Purpose
To evaluate the long-term corneal graft survival and risk factors for graft failure in pediatric eyes.
Design
Retrospective, interventional consecutive case series.
Methods
Unilateral eyes of 105 patients aged 16 years and below were included from the Singapore Corneal Transplant Study between April 4, 1991 and April 4, 2011. Corneal graft survival was calculated using Kaplan-Meier survival analysis, and survival distributions were compared using log-rank test.
Results
Mean recipient age was 8.38 ± 5.63 years (range 0.18–15.92 years). Mean follow-up time was 34.16 ± 39.10 months. Main diagnoses were corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis (15.2%), and keratoconus (14.3%). Forty-four eyes (41.9%) underwent penetrating keratoplasty (PK), 37 (35.2%) underwent anterior lamellar keratoplasty (ALK), 22 (21.0%) underwent lamellar corneal patch graft, and 2 (1.9%) underwent Descemet stripping automated endothelial keratoplasty (DSAEK). Kaplan-Meier survival rates for PK were 92.8% at 1 year, 88.9% at 2–4 years, and 80.9% at 5–16 years; survival rates for ALK were 88.0% at 1 year and 84.3% at 2–7 years; survival rates for corneal patch graft were 100% at 1–3 years and 90% at 4–10 years; these were not statistically significant ( P = .362). Deep corneal vascularization ( P = .012), preexisting active inflammation ( P = .023), preexisting glaucoma drainage device ( P = .023), and preexisting ocular surface disease ( P = .037) were associated with reduced graft survival in a univariate analysis.
Conclusions
We report good long-term graft survival following pediatric keratoplasty for various indications. Lamellar keratoplasty, when indicated, should be the procedure of choice in high-risk keratoplasties.
Pediatric keratoplasty is considered high-risk keratoplasty and was uncommonly performed before the 1970s, and was recommended only for pediatric patients with bilateral corneal involvement. Over the past 20 years, there has been increasing frequency and success rates of pediatric keratoplasty owing to advances in corneal microsurgery, postoperative management, and better understanding of risk factors that may help predict and prevent poor outcomes. Nevertheless, higher graft failure rates and poorer visual prognosis have been reported in pediatric keratoplasty compared to adult keratoplasty. There are many challenges unique to pediatric keratoplasty. Preoperatively, there is difficult assessment of visual function and potential in preverbal children. Intraoperative challenges include thinner and less rigid cornea, smaller and more crowded anterior segment, and decreased scleral rigidity, which require specialized surgical techniques. Postoperative problems include difficulty of the child in communicating postoperative symptoms, difficulty with refractive error assessments, need for frequent examinations under anesthesia (EUA) for postoperative follow-up evaluations, increased fibrinous reactions and possible vitreous pressure, graft rejection (which occurs both more frequently and more rapidly, and is less responsive to treatment), increased infection and rejection risks associated with loose sutures, and challenges of amblyopia therapy.
Although there have been a few studies reporting on pediatric keratoplasty in developed Western countries, there have been few studies on pediatric keratoplasty in Asian populations and even fewer evaluating its long-term outcomes. We report the indications, risk factors, postoperative complications, and long-term graft survival of primary pediatric keratoplasties performed at the Singapore National Eye Centre, with a significant referral base of corneal diseases from less developed countries in Southeast Asia.
Methods
The Singapore Corneal Transplant Study is a long-term ongoing prospective cohort study started in 1991, tracking all consecutive corneal transplants performed at a single ophthalmic tertiary referral center in Singapore, the Singapore National Eye Centre, which provides approximately 60% of eye care delivery in Singapore and performs approximately 80% of all corneal transplants locally. Approval was prospectively obtained for this study from the Singapore Eye Research Institute institutional review board.
In this retrospective, interventional consecutive case series, we recruited 168 patients aged 16 years and below at time of corneal transplant from the Singapore Corneal Transplant Study cohort between April 4, 1991 and April 4, 2011. After excluding 6 cases with bilateral corneal grafts, 22 cases of repeat corneal grafts, and 35 cases lost to follow-up, 105 eyes of 105 patients were included for analysis.
Main outcome measure was graft failure, defined as the irreversible loss of optical clarity, with date of onset of corneal clouding selected as time point of graft failure. Survival time of failed grafts was defined as the time between the date of surgery and recorded date of failure. For currently surviving clear grafts or cases lost to follow-up, survival time was calculated as the interval between the date of surgery and the date when the patient was last seen. Corneal graft survival time and probabilities were calculated using Kaplan-Meier survival analysis. Kaplan-Meier survival distributions were compared for significant differences using log-rank test. All variables, categorical and continuous, were individually subjected to univariate analysis to assess their significance for graft failure. A P value (2-tailed) of <.05 was considered to be statistically significant. All analyses were conducted using IBM SPSS Statistics for Windows, Version 19.0 (IBM Corp, Armonk, New York, USA).
The pediatric keratoplasty regimen involved team management by the cornea specialists, pediatric ophthalmologists, and, if necessary, the pediatric glaucoma specialist and retina specialists, as well as pediatric anesthetists and pediatric transplant immunologist for systemic immunosuppression in selected cases. We practiced in-depth counseling of parents regarding the importance of compliance with postoperative follow-up, multiple EUAs, and patching, especially for patients who are based overseas. A much closer and more frequent follow-up was carried out for these patients compared to adult keratoplasty patients. For instance, the first EUA to start suture removal was as early as 2 weeks post operation.
Results
A total of 105 eyes of 105 pediatric patients up to 16 years of age underwent keratoplasty in the 20-year study period. Of these patients, 67 (63.8%) were boys and 38 (36.2%) were girls. The mean recipient age at surgery was 8.38 ± 5.63 years (range 0.18–15.92 years). The mean follow-up time was 34.16 ± 39.10 months (range 0.26–206.26 months). All pediatric keratoplasties were performed by 1 surgeon (D.T.).
Indications for Surgery
The majority of pediatric keratoplasties were performed for optical reasons (67.7%), whereas therapeutic and tectonic indications accounted for 18.6% and 13.7% of cases, respectively. The most common diagnoses were corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis (15.2%), keratoconus (14.3%), and infectious keratitis (6.7%). Cases of anterior segment dysgenesis comprised Peters anomaly (62.5%), sclerocornea (25.0%), and Rieger’s anomaly (12.5%). For penetrating keratoplasty, the most common indications were anterior segment dysgenesis (34.1%), keratoconus (22.7%), and corneal scar (18.2%). For anterior lamellar keratoplasty, the most common indications were corneal scar (40.5%), limbal dermoid (18.9%), and keratoconus (13.5%). Most cases that underwent lamellar corneal patch graft were for limbal dermoid (68.2%). The proportion of the type of surgery performed for each diagnosis is shown in Table 1 .
| Diagnosis | Total, n (%) | Penetrating Keratoplasty, n (%) | Anterior Lamellar Keratoplasty, n (%) | Corneal Patch Graft, n (%) | Descemet Stripping Automated 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 keratopathy | 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) |
Overall Graft Survival
Overall Kaplan-Meier mean graft survival time was 174.0 months (95% confidence interval [CI], 154.3–193.7). Kaplan-Meier mean graft survival times for optical grafts, therapeutic grafts, and tectonic grafts were 171.9 months (95% CI, 146.5–197.4), 135.9 months (95% CI, 121.0–150.7), and 93.5 months (95% CI, 59.5–127.5), respectively. Kaplan-Meier survival rates for optical grafts were 92.3% at 1 year, 88.0% at 2–4 years, and 81.2% at 5–16 years; survival rates for therapeutic grafts were 94.1% at 1–12 years; survival rates for tectonic grafts were 90.9% at 1–3 years and 68.2% at 4–10 years ( Figure 1 ). The Kaplan-Meier survival distributions for optical, therapeutic, and tectonic grafts were similar and had no statistically significant differences ( P = .556).
Graft Survival Based on Type of Surgery
Forty-four eyes (41.9%) underwent penetrating keratoplasty (PK), 37 eyes (35.2%) underwent anterior lamellar keratoplasty (ALK), 22 eyes (21.0%) underwent lamellar corneal patch graft, and 2 eyes (1.9%) underwent Descemet stripping automated endothelial keratoplasty (DSAEK). Of the eyes that underwent ALK, 28 (75.7%) underwent pre-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 automated lamellar therapeutic keratoplasty (ALTK).
Kaplan-Meier mean graft survival times for PK, ALK, and corneal patch grafts were 171.7 months (95% CI, 141.3–202.2), 74.5 months (95% CI, 64.4–84.5), and 115.8 months (95% CI, 101.0–130.5), respectively. Kaplan-Meier survival rates for PK were 92.6% at 1 year, 88.9% at 2–4 years, and 80.9% at 5–16 years; survival rates for ALK were 88.0% at 1 year and 84.3% at 2–7 years; survival rates of corneal patch graft were 100% at 1–3 years and 90% at 4–10 years ( Figure 2 ). The Kaplan-Meier survival distributions for PK, ALK, and corneal patch grafts were similar ( P = .362).
For optical grafts, the Kaplan-Meier survival rates for PK were 91.4% at 1 year, 87.0% at 2–4 years, and 77.4% at 5–17 years; survival rates for DALKm were 88.0% at 1 year and 78.2% at 2–4 years; survival rates for DALKa were 100% at 1–7 years; and survival rates for ALTK were 100% at 1–3 years.
Graft Survival Based on Diagnosis
Kaplan-Meier survival rates for patients with corneal scar were 85.2% at 1–11 years; survival rates for patients with limbal dermoid were 95.0% at 1–10 years; survival rates for patients with keratoconus were 92.9% at 1–17 years; survival rates for patients with anterior segment dysgenesis were 93.8% at 1 year and 78.1% at 2–4 years; and survival rates for patients with active infectious keratitis were 100% at 1–12 years ( Figure 3 ).
Graft Survival Based on Age at Time of Surgery
Kaplan-Meier survival rates for patients aged 0–1 year were 84.8% at 1 year and 74.2% at 2–6 years; survival rates for patients aged 2–5 years were 94.1% at 1–12 years; survival rates for patients aged 6–10 years were 94.4% at 1 year, 87.7 at 2–3 years, and 70.2% at 4 years; and survival rates for patients aged 11–16 years were 94.5% at 1–4 years and 84.0% at 5–17 years ( Figure 4 ). However, there was no statistically significant difference in graft survival distributions among the different age groups ( P = .256).
Risk Factor Analysis
Seventeen putative risk factors for graft failure were grouped into patient demographics and clinical diagnosis, preoperative recipient corneal status, and intraoperative categories. These included 6 patient- and disease-related factors (recipient age, sex, ethnic group, nationality, clinical diagnosis, and primary indication for transplantation), 8 preoperative risk factors (preoperative corneal vascularization; previous grafts; preexisting glaucoma; and the presence of active infection, active inflammation, ocular surface disease, lid disease, and globe perforation at time of surgery), and 3 intraoperative risk factors (concurrent cataract surgery [intracapsular or extracapsular cataract extraction or phacoemulsification], concurrent anterior chamber intraocular lens implantation, and concurrent anterior vitrectomy). These were the same risk factors as described in our previous Singapore Corneal Transplant Study publications.
Univariate analysis identified 4 risk factors that were significantly associated with reduced graft survival. They were deep corneal vascularization ( P = .012), active inflammation ( P = .023), preexisting glaucoma drainage device ( P = .023), and preexisting ocular surface disease ( P = .037).
Complications
The most common postoperative complications were ocular surface disease (15.2%) (16 of 105 eyes), such as limbal stem cell deficiency and nonhealing epithelial defects; glaucoma (13.3%) (14 of 105 eyes); and cataract (10.5%) (11 of 105 eyes) ( Table 2 ). For eyes that underwent PK, the most common complications were glaucoma (25.0%) (11 of 44 eyes), cataract (20.5%) (9 of 44 eyes), and ocular surface disease (18.2%) (8 of 44 eyes); for eyes that underwent lamellar keratoplasty, the most common complications were ocular surface disease largely secondary to limbal stem cell deficiency (12.8%) (5 of 39 eyes), glaucoma (5.1%) (2 of 39 eyes), and late graft failure (5.1%) (2 of 39 eyes); for eyes that underwent lamellar corneal patch graft, the most common complications were ocular surface disease (13.6%) (3 of 22 eyes) and recurrence of primary disease (13.6%) (3 of 22 eyes).
