Collin M. McClelland

Leber hereditary optic neuropathy: current perspectives

Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.

Periorbital edema secondary to imatinib mesylate

Imatinib mesylate (Gleevec®) is a well-established pharmacologic treatment for all phases of chronic myeloid leukemia and for advanced gastrointestinal stromal tumors (GISTs). Edema-related side effects are relatively common in imatinib therapy with the periocular skin representing one of the most common sites for localized edema. While the adverse effect of periorbital edema with imatinib is well documented in the oncology literature, there is limited reference to this common reaction in the ophthalmology literature. We report two patients with upper eyelid edema associated with imatinib therapy who required surgical intervention to ameliorate significant visual field obstruction. We highlight the details of each case including the histopathologic findings of excised redundant skin followed by a thorough review of the literature on imatinib related periorbital edema.

Leber hereditary optic neuropathy mimicking neuromyelitis optica.

Leber hereditary optic neuropathy (LHON) is rarely associated with multiple sclerosis-like features. We present a case of a 65-year-old African American woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the features of the clinical examination and MRI that were suggestive of an alternative diagnosis and review the literature regarding LHON and multiple sclerosis. The diagnosis of LHON should be considered in all cases of acute or subacute bilateral optic neuropathy, including presumed seronegative NMO.

Neuroimaging in Patients Referred to a Neuro-ophthalmology Service: The Rates of Appropriateness and Concordance in Interpretation

OBJECTIVE Neuroimaging studies frequently are ordered to investigate neuro-ophthalmic symptoms. When misused, these studies are expensive and time consuming. This study describes the type and frequency of neuroimaging errors in patients referred to an academic neuro-ophthalmology service and measures how frequently these neuroimaging studies were reinterpreted. DESIGN Prospective cohort study. PARTICIPANTS Eighty-four consecutive patients referred to an academic neuro-ophthalmology practice. METHODS From November 2009 through July 2010, 84 consecutive new patients who had undergone a neuroimaging study in the last 12 months specifically to evaluate their presenting neuro-ophthalmic symptoms were enrolled prospectively. Participants then underwent a complete neuro-ophthalmic evaluation, followed by a review of prior neuroimaging. Questions regarding appropriateness of the most recent imaging, concordance of radiologic interpretation, and re-evaluation of referring diagnoses were answered by the attending physician. MAIN OUTCOME MEASURES The frequency and types of errors committed in the use of neuroimaging and the frequency of reinterpretation of prereferral neuroimaging studies after neuro-ophthalmic history and examination. RESULTS Most study participants (84.5%; 71/84) underwent magnetic resonance imaging before referral; 15.5% (13/84) underwent only computed tomography. The rate of suboptimal neuroimaging studies was 38.1% (32/84). The 3 most common reasons for suboptimal studies were incomplete area of imaging (34.4%; 11/32), wrong study type (28.1%; 9/32), and poor image quality (21.9%; 7/32). Twenty-four of 84 subjects (28.6%) required additional neuroimaging. The authors agreed with the radiology interpretation of the prior neuroimaging studies in most patients (77.4%; 65/84). The most common anatomic locations for discordance in interpretation were the intraorbital optic nerve (35%; 7/20) and the brainstem (20%; 4/20). CONCLUSIONS There was a high rate of suboptimal neuroimaging studies performed in patients referred for neuro-ophthalmology examination. These findings have significant implications given the increasing attention to resource use currently and in the near future.

Optic perineuritis as the presenting feature of Crohn disease.

Crohn disease (CD) is primarily considered an inflammatory condition of the small and large intestine although associated extraintestinal inflammation is relatively common. Ocular manifestations are generally localized to the anterior chamber and ocular surface but rarely can involve the posterior pole, orbit, and optic nerve. We report a case of an otherwise healthy 42-year-old man who was diagnosed with CD after presenting with acute vision loss from optic perineuritis.

Progressive External Ophthalmoplegia

Progressive external ophthalmoplegia (PEO), marked by progressive bilateral ptosis and diffuse reduction in ocular motility, represents a finding of mitochondrial myopathy rather than a true diagnosis. PEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality. Accurate and early recognition of PEO is paramount for the optimal care of these patients. We present an evidence-based review of the presenting neuro-ophthalmic features, differential diagnosis, diagnostic tools, systemic implications, and treatment options for isolated PEO and other PEO-associated mitochondrial syndromes.

The long-term outcomes of ocular tics in a pediatric neuro-ophthalmology practice

PURPOSE To describe the outcome and comorbidities of ocular tics in children evaluated by a pediatric neuro-ophthalmologist. METHODS The medical records of all consecutive patients in a pediatric neuro-ophthalmology practice diagnosed with ocular tics (eye rolling, blinking, and widening) were retrospectively reviewed. Children with known secondary causes for tics were excluded. Patients, parents, and/or guardians were contacted by telephone to obtain follow-up information. RESULTS A total of 43 patients were included in the retrospective cohort, with a mean age of 7.8 ± 4.8 years at diagnosis. Thirty-two patients participated in the follow-up survey, with an average follow-up of 6.1 ± 3.9 years. None of the 43 children carried a diagnosis of Tourette syndrome or obsessive-compulsive disorder (OCD) at presentation; 1 child had attention deficit hyperactivity disorder (ADHD). At follow-up, 14 of the 32 children (44%) had persistent ocular tics, 3 (9%) reported new nonocular motor tics, 5 (16%) reported new vocal tics, and 4 (13%) developed both nonocular motor and vocal tics. One patient (3%) was formally diagnosed with Tourette syndrome during the follow-up interval, and 3 (9%) were diagnosed with ADHD. CONCLUSIONS Almost half of the children with ocular tics at presentation had persistent ocular tics on follow-up. New nonocular motor and vocal tics occurred in several patients.

Primary adenoid cystic carcinoma of the orbital apex

Adenoid cystic carcinoma is an uncommon malignant tumor of epithelial origin typically arising from salivary glands. Orbital involvement may occur via direct or perineural spread from a lacrimal gland or sinonasal source. Primary orbital adenoid cystic carcinoma without involvement of the lacrimal gland is rare. The authors report a 53-year-old woman who was examined for insidious monocular vision loss and was found to have a primary adenoid cystic carcinoma of the orbital apex and cavernous sinus. Systemic workup for a primary source, including ipsilateral lacrimal gland biopsy, was negative. One must maintain a high index of suspicion for adenoid cystic carcinoma when evaluating orbital tumors.

Congenital mydriasis associated with megacystis microcolon intestinal hypoperistalsis syndrome.

We report a case of congenital mydriasis in a neonate with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS). Pilocarpine testing and gastrointestinal pathology in our patient suggest that the mydriasis is due to an underlying smooth muscle myopathy of the iris sphincter muscle. These findings may have important implications regarding the pathogenesis of MMIHS.

Incidence and Causes of Overdiagnosis of Optic Neuritis

Importance Diagnostic error is an important source of medical error. Overdiagnosis of optic neuritis may prompt unnecessary and costly diagnostic tests, procedures, and treatments. Objective To assess the incidence of and characterize factors contributing to overdiagnosis of acute optic neuritis. Design, Setting, and Participants In this retrospective clinic-based cross-sectional study of new patient encounters, 122 patients referred for acute optic neuritis at a university-based Midwestern neuro-ophthalmology clinic between January 2014 and October 2016 were studied. Data were analyzed from September 2016 to July 2017. Interventions Definite diagnosis was determined by neuro-ophthalmologists. For patients with alterative diagnoses, the Diagnosis Error Evaluation and Research taxonomy tool was applied to categorize the type of diagnostic error. Main Outcomes and Measures The primary outcome was the primary type of diagnostic error in patients erroneously diagnosed as having optic neuritis. Secondary outcomes included final diagnosis and interventions undergone prior to referral. Results A total of 122 patients were referred with acute optic neuritis during the study period; 88 (72.1%) were female, and the mean (SD) age was 42.6 (14.0) years. Of these, 49 patients (40.2%; 95% CI, 31.4-49.4) were confirmed to have optic neuritis, and 73 (59.8%; 95% CI, 50.6-68.6) had an alternative diagnosis. The most common alternative diagnoses were headache and eye pain, functional visual loss, and other optic neuropathies, particularly nonarteritic anterior ischemic optic neuropathy. The most common diagnostic error was eliciting or interpreting critical elements of history, which occurred in 24 of 73 patients (33%) with alternative diagnoses. Other common errors included errors weighing or considering alternative diagnoses (23 patients [32%]), errors weighing or interpreting physical examination findings (15 patients [21%]), and misinterpreting diagnostic test results (11 patients [15%]). In patients with alterative diagnoses, 12 (16%) had normal magnetic resonance imaging findings preceding the referral, 12 (16%) had received a lumbar puncture, and 8 (11%) had received unnecessary treatment with intravenous steroids. Conclusions and Relevance These data suggest that nearly 60% (95% CI, 50.6-68.6) of patients referred for optic neuritis have an alternative diagnosis, with the most common errors being overreliance on a single item of history and failure to consider alternative diagnoses. Understanding pitfalls leading to overdiagnosis of optic neuritis may improve clinicians’ diagnostic process.