Optical coherence tomography angiography in neuro-ophthalmology.

PURPOSE OF REVIEW: Optical coherence tomography angiography (OCTA) is a novel, noninvasive imaging technique, which provides depth resolved visualization of microvasculature of the retina and choroid. Although OCTA has been widely used for the evaluation of a number of retinal diseases, its use in the field of neuro-ophthalmology has been less studied. In this review, we provide an update on the utility of OCTA in neuro-ophthalmic conditions. RECENT FINDINGS: Peripapillary and macular microvasculature analyses have indicated that OCTA can be a promising tool for early detection of a number of neuro-ophthalmic diseases, differential diagnosis, and monitoring of disease progression. Recent studies have demonstrated that structural and functional impairment can develop at early stages in some conditions such as in multiple sclerosis and Alzheimer's disease even in the absence of overt clinical symptoms. Furthermore, this dye-less technique can be a valuable adjunct tool in the detection of complications commonly seen in some congenital entities such optic disc drusen. SUMMARY: Since its introduction, OCTA has emerged as an important imaging approach shedding light on unrevealed pathophysiological mechanisms of several ocular diseases. The use of OCTA as a biomarker in the field of neuro-ophthalmology has recently gained considerable attention with studies supporting its role in clinical setting while larger studies are warranted for correlating these findings with traditional diagnostic procedures and clinical features and outcomes.

Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms.

Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.

Variation in Evolving Optic Neuritis.

BACKGROUND: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. METHODS: Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. RESULTS: Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. CONCLUSIONS: This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.

Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

Advances in the diagnosis of giant cell arteritis.

PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.

Systematic Review of the Yield of Temporal Artery Biopsy for Suspected Giant Cell Arteritis.

PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The I 2 was 92%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012, p = 0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.

Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management.

Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.

Angiographic Findings in the Tolosa-Hunt Syndrome and Resolution after Corticosteroid Treatment.

The Tolosa-Hunt syndrome is a rare clinical condition characterized by painful opthalmoparesis associated with idiopathic granulomatous inflammation of the orbital apex and cavernous sinus. Historically, this condition was thought to result from arteritic changes in the internal carotid artery and cavernous sinus. Modern digital angiographic techniques were unavailable when THS was initially described, and few reports exist on its high-resolution angiographic findings. Painful ophthalmoparesis, especially of the oculomotor nerve, warrants vascular imaging because of the concern for an underlying aneurysm. Here, we describe angiographic findings of THS which may be useful for clinicians when encountering patients presenting with painful ophthalmoplegia.

Re-Treatment With Ethambutol After Toxic Optic Neuropathy.

There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy.

Transient Monocular Vision Loss on Awakening: A Benign Amaurotic Phenomenon.

BACKGROUND: Transient monocular vision loss (TMVL) is an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Our objective is to describe the phenomenon of TMVL present on awakening, which may represent a distinct and benign entity. METHODS: We performed a retrospective observational case series of 29 patients who experienced TMVL on awakening. Patients who described monocular dimming or blackout of vision were included, and those with blurred vision, concurrent eye pain, and binocular vision loss were excluded. Descriptive statistics were used to summarize the study population. RESULTS: Of the 29 patients we studied, 90% (n = 26) were female and 48% had crowded discs (cup-to-disc ratio ≤0.2). The mean age was 45.4 years, although women were significantly younger than men (mean ages 43.4 and 62.7 years, respectively, P = 0.017). Brain magnetic resonance imaging and vascular imaging (magnetic resonance angiography, computed tomographic angiography, or carotid Doppler) were performed in 69% and 55% of cases, respectively, and were uniformly negative. In 14 patients for whom clear follow-up data could be obtained, no medically or visually significant sequelae of this syndrome were found, and 50% experienced resolution of symptoms. CONCLUSIONS: Evaluation was uniformly negative when patients described waking with isolated vision loss in 1 eye with subsequent resolution, usually in less than 15 minutes. The natural history seems benign with symptoms frequently remitting spontaneously. This visual phenomenon may represent an autoregulatory failure resulting in a supply/demand mismatch during low-light conditions.

The enigma of nonarteritic anterior ischemic optic neuropathy: an update for the comprehensive ophthalmologist.

PURPOSE OF REVIEW: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. RECENT FINDINGS: The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. SUMMARY: NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.

Floppy Eyelid Syndrome: an Overlooked Comorbidity Among Bariatric Patients.

PURPOSE: Floppy eyelid syndrome (FES) is a clinical entity characterized by palpebral hyperlaxity and chronic conjunctivitis. Patients' eyelids evert ("flip inside out"), leading to eye irritation, dryness, grittiness, and tearing. More severe cases can lead to significant ocular complications, such as keratoconus and impaired eyesight. Research has revealed an association between FES and obstructive sleep apnea syndrome (OSAS). OSAS is also one of the most common comorbidities among patients with obesity and an indication for bariatric surgery. This is one of the first studies to explore FES in a group of patients who have undergone bariatric surgery. MATERIALS AND METHODS: This was a retrospective study. A total of 88 patients completed a survey by mail or telephone. Additional data on demographics and baseline preoperative clinical information was extracted from the online medical records and the MBSAQIP database. RESULTS: Thirty-nine patients (44%) recalled having chronic ocular symptoms before their bariatric surgery, among whom six reported palpebral laxity and/or an established diagnosis of FES. The majority of them (67%) rated their symptoms postoperatively as "somewhat" or "significantly improved." The patients that reported improvement in their ocular symptoms also experienced an improvement in their OSAS severity. CONCLUSION: Bariatric surgery might affect the clinical course of FES and the severity of symptoms. Treating OSAS, the underlying mechanism of FES, is a possible mechanism of how bariatric surgery can help patients. It is also critical for bariatric surgeons to consider FES when patients with obesity, particularly those with OSAS, present with chronic eye symptoms.

The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis.

PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.

Oculomotor nerve schwannoma: case series and literature review.

Oculomotor nerve schwannomas are rare benign cranial nerve tumors. There are only a limited number of reports on this pathology in the literature, and there are currently no established management guidelines that aid providers in deciding on surgical versus nonsurgical management. We assess the published literature on the topic to identify indications for treatment as well as outcome measures (e.g., local control rates, survival rates, and complication rates) that have been reported as associated with the various treatment modalities. We attempt to develop an algorithm for evaluation and treatment of oculomotor nerve schwannomas in order to establish consensus on how these tumors should be treated.

Clinical and neuroradiologic characteristics in varicella zoster virus reactivation with central nervous system involvement.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS). METHODS: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS. RESULTS: The median age was 71 years [IQR 51.5-76]; 21 (57%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65%); median CSF white blood cell count was 11 [IQR 2-23] cells/µL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29%) CSF and 8/9 (89%) ocular samples. Clinical involvement included the optic nerve in 12 (32%), other cranial nerves in 20 (54%), brain parenchyma in 12 (32%) and spinal cord or nerve roots in 4 (11%). Twenty-seven/28 immunocompetent patients' MRIs were available for review (96%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN. CONCLUSION: OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation.

Incidence of nonarteritic ischemic optic neuropathy following topical clear corneal cataract surgery: survey and meta-analysis.

OBJECTIVE: We estimate the incidence and characteristics of post-cataract-surgery nonarteritic ischemic optic neuropathy (PCNAION) after topical clear corneal cataract extraction (CCCE) in Canada. DESIGN: Canada-wide internet survey and meta-analysis PARTICIPANTS: All certified Canadian ophthalmologists in the Canadian Ophthalmological Society directory, or belonging to a provincial ophthalmology internet group. METHODS: Identical surveys were distributed to 5 regions in Canada. CCCE surgeons were asked to estimate the number of CCCE they had performed in their career, and the number of PCNAION events that occurred within 1 year after CCCE. The results were analyzed using a random effects meta-analysis of proportions for rare events. RESULTS: The estimated survey response rate was 18%-32%. The 182 survey respondents performed a total of 1 499 694 CCCE with 107 events of PCNAION. Twenty-six percent of surgeons had at least one patient with PCNAION. Meta-analysis revealed a pooled estimate incidence of 2.8 PCNAION events (95% confidence interval 1.6-4.7) per 100 000 cataract procedures during the year after cataract surgery. Seventy-seven percent (82/107) of the PCNAION cases occurred within 3 weeks of surgery, and 7 patients had bilateral PCNAION. CONCLUSIONS: PCNAION is a rare complication after topical CCCE. Its incidence is important to estimate for patient care and epidemiologic reasons.