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The Outcomes of Primary Pediatric Keratoplasty in



 PURPOSE: To evaluate the long-term corneal graft sur- EDIATRIC KERATOPLASTY IS CONSIDERED HIGH-RISK
vival and risk factors for graft failure in pediatric eyes. keratoplasty and was uncommonly performed before
 DESIGN: Retrospective, interventional consecutive the 1970s, and was recommended only for pediatric
case series. patients with bilateral corneal involvement.1,2 Over the
 METHODS: Unilateral eyes of 105 patients aged 16 past 20 years, there has been increasing frequency and
years and below were included from the Singapore success rates of pediatric keratoplasty3 owing to advances
Corneal Transplant Study between April 4, 1991 and in corneal microsurgery, postoperative management, and
April 4, 2011. Corneal graft survival was calculated using better understanding of risk factors that may help predict
Kaplan-Meier survival analysis, and survival distributions and prevent poor outcomes.4,5 Nevertheless, higher graft
were compared using log-rank test. failure rates and poorer visual prognosis have been
 RESULTS: Mean recipient age was 8.38 ± 5.63 years reported in pediatric keratoplasty compared to adult
(range 0.18–15.92 years). Mean follow-up time was keratoplasty.3,6–9 There are many challenges unique to
34.16 ± 39.10 months. Main diagnoses were corneal pediatric keratoplasty. Preoperatively, there is difficult
scar (22.9%), limbal dermoid (21.9%), anterior segment assessment of visual function and potential in preverbal
dysgenesis (15.2%), and keratoconus (14.3%). Forty- children.3,5 Intraoperative challenges include thinner and
four eyes (41.9%) underwent penetrating keratoplasty less rigid cornea, smaller and more crowded anterior
(PK), 37 (35.2%) underwent anterior lamellar kerato- segment, and decreased scleral rigidity, which require
plasty (ALK), 22 (21.0%) underwent lamellar corneal specialized surgical techniques.3,5,10 Postoperative
patch graft, and 2 (1.9%) underwent Descemet stripping problems include difficulty of the child in communicating
automated endothelial keratoplasty (DSAEK). Kaplan- postoperative symptoms, difficulty with refractive error
Meier survival rates for PK were 92.8% at 1 year, assessments, need for frequent examinations under
88.9% at 2–4 years, and 80.9% at 5–16 years; survival anesthesia (EUA) for postoperative follow-up evaluations,
rates for ALK were 88.0% at 1 year and 84.3% at 2–7 increased fibrinous reactions and possible vitreous pressure,
years; survival rates for corneal patch graft were 100% graft rejection (which occurs both more frequently and
at 1–3 years and 90% at 4–10 years; these were not sta- more rapidly, and is less responsive to treatment), increased
tistically significant (P [ .362). Deep corneal vasculari- infection and rejection risks associated with loose sutures,
zation (P [ .012), preexisting active inflammation (P [ and challenges of amblyopia therapy.3,5,10
.023), preexisting glaucoma drainage device (P [ .023), Although there have been a few studies reporting on pe-
and preexisting ocular surface disease (P [ .037) were diatric keratoplasty in developed Western countries, there
associated with reduced graft survival in a univariate have been few studies on pediatric keratoplasty in Asian
analysis. populations7,11–13 and even fewer evaluating its long-
 CONCLUSIONS: We report good long-term graft survival term outcomes.14 We report the indications, risk factors,
following pediatric keratoplasty for various indications. postoperative complications, and long-term graft survival
Lamellar keratoplasty, when indicated, should be the pro- of primary pediatric keratoplasties performed at the
cedure of choice in high-risk keratoplasties. (Am J Singapore National Eye Centre, with a significant referral
Ophthalmol 2014;158:496–502. Ó 2014 by Elsevier Inc. base of corneal diseases from less developed countries in
All rights reserved.) Southeast Asia.

Accepted for publication May 19, 2014.

From Singapore National Eye Centre (J.R.L., A.A., A.C.S.T., METHODS
D.T.H.T.), Singapore Eye Research Institute (H.M.H., D.T.H.T.),
Duke-National University of Singapore Graduate Medical School
Singapore (A.A., A.C.S.T., H.M.H., D.T.H.T.), and Department of THE SINGAPORE CORNEAL TRANSPLANT STUDY IS A LONG-
Ophthalmology, Yong Loo Lin School of Medicine, National University term ongoing prospective cohort study started in 1991,
of Singapore (A.A., D.T.H.T.), Singapore. tracking all consecutive corneal transplants performed at
Inquiries to Prof Donald Tiang Hwee Tan, Singapore National Eye
Centre, 11 Third Hospital Avenue Singapore 168751, Singapore; a single ophthalmic tertiary referral center in Singapore,
e-mail: donald.tan.t.h@snec.com.sg the Singapore National Eye Centre, which provides

496 Ó 2014 BY ELSEVIER INC. ALL RIGHTS RESERVED. 0002-9394/$36.00

approximately 60% of eye care delivery in Singapore and  INDICATIONS FOR SURGERY: The majority of pediatric
performs approximately 80% of all corneal transplants keratoplasties were performed for optical reasons
locally.15,16 Approval was prospectively obtained for this (67.7%), whereas therapeutic and tectonic indications
study from the Singapore Eye Research Institute accounted for 18.6% and 13.7% of cases, respectively.
institutional review board. The most common diagnoses were corneal scar (22.9%),
In this retrospective, interventional consecutive case se- limbal dermoid (21.9%), anterior segment dysgenesis
ries, we recruited 168 patients aged 16 years and below at (15.2%), keratoconus (14.3%), and infectious keratitis
time of corneal transplant from the Singapore Corneal (6.7%). Cases of anterior segment dysgenesis comprised Pe-
Transplant Study cohort between April 4, 1991 and April ters anomaly (62.5%), sclerocornea (25.0%), and Rieger’s
4, 2011. After excluding 6 cases with bilateral corneal grafts, anomaly (12.5%). For penetrating keratoplasty, the most
22 cases of repeat corneal grafts, and 35 cases lost to follow- common indications were anterior segment dysgenesis
up, 105 eyes of 105 patients were included for analysis. (34.1%), keratoconus (22.7%), and corneal scar (18.2%).
Main outcome measure was graft failure, defined as the For anterior lamellar keratoplasty, the most common indi-
irreversible loss of optical clarity, with date of onset of cations were corneal scar (40.5%), limbal dermoid
corneal clouding selected as time point of graft failure. Sur- (18.9%), and keratoconus (13.5%). Most cases that under-
vival time of failed grafts was defined as the time between went lamellar corneal patch graft were for limbal dermoid
the date of surgery and recorded date of failure. For (68.2%). The proportion of the type of surgery performed
currently surviving clear grafts or cases lost to follow-up, for each diagnosis is shown in Table 1.
survival time was calculated as the interval between the
date of surgery and the date when the patient was last  OVERALL GRAFT SURVIVAL: Overall Kaplan-Meier
seen. Corneal graft survival time and probabilities were mean graft survival time was 174.0 months (95% confi-
calculated using Kaplan-Meier survival analysis. Kaplan- dence interval [CI], 154.3–193.7). Kaplan-Meier mean
Meier survival distributions were compared for significant graft survival times for optical grafts, therapeutic grafts,
differences using log-rank test. All variables, categorical and tectonic grafts were 171.9 months (95% CI, 146.5–
and continuous, were individually subjected to univariate 197.4), 135.9 months (95% CI, 121.0–150.7), and
analysis to assess their significance for graft failure. A P 93.5 months (95% CI, 59.5–127.5), respectively. Kaplan-
value (2-tailed) of <.05 was considered to be statistically Meier survival rates for optical grafts were 92.3% at 1
significant. All analyses were conducted using IBM SPSS year, 88.0% at 2–4 years, and 81.2% at 5–16 years; survival
Statistics for Windows, Version 19.0 (IBM Corp, Armonk, rates for therapeutic grafts were 94.1% at 1–12 years; sur-
New York, USA). vival rates for tectonic grafts were 90.9% at 1–3 years and
The pediatric keratoplasty regimen involved team man- 68.2% at 4–10 years (Figure 1). The Kaplan-Meier survival
agement by the cornea specialists, pediatric ophthalmolo- distributions for optical, therapeutic, and tectonic grafts
gists, and, if necessary, the pediatric glaucoma specialist were similar and had no statistically significant differences
and retina specialists, as well as pediatric anesthetists and (P ¼ .556).
pediatric transplant immunologist for systemic immuno-
suppression in selected cases. We practiced in-depth coun-  GRAFT SURVIVAL BASED ON TYPE OF SURGERY: Forty-
seling of parents regarding the importance of compliance four eyes (41.9%) underwent penetrating keratoplasty
with postoperative follow-up, multiple EUAs, and patch- (PK), 37 eyes (35.2%) underwent anterior lamellar kerato-
ing, especially for patients who are based overseas. A plasty (ALK), 22 eyes (21.0%) underwent lamellar corneal
much closer and more frequent follow-up was carried out patch graft, and 2 eyes (1.9%) underwent Descemet strip-
for these patients compared to adult keratoplasty patients. ping automated endothelial keratoplasty (DSAEK). Of the
For instance, the first EUA to start suture removal was as eyes that underwent ALK, 28 (75.7%) underwent pre-
early as 2 weeks post operation. Descemetic deep anterior lamellar keratoplasty (manual
dissection technique) (DALKm), 5 (13.5%) underwent
Descemet-bearing deep anterior lamellar keratoplasty (big
bubble technique) (DALKa), and 4 (10.8%) underwent
RESULTS automated lamellar therapeutic keratoplasty (ALTK).
Kaplan-Meier mean graft survival times for PK, ALK,
A TOTAL OF 105 EYES OF 105 PEDIATRIC PATIENTS UP TO 16 and corneal patch grafts were 171.7 months (95% CI,
years of age underwent keratoplasty in the 20-year study 141.3–202.2), 74.5 months (95% CI, 64.4–84.5), and
period. Of these patients, 67 (63.8%) were boys and 38 115.8 months (95% CI, 101.0–130.5), respectively.
(36.2%) were girls. The mean recipient age at surgery Kaplan-Meier survival rates for PK were 92.6% at 1 year,
was 8.38 6 5.63 years (range 0.18–15.92 years). The 88.9% at 2–4 years, and 80.9% at 5–16 years; survival rates
mean follow-up time was 34.16 6 39.10 months (range for ALK were 88.0% at 1 year and 84.3% at 2–7 years; sur-
0.26–206.26 months). All pediatric keratoplasties were vival rates of corneal patch graft were 100% at 1–3 years
performed by 1 surgeon (D.T.). and 90% at 4–10 years (Figure 2). The Kaplan-Meier


TABLE 1. Frequency and Proportion of Infants and Children who Underwent Keratoplasty for Each Primary Clinical Diagnosis

Penetrating Anterior Lamellar Descemet Stripping Automated

Diagnosis Total, n (%) Keratoplasty, n (%) Keratoplasty, n (%) Corneal Patch Graft, n (%) Endothelial Keratoplasty, n (%)

Corneal scar 24 (100.0) 8 (33.3) 15 (62.5) 1 (4.2) 0 (0.0)

Limbal dermoid 23 (100.0) 1 (4.3) 7 (30.4) 15 (65.2) 0 (0.0)
Anterior segment dysgenesis 16 (100.0) 15 (93.8) 0 (0.0) 0 (0.0) 1 (6.3)
Keratoconus 15 (100.0) 10 (66.7) 5 (33.3) 0 (0.0) 0 (0.0)
Infectious keratitis 7 (100.0) 4 (57.1) 3 (42.9) 0 (0.0) 0 (0.0)
Corneal melt or perforation 5 (100.0) 2 (40.0) 3 (60.0) 0 (0.0) 0 (0.0)
Iris tumor 3 (100.0) 1 (33.3) 0 (0.0) 2 (66.7) 0 (0.0)
Pseudophakic or aphakic bullous 2 (100.0) 1 (50.0) 0 (0.0) 0 (0.0) 1 (50.0)
Bullous oculocutaneous disease 2 (100.0) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0)
Limbal tumor 2 (100.0) 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0)
Tube extrusion 2 (100.0) 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0)
Congenital hereditary endothelial dystrophy 1 (100.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0)
Reis-Bucklers corneal dystrophy 1 (100.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0)
Glaucoma 1 (100.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0)
Aniridia 1 (100.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0)

FIGURE 1. Kaplan-Meier survival curves of keratoplasty in infants and children by optical, tectonic, and therapeutic indications.

survival distributions for PK, ALK, and corneal patch grafts  GRAFT SURVIVAL BASED ON DIAGNOSIS: Kaplan-Meier
were similar (P ¼ .362). survival rates for patients with corneal scar were 85.2% at 1–
For optical grafts, the Kaplan-Meier survival rates for PK 11 years; survival rates for patients with limbal dermoid were
were 91.4% at 1 year, 87.0% at 2–4 years, and 77.4% at 5– 95.0% at 1–10 years; survival rates for patients with keratoco-
17 years; survival rates for DALKm were 88.0% at 1 year nus were 92.9% at 1–17 years; survival rates for patients with
and 78.2% at 2–4 years; survival rates for DALKa were anterior segment dysgenesis were 93.8% at 1 year and 78.1%
100% at 1–7 years; and survival rates for ALTK were at 2–4 years; and survival rates for patients with active infec-
100% at 1–3 years. tious keratitis were 100% at 1–12 years (Figure 3).


FIGURE 2. Kaplan-Meier survival curves of keratoplasty in infants and children by type of surgery.

 GRAFT SURVIVAL BASED ON AGE AT TIME OF SURGERY: Univariate analysis identified 4 risk factors that were
Kaplan-Meier survival rates for patients aged 0–1 year were significantly associated with reduced graft survival. They
84.8% at 1 year and 74.2% at 2–6 years; survival rates for were deep corneal vascularization (P ¼ .012), active inflam-
patients aged 2–5 years were 94.1% at 1–12 years; survival mation (P ¼ .023), preexisting glaucoma drainage device
rates for patients aged 6–10 years were 94.4% at 1 year, 87.7 (P ¼ .023), and preexisting ocular surface disease (P ¼ .037).
at 2–3 years, and 70.2% at 4 years; and survival rates for pa-
tients aged 11–16 years were 94.5% at 1–4 years and 84.0%  COMPLICATIONS: The most common postoperative
at 5–17 years (Figure 4). However, there was no statistically complications were ocular surface disease (15.2%) (16 of
significant difference in graft survival distributions among 105 eyes), such as limbal stem cell deficiency and nonheal-
the different age groups (P ¼ .256). ing epithelial defects; glaucoma (13.3%) (14 of 105 eyes);
and cataract (10.5%) (11 of 105 eyes) (Table 2). For eyes
 RISK FACTOR ANALYSIS: Seventeen putative risk fac- that underwent PK, the most common complications
tors for graft failure were grouped into patient demo- were glaucoma (25.0%) (11 of 44 eyes), cataract (20.5%)
graphics and clinical diagnosis, preoperative recipient (9 of 44 eyes), and ocular surface disease (18.2%) (8 of 44
corneal status, and intraoperative categories. These eyes); for eyes that underwent lamellar keratoplasty, the
included 6 patient- and disease-related factors (recipient most common complications were ocular surface disease
age, sex, ethnic group, nationality, clinical diagnosis, largely secondary to limbal stem cell deficiency (12.8%)
and primary indication for transplantation), 8 preopera- (5 of 39 eyes), glaucoma (5.1%) (2 of 39 eyes), and late graft
tive risk factors (preoperative corneal vascularization; failure (5.1%) (2 of 39 eyes); for eyes that underwent
previous grafts; preexisting glaucoma; and the presence lamellar corneal patch graft, the most common complica-
of active infection, active inflammation, ocular surface tions were ocular surface disease (13.6%) (3 of 22 eyes)
disease, lid disease, and globe perforation at time of sur- and recurrence of primary disease (13.6%) (3 of 22 eyes).
gery), and 3 intraoperative risk factors (concurrent cata-
ract surgery [intracapsular or extracapsular cataract
extraction or phacoemulsification], concurrent anterior
chamber intraocular lens implantation, and concurrent DISCUSSION
anterior vitrectomy). These were the same risk factors as
described in our previous Singapore Corneal Transplant INDICATIONS FOR PEDIATRIC KERATOPLASTY IN DEVELOPED
Study publications.15,16 and developing countries vary according to the different


FIGURE 3. Kaplan-Meier survival curves of the most common diagnoses after pediatric keratoplasty.

spectrum of corneal disease in each country.3,5,11,12,17 A rates of 40%–85%.3 Our overall graft survival was better
review by Vanathi and associates showed that congenital than that of similar studies.7,11,14,17 This may be
causes ranged from 14% to 64%, acquired nontraumatic attributable to the majority of our cases being acquired
causes ranged from 19% to 80%, and acquired traumatic and the higher mean age at time of transplant of our
causes ranged from 6% to 29%.3 Although congenital cases. In our study, cases that underwent keratoplasty for
corneal opacification and corneal dystrophies are the pri- keratoconus had an excellent long-term graft survival
mary indications for pediatric keratoplasty in the developed rate of 92.9% at 17 years, which was similar to findings in
world, infectious keratitis, corneal scar, and perforation other studies.3,10,17 Peters anomaly is known to be
caused by ulceration are the major indications for pediatric associated with a guarded postoperative visual prognosis
keratoplasty in the Asia-Pacific region.11–13 In our study, and a higher incidence of graft failure.3,19,20 A large
the majority of the patients had acquired causes (60%), series by Yang and associates reported that the graft
and corneal scar, limbal dermoid, and keratoconus were survival rate of Peters anomaly was 39% with a median
the most common indications for pediatric keratoplasty. follow-up time of 11.1 years.21 Our study, however, showed
These represent a spectrum of Asian corneal disease from good 4-year graft survival rates of 100% for Peters anomaly,
a combination of patients from an urban developed which we attributed to close postoperative monitoring and
population (similar to the West [eg, keratoconus, anterior follow-up, intensive steroid regimens, and a single, highly
segment dysgenesis]) and referrals from more developing experienced surgeon who performed all keratoplasties.
surrounding populations in Southeast Asia (infectious Another series, by Zaidman and associates, similarly re-
keratitis and postinfectious scarring).11,12 ported good graft survival of 70% at 200 months after PK
Comparison of overall corneal graft survival with in 24 children with Peters anomaly Type I.22
different studies in literature is difficult owing to the het- Several risk factors are known to affect long-term corneal
erogeneity of etiology, as well as varying sample sizes and graft survival. In our series, deep corneal vascularization,
differing follow-up periods. Vanathi and associates showed active inflammation, preexisting glaucoma drainage device,
that graft survival rates of congenital opacities vary widely and preexisting ocular surface disease affected graft survival
in literature: congenital hereditary endothelial dystrophy time more than other factors. These risk factors were consis-
(25%–90%), congenital glaucoma (50%), and sclerocor- tent with those reported in other studies2,7,10,17,18 and were
nea (50%–83%).3 Acquired opacities were found to have similar to what we have reported in an earlier study
better visual outcomes compared to congenital opaci- consisting mainly of adult keratoplasties.15
ties.3,7,18 Of these, traumatic causes had survival rates of Literature has shown mixed results for graft survival rela-
55%–100%, whereas nontraumatic causes had survival tive to age of patient at the time of keratoplasty.5 Two


FIGURE 4. Kaplan-Meier survival curves by recipient age at time of pediatric keratoplasty.

findings in another series of 50 children who underwent

TABLE 2. Frequency and Proportion of Infants and Children PK.16 Others found no difference in graft survival based
who Developed Complications After Keratoplasty on age at the time of transplant.5,6,8
Commonly reported postoperative complications
Penetrating Corneal
Keratoplasty, Lamellar Patch
include infectious keratitis (10%–50%), graft rejection
Complications n (%) Keratoplasty, n (%) Graft, n (%) (22%–43.4%), glaucoma (5%–9%), and cataract (2%–
Ocular surface disease 8 (18.2) 5 (12.8) 3 (13.6)
7%),3,6,7,11 and this is in keeping with the findings in our
Glaucoma 11 (25.0) 2 (5.1) 1 (4.5) study. Complications such as infectious keratitis,
Cataract 9 (20.5) 1 (2.6) 1 (4.5) epithelial defects, band keratopathy, wound leakage,
Late graft failure 4 (9.1) 2 (5.1) 0 (0.0) retrocorneal membrane, cataract formation, secondary
Recurrence of primary 0 (0.0) 1 (2.6) 3 (13.6) glaucoma, and retinal detachment cause challenges to
disease postoperative management and frequently result in
Allograft rejection 4 (9.1) 0 (0.0) 0 (0.0) regrafting.23
Wound dehiscence 3 (6.8) 0 (0.0) 0 (0.0) Unlike most reported series in literature, which
Endophthalmitis 1 (2.3) 0 (0.0) 0 (0.0) evaluated PK as the only modality of pediatric kerato-
Infectious keratitis 0 (0.0) 0 (0.0) 1 (4.5)
plasty,1–11,13,18,20–24 the present study analyzed and
Descemet membrane 0 (0.0) 1 (2.6) 0 (0.0)
compared the outcomes of PK, ALK, and lamellar corneal
Cystoid macular edema 1 (2.3) 0 (0.0) 0 (0.0)
patch grafts. Although 2 other studies included patients
Retinal detachment 1 (2.3) 0 (0.0) 0 (0.0) who underwent PK and ALK,12,17 none compared the
Suture abscess 0 (0.0) 0 (0.0) 1 (4.5) graft survival outcomes between the different types of
Irregular astigmatism with 0 (0.0) 1 (2.6) 0 (0.0) surgery. ALK may be more technically challenging, but it
corneal scar offers several advantages over PK in terms of lower
incidence of graft rejection and failure.14,25–27 Hence, it
should be performed when indicated and possible,
studies concluded that patients aged less than 5 years have particularly in children who have a higher risk of graft
worse graft survival.7,10 Our study showed a trend toward failure. While our series had only 2 cases that underwent
better graft survival in patients older than 1 year, DSAEK, which limited meaningful analysis, a few series
compared to patients aged less than 1 year, although the have shown promising results following DSAEK in
trend was not statistically significant. This mirrors the pediatric eyes with endothelial diseases.25,26


The main limitation in this retrospective study is the acquired and congenital corneal opacities. Some of the rea-
relatively small sample size and variable follow-up periods, sons for the positive survival outcomes in this series include a
although these same limitations are mirrored in many other single surgeon, choice of selective lamellar keratoplasty
published series, simply because pediatric keratoplasty is when indicated, frequent and close follow-up with EUAs,
not that commonly indicated or performed, as compared intensive steroid management, and co-management by a
to adult keratoplasties. Nevertheless, this study provided team of doctors that comprises the cornea surgeon, pediatric
valuable information regarding the indications, risk factors, ophthalmologists, and glaucoma and retina specialists. As in
and long-term outcomes of pediatric keratoplasty in Asian adult keratoplasties, deep corneal vascularization, active
eyes. A larger prospective study is currently being conduct- inflammation, preexisting glaucoma drainage device, and
ed to evaluate visual acuity outcomes and to discuss the is- preexisting ocular surface disease were found to be signifi-
sues of immunosuppression in children with repeat grafts. cant risk factors for graft failure. Better understanding and
Pediatric keratoplasty remains a challenge to most ante- management of these risk factors may help to further
rior segment surgeons. We report good long-term graft improve graft survival outcomes in these high-risk kerato-
survival following primary pediatric keratoplasty for both plasties.

and none were reported. The authors indicate no funding support. Contributions of authors: design of the study (D.T.H.T., A.A.); conduct of the study
(J.R.L., A.C.S.T., A.A., D.T.H.T.); data collection (A.C.S.T., J.R.L., H.M.H., A.A.); analysis and data interpretation (J.R.L., A.A., H.M.H., A.C.S.T.,
D.T.H.T.); preparation and writing of the manuscript (J.R.L., A.A., H.M.H., D.T.H.T.); and review and approval of the manuscript (A.A., D.T.H.T.).

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