm; basis weight, 30.0 g/m2; thickness, 0.23
mm; pore diameter, 30-60 µm). The S-KPros were implanted in the more
visually impaired eyes. The surgical technique for S-KPro implantation was
followed as previously mentioned.10
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Figure 1. A schematic illustration of the
design of the Seoul-type keratoprosthesis (S-KPro). The S-KPRo consists of
an optic made of polymethyl methacrylate (PMMA), a skirt of polyurethane or
polypropylene, and haptics of monofilament polypropylene.
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Postoperatively, ointments of topical dexamethasone with polymyxin B
sulfate and neomycin sulfate, and oxytetracycline hydrochloride with polymyxin
B sulfate, were administered twice a day for 1 month. Ofloxacin and prednisolone
acetate were subsequently applied 4 times a day until 2 months postoperatively.
Dextran 70 and hydroxypropyl methylcellulose were instilled frequently, and
hyaluronate sodium was applied 4 times a day and timolol maleate twice a day
up to the present. Whenever the repair surgery was repeated during follow-up,
ofloxacin and prednisolone acetate were reapplied for 2 months.
EVALUATION OF KERATOPROSTHETIC EYES
Best-corrected visual acuity, the anterior segment, retinal status,
and anatomical stability were examined. The visual field was evaluated in
4 eyes using Goldmann perimetry.
HISTOLOGICAL EXAMINATION
Unfortunately, 1 patient experienced endophthalmitis and underwent evisceration
after 7 months of follow-up. This specimen was stained with hematoxylin-eosin
to evaluate fibrovascular invasion.
The skirt of the first implanted polyurethane S-KPro partially degenerated.
A part of the degenerated skirt was obtained, treated with the same fixation
and dehydration method as stated previously,10
and examined using transmission electron microscopy (H-7100; Hitachi, Tokyo,
Japan).
RESULTS
The S-KPro was anatomically well attached in 6 of the 7 eyes. The outcomes
are shown in Table 1. The clinical
course of each patient was as follows.
CASE 1
This 59-year-old patient had had SJS for 14 years. Initially, an S-KPro
made with an expanded polytetrafluoroethylene (e-PTFE) skirt (Gore-Tex; W.
L. Gore and Associates Inc, Flagstaff, Ariz) was implanted. The best-corrected
visual acuity had been 20/100 for 18 months, as previously reported.10 Although the S-KPro had been well placed, the skirt
was gradually being exposed. Therefore, the S-KPro was exchanged with another
one, made with a polyurethane skirt, 19 months postoperatively. Even though
a retinal detachment occurred 3 days after the operation, the reimplanted
S-KPro has been well placed up to now (Figure
2A). Partial degeneration and occluded pores were observed in the
polyurethane skirt after 27 months of follow-up (Figure 2B).
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Figure 2. A, A well-placed Seoul-type keratoprosthesis
with a degenerated and exposed skirt in case 1 after 27 months of follow-up.
B, Transmission electron microscopy reveals mostly occluded pores (black arrows)
in the polyurethane skirt in case 1, interfering with fibroblast (white arrow)
invasion.
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CASE 2
This 31-year-old patient experienced a chemical burn in both eyes. An
S-KPro made with a polyurethane skirt was implanted. The patient's visual
acuity improved to 20/50 with a myopic correction of 7.5 diopters (D).10 Although the S-KPro had been well placed, tissue
breakdown around the prosthesis occurred. Repeated buccal mucosa transplantation
followed but failed. Retransplantation was frequently postponed for 5 or 6
months because of the patient's personal work commitments, but the S-KPro
was well maintained (even with a totally exposed skirt), and the visual acuity
was 20/100 (Figure 3). After scleral
grafting was conducted, the S-KPro was well maintained in the keratoprosthetic
eye up to the last follow-up visit, 36 months after the operation. No retroprosthetic
membrane or retinal abnormality was observed.
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Figure 3. A well-maintained Seoul-type keratoprosthesis
that resulted in a visual acuity of 20/100 in the affected eye in case 2 for
24 months, even though the skirt had been exposed.
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CASE 3
A 61-year-old man had SJS, and an S-KPro with a polyurethane skirt was
implanted. The patient's best-corrected visual acuity was 20/200 with a myopic
correction of -5.0 D. The skirt of the S-KPro gradually became exposed.
Buccal mucosas were grafted repeatedly, and the S-KPro was well positioned
for 23 months. However, the superior part of the S-KPro was partially extruded
24 months after the operation. The allosclera and buccal mucosa were grafted,
which restabilized the S-KPro. Although a diffuse retroprosthetic membrane
formed repeatedly after 29 months, it was treated 4 times with Nd:YAG laser
membranotomy. The patient's visual acuity then returned to 20/200. The S-KPro
was well attached at the last follow-up visit (Figure 4). No glaucomatous visual field defect was found (Figure 5).
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Figure 4. Repair surgery with the graft
for partial extrusion allowed the Seoul-type keratoprosthesis to remain stable
for 12 months. The patient's visual acuity was 20/200 in the affected eye.
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Figure 5. The visual field after 14 months
of follow-up in case 3, as examined using Goldmann perimetry. No glaucomatous
visual field defect was found.
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CASE 4
This 57-year-old patient had SJS and underwent S-KPro implantation.
Its skirt was made of polypropylene. The patient's visual acuity was 20/200
with a hyperopic correction of 2.5 D. However, the skirt gradually became
exposed after 6 months, and buccal mucosas were grafted 5 times. No glaucomatous
defect was found during 2 years of follow-up. The S-KPro is well placed, and
the retina has remained flat. No retroprosthetic membrane has been observed.
CASE 5
A 55-year-old woman had had an OCP for 20 years. She underwent implantation
with an S-KPro that had a polypropylene skirt. Her best-corrected visual acuity
was 20/60 with a myopic correction of 4 D. The retina was flat, and the visual
field was nearly normal. Even with an episode of endophthalmitis at 2 months
postoperatively, the visual acuity and electroretinal response were recovered
with the application of topical antibiotics. The S-KPro was well attached
until 7 months after the operation. Unfortunately, increasing pain with a
sudden decrease in visual acuity recurred and resulted in evisceration, even
though fortified antibiotics were aggressively administered. The vitreous
culture was positive for Enterococcus fascia. A histologic
examination revealed that no matrix had accumulated in the skirt, with little
fibroblast invasion (Figure 6A).
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Figure 6. A, Histologic staining revealed
that no matrix had accumulated in the skirt, with little fibroblast invasion
(black arrows) (hematoxylin-eosin, original magnification x400). B,
An abnormally thickened metaplastic epithelial layer (white arrows) occupied
more than half of the corneal thickness and accounted for the isolation of
the skirt (black arrow) from the stroma (hematoxylin-eosin, original magnification
x100).
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CASE 6
A 31-year-old woman had developed SJS when she was 6 years old. She
had an S-KPro with a polypropylene skirt implanted. Even though her visual
acuity did not improve because of an amblyopia, the S-KPro has remained well
attached, with skirt exposure, for 21 months. No other complication has since
been detected.
CASE 7
This 33-year-old patient had had SJS for 20 years. A high intraocular
pressure was incidentally detected. A polypropylene S-KPro was implanted and
remained in place for 11 months. The patient's visual acuity did not improve
because of a total cupping of the disc. A partial dislocation of the S-KPro
was detected 11 months after the procedure. An additional repair procedure
was recommended, but the patient refused because the eye was unsighted.
COMMENT
The purpose of this study was to examine the biocompatibility of the
double-fixed design of the S-KPro. The main problem with keratoprosthetic
surgery is the extrusion of an implant. Tissue breakdown, the main cause of
extrusion, seems to be inevitable surrounding the skirt of the keratoprosthesis.
To enhance fibrovascular tissue invasion, a porous polymer with a pore diameter
of 30 µm or larger was used for the skirt. Nevertheless, the cornea
melted and exposed the skirt, thereby requiring an additional tissue graft.
Buccal mucosal or scleral grafts were conducted repeatedly. The double-fixed
design provided sufficient time to allow proper management of the exposed
skirt, with improved stability. Even though the corneal fixation loosened,
the S-KPro was well placed in most of the eyes. This suggests that the haptics
anchored to the sclera may play an important role in extrusion.
In case 1, to cover the wound exposure between the cornea and skirt,
the e-PTFE S-KPro was exchanged with one with a more porous skirt; this resulted
in retinal detachment. Therefore, tissue grafts with the buccal mucosa and
sclera were performed on the other eyes with skirt exposure instead of exchanging
the S-KPro. The sclera was used to remove the dead space between the skirt
and surrounding tissue. These procedures were relatively safe compared with
the exchange and helped to stabilize the S-KPro. In conclusion, reinforcement
with tissue grafting was regarded as a better choice than S-KPro exchange
as a way to manage skirt exposure.
In case 1, an S-KPro made with an e-PTFE skirt with an average pore
diameter of 20 µm was initially implanted. The pore size of the skirt
material was too small to accept fibrovascular ingrowth, which was considered
to be the cause of the skirt exposure. The e-PTFE S-KPro was replaced with
one made with a polyurethane skirt (pore size  30 µm) because e-PTFE
with a pore diameter of 20 µm or more is not commercially available
and the pore size of polyurethane is easily fabricated.10
However, after long-term follow-up in humans, polyurethane with a large pore
size was found to dissolve easily (cases 1 and 3). Additionally, with in vivo
experiments, nonwoven polypropylene was found to have an excellent property
that encourages fibroblast ingrowth compared with polyurethane (Mee Kum Kim,
MD, unpublished data, 2001). Given this data, we finally exchanged polyurethane
with polyproplyene as the skirt material for the other patients. Researchers
have paid much attention to porous polymers such as Proplast12-13
(a combination of polytetrafluoroethylene and vitreous carbon), e-PTFE,14 polyurethane,15 and
hydrogels16-17 to enhance fibrovascular
invasion. However, the effect of such porous materials on fibrovascular invasion
is somewhat controversial. Whereas sufficient fibroblast ingrowth and matrix
accumulation without any skirt exposure were found in both polyurethane and
polypropylene in an animal study (Mee Kum Kim, MD, unpublished data, 2001),
skirt exposure was observed in all human eyes in our study irrespective of
the skirt material. This difference might result either from the insufficient
protection from tears, mechanical stress by fibrotic eyelids with trichiasis,
or abnormally malfunctioning fibroblasts in the diseased human eye. In particular,
surgically induced inflammation in SJS may be the leading cause of tissue
necrosis. Management of these factors should be considered important, as well
as the choice of porous polymer.
Although a retroprosthetic membrane developed repeatedly in case 3,
it was handled 4 times with Nd:YAG laser membranotomy. Repeated laser membranotomy
was known to be efficient for treating the retroprosthetic membrane18-19 and was performed up to 7 times.20 Therefore, Nd:YAG laser treatment seems to be relatively
safe and effective in treating eyes that have undergone S-KPro implantation.
Endophthalmitis, known to occur frequently in patients with keratoprosthetics,21 developed in case 5. Most cases of endophthalmitis
are due to gram-positive cocci.22 This patient
also had an Enterococcus infection, which is reported
to be a common cause of endophthalmitis23 and
keratitis.24 The patient was diagnosed as having
OCP, and preoperative diagnosis of this condition or SJS is a major risk factor
for endophthalmitis in keratoprosthetic eyes. Although skirt exposure was
found in all eyes implanted with S-KPros, most patients did not experience
endophthalmitis. Therefore, altered ocular immunity, as suggested by Nouri
et al,22 may be related to endophthalmitis.
The microscopic findings were also remarkable. An abnormally thickened,
squamous, metaplastic epithelial layer occupied more than half of the corneal
thickness and accounted for the isolation of the skirt from the stroma, which
interfered with the fibroblast invasion (Figure 6B). As usual, an intrastromal pocket was made halfway into
the cornea for S-KPro implantation; however, the pocket should have been situated
deeper than halfway for patients with a metaplastic cornea.
Another characteristic of the S-KPro is polyethylene glycol-grafting
polymerization of the optics to reduce cell adhesion, in expectation of a
decrease in retroprosthetic membrane formation. A retroprosthetic membrane
was not found in most patients with the exception of case 3. Therefore, this
modification might contribute to a decrease in the formation of the membrane.
However, its effect on the reduction of retroprosthetic membrane formation
is somewhat unclear because many factors are involved, such as inflammation,
wound exposure, and bleeding during surgery. Future studies should examine
the effect of polyethylene glycol-grafting polymerization on decrease in retroprosthetic
membrane formation.
One of the disadvantages of the S-KPro is that the intraocular pressure
cannot be measured. Therefore,  -blockers were routinely applied, and
the visual field was periodically examined. No glaucomatous visual field defects
were found in any of the sighted patients during follow-up. The threat of
uncontrolled glaucoma often requires simultaneous or subsequent implantation
of a drainage shunt.25 However, an additional
drainage implant could not be used with the S-KPro implant, so more work is
recommended to enable the installation of a drainage device with the S-KPro.
The outcome of the keratoprosthetic surgery was related to the preoperative
diagnosis.20 Patients who underwent S-KPro
implantation had either SJS, OCP, or a chemical burn with a severely damaged
ocular surface. Accordingly, the outcome tended to be less favorable compared
with the results reported by other groups. However, it is important to evaluate
the feasibility of the S-KPro and to learn adequate treatment for its complications.
In conclusion, the double-fixed design improves the mechanical stability
of the S-KPro when used with additional grafting. The S-KPro enables 3 of
5 sighted patients to perform daily activities and continue their normal routine.
The long-term outcome is pending.
AUTHOR INFORMATION
Submitted for publication August 29, 2001; final revision received January
31, 2002; accepted February 12, 2002.
This study was supported by grant HMP-98-G-2-048-a from the Highly Advanced
National Project, Ministry of Health & Welfare, and in part by the Year
2000 BK21 Project for Medicine, Dentistry, and Pharmacy, Seoul, Korea.
Corresponding author and reprints: Jin Hak Lee, MD, Department of
Ophthalmology, Seoul National University College of Medicine, 28 Yongon-dong,
Chongno-gu, Seoul 110-744, Korea (e-mail: jjhlee{at}plaza.snu.ac.kr).
From the Departments of Ophthalmology, Seoul Municipal Boramae Hospital,
Seoul (Dr Kim), Chungnam National University Hospital, Taejon (Dr J. L. Lee),
and Seoul National University College of Medicine and Seoul Artificial Eye
Center, Seoul National University Hospital Clinical Research Center, Seoul
(Drs Wee and J. H. Lee), Korea.
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