Transient Monocular Visual Loss (Amaurosis Fugax): How Does Age Impact Diagnosis?

Transient monocular visual loss (TMVL), also known as transient monocular blindness or amaurosis fugax ("fleeting blindness"), is a temporary loss of vision often due to ischemia to the retina. While acute TMVL should be considered an emergency that further requires exhaustive investigation, there are some cases in which TMVL arises secondary to benign causes. Age has a major impact in the diagnosis of ischemia and although the differential diagnosis of TMVL can be broad, timely and appropriate history, examination, diagnostic testing, and treatment can be vision- or life-saving. We review the causes of TMVL and the impact of age on the differential diagnoses and management.

The epidemiology of pediatric dry eye disease in the United States: An IRIS® registry (Intelligent Research in Sight) analysis.

PURPOSE: Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology's IRIS® Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients <18 years old) and the demographic differences of DED between pediatric and adult patients (ADED). METHODS: Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N = 4,795,979) were included. Descriptive statistics, Pearson's chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts. RESULTS: The average age at onset for ADED patients was 61.06 (±14.75) years and for PDED patients was 12.51 (±3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p < 0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08 % vs. 50.60 %), male sex (41.58 % vs. 48.78 %) and Asian race (6.02 % vs. 3.11 %) respectively. Within the PDED cohort, females were at higher risk of PDED (58 % vs. 42 %). PDED was more prevalent in children with refractive errors (76 %) and eyelid/conjunctival disorders (41 %). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 % vs. 68.12 %), male sex (41.58 % vs. 31.55 %) and Caucasian race (50.24 % vs. 67.06 %) respectively. CONCLUSIONS: Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders.

The Epidemiology and Risk Factors for the Progression of Sympathetic Ophthalmia in the United States: An IRIS Registry Analysis.

PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology's (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (ß) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87%) were female, 1336 (87.72%) belonged to the Procedure Only cohort, and 187 (12.28%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207%, whereas after procedures it was 0.0124%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122%) followed by glaucoma (0.066%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011%). The average time to onset of SO across both cohorts combined was 527.44 (±715.60) days, with statistically significant differences between the 2 cohorts (P < .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.

Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions.

A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.

Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration.

Purpose: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Design: Prospectively designed, cross-sectional study. Participants: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. Methods: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Main Outcome Measures: Plasma metabolite levels associated with OCT features. Results: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. Conclusions: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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.

Subthreshold Exudative Choroidal Neovascularization (CNV): Presentation of This Uncommon Subtype and Other CNVs in Age-Related Macular Degeneration (AMD).

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in people over the age of 50 worldwide. Exudative or neovascular AMD is a more severe subset of AMD which is characterized by the presence of choroidal neovascularization (CNV). Recent advancements in multimodal ophthalmic imaging, including optical coherence tomography (OCT) and OCT-angiography (OCT-A), have facilitated the detection and characterization of previously undetectable neovascular lesions and have enabled a more refined classification of CNV in exudative as well as nonexudative AMD patients. Subthreshold exudative CNV is a novel subtype of exudative AMD that typically presents asymptomatically with good visual acuity and is characterized by stable persistent or intermittent subretinal fluid (SRF). This review aims to provide an overview of the clinical as well as multimodal imaging characteristics of CNV in AMD, including this new clinical phenotype, and propose effective approaches for management.

Short- and Long-Term Visual Outcomes in Patients Receiving Intravitreal Injections: The Impact of the Coronavirus 2019 Disease (COVID-19)-Related Lockdown.

Purpose: To investigate the short- and long-term impact of COVID-19­related lockdown on the vision of patients requiring intravitreal injections (IVI) for neovascular Age-related Macular degeneration (nvAMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO). Methods: This is a retrospective study from the Retina department of three Mass Eye and Ear centers. Charts of patients age of ≥ 18 years with any of the abovementioned diagnoses who had a scheduled appointment anytime between 17 March 2020 until 18 May 2020 (lockdown period in Boston, Massachusetts) were reviewed at baseline (up to 12 weeks before the lockdown), at first available follow-up (=actual f/u) during or after the lockdown period, at 3 months, 6 months, and at last available completed appointment of 2020. Results: A total of 1001 patients met the inclusion criteria. Of those patients, 479 (47.9%) completed their intended f/u appointment, while 522 missed it (canceled and "no show"). The delay in care of those who missed it was 59.15 days [standard deviation (SD) ± 49.6]. In these patients, significant loss of vision was noted at actual f/u [Best corrected visual acuity (BCVA) in LogMAR (Logarithm of the Minimum Angle of Resolution)­mean (±SD)­completed: 0.45 (±0.46), missed: 0.53 (±0.55); p = 0.01], which was more prominent in the DR group [Visual acuity (VA) change in LogMAR­mean (±SD); completed: 0.04 (±0.28), missed: 0.18 (±0.44); p = 0.02] and CRVO [completed: −0.06 (±0.27), missed: 0.11 (±0.35); p = <0.001] groups followed by nvAMD [completed: 0.006 (±0.16), missed: 0.06 (±0.27); p = 0.004] and BRVO [completed: −0.02 (±0.1), missed: 0.03 (±0.14); p = 0.02] ones. Overall, a higher percent of people who missed their intended f/u experienced vision loss of more than 15 letters at last f/u compared to those who completed it [missed vs. completed; 13.4% vs. 7.4% in nvAMD (p = 0.72), 7.8% vs. 6.3% in DR (0.84), 15.5% vs. 9.9% in CRVO (p < 0.001) and 9.6% vs. 2% in BRVO (p = 0.48)]. Conclusions: Delay in care of about 8.45 weeks can lead to loss of vision in patients who receive IVI with DR and CRVO patients being more vulnerable in the short-term, whereas in the long-term, CRVO patients followed by the nvAMD patients demonstrating the least vision recovery. BRVO patients were less likely to be affected by the delay in care. Adherence to treatment is key for maintaining and improving visual outcomes in patients who require IVI.

Juxtapapillary Choroidal Neovascular Membrane as a Complication of Optic Disc Drusen: Multimodal Imaging With Swept Source-Optical Coherence Tomography and Optical Coherence Tomography Angiography.

ABSTRACT: A 55-year-old Caucasian man presented to the neuro-ophthalmology department for follow-up evaluation due to long-standing bilateral optic nerve head drusen (ONHD). On examination, the BCVA was 20/20-2 in both eyes. Dilated fundus examination revealed extensive ONHD in both eyes, retinal hemorrhages, exudates inferonasal to the macula, and macular edema inferotemporal to the disc margin. Automated visual field testing revealed generalized depression in both eyes. Late phase leakage was observed on fluorescein angiography (FA). Optical coherence tomography angiography identified a small juxtapapillary choroidal neovascular membrane inferonasal to the macula in the right eye correlating with the area of retinal hemorrhage and exudates.

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.

Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-Related Macular Degeneration.

Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p < 0.01) and 19 (p < 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p < 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.

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.

Ophthalmic manifestations of dementing disorders.

PURPOSE OF REVIEW: Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing conditions may also affect visual function. The eye is an accessible window to the brain that can provide valuable information for the early diagnosis of people who suffer from Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies as well as from more rare causes of dementias, such as Creutzfeldt-Jacob and Huntington's diseases. Herein, we present the ocular manifestations of neurocognitive disorders focusing on the neuro-ophthalmic ones and further discuss potential ocular biomarkers that could help in early detection of these disorders. RECENT FINDINGS: Ophthalmic examination along with the recent developments in in-vivo testing have provided a strong foundation of useful knowledge about brain disorder in neurodegenerative diseases without the need for invasive studies. Currently, a number of visual measures, such as visual acuity, contrast sensitivity, pupil response, and saccades in addition to various ophthalmic tests, such as electroretinogram, visual evoked potential, optical coherence tomography (OCT), and OCT-angiography have been widely used and evaluated as potential biomarkers for different stages of dementia. SUMMARY: Ophthalmologic and neuro-ophthalmic evaluation is evolving as an important part of the early diagnosis and management of people with dementia. A particular focus on ocular biomarkers in dementing illnesses has arisen over the past few years and there are several promising measures and imaging tools that have been proposed as potential biomarkers for these diseases.

Metabolic modeling of single Th17 cells reveals regulators of autoimmunity.

Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T cells and attenuated tissue inflammation in CNS autoimmunity.

Case 292: Lyme Neuroborreliosis.

History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed.