Venkateswaran N, Sripawadkul W, Karp CL. The role of imaging technologies for ocular surface tumors. Curr Opin Ophthalmol 2021;32(4):369-378.Abstract
PURPOSE OF REVIEW: This review will discuss the utility of high-resolution anterior segment optical coherence tomography (HR-OCT), in-vivo confocal microscopy (IVCM) and ultrasound biomicroscopy (UBM) in characterizing and diagnosing various ocular surface tumors, namely ocular surface squamous neoplasia (OSSN), conjunctival lymphoma and conjunctival melanoma. The strengths and limitations of each imaging modality will be discussed along with the characteristics findings of each lesion on each imaging platform. RECENT FINDINGS: HR-OCT can consistently be utilized in the clinic setting to distinguish between epithelial ocular surface tumors such as OSSN as compared with subepithelial tumors such as conjunctival lymphoma and conjunctival melanoma given their distinctive findings. IVCM can be used as an adjunct to HR-OCT to obtain cellular and surface characteristics, whereas UBM can be used to assess tumor depth and thickness for larger and highly pigmented lesions as well as to detect intraocular invasion. SUMMARY: HR-OCT, IVCM and UBM are all helpful imaging modalities to diagnose and characterize various ocular surface tumors and can serve as valuable adjuncts to monitor treatment response and assess for recurrence ocular surface tumors.
Vingopoulos F, Koulouri I, Miller JB, Vavvas DG. Anatomical and Functional Recovery Kinetics After Epiretinal Membrane Removal. Clin Ophthalmol 2021;15:175-181.Abstract
Purpose: To investigate the nature of anatomical and functional recovery kinetics after epiretinal membrane (ERM) removal. Methods: The records of 42 patients (45 eyes) with idiopathic ERM treated with pars plana vitrectomy and surgical peeling of the ERM performed by a single surgeon at Massachusetts Eye and Ear between 2012 and 2017 were retrospectively reviewed. Outcome measures included spectral domain optical coherence tomography-measured central macular thickness (CMT) pre-operatively and at post-operative day 1, week 1, months 1, 3, 6, 12 and 24 as well as best-corrected visual acuity (BCVA). Correlations between baseline or early values and final anatomical and functional outcomes were investigated. Results: Improvement in CMT was statistically significant after 1 week, 1, 3, 6, 12 and 24 months ( < 0.01). BCVA improvement was statistically significant after 1, 6, 12 and 24 months follow-up (<0.01). The improvement of BCVA and CMT with time was found to be logarithmic (R =0.96, R =0.84) suggesting that early (<30 days) post-operative functional and anatomical changes may be predictive of long-term outcomes. Preoperative BCVA and CMT revealed a weak positive correlation with the respective BCVA and CMT at 24 months (R=0.13 and R=0.16). When plotted as a percentage of the fellow normal eye CMT, first week proportional improvement in CMT from pre-operative baseline was found to be correlated with final CMT proportional decrease (R=0.72) suggesting that first week postoperative CMT could be predictive of final CMT. Conclusion: There is a logarithmic improvement in CMT and BCVA after ERM peel with BCVA improvement following the CMT improvement. Early (less than 30 days) post-operative anatomical changes can be predictive of long-term anatomical outcomes.
Vinken K, Op de Beeck H. Using deep neural networks to evaluate object vision tasks in rats. PLoS Comput Biol 2021;17(3):e1008714.Abstract
In the last two decades rodents have been on the rise as a dominant model for visual neuroscience. This is particularly true for earlier levels of information processing, but a number of studies have suggested that also higher levels of processing such as invariant object recognition occur in rodents. Here we provide a quantitative and comprehensive assessment of this claim by comparing a wide range of rodent behavioral and neural data with convolutional deep neural networks. These networks have been shown to capture hallmark properties of information processing in primates through a succession of convolutional and fully connected layers. We find that performance on rodent object vision tasks can be captured using low to mid-level convolutional layers only, without any convincing evidence for the need of higher layers known to simulate complex object recognition in primates. Our approach also reveals surprising insights on assumptions made before, for example, that the best performing animals would be the ones using the most abstract representations-which we show to likely be incorrect. Our findings suggest a road ahead for further studies aiming at quantifying and establishing the richness of representations underlying information processing in animal models at large.
Wagner A, Wang C, Fessler J, DeTomaso D, Avila-Pacheco J, Kaminski J, Zaghouani S, Christian E, Thakore P, Schellhaass B, Akama-Garren E, Pierce K, Singh V, Ron-Harel N, Douglas VP, Bod L, Schnell A, Puleston D, Sobel RA, Haigis M, Pearce EL, Soleimani M, Clish C, Regev A, Kuchroo VK, Yosef N. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 2021;184(16):4168-4185.e21.Abstract
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.
Wai KM, Locascio JJ, Wolkow N. Bacterial dacryoadenitis: clinical features, microbiology, and management of 45 cases, with a recent uptick in incidence. Orbit 2021;:1-9.Abstract
PURPOSE: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. METHODS: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. RESULTS: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis. CONCLUSIONS: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.
Wai KM, Vingopoulos F, Garg I, Kasetty M, Silverman RF, Katz R, Laíns I, Miller JW, Husain D, Vavvas DG, Kim LA, Miller JB. Contrast sensitivity function in patients with macular disease and good visual acuity. Br J Ophthalmol 2021;Abstract
INTRODUCTION: Contrast sensitivity function (CSF) may better estimate a patient's visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity. METHODS: Patients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd. RESULTS: 151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: -0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: -0.094 to -0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd). CONCLUSION: CSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.
Waksmunski AR, Song YE, Kinzy TG, Laux RA, Sewell J, Fuzzell D, Fuzzell S, Miller S, Wiggs JL, Pasquale LR, Skarie JM, Haines JL, Cooke Bailey JN. The GGLEAM Study: Understanding Glaucoma in the Ohio Amish. Int J Environ Res Public Health 2021;18(4)Abstract
Glaucoma leads to millions of cases of visual impairment and blindness around the world. Its susceptibility is shaped by both environmental and genetic risk factors. Although over 120 risk loci have been identified for glaucoma, a large portion of its heritability is still unexplained. Here we describe the foundation of the Genetics of GLaucoma Evaluation in the AMish (GGLEAM) study to investigate the genetic architecture of glaucoma in the Ohio Amish, which exhibits lower genetic and environmental heterogeneity compared to the general population. To date, we have enrolled 81 Amish individuals in our study from Holmes County, Ohio. As a part of our enrollment process, 62 GGLEAM study participants (42 glaucoma-affected and 20 unaffected individuals) received comprehensive eye examinations and glaucoma evaluations. Using the data from the Anabaptist Genealogy Database, we found that 80 of the GGLEAM study participants were related to one another through a large, multigenerational pedigree containing 1586 people. We plan to integrate the health and kinship data obtained for the GGLEAM study to interrogate glaucoma genetics and pathophysiology in this unique population.
Walton DS, Yeung HH. Glaucoma following Infant Lensectomy: 2021 Update. Klin Monbl Augenheilkd 2021;238(10):1065-1068.Abstract
PURPOSE: To review information pertaining to glaucoma following infant lensectomy surgery and to provide evidence to support the responsible mechanism of this condition. METHODS AND RESULTS: Described risk factors and proposed mechanisms for infantile aphakic glaucoma were assessed. The clinical evidence observed in affected glaucoma patients was analyzed, and evidence of postoperative anterior chamber fibrosis was reviewed and interpreted. CONCLUSION: The review and assessment of laboratory and clinical evidence support the proposal that infantile aphakic glaucoma is caused, in part, by postoperative anterior chamber fibroization related to lens cell dispersion and active epithelial-mesenchymal transition with resultant filtration angle tissue injury and loss of function.
Wan MJ, AlShaker S, Hunter DG. Correction to: Use of Botulinum Toxin in Ophthalmology. Handb Exp Pharmacol 2021;263:283.
Wan MJ, AlShaker S, Hunter DG. Use of Botulinum Toxin in Ophthalmology. Handb Exp Pharmacol 2021;263:147-160.Abstract
Botulinum toxin is an important treatment for many conditions in ophthalmology, including strabismus, nystagmus, blepharospasm, hemifacial spasm, spastic and congenital entropion, corneal exposure, and persistent epithelial defects. The mechanism of action of botulinum toxin for both strabismus and nystagmus is the neuromuscular blockade and transient paralysis of extraocular muscles, but when botulinum toxin is used for some forms of strabismus, a single injection can convey indefinite benefits. There are two unique mechanisms of action that account for the long-term effect on ocular alignment: (1) the disruption of a balanced system of agonist-antagonist extraocular muscles and (2) the reestablishment of central control of alignment by the binocular visual system. For other ocular conditions, botulinum toxin acts through transient paralysis of periocular muscles. Botulinum toxin is a powerful tool in ophthalmology, achieving its therapeutic effects by direct neuromuscular blockade of extraocular and periocular muscles and by unique mechanisms related to the underlying structure and function of the visual system.
Wang T, Zhou P, Xie X, Tomita Y, Cho S, Tsirukis D, Lam E, Luo HR, Sun Y. Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3. EBioMedicine 2021;73:103632.Abstract
BACKGROUND: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. METHODS: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. FINDINGS: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. INTERPRETATION: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. FUNDING: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.
Wang M, Garg I, Miller JB. Wide Field Swept Source Optical Coherence Tomography Angiography for the Evaluation of Proliferative Diabetic Retinopathy and Associated Lesions: A Review. Semin Ophthalmol 2021;36(4):162-167.Abstract
Retinal imaging remains the mainstay for monitoring and grading diabetic retinopathy. The gold standard for detecting proliferative diabetic retinopathy (PDR) requiring treatment has long been the seven-field stereoscopic fundus photography and fluorescein angiography. In the past decade, ultra-wide field fluorescein angiography (UWF-FA) has become more commonly used in clinical practice for the evaluation of more advanced diabetic retinopathy. Since its invention, optical coherence tomography (OCT) has been an important tool for the assessment of diabetic macular edema; however, OCT offered little in the assessment of neovascular changes associated with PDR until OCT-A became available. More recently, swept source OCT allowed larger field of view scans to assess a variety of DR lesions with wide field swept source optical coherence tomography (WF-SS-OCTA). This paper reviews the role of WF-SS-OCTA in detecting neovascularization of the disc (NVD), and elsewhere (NVE), microaneurysms, changes of the foveal avascular zone (FAZ), intraretinal microvascular abnormalities (IRMA), and capillary non-perfusion, as well as limitations of this evolving technology.
Wang Y, Carreno-Galeano JT, Singh RB, Dana R, Yin J. Long-term Outcomes of Punctal Cauterization in the Management of Ocular Surface Diseases. Cornea 2021;40(2):168-171.Abstract
PURPOSE: To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases. METHODS: We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded. RESULTS: A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21%) and moderate (25%) dry eye decreased significantly (8% and 19% at 3 months and 6% and 17% at 12 months, P = 0.0006). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling. CONCLUSIONS: Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization.
Warkad VU, Hunter DG, Dagi AF, MacKinnon S, Kazlas MA, Heidary G, Staffa SJ, Dagi LR. Impact of Adding Augmented Superior Rectus Transpositions to Medial Rectus Muscle Recessions When Treating Esotropic Moebius Syndrome. Am J Ophthalmol 2021;Abstract
PURPOSE: Describe outcomes after treatment of Moebius syndrome (MBS) esotropia by adjustable bilateral medial rectus recession (BMR) with and without augmented superior rectus transposition (SRT) DESIGN: Retrospective case series METHODS: Patients meeting 2014 diagnostic criteria for MBS and treated at Boston Children's Hospital between 2003 and 2019 were identified via billing records and chart review. Visual acuity, sensorimotor evaluations, strabismus procedures, and other clinical features were recorded. Surgical outcomes for patients treated with strabismus surgery (excluding those with prior surgery elsewhere) were evaluated. Primary outcome measure was post-operative alignment comparing treatment by adjustable BMR versus adjustable BMR+SRT. RESULTS: Twenty patients had MBS, 12/20 (60%) were male. Fifteen (75%) had primary position esotropia, and all had bilateral abduction deficit. Eight of 20 met inclusion criteria for primary strabismus surgery outcome. Five had undergone adjustable BMR ranging from 4.5-6.5 mm. Three had undergone adjustable BMR+SRT, all with 4 mm medial rectus muscle recessions. Mean pre-operative esotropia before treatment by BMR was 39.5 PD (+/- 15 PD) with mean post-operative esotropia 9 PD (+/- 7.9 PD) at six months. Mean pre-operative esotropia before treatment by BMR+SRT was 70.8 PD (+/- 5.9 PD) with mean post-operative esotropia 2.5 PD (+/- 3.5 PD) at six months. Significantly greater reduction in esotropia resulted from BMR+SRT than BMR (P=0.036). CONCLUSIONS: BMR proved sufficient to treat esotropia < 50 PD and BMR+SRT for greater esotropia in patients with MBS-associated abduction limitation.
Webb BD, Manoli I, Engle EC, Jabs EW. A framework for the evaluation of patients with congenital facial weakness. Orphanet J Rare Dis 2021;16(1):158.Abstract
There is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.
Wendt S, Abdullah Z, Barrett S, Daruwalla C, Go JA, Le B, Li E, Livingston C, Miller M, Nakhleh L, Pecha J, Pothula S, Pradhan S, Sathappan V, Shah A, Sonuyi A-M, Ugoh P, Wang Q, Weber N, Succar T, Blieden L, Mortensen P, Elkin Z, Sun G, Lee AG. A virtual COVID-19 ophthalmology rotation. Surv Ophthalmol 2021;66(2):354-361.Abstract
The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.
White TL, Deshpande N, Kumar V, Gauthier AG, Jurkunas UV. Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy. Free Radic Biol Med 2021;164:34-43.Abstract
Fuchs endothelial corneal dystrophy (FECD) is an age-related disease whereby progressive loss of corneal endothelial cells (CEnCs) leads to loss of vision. There is currently a lack of therapeutic interventions as the etiology of the disease is complex, with both genetic and environmental factors. In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectively eliminating senescent cells using the senolytic cocktail of dasatinib and quercetin attenuated UVA-induced fibrosis, highlighting the potential for a new therapeutic intervention for FECD.
Whitman MC, Barry BJ, Robson CD, Facio FM, Van Ryzin C, Chan W-M, Lehky TJ, Thurm A, Zalewski C, King KA, Brewer C, Almpani K, Lee JS, Delaney A, FitzGibbon EJ, Lee PR, Toro C, Paul SM, Abdul-Rahman OA, Webb BD, Jabs EW, Moller HU, Larsen DA, Antony JH, Troedson C, Ma A, Ragnhild G, Wirgenes KV, Tham E, Kvarnung M, Maarup TJ, MacKinnon S, Hunter DG, Collins FS, Manoli I, Engle EC. TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy. Hum Genet 2021;140(12):1709-1731.Abstract
Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.
Whitman MC. Axonal Growth Abnormalities Underlying Ocular Cranial Nerve Disorders. Annu Rev Vis Sci 2021;7:827-850.Abstract
Abnormalities in cranial motor nerve development cause paralytic strabismus syndromes, collectively referred to as congenital cranial dysinnervation disorders, in which patients cannot fully move their eyes. These disorders can arise through one of two mechanisms: (a) defective motor neuron specification, usually by loss of a transcription factor necessary for brainstem patterning, or (b) axon growth and guidance abnormalities of the oculomotor, trochlear, and abducens nerves. This review focuses on our current understanding of axon guidance mechanisms in the cranial motor nerves and how disease-causing mutations disrupt axon targeting. Abnormalities of axon growth and guidance are often limited to a single nerve or subdivision, even when the causative gene is ubiquitously expressed. Additionally, when one nerve is absent, its normal target muscles attract other motor neurons. Study of these disorders highlights the complexities of axon guidance and how each population of neurons uses a unique but overlapping set of axon guidance pathways.
Whitmore HAB, Kim LA. Understanding the Role of Blood Vessels in the Neurologic Manifestations of Coronavirus Disease 2019 (COVID-19). Am J Pathol 2021;191(11):1946-1954.Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally identified as an outbreak in Wuhan, China, toward the end of 2019 and quickly became a global pandemic, with a large death toll. Originally identified as a respiratory disease, similar to previously discovered SARS and Middle East respiratory syndrome (MERS), concern has since been raised about the effects of SARS-CoV-2 infection on the vasculature. This viral-vascular involvement is of particular concern with regards to the small vessels present in the brain, with mounting evidence demonstrating that SARS-CoV-2 is capable of crossing the blood-brain barrier. Severe symptoms, termed coronavirus disease 2019 (COVID-19), often result in neurologic complications, regardless of patient age. These neurologic complications range from mild to severe across all demographics; however, the long-term repercussions of neurologic involvement on patient health are still unknown.