Marc Dinkin

Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial.

Background: Our goal was to evaluate the safety and efficacy of stenting of venous sinus stenosis (VSS) in patients with medically-refractory, medically-intolerant or fulminant idiopathic intracranial hypertension (IIH) in a prospective, observational study. Methods: Thirteen patients with IIH who were refractory or intolerant to medical therapy or who presented with fulminant visual field (VF) loss underwent stenting of VSS at the transverse-sinus sigmoid sinus junction, using a Precise Pro carotid stent system (Cordis). Inclusion criteria included papilledema-related VF loss with mean deviation (MD) worse than or equal to −6.00 dB, elevated opening pressure (OP) on lumbar puncture (LP), VSS (either bilateral or unilateral in a dominant sinus), and an elevated (≥8 mm Hg) trans-stenotic gradient (TSG). The main outcome measures were pre- to post-stent change in symptoms related to intracranial hypertension, MD (in dB) on automated (Humphrey) VFs, grade of papilledema (1–5), retinal nerve fiber layer (RNFL) thickness as measured by spectral domain optical coherence tomography (SD-OCT), TSG (mm Hg), and OP on LP (cm H20). Results: Improvement or resolution of headaches occurred in 84.7% of patients, pulse-synchronous tinnitus in 100%, diplopia in 100%, and transient visual obscuration in 100%. Out of 26 eyes, 21 showed an improvement in MD, with an average improvement of +5.40 dB. Of 24 eyes with initial papilledema, 20 showed an improvement in Frisen grade, (mean change in grade of 1.90). Of 23 eyes undergoing SD-OCT, 21 (91.3%) demonstrated a reduction in RNFL thickness, with a poststent mean thickness of 90.48 &mgr;m. Mean change in OP was −20 cm H2O (reduction in mean from 42 to 22 cm H20) with all subjects demonstrating a reduction, although a second stenting procedure was necessary in one patient. Complications of the stenting procedure included one small, self-limited retroperitoneal hemorrhage, transient head or pelvic pain, and one allergic reaction to contrast. No serious adverse events occurred. Conclusions: Stenting of VSS is safe and results in reduction of intracranial pressure in patients with IIH. This is associated with improvement in papilledema, RNFL thickness, VF parameters, and symptoms associated with intracranial hypertension.

Diffusion-weighted magnetic resonance imaging of bilateral simultaneous optic nerve infarctions

AN 85-YEAR-OLD MAN presentedwithcomplete loss of vision. Duringtheweekprior topresentation,hereportedgraduallyprogressiveblurred anddarkvisioninbotheyeswithdramaticworseningonthedayofpresentation.Hehadnoothersymptoms,includingheadache.Hismedicalhistory was significant for hypertension and peripheral vascular disease. On examination, his blood pressure was elevated. There was no cranial artery tenderness. He was alert withintactlanguageandmemory.Visual acuity was light perception OU. Both pupils were 4 mm and nonreactive to light. Eye movements were normal,andcornealreflexeswereintactandsymmetric.Funduscopicexamination showed bilateral optic nerve head edema with right optic nervesectoralpallorandaleftmacularinfarction(Figure,AandB).The remainderoftheneurologicalexamination was normal. Magnetic resonanceimagingshowedrestricteddiffusion (Figure, C and D) with a reduced apparent diffusion coefficient signal (not shown) within the leftintraorbitalopticnerveandatthe right anterior optic nerve. The platelet count was 1134/µL, the erythrocytesedimentationratewas40mm/h, and the C-reactive protein level was 17.7 mg/L (to convert to nanomoles per liter, multiply by 9.524). COMMENT

Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus neoformans in an Immunocompetent Host

Cryptococcus spp is a common fungal infection and frequent cause of meningitis in immunocompromised patients; however, immunocompetent patients are also at risk of infection. Visual loss often occurs via elevated intracranial hypertension but can rarely occur through direct optic nerve, chiasm, or tract invasion. We report a case of a 38-year-old woman who presented with decreased acuity in both eyes. She had generalized visual field constriction in the right eye and temporal hemianopsia in the left eye. Magnetic resonance imaging of the brain and orbits showed multiple areas of ill-defined enhancement in the optic chiasm and tracts as well as in the diaphragmatic sella, prepontine and interpeduncular cisterns, and along cranial nerves VI, VII, and VIII bilaterally. Initial cerebrospinal fluid (CSF) showed 34 white blood cells, hypoglycorrhachia, and negative cryptococcal antigen and bacterial and fungal cultures. A transphenoidal biopsy of the dura and pituitary gland was unremarkable. Empiric steroids resulted in marked improvement in visual acuity in both eyes, but while tapering steroids, she developed rapid visual loss bilaterally. Repeat CSF performed 6 weeks later demonstrated a cryptococcal antigen titer of 1:512. Retroactive staining of the pituitary biopsy was positive for mucicarmine, a component of the polysaccharide capsule of Cryptococcus spp. After induction therapy with amphotericin B and flucytosine and 1 year of fluconazole, her visual acuity was 20/20 in both eyes. In summary, Cryptococcus can affect immunocompetent patients and often presents with insidious, chronic meningitis. Visual loss is common in cryptococcal meningitis but usually results from fulminant papilledema related to elevated intracranial pressure. In rare cases, direct nerve or chiasm infiltration by the fungus results in vision loss.

Unexpected late radiation neurotoxicity following bevacizumab use: a case series

The purpose of this case series is to report the unexpected occurrence of four cases of late radiation-induced neurotoxicity with bevacizumab use following radiotherapy to the CNS. We retrospectively reviewed the case records of four patients, three with glioblastoma and one with bone metastases secondary to metastatic breast cancer, who were treated with radiotherapy and developed late radiation-induced neurotoxicity following bevacizumab use. Three cases of optic neuropathy in glioblastoma patients and a single case of Brown-Séquard syndrome in the thoracic spine of a patient with metastatic breast cancer are reported. We hypothesize that bevacizumab use following radiotherapy to the CNS may inhibit vascular endothelial growth factor-dependent repair of normal neural tissue, and thus may increase the risk of late radiation neurotoxicity. Phase III data on the safety and efficacy of bevacizumab use with radiation in the setting of glioblastoma is awaited.

Corresponding Ganglion Cell Atrophy in Patients With Postgeniculate Homonymous Visual Field Loss.

Background: The goal of our study was to look for the presence of homonymous ganglion cell layer–inner plexiform layer complex (GCL-IPL) thinning using spectral-domain optical coherence tomography (SD-OCT) in patients with a history of adult-onset injury to the postgeniculate pathways with rigorous radiological exclusion of geniculate and pregeniculate pathology. Methods: We performed a retrospective review of twenty-two patients (ages 24–75 y, 6 men, 16 women) with homonymous visual field (VF) defects secondary to postgeniculate injury examining the GCL-IPL with SD-OCT. An additional fifteen patients (ages 28–85 y, 5 men, 10 women) with no visual pathway pathology served as controls. Using segmentation analysis software applied to the macular scan, a normalized asymmetry score was calculated for each eye comparing GCL-IPL thickness ipsilateral vs contralateral to the patients brain lesions. Results: We found that 15 of the twenty-two subjects had a relative thinning of the GCL-IPL ipsilateral to the postgeniculate lesion in both eyes (represented by a positive normalized asymmetry score in both eyes), whereas a similar pattern of right/left asymmetry was found in 4 controls (P = 0.0498). The magnitude of asymmetry was much greater in subjects compared with controls (P = 0.0004). There was no association between the degree of GCL-IPL thinning and the mean deviation on automated VF testing. A moderate correlation (R = 0.782, P = 0.004) between the magnitude of thinning and latency from onset of retrogeniculate injury was observed only after excluding patients beyond a cutoff point of 150 months. Conclusions: This data provides compelling new evidence of retrograde transsynaptic degeneration causing retinal ganglion cell loss after postgeniculate visual pathway injury.

Higher macular volume in patients with MS receiving fingolimod: Positive outcome or side effect?

In the evaluation of patients with multiple sclerosis (MS), optical coherence tomography (OCT) is gaining traction as a tool to assess thinning of the retinal nerve fiber layer (RNFL) and, more recently, for looking at total macular volume (TMV) thickness, with both measures used as potential biomarkers for progression of disease. In medicine, it is not uncommon for structural changes to be presumed to reflect a certain physiologic process, when in fact an alternative mechanism is at play. Fingolimod (FTY-720) is a sphingosine-1-phosphate receptor modulator that is an approved oral treatment for MS and leads to reduced cortical volume loss in patients with MS.1 Similar to other disease-modifying agents, it is likely to be judged in part by its ability to slow loss of the RNFL and TMV. But would such a judgment be valid?

Multifocal electroretinographic abnormalities in ethambutol-induced visual loss.

Two patients who developed decreased visual acuity after several months of ethambutol treatment for Mycobacterium avium-intracellulare infection had bitemporal visual field defects that suggested optic chiasm damage. Multifocal electroretinography (mfERG) disclosed markedly low-amplitude responses at fixation and in the regions corresponding to the visual field defects. These results suggested that the visual dysfunction might be entirely attributable to retinal rather than optic nerve toxicity. These are the first reported patients to show mfERG abnormalities that correspond to bitemporal visual field defects and add to the growing evidence that ethambutol damages the retina.

Venous Sinus Stenting for Idiopathic Intracranial Hypertension: Where Are We Now?

Idiopathic intracranial hypertension causes headache, papilledema and visual field loss, typically in obese women of childbearing age. Its anatomical underpinnings remain unclear, but a stenosis at the junction of the transverse and sigmoid sinuses has been recognized in the majority of patients through venography. The stenosis may result from intrinsic dural sinus anatomy or extrinsic compression by increased intracranial pressure, but in either case, its stenting has been shown to lead to an improvement in symptoms of intracranial hypertension and papilledema in multiple retrospective, non-controlled studies. Prospective, controlled trials are needed to confirm its efficacy and safety.

Abnormal eye movements in children.

The recognition and evaluation of abnormal eye movements in children is an essential task for the pediatric ophthalmologist that may lead to the discovery of systemic and neurologic disease and even preventable visual loss. With few exceptions, the eye movements discussed in this chapter can occur at all stages of life, but their presentation in infancy and childhood has a unique significance that merits their inclusion in this textbook on pediatric manifestations of ophthalmic disease. The first step in approaching abnormal eye movements is to categorize them into broad categories, such as ‘‘roving’’ eye movements that are commonly seen in patients who develop visual-impairment early in life, saccadic intrusions (see below), or the true forms of nystagmus. With a cursory examination, these manifestations of ocular motor pathology may be confused, but each has its own implications for diagnosis and management. Roving eye movements are very slow, large amplitude, and seemingly aimless movements of the eyes that are seen in patients who are severely blind early in life. Saccadic intrusions are relatively fast, conjugate eye movements of relatively small amplitude that often occur in short bursts or as single events. Saccadic intrusions may occur as back-andforth movements across the point of fixation (ie, ‘‘saccadic oscillations’’), or as equal amplitude movements off to one side and then back onto the point of fixation (ie, ‘‘square-wave jerks’’). For both types of saccadic intrusions, there is an almost imperceptible delay between one saccadic movement and the next (ie, intersaccadic interval). In distinction,

Trans-synaptic Retrograde Degeneration in the Human Visual System: Slow, Silent, and Real

Degeneration of neuron and axons following injury to cells with which they synapse is termed trans-synaptic degeneration. This phenomenon may be seen in postsynaptic neurons (anterograde) or in presynaptic neurons (retrograde). Retrograde trans-synaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer following injury to the occipital lobe has been well documented histologically in animal studies, but its occurrence in the human retina was, for many years, felt to be limited to cases of neonatal injury during a critical period of neuronal development. Over the last decade, imaging techniques such as MRI and optical coherence tomography have allowed us to visualize and quantify RTSD and analyze its time course and relationship to degree of vision loss and age of cortical injury. A deeper understanding of RTSD in the human visual system may allow us to interfere with its occurrence, potentially allowing for greater recovery following visual cortex injury.