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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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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8/

40

0

un

bn

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