Mark Borchert

Idiopathic intracranial hypertension in prepubertal pediatric patients: characteristics, treatment, and outcome.

PURPOSE To report the features of idiopathic intracranial hypertension in prepubertal children, with emphasis on presentation, treatment, and outcome. METHODS We retrospectively reviewed the charts of all patients 11 years and younger diagnosed with idiopathic intracranial hypertension at two university-affiliated medical centers. Inclusion critera included papilledema, normal brain computed tomography or magnetic resonance imaging, cerebrospinal fluid pressure greater than 200 mm H2O, normal cerebrospinal fluid content, and a nonfocal neurologic examination except for sixth nerve palsy. Patients with concomitant systemic illness were excluded. RESULTS Of the 10 patients, four were girls and six were boys. Only one patient was obese. The most common presenting symptoms were stiff neck (four patients) and diplopia (four patients), and the most common presenting sign was strabismus (eight patients). Six of eight patients with strabismus had abducens nerve palsy (four bilateral), one patient had a sensory exotropia, and one had a comitant esotropia. Visual field abnormalities were present in 11 of 13 eyes (85%), and severe visual loss resulting in no light perception vision occurred in one eye of one patient. Nine patients were treated medically, four with a combination of prednisone or dexamethasone and acetazolamide and five with acetazolamide alone. One patient in this group also required a lumboperitoneal shunt. One patient was treated with lumbar puncture only. Resolution of papilledema occurred rapidly in all patients, with a mean of 4.7 +/- 2.6 months. Resolution of sixth nerve palsy also occurred rapidly in four of six patients in a mean of 1.6 +/- 1.2 months. One patient required strabismus surgery for persistent esotropia and one was lost to follow-up. CONCLUSIONS Idiopathic intracranial hypertension in prepubertal children is rare and is different than the disease in adults. In our series, there appeared to be no sex predilection, and obesity was uncommon. Children are likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.

Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31

Duane retraction syndrome (DRS) is a congenital eye-movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, restricted adduction, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. DRS has a prevalence of approximately 0.1% in the general population and accounts for 5% of all strabismus cases. Undiagnosed DRS in children can lead to amblyopia, a permanent uncorrectable loss of vision. A large family with autosomal dominant DRS was examined and tested for genetic linkage. After exclusion of candidate regions previously associated with DRS, a genomewide search with highly polymorphic microsatellite markers was performed, and significant evidence for linkage was obtained at chromosome 2q31 (D2S2314 maximum LOD score 11.73 at maximum recombination fraction. 0). Haplotype analysis places the affected gene in a 17.8-cM region between the markers D2S2330 and D2S364. No recombinants were seen with markers between these two loci. The linked region contains the homeobox D gene cluster. Three of the genes within this cluster, known to participate in hindbrain development, were sequenced in affected and control individuals. Coding sequences for these genes were normal or had genetic alterations unlikely to be responsible for the DRS phenotype. Identifying the gene responsible for DRS may lead to an improved understanding of early cranial-nerve development.

Clinical diversity of hereditary Duane’s retraction syndrome

OBJECTIVE To define the spectrum of ophthalmic manifestations of Duanes retraction syndrome (DRS) in a large family. DESIGN Cross-sectional study of 110 among 114 living relatives in an extended family. METHODS History and ophthalmic examination obtained on all participants. MAIN OUTCOME MEASURES Ocular motility, strabismus, visual acuity, binocularity, associated neurologic problems. RESULTS Twenty-five individuals were affected with DRS. Twenty-four subjects (96%) had bilateral DRS, but there was a broad spectrum of severity. Strabismus occurred in 76% and amblyopia in 48%. Associated findings included fourth cranial nerve palsy, partial third cranial nerve palsy, nystagmus, seizures, and deafness. Fourth cranial nerve palsies and manifest strabismus tended to cluster within single family units. CONCLUSIONS Strabismus and amblyopia are much more common with bilateral DRS than with unilateral DRS. There is much phenotypic variability among individuals within families with hereditary Duanes syndrome. The responsible gene(s) may affect the development of many cranial nerves. Genetic compounding may play a role in the phenotypic segregation seen within this large family.

Risk Factors Associated with Childhood Strabismus: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

OBJECTIVE To investigate risk factors associated with esotropia or exotropia in infants and young children. DESIGN Population-based cross-sectional prevalence study. PARTICIPANTS Population-based samples of 9970 children 6 to 72 months of age from California and Maryland. METHODS Participants were preschool African-American, Hispanic, and non-Hispanic white children participating in the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were obtained by parental interview and ocular examination. Odd ratios and 95% confidence intervals were calculated to evaluate the association of demographic, behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME MEASURES Odds ratios (ORs) for various risk factors associated with esotropia or exotropia diagnosis based on cover testing. RESULTS In multivariate logistic regression analysis, esotropia was associated independently with prematurity, maternal smoking during pregnancy, older preschool age (48-72 months), anisometropia, and hyperopia. There was a severity-dependent association of hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00 diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of hyperopia. Exotropia was associated with prematurity, maternal smoking during pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for 1.50 to <2.50 D of astigmatism, and 5.9 for ≥2.5 D of astigmatism), and anisoastigmatism in the J0 component (OR, ≥2 for J0 anisoastigmatism of ≥0.25 D). CONCLUSIONS Prematurity and maternal smoking during pregnancy are associated with a higher risk of having esotropia and exotropia. Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia. Because refractive error is correctable, these risk associations should be considered when developing guidelines for the screening and management of refractive error in infants and young children. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Neuroradiographic, Endocrinologic, and Ophthalmic Correlates of Adverse Developmental Outcomes in Children With Optic Nerve Hypoplasia: A Prospective Study

BACKGROUND. Developmental delay has been reported to occur with optic nerve hypoplasia, a leading cause of pediatric blindness, but has not been systematically examined for its prevalence and correlation with associated pathologies of optic nerve hypoplasia. OBJECTIVE. The purpose of this study was to determine the developmental outcomes of children with optic nerve hypoplasia and the correlation of development with neuroradiographic, endocrinologic, and ophthalmic findings. METHODS. We conducted a prospective analysis of 73 subjects diagnosed with optic nerve hypoplasia at <36 months of age for developmental outcomes at 5 years of age. Subjects underwent neuroradiographic imaging, endocrinologic testing and examination, and ophthalmologic examination; developmental outcomes were assessed by using the Battelle Developmental Inventory. RESULTS. At 5 years of age, developmental delay was present in 71% of subjects with optic nerve hypoplasia. Of patients with unilateral (18%) and bilateral optic nerve hypoplasia, 39% and 78%, respectively, experienced developmental delay. Corpus callosum hypoplasia and hypothyroidism were significantly associated with poor outcome in all of the developmental domains and an increased risk of delay. Absence of the septum pellucidum was not associated with adverse development. Six subjects had neither a neuroradiographic nor an endocrinologic abnormality, and of those, 4 were developmentally delayed. CONCLUSIOONS. These prospective data confirm the significant association of developmental delay with optic nerve hypoplasia and identify corpus callosum hypoplasia and hypothyroidism as strong correlates. A diagnosis of optic nerve hypoplasia warrants neuroradiographic and endocrinologic testing for risk factors of delay and developmental assessments for early intervention planning.

Prevalence of Myopia, Hyperopia, and Astigmatism in Non-Hispanic White and Asian Children: Multi-Ethnic Pediatric Eye Disease Study

PURPOSE To determine the age-, gender-, and ethnicity-specific prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white (NHW) and Asian preschool children. DESIGN Population-based, cross-sectional study. PARTICIPANTS A population-based sample of 1501 NHW children and 1507 Asian children aged 6-72 months from Los Angeles County and Riverside County, California. METHODS Eligible children underwent an in-home and in-clinic interview and a comprehensive eye examination including cycloplegic autorefraction from 100 census tracts. MAIN OUTCOME MEASURES The proportion of children with myopia (spherical equivalent [SE] ≤-1.00 diopter [D]), hyperopia (SE ≥ +2.00 D) and cylindrical refractive error ≥1.50 D in the worse eye. The astigmatism type was defined as with-the-rule (WTR; +cylinder axis 90°±15°) and against-the-rule (ATR; + cylinder axis 180°±15°); all other orientations were considered oblique (OBL). RESULTS The prevalence of myopia, hyperopia, and astigmatism in NHW children was 1.20% (95% confidence interval [CI], 0.76%-1.89%), 25.65% (95% CI, 23.5%-27.9%), and 6.33% (95% CI, 5.21%-7.68%), respectively. The prevalence of WTR, ATR, and OBL astigmatism in NHW children was 4.33%, 1.00%, and 1.00%, respectively. Prevalence was lower with older age groups for astigmatism (P = 0.0002), but not for myopia (P = 0.82) or hyperopia (P = 0.31). In Asian children, the prevalence of myopia, hyperopia, and astigmatism was 3.98% (95% CI, 3.11%-5.09%), 13.47% (95% CI, 11.8%-15.3%), and 8.29% (95% CI, 7.01%-9.80%), respectively. The prevalence of WTR, ATR, and OBL astigmatism was 6.50%, 0.80%, and 1.00% respectively. The prevalence of hyperopia was higher in girls than boys (P = 0.0002), but no differences were found for myopia and astigmatism. CONCLUSIONS Hyperopia was the most common refractive error in both Asian and NHW children. However, compared with NHW children, myopia was relatively more prevalent, and hyperopia less prevalent, among Asian children. The prevalence of astigmatism was greatest in infants, and WTR astigmatism predominated at all ages. Myopia showed relatively stable prevalence across age groups, whereas hyperopia prevalence decreased after infancy and then increased again in older age groups; however, longitudinal studies are needed to evaluate refractive changes over time in individual children. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Non-invasive measurement of intracranial pressure

The invention provides a method of non-invasiveness determining intracranial pressure from measurements of an eye. A parameter of an optic nerve of the eye is determined, along with an intraocular pressure of the eye. The intracranial pressure may be determined from the intraocular pressure and the parameter. The invention for carrying out the method includes illumination means (34), fiber optic splitter (36), oscillating mirror (46), and x/y scanner (32).

Glucose determination in human aqueous humor with Raman spectroscopy

It has been suggested that spectroscopic analysis of the aqueous humor of the eye could be used to indirectly predict blood glucose levels in diabetics noninvasively. We have been investigating this potential using Raman spectroscopy in combination with partial least squares (PLS) analysis. We have determined that glucose at clinically relevant concentrations can be accurately predicted in human aqueous humor in vitro using a PLS model based on artificial aqueous humor. We have further determined that with proper instrument design, the light energy necessary to achieve clinically acceptable prediction of glucose does not damage the retinas of rabbits and can be delivered at powers below internationally acceptable safety limits. Herein we summarize our current results and address our strategies to improve instrument design.

Open Globe Injuries in Children

PURPOSE A retrospective review of open globe injuries in children was performed to identify the common types of injury and to correlate features of the injuries and surgical management with visual prognosis. METHODS The hospital records of 70 patients were reviewed to determine demographic data, the nature and location of the injuries, the anatomic and functional status of the injured eye before the initial repair, the details of all primary and subsequent surgical procedures, and the final visual outcome. RESULTS Fifty of the patients studied (71%) were male and 20 (29%) were female. The average age of the patients was 5 years. Sharp objects caused the majority of injuries (67%). Most of the injuries happened at home (72%). The cornea was involved in a majority of the injuries (92%). Thirty-two eyes (46%) required only primary repair; 15 eyes (21%) required primary repair with anterior vitrectomy and primary lensectomy; 17 eyes (24%) underwent secondary lensectomy or vitreoretinal surgeries, and 5 eyes (7%) were enucleated. Visual acuity of 20/40 or better was achieved by 45% of those patients who required only primary repair. Of those patients requiring a second procedure, 19% had a visual acuity of 20/40 or better. Initial clinical findings associated with an unfavorable visual outcome were retinal detachment, relative afferent pupillary defect, vitreous hemorrhage, and hyphema. CONCLUSION The prognosis after an open globe injury in children is strongly influenced by the nature of the injury and the extent of the initial damage. Visual outcome is better in eyes that require only primary repair.

Visual acuity norms in pre-school children: the Multi-Ethnic Pediatric Eye Disease Study.

Purpose. To provide population-based normative data for monocular visual acuity (VA) and interocular differences in VA (IOD) in Black and Hispanic children 30 to 72 months of age without visually significant refractive errors or ophthalmic abnormalities. Methods. In a population-based cohort of children in the Multi-Ethnic Pediatric Eye Disease Study, monocular HOTV VA measurements using the Amblyopia Treatment Study protocol were analyzed using continuous and dichotomous outcomes for VA and IOD, after excluding subjects with ophthalmic abnormalities or refractive error. Results. The analysis cohort consisted of 1722 Black and Hispanic children aged 30 to 72 months. Mean logMAR VA improved with age (p < 0.0001) and male gender (p = 0.0008). The proportion of children achieving VA 20/40 or better was associated with age (p < 0.0001), but not ethnicity or gender, and was 81, 94, 99, and virtually 100% in children aged 30 to 35, 36 to 47, 48 to 59, and 60 to 72 months of age, respectively. The most stringent VA threshold that excluded <5% of normal children was 20/63, 20/50, 20/32, and 20/32 for children aged 30 to 35, 36 to 47, 48 to 59, and 60 to 72 months, respectively. Children attending preschool or daycare achieved VA 20/32 more often than those not attending, after age adjustment (p = 0.01), as did children from higher-income families (p = 0.04). There was no association between mean absolute IOD and age (p = 0.45), ethnicity (p = 0.12), or gender (p = 0.19). The proportion of children with an IOD of 0 to 1 lines was higher in males than females (p = 0.02); it did not vary by age (p = 0.06) or ethnicity (p = 0.17). An IOD of 2 or more lines occurred in 6% of normal children. Conclusions. VA test performance in normal pre-school children improves with age. We propose new age-specific thresholds for defining abnormal monocular VA using HOTV optotypes in children between 2 and 5 years of age, for use in screening, clinical practice, and research.