June 2021

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Than T, Morettin CE, Harthan JS, Hartwick ATE, Huecker JB, Johnson SD, Migneco MK, Shorter E, Whiteside M, Margolis MS, Olson CK, Alferez CS, van Zyl T, Rodic-Polic B, Storch GA, Gordon MO. Efficacy of a Single Administration of 5% Povidone-Iodine in the Treatment of Adenoviral Conjunctivitis. Am J Ophthalmol 2021;Abstract
PURPOSE: To evaluate the safety and efficacy of a single, in-office administration of 5% povidone-iodine (PVP-I) compared to artificial tears (AT) for adenoviral conjunctivitis (Ad-Cs). DESIGN: Double-masked pilot randomized trial METHODS: Patients presenting with presumed adenoviral conjunctivitis were screened at 9 U.S. clinics. INCLUSION CRITERIA: ≥ 18 years of age, symptoms ≤ 4 days and a positive AdenoPlus® test. EXCLUSION CRITERIA: thyroid disease, iodine allergy, recent ocular surgery, and ocular findings inconsistent with early-stage Ad-Cs. Randomization was to a single administration of 5% PVP-I or AT in one eye and examinations on days 1-2, 4, 7, 14 and 21 with conjunctival swabs taken each visit for quantitative polymerase chain reaction. Primary outcome was percent reduction from peak viral load. Secondary outcomes were improvement in clinical signs and symptoms. RESULTS: Of 56 patients randomized, 28 had detectable viral titers at baseline. Day 4 post-treatment, viral titers in the 5% PVP-I and AT groups were 2.5% ± 2.7% and 14.4% ± 10.5% of peak respectively (p=0.020). Severity of participant-reported tearing, lid swelling and redness as well as clinician-graded mucoid discharge, bulbar redness and bulbar edema were lower in the 5% PVP-I group than AT group on Day 4 (p< 0.05). After Day 4, viral titers, severity of signs and symptoms decreased markedly in both groups and no differences between groups were detected. CONCLUSIONS: Pilot data suggest a single, in-office administration of 5% PVP-I could reduce viral load and hasten improvement of clinical signs and symptoms in patients with Ad-Cs.
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.
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Ung L, Agarwala AV, Chodosh J. Achieving Racial Equity Within Medical Institutions: An Appeal for Action. Mayo Clin Proc 2021;96(6):1401-1403.
Ung L, Chodosh J. Foundational concepts in the biology of bacterial keratitis. Exp Eye Res 2021;:108647.Abstract
Bacterial infections of the cornea, or bacterial keratitis (BK), are notorious for causing rapidly fulminant disease and permanent vision loss, even among treated patients. In the last sixty years, dramatic upward trajectories in the frequency of BK have been observed internationally, driven in large part by the commercialization of hydrogel contact lenses in the late 1960s. Despite this worsening burden of disease, current evidence-based therapies for BK - including broad-spectrum topical antibiotics and, if indicated, topical corticosteroids - fail to salvage vision in a substantial proportion of affected patients. Amid growing concerns of rapidly diminishing antibiotic utility, there has been renewed interest in urgently needed novel treatments that may improve clinical outcomes on an individual and public health level. Bridging the translational gap in the care of BK requires the identification of new therapeutic targets and rational treatment design, but neither of these aims can be achieved without understanding the complex biological processes that determine how bacterial corneal infections arise, progress, and resolve. In this chapter, we synthesize the current wealth of human and animal experimental data that now inform our understanding of basic BK pathophysiology, in context with modern concepts in ocular immunology and microbiology. By identifying the key molecular determinants of clinical disease, we explore how novel treatments can be developed and translated into routine patient care.
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Wladis EJ, Aakalu VK, Sobel RK, McCulley TJ, Foster JA, Tao JP, Freitag SK, Yen MT. Interventions for Indirect Traumatic Optic Neuropathy: A Report by the American Academy of Ophthalmology. Ophthalmology 2021;128(6):928-937.Abstract
PURPOSE: To review the literature on the efficacy and safety of medical and surgical interventions for indirect traumatic optic neuropathy (TON), defined as injury to the nerve that occurs distal to the optic nerve head. METHODS: A literature search was conducted on October 22, 2019, and updated on April 8, 2020, in the PubMed database for English language original research that assessed the effect of various interventions for indirect TON. One hundred seventy-two articles were identified; 41 met the inclusion criteria outlined for assessment and were selected for full-text review and abstraction. On full-text review, a total of 32 studies met all of the study criteria and were included in the analysis. RESULTS: No study met criteria for level I evidence. Seven studies (1 level II study and 6 level III studies) explored corticosteroid therapy that did not have uniformly better outcomes than observation. Twenty studies (3 level II studies and 17 level III studies) assessed optic canal decompression and the use of corticosteroids. Although visual improvement was noted after decompression, studies that directly compared surgery with medical therapy did not report uniformly improved outcomes after decompression. Four studies (1 level II study and 3 level III studies) evaluated the use of erythropoietin. Although initial studies demonstrated benefit, a direct comparison of its use with observation and corticosteroids failed to confirm the usefulness of this medication. One study (level II) documented visual improvement with levodopa plus carbidopa. Complication rates were variable with all of these interventions. Pharmacologic interventions generally were associated with few complications, whereas optical canal decompression carried risks of serious side effects, including hemorrhages and cerebrospinal fluid leakage. CONCLUSIONS: Despite reports of visual improvement with corticosteroids, optic canal decompression, and medical therapy for indirect TON, the weight of published evidence does not demonstrate a consistent benefit for any of these interventions. In summary, no consensus exists from studies published to date on a preferred treatment for TON. Treatment strategies should be customized for each individual patient. More definitive treatment trials will be needed to identify optimal treatment strategies for indirect TON.
Wu F, Goldenberg PC, Mukai S. Bilateral anterior segment dysgenesis and peripheral avascular retina with tractional retinal detachment in an infant with multiple congenital anomalies-hypotony-seizures syndrome 3. Ophthalmic Genet 2021;42(3):334-337.Abstract
Background: Multiple congenital anomalies-hypotony-seizures syndrome 3 (MCAHS3) is a rare autosomal recessive disorder caused by mutations in the PIGT gene. PIGT encodes phosphatidylinositol-glycan biosynthesis class T, which plays a crucial role in protein anchoring to cell membranes. The clinical presentation of MCAHS3 is variable in expression and severity, but can be characterized by developmental delay, seizures, hypotonia, facial dysmorphism, and other abnormalities.Materials and Methods: Case report.Results: We report unusual ocular findings including bilateral anterior segment dysgenesis, avascular retinal periphery, and tractional retinal detachment in a 1-month-old male infant with compound heterozygous PIGT mutations consistent with MCAHS3. Whole-exome sequencing did not detect any other genetic abnormalities.Conclusions: This case expands the clinical spectrum of MCAHS3 to include anomalies in ocular anterior segment and retinal vascular development. Given the rarity and the genetic heterogeneity of MCAHS3, giving rise to varied non-ocular phenotypes, it is possible that milder intraocular phenotypes could have gone unrecognized in the past.
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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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Yu K, Guo Y, Ge Q-M, Su T, Shi W-Q, Zhang L-J, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study. Sci Rep 2021;11(1):12943.Abstract
This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P < 0.0001). The ReHo values of the middle frontal gyrus and dorsolateral superior frontal gyrus were correlated to disease duration (P < 0.05). Symptoms of ocular surface injury in DE patients are associated with dysfunction in specific brain regions, which may underlie the cognitive impairment, psychiatric symptoms, and depressive mood observed in DE patients. The decreased ReHo values of some brain gyri in this study may provide a reference for clinical diagnosis and determination of treatment efficacy.
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Zhang YJ, Jimenez L, Azova S, Kremen J, Chan Y-M, Elhusseiny AM, Saeed H, Goldsmith J, Al-Ibraheemi A, O'Connell AE, Kovbasnjuk O, Rodan L, Agrawal PB, Thiagarajah JR. Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis. Eur J Hum Genet 2021;29(6):998-1007.Abstract
WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein's putative involvement in multiple developmental and stem cell maintenance pathways.

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