Natalie C. Kerr

Rickets Secondary to Phosphate Depletion: A Sequela of Antacid Use in Infancy

Two infants presented with growth failure and were found to have generalized osteomalacia (rickets) due to phosphate depletion from prolonged administration of an aluminum-containing antacid given for the symptoms of colic. One of the infants developed bilateral proptosis due to craniosynostosis related to the underlying metabolic bone disease. The chronic use of aluminum-containing antacids in infants has potential risk for the growing skeleton and is not innocuous. Therefore, antacid therapy should be used in low doses and very cautiously, with routine monitoring of serum calcium and phosphorus in children taking medications which reduce gastrointestinal phosphate absorption.

Sickle Cell Trait as a Risk Factor for Secondary Hemorrhage in Children With Traumatic Hyphema

PURPOSE To determine risk factors for secondary hemorrhage and poor visual outcome in children with traumatic hyphemas. METHODS We reviewed 99 eyes of 97 children younger than 18 years who had been hospitalized for hyphema within 48 hours of blunt eye trauma. Inpatient records were examined for race, age, sickle cell trait status, size of hyphema and intraocular pressure at admission, secondary hemorrhage (rebleed of hyphema), and medications while hospitalized. Fifty-five eyes of 53 children had at least 1 month of follow-up or attained best-corrected visual acuity of 20/50 or better at their last outpatient visit. RESULTS Among 99 eyes of 97 children with traumatic hyphema, secondary hemorrhage occurred in nine eyes (9%). Among 72 eyes of 70 African-American children, secondary hemorrhage occurred in nine eyes (14%), whereas in 27 eyes of 27 white children, there were no secondary hemorrhages. However, when the 14 eyes of 13 sickle cell trait-positive children were excluded from the African-American group, the 57 eyes of sickle cell trait-negative African-American and white children did not have any secondary hemorrhages. The sickle cell trait-positive group had secondary hemorrhages in nine of 14 eyes (64%), significantly (P < .005) different from the 0% rate in the 57 eyes of African-American sickle cell trait-negative and white children. The sickle cell trait-positive group also had higher intraocular pressure and permanent visual impairment. CONCLUSION Sickle cell trait is a significant risk factor for secondary hemorrhage, increased intraocular pressure, and permanent visual impairment in children who have traumatic hyphemas following blunt trauma.

Autosomal Recessive Best Vitelliform Macular Dystrophy Report of a Family and Management of Early-Onset Neovascular Complications

OBJECTIVES To report a child with early-onset autosomal recessive Best vitelliform macular dystrophy and compound heterozygous BEST1 mutations, the management of a choroidal neovascular membrane with intravitreal bevacizumab in the proband, the benefits of amblyopia therapy in the fellow eye, and the findings in the parents, carriers of heterozygous BEST1 mutations. METHODS A 5-year-old white girl presented with monocular visual acuity loss and bilateral vitelliform macular lesions. Her parents were also examined. Examinations included electro-oculograms (EOGs), electroretinograms, imaging studies, and BEST1 gene testing. Interventions included off-label treatment with intravitreal bevacizumab in the left eye and amblyopia therapy in the right eye. RESULTS The proband presented with visual acuity of 20/200 OD with an atypical subfoveal vitelliform scar and 20/16 OS with asymptomatic vitelliform deposits. Subfoveal choroidal neovascularization developed at age 6 years, causing marked vision loss (20/200 OS). Visual acuity recovered to 20/20 OS after serial intravitreal bevacizumab injections. Amblyopia therapy improved visual acuity to 20/50 OD. The proband showed subnormal EOG Arden ratios and mild electroretinogram changes. Molecular testing showed missense BEST1 mutations (R141S and R141H) in the proband. Unlike dominant Best vitelliform macular dystrophy, in the heterozygous parents EOGs were normal and minimal autofluorescence changes were seen. CONCLUSIONS Choroidal neovascularization treatment with bevacizumab was associated with vision restoration. Amblyopia treatment also yielded significant benefit. Patients presenting with vitelliform lesions should be screened for BEST1 mutations, even when parents have normal EOG and imaging results. CLINICAL RELEVANCE Prompt recognition and treatment of choroidal neovascularization and amblyopia management effectively restores vision. Awareness and recognition of recessive inheritance permits correct diagnosis and counseling.

Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene

PURPOSE To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation. METHODS Three patients [PT1, F, 27 years old (yo) at last examination, 14-year follow-up (F/U) PT2, F, 15-yo PT3, M, 15-yo, both 1-year F/U] underwent eye exams, Goldmann visual fields (GVFs), dark- (DA) and light-adapted (LA) electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Vision and systemic history were also collected. RESULTS All patients had night blindness, hyperopic astigmatism, ptosis or mild blepharospasm, foot polydactyly, 5th finger clinodactyly, history of headaches, and variable, diet-responsive obesity. Two had asthma, PT1 was developmentally delayed, PT2 had Asperger-like symptoms, and PT3 had normal cognition. At age 14, acuity was 20/100 in PT1, who had nystagmus since age 2, 20/40 in PT2 and 20/30 in PT3. By 27yo PT1 progressed to 20/320, by 15 yo PT2 was 20/60 and PT3 remained stable. PT1 had well preserved peripheral GVFs, with minimal progression over 10 years of F/U. PT2 and PT3 presented with ring scotomas and I4e<5°. All patients had severe generalized visual sensitivity depression. ERGs were consistently recordable (also rod ERG in PT3 after 60 min DA), but progressed to non-recordable in PT1. Mixed DA ERGs exhibited electronegativity. In PT3, this was partly due to a bleaching effect during bright-flash DA averaging, partly to ON≫OFF LA response compromise. PT2 and 3 had, on SD-OCTs, generalized macular thinning, normal retinal lamination, and widespread photoreceptor outer/inner segment attenuation except foveally, and multiple rings of abnormal FAF configuring a complex bulls eye-pattern. PT1 had macular atrophy. All patients also had peripapillary nerve fiber layer thickening. CONCLUSIONS The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation.

Visual evoked potentials in children with neurofibromatosis type 1

The purposes of this investigation were to determine: (a) if visual evoked potential (VEP) abnormalities could be identified in children with neurofibromatosis type 1 (NF1) with no evidence of optic pathway or brain neoplasias on MRI; and (b) if VEP abnormalities could be explained by the presence of hyperintense T2-weighted foci on MRI testing, known as unidentified bright objects (UBOs). To answer these questions, VEPs were recorded from 16 children with NF1 and compared to 13 normal subjects in the same age range tested with the same protocol. Pattern-reversal VEPs were recorded at four stimulus sizes both monocularly and binocularly, the latter to hemi-field stimuli. Flash VEPs were recorded in dark- and light-adapted conditions. VEP measurements and MRI readings for UBOs were conducted in a masked fashion. Ten of the 16 children with NF1 had abnormal VEPs to at least one of the four types of stimuli. Abnormalities included delayed responses (n=6), absent flash VEP P2 component (n=3), or both (n=1). Abnormalities of the P2 component of the dark-adapted flash VEP were the most common finding (n=7), although no single testing strategy was able to identify all children with abnormal VEPs. UBOs were present in all children, demonstrating that their presence does not fully account for VEP abnormalities in children with NF1. This study also demonstrates that VEP abnormalities are present also in the absence of neoplasias of the optic pathways or of the brain. Our results are suggestive of a primary abnormality of visual processing in children with NF1.

Ocular disease in children with vertically acquired human immunodeficiency virus infection.

BACKGROUND Clinical reports suggest that ocular disease in infants and children vertically infected with human immunodeficiency virus (HIV) is different from that in adults. Pediatric patients with acquired immunodeficiency syndrome (AIDS) and HIV infection are being treated more aggressively and are living longer, but current literature on the incidence of AIDS-related ocular disease in vertically acquired HIV infection is limited. METHODS Thirty-three children with culture-positive, vertically acquired HIV infections were prospectively followed with ophthalmic examinations between September 1991 and August 1996 at the University of Massachusetts. Patients were categorized as having symptomatic or asymptomatic HIV disease according to the U.S. Centers for Disease Control and Prevention guidelines. Absolute CD4 counts and other measures of immune function were obtained. RESULTS The average length of follow-up was 30 months, and the average number of ophthalmic examinations per patient was 4.8. Ten patients developed ophthalmic findings. Nine of 18 (50%) patients with symptomatic AIDS disease developed ophthalmic findings. One of 15 asymptomatic HIV-infected patients developed ocular findings. Two patients with absolute CD4 counts less than 10 developed cytomegalovirus retinitis. CONCLUSIONS These results suggest that AIDS-related ophthalmic disease is less common in vertically infected children than in adult AIDS patients. It also supports intensified clinical surveillance for cytomegalovirus retinitis in children with end-stage disease and very low CD4 counts.

Outcomes after cataract extraction in young children with radiation-induced cataracts and retinoblastoma

BACKGROUND An expected side effect of external beam radiation therapy for retinoblastoma is cataract formation, which impairs a childs visual development and an ophthalmologists ability to examine the eye. When surgery is indicated, the potential complications can be vision-or life-threatening. Here we report the results of cataract extraction with intraocular lens placement in young children with retinoblastoma. METHODS A retrospective chart review of all patients at St. Judes Childrens Research Hospital who had undergone external beam radiation therapy for retinoblastoma during a 25-year period was performed. Patients who required cataract extraction with IOL placement were included. Preoperative and postoperative visual acuity and ocular complications were recorded. RESULTS The chart review identified 40 patients (53 eyes) with cataracts, of whom 15 (19 eyes) had surgery. Of the 19 eyes, 2 (10.5%) developed a vitreous hemorrhage (one of which was subsequently enucleated secondary to phthisis, whereas the other resolved without further complications). A total of 12 eyes (63.2%) required Nd:YAG laser capsulotomies (mean, 3.6 months; range, 1-7 months). None developed recurrence or spread of disease. Thirteen eyes (68.4%) had improved visual acuity after cataract extraction and intraocular lens placement, 4 of which (30.8%) subsequently lost vision as the result of other complications of retinoblastoma treatment. Visual acuity outcomes were 20/20 to 20/60 in 3 eyes (15.8%); 20/70 to 20/200 in 4 (21.1%); and 20/400 or less in 10 (52.6%). One patient (5.2%) required enucleation. CONCLUSIONS Patients who underwent cataract extraction after treatment for retinoblastoma had few postoperative adverse outcomes, and visual acuity improved in most patients immediately after surgery. However, some patients who showed initial improvement subsequently lost vision as the result of other complications from retinoblastoma treatment.

Traumatic hyphemas in children secondary to corporal punishment with a belt.

PURPOSE To report the severity of ocular injury in seven children with traumatic hyphemas resulting from the accidental striking of the child in the face with a belt during the administration of corporal punishment. DESIGN Observational case series. METHODS We retrospectively reviewed the records of all patients (n = 7, aged 4 to 14 years) with traumatic hyphemas secondary to belt injuries evaluated by the senior author between 1989 to 2002 at Le Bonheur Childrens Medical Center, a regional pediatric referral hospital in Memphis, Tennessee. RESULTS Anterior segment injuries ranged from small hyphemas with normal intraocular pressure and no vision loss to injuries with severe elevations of intraocular pressure and permanent, significant loss of vision. CONCLUSIONS Ocular injury to a child can result from trauma inflicted with a belt by a parent or caretaker during corporal punishment and may result in permanent loss of vision.

Abnormal cone ERGs in a family with congenital nystagmus and photophobia harboring a p.X423Lfs mutation in the PAX6 gene

PurposeTo describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified.MethodsDetailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period.ResultsAt presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function.ConclusionsThe p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.

Management of vertical deviations secondary to other anatomical abnormalities.

Background and Purpose To review the surgical management of five vertical strabismus syndromes secondary to anatomical abnormalities. These syndromes are: 1) craniosynostosis; 2) “heavy eye syndrome” of high myopia; 3) Brown syndrome; 4) upshoot-downshoot in Duane retraction syndrome (DRS); and 5) anti-elevation syndrome after inferior oblique anteriorization. Methods The syndromes are presented from evolving to well-accepted surgical management practices based on review of the current literature. Results Surgical management techniques discussed include: 1) excyclotorsion of the muscle cones inducing elevation in adduction craniosynostosis, and surgery to stabilize the globe vertically in adduction in this situation; 2) loop myopexy to prevent prolapse of the elongated, highly myopic eye posteriorly between the superior and lateral recti; 3) superior oblique tenotomy and lengthening procedures to address inability to elevate the adducted eye in Brown syndrome; 4) Y-splitting of the lateral rectus to stabilize the adducted globe vertically in Duane retraction syndrome; and 5) re-recession of the anteriorized inferior oblique to a position posterior to the inferior rectus insertion in anti-elevation syndrome. Conclusions The surgeon can, through careful surgical management techniques, alter the form of anatomy in these conditions and thereby provide more normally functioning binocular systems.