Tacrolimus Optic Neuropathy.

BACKGROUND: Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. METHODS: Case series and review of the literature. RESULTS: We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. CONCLUSIONS: Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.

Early Diagnosis of Subclinical Interferon Alpha-Associated Optic Neuropathy Using Fluorescein Angiography.

We report a case of a 57-year-old man who presented with decreased visual acuity in the left eye secondary to nonarteritic anterior ischemic optic neuropathy (NAION) while on therapy with interferon-α for hepatitis C. Fundus fluorescein angiography revealed late leakage of both optic discs, consistent with bilateral disease. One week later, the patient developed clinical signs and symptoms consistent with NAION in the fellow eye. Fluorescein angiography may play an important role in identifying subclinical NAION in patients taking interferon-α.

Idiopathic opticochiasmatic arachnoiditis.

: A critical review of the literature indicates that idiopathic opticochiasmatic arachnoiditis, once considered an important consideration in patients with otherwise unexplained optic atrophy, is not a valid disease entity.

Monocular nasal hemianopia from atypical sphenoid wing meningioma.

Neurogenic monocular nasal field defects respecting the vertical midline are quite uncommon. We report a case of a unilateral nasal hemianopia that was caused by compression of the left optic nerve by a sphenoid wing meningioma. Histological examination revealed that the pathology of the meningioma was consistent with that of an atypical meningioma, which carries a guarded prognosis with increased chance of recurrence. The tumor was debulked surgically, and the patient's visual field defect improved.

Radiation tolerance of the optic pathway in patients treated with proton and photon radiotherapy.

INTRODUCTION: Radiation-induced optic neuropathy (RION) is a complication of radiation therapy (RT) that causes blindness. We aimed to define the tolerance of the anterior optic pathway to fractionated RT and identify risk factors for RION. MATERIALS/METHODS: Patients with chordoma or chondrosarcoma of the skull base treated with proton and photon therapy between 1983 and 2013, who received a minimum of 30 Gy (relative biologic effectiveness [RBE]) to the anterior optic pathway were assessed. Optic neuropathy with radiographic correlation occurring ≥6 months after completion of RT in the absence of tumor recurrence or other probable cause was diagnosed as RION. RESULTS: Of 514 patients, 17 developed RION. With median follow-up of 4.8 years, cumulative incidence of RION was 1% among patients receiving <59 Gy (RBE) and 5.8% among patients receiving ≥60 Gy (RBE) to the optic pathway. Higher maximum point dose to the optic pathway (subhazard ratio [SHR] = 1.2, 95% CI 1.05-1.2, p = 0.001), older age (SHR = 1.1, 95% CI 1.02-1.08, p < 0.0005), and female sex (SHR = 16.3, 95% CI 2.2-122.4, p = 0.007) were statistically significant risk factors for RION in multivariate analysis. CONCLUSION: In our study cohort, rates of RION were very low with conventionally fractionated RT up to 59 Gy. At doses ≥60 Gy, there is an increased risk of RION, with greater risk for women and older patients.

Optic neuropathy after epi-LASIK.

PURPOSE: To report a case of optic neuropathy after epi-LASIK. METHODS: A 24-year-old man developed optic neuropathy after epi-LASIK, possibly related to the barotrauma created by the suction ring. Optic neuropathy and steroid-induced ocular hypertension were diagnosed. Prednisolone drops were discontinued and timolol was started. RESULTS: After 2 weeks, his symptoms improved and the pain resolved. CONCLUSIONS: Optic neuropathy is a potentially vision-threatening complication of epi-LASIK. Barotrauma from a transient increase in intraocular pressure created by the suction ring can be an important factor in this entity.

Ocular pathologic findings of neurofibromatosis type 2.

OBJECTIVE: To gain insight into the pathogenesis of neurofibromatosis type 2 (NF2) by investigating the ocular manifestations of this disease. METHODS: Using standard histologic techniques, immunohistochemistry, and electron microscopy, we described the ocular pathologic findings of a 34-year-old woman who died from complications of NF2. RESULTS: We identified 3 types of NF2-associated lesions: juvenile posterior subcapsular cataracts, epiretinal membranes, and an intrascleral schwannoma. CONCLUSIONS: Our analysis indicated that dysplastic lens cells accumulate just anterior to the posterior lens capsule in juvenile posterior subcapsular cataracts and that dysplastic Müller cells may be a major component of NF2-associated epiretinal membranes. Clinical Relevance Our findings suggest that a subset of glial cells with epithelial features (Schwann cells, ependymal cells, and Müller cells) may be particularly sensitive to loss of the NF2 gene. Understanding the molecular basis for this sensitivity may lead to novel strategies for treating NF2.

Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons.

PURPOSE: To investigate the visual outcomes of patients with advanced sinonasal malignancies treated with proton/photon accelerated fractionated radiation (AFR). PATIENTS AND METHODS: Between 1991 and 2001, AFR was used to treat 36 patients with advanced stage primary (n=33) or recurrent (n=3) nasal or paranasal malignant tumors. Full ophthalmologic follow-up was documented. The median dose to the gross tumor volume (GTV) was 69.6 CGE (range 60.8-77). Visual complications were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) and the late effects of normal tissue (LENT) scoring systems. The median follow-up was 52.4 months (range 17-122.8). RESULTS: Thirteen patients developed late visual/ocular toxicity. Cataracts were LENT grade 1 and 3 in 2 patients and 1 patient, respectively. One LENT grade 1 vascular retinopathy and 1 optic neuropathy were also observed. Three and five patients presented with nasolacrimal duct stenosis (CTC grade 2, 2 patients; CTC grade 3, 1 patient) and dry-eye syndrome (CTC grade 1, 1 patient; CTC grade 2, 4 patients), respectively. The 3- and 5-year probability of LENT/CTC grade > or =2 visual toxicity were 15.8+/-6.7% and 20.7+/-7.8%, respectively. CONCLUSIONS: AFR for locally advanced nasal cavity and paranasal sinus tumors enables delivery of 70 CGE to the tumor with acceptable ophthalmologic complications.

Anterior visual pathway gliomas: The last 30 years.

Modern neuroimaging provides excellent characterization of anterior visual pathway gliomas, often obviating the need for biopsy of the tumor. Management remains controversial, but if there is progression, chemotherapy is preferred for young patients. Stereotactically guided conformal radiotherapy and proton beam radiotherapy allow smaller, more precise doses of radiation to be administered and can be considered in older children with progressive disease. A mouse model of NF-1 with optic pathway gliomas has the potential to provide important insights into the development of gliomas as well as serving as a model for their effective treatment.

Leber Hereditary Optic Neuropathy: Bringing the Lab to the Clinic.

Leber hereditary optic neuropathy (LHON) was the first clinically characterized mitochondrial disorder. Since its first description in 1871, much has been discovered regarding the genetics and pathophysiology of the disease. This has enabled the development of in vitro cell and animal models that can be used to try to determine not only the effects of the genetic mutation upon the clinical phenotype but to also test potential novel therapies. Treatments for LHON have ranged from vitamins and minerals to immunosuppressants and, more recently, targeted gene therapy. This article reviews the pathophysiology and clinical features of LHON with a focus on translational research.

Idiopathic repetitive oculomotor nerve palsies in otherwise normal patients.

OBJECTIVE: To describe a unique idiopathic disorder characterized by transient repetitive unilateral oculomotor pareses. DESIGN: Retrospective observational case series. PARTICIPANTS: Three women presenting for tertiary neuro-ophthalmologic evaluation. METHODS: Review of patient records. MAIN OUTCOME MEASURES: Historical information, clinical examination, neuroimaging, and laboratory evaluation for myasthenia gravis. RESULTS: Three 44- to 69-year-old women had recurrent unilateral ptosis over the course of 2 to 4 years. Two had concurrent diplopia with ipsilateral limitation of adduction, and 2 also had a large poorly reactive pupil in the involved eye during the episodes. The attacks lasted between 30 seconds and 4 hours and occurred up to 6 times daily. None of the patients were migraineurs, nor had they received radiation therapy. Neuro-ophthalmologically normal between episodes, all patients had normal magnetic resonance imaging/angiography and testing for myasthenia gravis. CONCLUSION: Transient, recurrent, unilateral oculomotor nerve palsies may occur spontaneously in healthy individuals. The pathogenesis remains obscure, but the multiple recurrences without evident sequelae and the failure to develop any systemic or neurological disorder suggest that this phenomenon is not indicative of a serious underlying disorder.

Delayed visual decline in patients with "stable" optic neuropathy.

BACKGROUND: Histological studies on the human optic nerve have documented decreasing axonal nerve fiber counts with age. In patients with optic atrophy, a nonpathological dropout of ganglion cell axons as part of the normal aging process may become clinically significant. OBJECTIVE: To describe the occurrence of delayed visual loss in patients with presumably "stable" optic neuropathy. METHODS: We reviewed the medical records of 3 patients who experienced slowly progressive visual loss in adulthood after suffering childhood optic nerve injury. RESULTS: All 3 patients had a monophasic illness in childhood that caused bilateral optic atrophy and visual impairment. Following decades of stability, each suffered a gradual, symptomatic visual decline that extended over years. No new ophthalmologic, systemic, or neurologic disorder was found that explained the visual decline in any of these patients. CONCLUSION: We hypothesize that the late visual decline in these 3 patients resulted from deleterious effects of age-related axonal loss on an already depleted population of neurons.

A rod-sparing retinopathy in bardet-biedl syndrome.

Bardet-Biedl syndrome is a continuum of disorders characterized by systemic and ocular findings. Retinal abnormalities typically present as diffuse photoreceptor degeneration. Here, we report a novel case that suggests a rod-sparing variant of Bardet-Biedl syndrome.

Orbital myositis posing as cluster headache.

OBJECTIVE: To describe the case of a patient with recurrent orbital myositis who was thought to have cluster headaches for 6 years. DESIGN AND SETTING: Case report in an outpatient neuro-ophthalmology clinic. PATIENT: A 24-year-old man developed unilateral supraorbital pain, lacrimation, conjunctival hyperemia, nasal congestion, proptosis, and painful eye movements. The pain intensity varied over the course of each day and disappeared after 1 month. He had multiple attacks responsive to prednisone that were separated by months over the ensuing 6 years. Neuroimaging revealed an enlarged extraocular muscle. CONCLUSIONS: Overlap in symptoms between recurrent orbital myositis and cluster headache delayed the diagnosis in this patient. Orbital myositis should be considered in patients with atypical cluster headache characterized by proptosis, painful eye movements, and pain that does not completely resolve after 3 hours.

A contribution to the natural history of optic nerve sheath meningiomas.

OBJECTIVE: To describe the natural history of patients with primary optic nerve sheath meningioma (ONSM) who were cared for without intervention. METHODS: A retrospective review of the medical records of 42 patients identified in the database of an academic neuro-ophthalmology unit who had been diagnosed with a unilateral ONSM. Twenty-five had been referred after treatment had been implemented, and 1 was blind at referral. The remaining 16 patients who were followed up with observation only are the focus of this study. RESULTS: The study subjects were followed up for a mean of 6.2 years (range, 2-18 years). The mean follow-up from the time of the first symptom was 10.2 years (range, 3-28 years). No patient died or incurred neurological deficits other than vision loss. At diagnosis, 12 of 16 had a visual acuity of 20/100 or better; 11 had a visual acuity of 20/30 or better. At follow-up, 8 of 16 had a visual acuity of 20/100 or better; 6 had a visual acuity of 20/30 or better. Three patients had slight improvement. Visual fields remained stable in 4 patients and improved in the 3 patients whose visual acuity also improved. CONCLUSIONS: Some patients with ONSM have a stable course for many years, and a few may even show slight improvement. The routine application of radiation therapy may unnecessarily expose some patients to complications and should be reserved for those patients whose visual function declines under observation.

Ehrlichiosis optic neuritis.

PURPOSE: To describe a case of ehrlichiosis optic neuritis. DESIGN: Single observational case report. METHODS: A 41-year-old woman with symptoms and clinical and imaging signs consistent with optic neuritis presented to a tertiary care academic center for comprehensive neuro-ophthalmic evaluation. Main outcome measures included preoptic and postoptic neuritis polyvalent ehrlichiosis titers and magnetic resonance imaging (MRI) of orbits with gadolinium. RESULTS: Ehrlichiosis titers drawn 11 days before onset of eye symptoms were negative. Titers drawn 7 days after symptoms began were positive. The optic nerve enhanced with gadolinium on MRI. CONCLUSIONS: Ehrlichiosis can cause optic neuritis and should be considered in patients with optic neuritis after a febrile, flu-like illness in an endemic area.

Neuro-ophthalmologic complications of cataract surgery.

Neuro-ophthalmologic complications from cataract surgery are uncommon and include central nervous system toxicity, binocular diplopia, traumatic optic neuropathy and ischemic optic neuropathy. Retrobulbar blocks may be accidentally injected into the subarachnoid space with diffusion to the brainstem. This leads to cardiovascular, respiratory, and mental status compromise. Most patients have complete recovery with adequate support. Post-operative, binocular diplopia may occur secondary to anisometropia or previously unrecognized misalignment. Periocular injection may cause paresis or fibrosis of extraocular muscles. Anterior or posterior ischemic optic neuropathy can occur in the first 6 weeks after cataract surgery with or without periocular injection. The risk to the other eye is high with subsequent contralateral cataract extraction. Post-operative vision loss associated with direct traumatic needle injury is recognized immediately. Therefore, an orbital MRI may be warranted for a patient with an optic neuropathy in the first 24 hours after cataract surgery using periocular anesthesia. If evidence of needle injury is present on neuroimaging, a trial of steroids should be considered.

Teaching video neuroimages: pulsatile proptosis.

A 44-year-old man with neurofibromatosis type 1 had been aware that his right eye pulsated. His visual acuity was 20/15 in both eyes and his intraocular pressures were normal. He had 4 mm of right exophthalmos and there was pulse-synchronous pulsation of the right eye (video on the Neurology® Web site at www.neurology.org). No bruit was heard. Lisch nodules were present on both irides. CT showed a large osseous defect of the greater wing of the right sphenoid bone. The differential diagnosis of pulsatile proptosis includes absence of the sphenoid wing in patients with neurofibromatosis 1,(1) carotid-cavernous fistula, orbital roof fractures, and arteriovenous malformations.(2.)