Impact of Ocular Conditions and Improvements After Refractive Surgery in Quality of Life for Children With Neurodevelopmental Disorders.

PURPOSE: This study aims to characterize the eye-related quality of life of children with neurodevelopmental and ocular disorders at baseline and after refractive surgery. DESIGN: Prospective interventional case series. METHODS: We enrolled children and adolescents 5 to 18 of age with neurodevelopmental disorders undergoing refractive surgery (6 for pre-/postsurgical assessment and 14 for baseline analysis). Eye-related quality of life was measured using the Pediatric Eye Questionnaire (PedEyeQ). Baseline levels of adaptive functioning and social behaviors were measured using the Adaptive Behavioral Assessment System (ABAS-3) and Social Responsiveness Scale (SRS-2). We assessed the correlation between baseline PedEyeQ scores, number of ocular comorbidities, magnitude of refractive error, and ABAS-3 and SRS-2 scores. RESULTS: At baseline, 14 patients demonstrated decreased median eye-related quality of life (<60/100) in 5 of 9 PedEyeQ domains, moderate deficiencies in social behaviors (SRS-2 median 71, range 49-90), and low adaptive functioning (ABAS-3 median percentile for age of 0.100). Baseline PedEyeQ scores did not correlate with magnitude of refractive error or adaptive functioning scores but did correlate with number of ocular comorbidities and social behavior scores. Six patients have undergone refractive surgery without complication. Postoperatively, 11 of 11 eyes were within ±1.5 diopters spherical equivalent. Four of 6 patients exhibited clinically significant improvements in PedEyeQ scores after surgery. CONCLUSIONS: Even in the presence of significant social and adaptive impairments, quality of life in children with neurodevelopmental disorders is decreased by ocular disorders. Refractive surgery is associated with clinically significant improvements in eye-related quality of life.

Refractive Surgery for Special-Needs Children with High Myopia.

Refractive surgery is useful in children with high isoametropic or anisometropic myopia who are aversive to spectacles or contact lenses. The majority have a neurodevelopmental disorder and the equivalent of legal blindness before surgery. Correction of myopia < 6 Diopters (D) is achieved by photorefractive keratectomy (PRK). Those with myopia > 6 D benefit from phakic IOL implantation, clear lens extraction (CLE), or refractive lens exchange (RLE). The rate of adverse events is low.

Prevalence of the Infantile Strabismus Complex in Premature Children With and Without Periventricular Leukomalacia.

PURPOSE: To determine whether rates of strabismus and associated visuomotor deficits differed among children with different severities of periventricular leukomalacia (PVL). DESIGN: Retrospective, case-control study. METHODS: Brain magnetic resonance images (MRI) obtained from 98 children aged ≥2 years were analyzed using a standardized scoring system: 67 of 98 had PVL (mean GA 31 weeks) and 31 of 98 did not have PVL (mean GA 29 weeks). Severity of PVL was scored as degree of damage to the posterior optic radiations and the splenium of the corpus callosum on MRI. Ophthalmologic examination data were collated to assess the prevalence of visuomotor deficits and the relationship to PVL severity (grades 1-3, mild to severe). RESULTS: Infantile strabismus was documented in 61% of children with mild, 74% with moderate, and 88% with severe PVL (esotropia: exotropia ratio 3.5:1). Associated ocular motor deficits also increased systematically with PVL severity: latent ("fusion maldevelopment") nystagmus (20%, 47%, and 40%, respectively), dissociated vertical deviation (13%, 28%, and 30%), and nasotemporal pursuit/optokinetic nystagmus asymmetry (23%, 38%, and 54%). Additionally, the prevalence of retrograde optic neuropathy increased with PVL severity (5%, 26%, and 38%). The prevalence of each of these signs was substantially lower in children who had no PVL. CONCLUSIONS: Children who suffer PVL are likely to develop the deficits of the infantile strabismus complex. The deficits tend to increase systematically as a function of PVL severity. These findings provide evidence that infantile strabismus is linked to perinatal damage to cerebral vergence and gaze pathways.

Safety of phakic intraocular collamer lens implantation in 95 highly myopic special-needs children.

PURPOSE: To assess the safety of intraocular collamer lens (ICL) implantation in children with high ametropia by reporting rates and case specifics of perioperative and longer-term adverse events (AEs).. SETTING: St. Louis Children's Hospital at Washington University Medical Center, St. Louis, Missouri. DESIGN: Retrospective case series. METHODS: Clinical data were collated retrospectively for 95 special-needs children (160 eyes) implanted with a Visian ICL over the past 5 years. All surgeries were performed at St Louis Children's Hospital under brief general anesthesia. The mean follow-up period was 2.0 ± 1.4 years (range, 0.5 to 5.2). RESULTS: The mean age at implantation was 9.3 ± 5.2 years (range, 1.8 to 25) and mean preoperative spherical equivalent refractive error was -11.20 ± 3.90 diopters (range, 4 to 22). 62 children (62/95, 65%) had a neurodevelopmental disorder. 3 eyes (3/160, 2%) reported minor AE, consisting of steroid-response ocular hypertension, which resolved with cessation of topical steroid drops. Endothelial cell loss averaged 8.1% over 2 years, comparable with that reported in ICL-implanted adults. The most common major AE (7 eyes [7/160, 4%]) was postoperative pupillary block, requiring revision of the peripheral iridotomy. 1 child (1 eye [1/160, 0.6%]) with self-injurious behavior required repair of a wound leak. 1 child (1 eye [1/160, 0.6%]) with Down syndrome developed a cataract 2.8 years after ICL surgery, and 1 child (1 eye [1/160, 0.6%]) with severe autism spectrum disorder experienced traumatic retinal detachment 1.2 years after implantation. CONCLUSIONS: The most common major AE among the cohort with Visian ICL was pupillary block due to closure of the iridotomy. Overall, the AE rate was low in this higher risk, difficult-to-manage population of special-needs children.

Visual acuity, refractive error, and regression outcomes in 169 children with high myopia who were implanted with Ophtec-Artisan or Visian phakic IOLs.

PURPOSE: To analyze outcomes in a large cohort of spectacle-aversive children with high myopia who were treated by implantation of the Ophtec-Artisan or Visian phakic intraocular lens (pIOL). METHODS: Outcome data were collated retrospectively in 78 children (115 eyes) implanted with the Ophtec-Artisan iris-enclaved anterior chamber pIOL and 91 children (154 eyes) implanted with the Visian ICL (intraocular collamer lens) sulcus pIOL. All children had difficulties with spectacle or contact lens wear. Mean age at surgery was 9.9 years; mean follow-up was 3.9 years (range, 0.6-14.1 years). RESULTS: A total of 248 of 269 eyes (92%) were corrected to within ± 0.5 D of their target value. Spherical correction averaged 12.3 ± 1.0 D. Refractive spherical regression was -0.04 D/year at last follow-up. Uncorrected distance visual acuity improved from an average logMAR 1.8 to 0.4; corrected distance visual acuity improved an average 0.3 logMAR. Of the treated children, 68% had a gain in binocular fusion. Neurobehavioral and/or visuomotor comorbidities were present in 87% of children. Five eyes (2%) developed retinal detachment an average 6 years after implantation. Nine eyes (3%) implanted with the Ophtec-Artisan pIOL required repositioning after trauma. CONCLUSIONS: Implantation of pIOLs in children is an effective method for correcting high myopia in spectacle noncompliant children. Rates of myopic regression after pIOL surgery are substantially lower than those reported for children treated by excimer laser photorefractive keratectomy (PRK). The prevalence of major complications was relatively low in this high-risk population.

Successful treatment of an exudative choroidal hemangioma with oral propranolol in a 10-year-old boy.

A 10-year-old boy was referred for a circumscribed choroidal hemangioma with underlying exudative detachment of the left eye. To avoid general anesthetics required for laser-based therapy in a child, we began a trial of oral propranolol. The patient's exudative detachment resolved, with resulting improvement in visual acuity, and remained quiescent for 3 years.

Phakic Intraocular Collamer Lens (Visian ICL) Implantation for Correction of Myopia in Spectacle-Aversive Special Needs Children.

PURPOSE: A subset of children with high anisometropia or isoametropia and neurobehavioral disorders have chronic difficulties with spectacle or contact lens wear. We report the results of refractive surgery in a series of these children treated using bilateral or unilateral intraocular collamer lens (Visian ICL) implantation for moderate to high myopia. DESIGN: Prospective nonrandomized cohort study. METHODS: Clinical course and outcome data were collated prospectively for 40 implanted eyes in 23 children (mean age 10.2 ± 5.3 years, range, 1.8-17 years). Myopia ranged from -3.0 to -14.5 diopters (D), mean -9.2 ± 3.5 D. Goal refraction was plano to +1 D. Correction was achieved by sulcus implantation of a Visian ICL (STAAR Surgical, Monrovia, California, USA) under general anesthesia. Mean follow-up was 15.1 months (range, 6-22 months). RESULTS: Thirty-five eyes (88%) were corrected to within ±1.0 D of goal refraction; the other 5 (12%) were corrected to within 1.5 D. Uncorrected distance visual acuity improved substantially in all eyes (from mean 20/1050 [logMAR 1.72] to mean 20/42 [logMAR 0.48]). Spherical regression at last follow-up was an average of +0.59 D. Visuomotor comorbidities (eg, amblyopia, nystagmus, foveopathy, optic neuropathy) accounted for residual postoperative subnormal visual acuity. Thirteen of the 23 children (57%) had a neurobehavioral disorder (eg, developmental delay/intellectual disability/mental retardation, Down syndrome, cerebral palsy, autism spectrum disorder). Eighty-five percent (11/13) of those children were reported to have enhanced visual awareness, attentiveness, or social interactions. Endothelial cell density was measureable in 6 cooperative children (10 eyes), showing an average 1% decline. Central corneal thickness, measured in all children, increased an average of 8 µm. Two children (8%) required unplanned return to the operating room on the first postoperative day to alleviate pupillary block caused by a nonpatent iridotomy. No other complications were encounterd. CONCLUSION: Visian ICL implantation improves visual function in special needs children who have moderate to high myopia and difficulties wearing glasses or contact lenses.

Pseudopapilledema and association with idiopathic intracranial hypertension.

PURPOSE: Diagnosing idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, can be challenging in children. Diagnosis is based on lumbar puncture, opening pressures, and appearance of the optic disk. Misdiagnosis of papilledema, a typical finding, may lead to unnecessary treatments and procedures. We report 52 children over a 6-year period to better identify the true incidence of pseudopapilledema and other factors that may confound the diagnosis of IIH. METHODS: A retrospective chart review approved by the Institutional Review Board was performed. Fifty-two children under the age of 21 referred to us based on suspected IIH or papilledema from 2007 to 2013 are included in this study. Patients were assessed by a pediatric ophthalmologist and a neurosurgeon. RESULTS: Fifty-two children were initially diagnosed with IIH and/or papilledema; 26 diagnoses were revised to pseudopapilledema after pediatric ophthalmological review. Out of those 26 patients with pseudopapilledema, 14 had undergone lumbar punctures, 19 had MRIs, 9 had CTs, and 12 were taking medications-these medications were discontinued upon revision of the diagnoses. The difference in the CSF opening pressure between children diagnosed with true IIH (32.7 cm H2O) and children diagnosed with pseudopapilledema (24.7 cm H2O) was statistically significant. CONCLUSIONS: IIH diagnosis is heavily reliant on the appearance of the optic disk. Pediatric ophthalmological assessment is essential to carefully examine the optic disk and prevent further unnecessary investigation and treatments. Close communication between pediatricians, ophthalmologists, and neurosurgeons can avoid invasive procedures for children who do have pseudopapilledema, and not IIH or associated papilledema.

Comparison of the effectiveness and safety of transscleral cyclophotocoagulation and endoscopic cyclophotocoagulation in pediatric glaucoma.

PURPOSE: Among the options for surgical management of pediatric glaucoma, destruction of the ciliary body reduces aqueous production and, consequently, intraocular pressure (IOP). Compared to more invasive filtering and shunt procedures, cyclodestruction is an attractive option for control of IOP in pediatric glaucomas. METHODS: The relative reduction in IOP, duration of effect, and comparable safety and efficacy of transscleral cyclophotocoagulation (TSCP) and endoscopic cyclophotocoagulation (ECP) in pediatric patients with glaucoma was studied in this retrospective chart review. RESULTS: A reduction in IOP of 28.6% and 33.2% with TSCP and ECP, respectively, was found. Eyes treated with ECP underwent an average of 3.24 cyclodestructive procedures; eyes treated with TSCP underwent an average of 2.29 cyclodestructive treatments. These differences were not statistically significant. A final success rate of 67.6% after TSCP and 62% after ECP failed to significantly differ between the two groups. Consequently, two-thirds of the patients were able to avoid penetrating surgery and the associated risks after one or more cyclodestructive procedures. CONCLUSIONS: TSCP and ECP are safe, effective, and comparable treatments for pediatric glaucomas. The results suggest that TSCP and ECP may be considered first-line therapy to achieve control of IOP in all forms of pediatric glaucoma. [J Pediatr Ophthalmol Strabismus 2014;51(2):120-127.].

Pediatric refractive surgery: corneal and intraocular techniques and beyond.

Refractive surgery has now been used successfully to treat severe anisometropia and isoametropia associated with amblyopia in children who cannot wear standard spectacles or contact lenses. Extraocular techniques include photorefractive keratectomy, laser-assisted subepithelial keratomileusis, and laser-assisted in situ keratomileusis. Intraocular techniques include refractive lensectomy and phakic intraocular lenses and are still being investigated in children for refractive errors outside the treatment dose capabilities of the excimer laser. This workshop discusses the various techniques, how and when to use each, and their risks and benefits. Newer techniques currently being used in adults that may someday be used in children are also introduced.

Long-term results of botulinum toxin-augmented medial rectus recessions for large-angle infantile esotropia.

PURPOSE: To evaluate the long-term results of medial rectus recessions augmented by botulinum toxin injection for treating infants with large-angle (> 60 prism diopters [PD]) infantile esotropia. DESIGN: Interventional case series. SETTINGS: Hospital-based clinical practice. PATIENT POPULATION: Twenty-three patients with large-angle infantile esotropia who were followed for at least 2 years postoperatively. INTERVENTION: Surgical treatment with botulinum toxin in addition to bilateral medial rectus muscle recessions. The preoperative findings, treatment, and outcomes were reviewed. MAIN OUTCOME MEASURES: Surgery was considered successful if the patients did not require additional horizontal strabismus surgery and had less than 10 PD of horizontal deviation. RESULTS: The age at surgery ranged from 4 to 36 months (mean 14.5 months) and the angle of esotropia ranged from 65 to 100 PD (mean 72 PD). Treatment was successful in 17 of 23 patients (74%), with follow-up of 2 to 13 years (mean 6.6 years). CONCLUSION: Botulinum toxin-augmented medial rectus recession is an effective treatment for large-angle infantile esotropia, with stable results over time.

Repair of strabismus and binocular fusion in children with cerebral palsy: gross motor function classification scale.

PURPOSE: Children with cerebral palsy (CP) tend to be either excluded from studies of strabismus repair or pooled with children who have other neurologic disorders. The authors limited this study to children with defined CP to determine the success or failure of restoring eye alignment and fusion. METHODS: An observational, cross-sectional, prospective study was conducted on a representative cohort of 50 children. CP severity ranged from Gross Motor Function Classification System (GMFCS) level 1 (least severe) to 5 (most severe). Mean age at entrance and surgery was 3.5 years, and mean follow-up was 4.1 years (minimum 1 year). RESULTS: The predominant form of strabismus was infantile-onset: esotropia in 54%, exotropia in 26%, and dyskinesia in 10%. Sixty-six percent of esotropic children and 61% of exotropic children achieved optimal (microtropic) alignment after an average of 2 and 1.8 surgical procedures, respectively. The likelihood of optimal alignment was similar in children with mild (GMFCS level 1-2) versus severe (GMFCS level 3-5) CP (P = 0.7; χ(2)). Irrespective of GMFCS severity, 46% of children gained binocular fusion/stereopsis, but the quality of fusion gained was greater in children with mild CP (P < 0.05). Earlier surgery was more likely to be successful (P < 0.05). CONCLUSIONS: Restoration of binocular alignment and a degree of fusion is a realistic goal in the majority of strabismic CP children. Repair may be achieved in children at both the mild and the severe ends of the GMFCS spectrum, without undue concern about treatment futility or excessive reoperation.

Phakic intraocular lens correction of high ametropia in children with neurobehavioral disorders.

PURPOSE: A subset of children with high ametropia and neurobehavioral disorders have chronic difficulties with spectacle or contact lens wear. We report the results of refractive surgery in a series of these children treated using bilateral or unilateral phakic intraocular lenses (IOLs) for ametropia >10 D. METHODS: Clinical course and outcome data were collated prospectively in a group of 12 children (mean age, 10.1 years; range, 4-17 years) with neurobehavioral disorders exacerbated by poor compliance with spectacles. Myopia in 18 eyes ranged from -10.0 to -22.75 D (mean, -15.2 D) and in 2 hyperopic eyes from +10.25 to +10.75 (mean, +10.5 D). Goal refraction was approximately 0 to +1 D. Correction was achieved by implantation of an iris-enclaved phakic IOL under general anesthesia. Mean follow-up was 9.1 months (range, 3-15 months). RESULTS: Myopia correction averaged 14.5 D and hyperopia correction 9.4 D. Eighty-six percent of eyes (17/20 eyes) were corrected to within +/- 1 D of emmetropia and the remaining 14% (3 eyes) to within +/- 2 D. Uncorrected visual acuity improved substantially in all 20 eyes (60-fold; from a mean of 20/3400 to a mean of 20/57). Ocular comorbidities in each child accounted for residual postoperative, subnormal visual acuity (eg, amblyopia, nystagmus, albinism, regressed retinopathy of prematurity). Visual functions (measured using a 23-item validated survey) improved. One eye required IOL exchange; no other clinically significant complications have been encountered. CONCLUSIONS: Phakic IOL implantation improves visual function substantially in neurobehaviorally impaired children who have high ametropia and difficulties wearing glasses.

Refractive surgery for children: excimer laser, phakic intraocular lens, and clear lens extraction.

PURPOSE OF REVIEW: The article summarizes current recommendations for refractive surgery and outcomes in ametropic children who are spectacle noncompliant and unsuitable for contact lens wear. RECENT FINDINGS: The majority of those treated have anisometropic amblyopia. The most common method employed is advanced surface ablation using the excimer laser, such as photorefractive keratectomy or laser-assisted subepithelial keratomileusis. Surface ablation is safe in children; the drawback is the high rate of refractive regression, which is most pronounced in children with myopia beyond 10.0 D and hyperopia beyond 4.5 D. Those with more extreme ametropia--beyond the effective range for surface ablation--need phakic intraocular lens implantation or clear lens extraction, with or without implantation of a posterior chamber intraocular lens (refractive lens exchange). Children with neurobehavioral disorders and high bilateral ametropia may be functionally blind without the surgery. The prevalence of complications with each of these techniques--over follow-up generally less than 5 years--has been low. Longer follow-up will be more revealing. SUMMARY: The majority of children with ametropia--unilateral or bilateral--do well with glasses or contact lenses, but a minority do not. Pediatric refractive surgery meets an important need for this minority.

Unilateral lens extraction for high anisometropic myopia in children and adolescents.

INTRODUCTION: A subpopulation of children with anisometropic myopia, amblyopia, and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction) or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange). METHODS: Clinical course and outcome data were collated retrospectively in a group of 7 children and adolescents (mean age, 9.1 years; range, 4-20 years) with neurobehavioral disorders and noncompliance with spectacle wear for anisometropic myopia. Myopia in the 7 eyes ranged -11.9 to -24.5 D (mean, -16.7 D). Goal refraction was 0 to + 4 D. Correction was achieved by lensectomy in 5 eyes and lensectomy with intraocular lens implantation in 2 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 5 eyes (71%). Mean follow-up was 3.8 years (range, 0.5-5.4 years). RESULTS: Myopia correction averaged 17.3 D. A total of 86% (6 eyes) were corrected within +/- 3 D of the goal refraction and the remaining 14% to within +/- 4 D. Uncorrected visual acuity improved postoperatively in all 7 eyes, albeit modestly (average gain 0.14 Snellen fraction; gain from a mean 20/2550 to a mean 20/130). Myopic regression averaged approximately 0.43 D/year. Capsular opacification necessitated YAG-laser membranectomy in the 2 eyes that had preservation of the posterior capsule at the primary procedure. Retinal detachment has not occurred in any of the eyes during the follow-up period. CONCLUSIONS: Refractive myopic lensectomy reduced high anisometropia and improved functional vision in children who have high myopia beyond the range of excimer laser correction and who will not wear glasses. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 1. Clear lens extraction and refractive lens exchange.

INTRODUCTION: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction), or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange). METHODS: Clinical course and outcome data were collated prospectively in a group of 13 children (mean age 10.4 years, range 1 to 18 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 26 eyes ranged from -14.25 to -26.00 D (mean -19.1 D). Goal refraction was approximately +1 D. Correction was achieved by lensectomy alone in 10 eyes, and lensectomy with intraocular lens implantation in 16 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 11 eyes (42%). Mean follow-up was 4.5 years (range 1.3 to 7.5 years). RESULTS: Myopia correction averaged 19.9 D. Eighty-one percent (21 eyes) were corrected to within +/-2 D of goal refraction and the remaining 19% (5 eyes) to within +/-4 D. Uncorrected acuity improved substantially (ie, an average 2 log units) in all 26 eyes, with commensurate gains in behavior and environmental visual interaction in 85% [corrected] of children (11/13) [corrected] Myopic regression averaged -0.16 D/year. Capsular regrowth and/or opacification necessitated vitrector or YAG-laser membranectomy in 13 [corrected] eyes (50%) [corrected] Focal retinal detachment (successfully repaired) occurred after eye contusion in one eye (4%) with cicatricial retinopathy of prematurity. CONCLUSIONS: Bilateral refractive lensectomy is effective for improving functional vision in neurobehaviorally impaired children who have high myopia (beyond the range of excimer laser correction: see companion publication) and difficulties wearing glasses. Posterior capsule regrowth/opacification is common, necessitating secondary membranectomy. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.

Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK).

INTRODUCTION: A subpopulation of children with high myopia and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated bilaterally using excimer laser technology. METHODS: Clinical course and outcome data were collated prospectively in a group of 9 children (mean age, 10.2 years; range, 3-16 years) with neurobehavioral disorders exacerbated by chronic noncompliance with spectacle wear, causing profoundly low functional vision. Myopia in the 18 eyes ranged from -3.75 to -11.5 D (mean -16.6 D) and the desired refraction was approximately +1D. Correction was achieved by bilateral laser-assisted subepithelial keratectomy (ie, LASEK) performed under brief general anesthesia. Mean follow-up was 17 months (range, 6-36 months). RESULTS: Myopia correction averaged 7.9 D. Eighty-nine percent (16/18 eyes) were corrected to within +/-1 D of goal refraction. Uncorrected acuity improved postoperatively in all 18 eyes, with commensurate gains in behavior and environmental visual interaction in 88% (15/17 children). Myopic regression averaged approximately 0.8 d/year. the only complication encountered was mild (1+) corneal haze in 35% of treated eyes. DISCUSSION/CONCLUSIONS: Bilateral excimer laser surgery is effective for improving functional vision substantially in highly myopic, neurobehaviorally impaired children who have difficulties wearing glasses. Myopic regression is common. Further study is indicated to determine the long-term safety of these and alternative refractive procedures in similar pediatric populations.