Serial, Visually-Evoked Potentials for the Assessment of Visual Function in Patients with Craniosynostosis.

This study aimed to evaluate the effect of craniofacial surgical intervention on the visual pathway's function by comparing pre- to post-operative patterned, visually-evoked potentials (pVEP). A retrospective review was conducted on craniosynostosis patients who had pre- and post-craniofacial surgery pVEP testing. The pVEP measured grade in terms of amplitude latency and morphology of the waveforms. The pre- and post-operative results were compared. The study identified 63 patients (mean age at preoperative pVEP of 16.9 months). Preoperatively, 33 patients (52.4%) had abnormal pVEP. Nine patients had evidence of intracranial hypertension, and of those, eight (88.9%) had abnormal pVEP. Within 6 months postoperatively, 24 of 33 patients (72.7%) with abnormal preoperative pVEP developed normal postoperative pVEP, while all 30 patients with normal preoperative VEP maintained their normal results postoperatively. Significant improvements in pVEP latency in patients with broad or delayed latency waveforms was evident for subjects with preoperative grades 2-4 (grade 2, p = 0.015; grade 3, p = 0.029; grade 4; p = 0.007), while significant postoperative increase in amplitude was significant for patients with abnormally low amplitude grade 3 and 5 waveforms (grade 3, p = 0.011; grade 5, p = 0.029). Serial pVEP testing represents a useful tool for the early detection of visual pathway dysfunction and follow up visual pathway function in craniosynostosis. Surgical intervention for craniosynostosis can result in the reversal of preoperative pVEP abnormalities seen in these patients, resulting in the normalization of the pVEP waveform, amplitude and latency, depending on the preoperative pVEP abnormality.

Author Correction: Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Serial Visual Evoked Potentials in Patients with Craniosynostosis and Invasive Intracranial Pressure Monitoring.

This study aimed to detect the ability of pattern visual evoked potentials to detect visual pathway dysfunction in a cohort of patients with craniosynostosis who also had invasive intracranial pressure measurement. A retrospective review was conducted on craniosynostosis patients who had invasive intracranial pressure measurement and at least one pattern visual evoked potentials test. Reversal pattern visual evoked potentials were performed with both eyes open. Thirteen patients met the inclusion criteria (mean age at intracranial pressure measurement, 5.7 years). Seven patients had raised intracranial pressure, and of these, five (71.4 percent) had abnormal or deteriorated pattern visual evoked potentials parameters on serial testing, whereas all patients (100 percent) with normal intracranial pressure had normal pattern visual evoked potentials amplitude and latency. Four of the five patients (80 percent) with raised intracranial pressure and abnormal pattern visual evoked potentials did not show evidence of papilledema. The mean latency in patients with raised intracranial pressure (118.7 msec) was longer than in those with normal intracranial pressure (108.1 msec), although it did not reach statistical significance (p = 0.09), whereas the mean amplitude in patients with raised intracranial pressure (12.4 µV) was significantly lower than in patients with normal intracranial pressure (23.3 µV) (p = 0.03). The authors' results showed that serial pattern visual evoked potentials testing was able to detect visual pathway dysfunction resulting from raised intracranial pressure in five of seven craniosynostosis patients, and of these five patients, 80 percent had no evidence of papilledema, demonstrating the utility of serial pattern visual evoked potentials in follow-up of the visual function in craniosynostosis patients. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, II.

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function.

Injury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.

Improved visual function with dietary intervention in a child with lipemia retinalis.

We present a 4.8-year-old female with grade 3 lipemia retinalis due to lipoprotein lipase deficiency, an abnormal electroretinogram, and bilateral decreased visual acuity. Strict dietary intervention resulted in reversal of lipemia retinalis, normalization of her electroretinogram, and improved visual acuity in both eyes.

Carcinoma-associated retinopathy in a young teenager with immature teratoma of the ovary.

A 14-year-old African American girl presented with diminished vision in both eyes 1 week after undergoing an oophorectomy for a right ovarian mass. Systemic metastatic work-up was negative. Visual acuity was 20/40 in the right eye and 20/50 in the left eye. Slit-lamp biomicroscopy was unremarkable in both eyes. Fundus examination showed diffuse patchy areas of retinal pigment epithelial atrophy in the macula and peripheral retina bilaterally. Color vision had decreased in each eye. Electroretinography revealed nondetectable rod and cone responses. Both pattern and flash visual evoked potential (VEP) testing showed delayed latency in both eyes. She was treated with pulse intravenous methylprednisolone for 3 days along with intravenous immunoglobulins and rituximab, followed by systemic prednisolone and biweekly intravenous immunoglobulins and rituximab for 3 months. Antiretinal autoantibodies against 48-kDa (arrestin) and 64-kDa and 94-kDa proteins were positive, suggestive of carcinoma-associated retinopathy. After 3 months, visual acuity was 20/40 in each eye with improvement in color vision and VEP findings.

A laser-induced mouse model with long-term intraocular pressure elevation.

PURPOSE: To develop and characterize a mouse model with intraocular pressure (IOP) elevation after laser photocoagulation on the trabecular meshwork (TM), which may serve as a model to investigate the potential of stem cell-based therapies for glaucoma. METHODS: IOP was measured in 281 adult C57BL/6 mice to determine normal IOP range. IOP elevation was induced unilaterally in 50 adult mice, by targeting the TM through the limbus with a 532-nm diode laser. IOP was measured up to 24 weeks post-treatment. The optic nerve damage was detected by electroretinography and assessed by semiautomatic counting of optic nerve axons. Effects of laser treatment on the TM were evaluated by histology, immunofluorescence staining, optical coherence tomography (OCT) and transmission electron microscopy (TEM). RESULTS: The average IOP of C57BL/6 mice was 14.5 ± 2.6 mmHg (Mean ± SD). After laser treatment, IOP averaged above 20 mmHg throughout the follow-up period of 24 weeks. At 24 weeks, 57% of treated eyes had elevated IOP with the mean IOP of 22.5 ± 2.5 mmHg (Mean ± SED). The difference of average axon count (59.0%) between laser treated and untreated eyes was statistically significant. Photopic negative response (PhNR) by electroretinography was significantly decreased. CD45+ inflammatory cells invaded the TM within 1 week. The expression of SPARC was increased in the TM from 1 to 12 weeks. Histology showed the anterior chamber angle open after laser treatment. OCT indicated that most of the eyes with laser treatment had no synechia in the anterior chamber angles. TEM demonstrated disorganized and compacted extracellular matrix in the TM. CONCLUSIONS: An experimental murine ocular hypertension model with an open angle and optic nerve axon loss was produced with laser photocoagulation, which could be used to investigate stem cell-based therapies for restoration of the outflow pathway integrity for ocular hypertension or glaucoma.

Quantifying nystagmus in infants and young children: relation between foveation and visual acuity deficit.

PURPOSE: Nystagmus eye movement data from infants and young children are often not suitable for advanced quantitative analysis. A method was developed to capture useful information from noisy data and validate the technique by showing meaningful relationships with visual functioning. METHODS: Horizontal eye movements from patients (age 5 months-8 years) with idiopathic infantile nystagmus syndrome (INS) were used to develop a quantitative outcome measure that allowed for head and body movement during the recording. The validity of this outcome was assessed by evaluating its relation to visual acuity deficit in 130 subjects, its relation to actual fixation as assessed under simultaneous fundus imaging, its correlation with the established expanded nystagmus acuity function (NAFX), and its test-retest variability. RESULTS: The nystagmus optimal fixation function (NOFF) was defined as the logit transform of the fraction of data points meeting position and velocity criteria within a moving window. A decreasing exponential relationship was found between visual acuity deficit and the NOFF, yielding a 0.75 logMAR deficit for the poorest NOFF and diminishing deficits with improving foveation. As much as 96% of the points identified as foveation events fell within 0.25° of the actual target. Good correlation (r = 0.96) was found between NOFF and NAFX. Test-retest variability was 0.49 logit units. CONCLUSIONS: The NOFF is a feasible method to quantify noisy nystagmus eye movement data. Its validation makes it a promising outcome measure for the progression and treatment of nystagmus during early childhood.

Visual acuity development of children with infantile nystagmus syndrome.

PURPOSE: Infantile nystagmus syndrome (INS) can be idiopathic or associated with ocular or systemic disease. The ocular oscillation of INS directly contributes to loss of visual acuity. In this study, visual acuity development in patients with INS was examined. METHODS: Children with INS were classified as having idiopathic INS (n = 84) or INS with an associated sensory deficit: INS and albinism (n = 71), bilateral optic nerve hypoplasia (ONH; n = 23), or congenital retinal disorder (n = 36). Visual acuity was assessed with Teller cards and/or optotypes, and the data were analyzed for three age groups (<24 months, 24-48 months, and >48 months). RESULTS: Patients with idiopathic INS showed mildly reduced visual acuity early in life and gradual maturation with age that paralleled a normative curve. Patients with albinism also showed a mild visual deficit early in life but failed to keep pace with the normative curve, showing a gradual increase in visual acuity deficit. Patients with ONH and congenital retinal disorders exhibited more severe visual acuity deficits during infancy. The ONH group displayed slow improvement of visual acuity with a plateau at 24 months through >48 months, with a small increase in visual acuity deficit. The congenital retinal disorder group had no significant change in visual acuity across age and had a rapid increase in visual acuity deficit. CONCLUSIONS: The pattern of visual acuity development differs among children with INS, depending on the presence or absence of associated sensory system deficits. Careful characterization of visual system differences in patients with INS is important if visual acuity is an outcome in clinical trials.

The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid.

BACKGROUND: The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date. OBJECTIVE: The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events. DESIGN: This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination. RESULTS: Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested. CONCLUSIONS: DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.

Randot Preschool Stereoacuity Test: normative data and validity.

INTRODUCTION: The Randot Preschool Stereoacuity Test is a widely used three-book test for the assessment of binocular status. Using a prototype, we previously reported high testability in children as young as 3 years, validity data, and some normative data. Here we report extensive normative and validity data for the final version of the test. In addition, we report normative data for a new, fourth book that adds finer disparities. METHODS: The Randot Preschool Stereoacuity Test was administered to 4355 normal children aged 3 to 18 years and 39 adults in multiple settings. In addition, the Randot Preschool Stereoacuity Test along with the new, fourth book that added 30 arcsec and 20 arcsec disparity levels was administered to 1402 normal children aged 3 to 18 years and 33 normal adults. Both the four-book Randot((R)) Preschool Stereoacuity Test and the Randot circles were administered to 242 patients with amblyogenic conditions aged 3 to 18 years. RESULTS: Mean normal stereoacuity improved from 100 arcsec at 3 years of age to 60 arcsec by 5 years and 40 arcsec by 7 years. The lower limit of normal was 400 arcsec at 3 years, 200 arcsec at 4 years, and 60 arcsec at 7 years. Using the new four-book version, further improvement in mean stereoacuity could be appreciated beyond 7 years of age to 30 arcsec in the 11- to 18-year-old and adult groups. Among the 242 patients, Randot Preschool Stereoacuity Test stereoacuity was strongly associated with Randot circle stereoacuity (chi(2) = 261.0, p < 0.001). CONCLUSIONS: Normative data for the Randot Preschool Stereoacuity Test show a monotonic improvement of stereoacuity from age 3 years through the teen years. Patient data support the validity of the Randot Preschool Stereoacuity Test.

New tests of distance stereoacuity and their role in evaluating intermittent exotropia.

PURPOSE: Poor control of intermittent exotropia has been considered an indication for surgical intervention, and poor distance stereoacuity may be an indicator of poor control. Two new measures of distance stereoacuity, the Frisby-Davis Distance test (FD2) and Distance Randot test (DR), both of which have been validated in normal and strabismic subjects, were evaluated, and we compared stereoacuity with scores on a recently described control scale. DESIGN: Prospective case series. PARTICIPANTS: Twenty-five consecutive patients with intermittent exotropia. METHODS: Office-based control was graded at distance and near on a 0 to 5 scale, and distance control ranged from 1 (recovery in 1-5 seconds after monocular occlusion) to 4 (>50% spontaneously tropic). Stereoacuity was measured using the FD2 and DR at distance and the Preschool Randot and Frisby tests at near. MAIN OUTCOME MEASURE: Distance stereoacuity measured using the FD2 and DR. RESULTS: Measurable distance stereoacuity thresholds in intermittent exotropia were poor with the DR and excellent with the FD2 (medians, nil and 40''; P<0.0001). Near stereoacuity was excellent with both the Preschool Randot and Frisby (medians, 60'' and 60''; P = 0.99). There was poor correlation between distance control score and either FD2 (r(s) = 0.1, P = 0.6) or DR (r(s) = 0.3, P = 0.2). Control scores correlated with magnitude of deviation at distance (r(s) = 0.5, P = 0.02) and near (r(s) = 0.5, P = 0.01). CONCLUSIONS: The real-world contour-based targets of the new distance FD2 appear to stimulate fusion in intermittent exotropia, even when distance control is poor. In contrast, the new Polaroid vectograph-based DR is very sensitive to disturbances of binocularity. Two new distance stereoacuity tests appear sensitive to opposite ends of the intermittent exotropia spectrum; FD2 performance deteriorates when the patient is constantly tropic, whereas DR performance deteriorates at the earliest stages of intermittency.

Progression of intermittent, small-angle, and variable esotropia in infancy.

PURPOSE: Esotropia (ET) in infancy may initially manifest as a small-angle, variable-angle, or intermittent deviation. Some patients experience spontaneous resolution and become orthophoric. Others progress to constant large-angle ET and require surgery. The authors examined factors that may be associated with risk for progression to constant large-angle ET. METHODS: Seventy-seven infants who initially presented with intermittent, small (<20 prism diopter [pd]) or variable-angle ET at 2 to 12 months of age were followed up until the ET was resolved, the infants had surgery, or the parents or guardians refused surgery. All infants with refractive correction >/=+3.50 D were treated initially with glasses. Four risk factors were examined: prescription of occlusion therapy, initial visit before 6 months of age, presence of amblyopia, and abnormal stereoacuity. RESULTS: All 12 infants with small or variable angles progressed to constant large-angle ET and surgery. ET resolved spontaneously in 44.6% (29/65) infants in whom it was intermittent. Infants with intermittent ET who received patches as initial treatment and who had abnormal stereoacuity had 3.4x (95% confidence interval [CI], 1.83-6.29) and 3.4x (95% CI, 1.66-6.78) higher risk for progression to constant large-angle ET, respectively. Neither age at initial visit nor amblyopia presented risk for progression. CONCLUSIONS: Abnormal stereoacuity and occlusion therapy pose significant risks for progression from intermittent to constant large-angle ET. Intermittent ET that develops during the first year of life has a high likelihood of spontaneous resolution, whereas constant small-angle or variable-angle ET seldom resolves.

Assessment of a new Distance Randot stereoacuity test.

PURPOSE: We sought to develop a new "Distance Randot" test, establish a normative data set for children and adults, and compare with established measures of stereoacuity. METHODS: Distance Randot, distance Frisby-Davis 2 (FD2), and near Preschool Randot stereoacuity (Stereo Optical Co., Inc., Chicago, IL) were assessed in 23 normal children (ages 4-14 years), 21 normal adults (ages 20-36 years), and 131 patients with a variety of strabismic conditions (ages 4-85 years). For each test, stereoacuity was defined as the smallest disparity in which 2 targets were correctly identified. The simultaneous prism and cover test (SPCT) and the alternate prism and cover test (APCT) were used to assess misalignment. RESULTS: For the new Distance Randot test, normative results were similar to published data obtained with established near and distance stereoacuity tests. In the patient cohort, comparing stereoacuity data obtained from Distance Randot stereoacuity test and the Near Preschool Randot stereoacuity test, most of the patients with discordant scores had poorer distance than near stereoacuity. Comparing the Distance Randot stereoacuity test and the Distance FD2, all of the patients with discordant scores had poorer Distance Randot than FD2 scores. CONCLUSIONS: Distance Randot test is more likely to detect abnormalities in distance stereopsis and may provide a useful tool in measuring distance stereoacuity in patients with and without strabismus. However, further studies are needed to define the efficacy of the Distance Randot test in monitoring progression specific conditions such as intermittent exotropia, where it may prove useful as a guide to the timing of intervention.