Cranial Nerve Palsies in the Setting of Arachnoid Cysts: A Case Series and Literature Review.

BACKGROUND: Arachnoid cysts (ACs) are benign lesions typically believed to not cause neurologic defects in the adult population and are most often found incidentally on imaging. We describe 2 patients with ACs potentially leading to isolated cranial nerve (CN) dysfunction. METHODS: We describe 2 patients, 1 with a fourth nerve palsy and the other with a sixth nerve palsy found to have ACs on MRI brain imaging in locations that potentially caused a compressive CN palsy. We review previous literature of ACs presenting with CN III, IV, or VI palsy. RESULTS: Patient 1 was a 62-year-old man who presented with a 22-year history of diplopia with strabismus examination consistent with a congenital CN IV palsy. Despite multiple surgeries, his CN IV palsy insidiously worsened. An AC in the posterior fossa with mass effect on the quadrigeminal plate and asymmetric atrophy of the right superior oblique was identified on imaging. Patient 2 was an 80-year-old man who presented with an 18-year history of diplopia and was found to have a left esotropia and abduction deficit consistent with complete CN VI palsy. An AC in the left cavernous sinus was identified on imaging. He underwent strabismus surgery with satisfactory resolution of diplopia. We identified a total of 18 previously published cases: 8 reports of CN III palsy, 4 reports of CN IV palsy, and 6 reports of CN VI palsy. Patient ages ranged from 1 to 67 with a median of 34.5. In 16/18 (89%) cases, the diagnosis of ACs was made within 1 year of symptom onset. Surgical removal of the AC was successful in resolving diplopia in 7/12 (58%) cases. In no case was strabismus surgery performed as primary treatment. CONCLUSIONS: Although ACs are typically congenital asymptomatic lesions, we present a case series of 2 patients with ACs in anatomic locations that potentially caused chronic, progressive, isolated CN palsies leading to strabismus. Our literature review revealed that most published cases detailing this clinical scenario resulted in neurosurgical fenestration of ACs with mixed results. Our cases represent 2 patients with AC-associated CN palsy treated with strabismus surgery.

A Tale of Progressive Painless Vision Loss in a 64-Year-Old Man Due to Leber Hereditary Optic Neuropathy.

ABSTRACT: A 64-year-old man presented with painless sequential bilateral vision loss, consistent with optic neuropathy, over the span of months. The significant decline in his visual function was out of proportion to the appearance of the optic nerves (which were not pale) or changes in his retinal nerve fiber layer thickness on optical coherence tomography. Neuroimaging revealed only mild T2 signal abnormality and faint enhancement in the left optic nerve. Extensive workup for potential infectious, metabolic, inflammatory, and ischemic etiologies was unremarkable. Empiric treatment with intravenous steroids did not slow or ameliorate the vision loss. Ultimately, genetic analysis revealed a missense m.11778G>A mutation in mitochondrial MT-ND4 gene, consistent with Leber hereditary optic neuropathy. Initiation of multivitamin supplements and idebenone unfortunately did not result in recovery of vision.

Retinal disease in the neurology clinic.

PURPOSE OF REVIEW: Retinal disease can manifest with visual symptoms similar to those which result from central nervous system disorders. We provide a framework for considering retinal causes of common visual complaints presenting to a neurology clinic. RECENT FINDINGS: Technological advances have afforded quicker detection and a more thorough understanding of these retinal entities and are crucial to consider when evaluating visual complaints in the neurology clinic. SUMMARY: It is essential to maintain a working knowledge of common retinal conditions that symptomatically overlap with common neurologic conditions. Furthermore, the ophthalmoscopic exam and retinal imaging modalities can both aid in the diagnosis and workup of visual complaints and neurologic disease.

Automated Pupillometry as an Adjunct to Clinical Examination in Patients With Acute Vision Loss.

BACKGROUND: Despite automated pupillometry's (AP) improved detection of relative afferent pupillary defects (RAPDs) compared with the Swinging Flashlight Test (SFT), AP remains uncommon in clinical practice. This study examined barriers to routine use of AP in evaluation of acute vision loss. METHODS: (1) Ophthalmologists and optometrists' perceptions of AP were captured via electronic survey. (2) Ophthalmologists were presented with clinical vignettes to assess their use of AP in clinical decision-making. (3) Patients presenting with decreased vision to an ophthalmology urgent care clinic underwent manual SFT and AP screening to evaluate ophthalmologists' perceptions of the device. RESULTS: Surveys indicated that clinicians were "neutral" to "somewhat likely" to use AP. In clinical vignettes, more physicians proceeded with workup for optic nerve pathology when presented with an RAPD by AP than SFT (77% vs 26%, P = 0.003). When SFT and AP results were discordant, more physicians proceeded with workup for optic nerve disease when AP was positive and SFT was negative than vice versa (61% vs 18%, P = 0.008). In the clinical study of 21 patients, 50% of RAPDs detected by AP were not detected by SFT, although ophthalmologists rated AP's usefulness as only "neutral" to "somewhat useful." CONCLUSION: Clinicians value pupillary examination and trust AP over SFT; however, widespread adoption and perceived value of AP may depend on its impact on clinical outcomes. Within a comprehensive diagnostic device, AP may be an important tool, but is not necessary to screen for optic nerve disease or evaluate acute vision loss.

Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort.

PURPOSE: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants. METHODS: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions. RESULTS: Analyses of age group differences revealed that participants 12-21 years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18 years old had a slower maximum constriction velocity than participants 6-11 years old, with no sex differences (ps < 0.05). Furthermore, males aged 12-18 years old had a smaller percent constriction than males 6-11 years old (ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically. CONCLUSIONS: Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

Orbital ultrasonography in the diagnosis of neoplastic extraocular muscle enlargement.

Neoplastic infiltration of the extraocular muscle (EOM) is a rare condition which can pose a diagnostic dilemma due to its rarity and overlapping ultrasonographic features with orbital myositis. The ultrasonographic features of neoplastic enlargement of EOM have not been systematically studied and previously have been described in only a few case reports. Orbital ultrasonography, in conjunction with the pattern of ocular misalignment, was assessed for its potential role in identifying patients with neoplastic EOM enlargement. Retrospective chart review of patients with neoplasm and myositis. The clinical features of 8 patients with neoplastic infiltration of the EOM were compared to 15 patients with myositis. In the neoplastic group the width of the EOM was (10.5 mm) almost twice the normal width of the muscle with myositis (p < 0.001). All the muscles in the neoplastic category were low to medium reflective. Paretic deviation was seen in 4/8(50%), purely restrictive in 2/8 (25%) and combined pattern in 2/8 (25%) were noted. In the myositis group the average EOM enlargement was 5.8 mm and all muscles showed low reflectivity. Although ultrasonographic features overlapped between the 2 groups paretic deviations were more common in the neoplastic group versus the myositis group (50% versus 7%). Neoplastic muscle enlargement tends to be larger with paretic deviations of ocular motility seen clinically. These findings in a patient with EOM enlargement should raise the suspicion of neoplasm as the etiology and further work up should be considered.

Integrating the Internship into Ophthalmology Residency Programs: Association of University Professors of Ophthalmology American Academy of Ophthalmology White Paper.

Future ophthalmologists will need to have broad skills to thrive in complex health care organizations. However, training for ophthalmologists does not take advantage of all of the postgraduate years (PGYs). Although the traditional residency years seem to have little excess capacity, enhancing the internship year does offer an opportunity to expand the time for ophthalmology training in the same 4 PGYs. Integrating the internship year into residency would allow control of all of the PGYs, allowing our profession to optimize training for ophthalmology. In this white paper, we propose that we could capture an additional 6 months of training time by integrating basic ophthalmology training into the intern year. This would allow 6 additional months to expand training in areas such as quality improvement or time for "mini-fellowships" to allow graduates to develop a deeper set of skills.

Management of acute cranial nerve 3, 4 and 6 palsies: role of neuroimaging.

PURPOSE OF REVIEW: This article will discuss the management of isolated, acute cranial nerve 3,4 and 6 palsies with special focus on the role of neuroimaging in older adults based on recently published data. RECENT FINDINGS: Acute cranial nerve palsies affecting the third, fourth or sixth cranial nerves in isolation or in combination with other neurological signs and symptoms can be due to a variety of causes such as ischemia, inflammation, infection and compression of the ocular motor nerves. Although neuroimaging is generally recommended in all individuals presenting with ocular motor nerve palsies that occur in association with other neurological signs and symptoms, the indications for neuroimaging in older individuals (age > 50 years) who present with acute isolated ocular motor nerve palsies are less clear and controversial. Past and recent studies have attempted to address this question. A recent prospective study found that overall 16.5% of adult patients presenting with acute ocular motor mononeuropathy had structural lesions on MRI scan and 4.6% with fourth and sixth nerve palsies and no risk factors were found to have positive MRI scans. SUMMARY: On the basis of recently published data, we recommend contrast-enhanced MRI for all patients presenting with acute, isolated ocular motor mononeuropathies irrespective of age. Studies have clearly shown a small but significant prevalence of important findings in this group of patients thus favoring neuroimaging at the time of diagnosis.

Isolated third, fourth, and sixth cranial nerve palsies from presumed microvascular versus other causes: a prospective study.

PURPOSE: To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes. DESIGN: Prospective, multicenter, observational case series. PARTICIPANTS: A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy. TESTING: Magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES: Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment. RESULTS: Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64). CONCLUSIONS: In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present.

Long-Term Results of Optic Nerve Sheath Fenestration for Idiopathic Intracranial Hypertension: Earlier Intervention Favours Improved Outcomes.

The role of optic nerve sheath fenestration (ONSF) in the management of idiopathic intracranial hypertension remains controversial, with indications, risks, and benefits compared to cerebro-spinal fluid diversion procedures not fully elucidated. We report a retrospective record review of 37 patients (50 eyes) which had undergone ONSF by a single surgeon. Visual acuity (VA) improved in 22% of operated eyes and 17% of fellow eyes; stabilized in 54% of operated and 74% of fellow eyes; and deteriorated in 24% of operated and 9% of fellow eyes. Better pre-operative VA (p = 0.01), colour vision (p = 0.002), and earlier intervention (p = 0.04) were associated with stabilization. We conclude that ONSF often stabilizes vision and visual fields. Our results were best in patients with better pre-operative vision and in those with earlier intervention.

The diagnostic and economic yield of neuroimaging in neuro-ophthalmology.

BACKGROUND: Diagnostic studies such as computed tomography scans (CT) and magnetic resonance imaging (MRI) are ordered frequently in neuro-ophthalmic practice, although the diagnostic yield and cost-effectiveness of these tests have been studied for only a few conditions. We assessed the diagnostic and economic yield of CT and MRI across all patients evaluated in a neuro-ophthalmology practice. METHODS: This retrospective review included all patients referred by the division of neuro-ophthalmology at the Scheie Eye Institute for CT, CT angiography, MRI, MRA, or magnetic resonance venography over a 12-month period. Abnormal imaging findings were categorized as significant (one that elicited changes in management) and/or relevant (one that related to the patient's neuro-ophthalmic complaint or examination findings). The diagnostic yield of the test ordered was analyzed according to the patient's chief complaint, neuro-ophthalmic examination findings, and indication for imaging. The total costs for each diagnostic group and costs per significant finding were calculated using the global Resource-Based Relative Value Units for each examination from the Centers for Medicare and Medicaid Services Web site. RESULTS: Two hundred eleven imaging studies in 157 patients were evaluated. 28.9% (95% confidence interval, 22.5%-36.2%) of imaging studies had significant abnormalities relevant to the neuro-ophthalmic complaint. Imaging obtained for evaluation of progressive optic nerve dysfunction and cranial nerve palsy had statistically significant higher diagnostic yield than studies performed for other reasons. Total cost of all imaging studies performed was $107,615.72. Cost per clinically significant and relevant finding was $1,764.19. CONCLUSIONS: In comparison to the diagnostic yield of neuroimaging studies in other specialties, CT and MRI of the brain requested by neuro-ophthalmologists provide significant and relevant data at a reasonable cost.

Optic nerve biopsy in the management of progressive optic neuropathy.

BACKGROUND: In cases of progressive optic neuropathy, diagnostic uncertainty often persists despite extensive work-up. Optic nerve biopsy (ONB) can be considered, especially when visual decline of the affected or fellow eye ensues despite empiric therapy. We aimed to evaluate both diagnostic and therapeutic utilities of ONB based on the long-term experience at a tertiary care institution. METHODS: This was a retrospective chart review of biopsies over 20 years at a single institution involving intrinsic or adherent optic nerve masses. Main outcome measures included the impact of tissue sampling on reaching a diagnosis and on guiding treatment. Secondary measures included vision in the eye of the ONB and the fellow eye. RESULTS: Fifteen patients with a mean age of 51.7 ± 17.4 years underwent biopsies. At the time of biopsy, visual acuity was no light perception in 8 (53%) eyes, light perception to counting fingers in 5 (33%), and 20/400 or better in 2 (13%). The fellow eye of 7 patients (47%) experienced some degree of sequential vision loss before biopsy. Seven specimens included en bloc biopsy of the nerve, 7 contained the dural sheath (usually with a portion of the optic nerve), and 1 only of the compressive mass. Six patients (40%) had tumors. Six of 8 inflammatory lesions biopsied required further clinical data to arrive at specific diagnoses. In one case, a clinical diagnosis could not be made. No patients experienced further vision loss in the fellow eye at last follow-up (median, 8 months). CONCLUSIONS: In diverse circumstances of progressive optic neuropathy, ONB can be beneficial in establishing the diagnosis. ONB can help direct specific local or systemic treatment, particularly when infectious or inflammatory etiologies are identified. ONB, if considered early in the disease course, can potentially halt or prevent vision loss when the fellow eye is threatened.

Neuro-ophthalmic manifestations of cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmic manifestations of cancer are vast and early recognition of a serious ocular condition due to either cancer or its therapy is important for both vision preservation as well as providing valuable treatment and prognostic information regarding the underlying malignancy. This review focuses on direct and indirect effects of cancer on the eye and its adnexa, hematologic malignancy, complications of traditional and novel oncologic therapies, and paraneoplastic syndromes as they relate to the eye as these disorders can lead to potentially devastating or irreversible vision loss. METHODS: PubMed was searched primarily for the following topics: optic nerve infiltration, primary vitreoretinal lymphoma (PVRL), ocular paraneoplastic disorders, and ophthalmic complications of cancer therapeutics. Literature was selected based on historical significance and landmark studies (e.g., Cross et al. series of paraneoplastic optic neuritis patients; Chan's textbook on primary intraocular lymphoma) as well as publications published after 2000. References from select studies were additionally included. Given the sparsity of literature on many subjects, most publications were included during this time frame in our review. KEY CONTENT AND FINDINGS: There are several ophthalmic entities that the oncologist should be aware of including leukemic optic nerve infiltration, PVRL, paraneoplastic syndromes as they related to the eye, and adverse effects of therapeutics. Unfortunately, given the rarity of some of these entities [e.g., paraneoplastic optic neuropathy (PON), cancer-associated retinopathy (CAR)], diagnosis can be difficult and treatment options are often limited. CONCLUSIONS: Oncologists can develop a set of basic ophthalmology examination skills that will help to triage and manage patient eye complaints. In certain instances, oncologists have the potential to avert devastating vision loss with early recognition of neuro-ophthalmic complications.

High-Speed Balanced-Detection Visible-Light Optical Coherence Tomography in the Human Retina Using Subpixel Spectrometer Calibration.

Increases in speed and sensitivity enabled rapid clinical adoption of optical coherence tomography (OCT) in ophthalmology. Recently, visible-light OCT (vis-OCT) achieved ultrahigh axial resolution, improved tissue contrast, and provided new functional imaging capabilities, demonstrating the potential to improve clinical care further. However, limited speed and sensitivity caused by the high relative intensity noise (RIN) in supercontinuum lasers impeded the clinical adoption of vis-OCT. To overcome these limitations, we developed balanced-detection vis-OCT (BD-vis-OCT), which uses two calibrated spectrometers to cancel RIN and other noises. We analyzed the RIN to achieve robust subpixel calibration between the two spectrometers and showed that BD-vis-OCT reduced the A-line noise floor by up to 20.5 dB. Metrics comparing signal-to-noise-ratios showed similar image qualities across multiple reference arm powers, a hallmark of operation near the shot-noise limit. We imaged healthy human retinas at an A-line rate of 125 kHz and a field-of-view up to 10 mm ×4 mm. We found that BD-vis-OCT revealed retinal anatomical features previously obscured by the noise floor.

Safety and efficacy of gene transfer for Leber's congenital amaurosis.

Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.

Success of prisms in the management of diplopia due to fourth nerve palsy.

BACKGROUND: To analyze the success of prism use in alleviating diplopia in patients with fourth nerve palsy and to provide recommendations for prism prescription. METHODS: In this retrospective cohort study, the medical records of 83 patients who were prescribed prisms for symptomatic diplopia due to fourth nerve palsy were analyzed. Data on the nature and duration of diplopia, motility and alignment findings, and amount and type of prism prescribed were recorded. The success of prescribed prismatic correction was assessed by the patient's self-reporting of satisfaction with prism use and follow-up records. The main outcome measure was the satisfaction rate associated with the use of prisms (satisfaction score 1 or 2) in patients with fourth nerve palsy. RESULTS: There were 69 patients with congenital fourth nerve palsy and 14 patients with acquired fourth nerve palsy who received prisms. The mean primary position (± SD) deviation in this group was 7.8 (± 4.6) prism diopters (PD). The mean prism prescription was 6 (± 2.9) PD. Overall, 92% of patients were satisfied with the use of prisms. During the length of follow-up, which ranged from 2 months to more than 6 years (median: 18 months), 86% of the cohort continued using prisms while 14% of patients underwent strabismus surgery. Among 15 patients who had primary position deviation greater than 15 PD, 80% of the patients reported satisfaction with prisms, and in the 11 patients who received 10 PD or more of prismatic correction, 82% were satisfied. CONCLUSION: Prisms are an effective modality for the management of patients with symptomatic diplopia due to fourth nerve palsy. Even in patients with larger deviations including those who were prescribed greater than 10 PD of correction, the success rate of prisms in alleviating diplopia was high. Prisms should be considered as initial therapy in symptomatic patients with fourth nerve palsy.