Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features.
ABSTRACT: Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with "occult" GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.
Optic disc drusen may be a cause of visual field defects and visual loss. The mechanism by which this occurs is unclear. We report a patient who developed decreased vision in the right eye and was found to have a heavy burden of superficial optic disc drusen. Optical coherence tomography (OCT) confirmed focal retinal nerve fiber layer thinning that corresponded with the distribution of drusen. OCT angiography, with superficial laminar segmentation, showed focal capillary attenuation overlying the most prominent drusen. These findings demonstrate alterations in the superficial retinal capillary network associated with optic disc drusen.
PURPOSE OF REVIEW: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. RECENT FINDINGS: The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. SUMMARY: NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.
BACKGROUND: Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear. METHODS: We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up. RESULTS: Of the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004). CONCLUSION: In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.
Children with cerebral palsy often present with cognitive-visual dysfunctions characterized by visuo-perceptual and/or visuo-spatial deficits associated with a malfunctioning of visual-associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive-visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub-serving cognitive-visual functions, in order to better understand the basis of cognitive-visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive-visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive-visual deficits than in those without cognitive-visual deficits. Our findings reveal an association between cognitive-visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo-associative deficits are related to changes in fibers connecting the occipital cortex with the parietal-frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive-visual dysfunctions.
OBJECTIVE: Emotion processing is known to be mediated by a complex network of cortical and subcortical regions with evidence of specialized hemispheric lateralization within the brain. In light of prior evidence indicating that lateralization of cognitive functions (such as language) may depend on normal visual development, we investigated whether the lack of prior visual experience would have an impact on the development of specialized hemispheric lateralization in emotional processing. METHOD: We addressed this issue by comparing performance in early blind and sighted controls on a dichotic listening task requiring the detection of specific emotional vocalizations (i.e., suggestive of happiness or sadness) presented independently to either ear. RESULTS: Consistent with previous studies, we found that sighted individuals showed enhanced detection of positive vocalizations when presented in the right ear (i.e., processed within the left hemisphere) and negative vocalizations when presented in the left ear (i.e., right hemisphere). It is interesting to note that although blind individuals were as accurate as sighted controls in detecting the valance of the vocalization, performance was not consistent with any pattern of specialized hemispheric lateralization. CONCLUSIONS: Overall, these results suggest that although the lack of prior visual experience may not lead to impaired emotion processing performance, the underlying neurophysiological substrate (i.e., degree of special hemispheric lateralization) may depend on normal visual development. (PsycINFO Database Record
The presence of optic nerve swelling in pediatric patients is a frequent cause for referral to pediatric ophthalmologists and neuro-ophthalmologists because this finding can be the harbinger of serious neurologic disease including brain tumor, demyelinating disease, infiltrative disease of the optic nerve, or idiopathic intracranial hypertension. Optic nerve head drusen (ONHD) are common and can be particularly difficult to distinguish from true optic nerve swelling in pediatric patients because the ONHD are typically buried beneath the substance of the optic nerve. Correct identification of ONHD is relevant because of the visual morbidity associated with this condition and because of the need to distinguish pseudopapilledema secondary to ONHD from true optic nerve swelling. A variety of imaging modalities may be employed to evaluate for the presence of ONHD, including ultrasound, optical coherence tomography (OCT), enhanced depth imaging-OCT, fluorescein angiography, fundus autofluorescence, and optical coherence tomography angiography. To date, there is no consensus as to which of these techniques is most accurate and which should be part of a standardized evaluation for children suspected of ONHD. This review examines the recent literature analyzing these diagnostic tools and summarizes data regarding best practices for identifying ONHD.
Neurons in the cerebral cortex respond inconsistently to a repeated sensory stimulus, yet they underlie our stable sensory experiences. Although the nature of this variability is unknown, its ubiquity has encouraged the general view that each cell produces random spike patterns that noisily represent its response rate. In contrast, here we show that reversibly inactivating distant sources of either bottom-up or top-down input to cortical visual areas in the alert primate reduces both the spike train irregularity and the trial-to-trial variability of single neurons. A simple model in which a fraction of the pre-synaptic input is silenced can reproduce this reduction in variability, provided that there exist temporal correlations primarily within, but not between, excitatory and inhibitory input pools. A large component of the variability of cortical neurons may therefore arise from synchronous input produced by signals arriving from multiple sources.
PURPOSE: To examine the association between Post-Concussion Symptom Scale (PCSS) scores, Convergence Insufficiency Symptom Survey (CISS) scores, and oculomotor deficits post-concussion. METHODS: Records of adolescent patients examined in a multidisciplinary concussion clinic between July 2014 and May 2019 were reviewed. PCSS and CISS scores, results of eye examination and oculomotor assessment, concussion history, and demographics were abstracted. RESULTS: One hundred and forty patient records (median age, 15.3 years; 52 males, presented 109 days (median) from their most recent concussion) met inclusion criteria. Mean total scores on PCSS and CISS were 46.67 ± 25.89 and 27.13 ± 13.22, respectively, and were moderately correlated with each other (r = 0.53, p < .001). Oculomotor deficits were observed in 123 (88%) patients. Step-wise linear regression identified increased PCSS total score to be significantly associated with decreased amplitude of accommodation (p < .001). Increased CISS total score was significantly associated with receded near point of convergence, developmental eye movement test error scores, and cause of concussion. CONCLUSION: High PCSS scores may indicate an accommodation deficit and thus prompt an oculomotor assessment in patients following a concussion. Using the CISS and a detailed oculomotor assessment may reveal underlying oculomotor deficits, which may benefit from treatment.
A 49-year-old woman with a known right optic disc cavernous hemangioma experienced pain with eye movements and worsening of a superior visual field defect. While she retained 20/20 visual acuity in each eye, findings on magnetic resonance imaging were consistent with a hemorrhage in the anterior portion of the right intraorbital optic nerve. Her visual function stabilized spontaneously. We are unaware of previous reports of hemorrhage into the optic nerve from a cavernous hemangioma of the optic disc.
The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE: Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.
Intermittent Horner syndrome is uncommon in both the adult and pediatric population. We describe a case of a pediatric patient with an intermittent Horner syndrome. Infrared photography and videography were used to help establish the diagnosis.
BACKGROUND: Posterior ischemic optic neuropathy results from ischemia of the retrobulbar aspect of the optic nerve. It presents as acute loss of vision without optic disc swelling. This is rare in children, with only seven cases reported to date. Neuroimaging is frequently used to aid in the diagnosis of acute visual complaints in children; however, none of the cases described to date delineate the neuroimaging findings of this entity in children. METHODS: We retrospectively reviewed the electronic medical record. RESULTS: We describe the MRI findings in a 10-month-old boy with posterior ischemic optic neuropathy after intraophthalmic artery injection of chemotherapy for retinoblastoma. CONCLUSIONS: As targeted therapies for retinoblastoma and other diseases amenable to intravascular treatment delivery are more frequently used, the risk of grave vision-related side effects increases. Posterior ischemic optic neuropathy should be considered in the differential diagnosis of any child presenting with acute loss of vision. Dedicated imaging of the orbits can elucidate specific findings that may aid in the diagnosis of this entity in children.
The topic of pediatric neurodegenerative disease is broad and ever expanding. Children who suffer from neurodegenerative disease often have concomitant visual dysfunction. Neuro-ophthalmologists may become involved in clinical care to identify corroborating eye findings when a specific condition is suspected, to monitor for disease progression, and in some cases, to assess treatment efficacy. Ophthalmic findings also may be the harbinger of a neurodegenerative process so a keen awareness of the possible manifestations of these conditions is important. The purpose of this review is to highlight common examples of the neuro-ophthalmic manifestations of pediatric neurodegenerative disease using a case-based approach in an effort to provide a framework for approaching these complex patients.
Aims. Increasing evidence shows that imbalanced suppressive drive prior to binocular combination may be the key factor in amblyopia. We described a novel binocular approach, interocular shift of visual attention (ISVA), for treatment of amblyopia in adult patients. Methods. Visual stimuli were presented anaglyphically on a computer screen. A square target resembling Landolt C had 2 openings, one in red and one in cyan color. Through blue-red goggles, each eye could only see one of the two openings. The patient was required to report the location of the opening presented to the amblyopic eye. It started at an opening size of 800 sec of arc, went up and down in 160 sec of arc step, and stopped when reaching the 5th reversals. Ten patients with anisometropic amblyopia older than age 14 (average age: 26.7) were recruited and received ISVA treatment for 6 weeks, with 2 training sessions per day. Results. Both Titmus stereopsis (z = -2.809, P = 0.005) and Random-dot stereopsis (z = -2.317, P = 0.018) were significantly improved. Average improvement in best corrected visual acuity (BCVA) was 0.74 line (t = 5.842, P < 0.001). Conclusions. The ISVA treatment may be effective in treating amblyopia and restoring stereoscopic function.
Purpose: Traumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON. Methods: We defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions. Results: The key results of validating this newly modified model, "controlled orbital impact (COI)," included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of naïve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare. Conclusions: Taken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.