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.

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.

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.

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.

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.

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.

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.)

Neuro-imaging: a review for the general ophthalmologist.

The diagnosis of many neuro-ophthalmic conditions is facilitated with neuro-imaging. The two main modalities are Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Clinicians who refer patients for either of these techniques must not only know which of them to choose, but also where the imaging should be performed (e.g. brain, orbit), whether or not contrast is indicated, and if angiography should be supplemented. These complexities often result in imaging studies that are either unneeded or unhelpful. The goal of this manuscript is to provide a practical set of guidelines for the general ophthalmologist of how to choose the correct parameters for neuro-imaging studies.

Dorsal midbrain syndrome from a ring-enhancing lesion.

A ring-enhancing lesion is an uncommon cause of a dorsal midbrain syndrome. Here, we describe the case of a 60-year-old man with eye movement and pupillary findings consistent with dorsal midbrain syndrome, and in whom neuroimaging showed a single ring-enhancing lesion in the right midbrain and thalamus. Further investigation revealed a longstanding right groin mass which proved to be a malignant melanoma. His intracranial lesion was presumed to be a metastatic lesion, and treated with stereotactic radiosurgery. We report the patient's clinical course, and discuss the diagnosis and management of the solitary midbrain lesion.

Syphilis and the monk.

Primary orbital aspergillus infection may occur in immunocompetent individuals. It frequently represents a diagnostic challenge for clinicians due to nonspecific clinical presentations and neuroimaging signs. We present a 47-year-old otherwise healthy man with an isolated unilateral optic neuropathy secondary to primary orbital aspergillosis. He had a remote history of tuberculosis and positive syphilis serologies. After he worsened despite intravenous penicillin therapy, a biopsy showed chronic inflammation. Corticosteroids treatment was followed by further deterioration of his clinical condition. Finally, a repeat biopsy revealed the aspergillus infection. Despite antifungal therapy, the outcome was unfavorable. A high index of suspicion should result in aggressive diagnostic testing and prompt institution of antifungal therapy in patients with primary orbital aspergillosis.

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.

Visual outcome and tumor control after conformal radiotherapy for patients with optic nerve sheath meningioma.

PURPOSE: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost uniformly leads to visual dysfunction and even blindness without intervention. Because surgical extirpation carries a high risk of postoperative blindness, vision-sparing treatment strategies are desirable. METHODS AND MATERIALS: We retrospectively reviewed the outcomes of 25 patients (25 optic nerves) with ONSM, treated at a single institution with conformal fractionated radiotherapy by either stereotactic photon or proton radiation. Primary endpoints were local control and visual acuity. RESULTS: The patients presented with symptoms of visual loss (21) or orbital pain (3) or were incidentally diagnosed by imaging (3). The mean age was 44 years, and 64% were female patients. The indication for treatment was the development or progression of symptoms. Of the patients, 13 were treated with photons, 9 were treated with protons, and 3 received a combination of photons and protons. The median dose delivered was 50.4 gray equivalents (range, 45-59.4 gray equivalents). Median follow-up after radiotherapy was 30 months (range, 3-168 months), with 3 patients lost to follow-up. At most recent follow-up, 21 of 22 patients (95%) had improved (14) or stable (7) visual acuity. One patient had worsened visual acuity after initial postirradiation improvement. Of the 22 patients, 20 (95%) had no radiographic progression. Three patients had evidence of asymptomatic, limited retinopathy on ophthalmologic examination, and one had recurrent ONSM 11 years after treatment. CONCLUSIONS: Highly conformal, fractionated radiation therapy for symptomatic primary ONSM provides tumor control and improvement in visual function in most cases, with minimal treatment-induced morbidity. Longer follow-up is needed to assess the durability of tumor control and treatment-related late effects.

Angiogenesis and pituitary tumors.

Pituitary adenomas often first manifest through visual symptoms. They are typically slow-growing and histologically benign tumors, but can become clinically destructive, invade adjacent structures, and recur after treatment. Unlike many other tumors that become aggressive and appear to depend upon angiogenesis in the process, pituitary adenomas tend to do so through non-angiogenic means. This article examines the role of angiogenesis in pituitary adenomas.

Recurrent isolated sixth nerve palsy after consecutive annual influenza vaccinations in a child.

Recurrent sixth nerve palsy in children in the absence of structural or other neurological abnormality is a rare occurrence. We report the case of recurrent isolated sixth (abducens) nerve palsy after consecutive annual influenza vaccinations in an otherwise-healthy 2-year-old boy. Investigations including magnetic resonance imaging of the brain and orbits after each episode failed to reveal any abnormality. The temporal relation to the immunizations supports but does not prove that the influenza immunization regimen was responsible.