-
AM, M
and 2Pediatric Ophthalmology Services,
associated with a high risk of graft failure or failure of
amblyopia therapy in clear grafts. Nonetheless,
dysgenesis congenital corneal opacity congenital glaucoma
congenital hereditary
In order to achieve optimal visual results and
avoidvisual-deprivation amblyopia, corneal transplanta-tion must be
performed in the early months of life.Penetrating keratoplasty in
children has a higher
resulted in more successful pediatric corneal grafts.Pediatric
keratoplasty was performed infrequently
prior to the mid 1970s18 and was recommended only
children include difficult preoperative
evaluation;intraoperative problems such as low scleral
rigidity,increased fibrin reaction, and positive vitreouspressure;
the need for frequent examinations under
ment/early removal; increased risk of rejection andinfections;
and the difficulties with repeated refrac-tive error assessments,
and reversal of amblyopia.
SURVEY OF OPHTHALMOLOGY VOLUME 54 NUMBER 2 MARCHAPRIL 2009rate
of graft failure and a poorer visual prognosisthan adult
keratoplasty. Improved understanding ofintraoperative and
postoperative problems has
anesthesia for postoperative follow-up evaluations;frequent
loosening of sutures necessitating replace-I. Introduction
Congenital eye disorders, although infrequent, areimportant
causes of childhood blindness. Visualdeprivation due to corneal
opacification can lead tolong-term changes in the central nervous
system.161
in pediatric patients with bilateral corneal involve-ment.159
Technical advances, however, have nowlowered the age at which
keratoplasty is performedand indications have increased with
improvement insurgical techniques and therapies.
Special problems in corneal transplantation inendothelial
dystrophy corneal transplantation endothelial rejection
keratoplasty inchildren pediatric keratoplasty Peters anomaly 2009
byAll rightskeratoplasty remains the surgery of choice for the
management of pediatric corneal stromal opacitiesor edema.
Allograft rejection, graft infection, corneal neovascularization,
glaucoma, trauma to theanterior segment, vitreous pathology, and
additional surgical interventions, especially those related
toglaucoma management, are important risk factors. Successful
penetrating keratoplasty in childrenrequires careful preoperative
evaluation and selection of patients follow-up by well-motivated
parents,an expert corneal transplant surgeon, and a devoted
pediatric ophthalmologist. (Surv Ophthalmol54:245--271, 2009. 2009
Elsevier Inc. All rights reserved.)
Key words. acquired non-traumatic opacity acquired traumatic
opacity anterior segmentAzad Medical College, New Delhi, India
Abstract. Penetrating keratoplasty in children is a highly
challenging and demanding procedureAll India Institute of Medical
Sciences, New Delhi, India;Maulana1Cornea and Refractive Surgery
Services, Dr Rajendra Prasad Centre for Ophthalmic Sciences,MAJOR
REVIEW
Pediatric KeratoplastyM. Vanathi, MD,1 Anita Panda, MD, FICS,
FZia Chaudhuri, MS, FRCS,2 and Tanuj Dada245
Elsevier Inc.reserved.S, MRCOphth,1 Sujith Vengayil, MD,1
D10039-6257/09/$--see front
matterdoi:10.1016/j.survophthal.2008.12.011
-
Even with increased anatomic success of pedi-atric corneal
grafts, visual rehabilitation remainsa concern.
In developing nations an increasing number ofgrafts are
performed for infectious keratitis, post-infectious keratitis
corneo-iridic scars, or keratoma-lacia. Measures to maintain clear
graft and success-ful visual rehabilitation following
keratoplastyarerequired to achieve a successful anatomical
andfunctional outcome. This review of corneal graftingin infants
and children evaluates the variousindications, as well as factors
affecting graft prog-nosis, technique, special problems, and
outcome ofpediatric keratoplasty.
II. Indications
Pediatric corneal opacities have been classifiedinto three
categories:133,134 congenital, traumatic,and acquired
non-traumatic. Indications for pediat-
thelial dystrophy
246 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET ALB.
Congenital opacities: Non-CHED1. With associated glaucoma
a. Congenital glaucomab. Peters anomalyc. Other anterior segment
dysgenesis
2. Without glaucomaa. Sclerocorneab. Dermoidc. birth traumad.
Metabolic diseasese. Keloidf. Aniridia
C. Acquired traumaticD. Acquired non-traumatic
a. Keratoconusb. Infectious keratitis with or without
perforationc. Postinfectious corneal/corneo-iridic scarsd.
Keratomalaciaric corneal transplantation (Table 1) vary widely;
theproportion of keratoplasties performed for congen-ital
indications range from 14--64%, for acquirednon-traumatic
conditions they range from 19--80%,and for acquired traumatic
conditions they rangefrom 6--29%.1,31--34,95,134 Al-Ghamdi et al5
proposea newer classification that takes into account
visualprognosis in pediatric keratoplasty:
A. Congenital opacities--Congenital hereditaryendothelial
dystrophy (CHED)
B. Congenital opacities--Non-CHED
B1. Frequently associated with glaucomaB2. Infrequently
associated with glaucoma
TABLE 1
Indications for Pediatric Keratoplasty
A. Congenital opacities: Congenital hereditary endo-C. Acquired
traumaticD. Acquired non-traumatic
Developmental influences affecting anterior seg-ment
differentiation between the 6th to 16th week ofgestation result in
congenital corneal opacities.110,162
These influences may be genetic, infectious, trau-matic, toxic
or a combination of these factors. Theprevalence of congenital
corneal opacities is approx-imately 3/100,000. With congenital
glaucomaincluded this rises to 6/100,000.92,142 The mostcommon
primary cause of congenital corneal abnor-malities in the developed
nations is Peters anomaly(40.3%), followed by sclerocornea (18.1%),
dermoid(15.3%), congenital glaucoma (6.9%), microphthal-mia (4.2%),
birth trauma, and metabolic disease(2.8%).110
A. CONGENITAL OPACITIES: CHED
CHED presents as bilaterally symmetrical diffusecorneal
opacification and edema of varyingdegree.39,74,99,158 The stromal
opacity is thought toresult from terminal misdifferentiation of
theendothelial cells. Corneal clouding in the autosomalrecessive
type of congenital hereditary endothelialdystrophy is present at
birth or within the neonatalperiod. Nystagmus is often present, and
there are noother signs or symptoms. The autosomal recessiveform is
more prevalent in countries where consan-guineous marriage is
frequent.6,115 Patients with theautosomal dominant type of
endothelial dystrophyusually have clear corneas early in life, with
cornealopacification being slowly progressive and nystag-mus
infrequent. Photophobia and epiphora, may bethe first indications
of the dystrophy. As the opacitydevelops later in the dominant
type, infantile orautosomal dominant hereditary endothelial
dystro-phy have been considered to be more appropriatenames for
this variant.64
CHED may be associated with congenital glaucoma.Deafness may
accompany the autosomal dominanttype. Corneal sensitivity is
usually normal. On slit-lampevaluation, Descemets membrane is
thickened and,on retroillumination, has a beaten copper
appear-ance. Increase in thickness of Bowmans layer has alsobeen
reported.75 Widespread edema with hyalinedegeneration, superficial
vascularization, scarring,and calcium deposits may occur.99 Band
keratopathyand spheroidal degeneration have also been reportedin
some cases of CHED.115 The most importantpathologic finding is the
increased thickness of thenon-banded portion of the Descemets
membrane.The autosomal dominant (AD) form of CHED hasbeen mapped to
the pericentromeric region ofchromosome 20.26 Mutations in the
SLC4A11 gene
65,77cause autosomal recessive CHED.
-
geries may predispose to graft failure by disruption of
PEDIATRIC KERATOPLASTY 247The primary defect in patients with
CHED isa degenerated and dysfunctional corneal endothe-lium,
characterized by an increased permeabilityand an abnormal and
accelerated Descemetsmembrane secretion.9,70 The underlying
pathophys-iological mechanism may be related to an
abnormalendothelial barrier function, leading to secondaryswelling
of the stroma and epithelium. Histopatho-logic examination shows an
absence of the endo-thelial cell layer with presence of a variably
thickcollagenous layer posterior to the anterior bandedzone of
Descemets membrane.
CHED is not generally thought to be associatedwith other ocular
abnormalities. An ultrasono-graphic study of 20 eyes (10 patients)
with CHEDshowed ocular enlargement similar to that occur-ring in
uncomplicated axial myopia with an inverserelationship between the
degree of enlargementand the visual acuity or visual result
followingpenetrating keratoplasty. This suggests that
infantilecorneal edema sufficient to cause stimulus depriva-tion
may result in abnormal enlargement of theglobe.143
The dystrophy may be misdiagnosed as congenitalglaucoma. Birth
trauma, mucopolysaccharidosis,and intrauterine infections should
also be consid-ered in the differential diagnosis. Visual acuity
maybe surprisingly better than the clinical appearanceof the
eyes,117,131 but CHED can lead to ambylopia.Penetrating
keratoplasty in congenital hereditaryendothelial dystrophy is
moderately successful, andgraft survival and visual outcome is
better in caseswith delayed onset.
B. CONGENITAL OPACITIES: NON-CHED
The non-CHED congenital corneal opacities canbe subdivided into
those that are frequentlyassociated with glaucoma and those that
areinfrequently associated with glaucoma.
1. Frequently Associated with Glaucoma
a. Congenital Glaucoma
The causes of congenital corneal opacificationassociated with
glaucoma include congenital glau-coma, Peters anomaly with
glaucoma, and CHEDwith glaucoma. CHED with congenital
glaucomaoccurs infrequently.89,100 The combination ofCHED or Peters
anomaly with congenital glau-coma100 originates from defects in the
neural crestcell contribution with abnormal neural crest
cellmigration, resulting in congenital glaucoma andneural crest
cell differentiation, which results inCHED.16 Histopathological
evaluation revealsabsence of the endothelial layer with
variably
thickened collagenous posterior nonbanded zoneblood--aqueous
barriers. The simultaneous place-ment of glaucoma-filtering implant
at the time ofprimary penetrating keratoplasty has been
de-scribed.15 Reports of corneal grafting for congenitalglaucoma
after treatment with cyclophotocoagula-tion46 and glaucoma
filtering implants have appearedinfrequently.5
b. Peters Anomaly
Peters anomaly is one of the most commoncongenital corneal
opacification encountered incorneal practice. It is bilateral in
approximately80% of the cases. This congenital malformation ofthe
anterior segment is characterized by a centralcorneal opacity with
corresponding defects in theposterior stroma, Descemets membrane,
and endo-thelium. Iris strands typically arise from the collar-ette
and extend to the periphery of the cornealleucoma. The peripheral
cornea is usually relativelyclear. Peters anomaly is associated
with a wide rangeof congenital ocular and systemic abnormalities
andcommonly occurs as a sporadic disorder. A few caseshave
autosomal recessive and autosomal dominantinheritance.36,110 The
co-existing glaucoma cancomplicate the graft and visual prognosis
in themanagement of these cases.
The extent of ocular involvement varies from mildto severe.149
Mild disease is defined by the presenceof normal iris and lens.
Moderate disease is definedby the presence of central iridocorneal
adhesionsof the Descemets membrane. Abnormalities of crestcell
migration, proliferation, and differentiationcontribute to
disorders of the corneal stroma,endothelium, trabecular meshwork,
and iris. Thecoexistence of different anterior segment anomalieshas
been termed combined mesenchymal dysgenesis.100
Concurrent management of glaucoma and cornealopacification is
sometimes required. CHED shouldbe suspected if persistent and total
corneal opacifi-cation fails to resolve after normalization
ofIOP.89,106 Corneal decompensation due to congen-ital glaucoma is
a rare indication for cornealtransplantation in
childhood13,18,31,42,44,46,134,161
and usually confers a poor prognosis.Preoperative control of
intraocular pressure is
required before penetrating keratoplasty. Cyclodes-tructive
procedures for control of pharmacologicallyresistant elevated
intraocular pressure (IOP)46 maybe required to reducing the size of
eyes withbuphthalmos before performing keratoplasty. Mito-mycin C
trabeculectomy and glaucoma drainageimplant surgery are other
options in treatment ofpostkeratoplasty glaucoma. These penetrating
sur-(anterior synechiae), or other iris defects such as
-
248 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALatrophy, abnormal vasculature, or coloboma. Severedisease is
defined by the presence of corneo-lenticular adhesion, or by the
presence of cornealstaphyloma with or without corneal
adhesions.167
Peters anomaly has been associated with congen-ital anterior and
posterior segment anomalies aswell as systemic abnormalities.165
Glaucoma is themost common of the ocular anomalies, observed
in30--70% of eyes, and is considered the most difficultto control
among all the childhood glaucoma types.Peters anomaly patients are
at risk for developingglaucoma even if they present without
glaucoma atthe outset. Eyes presenting with glaucoma usuallyare
found to have the lens cataractous with orwithout adherence to the
posterior cornea. Micro-phthalmia occurs in 25--50% of the eyes.
Irisabnormalities, chorioretinal coloboma, staphyloma,retinal
dysplasia, cataract, ptosis, persistent hyper-plasic primary
vitreous, optic nerve hypoplasia,foveal hypoplasia, macular pigment
epitheliopathy,and colobomas are sometime associated.
Systemicanomalies, seen in 60% of the patients,
includedevelopmental delay, central nervous system
defects,craniofacial abnormalities, microcephaly, seizuredisorder,
fetal alcohol syndrome, and autism.Congenital cardiac
malformations, skeletal defor-mities, genitourinary malformations,
ear defects, aswell as cleft lip and palate may also be
present.
Histopathological evaluations132 indicate a centralabsence of
Bowmans membrane and iris synechia tothe periphery of the central
corneal leucoma.Extensive keratolenticular adhesions with
retrocor-neal fibrous tissue fill the central defect of
endo-thelium and Descemets membrane, suggestinga late anterior
displacement of the normallydeveloped lens leading to a secondary
endothelialdegeneration. Attenuated endothelium and abnor-mally
composed Descemets membrane indicatesprimary dysgenesis of the
endothelium. Extensivedefects of posterior stroma with anterior
stromaldisorganization and endothelial metaplasia suggestdysgenesis
of both the keratocytic and endothelialmesoderm. Although a unified
pathogenic mecha-nism is not consistently applicable, either
primary orsecondary dysgenesis of the corneal mesoderm maybe
responsible for the occurrence of Petersanomaly.
c. Other Mesenchymal Dysgenesis
The terms mesenchymal dysgenesis and anteriorchamber cleavage
syndrome refer to a spectrum ofcongenital ocular disorders ranging
from posteriorembryotoxon in its simplest form to Peters anomalyat
its most complex. Other conditions that areincluded in this
spectrum of congenital ocular
disorders are Axenfeld anomaly, Reiger anomaly,and syndrome and
posterior keratoconus.157 Allpatients with the Axenfeld-Reiger
(A-R) syndrome,irrespective of their ocular manifestations, share
thesame general features: a bilateral developmentaldisorder of the
eyes, a frequent family history, no sexpredilection, frequent
systemic developmentaldefects, and a high incidence of associated
glau-coma. The age at which A-R syndrome is diagnosedvaries from
birth to late childhood, most commonlyearly infancy or childhood.
Clinical features includeperipheral anterior segment anomalies and
irido-corneal abnormalities with or without other associ-ated
ocular and systemic anomalies.
2. Infrequently Associated with Glaucoma
a. Dermoids
Dermoids are classified as choristomas, and theopacification is
usually peripheral. They present asround or oval, whitish or
yellowish cones protrudingon the anterior surface of the eyeball.
They consistof ectodermal (keratinized epithelium, hairs,
seba-ceous and sudoriferous glands, nerves, smoothmuscles, and,
less frequently, teeth) and mesoder-mal elements (fibrous tissue,
fat, blood vessels, andcartilage) combined in different
proportion.124
Indications for surgery are astigmatism and cosm-esis.
Ultrasound biomicroscopy (UBM) evaluationcan be helpful in
determining the depth ofdermoids. Most cases may require simple
excisionwith or without amniotic membrane or only
lamellarkeratoplasty.
b. Metabolic Causes
Most metabolic causes are of autosomal recessiveinheritance. The
corneas are usually clear at birth,followed by progressive
opacification. Corneal cloud-ing may be a part of many metabolic
disorders,including those involving amino acids, lipids,
carbo-hydrates, purines, and so forth. Systemic
mucopoly-saccharidoses (MPS) are lysosomal storage disordersthat
affect the glycosaminoglycan catabolism. Seventypes of MPS have
been described, based on theenzymes affected and the clinical
manifestations.Because cornea contains glycosaminoglycans,
cornealclouding is a part of many of these MPS syndromes.MPS I-H
(Hurler), MPS I-S (Scheie), MPS- IV(Morquio), MPS VI
(Maroteaux-Lamy) and MPS VIII(Sly) are associated with variable
amounts of cornealclouding. Hurlers syndrome and Scheies
syndromeshare the deficiency of same enzyme (alpha--iduronidase).
The corneal clouding in the former ismore diffuse and central,
whereas the latter hasperipheral clouding progressing centrally
withage.118 Open-angle glaucoma may occur in
105,130both. Intelligence, stature, and lifespan are
-
PEDIATRIC KERATOPLASTY 249increased in Scheies syndrome compared
to Hurlerssyndrome. Pigmentary retinopathy and optic atrophyare
complicate the visual prognosis in thesesyndromes.43
Morquio syndrome and Maroteaux-Lamy syndromepresents with marked
dwarfism, chest wall deformities,cardiovascular abnormalities, and
corneal clouding.There is diffuse ground glass corneal stromal
opacifi-cation in Morquio syndrome155 and is of varyingseverity in
Maroteaux-Lamy syndrome. The morerecently described MPS VIII (Sly
syndrome) also hascorneal clouding (mild to severe), papilledema,
andretinal pigmentary degeneration.43
c. Sclerocornea
Sclerocornea is a primary, nonprogressive anomalyin which
scleralization of part or all of the corneaoccurs. In the
peripheral type of sclerocornea, theaffected area is vascularized
with peripheral arcades ofsuperficial scleral vessels. The corneas
in sclerocorneamay be smaller in diameter with diffuse
anteriorstromal opacification and may be associated focalnebular
densities and extensive superficialvascularization.
Sclerocornea can present either as a primary anom-aly or in
association with cornea plana17,40,72 and hasbeen reported to occur
in isolation or with associatedocular and systemic
anomalies.48,55,60,81,88,113,116,138
Histopathologically, vascularized collagenous tissueoccupies the
anterior one-fourth of the cornealstroma, with bundles of collagen
fibrils 75--90 nm indiameter. Descemets membrane shows
abnormalanterior lamination.102 The results of keratoplasty
insclerocornea have not been encouraging.37,52,163,172
Frucht-Pery45 observed reduced nystagmus excursionsand
attainment of reading vision in two children withbilateral
sclerocornea after unilateral corneal trans-plants at the ages of
4.5 and 16 years, respectively.
d. Birth Trauma
Birth trauma caused by forceps blade placementacross the orbit
and globe during delivery can resultin blunt trauma and rupture of
Descemets mem-brane. Descemets tears in birth trauma are
usuallycentral and unilateral in a vertical or obliquepattern.
Diffuse stromal and epithelial edema dueto birth trauma usually
clears within weeks ormonths. The residual high astigmatism
necessitatespenetrating keratoplasty when contact lens wear isnot
possible.11
e. Corneal Keloid
Congenital corneal keloids are a rare entity thatpresent as
white glistening benign protuberant
masses, appearing as single, solitary nodules orinvolving the
entire corneal stroma. Keloids occurmore frequently in males than
females. Congenitalkeloids usually occur in the presence of other
ocularanomalies,150 including peripheral iridocornealadhesions,
anterior segment mesenchymal dysgene-sis, aniridia, and cataract
with subluxated lenses.Corneal keloids also have been described
inchildren with Lowes syndrome, Rubinstein Taybisyndrome, and
fibrodysplasia ossificans progressive.Corneal keloid may mimic a
limbal dermoid.
Congenital keloids have been attributed toundifferentiated
hyperplasia of opaque cornealand scleral tissue. Corneal keloid in
Lowes syn-drome is major cause of visual disability in childrenover
the age of 6 or 7 years in whom glaucoma andcataract have treated
surgically. In cases of Lowessyndrome, it has been suggested that
amino acidsfilter into the cornea from abnormal vessels or
thatsubstances from within the anterior chamber gothrough a
defective endothelium. Histopathologi-cally, keloids are
characterized by a haphazardarrangement of fibroblasts, collagen
bundles, andblood vessels.
f. Aniridia
Absence of iris tissue is the sentinel finding, butadditional
ocular structures are often affected.Mutations of the Pax 6 gene
have been identifiedalso in families affected by aniridia. Corneal
lesionsin aniridia include peripheral pannus and
epithelialabnormalities that may advance centrally, resultingin the
need for penetrating keratoplasty.79 Aniridickeratopathy remains a
significant cause for visualloss. Poor vision in aniridic eyes may
be the result ofmacular hypoplasia, nystagmus, amblyopia,
cata-racts, glaucoma, and corneal disease, termed
aniridickeratopathy. Congenital aniridia rarely requires
kera-toplasty at an early age except when associated
withsignificant opacification or with glaucoma leadingto corneal
decompensation. Penetrating kerato-plasty alone is not adequate
treatment for severestromal scarring in aniridia, as it does not
treat theunderlying epithelial disease, which requries limbalstem
cell transplantation.57,76,82,139
g. Posterior Polymorphous Dystrophy (PPMD)
PPMD56 is autosomal dominant in inheritancewith high penetrance.
It is a bilateral disease, butmay be asymmetrical. Although it
typically occurs inthe second or third decade of life, it may also
becongenital or develop early in life. It may be seen inAlport
syndrome. The corneal lesions in PPMD arethe level of the Descemets
membrane and endo-thelium and may be vesicle-like, bands, or
diffuse
opacities. The vesicular lesions that are the hallmark
-
proper counseling for the social, economic, andpsychological
demands on them following surgery is
250 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET ALof
PPMD are seen as a transparent cyst witha surrounding gray halo at
the level of theDescemets membrane and the endothelium,appearing in
the entire cornea or as isolated lesions.Sinous brad bands and gray
thickened Descemetsmembrane may be seen. Endothelial guttae can
alsobe seen in PPMD. These may produce cornealedema ranging from
severe stromal edema tobullous keratopathy.
Peripheral anterior synechia, raised intraocularpressure,
corectopia, calcific band keratopathy,hydroxyapatite deposition in
the corneal stroma,and posterior keratoconus occur in PPMD. PPMDmay
be confused with iridocorneal endothelialsyndrome (ICE), but the
sporadic nature andunilateral involvement distinguishes ICE. The
char-acteristic pathologic changes in PPMD are theappearance of
epithelial like cells on the posteriorcorneal surface.
C. ACQUIRED TRAUMATIC
Penetrating injuries remain an important cause ofacquired
corneal scarring in the pediatric agegroup.159 Acquired traumatic
corneal scars are theindication for 8--26% of penetrating
keratoplastiesin children.5,20,32,33,95 The most important issue
tobe considered in the timing of keratoplasty forpenetrating trauma
is the threat of amblyopia.
D. ACQUIRED NON-TRAUMATIC
One of the most common causes of acquiredcorneal scarring in
children under the age of 6 yearsis Herpes simplex keratitis.159 In
developing nations,other infectious keratitides remain the
mainindications for pediatric keratoplasty.1,32,123,146--148
Penetrating keratoplasty for post keratomalaciacorneal melts are
also common.21,126,148
Keratomalacia from vitamin A deficiency as animportant cause of
preventable corneal opacifica-tion has a reported incidence varying
between 8%and 27.3%71,108,109,128 and remains a major cause
ofpediatric ocular morbidity and severe visual impair-ment in
developing countries.108,109,127 Ocularsurface changes include
xerosis, keratinised pla-ques, stromal punched out ulcers, and
focal ordiffuse stromal melting.127 Malnutrition, systemicdiseases,
and lack of immunization predispose tokeratomalacia. Acute corneal
melting results fromthe ocular pathological changes in severe
vitamin Adeficiency.128
Acquired non-traumatic corneal opacities werethe major
indication (71.32%) for pediatric kerato-plasty in a tertiary care
center in north India,32
which is in contrast to series from the western world.
Infectious keratitis (72.6%) and keratomalaciavital for a
successive outcome in pediatrickeratoplasty.
Early penetrating keratoplasty for congenitalcorneal opacity may
prevent deprivation amblyopia.However the increased risk of
failure, especially inneonatal and infant eyes, requires careful
caseselection. Younger age at the time of surgeryappears to
increase the risk of failure due todifficulties with intra- and
postoperativemanagement.
The decision regarding surgery in CHED cases is(27.36%)
constituted the major causes for kerato-plasty. Fever, diarrhea,
and malnutrition were thecommonly associated systemic presentations
in theacquired non-traumatic group in this large retro-spective
series. Poverty and low socioeconomicstatus prevalent in developing
nations predisposethose individuals to corneal infection and
malnutri-tion.32,122,146,148 Keratomalacia in children is has-tened
by protein-caloric malnutrition precipitatedby childhood
communicable diseases such asmeasles.129
III. Technique
Pediatric keratoplasty was considered previouslyto be
contraindicated because of its technicalchallenges due to a low
scleral rigidity and forwarddisplacement of lens--iris
diaphragm.13,47,103,115
Although pediatric keratoplasty is now consideredto be a safe
and effective procedure, specificproblems do exist in the
management of childrenwho undergo corneal transplantation.
A. PREOPERATIVE EVALUATION AND DECISION-
MAKING
An examination under anesthesia (EUA), includ-ing A and B scans,
is usually done prior topenetrating keratoplasty. A portable
hand-held slit-lamp evaluation immediately preoperatively
caneliminate the need for another EUA. In cases withposterior
segment pathology, electrophysiologicaltests, such as visual evoked
responses and electro-retinography, can help decide on the need
toproceed with surgery. The decision of surgery atan earlier age
will depend on the laterality of thecorneal condition and its
severity, the risks ofgeneral anesthesia for initial surgery and
forrepeated postoperative EUAs, and the associatedsystemic
abnormalities and metabolic conditions.
The commitment of parents to the long-term careof the child
after surgery plays a crucial role. Hence,difficult. Although the
cornea appears hazy and no
-
forming keratoplasty in one eye with the hope of
PEDIATRIC KERATOPLASTY 251achieving better visual acuity.115
In cases of Peters anomaly, the extent of ocularinvolvement is
to be graded preoperatively. Theassociation of central nervous
system abnormalitieswith in Peters anomaly, should prompt the
treatingophthalmologist to look for signs of central nervoussystem
problems (developmental delay, structuraldefects, seizure
disorders, fetal alcohol syndrome) asthese increase the difficulty
of caring for the child. Apediatric neurological examination and
neuroimag-ing may be required in such cases.
The important issue considered in keratoplastyfor traumatic
corneal scarring is the threat ofamblyopia. It has been recommended
not to delaykeratoplasty for penetrating trauma in childrenonce the
decision is made to perform the surgery.34
The optimal timing and sequence of penetratingkeratoplasty and
glaucoma drainage implant surgeryin refractory congenital glaucoma
patients whorequire corneal and glaucoma surgery is
stillunclear.8
The decision to perform regrafts is made in thelight of factors
such as age, risk of glaucoma, andrisk of amblyopia. When graft
failure occurs,regrafting is required to visually rehabilitate
thechild. The causes of the corneal graft failureinfluence the
outcome of the regraft. When therisk of surgical complications and
glaucoma out-weigh the benefits of the surgery, it is wise to
avoidregrafting.
Lamellar keratoplasty should be considered inorder to obtain
desired results in conditions such assuperficial scars or limbal
dermoid because of thesignificantly lower risk of rejection and
avoidance ofintraocular surgery. Tectonic patch grafts,148,152
rotational keratoplasty,84,90 and optical iridectomymay also be
considered in selective cases of pediatriccorneal opacification as
an effective alternativemanagement option to keratoplasty.
B. ANESTHESIA
When performing pediatric keratoplasty, it isdesirable to have
an anesthesiologist with experi-ence in pediatric anesthesia. It is
imperative to beable to maintain the optimal depth of
anesthesiathroughout the entire procedure. Use of a non-red reflex
is seen, these patients seem to see muchbetter than would be
predicted. If the patient hasgood fixation and the eyes are
orthophoric, surgerymay be delayed. However, if fixation is lost
andnystagmus develops, penetrating keratoplastyshould be performed
promptly. When the childpresents with nystagmus, some recommend
per-polarizing muscle relaxant with a peripheral nervestimulator
can help eliminate the risk of movementand contraction of the
extraocular muscles.47
Hyperventilation of the patient can help reduceintraocular
pressure.7 A slightly higher positioningof the head aids in
lowering positive pressure.
C. PREPARATION OF GLOBE
Increased positive pressure during surgery isa major problem in
pediatric keratoplasty. Afteranesthesia is induced, 20% intravenous
mannitol(0.5--1.5 g/kg body weight over a period of 20--30minutes)
and/or digital massage aid in achievingoptimal ocular hypotony
during surgery. Somesurgeons prefer to use preoperative Honan
balloonand intravenous mannitol to reduce positive vitre-ous
pressure and the possible risk of anteriordisplacement of the
lens--iris diaphragm. Preopera-tive mydriatics or miotics may be
used depending onthe procedure. The surgical table should contain
allinstruments necessary to deal with an unexpectedlens loss in the
even of raised positive pressure. Thesurgeon should ensure that the
donor button hasbeen punched and is ready before anterior
chamberentry.
A lid speculum with or without Flieringa ring isused. Care
should be taken to ensure that thespeculum, surgeon, and assistant
do not applypressure on the globe. A lateral canthotomy maybe
considered. As pediatric eyes have an increasedscleral elasticity
and decreased scleral rigidity, theuse of a Flieringa ring provides
scleral support forthe immature and lax infant tissue, thereby
prevent-ing collapse of sclera after host trephination.
TheFlieringa ring must be sutured with care in infantsbecause the
needle can penetrate the thin sclera ofpediatric eyes and cause
retinal tears. In addition,unequal placement of the fixation
sutures can resultin irregularity of the graft recipient bed
andconsiderable astigmatism.
D. TREPHINATION
The recipient cornea is trephined to 70--80%depth by using
disposable suction trephines. Cor-neal trephination is technically
demanding inyounger patients because of the increased elasticityof
infant tissue.18,116 Anterior chamber entry ismade with an MVR
blade through the incision, andthe chamber is filled with
viscoelastic to protect thelens and iris from injury. The incision
is thencompleted with scissors. The donor cornea ispunched out from
the endothelial side, and a grafthost disparity of 0.2--0.5 mm is
used by most cornealsurgeons. Rapid formation of peripheral
anteriorsynechias (PAS) and difficulty reforming the cham-
ber are also important problems faced while
-
chamber is entered may decrease the risk of PASimplantation,
synechiolysis, and anterior vitrectomy
252 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALformation and secondary glaucoma. Performingseveral peripheral
iridectomies has been found tobe important in preventing synechia
formation.Hemorrhage in the anterior chamber should becontrolled
and clots removed as fibrin remainingcan lead to formation of
posterior synechia and PASformation. Although would closure is
faster witha running suture, interrupted single sutures
forkeratoplasties is usually preferred in children as theyallow for
an earlier suture removal to avoid suture-related problems.
Oversized corneal grafts (1 mm) have been usedin keratoplasty in
an attempt to increase themorphologic success of corneal grafting
in chil-dren.147 In a prospective, nonrandomized clinicaltrial, 40
pediatric patients with unilateral or bilateralcorneal
opacification of congenital or acquiredorigin (post infectious
keratitis corneal opacifica-tion, 25%; traumatic corneal scars,
20%; sclerocor-nea, 20%) underwent corneal grafting surgery
withdonor corneal buttons oversized by 1 mm. At theend of 1 year,
85% of grafts remained clear,providing an adequate anterior chamber
depth(2.20 0.612 mm in the congenital group and2.36 0.302 mm in the
acquired group). Althoughthe authors concluded that oversizing
donor cor-neal buttons achieves adequate anterior chamberdepth in
pediatric cases and can help preventpostkeratoplasty glaucoma, a
longer follow-up willbe required to confirm these conclusions.
Larger grafts have been used in patients withkeratoconus and
buphthalmos.31,140 Failed regraftsin congenital glaucoma have been
found to beassociated with smaller diameter of the graft.
Trans-planted endothelial cells migrate over graft--hostjunction to
the recipient rim; the fewer number oftransplanted endothelial
cells in small-sized graftsmigrating over to the relatively larger
sized recipientrim in buphthalmos has been thought to beresponsible
for graft failure. Toker et al140 thereforerecommend adjusting the
graft size in each eyebefore surgery. Surgery in buphthalmic eyes
can becomplicated as the corneas are thinner.
E. CONCOMITANT PROCEDURES
Loss of crystalline lens and vitreous at the time
oftransplantation may occur despite rigorous pre-ventive measures.
When the posterior capsule isperforming pediatric keratoplasty. The
use of 100U/ml of heparin solution to irrigate the anteriorchamber
to prevent fibrin formation and subse-quent synechia is preferred
by some. The injectionof sodium hyaluronate into the angle after
anteriorintact, a thorough aspiration of cortical remains ismay be
performed as required. Performance of anadditional surgical
procedure at the time kerato-plasty is strongly associated with
decreased graftsurvival rate.1,8,31 Among the variables
analyzed,corneal ulceration, vitrectomy-lensectomy, persis-tent
inflammation, posterior segment anomalies,regrafts, and
postoperative complications have beenfound to be associated with
poor visual outcome andallograft survival.33,34
F. SIMULTANEOUS KERATOPLASTY WITH
GLAUCOMA FILTERING DEVICE IMPLANTATION
Upon completion of the keratoplasty, a limbal-based conjunctival
flap is created in the super-otemporal quadrant. The plate of the
primeddrainage device is sutured to the sclera with
8.0non-absorbable sutures, 8--10 mm posterior to thelimbus. The
tube is cut to an appropriate lengthwith an anterior bevel and
inserted into the anteriorchamber through a 23-gauge needle track
and iscovered by a donor scleral patch. In patientsyounger than 6
months with anteroposteriordiameter less than 22 mm, a
pediatric-sized implantis preferred.7 When cyclocryotherapy is
necessary incases of refractory glaucoma requiring
penetratingkeratoplasty, it is typically performed in two or
threequadrants with two to four spots in each quadrant.
Problems in pediatric keratoplasty can be sub-divided into those
arising in the preoperative,intraoperative, and postoperative
periods.18
Preoperative problems
1. Complete preoperative evaluation of thecorneal pathology is
usually not possible.
2. Need for specialized investigations such
asultrabiomicroscopic examination.
3. IOP evaluation usually not accurate in opaquecorneas.
4. Patient should be evaluated for systemic asso-ciations in
cases of congenital corneal opacities.
Intraoperative problems
1. Small size of the palpebral fissure reduces theworking space
available for manipulations.
2. Excessive lowering of the intraocular pressureis to be
avoided as severe hypotony preventsrequired. If vitreous prolapse
occurs, anteriorvitrectomy with an automated vitreous cutter mustbe
performed. Any vitreous strands adherent to thewound or iris are
removed to prevent vitreousadhesive syndromes and PAS formation.
Plannedadditional procedures, such as lens extraction, IOLoptimal
trephination of the recipient cornea.
-
and less frequently thereafter. Frequent EUAs arealso required
to detect problems such as glaucoma
PEDIATRIC KERATOPLASTY 2533. Caution is to be exercised while
performingthe scleral fixation due to the higher risk ofperforation
as the sclera is thinner in pediatriceyes.
4. Use of Flieringa rings with unequal placementof fixation
sutures may also result in increaseddistortion resulting in
difficulty whilesuturing.
5. Need for performing associated proceduressuch as lensectomy,
anterior vitrectomy, glau-coma procedures, and so on, is high.
6. Increased positive pressure of vitreous withforward shift of
lens--iris diaphragm due to thelow scleral rigidity and increased
elasticity ofpediatric eyes.
7. Increased difficulty in suturing and cheesewiring due to the
thin peripheral cornealtissue in certain cases.
G. PEDIATRIC KERATOPROSTHESIS
Use of keratoprosthesis to treat pediatric
cornealopacity11,25,114 offers an alternative treatment optionfor
those eyes with poor prognosis for graft survival.A retrospective
review of 22 eyes of 17 pediatricpatients with a history of corneal
opacification dueto primary congenital disease and/or previous
failedkeratoplasty treated with keratoprosthesis surgery
byAquavella et al11 explores the option of keratopros-thesis in
pediatric patients. Over a mean follow-upof 9.7 months (range 1--37
months), all 21 Bostonkeratoprostheses were retained without
dislocationor extrusion. In the two cases with AlphaCorimplants,
the keratoprosthesis was not retained(spontaneous extrusion in one
case and traumaticdislocation in the other) and had to be
replacedwith a Boston keratoprosthesis. The visual axisremained
clear in all cases, with five eyes havingundergone retroprosthetic
membranes removal.Reoperation for management of concurrent
glau-coma (three eyes) or retinopathy (two eyes) wassometimes
required. Although the authors11 con-clude that the Boston
keratoprosthesis implantationhelps to restore a clear visual axis
without extrusionor rejection and may be an appropriate
alternativefor the management of pediatric corneal
opacity,keratoprosthesis in pediatric cases should be con-sidered
only as the last resort. Keratoprosthesis mayoffer the possibility
of rapid visual rehabilitation dueto high optical quality, which
enables early ambly-opia treatment.
H. EPIKERATOPLASTY
Epikeratoplasty has been performed to providerefractive
correction of pediatric aphakia.
Epikeratoplasty in children is more successful if riskand
retinal detachment.All sutures are usually removed within 3
months
in children younger than 8 years and by 6 months inolder
children. Different centers follow their ownset routines for suture
removal in pediatric kerato-plasty. An increased frequency of
topical steroid andantibiotics is required for a week after
sutureremoval. Suture loosening and graft rejection canfactors,
such as younger patient age, microcornea,corneal endothelial cell
dysfunction, mentalretardation, and combined cataract surgery,
areavoided.28 Complications such as residual refractiveerror,
epithelial defect, interface opacities, graftvascularization and
graft infection, graft necrosis,graft haziness or opacification,
and graft dehiscencehave made this procedure less desirable.
IV. Postoperative Management
Postoperative management of pediatric cornealgrafts demands
dedicated follow-up evaluationsunder anesthesia, monitoring of
postoperativemedications for frequency alterations,
appropriatemanagement of sutures, close watch for
rejection,frequent correction of refractive errors, initiation
ofamblyopia therapy, and ensuring compliance tolong-term amblyopia
therapy. Hence, the need toemphasize on the biphasic approach of 1)
main-taining a clear graft, and 2) reversing amblyopia, isof
paramount importance in the postoperativemanagement.
A. IMMEDIATE POSTOPERATIVE MANAGEMENT
Postoperative treatment regimen involves topicalcorticosteroid
along with antibiotics and lubricants.Topical steroids are given
more frequently in theinitial postoperative period and gradually
taperedand changed to less potent steroids such asfluoromethalone
in 3--6 months. Topical CsA 2%when used in pediatric keratoplasty
can help reducefrequency and duration of postoperative
topicalsteroids. EUAs in the early postoperative period
areimportant in order to assess the graft status, assessintraocular
pressure, and initiate prompt treatment,if required.
B. SUTURE REMOVAL
Loosening of sutures or vascularization requiresan urgent EUA.
Frequent EUAs during the first 2months after pediatric
keratroplasty in children lessthan 6 months of age is mandatory
until all suturesare removed and at monthly intervals for 6
monthsoccur insidiously in young children who cannot
-
postures, and so forth, removal of any media opacity,correction
of refractive errors, and providing the
254 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALcommunicate discomfort and vision changes. Graftrejection is
thought to occur more quickly inchildren due to an amplified wound
healingresponse.24
C. REFRACTIVE CORRECTION
Refraction is done after suture removal for opticalcorrection,
and amblyopia therapy is initiated assoon as possible. In cases of
potential risk of denseamblyopia, early refractive correction may
be pro-visionally prescribed with frequent changes asrequired in an
attempt to increase the efficacy ofamblyopia therapy. Early
refractive rehabilitation byspectacle correction or contact lenses
to correctresidual astigmatism and contact lenses or intraoc-ular
lens implants for aphakia are required.
D. AMBLYOPIA MANAGEMENT
The neurological basis of amblyopia is related tothe concept of
cortical competition. Visual corticalcells are potentially
connected to both the eyesequally, provided both eyes are
functioning.49,59,135,153
If one eye predominates, these cortical cells arestolen by the
dominating side. The dominance ofone eye over the other is usually
a result of bettervisual acuity in that eye, especially if
primarystrabismus is not present. It is postulated thatstrabismic
amblyopia is initiated as a maladaptivedifferentiation in the
ocular dominance columns,whereas the non-strabismic amblyopias
(anisome-tropic and the deprivation amblyopias) may beinitiated
from the malfunctioning of the ganglioncell population of the
amblyopic eye.41,69,135 Thusthe non-strabismic amblyopias are
caused by opticaldegradation of one retinal image while in
strabismicamblyopias both retinal images are initially clear.The
total clinical picture is confusing because ofsecondary changes in
other parts of the centralnervous system that occurs subsequently.
Themanifest features can be due to a slower, moreenduring type of
change (pooling, loss, andre-wiring of the neurons) as well as a
more transient,adaptive type of response (such as suppression
ofdiplopia). Thus, mechanisms leading to amblyopiahave been divided
into two basic types, thosecausing form deprivation and those
resulting inabnormal binocular interaction.86,120,135,136,153,154
Itis of importance to realize that the process of visualmaturation
and development of amblyopia becomesespecially significant in the
early period of visualdevelopment, also called the critical period,
whenneural plasticity makes the visual system vulnerable.This may
last is up to 7--8 years inhumans.69,135,153,154 Once this period
is over ambly-
opia cannot occur. This is the time when amblyopiaworse eye a
competitive advantage over the bettereye by occluding the better
eye, either physicallywith a patch or with the help of cycloplegic
drugs.Strict vigilance and monitoring of therapy isimportant.
Aggressive amblyopia management ismandatory for good visual
outcomes in pediatricpatients undergoing
keratoplasty.29,33,34,135,153,171
Occlusion of the better eye by direct patchingforms the mainstay
of the treatment for amblyopia.A patch applied over the skin is
preferred to a patchover the spectacles as the child can easily
take off thespectacles or look outside through the sides of
theoccluded spectacle. The principle of this therapy isto provide a
competitive advantage to the worse eye,which will eliminate the
components of abnormalbinocular interaction and the inhibitory
influencesof the better eye on the receptive fields of the
worseeye. Occlusion should be started as soon as possible.The
family should be educated to recognize thefixating eye and guide
the patient toward freealternation.19,85,101,104,111,112
E. REGRAFTS
Repeat penetrating keratoplasty is quite oftenrequired in
pediatric eyes as there is high chance offailure of the primary
graft. The graft survival rate islower in eyes undergoing multiple
regrafts.151
Regrafts in congenital glaucoma tend to fail earlierthan primary
grafts.2,140 In the heterogenous groupstudied by Dana et al,33 20%
of eyes had undergoneregrafting at a mean of 17 months after the
firstsurgery, of which 22% had a second regraft ata mean of 62
months after the original procedure.Anatomical success of the
grafts dropped from 78%in the eyes that had one graft, to 19% in
those eyesthat had two grafts, and to nil in those eyes that
hadtherapy is maximally effective as the immature visualsystem can
be modulated.41,49,69,135,153,154
As the visual deprivation in amblyopia is morerelated to the
competitive interaction between boththe eyes rather than disuse in
most cases, results oftreatment are better if started within the
criticalperiod as this is the time when changes in the
lateralgeniculate body and the visual cortex are partially
orcompletely reversible.135,153 The key for the man-agement of
amblyopia is equalization of visual acuityin both the eyes so that
they can function together.The modalities include a high degree of
suspicion ofthe condition, early detection, observation
ofassociated abnormal eye movements in the form ofroving eye
movements, nystagmus, abnormal headthree grafts.
-
10%. Ten out of 26 transplants in the series ofComer et al29
were regrafts, of which seven sub-
late for management. Seventeen of 19 grafts withrejection failed
in the series reported by Cowden.31
PEDIATRIC KERATOPLASTY 255sequently failed. Of 58 eyes (the
majority of whichhad Peters anomaly or sclerocornea) 23
eyesrequired regrafting between 2 weeks and 110months
postoperatively.44 The probability of main-taining a clear graft,
calculated by survival analysis,was 75% (SE, 6%) at 1 year and 58%
(7%) at 2years. Rejection reversals tend to be more successfulin
the primary grafts compared to that in regrafts.68
The increased need for regrafting, besides the highincidence of
complications in pediatric cornealtransplantation, calls for a
cautious approach todecision-making before attempting surgical
inter-vention. Repeat grafts may still be indicated ininfants or
children in the amblyogenic age group aseven if the regraft
survives for only 1 year, this willenhance the visual development
of the child andreduce the risk of amblyopia.47
V. Complications
Acquired corneal scars, later corneal decompen-sation in older
children, and phakic eyes have thebest prognosis. Corneal
perforations, active inflam-mation or infection, and infants with
multipleocular anomalies have the poorest prognosis.Children
undergoing combined procedures havebeen found to have a less
favorable result than thoseundergoing a single- or two-staged
procedure.31
Complications such as cataract development, sec-ondary glaucoma,
epithelial defects, band keratop-athy, retinal detachment, wound
leakage,retrocorneal membrane, and microbial keratitismake the
postoperative course complex oftennecessitating regrafting.44
Preoperative vasculariza-tion of the cornea, persistent epithelial
defects, andParmley et al94 also had a high rate of regrafts in26
grafts on 16 eyes in 10 patients of which six eyesthat were grafted
two or more times over a meanfollow-up of 30 months. Of the six
eyes that wereregrafted, only one child obtained ambulatoryvision.4
Apart from the eight primary keratoplasties,three repeat
keratoplasties were required in theseries of Peters anomaly
described by Althaus andSundmacher.10
The Kaplain-Meier survival curve showed a highlysignificant
difference in the likelihood of maintain-ing a clear graft with
initial grafts compared withsecond, third, and fourth grafts in the
large series byYang et al.167 Thirty-six percent of first
graftsmaintained long-term clarity compared with just6% of second
grafts. The probability of second orsubsequent grafts surviving for
3 years was less thanperformance of lensectomy-vitrectomy were
factorsStulting et al134 reported 11% of graft failures to
berelated to allograft rejections; whereas more than50% of the
graft failures in the series by Dana et al33
were attributed to graft rejection. Although graftrejection was
the primary cause for graft failure intheir series, Dana et al 35
conclude that rejection isnot a significant predictor of failure as
most of theirmost highly correlated with poor graft
survival.134
Postoperative shallowing of the anterior chamberand the
occurrence of anterior synechiae leading tosecondary glaucoma are
other causes of graft failurein the pediatric age group.147 Other
factors limitingvisual outcome include glaucoma, hemorrhage,
andretinal complications.18
A. GRAFT REJECTION
Pediatric corneal transplantation has an increasedrejection rate
because of the more active immunesystem in younger patients.9
Endothelial immunerejection165 leading to graft failure is one of
themain causes for graft failure. Well-established graftrejection
in children is usually irreversible.18
Increased risk of allograft rejection after
bilateralkeratoplasty is controversial.9,12,38 Early
interventionmay be considered in both eyes in an attempt toprovide
useful vision and avoid irreversible ambly-opia. In infants with an
amplified inflammatoryresponse, graft rejection can occur rapidly
and beless responsive to treatment. Early symptoms of
graftrejection, such as reduced visual acuity and oculardiscomfort,
cannot be communicated, resulting ina delay in the diagnosis and
treatment and, hence,a higher degree of graft failure. The
reportedpercentages of graft rejection in pediatric keratro-plasty
vary between 22%146 and 43.4%.1,62 Graftrejection was the cause for
all graft failures in seriesof pediatric keratoplasty in CHED
reported byJavadi et al62 in which rejection had occurred in10 eyes
(43.4%), of which endothelial rejectionaccounted for 30.4% of
eyes.
Yang et al observed graft rejection to be the mostfrequent cause
for graft failure in their series (25%),with 48% of the rejection
episodes involving the firstgraft.167 Rejection was reversible in
only 28% ofepisodes, showing a much lower reversal rate inpediatric
grafts compared to that of 50--78% in adultgrafts.9 In the series
by Comer et al,29 53% of therejection episodes were not reversible
and resultedin failure. Vajpayee et al146 also noted rejection
in22.5% of cases with 55% of them not beingreversible, and all of
these children had reportedrejection episodes were successfully
treated.
-
[HLA]-matched) keratoplasties (11 autologous pen-etrating
rotating, 42 penetrating (homologous not
are attributed to suture-related causes. Completion
256 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALHLA-matched), and 3 penetrating homologousHLA-matched
keratoplasty) with the main indica-tions being traumatic scarring
(22 eyes), cornealdystrophy (13 eyes), scarring after keratitis
(10eyes), graft failure (7 eyes), and chemical burn (5eyes). Even
though 40 of 42 eyes after PK had a cleargraft, only 21 of the 42
eyes obtained a visual acuityof 0.5 or better. Graft rejection was
noted in 20% ofthe homologous PKs. Sufficient thought must gointo
evaluating tissue matching in PK.18
Topical cyclosporine (CsA) 2% is used four timesa day along with
systemic steroids as a routine in PKby some surgeons. It is then
tapered over 3 monthsto once a day. CsA is a potent
immunomodulatorthat affects early stages of antigenic sensitization
andsubsequent proliferation of immunocompetentcells. The available
reports in literature on efficacyand safety of topical CsA in PK
are few. Cosar et al30
observed that the rejection-free graft survival rate intheir
study was higher with use of topical CsA.Although the difference in
graft survival ratesbetween the CsA cases and control group was
notstatistically significant, Cosar et al30 consider theirresults
to be impressive as use of topical CsA hadprolonged graft survival
rates in the corneal grafts ofmuch younger children who have a high
risk of graftrejection. Prolonged use of topical corticosteroids
isassociated with increased risk of cataract formation,glaucoma,
and delayed wound healing. Use oftopical CsA eliminates these risks
of topical steroids.Whereas steroids induce a general ocular
immuno-suppresion with an enhanced risk for secondaryinfection,
topical CsA, being a specific immuno-modulator by nature of its
action on T lymphocytesonly, does not affect the antimicrobial arm
of theimmune system. Therefore there is less risk of
graftinfection. Early suture removal can also be donewith use of
topical CsA as this does not delay woundhealing, which is
beneficial in pediatric cornealgrafts as the suture related
problems can beminimized.
B. GRAFT INFECTION
Bacterial keratitis after primary penetrating kera-toplasty in
children is a serious complicationresulting in graft failure and
poor visual outcome.McClellan et al83 were successful in retaining
cleargrafts with five out of six rejections.
Schonherr et al119 reported results of 71 kerato-plasties in 66
eyes of 61 patients (15 lamellar(homologous not human leucocyte
antigenData on pediatric corneal graft infections isof suture
removal as early as possible should beconsidered. A close follow-up
is required even afterremoval of sutures, especially in eyes with
glaucomaor ocular surface disorders. Prolonged use ofantibiotics
until all sutures have been removedmay decrease the risk of
development of graftinfection. Non-compliance to follow-up,
resultingin the failure to recognize irritation due to
loosesutures, is the most important risk factor for graftinfection
in developing countries. Lower socioeco-nomic status and long
distance from the treatingreferral center contributes to delay in
diagnosis andtreatment.1 There is a higher prevalence of
graftinfection in eyes with congenital corneal opacity(especially
in eyes with congenital glaucoma)compared to acquired causes. The
requirement toperform multiple glaucoma and other
surgicaldiagnostic procedures may explain the increasedprevalence
of graft infection in congenital glaucomaeyes undergoing
penetrating keratoplasty.
Wagoner et al156 report culture-positive bacterialkeratitis in
35 (17.3%) of their 202 primary pediatrickeratoplasties with
Gram-positive organismsaccounting for infection in 91.4% cases and
77.6%of isolates. Streptococcus pneumoniae is the mostcommon
organism causing pediatric graft infectionin most studies. Final
visual outcome is poor ingrafts affected by bacterial infection,
with 65.7%retaining a visual acuity of hand movement or
less.Infectious corneal ulcer resulted in graft failure insix eyes
(30%) of cases with loose sutures accountingfor infection in four
eyes (67%). Wagoner et al156
also report a higher prevalence of bacterial keratitisin eyes
with congenital than in acquired opacities.In eyes with
endophthalmitis secondary to graftinfection, Haemophilus influenza
and Streptococcuspneumoniae have been isolated from the
vitreous.8
Frequent postoperative examinations as long assutures are
present will help in reducing risk ofinfections due to neglected
sutures. Prolonged useof broad spectrum prophylactic antibiotic
therapyuntil all sutures removed can also help in
reducingsuture-related complications.
C. PERSISTENT EPITHELIAL DEFECT
Persistent epithelial defects (PED) in pediatriccorneal
grafts47,133,134 can result in graft failure.PED resulting from
poor graft host junctionlimited.5,33,134 Reported incidences of
graft infec-tion vary from 10--50% in pediatric grafts.156
Graft survival prognosis becomes bleak after onsetof bacterial
infection and hence calls for aggressivepreventive measures. Most
pediatric graft infectionsapposition and faulty suturing, early
suture
-
of vision.
dehiscence is now rarely seen.
keratoplasty.
cedures for IOP control and visual rehabilitation.
continues to remain less than satisfactory.With results varying
in different etiological
PEDIATRIC KERATOPLASTY 257I. AMBLYOPIA
As already discussed amblyopia is the mostimportant factors for
visual outcome in anatomicallyH. RETINAL DETACHMENT AND
PHTHISIS
Other vitreoretinal complications are expulsivechoroidal
hemorrhage (2--3%), retinal detachment(3--5%), and phthisis
(4--13%).47 Yang et al166
reported a relatively high rate of retinal detach-ments (35%)
and phthisis (18%) in eyes with Petersanomaly that underwent
multiple intraocular pro-G. GLAUCOMA
The incidence of post-penetrating keratoplastyglaucoma has been
found to be 5--9%.47 Yang et alreported166 126 glaucoma procedures
performed in34 eyes children with Peters anomaly followingF.
ENDOPHTHALMITIS
The reported rate of endophthalmitis followingpediatric
keratoplasty is about 2%.31,42,134 Theincidence of ocular
infections (4--9%)31,42,134 fol-lowing pediatric keratoplasty is
higher in cases ofchildren undergoing multiple procedures, as
inglaucoma patients where there is a need formultiple intraocular
interventions.E. CATARACT
The reported rates of cataract vary between 2%and 7%,18,33,42
with as much as 18%166 in eyes withmultiple interventions.D. WOUND
DEHISCENCE
Wound leak and dehiscence (2--10%)18,31,33,42
due to suboptimal suturing can lead to postopera-tive shallowing
of the anterior chamber necessitat-ing immediate postoperative
suturing underanesthesia. With improved surgical technique
andsuture materials, postoperative wound leak andloosening, drug
toxicity, tear, and surface abnormal-ities may predispose to graft
infection. Prolongedepithelialisation, subsequent to PED also lead
tosignificant graft haze compromising optical qualitysuccessful
grafts.conditions for which corneal transplantation isdone in the
children, it seems more logical toanalyze the outcomes in
accordance to theindications for which the grafts are
performed.
A. CONGENITAL OPACITIES: CHED
Graft survival rates in cases of CHED vary widelywith reported
percentages ranging from 25% to90% in most
series.5,6,62,75,99,115,117Keratoplasty forCHED has a higher degree
of success whencompared with transplantation for other causes
ofcorneal opacification, as the pathology in CHED isusually limited
to the cornea only. When performedearly, the prognosis for improved
visual acuity inchildren appears to be good.6 Two series of
CHEDhave proposed delaying surgery in patients when-ever
possible,75,115 whereas a third series6 hasrecommended early
surgical intervention. Theseries by Schaumberg et al117 dealt with
only thosecases of CHED in which surgery was performed ata young
age (predominantly autosomal recessivetype). Although the threat of
dense amblyopia inuntreated eyes and good surgical success rates
invery young children favor consideration of relativelyearly
surgical intervention in the most severelyaffected cases, there
seems to be evidence to supportdelaying surgery in some cases.117
Consideration ofhow differences in age of onset, severity of theVI.
Outcome of Pediatric Keratoplasty
Comparison of graft survival outcomes among thereported studies
is difficult due to the heterogeneityof the involved conditions,
varying size of the studygroup, and varying periods of follow-up
(Table 2).
Poor results in corneal grafting in congenital,central corneal
opacities prompts surgeons to avoidpenetrating keratoplasty in
patients with unilateral,congenital corneal
opacities.61,96,126,134,159,164 Irre-versible amblyopia, glaucoma,
other structuralabnormalities of the anterior segment, and
mentalretardation further worsens visual rehabilitation inthe
congenital corneal opacity cases.134 However,encouraged by their
good results, Frueh andBrown44 advocated corneal grafting for
congenitalopacities in infants prompting an early interventionin
unilateral as well as bilateral involvement.Pediatric keratoplasty
is associated with an excellentprognosis for graft survival in eyes
with CHED anda fair prognosis for graft survival in eyes with
non-CHED congenital opacities and acquired opacities.However, even
with increasingly better anatomicalsuccess of corneal grafts in
children, visual outcomedisease, and timing of surgery influence
the
-
TABLE 2
Outcome of Pediatric Keratoplasty in Reported Major Studies
StudyNo
of Eyes IndicationsMean Ageat Surgery
MeanFollow-Up
AnatomicalSuccess
FunctionalSuccess
Graft Survival
1 Year 2 Years3 Years or
More
Zaidman2007170
38 eyes Peters anomaly 5 mo 78.9 mo 90% 54%(O20/200)
-- -- --
Sharmaet al2007122
168 eyesof 154children
Acquirednontraumatic-53.4%
Congenital - 33.7%Acquired
traumatic - 14%
5.4 3.9 yr 14.52 8.54 mo - 30.1%(O20/200)
-- -- 77%
Al Ghamadi20075
165 graftsin 134children!12 years
CongenitalCO-78.8%
Traumatic - 10.9%Acquired
nontraumatic -10.3%
50 mo 44.2%
Michalli200587
86 grafts in63 eyes
Congenital CO 40.4 mo 78%
Patel et al200598
65 grafts in58 eyes of52 children!14 yr
Congenital CO - 16%Acquired
nontraumatic - 74%Traumatic - 10%
CongenitalCO - 3 yr
Acquirednontraumatic- 12.4 yr
Traumatic -10.8 yr
-- -- 60% (O6/18) 82%(Congenital
CO -78%Nontraumatic85%Traumatic100%)
-- --
Al Torbak20048
20 eyes of17 children!14 mo
Congenitalglaucoma(simultaneousAGV PK)
11.7 mo 30.8 ( 11.1) mo 35% (35% hadambulatoryvision)
-- 43%17%at4 yr
McClellan etal 200383
19 grafts in18 eyes of16 children!15 yr
Congenital COAcquired
9.24 yr 6.6 years 73.7%(Congenital
CO 71.4%Acquired75%)
Cong.CO - 14.4%(O6/60)
-- -- --
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VANATHIETAL
-
Javadi et al200362
24 eyes of15 children!12 yr
CHED 8.1 ( 2.5)yr 35.5 ( 36.2) mo 79.1% 94.7%(* 19
eyes,O20/120)
88% 88% 88% at3 yr
74% at5 yr
Comer etal 200129
26 grafts in16 eyes of11 children
Congenital CO 13 weeks 62.5% 68.75%(ambulatoryvision)
61%
Aasuri et al20001
154 grafts in140 children!14 yr
Congenital CO -30.5%
Traumatic - 14.2%Nontraumatic
acquired - 55.1%
6.5 yr 1.3 yr 66.2% 43.8%(* 121 eyesO20/400)
(CongenitalCO - 63.8%
Traumatic -54.5%
Acquirednontraumatic -70.6%)
-- --
Dada et al199932
(study onindications)
415 grafts(!12 yr)
Congenital CO -12.28%
Acquired nontrau-matic - 71.3%
Regrafts - 10.8%Acquired traumatic -
5.4%
- -- -- -- -- -- --
Yang et al1999167
144 graftsin 72eyes of47children!12 yr
Peters anomaly 4.4 mo 11.1yr
39%(35% -primary grafts)
-- 49% - 44% at3yr
35% at10 yr
Schaumberget al1999117
21 grafts in16 eyes of9 children!12 yr
CHED 40 mo 70 mo 69% 40%(* 10 eyes,O20/200)
-- 71% -
Danaet al199735
47 grafts(36 eyesof 29children!12 yr)
Peters anomaly (83%)&Mesenchymaldysgenesis
7 mo 38 mo 61% 50%(* 24 eyes,O20/200)
79% -- 62%
Al-RajhiandWagoner19976
56 eyes of40 children
CHED 11.8 yr 37 mo 62.5% 69.8%(O20/300)
92% 72% 56.5% at5 yr
Freuh andBrown199744
58 eyes Sclerocornea 17/58Peters 17/58Partialsclerocornea
12/58Congenital glaucoma
2/58
6.3 mo 40m Overall 83%Sclerocornea -
70%,Partial sclero-
cornea - 83%,Peters anomaly
- 100%
- 75% 58% --
(Continued)
PEDIATRIC
KERATOPLASTY
259
-
TABLE 2 Continued
StudyNo
of Eyes IndicationsMean Ageat Surgery
MeanFollow-Up
AnatomicalSuccess
Fun tionalSu cess
Graft Survival
1 Year 2 Years3 Years or
More
ana et al199534
25 grafts in25 children! 12 yr
Ocular trauma 70 mo(# 12 mo)
42.5 mo -- 83%(* 1 eyes,O20 200)
84% 70% --
ana et al199533
164 grafts(131eyes/108children!12 yr)
CongenitalCO -64%
Traumatic - 17%Nontraumatic
acquired - 19%
62% 33%(* 8 eyes,(O2 /200)
Congenital CO- 80%
Traumatic -84%
Acquirednontraumatic -76%
(overall80%)
67% --
ajjadi et al1995115
37 eyes of21 children
CHED 9.5 yr 3 yr 92% 72.9%(O2 /200)
-- -- --
riyasu et al199413
9 grafts in 8eyes of 6infants
Congenital glaucoma !2 yr 24 mo 67% 75%amb latoryvisio
-- -- --
armley199394
26 grafts in16 eyes
Peters anomaly 18 weeks attime of 1stgraft
30 mo 15.3% 19.2%(am ulatoryvisio )
-- -- --
rlich et al199142
85 grafts in54 patients
Peters (16/54, 27PKs)
Congenitalglaucoma(8/54, 13 PKs)
HSK (5/54, 10 PKs)C Dystrophy
(8/54, 9 PKs)Trauma (17/54, 26
PKs)
Petersanomaly-12.3 moCong.
glc - 22.8mHSK - 5.9yr
C Dystrophy -11.4 yr
Trauma - 6y
20.5 mo Overall -22%(Peters
44% @ 22.3mo,
Congenitalglaucoma0% @16.6mo
HSK 40% @12.2 mo
Dystrophy75% @27.3 mo
Trauma 71%@ 3 mo
--
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0
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Cowden199031
66 grafts in57 eyes of50 children!14 yr
Cong. COCorneal
decompensationKeratoconus 10
Regrafts 10
-- 2 mo--10 yr Overall 48.4%Cong. CO - 39%Keratoconus -
70%Acquired
traumatic -88%
Acquirednon-traumatic- 33%
Regrafts - 11%Congenital
glaucoma -100%
- -- -- --
Stulting1984134
152 grafts in107 eyes of91 children!14 yr
Congenital COAcquired
traumaticAcquired
nontraumatic
98 mo(# 20 mo)
30.1 mo Cong. CO - 60%,Trauma - 70%Acquired non-
traumatic -73%
Cong. O -*29 ,O2 400
Traum tic -45% O20/400
Acqui dnon au-mat -67%O2 400
Cong. CO -60%
Traumatic -70%
Acquirednontraumatic -73%
-- --
AGV 5 Ahmed glaucoma valve; C glc 5 congenital glaucoma; CHED 5
congenital hereditary endothelial dystrophy; C 5 corneal
opacification; Cong. 5 congenital;HSK 5 herpes simplex keratitis;
mo 5 months; PK 5 pediatric keratoplasty; yr 5 years.*With
measurable preoperative and postoperative visual acuity.#Mean
interval between trauma and first PK.
PEDIATRIC
KERATOPLASTY
261C%0/a,
retric,
0/
O
-
262 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALoutcome is important when comparing results ofdifferent
series.
Pearce et al99 reported a 25% survival of firstgrafts and an
overall success rate of 43% (includingfive regrafts) after a
3-month follow-up. Kirkness etals75 results of keratoplasty for
CHED in 31 eyes of20 patients (median age at first keratoplasty of
13.5years) reported good surgical success. A retrospec-tive
analysis by Groh et al of penetrating keratoplastyoutcome in 13
eyes of 8 children of CHED witha mean age of 6.0 years (range,
3--14 years) overa mean follow-up of 4.0 years saw a good
prognosisfor graft survival and visual outcome.53
Results of penetrating keratoplasty in 37 eyes of21 patients
with CHED of the autosomal recessivetype (mean age at surgery 9.5
years) showed goodvisual and anatomical success.115 Al-Ghamdi et
als5
study also found significantly higher graft survival ineyes with
CHED than for other surgical indications.Review of the outcome of
penetrating keratoplastyin CHED patients6 showed that 62.5% of
theprimary corneal transplants remained grafts ata mean follow-up
of 37 months with graft survivalanalysis indicating better graft
survival in eyes withdelayed onset of the disease, with use of
younger agedonor corneas (between 5 and 30 years), and inpatients
compliant to follow-up. Results of Schaum-berg et al117 and Sajjadi
et al115 are consistent withthose of Al-Rajhi et al.6
Javadi et al reviewed the results of cornealtransplants in 24
eyes of 15 patients of CHED(mean age of 8.1 years at the time of
the primarygraft)62 found no relationship between age at initialPKP
and final visual outcome. In view of thedifficulties in pediatric
keratoplasty and the absenceof a relationship between postoperative
visual out-come and age at keratoplasty, a risk:benefit
ratioevaluation and conservative approach can perhapsbe adopted in
decision-making on the timing ofkeratoplasty in patients with
CHED.62 It is to bepointed out that graft survival is significantly
higherat all postoperative intervals in eyes with CHED thanfor
other surgical indications.5
Reaching a consensus regarding the crucial factorof timing of
surgery in CHED seems to be difficultdue to the heterogenic nature
of the study groupsinvolved. The mean age at diagnosis and mean
ageat surgery vary in most of the series. The grade ofseverity of
disease also influences the decision of thetiming of surgery in
patients in CHED apart fromthe type of the CHED being dealt with.
Visualoutcomes are also affected by the relative difficultyin
assessing visual acuity in infants and children. Amore severe grade
of corneal opacification associ-ated with nystagmus is associated
with a denser
ambylopia, thereby further influencing the visualoutcomes
compared to that of the autosomaldominant type in which
opacification is usuallymilder, and not associated with nystagmus;
in thosecases surgery is usually delayed. It can be unani-mously
agreed upon, however, that eyes with CHEDare significantly more
likely to achieve ambulatoryvision or vision O20/200, than eyes
with otherindications.5
1. CHED with Glaucoma
Congenital glaucoma and congenital hereditaryendothelial
dystrophy may coexist with the the needfor subsequent keratoplasty
for visual rehabilitationin these cases.106
Mullaney et al89 performed keratoplasty in threechildren
(ranging in age from 2 to 6 months) withdiffuse and homogeneously
opaque corneas afterthe haze failed to improve following
glaucomasurgery and histopathology evaluation of the excisedcorneal
buttons showed findings consistent withCHED.
B. CONGENITAL OPACITIES: NON-CHED
1. Frequently Associated with Glaucoma
a. Congenital Glaucoma
The efficacy of corneal transplantation in infantswith corneal
opacity secondary to congenital glau-coma has not been clearly
established as thepercentage of clear grafts in children with
congen-ital glaucoma varies significantly due to the smallnumber of
cases reported.13,168 The visual prognosisfollowing penetrating
keratoplasty in congenitalglaucoma is generally poor.42,46,159
The Cowden et als results were encouraging inseven cases of
congenital glaucoma eyes withcorneal grafts when IOP was controlled
before thekeratoplasty procedure.30 However, Erlich et alfound
dismal results, with none of the 13 kerato-plasties in eight
patients doing well.42 Ariyasu et al13
reported results of nine corneal grafts in eight eyesof six
patients with congenital glaucoma withmultiple risk factors for
poor prognosis (age ! 2years at the time of grafting, uncontrolled
glaucomain four eyes, concurrent lensectomy, retinal, orglaucoma
surgery in five eyes, aphakia in five eyesand an acute perforation
in one eye) which hadundergone previous glaucoma surgeries.
Despiteearlier glaucoma surgeries, five eyes needed simul-taneous
glaucoma filtering implant at the time ofkeratoplasty with only 67%
(nine grafts) found toremain clear at 30 months postoperatively
with sixeyes achieving ambulatory vision.
Congenital glaucoma has a 50% chance of
success, with the requirement of regrafts in several
-
early postoperative control of aqueous outflow
PEDIATRIC KERATOPLASTY 263thereby enhancing long-term graft
survival in suchdifficult cases. When the AGV implant is placed
atthe time of the keratoplasty, it is usually effective
incontrolling intraocular pressure over a span of 3years, whereas
the success of the transplantedcorneas remains poor.7,8 Long-term
success ratesof simultaneous AGV implants and
penetratingkeratoplasty in refractory congenital glaucoma
withcorneal opacity is low, with high risk forcomplications.8
Corneal grafts in eyes with congenital glaucomawith various risk
factors at the time of thekeratoplasty, such as younger age group,
uncon-trolled IOP, multiple intraocular surgeries, concur-rent
lensectomy, and retinal or glaucoma surgery,are associated with a
less favorable outcome. Usefulvision can be achieved after
penetrating keratoplastyeven in some high-risk infants with
congenitalglaucoma, but the risk of development of complica-tions
and graft failure is very high. Good control ofintraocular pressure
before and after corneal graft-ing is mandatory in eyes with
buphthalmos in orderto avoid graft failure and progress of
glaucomatousoptic nerve atrophy.140 Effective intraocular pres-sure
control before and after corneal grafting isimperative in eyes with
buphthalmos in order toprevent graft failure and progress of
glaucomatousoptic nerve atrophy, which will further increaseocular
morbidity in these eyes.
b. Peters Anomaly
Severe Peters anomaly with dense corneal opac-ities leads to
blindness unless corneal transplanta-tion is performed. The timing
for keratoplasty is stillnot very clear. In the multicenter study
by Dana etal,33 the congenital opacification group
comprisedpredominantly of anterior segment dysgenesis(30%) and
others (25%) with 62% of eyes retainingfull graft clarity. They
found no significant differ-ence noted in the retention of clarity
amongdiagnostic groups, whereas other studies 31,134eyes.87
Keratoplasty may be associated withimproved visual acuity in eyes
with marked buph-thalmos and congenitally opaque corneas
treatedwith cyclocryotherapy.46
Simultaneous penetrating keratoplasty andAhmed glaucoma valve
(AGV) implant surgery withmitomycin C can be successful but
multipleinterventions for glaucoma control may berequired.168 The
use of a valved implant can beconsidered in patients who require
emergencysimultaneous corneal and glaucoma surgery forsevere
congenital glaucoma. This could help inreport that the probability
of retaining clear graftsin eyes with congenital corneal
opacification wasfound to be less compared to that in eyes
withacquired corneal opacities. Complicated casesrequiring
additional surgical procedures are how-ever associated with a poor
prognosis.35
Rezende et al110 had obtained good results intheir small series
of patients with Peters anomalywith 9 out of 10 eyes retaining
clear grafts at a meanfollow-up of 64.2 months. However other
studieswarn of a more guarded prognosis in most cases ofPeters
anomaly.31,35,51,167,170 A large series of Petersanomaly by Yang et
al167 found 54% of eyes receivedone graft, 18% received two grafts,
and 28%received three or more grafts. Initial grafts weremore
likely to fail during the first two postoperativeyears, with more
than half of all the failuresoccurring within the first three
postoperativemonths.167 To be taken into further considerationis
the fact that substantial time and investment isrequired in
additional ocular surgeries besideskeratoplasty in these
children.165 Hence the needfor frequent evaluation in the initial
postoperativemonths along with counseling of the parents
isimperative.
Parmley et al94 reported dismal results in hisseries with a high
incidence of graft rejection incases requiring cyclodestructive
procedure for glau-coma control, resulting in partial or complete
graftfailure shortly after the procedure. In another smallseries of
penetrating keratoplasty in newborns withsevere Peters anomaly,10
repeat keratoplasties,lensectomies, and numerous glaucoma
operationshad to be performed. The results obtained innewborns
remain very poor. The performance ofpenetrating keratoplasty in
patients with Petersanomaly early after birth is associated with a
multi-tude of problems, especially glaucoma, making itdifficult to
retain clear grafts for an extendedperiod. Althaus and Sundmacher10
have suggestedpostponing surgery until the patient is about 1
yearold in order to obtain a better graft survival,although
persistent amblyopia might be quite severeand limit the functional
success.
In Zaidman et als170 study of 30 eyes with Petersanomaly type I
who had undergone corneal trans-plantation, five of six grafts were
clear (83%) in theyounger group of children although the oldergroup
of 24 eyes fared better with good visual andanatomical outcome.
Major complications in kera-toplasty in Peters anomaly included
cataract,secondary glaucoma, epithelial defects, band kerat-opathy,
retinal detachment, wound leakage, retro-corneal membranes, and
microbial keratitis.44 Aretrospective review of records of 11
patients withcongenital corneal opacity who had undergone
penetrating keratoplasty as infants by Comer et
-
keratoplasties in 34 eyes of Peters anomaly with
264 Surv Ophthalmol 54 (2) March--April 2009 VANATHI ET
ALglaucoma (median 2 surgeries; range 1--7) reportedthe need for
glaucoma surgery before first kerato-plasty in 17 eyes,
simultaneously with first kerato-plasty in 8 eyes, and after the
first keratoplasty in 9eyes. Although no graft infection was noted
in theirseries, major postoperative complications includedgraft
failure, retinal detachment, phthisis andcataract. Eyes with vision
of 20/400 or better wereobserved in those with clear grafts with an
intact lensand in moderate grade of Peters anomaly. Glau-coma
surgery combined with medical therapy resultsin adequate long-term
control of IOP in only 32% ofthe eyes with glaucoma in Peters
anomaly. Despitethe large number of cases, prognostic indicators
forvisual outcome in cases of Peters anomaly withglaucoma could not
be given in the study due to thelimitations of multiple procedures
performed pereye (1--14).166 Among the various glaucoma pro-cedures
performed in Peters anomaly with glau-coma,166 long-term IOP
control was found to bemaintained successfully in one of 11 eyes
thatunderwent cyclocryotherapy, in all four eyes thatunderwent
Molteno implantation, in two of seveneyes that underwent
trabeculectomy, and in none ofthe five eyes that underwent
goniotomy. Althoughal29 revealed a poor graft survival and a low
finalvisual acuity for Peters anomaly.
Corneal transplantation for congenital cornealopacities
(non-CHED) has the best prognosis forthe dystrophy group (posterior
polymorphous dys-trophy), followed by patients with Peters
anomaly.87
In contrast to penetrating keratoplasty, sectoriridectomy for
congenital corneal opacificationsecondary to Peters anomaly is not
followed bysecondary glaucoma postoperatively. The visualoutcome
has been found to be comparable to thatafter early keratoplasty.
Junemann et al63 recom-mend optical sector iridectomy as an
alternativesurgical approach to early penetrating keratoplastyin
patients of Peters anomaly. Optical sectoriridectomy was performed
in 13 patients withPeters anomaly (with diameter of corneal
opacifi-cation greater than half of the corneal diameter) ata mean
age at surgery of 1 year and 9 months. Overa mean follow-up of 3
years and 6 months, nine(47%) eyes had achieved a visual acuity was
20/500to 20/200.63 When the peripheral cornea is clearand cataract
is not associated, an optical sectoriridectomy is an effective
alternative to penetratingkeratoplasty.27,134,148
c. Peters Anomaly with Glaucoma
Yang et al report166 of a total of 79 penetratinga possible
comparison of glaucoma treatmentstrategies was not possible in this
study,166 it is tobe noted that better visual outcome is
associatedwith a clear graft, phakic eye, and moderate grade
ofPeters anomaly whereas graft failure, surgicalaphakia, and severe
grade of Peters anomaly haspoor visual outcome and also has the
coexistence ofdevastating postoperative complications.
Zaidman et als170 study on 30 eyes of Petersanomaly (type I)
with corneal grafts showed that 15(50%) required treatment for
glaucoma of whichonly four eyes were able to achieve good
visualacuity. Eyes with glaucoma have a poorer visualprognosis in
Peters anomaly. Secondary glaucomaseems to be the limiting
prognostic factor in thelong run with uncontrolled intraocular
pressuredespite multiple surgical interventions, and graftprognosis
remains poor in the long run.10 Mostcases of Pters anomaly may
develop glaucomapostoperatively or preexisting preoperative
glau-coma might worsen and medical control is usuallyunsuccessful
necessitating cyclodestructive or glau-coma filtering implants or
both, for control ofintraocular pressure.94
2. Infrequently Associated with Glaucoma
a. Dermoid, Birth Trauma, and Metabolic Diseases
Conditions such as dermoid, birth trauma, andmetabolic diseases
constitute about 15%, 2.8%, and2.8%, respectively, of the cases
with congenital cornealabnormalities.110 Dermoids not involving the
visual axiscan be effectively managed by simple excision orcombined
with lamellar grafting in cases of extensioninto the deeper tissue.
Dermoid infrequently may involvethe entire cornea, associated with
adherence of theatrophic iris to theposteriorcorneal
surfaceandcataract.Surgical excision of dermoid and penetrating
kerato-plasty for tectonic reconstruction is required in
suchcases.50 According to the size and location, the dermoidsmay be
managed either by sectoral, annular, or centrallamellar
keratoplasty.14,93,97,121,160 Corneoscleral lamel-lar grafts may be
required in advanced cases, especiallywhen the whole thickness of
the corneal stroma isinvolved or when the tumor deeply extends
around thelimbus. Dermoid excision with a 12-mm lamellarkeratectomy
and followed later by a smaller (8-mm)penetrating keratoplasty has
also been reported toprovide good results. This staged procedure
helps inminimizing the complications associated with largecorneal
transplants and increases the chance of long-term success.169 The
use of of full-thickness centralcorneal grafts in lamellar
keratoscleroplasty for limbaldermoids123 has also been found to
achieve goodcosmetic results and less corneal astigmatism.
In mucopolysaccharidosis (MPS), the outcome of
keratoplasty is weighed in view of the expected
-
need for regrafts was significant in eyes with
visually significant lesions and is to be limited to
PEDIATRIC KERATOPLASTY 265lifespan of the patient and the
particular syndromeinvolved. Because clinically significant
cornealclouding does not appear in Hunters and Sanfilli-pos
syndrome, no therapeutic intervention in termsof penetrating
keratoplasty is warranted. In otherMPS the decision to do
keratoplasty and the timingdepends on the particular syndrome and
theindividual case. The visual prognosis followingkeratoplasty is
hampered by the coexisting retinop-athy and optic nerve involvement
apart from theshortened life-span from the disease itself.
Cloudingof the transplant is often observed and is related
tostorage of glycosaminoglycans in the donor but-ton.67 Surgery
should be done at an early age,especially in Hurler syndrome and
Morquio syn-drome, which is associated with a short life-span,
sothat the child can be visually and vocationallyrehabilitated in
the limited time available.67,91
Bergwerk et al reported good visual outcomefollowing penetrating
keratoplasty in a patient withSly disease, in which the cornea
remained clear for 2years following surgery.22 Kasmann-Kellner
reportedpostoperative visual acuity improvement for nearlya year,
followed by progressive re-opacification ofthe corneal graft in a
case of Morquio syndrome thatwas also complicated by tapetoretinal
degenerationand optic atrophy.67 Naumann and Rummeltobserved a
partial, circular clearing of the hostscornea adjacent to the
transplant in three childrenwith Maroteaux--Lamy syndrome in which
the trans-plants remained clear during the follow-up of 2.5--5years
following penetrating keratoplasty.91
Recent advances in systemic treatments for MPS haveled to
therapies that improve the multiple somaticfeatures of this
disease, such as bone marrow trans-plantation (BMT) and enzyme
replacement.141 Tokic etal141 report improvements in cardiac
function, stoolhabits, visual acuity, corneal clouding, and hearing
afterenzyme replacementbut the
therapeuticeffectonocularmanifestations, such as corneal clouding,
is reported tobe not satisfactory. Huang et al also reported
limited roleof BMT in clearing of corneal clouding.58
Injection of adenovirus expressing human beta-glucuronidase
(AxCAhGUS) into the anterior chamberor intrastromal region of the
cornea in mice with MPStype VII (B6/MPS VII) has shown successful
results withclearing of corneal clouding.66 Intrastromal
vectoradministration did not generate significant levels
ofanti-adenovirus neutralizing antibodies, and secondaryvector
administration was also found effective.66
Ucakhan reports the longest follow-up of MPS type VIwho
underwent BMT for gene transfer at the age of 13,and penetrating
keratoplasty at the age of 17, andmaintained clear corneal grafts
bilaterally for 13 years.144
Corneal clearing is not considered an appropriate index
for measuring the success of systemic therapy in MPS
VIsymptomatic patients.23,107,150 Rao et al107
performed multiple penetrating keratoplasties totreat a case of
congenital corneal keloid withsclerocornea. The chance of success
of the cornealgraft in cases of sclerocornea is about 50%,
withrequirements of repeated transplants in severaleyes.87
In Frueh and Browns series,44 the overall success(including
regrafts) was found to be 70% in eyeswith sclerocornea and 83% for
partial sclerocornea.They recommend early keratoplasty for
congenitalopacities with unilateral as well as bilateralinvolvement
in infants, as they were able to achievean excellent long-term
survival; however, theincreased need for regrafting and a high
incidenceof complications in these cases is to be given
carefulconsideration before decision making for
surgicalintervention in congenital opaque corneas. Thebetter
prognosis in Peters anomaly and partialsclerocornea is related to
the lack of severeintraocular anomalies and the subsequent
lowerincidence of glaucoma along with lensectomy andanterior
vitrectomy not being required in these eyes.A prospective,
nonrandomized clinical trial byVajpayee et al147 reports on 40
pediatric patientswith unilateral or bilateral corneal
opacification,with corneal grafting using 1-mm oversized
donorcorneal buttons for the congenital opacities
(largelycomprising of sclerocornea) with v