Bilateral sequential nonarteritic anterior ischemic optic neuropathy: a comparison of visual outcomes in fellow eyes using quantitative analysis of goldmann visual fields.

OBJECTIVE To better define the concordance of visual loss in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS The medical records of 86 patients with bilateral sequential NAION were reviewed retrospectively, and visual function was assessed using visual acuity, Goldmann visual fields, color vision, and relative afferent papillary defect. A quantitative total visual field score and score per quadrant were analyzed for each eye using the numerical Goldmann visual field scoring method. RESULTS Outcome measures were visual acuity, visual field, color vision, and relative afferent papillary defect. A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P = .01), global visual field (P < .001), superior visual field (P < .001), and inferior visual field (P < .001). The mean deviation of total (P < .001) and pattern (P < .001) deviation analyses was significantly less between fellow eyes than between first and second eyes of different patients. CONCLUSIONS Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION.

Bilateral Sequential NAION: A Comparison of Visual Outcomes in Fellow Eyes Using Quantitative Analysis of Goldmann Visual Fields

Purpose: Previous studies of the visual outcome in bilateral non-arteritic anterior ischemic optic neuropathy (NAION) have yielded conflicting results, specifically regarding congruity between fellow eyes. Prior studies have used measures of acuity and computerized perimetry but none has compared Goldmann visual field outcomes between fellow eyes. In order to better define the concordance of visual loss in this condition, we reviewed our cases of bilateral sequential NAION, including measures of visual acuity, pupillary function and both pattern and severity of visual field loss.Methods: We performed a retrospective chart review of 102 patients with a diagnosis of bilateral sequential NAION. Of the 102 patients, 86 were included in the study for analysis of final visual outcome between the affected eyes. Visual function was assessed using visual acuity, Goldmann visual fields, color vision and RAPD. A quantitative total visual field score and score per quadrant was analyzed for each eye using the numerical Goldmann visual field scoring method previously described by Esterman and colleagues. Based upon these scores, we calculated the total deviation and pattern deviation between fellow eyes and between eyes of different patients. Statistical significance was determined using nonparametric tests.Results: A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P = 0.0101), global visual field (P = 0.0001), superior visual field (P = 0.0001), and inferior visual field (P = 0.0001). In addition, the mean deviation of both total (P = 0.0000000007) and pattern (P = 0.000000004) deviation analyses was significantly less between fellow eyes ("intra"-eyes) than between eyes of different patients ("inter"-eyes).Conclusions: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION. These findings may also be useful for evaluating efficacy of therapeutic interventions.

Long-term fluctuation of relative afferent pupillary defect in subjects with normal visual function.

PURPOSE: To determine whether the relative afferent pupillary defect (RAPD) remains constant over time in normal subjects. METHODS: Seventeen normal subjects were tested with infrared pupillography and automated perimetry in four sessions over 3 years. The changes in RAPD and visual field asymmetry between testing sessions were compared. RESULTS: The range of RAPD was 0.0 to 0.3 log unit, and the difference in the mean deviation between the eyes on automated static perimetry was 0 to 3 dB. Eight subjects repeatedly had an RAPD in the same eye. There was no correlation between the RAPD and the visual field asymmetry at the same visit. Changes in the magnitude of the RAPD between any two sessions were typically small (median, 0.08 log unit; 25th percentile, 0.04 log unit; 75th percentile, 0.15 log unit). CONCLUSIONS: Some normal subjects may show a persistent but small RAPD in the absence of detectable pathologic disease. Therefore, an isolated RAPD in the range of 0.3 log unit that is not associated with any other significant historical or clinical finding should probably be considered benign.

Photophobia as the presenting visual symptom of chiasmal compression.

Five patients with a chief visual complaint of photophobia were subsequently found to have compressive lesions of the optic chiasm. Visual acuity and visual field deficits were often subtle. Magnetic resonance imaging scanning revealed large suprasellar masses, including three pituitary adenomas, a craniopharyngioma, and a clivus chordoma. Photophobia resolved in all patients following treatment of the tumors. A compressive lesion of the optic chiasm should be considered in patients who experience persistent photophobia unexplained by ocular abnormalities.

Analysis of significant factors influencing visual acuity in ocular syphilis.

BACKGROUND: The aim of this study is to determine whether statistical associations can be demonstrated in ocular syphilis between baseline clinical and laboratory parameters with visual acuity at presentation and with any change in visual acuity after treatment. METHODS: Charts of 26 patients (42 eyes) with ocular syphilis presenting to the Uveitis clinic of the Jules-Gonin Eye Hospital were reviewed. A baseline cross-sectional analysis was performed in order to identify any association between visual acuity at presentation and demographic, clinical or laboratory parameters. After treatment, any analogy between these parameters and a change in visual acuity was subsequently assessed in a series of univariate comparisons. RESULTS: The following factors were associated with worse initial visual acuity: severity of visual field impairment at presentation (p=0.012), macular oedema (p=0.004) and optic neuropathy (p=0.031). There was a borderline association with the presence of vasculitis on fluroangiography (p=0.072). Improvement in best corrected visual acuity after treatment was significantly associated with the presence of vasculitis on fluroangiography (p=0.005), neurosyphilis, according to lumbar puncture findings (p=0.037) and marginally with anterior uveitis (p=0.070). Inflammation relapse was associated with the coexistence of pain as presenting sign (p<0.001) and with a longer duration of symptoms prior to the initial visit (p=0.023). CONCLUSIONS: Severe ocular inflammation associated with vasculitis, vitritis or anterior uveitis in ocular syphilis would appear to be a reversible phenomenon that responds well to appropriate antibiotic treatment, resulting in improvement in visual acuity. Prompt treatment enables a good visual prognosis, while any delay in therapy increases the risk of subsequent relapse.

Pupillographic investigation of the relative afferent pupillary defect associated with a midbrain lesion.

OBJECTIVE: To identify clinical and pupillographic features of patients with a relative afferent pupillary defect (RAPD) without visual acuity or visual field loss caused by a lesion in the dorsal midbrain. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Four patients with a dorsal midbrain lesion who had normal visual fields and a clinically detectable RAPD. METHODS: The pupil response from full-field and hemifield light stimulation over a range of light intensities was measured by computerized binocular pupillography. MAIN OUTCOME MEASURES: The mean of the direct and consensual pupil response to full-field and hemifield light stimulation was plotted as a function of stimulus light intensity. RESULTS: All 4 subjects showed decreased pupillographic responses at all intensities to full-field light stimulation in the eye with the clinical RAPD. The pupillographic responses to hemifield stimulation showed a homonymous pattern of deficit on the side ipsilateral to the RAPD, similar to that observed in a previously reported patient with an optic tract lesion. CONCLUSIONS: The basis of a midbrain RAPD is the nasal-temporal asymmetry of pupillomotor input that becomes manifest when a unilateral postchiasmal lesion interrupts homonymously paired fibers traveling in the contralateral optic tract or midbrain pathway to the pupillomotor center, respectively. The pupillographic characteristics of an RAPD resulting from a dorsal midbrain lesion thus resemble those of an RAPD resulting from a unilateral optic tract lesion, but without the homonymous visual field defect. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Interhemispheric visual integration in humans explored by multimodal brain imaging

Résumé: Les récents progrès techniques de l'imagerie cérébrale non invasives ont permis d'améliorer la compréhension des différents systèmes fonctionnels cérébraux. Les approches multimodales sont devenues indispensables en recherche, afin d'étudier dans sa globalité les différentes caractéristiques de l'activité neuronale qui sont à la base du fonctionnement cérébral. Dans cette étude combinée d'imagerie par résonance magnétique fonctionnelle (IRMf) et d'électroencéphalographie (EEG), nous avons exploité le potentiel de chacune d'elles, soit respectivement la résolution spatiale et temporelle élevée. Les processus cognitifs, de perception et de mouvement nécessitent le recrutement d'ensembles neuronaux. Dans la première partie de cette thèse nous étudions, grâce à la combinaison des techniques IRMf et EEG, la réponse des aires visuelles lors d'une stimulation qui demande le regroupement d'éléments cohérents appartenant aux deux hémi-champs visuels pour en faire une seule image. Nous utilisons une mesure de synchronisation (EEG de cohérence) comme quantification de l'intégration spatiale inter-hémisphérique et la réponse BOLD (Blood Oxygenation Level Dependent) pour évaluer l'activité cérébrale qui en résulte. L'augmentation de la cohérence de l'EEG dans la bande beta-gamma mesurée au niveau des électrodes occipitales et sa corrélation linéaire avec la réponse BOLD dans les aires de VP/V4, reflète et visualise un ensemble neuronal synchronisé qui est vraisemblablement impliqué dans le regroupement spatial visuel. Ces résultats nous ont permis d'étendre la recherche à l'étude de l'impact que le contenu en fréquence des stimuli a sur la synchronisation. Avec la même approche, nous avons donc identifié les réseaux qui montrent une sensibilité différente à l'intégration des caractéristiques globales ou détaillées des images. En particulier, les données montrent que l'implication des réseaux visuels ventral et dorsal est modulée par le contenu en fréquence des stimuli. Dans la deuxième partie nous avons a testé l'hypothèse que l'augmentation de l'activité cérébrale pendant le processus de regroupement inter-hémisphérique dépend de l'activité des axones calleux qui relient les aires visuelles. Comme le Corps Calleux présente une maturation progressive pendant les deux premières décennies, nous avons analysé le développement de la fonction d'intégration spatiale chez des enfants âgés de 7 à 13 ans et le rôle de la myelinisation des fibres calleuses dans la maturation de l'activité visuelle. Nous avons combiné l'IRMf et la technique de MTI (Magnetization Transfer Imaging) afin de suivre les signes de maturation cérébrale respectivement sous l'aspect fonctionnel et morphologique (myelinisation). Chez lés enfants, les activations associées au processus d'intégration entre les hémi-champs visuels sont, comme chez l'adulte, localisées dans le réseau ventral mais se limitent à une zone plus restreinte. La forte corrélation que le signal BOLD montre avec la myelinisation des fibres du splenium est le signe de la dépendance entre la maturation des fonctions visuelles de haut niveau et celle des connections cortico-corticales. Abstract: Recent advances in non-invasive brain imaging allow the visualization of the different aspects of complex brain dynamics. The approaches based on a combination of imaging techniques facilitate the investigation and the link of multiple aspects of information processing. They are getting a leading tool for understanding the neural basis of various brain functions. Perception, motion, and cognition involve the formation of cooperative neuronal assemblies distributed over the cerebral cortex. In this research, we explore the characteristics of interhemispheric assemblies in the visual brain by taking advantage of the complementary characteristics provided by EEG (electroencephalography) and fMRI (Functional Magnetic Resonance Imaging) techniques. These are the high temporal resolution for EEG and high spatial resolution for fMRI. In the first part of this thesis we investigate the response of the visual areas to the interhemispheric perceptual grouping task. We use EEG coherence as a measure of synchronization and BOLD (Blood Oxygenar tion Level Dependent) response as a measure of the related brain activation. The increase of the interhemispheric EEG coherence restricted to the occipital electrodes and to the EEG beta band and its linear relation to the BOLD responses in VP/V4 area points to a trans-hemispheric synchronous neuronal assembly involved in early perceptual grouping. This result encouraged us to explore the formation of synchronous trans-hemispheric networks induced by the stimuli of various spatial frequencies with this multimodal approach. We have found the involvement of ventral and medio-dorsal visual networks modulated by the spatial frequency content of the stimulus. Thus, based on the combination of EEG coherence and fMRI BOLD data, we have identified visual networks with different sensitivity to integrating low vs. high spatial frequencies. In the second part of this work we test the hypothesis that the increase of brain activity during perceptual grouping depends on the activity of callosal axons interconnecting the visual areas that are involved. To this end, in children of 7-13 years, we investigated functional (functional activation with fMRI) and morphological (myelination of the corpus callosum with Magnetization Transfer Imaging (MTI)) aspects of spatial integration. In children, the activation associated with the spatial integration across visual fields was localized in visual ventral stream and limited to a part of the area activated in adults. The strong correlation between individual BOLD responses in .this area and the myelination of the splenial system of fibers points to myelination as a significant factor in the development of the spatial integration ability.

Origin of the relative afferent pupillary defect in optic tract lesions.

OBJECTIVE: To determine the percent decussation of pupil input fibers in humans and to explain the size and range of the log unit relative afferent pupillary defect (RAPD) in patients with optic tract lesions. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Five patients with a unilateral optic tract lesion. METHODS: The pupil response from light stimulation of the nasal hemifield, temporal hemifield, and full field of each eye of 5 patients with a unilateral optic tract lesion was recorded using computerized binocular infrared pupillography. Six stimulus light intensities, separated by 0.5-log unit steps, were used; 12 stimulus repetitions were given for each stimulus condition. MAIN OUTCOME MEASURES: For each stimulus condition, the pupil response of each eye was characterized by plotting the mean pupil contraction amplitude as a function of stimulus light intensity. The percentage of decussating afferent pupillomotor input fibers was calculated from the ratio of the maximal pupil contractions elicited from each eye. The RAPD was determined pupillographically from full-field stimulation to each eye. RESULTS: In all patients, the pupil response from the functioning temporal hemifield ipsilateral to the tract lesion was greater than that from the functioning contralateral nasal hemifield. This temporal-nasal asymmetry increased with increasing stimulus intensity and was similar in hemifield and full-field stimuli, eventually saturating at maximal light intensity. The log unit RAPD did not correlate with the estimated percentage of decussating pupil fibers, which ranged from 54% to 67%. CONCLUSIONS: In patients with a unilateral optic tract lesion, the pupillary responses from full-field stimulation to each eye are the same as comparing the functioning temporal field with the functioning nasal field. The percentage of decussating fibers is reflected in the ratio of the maximal pupil contraction amplitudes resulting from stimulus input between the two eyes. The RAPD that occurs in this setting reflects the difference in light sensitivity between the intact temporal and nasal hemifields. Its magnitude does not correlate with the difference in the number of crossed and uncrossed axons, but its sidedness contralateral to the side of the optic tract lesion is consistent with the greater percentage of decussating pupillomotor input.

Differential effect of long versus short wavelength light exposure on pupillary re-dilation in patients with outer retinal disease.

BACKGROUND: In patients with outer retinal degeneration, a differential pupil response to long wavelength (red) versus short wavelength (blue) light stimulation has been previously observed. The goal of this study was to quantify differences in the pupillary re-dilation following exposure to red versus blue light in patients with outer retinal disease and compare them with patients with optic neuropathy and with healthy subjects. DESIGN: Prospective comparative cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13 patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were tested using continuous red and blue light stimulation at three intensities (1, 10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics following the brightest intensity was analysed and compared between the three groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this study were: time to recover 90% of baseline size; mean pupil size at early and late phases of re-dilation; and differential re-dilation time for blue versus red light. RESULTS: Patients with outer retinal disease showed a pupil that tended to stay smaller after light termination and thus had a longer time to recovery. The differential re-dilation time was significantly greater in patients with outer retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation following red versus blue light stimulation is present in patients with outer retinal disease but is not found in normal eyes or among patients with visual loss from optic neuropathy.

. Phenotype/genotype correlation associated with a novel nonsense Glu20stop mutation in the Rp2 gene in a three-generation family with x-linked retinitis pigmentosa

Purpose: To assess the phenotype of patients in a large 3 generation Swiss family with X-linked retinitis pigmentosa (XLRP) due to a novel nonsense mutation Glu20stop in RP2 gene and to correlate with the genotype. Methods: 6 affected patients (1 male, 5 females, age range: 23 - 73 years) were assessed with a complete ophthalmologic examination. All had fundus autofluorescence images, standardised electroretinography, Goldmann visual fields and Optical Coherence Tomography. In addition, medical records of 2 affected male patients were reviewed. Blood sample was taken for molecular analysis. Results: The male patients were severely affected at a young age with early macular involvement. The youngest 23 y old male had also high myopia and vision of less than 0.05 according to Snellen EDTRS chart bilaterally. All 5 female carriers had some degree of rod-cone dystrophy, but no macular involvement. The visual acuity was 1.0 in the younger carriers, while the 73 years old had VA of 0.5. Two females had mild myopia (range -0.75 to -2) and one had anisometropia of 3.5D, with the more severely affected eye being myopic. Three out of 5 female carriers had optic nerve drusen. Conclusions: We report a novel Glu20stop mutation in RP2 gene, which is a rare cause of XLRP. Our description of severe phenotype in male patients with high myopia and early macular atrophy confirms previous reports. Unlike previous reports, all our female carriers had RP, but not macular involvement or high myopia. The identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.

Photopsies: symptome souvent méconnu et apport de l'électrorétinographie [Photopsia: an often unrecognized symptom and sensitivity of electroretinography]

BACKGROUND: Photopsias are unformed luminous spontaneous visual hallucinations, often described as flickering or wiggling lights, sometimes like a glare. Phosphenes are more intense and of shorter duration whereas migraine fortifications have a specific time course and succession of events. Recognition of this symptom is often poor, hence patients are wrongly investigated. PURPOSE: To describe the clinical presentation and electroretinographic characteristics of patients with photopsias. METHODS: 4 patients were worked-up with clinical, psychophysical, angiographic and electroretinographic examinations. RESULTS: Despite normal fundus and angiographic examinations, full-field electroretinogram was diagnostic in all cases. Retinal dysfunction involved either inner or outer retina. Paraneoplastic, and probable autoimmune/inflammatory retinopathies were found in our cases. CONCLUSION: Photopsias are often secondary to sick retinal cells. In the presence of photopsias, investigations should be directed towards the retina and electroretinography is the gold standard. Recognition of the symptom should prevent useless and potentially harmful investigations for the patient.