Search

Objective: To determine the distribution of 2 intracellular oxygen-carrying molecules, neuroglobin (NGB) and cytoglobin (CYGB), in specific retinal cell types of human retinas., Methods: Specific antibodies against NGB and CYGB were used in immunohistochemical studies to examine their distribution patterns in human retinal sections. Double-labeling studies were performed with the anti-NGB and anti-CYGB antibodies along with antibodies against neuronal (microtubule-associated protein 2, class III beta-tubulin [TUJ1], protein kinase C alpha, calretinin) and glial (vimentin, glial fibrillary acid protein) markers. Confocal microscopy was used to examine the retinal sections., Results: Immunohistochemical analysis of human retinal tissue showed NGB and CYGB immunoreactivity in the ganglion cell layer, inner nuclear layer, inner and outer plexiform layers, and retinal pigment epithelium. Neuroglobin immunoreactivity was also present in the outer nuclear layer and photoreceptor inner segments. Neuroglobin and CYGB were coexpressed in the neurons in the ganglion cell layer and inner nuclear layer but not within glial cells., Conclusion: Neuroglobin and CYGB are colocalized within human retinal neurons and retinal pigment epithelium but not within glial cells. Clinical Relevance Our results suggest that NGB and CYGB may serve a neuroprotective role as scavengers of reactive oxygen species and therefore should be considered when developing therapeutic strategies for treatment of hypoxia-related ocular diseases.

Background: Optical coherence tomography (OCT)--measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS)., Methods: Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON., Findings: Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically-affected eyes of non-MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non-MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302)., Interpretation: Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non-MS patients over time.

This study provides a detailed description of immunolocalization of two oxygen-binding proteins, neuroglobin (Ngb) and cytoglobin (Cygb), in the anterior segment of healthy human and canine eyes. Specific antibodies against Ngb and Cygb were used to examine their distribution patterns in anterior segment structures including the cornea, iris, trabecular meshwork, canal of Schlemm, ciliary body, and lens. Patterns of immunoreactivity (IR) were imaged with confocal scanning laser and conventional microscopy. Analysis of sectioned human and canine eyes showed Ngb and Cygb IR in the corneal epithelium and endothelium. In the iris, Ngb and Cygb IR was localized to the anterior border and the stroma, iridal sphincter, and dilator muscle. In the iridocorneal angle, Ngb and Cygb were detected in endothelial cells of the trabecular meshwork and canal of Schlemm in human. In the ciliary body, Ngb and Cygb IR was localized to the non-pigmented ciliary epithelium of the pars plana and pars plicata and in ciliary body musculature. Ngb and Cygb distribution was similar and colocalized within the same structures of healthy human and canine anterior eye segments. Based on their immunolocalization and previously reported biochemical features, we hypothesize that Ngb and Cygb may function as scavengers of reactive oxygen species. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Introduction: Optic neuritis causes retinal nerve fiber layer damage, which can be quantified with optical coherence tomography. Optical coherence tomography may be used to track nerve fiber layer changes and to establish a time-dependent relationship between retinal nerve fiber layer thickness and visual function after optic neuritis., Methods: This prospective case series included 78 patients with optic neuritis, who underwent optical coherence tomography and visual testing over a mean period of 28 months. The main outcome measures included comparing inter-eye differences in retinal nerve fiber layer thickness between clinically affected and non-affected eyes over time; establishing when RNFL thinning stabilized after optic neuritis; and correlating retinal nerve fiber layer thickness and visual function., Results: The earliest significant inter-eye differences manifested 2-months after optic neuritis, in the temporal retinal nerve fiber layer. Inter-eye comparisons revealed significant retinal nerve fiber layer thinning in clinically affected eyes, which persisted for greater than 24 months. Retinal nerve fiber thinning manifested within 6 months and then stabilized from 7 to 12 months after optic neuritis. Regression analyses demonstrated a threshold of nerve fiber layer thickness (75 microm), which predicted visual recovery after optic neuritis., Conclusions: Retinal nerve fiber layer changes may be tracked and correlated with visual function within 12 months of an optic neuritis event.

Purpose: To report a case series of neuro-ophthalmic sarcoidosis manifestations from a predominantly Caucasian Midwest population., Design: Retrospective non-comparative case series and literature review., Participants: Twenty patients with biopsy proven sarcoidosis cases and neuro-ophthalmic manifestations., Methods: We reviewed 67 consecutive charts with the clinical diagnosis of neurosarcoidosis at the University of Iowa Hospital and Clinics (UIHC) Department of Ophthalmology database in Iowa City, Iowa, seen from 1984 to 2006., Main Outcome Measures: Charts were reviewed for the following: 1) demographic information; 2) neuro-ophthalmic findings; 3) biopsy location and results; 4) pre-existing sarcoidosis; 5) neuroimaging studies (e.g., cranial magnetic resonance imaging and computed tomography scans); 6) cerebrospinal fluid results; 7) sarcoid related testing (serum angiotensin converting enzyme, chest radiograph, chest computed tomography scans, Gallium scan, bronchoalveolar lavage, pulmonary function testing); 8) treatment; and 9) course of disease., Results: Twenty of the 67 charts (30%) had biopsy proven sarcoidosis and neuro-ophthalmic manifestations. Of the 20 included cases, 4 (20%) were men and 16 (80%) were women. Six (30%) patients were African-American and 14 (70%) were Caucasian. The average age at diagnosis was 43.1 years with a standard deviation of 14.1 and a range of 22 to 80 years. Neuro-ophthalmic manifestations included optic neuropathy (14), cranial neuropathy (4), Horner's Syndrome (1), tonic pupil (1), and optic tract involvement (1). Of the 14 patients presenting with optic neuropathy, 8 had optic disc edema, 5 had optic disc pallor and 1 had an optic disc granuloma. Contrast cranial magnetic resonance imaging (MRI) showed pathologic contrast enhancement (16 of 19 cases) involving optic nerve (9), optic chiasm (1), optic radiations (1), cavernous sinus (1), leptomeninges (3), and cerebral parenchyma (3). Chest imaging was abnormal in the course of disease for 12 of 18 and serum angiotensin-converting enzyme was only elevated in 5 of 15 patients tested. All 20 patients were treated with corticosteroids but five required additional immunosuppressive therapy to control disease activity. The neuro-ophthalmic course was relapsing and remitting in 8 cases, stable or resolved in 7, and chronic in 5 patients. After treatment of patients with optic neuropathy, visual acuity at last follow-up visit was improved in 5, worsened in 5, and stable (i.e., within one Snellen acuity line of baseline) in 4., Conclusion: In our Midwest retrospective case series of biopsy proven neuro-ophthalmic sarcoidosis, patients were predominately white females with a wide age range. Consideration for the diagnosis of neurosarcoidosis should therefore not be limited by age, gender, or race. Optic neuropathy was the most common manifestation, typically presenting with optic disc edema and severe visual loss. No light perception vision was relatively common and should be considered a "red flag" for the diagnosis. Contrast cranial MRI frequently shows pathologic enhancement of the visual pathway. Serum angiotensin converting enzyme and chest radiography had relatively poor sensitivity for detecting biopsy proven disease in our study and therefore additional testing for tissue diagnosis might still be necessary for extrapulmonary neuro-ophthalmic sarcoidosis. Corticosteroids are the mainstay of therapy but some patients may require additional immunosuppressive therapy.

Purpose: To test a linear model relating the regional loss in retinal nerve fiber (RNFL) thickness to the corresponding regional loss in sensitivity with data from patients with previous anterior ischemic optic neuropathy (AION)., Design: Case-control study., Participants: Twenty-four individuals with AION and 20 with normal vision were tested. The time since the AION attack ranged from 5.2 months to more than 20.3 years (median, 2.95 years)., Methods: Eyes were tested with standard automated perimetry (SAP) and with optical coherence tomography (OCT), both RNFL thickness scans. The average RNFL thickness of the inferior and superior disc sectors was plotted against the average total deviations (linear units) of the corresponding superior and inferior arcuate field regions, and a linear model was fitted. According to the model, the RNFL thickness R=s(o)T+b, (1), where T is the relative SAP sensitivity loss (on a linear scale; e.g., for -3 dB, T = 0.5), s(o) is the RNFL thickness attributable to axons in the healthy or normal state (T = 1.0), and b is the residual RNFL measured when all sensitivity and axons are lost., Main Outcome Measures: Optical coherence tomography RNFL thickness and SAP sensitivity., Results: The data from the AION patients resembled the data from glaucoma patients previously tested and were described by the linear model. For patients with SAP losses of more than -10 dB in the arcuate region, the RNFL thickness provided an estimate of residual RNFL thickness, b. The median value of b (45.5 microm) was similar to the value for patients with glaucoma. It varied among individuals (range, 30.4-63.3 microm), showing a very weak correlation with patient's age (r = 0.30) and the time since the AION episode (r = 0.26), but an excellent correlation (r(2) = 0.94; P<0.01) with the value of s(o), estimated from the unaffected eyes., Conclusions: The relationship between a structure (OCT RNFL thickness) and function (SAP sensitivity loss) is the same for patients with AION and glaucoma and can be approximated by a simple linear model. The model may provide a framework for identifying those patients with ganglion cell axons that are malfunctioning but are alive.

Objective: To compare empirical probability plots in patients with glaucoma for size V and III perimetry testing., Methods: We computed empirical probability plot percentile limits after testing 60 age-matched controls tested with both size III (Swedish interactive thresholding algorithm) and size V (full threshold) perimetry twice. Probability plots of 120 patients with glaucoma tested in the same way were computed. We compared the number of abnormal test locations in the 2 stimulus sizes; we then compared these results with those from size III StatPac software (Zeiss Humphrey Systems, Dublin, California) using 2-way repeated-measures analysis of variance., Results: We found a similar number of abnormal test locations (P < or = .05) for the size III and size V testing conditions identified by the probability plots (no significant difference); there were significantly fewer abnormal locations using StatPac (size III) than from our size III database. When results were stratified by mean deviation, the mild visual loss group again did not show any significant differences between sizes III and V., Conclusions: Size V full-threshold testing gives a similar number of abnormal test locations in patients with glaucoma compared with the size III Swedish interactive thresholding algorithm standard test. Size V testing, with its greater dynamic range and lower variability, may be a viable alternative to size III testing in patients with glaucoma.

Objective: To evaluate recurrent or delayed worsening of papilledema and visual function in patients with idiopathic intracranial hypertension (IIH) followed for more than 10 years., Methods: This is an Institutional Review Board approved retrospective chart review of 410 patients with the diagnosis of IIH evaluated at the University of Iowa Hospitals and Clinics from January 1984 to January 1996. Of the 410 patients, 20 patients with IIH who were followed over 10 years at the neuro-ophthalmology clinic met the inclusion criteria. Three neuro-ophthalmologists independently evaluated and graded the visual field examinations and optic disc stereo-photographs for each follow-up visit (median = 15)., Results: Of the 20 patients, 11 demonstrated a stable course of disease without worsening in papilledema or visual field, and 9 patients worsened after a stable course. Of these 9 patients, 6 patients experienced delayed worsening (range: 28 to 135 months from presentation) and 3 patients had recurrence after resolution of papilledema 12 to 78 months from initial resolution of the IIH., Conclusion: Idiopathic intracranial hypertension is a chronic condition that may worsen after a period of stability, warranting long-term follow-up.

Objective: To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPA1 gene., Design: Clinical examination and morphological, biochemical, and molecular analyses., Setting: Tertiary care university hospitals and molecular genetics and scientific computing laboratory., Patient: A 42-year-old man experienced hearing loss, progressive external ophthalmoplegia (PEO), loss of central vision, macrocytic anemia, and hypogonadism. His family history was negative for neurological disease, and his serum lactate level was normal., Results: A muscle biopsy specimen showed scattered intensely succinate dehydrogenase-positive and cytochrome-c oxidase-negative fibers. Southern blot of muscle mitochondrial DNA showed multiple deletions. The results of screening for mutations in the nuclear genes associated with PEO and multiple mitochondrial DNA deletions, including those in POLG (polymerase gamma gene), ANT1 (gene encoding adenine nucleotide translocator 1), and PEO1, were negative, but sequencing of POLG2 revealed a G1247C mutation in exon 7, resulting in the substitution of a highly conserved glycine with an alanine at codon 416 (G416A). Because biochemical analysis of the mutant protein showed no alteration in chromatographic properties and normal ability to protect the catalytic subunit from N-ethylmaleimide, we also sequenced the OPA1 gene and identified a novel heterozygous mutation (Y582C)., Conclusion: Although we initially focused on the mutation in POLG2, the mutation in OPA1 is more likely to explain the late-onset PEO and multisystem disorder in this patient.

Purpose: To characterize the timing and extent of functional recovery in healthy canine eyes exposed to acute elevation of intraocular pressure (IOP)., Methods: Acute elevation of IOP was induced in 14 healthy Beagles by elevating IOP above the levels of systolic blood pressure for 60 min (average elevation was between 100 and 160 mmHg). Menace, dazzle and pupillary light reflexes (PLR) were tested at 1, 7, 14 and 28 days post elevation. Optical coherence tomography was used to evaluate retinal thickness preoperatively and at 15 and 30 days post elevation., Results: One day post elevation all animals were blind in the operated eye (no positive menace), 5/14 had positive PLR and 10/14 had positive dazzle response. Seven days post elevation 4/14 animals had positive menace response and all animals (14/14) had positive dazzle and PLR responses. Fourteen and 28 days post elevation all animals had positive menace, PLR and dazzle responses. Optical coherence tomography analysis revealed significant thinning of the inferior retina (pre elevation: 156.3 +/- 4.8 microm; 15 days post elevation: 125 +/- 10.4 microm; 30 days post elevation 123 +/- 11.9 microm; P < 0.01, anova). The superior retina, however, did not show any detectable decrease in thickness compared to control eyes (pre elevation: 193.8 +/- 2.6 microm; 15 days post elevation: 176.9 +/- 8.5 microm; 30 days post elevation 176.9 +/- 7 microm; P = 0.057, anova)., Conclusions: Detailed functional and morphologic analysis revealed precise information about retinal damage after acute elevation of IOP. Canine retina has the capacity to recover at least some visual function even at 14 days after acute elevation of the IOP. More aggressive medical and surgical treatment of canine glaucomatous patients may be indicated despite complete loss of visual function, PLR and dazzle responses in early days after development of an acute glaucomatous attack.

Purpose: To differentiate rod-cone-mediated pupil light reflexes (PLRs) from intrinsic melanopsin-mediated pupil light reflexes by comparing pupil responses with red and blue light stimuli of differing intensities in normal dog eyes and in those with sudden acquired retinal degeneration syndrome (SARDS) exhibiting a nonrecordable electroretinogram., Methods: The PLR was evaluated in 14 healthy dogs using a computerized pupillometry system and in five dogs with SARDS. Contraction amplitude, velocity, and implicit time of the PLR were studied as a function of peak wavelength (480 nm vs. 630 nm) and light intensity (-0.29 to 5.3 log units) to determine characteristics of the rod-cone versus predominantly melanopsin-mediated PLR activity., Results: The PLR in healthy, mildly sedated dogs could be elicited at low light intensities (-0.29 log units; 0.51 cd/m(2)). Canine SARDS patients displayed a complete absence of vision, electroretinographic amplitude, and PLR at low light intensity. However, in SARDS dogs, a pupil light reflex could be elicited with wavelengths corresponding to the melanopsin spectral sensitivity (blue light - peak at 480 nm) and at relatively high intensity (4.3 log units or higher), whereas red light (630 nm peak wavelength) was ineffective in eliciting any detectable PLR response even at light intensities of 6 log units (1,000,000 cd/m(2))., Conclusions: The PLR in healthy canine eyes can be elicited at very low light intensities using red and blue wavelengths of light, but in dogs with blindness caused by SARDS, the pupil reacts only to high-intensity blue wavelength light, implying loss of the rod-cone-mediated PLR and most likely the presence of intrinsic, melanopsin-mediated, retinal ganglion cell-mediated PLR.

While it is often said that structural damage due to glaucoma precedes functional damage, it is not always clear what this statement means. This review has two purposes: first, to show that a simple linear relationship describes the data relating a particular functional test (standard automated perimetry (SAP)) to a particular structural test (optical coherence tomography (OCT)); and, second, to propose a general framework for relating structural and functional damage, and for evaluating if one precedes the other. The specific functional and structural tests employed are described in Section 2. To compare SAP sensitivity loss to loss of the retinal nerve fiber layer (RNFL) requires a map that relates local field regions to local regions of the optic disc as described in Section 3. When RNFL thickness in the superior and inferior arcuate sectors of the disc are plotted against SAP sensitivity loss (dB units) in the corresponding arcuate regions of the visual field, RNFL thickness becomes asymptotic for sensitivity losses greater than about 10dB. These data are well described by a simple linear model presented in Section 4. The model assumes that the RNFL thickness measured with OCT has two components. One component is the axons of the retinal ganglion cells and the other, the residual, is everything else (e.g. glial cells, blood vessels). The axon portion is assumed to decrease in a linear fashion with losses in SAP sensitivity (in linear units); the residual portion is assumed to remain constant. Based upon severe SAP losses in anterior ischemic optic neuropathy (AION), the residual RNFL thickness in the arcuate regions is, on average, about one-third of the premorbid (normal) thickness of that region. The model also predicts that, to a first approximation, SAP sensitivity in control subjects does not depend upon RNFL thickness. The data (Section 6) are, in general, consistent with this prediction showing a very weak correlation between RNFL thickness and SAP sensitivity. In Section 7, the model is used to estimate the proportion of patients showing statistical abnormalities (worse than the 5th percentile) on the OCT RNFL test before they show abnormalities on the 24-2 SAP field test. Ignoring measurement error, the patients with a relatively thick RNFL, when healthy, will be more likely to show significant SAP sensitivity loss before statistically significant OCT RNFL loss, while the reverse will be true for those who start with an average or a relatively thin RNFL when healthy. Thus, it is important to understand the implications of the wide variation in RNFL thickness among control subjects. Section 8 describes two of the factors contributing to this variation, variations in the position of blood vessels and variations in the mapping of field regions to disc sectors. Finally, in Sections 7 and 9, the findings are related to the general debate in the literature about the relationship between structural and functional glaucomatous damage and a framework is proposed for understanding what is meant by the question, 'Does structural damage precede functional damage in glaucoma?' An emphasis is placed upon the need to distinguish between "statistical" and "relational" meanings of this question.

The recent discovery of melanopsin-expressing retinal ganglion cells that mediate the pupil light reflex has provided new insights into how the pupil responds to different properties of light. These ganglion cells are unique in their ability to transduce light into electrical energy. There are parallels between the electrophysiologic behavior of these cells in primates and the clinical pupil response to chromatic stimuli. Under photopic conditions, a red light stimulus produces a pupil constriction mediated predominantly by cone input via trans-synaptic activation of melanopsin-expressing retinal ganglion cells, whereas a blue light stimulus at high intensity produces a steady-state pupil constriction mediated primarily by direct intrinsic photoactivation of the melanopsin-expressing ganglion cells. Preliminary data in humans suggest that under photopic conditions, cones primarily drive the transient phase of the pupil light reflex, whereas intrinsic activation of the melanopsin-expressing ganglion cells contributes heavily to sustained pupil constriction. The use of chromatic light stimuli to elicit transient and sustained pupil light reflexes may become a clinical pupil test that allows differentiation between disorders affecting photoreceptors and those affecting retinal ganglion cells.

Purpose: To evaluate a linear model that relates the glaucomatous loss in retinal nerve fiber (RNFL) thickness, measured with optical coherence tomography (OCT), to the loss in sensitivity, measured with standard automated perimetry (SAP)., Methods: Fifteen patients with asymmetrical glaucoma, whose better eye was normal or near normal (mean deviations better than -3 dB) on SAP, were tested. SITA 24-2 standard and OCT RNFL thickness measures were made on three to five different occasions and the mean values were obtained. For each eye, the mean SAP loss was calculated for an upper and lower arcuate field region by averaging the loss in relative sensitivity on a linear scale. The average RNFL thickness for corresponding arcuate sectors of the lower and upper optic disc was obtained for each eye. A linear model was fitted to the plots of RNFL thickness versus SAP loss. According to the linear model, the RNFL thickness R = s(o)T + b, where T is the SAP sensitivity loss relative to age-matched normal eyes (linear scale), (s(o) + b) is the RNFL thickness in the healthy/normal state (T = 1), and b is the residual RNFL thickness measured when all sensitivity and all axons are lost., Results: The model provided a reasonable fit to the data with best fitting values of (s(o); b) of (upper field: 80.6 microm; 50.5 microm) and (lower field: 67.4 microm; 50.5 microm) and (upper field: 78.8 microm; 54.9 microm; r = 0.82) and (lower field: 59.2 microm; 61.5 microm; r = 0.70) for two different methods of best fit., Conclusions: A linear model that relates RNFL thickness to losses in SAP sensitivity describes the results for arcuate regions of glaucomatous visual fields. The linear model provides a framework for assessing the relative efficacy of structural and functional tests throughout the course of the disease.

Objective: To report the abnormal multifocal electroretinogram (mfERG) findings in two cases of presumed ethambutol toxicity., Design: Retrospective observational case series., Participants: Two patients with ethambutol toxicity and visual loss., Testing: Multifocal electroretinography., Main Outcome Measure: Waveform measurements on multifocal electroretinography., Results: Two patients with bilateral visual loss due to ethambutol toxicity underwent mfERG testing that disclosed both diffuse and central field loss compatible with retinal dysfunction as a contributing mechanism to the visual field loss., Conclusion: Ethambutol toxicity affects not only the optic nerve but probably other retinal elements based upon abnormal mfERG findings.

The Argyll Robertson (AR) pupil has been defined as a pupil that is small and constricts poorly to direct light but briskly when a target within reading distance is viewed ("light-near dissociation"). Most descriptions of the AR pupil do not mention segmental iris sphincter constriction, or slow, sustained constriction with a near vision effort. Such features are considered typical of the light-near dissociation of Adie syndrome and of neuropathic tonic pupils, where damage to the ciliary ganglion or ciliary nerves is believed to be the mechanism. Because the AR pupil lacks these features, it has been attributed to a dorsal midbrain lesion that interrupts the pupillary light reflex pathway but spares the more ventral pupillary near reflex pathway. However, lesions in this region have not been reliably demonstrated in syphilis. Resolving the issue about the location of the syphilitic lesion that produces the AR pupil will depend on careful examination of patients with techniques designed to disclose segmental palsy of the iris. If segmental iris sphincter palsy is found and the light-near dissociation has tonic features, one must conclude that the mechanism of the pupil disorder is a ciliary (peripheral) rather than a midbrain (central) denervation. Until better evidence settles the localization of the AR pupil, it is appropriate to screen patients with bilateral tonic pupils for syphilis.

Irene E. Loewenfeld, PhD has devoted a long and vigorous professional life to understanding the workings of the pupil of the human eye. Her interest in the pupil began in 1940 when she went to work as a technician in the pupillography laboratory of Professor Otto Lowenstein at New York University. It culminated in her widely admired textbook The Pupil, published in 1993. Among her many contributions, Loewenfeld provided rigorous observations about Adie tonic pupil, anisocoria in optic tract lesions, Argyll Robertson pupil, oculomotor paresis with cyclic spasms, and innovations in electronic recordings of pupil movement.

We have functionally and morphologically characterized the retina and optic nerve after neural progenitor cell transplants to healthy rat eyes and eyes damaged by acute elevation of intraocular pressure (IOP). Green fluorescent protein-expressing adult rat hippocampal progenitor cells (AHPCs) were transplanted by intravitreal injection into healthy eyes and eyes damaged with acute ocular hypertension. Pupil light reflexes (PLR) and electroretinograms (ERGs) were recorded preoperatively and postoperatively. Eyes were subsequently prepared for immunohistochemical analysis and confocal imaging. Transplanted AHPCs were found in 8 of 15 (53%) acute ischemic eyes 62 days after surgery and 5 of 10 (50%) healthy eyes 32 days after grafting. Analysis of PLR and ERG function in acute ischemic eyes revealed no statistically significant difference compared to controls after transplantation for all observed functional parameters. Transplant into healthy rat eyes revealed no PLR or ERG amplitude deficits between transplanted and non-transplanted (control) eyes. Morphological and immunohistochemical analysis revealed that transplanted AHPCs survived and differentiated in both normal and injured retinal environments. Morphological integration occurred primarily within the inner retinal layers of the acute ischemic eyes. AHPCs were found to express neuronal and glial markers following transplantation. Transplanted AHPCs have the ability to integrate and differentiate in ischemia damaged retinas. PLR and ERG analysis revealed no significant difference in functional outcome in transplant recipient eyes.

Purpose: To define the prevalence, natural history, treatment, and prognosis of papilledema-related juxtapapillary subretinal neovascular membranes (SRNVMs)., Design: Retrospective observational case series., Methods: We conducted a retrospective chart review., Results: Of 1140 cases of idiopathic intracranial hypertension, six patients had juxtapapillary SRNVM. Three patients were observed, and their final visual acuities were 20/20, 20/50, and 20/200. Three SRNVM involved the fovea; two of the cases were treated with argon laser therapy, and one case was treated with photodynamic therapy., Conclusion: SRNVM in idiopathic intracranial hypertension is rare (0.53%). Most cases of juxtapapillary SRNVM are self-limited and regress, can be observed, and have a favorable visual prognosis. The progression of the SRNVM ophthalmoscopically or angiographically toward the fovea, however, might be an indication for laser treatment. Once subfoveal extension occurs, the visual outcome tends to be unfavorable. No patients had recurrence of SRNVM after the resolution of the papilledema.

Purpose: The goal of this study was to describe the detailed localization of the novel oxygen-binding molecules, neuroglobin (Ngb) and cytoglobin (Cygb), in mammalian retinas and to determine whether Ngb and Cygb are neuronal or glial proteins in the retina., Methods: Antibodies directed against Ngb and Cygb were used to examine their patterns of distribution in normal canine retinas. Immunoblot analysis was performed to verify antibody specificity and the presence of Ngb and Cygb in canine tissues. Double-labeling immunohistochemistry was performed with the Ngb and Cygb antibodies along with antibodies against neuronal (MAP-2, class III beta-tubulin (TUJ1), PKCalpha, and calretinin) and glial antigens (vimentin and CRALBP). Tissue sections were analyzed with light and confocal microscopy., Results: Ngb and Cygb proteins were observed in different retinal cells. Cygb (but not Ngb) was also present in canine kidney, liver, lung, and heart tissue. Immunohistochemical analysis of canine retinas demonstrated Ngb immunoreactivity (IR) in the ganglion cell layer (GCL), inner (INL) and outer (ONL) nuclear layers, inner (IPL) and outer plexiform (OPL) layers, photoreceptor inner segments (IS), and retinal pigment epithelium (RPE). Ngb IR was localized within retinal neurons, but not in glia. Cygb IR was found in neurons and their processes in the GCL, IPL, INL, and OPL and within the RPE, but not in glia., Conclusions: Ngb and Cygb are widely distributed in retinal neurons and RPE, but not in glial cells of the canine retina. Their structure and distribution is suggestive of a possible role in oxygen transport in the mammalian retina.

Purpose: To describe the pregnancy outcomes after the use of acetazolamide in pregnant patients with idiopathic intracranial hypertension (IIH)., Design: Observational case series., Methods: setting: Two tertiary care academic neuro-ophthalmology units. patient population: Patients with IIH treated with acetazolamide. observation procedure: Documentation of pregnancy outcome. main outcome measures: Normal pregnancy, fetal loss, or congenital malformation., Results: Twelve patients were treated with acetazolamide for IIH during pregnancy, and there were no adverse pregnancy outcomes. A critical review of the English language literature on the subject failed to demonstrate any convincing evidence for any adverse effect on pregnancy for acetazolamide., Conclusions: Acetazolamide at high doses may produce birth defects in animals, but there is little clinical or experimental evidence to support any adverse effect of the drug on pregnancy outcomes in humans. If the clinical situation warrants the use of acetazolamide in IIH, then the drug probably can be offered after appropriate informed consent.

When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host-graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal-like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.

Purpose: To report the diagnostic yield for the evaluation of isolated and unexplained optic atrophy., Setting: Two tertiary care academic neuroophthalmology clinics., Design: Retrospective case series., Participants: Patients with optic atrophy., Methods: Retrospective review of all charts with the diagnosis of optic atrophy. Included patients were adults with isolated, but unexplained, optic atrophy. Patients were excluded if they were children, had incomplete or inadequate documentation of the findings, had nonneurologically isolated optic atrophy (e.g., other localizing findings), or had a history (e.g., prior neuroimaging study showed a compressive lesion, prior ischemic optic neuropathy) or examination (e.g., central retinal artery occlusion) evidence for an etiology for the optic atrophy., Main Outcome Measure: Results of diagnostic evaluation., Results: A total of 1110 charts with the diagnosis of optic atrophy were reviewed from the 2 participating institutions (368 from the University of Cincinnati and 742 from the University of Iowa). Of these 1110 charts, 91 (8%) with isolated unexplained optic atrophy were included, and 1019 charts (92%) were excluded. Of 91 included patients, 18 (20%) had a compressive lesion causing optic atrophy, and 73 (80%) cases had no etiology for the optic atrophy on neuroimaging. Of the 18 patients with abnormal imaging (e.g., meningioma, pituitary adenoma, craniopharyngioma) studies, 11 had bilateral and 7 had unilateral optic atrophy. Five of the 18 patients had progressive visual loss, 3 had hemianopic visual field loss, and 11 were younger than 50 years old., Conclusions: Patients with optic atrophy in our study typically had historical or examination findings that led to an etiologic diagnosis. Neuroimaging showed an etiology in 20% of patients. Other laboratory testing did not produce an etiologic diagnosis in the absence of a suggestive history or examination. On the basis of our results, we recommend neuroimaging for all patients with unexplained optic atrophy and consideration for directed laboratory studies only.

Purpose: To compare the variation in thickness and reflectivity of the retinal nerve fibre layer (RNFL), circumferentially and on repeated testing., Methods: In 24 normal eyes and 38 eyes with different optic neuropathies or retinopathies, third-party optical coherence tomography (OCT) software defined the RNFL border based on the reflectivity pattern across the retina and also provided measurements of the mean reflectivity and total retinal thickness in addition to RNFL thickness. A new Gaussian filtering method was implemented so that the weight of the applied filter was varied for each of five individually repeated scans until an optimum weight filter was determined., Results: The scans requiring the highest weight filter could be identified as 'outlier' scans that contained measurement or alignment artifacts. There was no difference in the weights of filtering needed for normal and abnormal eyes. The RNFL thickness and reflectivity, and retinal thickness were highly correlated with one another in normal and abnormal eyes., Conclusions: A new Gaussian filtering routine was devised that not only defined the most reproducible substructure of the RNFL for a given patient's eye, but also provided a new method of quantifying measurement variability and identification of scans with measurement or alignment artifacts.

Purpose: To describe the neuro-ophthalmic presentations of a rare intracranial tumor, hemangiopericytoma., Methods: Retrospective multicenter case series., Results: The neuro-ophthalmic and radiographic features of hemangiopericytoma are reviewed. The clinical presentation may mimic meningioma and the pre-operative distinction between meningioma and hemangiopericytoma is important because the evaluation, management, treatment, and prognosis differ significantly for the two lesions., Conclusion: We report five cases of intracranial hemangiopericytoma and review the neuro-ophthalmic findings of this uncommon entity.

Purpose: To determine whether acetazolamide or furosemide produce allergic cross-reactions in patients with self-reported "sulfa allergy.", Design: Retrospective case series., Methods: A retrospective review included patients with intracranial hypertension and a self-reported sulfa allergy treated with either acetazolamide or furosemide seen at the University of Iowa Hospitals and Clinics from 1972 to 2003. All presumed medication-related side effects were collected, including both predictable adverse effects (for example, paresthesias, fatigue) and unpredictable adverse reactions (for example, cutaneous fixed eruptions, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylaxis)., Results: We reviewed 363 charts. Of these, 329 patients (91%) were excluded. Of the remaining 34 cases that did report a so-called sulfa allergy, 13 (38%) received acetazolamide alone, 7 (21%) received furosemide alone, and 14 (41%) received both acetazolamide and furosemide. Of the 27 patients who received acetazolamide, 10 (37%) had no documented allergic cross-reaction to sulfa, and 2 (7%) cases had urticaria. The remaining 15 (56%) of acetazolamide-treated patients experienced predictable adverse reactions for this drug (for example, paresthesias). No patient experienced a severe allergic cross-reaction to sulfa. Of 21 patients who received furosemide, no unpredictable adverse reactions or allergic cross-reactions to sulfa were noted., Conclusions: We find little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy is likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. These medications should be considered for intracranial hypertension if the risk-to-benefit ratio warrants their use.

Purpose: To functionally characterize the rat retina and optic nerve after chronic elevation of the intraocular pressure (IOP) using electroretinography (ERG) and computerized pupillometry., Methods: Chronic elevation of the IOP was induced in Brown Norway rats by combined injection of indocyanine green dye (ICG) into the anterior chamber and diode laser treatment, followed by ERG and pupil light reflex (PLR) monitoring., Results: Laser treatment induced significant elevation of the IOP in operated eyes for 6 weeks, with maximal values observed 14 days postoperatively (ctrl=18.4+/-2.4 and operated=35+/-8.4 mmHg; mean+/-sd). Preoperative values for the PLR(ratio) were 68.5+/-4% (mean+/-sem; %). Three days postoperatively the PLR(ratio) decreased to 60.3+/-10.3%, but was not significantly different compared to preoperative values (p > 0.05 Kruskal-Wallis non-parametric test with Dunn's post-test). However, 7, 14 and 21 days postoperatively the PLR function dramatically decreased to 14.6+8.6, 11.5+/-6.7 and 12.6+/-4%, respectively, and was significantly smaller compared to preoperative values (p < 0.01). At day 28 the PLR significantly recovered and was not significantly different compared to preoperative values (PLR(ratio)=38.5+/-8.6, p > 0.05). However, 35 days after surgery the PLR started to decrease once again in the operated eyes (PLR(ratio)=17.2+/-7.4%) and was significantly smaller again compared to preoperative values (p < 0.05) The PLR values continued to decrease until the end of experiment (60 days postoperatively). ERG analysis of operated eyes revealed significantly decreased amplitudes of a- and b-waves 10d postoperatively, while oscillatory potentials (OPs) and flicker ERG (flERG) amplitudes were not detectable. However, 28 days postoperatively OPs significantly, but temporarily recovered, while a-wave, b-wave and flERG amplitudes did not significantly change compared to values observed 10d postoperatively. The ERG analysis of the operated eyes revealed significantly reduced amplitudes 60 days postoperatively. Histological analysis revealed degeneration of all retina layers and optic nerve axons., Conclusions: Chronic ocular hypertension in rats produces dramatic damage to all retinal layers and optic nerves observed by morphological and functional methods which significantly correlate with the IOP elevation. Outer retina of glaucomatous rats seems to be more susceptible to the damage due to chronic elevation of the IOP. Chronic hypertensive rat eyes have capacity to temporarily recover function of the inner retina and optic nerve.

Purpose: To develop an inducible mouse model of glaucoma., Methods: An obstruction of aqueous humor outflow in adult C57BL6/J mice was induced by combined injection of indocyanine green (ICG) dye into the anterior chamber and diode laser treatment. To evaluate intraocular pressure (IOP), tonometry was performed with a modified Goldmann tonometer. The function of the retina was evaluated with electroretinography (ERG)., Results: IOP was significantly elevated in surgical eyes compared with control eyes: before surgery, 15.2 +/- 0.6 mm Hg; 10 days after surgery, 33.6 +/- 1.5 mm Hg (P < 0.001); and 30 days after surgery, 27.4 +/- 1.2 mm Hg (P < 0.001). However, 60 days after surgery, IOP in the surgical eyes decreased to 19.5 +/- 0.9 mm Hg and was not significantly different compared with control eyes (control, 17.3 +/- 0.7 mm Hg; P = 0.053). ERG amplitudes, expressed as a ratio (surgical/control), were decreased in surgical eyes. The amplitudes for b-wave were: before surgery, 107.6% +/- 4.6%; 28 days after surgery, 61% +/- 4% (P < 0.001); and 56 days after surgery, 62% +/- 5.6% (P < 0.001). Oscillatory potentials were the most dramatically affected: before surgery, 108.6% +/- 6.7%; 28 days after surgery, 57.5% +/- 5% (P < 0.01); and 56 days after surgery, 57% +/- 8.5% (P < 0.001). Amplitudes of the a-waves had relatively smaller but still significant deficits: before surgery, 105.8% +/- 6.9%; 28 days after surgery, 72.2% +/- 5.4% (P < 0.01); and 56 days after surgery, 79.8% +/- 11.0% (P < 0.01). Histologic analysis of the surgical eyes revealed development of anterior synechia, loss of retinal ganglion cells (RGCs), and thinning of all retinal layers. Electron microscopy of optic nerve cross sections revealed swelling and degeneration of the large diameter axons and gliosis., Conclusions: Diode laser treatment of ICG saturated episcleral veins causes a chronic elevation of IOP and sustained ERG deficits.

Purpose: To evaluate visual function in rats with chronic elevation of intraocular pressure (IOP)., Methods: Chronic ocular hypertension was induced in the left eye of 14 adult Brown Norway rats by cauterizing 3 vortex veins and 2 major episcleral veins; the right eye served as a non-operated control. A control group (n=5) was sham operated on the left eye. Prior to surgery, the IOP was measured with a Tonopen, the pupil light reflex (PLR) evaluated with a custom-made computerized pupillometer and electroretinograms (ERGs) were recorded simultaneously from both eyes post surgically: IOP was measured on weeks 1, 3, 5 and 8 post-operatively, pupil light reflexes on weeks 1, 4 and 8 post-operatively, and ERGs on weeks 4 and 8 post-operatively. Sixty five days postoperatively, rats were euthanized and optic nerves and eye globes were prepared for histological analysis., Results: Seven days after surgery 5/14 rats developed significant elevation of the IOP in operated eyes (control eyes: 25.1+/-0.5mmHg; operated eyes: 34.1+/-0.6mmHg; mean+/-SEM; p=0.0004; Paired t-test). Elevation of the IOP was sustained at 3 (p=0.002) and 5 (p=0.007) weeks postoperatively. However, IOP values did not significantly differ between control and operated eyes 8 weeks postoperatively (p=0.192, Paired t-test). Sham operated animals showed no elevation of the IOP 7 days postoperatively. When the ratio between consensual and direct PLR (PLR(ratio)=consensual/direct PLR; pupil of unoperated eye recorded) was examined in rats which developed elevation of the IOP, preoperative values were 92.2+/-4% (mean+/-SEM), 1 week postoperatively 65+/-4% (significantly different from preoperative values, p<0.05 Repeated Measures ANOVA with Dunnett's Multiple Comparison test, n=5), 4 weeks postoperatively 60.6+/-3.2% (p<0.01, n=5). By 8 weeks postoperatively, pupil responses had essentially recovered 75.4+/-6.9% (p>0.05, n=5). Rats whose IOP values did not rise after surgery and sham operated rats did not develop pupil deficits 4 weeks postoperatively. Rats with elevated IOP displayed a significant decrease in ERG amplitudes in operated eyes at 4 weeks (a-wave(operated)/a-wave(control) (a-wave ratio)=42+/-14% (mean+/-SEM); b-wave(operated)/b-wave(control) (b-wave ratio)=43+/-16%) but not at 8 weeks postoperatively (a-wave ratio=88+/-8.4%; b-wave ratio=82.9+/-9%). Sham operated and rats whose IOP values remained non-elevated after surgery did not develop ERG deficits 4 weeks after surgery. Histological analysis did not reveal any damage in the eyes of animals with elevated intraocular ocular pressure with the exception of one rat, which still had ERG and pupil deficits at the end of experiment., Conclusions: Development of ERG and PLR deficits are proportional to the elevation of the IOP in the rat model of chronic ocular hypertension. Functional monitoring of the ERG and PLR are useful objective techniques for the detection of retina and optic nerve deficits.

Purpose: To functionally characterize the status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP) and to determine the dynamics of the pathologic changes in the ischemic retina and optic nerve., Methods: Retinal ischemia was induced in rats by acutely increasing the IOP (110 mm Hg/60 minutes). Direct and indirect pupil light reflexes (PLRs) were recorded from the noninjured eye, and electroretinograms (flash and flicker ERG) were recorded from the injured and control eyes before and after surgery. Amplitudes and latencies were calculated for each recording session., Results: Preoperative PLR(ratio)s (indirect/direct PLR) were 76.7 +/- 2.6 (mean +/- SEM). Twenty-four hours after surgery the PLR(ratio) was 15.2 +/- 12.8, 10 days after surgery, 11.6 +/- 9.8; 20 days after surgery, 26.5 +/- 8.0; and 28 days after surgery, 33.27 +/- 9.3. However, at day 35, the PLR had significantly recovered (41.1 +/- 7.3) when compared with the 24-hour postoperative ratios (P < 0.01, repeated-measures ANOVA). Forty-two days after surgery, the PLR(ratio) started to decrease once again in the injured eyes (28.7 +/- 5.9). Electroretinographic amplitudes (full-field flash ERG) followed a similar pattern. Cone responses (flicker ERG) were measured 42 days after surgery and revealed defects in injured eyes (control eyes: 46.6 +/- 2.9 microV, injured eyes: 3.4 +/- 1.7 microV). Histologic analysis revealed ischemic damage to all retinal layers, with the primary defects localized to the central retina., Conclusions: Acute ocular ischemia causes a significant decrease in retinal function, as measured by PLR and ERG, although over time the rat retina and optic nerve show partial regain of function.

Purpose: To characterize the pupil light reflex (PLR), electroretinographic (ERG) and tonometric parameters which might be of importance for the in vivo characterization of mouse models of chronic ocular hypertension., Methods: C57/BL6 mice were used for experiments. The PLR was evaluated with a computerized pupillometer (n = 14), ERGs were recorded simultaneously from both eyes (n = 23) and IOP was measured with a modified Goldmann tonometer (n = 23)., Results: The analysis of the PLR parameters confirmed the consensual PLR did not have significantly different amplitude (p > 0.1) and latency time (p > 0.1) compared to the direct PLR. However, PLR velocity (p = 0.004) was significantly smaller in the consensual PLR. Electroretinography revealed a-wave amplitude of 168.3 +/- 9.6 microV with latency of 27.5 +/- 0.6 ms and b-wave 403 +/- 28.8 microV with latency of 22.7 +/- 0.6 ms. The flicker ERG recording revealed amplitudes of 20.6 +/- 2.4 microV. Tonometry experiments revealed that modified Goldmann tonometer measurements correlated well with invasive manometry (r(2) = 0.89). The mean IOP of the mouse was 15.3 +/- 0.6 mmHg., Conclusions: Consensual PLR in mice is relatively slower than the direct PLR, but retains the same degree of constriction comparing to the direct PLR. A modified Goldmann tonometer seems to be a reliable non-invasive tool for IOP measurements in mice.

Purpose: To investigate the clinical usefulness of the latency of the pupil light reflex by optimizing its measurement, characterizing its variability, and determining the sensitivity of pupil latency as a function of stimulus input in normal subjects., Methods: Computerized binocular infrared pupillography was performed in 14 eyes of seven healthy subjects. Pupils were recorded simultaneously at 60 and 1000 Hz. Each eye was alternatively stimulated eight times for 50 ms every 2.5 seconds, increasing by 0.5 log units over a 2.0-log-unit range. To determine intersubject and intereye variability, 98 eyes of 49 healthy subjects were recorded at 60 Hz over a 3.0-log-unit range (15 degrees radius stimulation, four repetitions at each intensity)., Results: Accuracy and resolution of latency were limited by the number of light reflexes used to estimate the average latency and were significantly affected by sampling rate when the number of reflexes recorded was fewer than four. Binocular recording and interpolation of the 60-Hz recording to 300 Hz added resolution to the latency. Biological variability contributed more to interindividual variability than did measurement variability. The range of intereye afferent asymmetry of latency in normal subjects was only between 8.3 and 35 ms-less with brighter stimulus intensity., Conclusions: An optimal method for determination of the onset of the pupil light reflex was devised that consisted of filtering, interpolation of pupil recordings, and analysis of the first and second derivative of the pupil movement. Most of the variability in latency as a function of intensity in normal subjects was due to interindividual variation and latency was well matched between the two eyes of the subjects.

Objective: To evaluate changes in pupil size (corresponding to neuronal firing) within different time windows of the pupil light reflex in patients and normal subjects to understand which segments of the pupil waveform are best able to differentiate normal from abnormal subjects., Design: Comparative, observational case series., Participants: Forty-nine normal subjects and 25 patients with known unilateral or asymmetric visual field damage were tested., Methods: A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz. Each eye was stimulated alternately (30 degrees full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus intensities. The recorded waveform of the pupil light reflex was subdivided into six time windows based on landmarks corresponding to contraction onset, maximum contraction velocity, peak contraction, and maximum dilation velocity to assess which portion was most affected by disease., Main Outcome Measures: The linear correlation between pupil contractions elicited by right versus left full-field stimulation at different light intensities provided diagnostic parameters (slope, intercept, and correlation coefficient R(2)) that were useful for differentiating normal subjects from patients and for categorizing disease. Sensitivity and specificity of the time windows were evaluated with receiver-operator curve analysis., Results: The diagnosis of asymmetric disease was greatest at time windows that included pupil contraction but not dilation. When the contraction phase was subdivided into an early phase and into a late phase, the late phase was the most diagnostic compared with the entire phase of contraction amplitude (onset to peak contraction)., Conclusions: By use of a range of light intensity, the change in pupil size measured between the time at which maximum contraction velocity occurs and the time to peak contraction provided the best response parameter for objective diagnosis of asymmetric disease of the anterior visual pathway. The waveform of the pupil light reflex may be an expression of the firing of retinal ganglion cells. Therefore, understanding which segment of the pupil light reflex provides maximal diagnostic power may give insight into how disease affects the pattern of neuronal firing rate.

A 17-year-old male presented with chronic diplopia and generalized motor weakness. He was previously diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and acute disseminated encephalomyelitis in childhood. Cranial magnetic resonance imaging (MRI) revealed a rarely reported finding of thickening and enhancement of multiple cranial nerves. Nerve conduction studies and electromyography showed peripheral nerve demyelination with axonal involvement. There was improvement in the clinical examination, MRI, and electrophysiologic studies after combined corticosteroid and plasma exchange therapy. We review the clinical presentation, course, and response to therapy among children with chronic inflammatory demyelinating polyradiculoneuropathy, with specific emphasis on the frequency and pattern of cranial nerve involvement.

A 63-year-old woman with headache, blurred vision, bilateral optic disc edema, and normal cranial magnetic resonance imaging scan underwent lumbar puncture that revealed an elevated opening pressure (290 mm water), a protein level of 114 mg/dl, and mild pleocytosis. Spinal magnetic resonance imaging later demonstrated a sacral tumor, which proved to be a schwannoma with sarcoid-like features. After surgical removal of the tumor, the patient's manifestations resolved. This case emphasizes that low spinal cord tumors can cause elevated intracranial pressure without causing markedly elevated cerebrospinal fluid protein or cells, or any myelopathic manifestations, perhaps by obstructing sacral cerebrospinal drainage. Comprehensive spine imaging should be a part of the evaluation of a patient with papilledema who has normal brain imaging but abnormal spinal fluid constituents.

Objectives: (1) To report the incidence and extent of visual improvement achieved by high-dose systemic corticosteroid treatment in eyes with visual loss due to giant-cell arteritis (GCA). (2) To understand the cause of the discrepancies between visual improvement revealed by routine visual acuity (VA) and by the central visual field in kinetic perimetry. (3) To review critically the contradictory literature on the effectiveness of corticosteroid therapy on visual recovery in GCA and to attempt to reconcile differences in the reported results., Methods: Clinical data were collected systematically on 84 consecutive patients (114 eyes) with visual loss, all of whom had GCA confirmed by temporal artery biopsy and treated by us with high-dose systemic corticosteroid therapy. The patients were treated between 1974 and 1999 and data were compiled retrospectively. All patients underwent a detailed visual and ophthalmic evaluation at the initial visit and at every follow-up. This included visual field testing (with a Goldmann perimeter). All were treated with systemic corticosteroid therapy (intravenous followed by oral in 41 patients and oral only in 43 patients)., Results: Visual loss was due to anterior ischaemic optic neuropathy (91%), central retinal artery occlusion (10.5%), cilioretinal artery occlusion (10%), and/or posterior ischaemic optic neuropathy (4%), either alone or in different combinations. Improvement in both VA (>or= 2 lines) and central visual field was found in only five (4%) eyes of five patients (three treated with intravenous and two with oral steroid therapy). Improvement in VA >or= 2 lines but not in the central visual field was found in seven eyes (in six patients). Visual improvement was seen in 7% of 41 patients treated initially with intravenous steroids versus 5% (p = 0.672) of 43 patients treated with oral steroids only. Comparison of patients with visual improvement in both VA and fields versus those with no improvement suggested a shorter interval (p = 0.065) between onset of visual loss and start of therapy in the improved patients., Conclusions: In our study, only 4% of eyes with visual loss due to GCA improved, as judged by improvement in both VA and central visual field (by kinetic perimetry and Amsler grid). The data also suggest that there is a better (p = 0.065) chance of visual improvement with early diagnosis and immediate start of steroid therapy. Improvement in VA without associated improvement in the central visual field or Amsler grid may simply represent a learned ability to fixate eccentrically with more effective use of remaining vision: this factor could help explain a number of reported cases in the literature of improved VA after steroid treatment for GCA. To prevent further visual loss in either eye and for management of systemic manifestations of GCA, all patients must be treated on a long-term basis with adequate amounts of systemic corticosteroids.

Purpose: To characterize the pupil light reflex (PLR), electroretinographic (ERG) and tonometric parameters in healthy rat eyes., Methods: Brown Norway rats were used for experiments. The PLR was evaluated with a computerized pupillometer (n = 27), ERGs were recorded simultaneously from both eyes (n = 27) and IOP was measured with a Tonopen (n = 15)., Results: The analysis of the PLR parameters confirmed that the consensual PLR had a significantly smaller amplitude (0.1-0.2 mm; p = 0.03) and an increased latency time (p = 0.001) compared to the direct PLR. Electroretinography revealed an a-wave amplitude of 207.2 +/- 13 microV with a latency of 25.6 +/- 0.7 ms, and a b-wave 554.3 +/- 24.5 microV with a latency of 21.4 + 1.8 ms. The flicker ERG recording revealed amplitudes of 40.6 +/- 2.4 microV. Tonometry measurements revealed that isoflurane, but not halothane, anesthesia suppressed the IOP (non-anesthetized: 25.3 +/- 1.0 mmHg; 1% halothane + 30% NO: 26.2 +/- 1.1 (p > 0.1); 1% isoflurane + 30% NO: 20.1 + 1.6 (p < 0.05))., Conclusions: Consensual PLR in rats has a relative deficit compared to the direct PLR. Isoflurane anesthesia has a suppressive effect on the IOP in healthy rat eyes.

Objective: To test whether pupil escape observed during a constant light stimulus was greater in eyes with central visual field loss compared to eyes with peripheral visual field loss and normal eyes., Design: Comparative, observational case series., Participants: Twenty-seven normal subjects, 5 patients with central field loss, 11 patients with peripheral field loss, and 8 patients with combined loss (central and peripheral visual field loss) were tested., Methods: A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz to characterize the initial, phasic pupil contraction, and the sustained, or prolonged, pupil contraction in response to a 5-second light stimulus. Full-field light stimuli with a diameter of 30 degrees were presented to each eye at seven different intensities., Main Outcome Measures: The amplitude of the phasic pupil contraction was compared with the amplitude of the sustained pupil contraction at the four brightest intensities (slope of phasic versus sustained contraction) in the normal eyes and in eyes with visual field loss in the center and the periphery., Results: The sustained pupillary contraction showed a statistically greater reduction in proportion to the phasic component in eyes with central field loss compared to those with peripheral field loss, combination central and peripheral field loss, and normal eyes., Conclusions: Afferent neurons from the central retina normally contribute a substantial component to the sustained pupil response. Eyes with central field loss can be distinguished from eyes with peripheral field loss by a relatively greater loss of the sustained response, causing greater pupil escape. This study showed that pupil movements in response to a nonperimetric full-field light stimulus may provide some degree of mapping of retinotopic sensitivity. This information may be of use in interpreting the pupillary movements during the swinging flashlight test and may help predict the pattern of visual field loss.

Objective: To report two cases of cerebral venous sinus thrombosis with papilledema and visual loss that improved after endovascular stent placement., Materials and Methods: Retrospective case series from a tertiary ophthalmic center., Results: Two cases of venous sinus occlusion treated with angioplasty and stenting are described. Both cases experienced improvement in optic disc edema and visual function following the procedures., Conclusion: Endovascular stent placement may relieve increased intracranial pressure and papilledema caused by cerebral sinus thrombosis and may prevent further visual loss.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), characterized by an autosomal dominant inheritance pattern, has recently been recognized as a distinct entity that can display a confusingly broad clinical phenotype. The pallido-ponto-nigral degeneration (PPND) variant is the prototypical example of the parkinsonism-predominant pattern of FTDP-17. A longitudinal videotape demonstration of the clinical progression of this entity in a single individual, along with brief videotape segments from three additional affected individuals, is presented in order to facilitate recognition of this disorder., (Copyright 2001 Movement Disorder Society.)

Purpose: To compare the sensitivity and variability of pupil perimetry with visual perimetry at the same retinal locations in normal subjects., Methods: Pupil perimetry was performed on the right and left eyes of 10 normal subjects using a computerized infrared pupillometer equipped to present perimetric light stimuli and record pupil light reflexes. Eleven locations were tested at different intensities along the horizontal meridian of each eye, and the decibel sensitivity of the pupil light reflex was compared with the visual threshold at the same location., Results: The shape and height of the hill of vision (retinal sensitivity) was very similar between the right and left eyes of each individual using either pupil perimetry (R2 = 0.69) or standard threshold perimetry (R2 = 0.62) but was less similar between subjects. Comparisons between pupil and visual sensitivity revealed a lack of correlation at the same retinal location in normal eyes (R2 = 0.19)., Conclusions: The high intereye correlation for either pupil or visual sensitivity may provide an important tool for detecting focal or asymmetric visual field damage. Although the basic shape of the sensitivity profile of pupil and visual responses was similar under the conditions of testing, the two did not correlate well within each eye among the normal subjects. This highlights that similarities do exist in the sensitivity profile of the two pathways, but they do not seem to vary in the same proportion between normal individuals.

The pupil is one objective marker of vision and autonomic pathways. A good understanding of its anatomy and careful examination techniques are the essential tools for proper clinical diagnosis of pupillary disorders.

Purpose: To compare visual sensitivity, fatigue effect, and probability plot data between Full Threshold (FT) Humphrey automated perimetry and Swedish Interactive Threshold Algorithm (SITA) standard strategies in patients with optic neuropathies and hemianopias., Methods: Twenty-four patients with nonglaucomatous optic neuropathies and 18 patients with a relative homonymous or bitemporal hemianopia were tested with both conventional perimetry (Humphrey 24-2 program) and "back to back" SITA standard tests (SITA 1, SITA 2) to approximate the test time of the FT test conditions. Also, 28 normal subjects between the ages of 20 and 80 were tested with this protocol. The visual field quadrants with the most damage were used to evaluate any fatigue effect (i.e., possible lack of fatigue effect with SITA standard due to the shorter test time) and to compare probability plot data between FT, SITA 1, and SITA 2. Pointwise total and pattern deviation probability plot defects were weighted by degree of significance and summed., Results: Test times for normal subjects were 45 seconds longer for FT than for the combined test time of SITA 1 + SITA 2. Patients' test times were 40 seconds longer for hemianopias and 90 seconds longer for optic neuropathies with FT than the combined times for two SITA tests. There were higher sensitivities found with SITA 1 compared with Full Threshold (1.06 dB, P< 0.001) and SITA 2 with Full Threshold (0.73 dB, P< 0.001) in the most damaged quadrant for the optic neuropathy patients; for the hemianopia patients the difference in values were between SITA 1 and Full Threshold (0.96 dB, P = 0.07) and between SITA 2 and Full Threshold (0.11 dB, P = 0.87). The second SITA standard test had lower sensitivity than the first SITA standard test by 0.82 dB in hemianopias and by 0.71 dB in optic neuropathy patients. Analysis of the total and pattern deviation probability plot data showed slightly more defects (number and magnitude) with SITA 1 compared to FT for both groups, but the differences were not statistically significant., Conclusions: Sensitivities were higher in patients with hemianopias or optic neuropathies using SITA standard compared with FT by approximately 1 dB. The probability plot comparison suggests SITA standard is at least as good as FT for detection of visual loss in individual examinations. However, efficacy of SITA standard for serial examinations has not yet been evaluated.

Purpose: To study and compare the findings on multifocal electroretinography (MERG) between multifocal choroiditis (MFC) and the multiple evanescent white dot syndrome (MEWDS)., Subject and Methods: Patients were recruited prospectively from the Department of Ophthalmology & Visual Sciences at the University of Iowa Hospitals & Clinics. They were evaluated using Goldmann visual fields (GVF) and MERG. Patients were diagnosed as having either MFC or MEWDS based on their clinical findings before MERG testing., Results: Nineteen patients (23 eyes) were included in the study. Eleven patients were diagnosed with MFC and eight patients with MEWDS. Fourteen eyes with MFC and seven eyes with MEWDS were tested with MERG during the acute phase of their respective conditions. Fourteen patients (8 MFC and 6 MEWDS) were followed serially with MERG. Patients with MEWDS demonstrated focal depression corresponding to GVF defects with subsequent near total recovery of the MERG to baseline. Patients with MFC typically demonstrated diffuse loss of function over the entire test field. Focal scotomata, in addition to the diffuse depression, could be identified in 7 of 14 patients. Patients with MFC demonstrated only partial or no recovery of MERG following acute episodes, which was significantly different from the course followed by patients with MEWDS (P < 0.001, Fisher's exact test)., Conclusion: Multifocal electroretinography differentiates MFC from MEWDS. Patients with MFC have permanent damage to the retina with diffuse depression of MERG. Patients with MEWDS, however, typically demonstrate greater focal loss initially on MERG followed by nearly full recovery of first order retinal function.

The aim of this study was to investigate the morphologic changes of the pituitary gland in patients with the clinical diagnosis of idiopathic intracranial hypertension (IIH). Qualitative and quantitative analyses of pituitary morphology were performed in normal subjects (n = 23), patients with the clinical diagnosis of IIH (n = 40), and patients with acute increased intracranial pressure (AICP; n = 37) caused by acute head trauma. The loss of pituitary height (concavity) on the sagittal T1-weighted image was classified into five categories: I = normal, II = superior concavity that was mild (<(1/3) the height of the sella), III = moderate (between (1/3) and (2/3) concavity of height of sella), IV = severe (>(2/3) concavity of height of sella), and V = empty sella. The area ratio of pituitary gland to sella turcica measured in the midsagittal plane was quantified. Clinical records were retrospectively reviewed to correlate with magnetic resonance (MR) findings. Using moderate concavity (>(1/3)) as the minimum criterion for abnormality, IIH patients had an 85% incidence of morphologic changes with 80% sensitivity and 92% specificity. Empty sella (almost complete concavity of the sella) was found in only 2.5% of patients with IIH. Quantitative analysis of the pituitary gland/sella turcica area ratio showed a significant decrease in patients with IIH (P < 0.0001) but no significant difference between the normal subjects and AICP patients. A posterior deviation of the pituitary stalk was seen in 43% of patients. No enlargement of the ventricles or sulcal effacement was seen in IIH patients. Routine brain MR examination of patients with IIH frequently shows morphologic changes of the pituitary gland ranging from various degrees of concavity to (rarely) the extreme case of an empty sella. The etiology is unknown and may be related to the severity and duration of elevated CSF pressure. Such findings may be useful to facilitate the diagnosis of IIH, particularly in patients with equivocal clinical findings or when IIH is not suspected. J. Magn. Reson. Imaging 2000;12:808-813., (Copyright 2000 Wiley-Liss, Inc.)