Patrick A. Sibony

Not looking while leaping: the linkage of blinking and saccadic gaze shifts

Many vertebrates generate blinks as a component of saccadic gaze shifts. We investigated the nature of this linkage between saccades and blinking in normal humans. Activation of the orbicularis oculi, the lid closing muscle, EMG occurred with 97% of saccadic gaze shifts larger than 33°. The blinks typically began simultaneously with the initiation of head and/or eye movement. To minimize the possibility that the blinks accompanying saccadic gaze shifts were reflex blinks evoked by the wind rushing across the cornea and eyelashes as the head and eyes turned, the subjects made saccadic head turns with their eyes closed. In this condition, orbicularis oculi EMG activity occurred with all head turns greater than 17° in amplitude and the EMG activity began an average of 39.3 ms before the start of the head movement. Thus, one component of the command for large saccadic gaze shifts appears to be a blink. We call these blinks gaze-evoked blinks. The linkage between saccadic gaze shifts and blinking is reciprocal. Evoking a reflex blink prior to initiating a voluntary saccadic gaze shift dramatically reduces the latency of the initiation of the head movement.

Optic Nerves Sheath Meningiomas: Clinical Manifestations

A retrospective clinical study of optic nerve sheath meningiomas based on 22 patients showed that symptoms most commonly develop in women between the ages of 35 and 60 years. The most common presenting symptoms were decreased vision and transient visual obscurations. In the earliest stages, many patients presented with normal to mildly impaired acuity (despite subjectively decreased vision), optic disc edema and enlargement of the blind spot. Optic disc edema was frequently associated with refractile bodies indicative of chronic swelling. Optic disc edema preceded the development of optic atrophy. Another group of patients presented with a history of longstanding vision loss, visual acuity of 20/200 or worse and optic atrophy. Optociliary shunt vessels were late findings only seen in five patients. The most consistent visual field abnormality was peripheral constriction. Cecocentral scotomas were uncommon. Intracranial involvement was present in five patients. There were two patients with bilateral optic nerve sheath meningiomas without CT evidence of intracranial involvement. Computerized tomography was found to be indispensable in the diagnosis of optic nerve sheath meningiomas and the detection of intracranial involvement.

A role for the basal ganglia in nicotinic modulation of the blink reflex

SummaryIn humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotines effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex.

Optical Coherence Tomography of the Swollen Optic Nerve Head: Deformation of the Peripapillary Retinal Pigment Epithelium Layer in Papilledema

PURPOSE. To examine the biomechanical deformation of load bearing structures of the optic nerve head (ONH) resulting from raised intracranial pressure, using high definition optical coherence tomography (HD-OCT). The authors postulate that elevated intracranial pressure induces forces in the retrolaminar subarachnoid space that can deform ONH structures, particularly the peripapillary Bruchs membrane (BM) and RPE layers. METHODS. The authors compared HD-OCT optic nerve and peripapillary retinal nerve fiber layer (RNFL) findings in eyes with papilledema caused by raised intracranial pressure to findings in eyes with optic disc swelling caused by optic neuritis and nonarteritic anterior ischemic optic neuropathy (NAION), conditions without intracranial hypertension. The authors measured average thickness of the RNFL and the angle of the RPE/BM at the temporal and nasal borders of the neural canal opening. The angle was measured as positive with inward (toward the vitreous) angulation and as negative with outward angulation. RESULTS. Of 30 eyes with papilledema, 20 eyes (67%) had positive RPE/BM rim angles. One of eight optic neuritis (12%) eyes and 1 of 12 NAION (8%) eyes had positive angulation. In five eyes with papilledema, RNFL thickening increased, three of which developed positive RPE/BM angles. On follow-up, 22 papilledema eyes had a reduction of RNFL swelling, and 17 of these eyes had less positive RPE/BM angulation. CONCLUSIONS. In papilledema, the RPE/BM is commonly deflected inward, in contrast to eyes with NAION or optic neuritis. The RPE/BM angulation is presumed to be caused by elevated pressure in the subarachnoid space, does not correlate with the amount of RNFL swelling, and resolves as papilledema subsides.

Shape analysis of the peripapillary RPE layer in papilledema and ischemic optic neuropathy.

PURPOSE Geometric morphometrics (GM) was used to analyze the shape of the peripapillary retinal pigment epithelium-Bruchs membrane (RPE/BM) layer imaged on the SD-OCT 5-line raster in normal subjects and in patients with papilledema and ischemic optic neuropathy. METHODS Three groups of subjects were compared: 30 normals, 20 with anterior ischemic optic neuropathy (AION), and 25 with papilledema and intracranial hypertension. Twenty equidistant semilandmarks were digitized on OCT images of the RPE/BM layer spanning 2500 μm on each side of the neural canal opening (NCO). The data were analyzed using standard GM techniques, including a generalized least-squares Procrustes superimposition, principal component analysis, thin-plate spline (to visualize deformations), and permutation statistical analysis to evaluate differences in shape variables. RESULTS The RPE/BM layer in normals and AION have a characteristic V shape pointing away from the vitreous; the RPE/BM layer in papilledema has an inverted U shape, skewed nasally inward toward the vitreous. The differences were statistically significant. There was no significant difference in shapes between normals and AION. Pre- and posttreatment OCTs, in select cases of papilledema, showed that the inverted U-shaped RPE/BM moved posteriorly into a normal V shape as the papilledema resolved with weight loss or shunting. CONCLUSIONS The shape difference in papilledema, absent in AION, cannot be explained by disc edema alone. The difference is a consequence of both the translaminar pressure gradient and the material properties of the peripapillary sclera. GM offers a novel way of statistically assessing shape differences of the peripapillary optic nerve head.

Enkephalin-like immunoreactivity in neurons in the human pineal gland

Adult human pineal glands were prepared for immunohistochemical analysis using antisera against Leu-enkephalin, neuropeptide Y, dopamine-beta-hydroxylase and vasoactive intestinal polypeptide. The material shows small neurons located in septae and along the capsule of the gland which exhibit enkephalin-like immunoreactivity. The neurons have fairly extensive dendritic arbors and immunoreactive axons are present in the septae and beneath the capsule, particularly in a perivascular location, and occasionally extend into lobules of the gland among parenchymal cells. No consistent immunoreactivity was observed with other antisera but bundles of axons exhibiting dopamine-beta-hydroxylase or neuropeptide Y-like immunoreactivity are observed in some of the material in a perivascular location.

Baseline OCT Measurements in the Idiopathic Intracranial Hypertension Treatment Trial, Part II: Correlations and Relationship to Clinical Features

PURPOSE The accepted method to evaluate and monitor papilledema, Frisén grading, uses an ordinal approach based on descriptive features. Part I showed that spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting provides reliable measurement of the effects of papilledema on the optic nerve head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is used for analysis.(1) We evaluated how OCT parameters are interrelated and how they correlate with vision and other clinical features in idiopathic intracranial hypertension (IIH) patients. METHODS A total of 126 subjects in the IIH Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) thickness, and ONH volume. The SD-OCT parameter values were correlated with high- and low-contrast acuity, perimetric mean deviation, Frisén grading, and IIH features. RESULTS At study entry, the average RNFL thickness, TRT, and ONH volume showed significant strong correlations (r ≥ 0.90) with each other. The same OCT parameters showed a strong (r > 0.76) correlation with Frisén grade and a mild (r > 0.24), but significant, correlation with lumbar puncture opening pressure. For all eyes at baseline, neither visual acuity (high or low contrast) nor mean deviation correlated with any OCT measure of swelling or GCL+IPL thickness. CONCLUSIONS In newly diagnosed IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate with Frisén grading of papilledema. At presentation, OCT measures of papilledema, in patients with newly diagnosed IIH and mild vision loss, do not correlate with clinical features or visual dysfunction. (ClinicalTrials.gov number, NCT01003639.).

Acquired oculomotor synkinesis

Paradoxical patterns of pupillary, lid and eye movement may follow oculomotor nerve palsy or they can develop spontaneously in patients with no known history of oculomotor palsy. The mechanism of this condition, known variously as aberrant regeneration of the third nerve, oculomotor misdirection or acquired oculomotor synkinesis, is not known, although the prevailing opinion has held that it occurs when axons regenerating within an oculomotor nerve become misdirected and innervate muscles for which they were not intended. However, there is evidence against this hypothesis. The authors critically review the various hypotheses and elucidate the controversy concerning the pathogenesis of acquired oculomotor synkinesis.

Baseline OCT measurements in the idiopathic intracranial hypertension treatment trial, part I: quality control, comparisons, and variability.

PURPOSE Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting. METHODS At entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods. RESULTS The average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods. CONCLUSIONS Spectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.).

Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension.

PURPOSE To analyze the deformations of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer in response to procedures that lower intracranial pressure (ICP). Second, to demonstrate how shape changes may complement the mean retinal nerve fiber layer (RNFL) thickness as a measure of intracranial hypertension (ICH) and papilledema. METHODS We used geometric morphometrics on spectral-domain optical coherence tomography images to analyze shape change of the ppRPE/BM layer after several interventions that lower cerebrospinal fluid (CSF) pressure. We also evaluated the effects of pressure-lowering interventions on both the anterior-posterior displacement of ppRPE/BM and the mean RNFL thickness. Forty-one patients with ICH and papilledema were studied before and after lumbar puncture (20), CSF shunt (9), and medical treatment of idiopathic ICH (23). We also compared the shape of 30 normal subjects to 23 patients whose papilledema resolved after medical treatment. RESULTS The ppRPE/BM-layer in ICH and papilledema is characterized by an asymmetric anterior deformation that moves posteriorly and becomes more V-shaped after each pressure-lowering intervention. The differences were statistically significant for all three groups. These shape changes also occur in patients with ongoing ICH who have secondary optic atrophy (without papilledema). Posterior displacement at the margin of the ppRPE/BM layer correlated strongly with overall shape changes. CONCLUSIONS The subsurface contour of the ppRPE/BM layer is a dynamic property that changes with CSF pressure-lowering interventions. It can supplement the RNFL thickness as an indirect gauge of ICP and is particularly helpful in patients with secondary optic atrophy. Direct measurements of displacement at the basement membrane opening may serve as a more convenient office-based surrogate for shape analysis.