Brian J. Forbes

Duarte (DG) galactosemia: A pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening

UNLABELLED Newborn screening for galactosemia has shown a high prevalence of partial galactose uridyl transferase deficiencies such as Duarte (DG) galactosemia. STUDY OBJECTIVE To determine whether (a) there is any clinical impact of DG galactosemia on development (b) there is a relationship between outcome and biochemical parameters in patients who receive no treatment. STUDY POPULATION Twenty-eight children with DG galactosemia. Group-I-17 children had a lactose restricted diet in the first year of life. Group-II-11 children had a regular diet since birth. METHODS Developmental, physical, and ophthalmologic assessments were completed on both DG groups. RBC gal-1-p and urine galactitol were monitored during the follow-up visits in every child with DG galactosemia. Gal-1-p, urine galactitol, liver function tests, and FSH were tested at the time of study visit. RESULTS The groups had statistically significant differences on RBC gal-1-p and urine galactitol at the 2 week, 1 month, 6 month, and 1 year time points. There was no statistical difference of gal-1-p or urine galactitol in group-I and -II at the time of study. The groups had statistically significant differences on adaptive scores, but not on language or IQ. None of the DG subjects had abnormal liver function at the time of diagnosis or the study visit. The FSH levels were normal. There were no statistically significant relationships between the first year metabolic values and developmental outcomes. CONCLUSIONS The data presented here indicate that clinical and developmental outcomes in DG galactosemics are good regardless of any diet changes.

Odds of abuse associated with retinal hemorrhages in children suspected of child abuse

PURPOSE To describe the prevalence of retinal hemorrhages in children being evaluated for abusive head trauma and quantify the association between the likelihood of abuse and the presence and severity of retinal hemorrhages. METHODS Retrospective cross-sectional study of 110 children aged 15 months or younger who were evaluated for abusive head trauma and received an ophthalmological examination. The child abuse specialists diagnosis was categorized as definite accident, probable accident, probable abuse, or definite abuse, according to an algorithm that excluded eye findings. Retinal hemorrhage severity was scored on a 12-point scale (6 points per eye) based on type, size, location, and extent. Higher scores indicated greater severity of eye findings. RESULTS Seventy-four percent of children were younger than 6 months old. Forty-five percent of cases were definite abuse and 37% were definite accident. The prevalence of retinal hemorrhages was 32%. Across all subjects, the presence of retinal hemorrhage was highly associated with definite or probable abuse versus definite or probable accident (age-adjusted odds ratio 5.4 [95% CI, 2.1-13.6]). The odds ratio in children younger than 6 months (n = 81) was 11.7 (95% CI, 2.9-66.8). Retinal hemorrhage severity was higher in abuse versus accident (p < 0.0001) and correlated positively with abuse (Spearman r = 0.406, p < 0.0001). Scores above 8 (n = 13) were only present in abused children. CONCLUSIONS Retinal hemorrhages are highly associated with abusive head trauma, particularly in children younger than 6 months of age. Increasing retinal hemorrhage severity is correlated with increasing likelihood of abuse.

Evaluation and management of retinal hemorrhages in infants with and without abusive head trauma

Extensive intraocular hemorrhage in young infants in the setting of acute brain injury and in the absence of a history of severe accidental trauma or underlying medical cause must be considered to be nonaccidental injury until otherwise proven. In the absence of any obvious explanation, the presence of any retinal hemorrhage should raise the possibility of abusive head trauma in the differential diagnosis and perhaps lead to such testing as skeletal radiography and neuroimaging, consultation with a child abuse specialist, as well as workup for other relevant systemic conditions. Physicians who treat infants and children are mandated to report suspected child abuse to child welfare agencies for investigation, and ophthalmologists who encounter children with ophthalmic manifestations of abuse need to ensure that the proper steps are taken to protect their patients from the potential for further harm. Ascertainment of abusive head trauma is critical to prevent a potentially fatal recurrence.

Inflicted childhood neurotrauma (shaken baby syndrome): ophthalmic findings.

Inflicted childhood neurotrauma (shaken baby syndrome) is the term used for violent, nonaccidental, repetitive, unrestrained acceleration-deceleration head and neck movements, with or without blunt head trauma, combined with a unique, age-related biomechanical sensitivity in children typically younger than 3 years. This syndrome is typically characterized by a combination of fractures, intracranial hemorrhages, and intraocular hemorrhages. Retinal hemorrhage is the most common ophthalmic finding, and usually occurs at all levels of the retina. In recent years, increasing pressure has been placed on ophthalmologists to render diagnostic interpretations of the retinal findings in children suspected to be victims, which may have great forensic implications in criminal proceedings. New research has increased our understanding of the pathophysiology of retinal hemorrhages, the importance of specifically characterizing the types, patterns, and extent of these retinal hemorrhages, and the differential diagnosis.

Sclerocornea associated with the chromosome 22q11.2 deletion syndrome

Reported ocular findings in the 22q11.2 deletion syndrome (which encompasses the phenotypes of DiGeorge, velocardiofacial, and Takao (conotruncal‐anomaly‐face) syndromes) have included posterior embryotoxon (prominent, anteriorly displaced Schwalbes line at the corneal limbus or edge), retinal vascular tortuosity, eyelid hooding, strabismus, and astigmatism. We present seven 22q11.2 patients from multiple centers with sclerocornea, an eye finding previously unreported in the literature. Four boys and three girls were identified with sclerocornea, systemic DGS/VCFS findings, and fluorescence in situ hybridization (FISH)‐confirmed microdeletion at chromosome 22q11.2. FISH diagnosis was perinatal in six patients but at 2 years of age in one child. Sclerocornea was bilateral in five patients. Findings included descemetocele (five eyes), microophthalmos (one eye), iridocorneal adhesions (one bilateral case), and severe anterior segment dysgenesis (one eye). Two patients underwent bilateral corneal transplantation; another two were scheduled for possible unilateral transplant. Sclerocornea is a static congenital condition in which the cornea is opaque and vascularized and resembles the sclera. The novel finding of sclerocornea suggests that a genetic locus at 22q11.2 may be involved in anterior segment embryogenesis. In most of our patients, the diagnostic process was underway, but in one patient 22q11.2 deletion was not suspected until after the child had already been undergoing treatment for sclerocornea for 2 years. Sclerocornea should be added to the clinical manifestations of the 22q11.2 deletion syndrome. Ophthalmologists diagnosing sclerocornea in children with systemic findings suggestive of 22q11.2 deletion should ensure appropriate genetic referral.

Patterns of Retinal Hemorrhage Associated With Increased Intracranial Pressure in Children

OBJECTIVE: Raised intracranial pressure (ICP) has been proposed as an isolated cause of retinal hemorrhages (RHs) in children with suspected traumatic head injury. We examined the incidence and patterns of RHs associated with increased ICP in children without trauma, measured by lumbar puncture (LP). METHODS: Children undergoing LP as part of their routine clinical care were studied prospectively at the Childrens Hospital of Philadelphia and retrospectively at Nationwide Children’s Hospital. Inclusion criteria were absence of trauma, LP opening pressure (OP) ≥20 cm of water (cm H2O), and a dilated fundus examination by an ophthalmologist or neuro-ophthalmologist. RESULTS: One hundred children were studied (mean age: 12 years; range: 3–17 years). Mean OP was 35 cm H2O (range: 20–56 cm H2O); 68 (68%) children had OP >28 cm H2O. The most frequent etiology was idiopathic intracranial hypertension (70%). Seventy-four children had papilledema. Sixteen children had RH: 8 had superficial intraretinal peripapillary RH adjacent to a swollen optic disc, and 8 had only splinter hemorrhages directly on a swollen disc. All had significantly elevated OP (mean: 42 cm H2O). CONCLUSIONS: Only a small proportion of children with nontraumatic elevated ICP have RHs. When present, RHs are associated with markedly elevated OP, intraretinal, and invariably located adjacent to a swollen optic disc. This peripapillary pattern is distinct from the multilayered, widespread pattern of RH in abusive head trauma. When RHs are numerous, multilayered, or not near a swollen optic disc (eg, elsewhere in the posterior pole or in the retinal periphery), increased ICP alone is unlikely to be the cause.

The eye in child abuse: Key points on retinal hemorrhages and abusive head trauma

This review presents an up-to-date overview of ocular injuries resulting from child abuse, with a spotlight on abusive head trauma. Retinal hemorrhage is a principle finding of inflicted head trauma. The specific pattern of hemorrhages holds valuable diagnostic information, which can help to guide multidisciplinary assessments of the likelihood of abuse. Indirect ophthalmoscopy through dilated pupils by an ophthalmologist is necessary for adequate examination and documentation of retinal findings. Initial pediatrician evaluation of the eye and indications for ophthalmological consultation are reviewed. Focus is then placed upon understanding retinal hemorrhage patterns, their diagnostic significance and likely pathophysiological mechanisms. The differential diagnosis of retinal hemorrhage in young children is discussed, highlighting key distinctions among retinal hemorrhage patterns, severity and frequencies, as well as other ocular findings. The most common cause of retinal hemorrhage in an infant is trauma, and most other causes can be identified by considering the hemorrhage pattern, ocular or systemic signs and the results of laboratory and imaging tests, when indicated.

Ocular Hemorrhages in Neonatal Porcine Eyes from Single, Rapid Rotational Events

PURPOSE To characterize ocular hemorrhages from single, rapid head rotations in the neonatal pig. METHODS Three- to 5-day-old anesthetized piglets (n=51) underwent a single, rapid (117-266 rad/s) head rotation in the sagittal (n=13), coronal (n=7), or axial (n=31) planes. Six hours after injury, the animals were euthanatized and perfusion fixed, and the brain and eyes were harvested for gross and histopathologic examination by masked neuro- and ocular pathologists. RESULTS Ocular hemorrhage was found in 73% of animals (51% bilateral). Intraocular hemorrhage was primarily located near the vitreous base (70% of injured animals had ciliary body hemorrhage, and 11% had peripheral retinal hemorrhage). Hemorrhages were also found in the anterior chamber (11%), vitreous (5%), and optic nerve (disc, 8%; nerve sheath, 57%). Rapid axial head rotations resulted in a higher incidence of intraocular hemorrhage than coronal or sagittal head rotations, but the difference did not reach statistical significance (P=0.06). Control eyes had no injuries. CONCLUSIONS Optic nerve sheath and ciliary body hemorrhages were common in piglets that experienced a single, rapid head rotation. Retinal hemorrhage was present in a smaller number of animals. Most intraocular hemorrhages were located in regions of strong vitreous attachment, suggesting that this animal model will be useful in investigating the effect of vitreoretinal adhesion on ocular hemorrhage caused by inertial head rotations. Extrapolation of this model to the human infant should not be made until the effect of anatomic differences between the human and pig on the occurrence and patterns of ocular injuries is further investigated.

Retinal hemorrhages in patients with epidural hematomas

PURPOSE To present a series of infants found to have sparse retinal hemorrhages associated with isolated epidural hematomas. None of these infants had other intracranial or subdural hemorrhages present. METHODS Children less than 3 years of age admitted to an urban childrens hospital between January 1998 and December 2002 with radiographic evidence of an isolated epidural hematoma at the time of presentation were eligible for this study. RESULTS During the time period of the study, 15 children were admitted with traumatic epidural hematomas. Nine patients had an ophthalmologic examination, of which five had evidence of sparse retinal hemorrhages. All five patients with retinal hemorrhages were less than 8 months of age and all required surgical evacuation of the epidural hematomas. Of the five patients with retinal hemorrhages, four were unilateral, one was bilateral, and in all cases, the retinal hemorrhages were superficial, few in number, and confined to the posterior pole. There were no deep retinal or subretinal hemorrhages present. The institutional child protection team evaluated all five patients with retinal hemorrhages and each case was felt to be consistent with the history provided and no history of shaking was elicited. CONCLUSIONS We found sparse retinal hemorrhages in five of nine patients who presented to our hospital with isolated epidural hematomas and who had had an ophthalmologic examination. All nine patients were evaluated by the institutional child protection team, who did not feel that there was sufficient evidence to be suspicious of nonaccidental trauma.

Ocular Complications in Children with Diabetes Mellitus

PURPOSE The effectiveness of annual eye examinations in diabetic children is unclear. We sought to determine the prevalence and onset of ocular pathology in children with diabetes mellitus (DM), identify risk factors for ocular disease, and recommend a screening regimen for asymptomatic children. DESIGN Retrospective, consecutive cohort study. PARTICIPANTS Children aged less than 18 years with type 1 or 2 DM examined over a 4-year period. METHODS All children underwent a complete eye examination, including dilated fundoscopy and cycloplegic refraction. A literature review was performed, identifying the youngest reported age and shortest reported duration of DM before the diagnosis of diabetic retinopathy (DR). MAIN OUTCOME MEASURES Prevalence of DR, cataract, high refractive error, and strabismus. RESULTS A total of 370 children (mean age, 11.2 years; range, 1-17.5 years) had 693 examinations, with a mean DM duration of 5.2 years (range, 0.1-16.2 years) and a mean hemoglobin A1c (HbA1c) of 8.6 (range, 5-≥14). No children had DR. A total of 12 children had cataract; 5 required extraction but were identified by decreased vision, not diabetic screening. A total of 19 children had strabismus; only 1 was microvascular paralytic strabismus. A total of 41 children had high refractive error. There were no associations between these conditions and duration or control of DM. In the literature, the youngest age at diagnosis of severe DR was 15 years, and the shortest duration of disease was 5 years. CONCLUSIONS Diabetic retinopathy is rare in children regardless of duration and control of DM. On the basis of our study and literature review, screening examinations for type 1 diabetes could begin at age 15 years or at 5 years after the diagnosis of DM, whichever occurs later, unless the child is judged by the endocrinologist as being at unusually high risk. Other ocular complications are identifiable through existing amblyopia screening methods.