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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.
Ashraf M, Rageh A, Gilbert M, Tolls D, Fleming A, Souka A, El-Baha S, Cavallerano JD, Sun JK, Aiello LP, Silva PS. Factors Affecting Predominantly Peripheral Lesion Identification and Grading. Transl Vis Sci Technol 2021;10(7):6.Abstract
Purpose: The purpose of this study was to determine factors affecting predominantly peripheral lesion (PPL) grading, such as qualitative versus quantitative assessment, device type, and severity of diabetic retinopathy (DR) in ultrawide field color images (UWF-CIs). Methods: Patients with DR had UWF-CI qualitatively graded for PPL using standardized techniques and had hemorrhages/microaneurysms (H/Mas) individually annotated for quantitative PPL grading on two different ultrawide field devices. Results: Among 791 eyes of 481 patients, 38.2% had mild nonproliferative DR (NPDR), 34.7% had moderate NPDR, and 27.1% had severe NPDR to proliferative DR (PDR). The overall agreement between qualitative and quantitative PPL grading was moderate (ĸ = 0.423, P < 0.001). Agreement rates were fair in eyes with mild NPDR (ĸ = 0.336, P < 0.001) but moderate in eyes with moderate NPDR (ĸ = 0.525, P < 0.001) and severe NPDR-PDR (ĸ = 0.409, P < 0.001). Increasing thresholds for quantitative PPL determination improved agreement rates, with peak agreements at H/Ma count differences of six for mild NPDR, five for moderate NPDR, and nine for severe NPDR-PDR. Based on ultrawide field device type (California = 412 eyes vs. 200Tx = 379 eyes), agreement between qualitative and quantitative PPL grading was moderate for all DR severities in both devices (ĸ = 0.369-0.526, P < 0.001) except for mild NPDR on the 200Tx, which had poor agreement (ĸ = 0.055, P = 0.478). Conclusions: Determination of PPL varies between standard qualitative and quantitative grading and is dependent on NPDR severity, device type, and magnitude of lesion differences used for quantitative assessment. Translational Relevance: Prior UWF studies have not accounted for imaging and grading factors that affect PPL, such factors need to be reviewed when assessing thresholds for DR progression rates.
Maallo AMS, Moulton EA, Sieberg CB, Giddon DB, Borsook D, Holmes SA. A lateralized model of the pain-depression dyad. Neurosci Biobehav Rev 2021;127:876-883.Abstract
Chronic pain and depression are two frequently co-occurring and debilitating conditions. Even though the former is treated as a physical affliction, and the latter as a mental illness, both disorders closely share neural substrates. Here, we review the association of pain with depression, especially when symptoms are lateralized on either side of the body. We also explore the overlapping regions in the forebrain implicated in these conditions. Finally, we synthesize these findings into a model, which addresses gaps in our understanding of comorbid pain and depression. Our lateralized pain-depression dyad model suggests that individuals diagnosed with depression should be closely monitored for pain symptoms in the left hemibody. Conversely, for patients in pain, with the exception of acute pain with a known source, referrals in today's pain centers for psychological evaluation should be part of standard practice, within the framework of an interdisciplinary approach to pain treatment.
Tisdale AK, Dinkin M, Chwalisz BK. Afferent and Efferent Neuro-Ophthalmic Complications of Coronavirus Disease 19. J Neuroophthalmol 2021;41(2):154-165.Abstract
PURPOSE: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19) documented in the literature thus far. METHODS: The PubMed and Google Scholar databases were searched using the keywords: Neuro-Ophthalmology, COVID-19, SARS-CoV-2, and coronavirus. A manual search through reference lists of relevant articles was also performed. RESULTS/CONCLUSIONS: The literature on COVID-associated neuro-ophthalmic disease continues to grow. Afferent neuro-ophthalmic complications associated with COVID-19 include optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. Efferent neuro-ophthalmic complications associated with COVID-19 include cranial neuropathies, Miller Fisher syndrome, Adie's pupils, ocular myasthenia gravis, nystagmus and eye movement disorders. Proposed mechanisms of neurologic disease include immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy, and direct viral neurotropism. When patients present to medical centers with new onset neuro-ophthalmic conditions during the pandemic, COVID-19 infection should be kept on the differential.
Elhusseiny AM, VanderVeen DK. Optical coherence tomography in the setting of optic nerve head cupping reversal in secondary childhood glaucoma. J AAPOS 2021;Abstract
Reversal of optic nerve head (ONH) cupping has been considered an important clinical observation that signals surgical success and control of intraocular pressure (IOP) in childhood glaucoma. Many theories based on elasticity of pediatric eyes have been proposed, including anterior movement of the elastic lamina cribrosa or shrinkage of the scleral canal. The relationship between these factors and axonal loss is unclear when reversal of cupping has been observed. Retinal nerve fiber layer (RNFL) optical coherence tomography (OCT) can help to clarify this. We present a case series of 4 pediatric patients with secondary glaucoma that demonstrated ONH cupping reversal with pre- and postoperative clinical images and RNFL OCT.
Mazzarino RC. Targeting Future Pandemics, a Case for De Novo Purine Synthesis and Basic Research. Front Immunol 2021;12:694300.Abstract
We are currently experiencing a deadly novel viral pandemic with no efficacious, readily available anti-viral therapies to SARS-CoV-2. Viruses will hijack host cellular machinery, including metabolic processes. Here, I provide theory and evidence for targeting the host de novo purine synthetic pathway for broad spectrum anti-viral drug development as well as the pursuit of basic science to mitigate the risks of future novel viral outbreaks.
da Palma MM, Igelman AD, Ku C, Burr A, You JY, Place EM, Wang N-K, Oh JK, Branham KE, Zhang X, Ahn J, Gorin MB, Lam BL, Ronquillo CC, Bernstein PS, Nagiel A, Huckfeldt R, Cabrera MT, Kelly JP, Bakall B, Iannaccone A, Hufnagel RB, Zein WM, Koenekoop RK, Birch DG, Yang P, Fahim AT, Pennesi ME. Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome. Invest Ophthalmol Vis Sci 2021;62(7):27.Abstract
Purpose: The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. Methods: We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings. Results: Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel. Conclusions: This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.
Aminkhani A, Sharifi S, Hosseinzadeh P. Chemical Constituent, Antimicrobial Activity, and Synergistic Effect of the Stem, Leaf, and Flower Essential Oil of the Artemisia fragrans Willd. from Khoy. Chem Biodivers 2021;18(8):e2100241.Abstract
Artemisia fragrans is commonly used as a folk medicine as antispasmodic, anti-pyretic, anti-inflammatory, and abortifacient agents. The villagers use its pungent odor to repel rodents, mites, and pests, as well as its essential oil and smoke after burning to treat lung infections after uprooting the plant. Herein, we extracted the essential oils (EOs) of different parts of the plant and analyzed their chemical compositions and antibacterial activities. The chemical analysis led to the identification of 73, 59, and 57 compounds in the EOs of the stem, leaf, and flower, respectively. All of the EOs exhibited antibacterial activities against both G+ and G- bacteria. The EOs of the leaf and flower were more effective against tested bacteria, except B. anthracis and P. aeruginosa, compared to that of the stem. The binary combination of the EOs (stem and flower) or (stem and leaf) showed a synergistic effect. Statistical analysis indicated EOs of leaf and flower are more potent than that of the stem. These findings suggest the application of leaf and flower of the plant, which not only can prevent its uprooting but also ensure better therapeutic function.
Green MB, Daly MK, Laver NMV, Lefebvre DR. Adult-onset asthma and periocular xanthogranuloma - A rare infiltrative disease of the orbit and eyelid. Am J Ophthalmol Case Rep 2021;22:101043.Abstract
Purpose: To present a case of adult onset asthma with periocular xanthogranuloma (AAPOX), and discuss existing literature on adult orbital xanthogranulomatous diseases (AOXGDs) and their treatment. Observations: A 63 year old male presented with progressive bilateral eyelid swelling with overlying yellow plaques associated with asthma. CT scan showed periorbital swelling with enlargement of the superior and lateral rectus muscles bilaterally. Biopsy demonstrated orbital xanthogranulomatous disease with increased IgG4 plasma cells. The patient was treated with intralesional triamcinolone, oral prednisone, and cyclophosphamide without significant improvement. Surgical debulking was eventually performed which improved his external symptoms until he was lost to follow up 15 months later. Conclusions and Importance: AOXGDs are a group of rare infiltrative diseases of the eyelids and orbit that can be associated with significant systemic morbidities. While they all have similar underlying histopathologic features, appreciating the clinical difference between these diseases is important in understanding patient prognosis and ensuring appropriate clinical monitoring. There is also growing research demonstrating that AAPOX, along with other AOXGDs, may represent part of a continuum of IgG4 related disease, similar to what is seen in this case. There is currently no reliably effective treatment for AOXGDs, and additional research into the management of these diseases is necessary.
Joseph S, Varadaraj V, Dave SR, Lage E, Lim D, Aziz K, Dudgeon S, Ravilla TD, Friedman DS. Investigation of the Accuracy of a Low-Cost, Portable Autorefractor to Provide Well-Tolerated Eyeglass Prescriptions: A Randomized Crossover Trial. Ophthalmology 2021;128(12):1672-1680.Abstract
PURPOSE: To compare patient preferences for eyeglasses prescribed using a low-cost, portable wavefront autorefractor versus standard subjective refraction (SR). DESIGN: Randomized, cross-over clinical trial. PARTICIPANTS: Patients aged 18 to 40 years presenting with refractive errors (REs) to a tertiary eye hospital in Southern India. METHODS: Participants underwent SR followed by autorefraction (AR) using the monocular version of the QuickSee device (PlenOptika Inc). An independent optician, masked to the refraction approach, prepared eyeglasses based on each refraction approach. Participants (masked to refraction source) were randomly assigned to use SR- or AR-based eyeglasses first, followed by the other pair, for 1 week each. At the end of each week, participants had their vision checked and were interviewed about their experience with the eyeglasses. MAIN OUTCOME MEASURES: Patients preferring eyeglasses were chosen using AR and SR. RESULTS: The 400 participants enrolled between March 26, 2018, and August 2, 2019, had a mean (standard deviation) age of 28.4 (6.6) years, and 68.8% were women. There was a strong correlation between spherical equivalents using SR and AR (r = 0.97, P < 0.001) with a mean difference of -0.07 diopters (D) (95% limits of agreement [LoA], -0.68 to 0.83). Of the 301 patients (75.2%) who completed both follow-up visits, 50.5% (n = 152) and 49.5% (n = 149) preferred glasses prescribed using SR and AR, respectively (95% CI, 45.7-56.3; P = 0.86). There were no differences in demographic or vision characteristics between participants with different preferences (P > 0.05 for all). CONCLUSIONS: We observed a strong agreement between the prescriptions from SR and AR, and eyeglasses prescribed using SR and AR were equally preferred by patients. Wider use of prescribing based on AR alone in resource-limited settings is supported by these findings.
Makuloluwa AK, Hamill KJ, Rauz S, Bosworth L, Haneef A, Romano V, Williams RL, Dartt DA, Kaye SB. Biological tissues and components, and synthetic substrates for conjunctival cell transplantation. Ocul Surf 2021;Abstract
The conjunctiva is the largest component of the ocular surface. It can be damaged by various pathological processes leading to scarring, loss of tissue and dysfunction. Depending on the amount of damage, restoration of function may require a conjunctival graft. Numerous studies have investigated biological and synthetic substrates in the search for optimal conditions for the ex vivo culture of conjunctival epithelial cells that can be used as tissue grafts for transplantation. These substrates have advantages and disadvantages that are specific to the characteristics of each material; the development of an improved material remains a priority. This review is the second of a two-part review in The Ocular Surface. In the first review, the structure and function of the conjunctiva was evaluated with a focus on the extracellular matrix and the basement membrane, and biological and mechanical characteristics of the ideal substrate with recommendations for further studies. In this review the types of biological and synthetic substrates used for conjunctival transplantation are discussed including substrates based on the extracellular matrix. .
Xiong J, Yu C, Su T, Ge Q-M, Shi W-Q, Tang L-Y, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Altered brain network centrality in patients with mild cognitive impairment: an fMRI study using a voxel-wise degree centrality approach. Aging (Albany NY) 2021;13(11):15491-15500.Abstract
PURPOSE: Previous studies in patients with Alzheimer's disease have shown amyloid beta accumulation in the brain and abnormal brain activity, with mild cognitive impairment (MCI) in early stages of the disease. The aim of the current study was to investigate functional connectivity in patients with MCI. METHODS: We recruited 24 subjects in total, including 12 patients with MCI (6 men and 6 women) and 12 healthy controls (HCs) (6 men and 6 women), matched for age, gender, and lifestyle factors. All subjects underwent resting-state functional magnetic resonance imaging scans and voxel-wise degree centrality (DC) was used to evaluate alterations in the strength of brain network connectivity. RESULTS: The DC value of the left inferior temporal gyrus was lower in MCI but significantly higher in the right fusiform gyrus and the left supplementary motor area, compared with HCs. The DC value in left inferior temporal gyrus correlated positively with disease duration and negatively with Mini-Mental State Examination. ROC curve analysis of brain regions showed acceptable specificity and accuracy of DC values between MCIs and HCs in the area under the curve (right fusiform gyrus, 0.955; left supplementary motor area, 0.992; left inferior temporal gyrus, 1.000). CONCLUSIONS: Abnormal functional connectivity in brain regions of patients with MCI may reflect the pathological process of Alzheimer's disease development and could prove useful in clinical diagnosis and treatment.

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