Clinical electrophysiology and visual outcome in optic nerve hypoplasia.

AIMS: In optic nerve hypoplasia (ONH), the extent of functional loss of retinal ganglion cells cannot be determined by ophthalmoscopic examination. The prognostic value of visual electrodiagnostic tests in infants and toddlers with ONH was assessed by comparison with visual outcome. METHODS: 85 participants with ONH had electroretinogram (ERG) and visual-evoked potential (VEP) testing to flash and to pattern-reversal checks and ocular fundus photography prior to 36 months of age. These initial measures were compared with visual acuity outcomes at 5 years of age in the better-seeing eye. RESULTS: Visual outcomes ranged from normal to no light perception. Electrodiagnostic tests with prognostic value were: the amplitude of the flash VEP (Spearman's rank correlations, p<0.001), the threshold category of stimulus (flash or check size) that elicited a VEP (p<0.001) and the amplitude of the N95 component of the pattern ERG (PERG) to 4-degree checks (p<0.02). Optic nerve size and co-existing pallor were also significant correlates. Stepwise regression analysis composed a best prediction model from VEP threshold category, optic nerve size and optic disc pallor (R(2)=58%; p<0.001). CONCLUSIONS: Optic disc diameter, observation of disc pallor, VEP and PERG testing in infancy are useful for establishing the visual prognosis at 5 years of age in children with ONH. This is consistent with the notion that these parameters are related to the anatomic and functional preservation of retinal ganglion cells.

Retinal function in infants with optic nerve hypoplasia: electroretinograms to large patterns and photopic flash.

AIMS: Optic nerve hypoplasia (ONH), which is defined as a congenital deficiency of retinal ganglion cells, may also involve more distal layers of the retina. We investigated electrophysiological function of the retina in ONH using electroretinograms (ERGs). METHODS: ERGs were recorded from 48 subjects (3.5-35 months) with unilateral or bilateral ONH. Pattern reversal (4 degrees checks) was presented under chloral hydrate sedation, using an optical system to correct a cycloplegic refraction. A photopic flash stimulus was also used. Fundus photographs were used to measure the disk diameter/disk macula ratio (DD/DM), and to document other clinical signs. Eyes were classified as moderate (0.15-0.3) or severe (<0.15) ONH, and those with DD/DM greater than 0.3 were used as reference eyes. RESULTS: Pattern ERG recording was completed in 89 eyes and was detectable in 80% of eyes with ONH (61/76 tested) and in all 13 reference eyes. Photopic flash ERGs were of good quality in all eyes. The severity of ONH correlates with the amplitude of the photopic flash b-waves and with the amplitude of the N95 component of the pattern ERG (P<0.01). However, the ERGs to large patterns were well preserved (>3.5 microV) in 10 of 35 eyes with severe ONH. Tortuous retinal vessels in eyes with either moderate or severe ONH were associated with smaller amplitude photopic b-waves and markedly diminished or undetectable pattern ERGs. CONCLUSIONS: This study supports the hypothesis that retinal dysfunction distal to the ganglion cells is common in ONH, but is not predictable on the basis of ONH severity alone. Additionally, tortuous retinal vessels in ONH may be a sign associated with retinal dysfunction.

Clinical diversity of hereditary Duane's retraction syndrome.

OBJECTIVE: To define the spectrum of ophthalmic manifestations of Duane's 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 Duane's 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.

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.

The relationship between stereopsis and monocular optokinetic optokinetic nystagmus after infantile cataracts.

PURPOSE: Visual deprivation disrupting binocular development, such as that occurring with congenital cataract, is reported to cause asymmetric monocular optokinetic nystagmus (MOKN), as well as poor sensory and motorfusional outcome. We wanted to determine if symmetric MOKN could develop in cases of congenital cataract with good fusional outcome. METHODS: We tested MOKN (with video and electro-oculographic recordings) and stereoacuity on 5 patients with good visual acuity and satisfactory ocular alignment after surgery for congenital cataract. RESULTS: Stereoacuity was better than 50 seconds of arc in 1 case of monocular cataract and 2 cases of bilateral cataract. These case patients had symmetric MOKN. In a monocular cataract case, symmetric MOKN was observed in spite of questionable stereoacuity (at least 500 arc/s). One patient showed asymmetric MOKN, despite good visual acuity, and stereoacuity of 200 arc/s. CONCLUSIONS: Patients with congenital cataract can have symmetric MOKN and good stereopsis. These cases suggest that MOKN symmetry develops along with good stereopsis, but the quality of stereopsis necessary for development of MOKN symmetry remains unclear.

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.

A noninvasive glucose monitor: preliminary results in rabbits.

BACKGROUND: Glucose in the aqueous humor appears to correlate with plasma glucose in humans. It is therefore a potential substrate for noninvasive optical glucose monitoring techniques. We wished to determine the potential for using rabbit aqueous humor as a model to develop a noninvasive method of measuring glucose with Raman spectroscopy. METHODS: Aqueous humor from 32 rabbit eyes was removed immediately after sacrifice by rapid exsanguination under anesthesia. Raman spectroscopy was performed on the aqueous humor using near infrared (NIR) excitation wavelengths. The Raman spectra from 785 nm and 787.2 nm were subtracted one from the other to eliminate broadband fluorescence. The spectra were then analyzed with linear and nonlinear multivariate analysis and assessed for ability to predict actual aqueous humor glucose concentration. Nine other rabbits were anesthetized with xylazine in order to cause elevation of blood glucose by blocking release of insulin. Blood and aqueous humor glucose were measured at various times after injection of xylazine. Correlation of aqueous humor glucose with simultaneous plasma glucose was assessed. RESULTS: Partial least squares analysis of raw Raman spectra of aqueous humor showed fair correlation with actual glucose concentration (r2 = 0.76). When the fluorescence spectrum was subtracted prior to linear multivariate analysis correlation was good (r2 = 0.90). When back-propagation with an artificial neural network was added to the analysis, correlation was further improved (r2 = 0.98). Aqueous humor glucose concentration exceeded blood glucose concentration at normoglycemic levels. When blood glucose rose above 200 mg/dL, aqueous humor glucose correlated linearly with plasma glucose. CONCLUSIONS: Raman spectroscopy can accurately predict glucose concentration in rabbit aqueous humor in vitro. Although rabbit aqueous humor is probably not a good model of human aqueous humor glucose physiology, its reliable correlation with plasma glucose makes it a good model on which to test noninvasive optical sensing techniques.

Comparisons of contact lens, foil, fiber and skin electrodes for patterns electroretinograms.

Pattern electroretinograms are small physiologic signals that require good patient cooperation and long recording times, particularly when conditions are not optimal. Six electrodes were compared to evaluate their efficacy. Pattern electroretinograms were recorded in eight healthy volunteers to high-contrast, pattern-reversal checks (40' width) with Burian-Allen, DTL fiber, C-glide, gold foil, HK loop and skin electrodes. Raw data for 320 reversals were analyzed off-line to evaluate signal amplitude, quality, P50 and N95 peak times, artifact rate and electrical noise. Insertion time, impedance and subjective comfort were also assessed. The Burian-Allen contact lens electrode gave the largest signal and lowest impedance but was the least comfortable and had the highest artifact rate (p < 0.01). A skin electrode on the lower eyelid produced the smallest pattern electroretinogram with the poorest quality (p < 0.05). The four other electrodes were foil or fiber electrodes in contact with the tear film, conjunctiva and/or the inferior cornea. The signal from these showed only minor differences. When electrodes are compared for pattern electroretinograms recording, the foil and fiber electrodes do not differ substantially but contact lens and skin electrodes show substantial disadvantages.

Visual outcome in high hypermetropia.

INTRODUCTION: We wished to determine whether final visual acuity is dependent on age at optical correction or presence of esotropia in children with bilateral high hypermetropia. METHODS: We reviewed the charts of all patients at Childrens Hospital Los Angeles Division of Ophthalmology with bilateral hypermetropia of greater than or equal to 5D who were able to provide objective visual acuity outcomes with Snellen letters or linear E. RESULTS: One hundred thirteen patients met entry criteria. The age at first optical correction ranged from 8 months to 141 months (average 45 months). Initial visual acuity (before optical correction) was obtainable in 82 patients. Initial visual acuity ranged from 20/20 to 20/200, with 57% of patients having acuity better than or equal to 20/40. Final visual acuity (after optical correction) ranged from 20/20 to 20/70, with 109 patients (96%) having acuity better than or equal to 20/40 and 104 patients (92%) having acuity better than or equal to 20/30. There was no relationship between final visual acuity and age that spectacles were first worn. Ninety-five patients (84%) had esotropia with or without glasses, and six of these (6%) had final visual acuity less than 20/30. Of the 18 patients with orthotropia, three (16%) had final visual acuity less than 20/30. The prevalence of ametropic amblyopia in patients with esotropia and orthotropia was not significantly different (p = 0.18). CONCLUSION: Visual acuity outcome in children with high hypermetropia is generally good regardless of age at initial optical correction or presence of strabismus. A significantly increased risk for ametropic amblyopia was not found in those patients with orthotropia.

Hemifield slide diplopia from altitudinal visual field defects.

We report two cases in which heteronymous, altitudinal visual field defects resulted in loss of fusion and transient overlap of preserved hemifields. This phenomenon resulted in complaints of diplopia similar to that described as "hemifield" slide previously described by temporal hemianopsias. These cases illustrate that generalized loss of fusion, and not the particular type of hemianopic field defect, is responsible for the symptoms known as hemifield slide.

Ocular findings in neonates after extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a modified, prolonged cardiopulmonary bypass procedure used to treat newborns who have reversible cardiac or respiratory failure. The venoarterial bypass technique requires cannulation of both the right carotid artery and the internal jugular vein, and after decannulation these vessels are permanently ligated. Left-sided retinal vascular changes after ECMO have been reported, and were attributed to ligation of these vessels. A retrospective review of the results of ocular examinations of 86 infants who had undergone ECMO therapy at Childrens Hospital in Los Angeles between March, 1987 and May, 1991 was conducted. Normal findings were noted in 73 infants. One infant had bilateral retinal vascular tortuosity, and 12 infants had incidental ocular findings, but there was no evidence of left-sided retinal hemorrhage, venous congestion, or tortuosity. Our results suggest that left-sided retinal vascular changes after ECMO do not occur, occur only rarely, or clear rapidly and result in no permanent retinal damage. To unequivocally rule out the possibility that ECMO can cause transitory retinal vascular changes, we recommend further prospective studies, with ocular examinations performed before, during, and after ECMO.

Third nerve palsy due to cerebral artery aneurysm in a child.

We report a case of cerebral aneurysm in a seven-year-old girl who presented with subacutely progressive third nerve palsy. To our knowledge this is the youngest reported patient with this condition. Confusion with myasthenia gravis occurred because of improvement in the patient's ptosis after intravenous edrophonium chloride. Cerebral CT revealed a hyperdense mass that was characterised on cerebral angiography as an aneurysm of the posterior communicating artery. Another occult aneurysm of the posterior cerebral artery was found at surgery. This case demonstrates that third nerve palsy due to cerebral aneurysm may affect patients at a younger age than has previously been recognised. Therefore we suggest that even young children should have aneurysm excluded by cerebral CT and angiography if they present with acquired third nerve palsy involving the pupil. In addition this case highlights the false-positive results that may occur with the edrophonium chloride test for myasthenia gravis.

Congenital ocular motor apraxia in twins. Findings with magnetic resonance imaging.

A pair of identical twins, whose features met Cogan's classic description of congenital ocular motor apraxia, were examined. Each had an absence of willed horizontal saccades and demonstrated classic head thrusting. Magnetic resonance imaging revealed hypoplasia of the corpus callosum. Fourth ventricle enlargement and generalized cerebral hypoplasia were also present but were more pronounced in the sibling with the more delayed motor development. The significance of these findings is discussed in light of our understanding of the control mechanism of volitional eye movements.