August 2020

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Bakshi SK, Lin SR, Ting DSW, Chiang MF, Chodosh J. The era of artificial intelligence and virtual reality: transforming surgical education in ophthalmology. Br J Ophthalmol 2020;Abstract
Training the modern ophthalmic surgeon is a challenging process. Microsurgical education can benefit from innovative methods to practice surgery in low-risk simulations, assess and refine skills in the operating room through video content analytics, and learn at a distance from experienced surgeons. Developments in emerging technologies may allow us to pursue novel forms of instruction and build on current educational models. Artificial intelligence, which has already seen numerous applications in ophthalmology, may be used to facilitate surgical tracking and evaluation. Within immersive technology, growth in the space of virtual reality head-mounted displays has created intriguing possibilities for operating room simulation and observation. Here, we explore the applications of these technologies and comment on their future in ophthalmic surgical education.
Barrero-Castillero A, Corwin BK, VanderVeen DK, Wang JC. Workforce Shortage for Retinopathy of Prematurity Care and Emerging Role of Telehealth and Artificial Intelligence. Pediatr Clin North Am 2020;67(4):725-733.Abstract
Retinopathy of prematurity (ROP) is the leading cause of childhood blindness in very-low-birthweight and very preterm infants in the United States. With improved survival of smaller babies, more infants are at risk for ROP, yet there is an increasing shortage of providers to screen and treat ROP. Through a literature review of new and emerging technologies, screening criteria, and analysis of a national survey of pediatric ophthalmologists and retinal specialists, the authors found the shortage of ophthalmology workforce for ROP a serious and growing concern. When used appropriately, emerging technologies have the potential to mitigate gaps in the ROP workforce.
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E J-Y, Mihailovic A, Kuo P-L, West SK, Friedman DS, Gitlin LN, Li T, Schrack JA, Ramulu PY. Characterizing the Impact of Fear of Falling on Activity and Falls in Older Adults with Glaucoma. J Am Geriatr Soc 2020;68(8):1847-1851.Abstract
OBJECTIVE: Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN: Prospective observational cohort study. SETTING: Hospital-based single-center recruitment. PARTICIPANTS: Individuals with glaucoma or suspected glaucoma. MEASUREMENTS: FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF≤0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF > 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95% CI = -743 to -71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.
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Franco JJ, Reyes Luis JL, Rahim S, Greenstein S, Pineda R. Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo. Br J Ophthalmol 2020;Abstract
AIM: To evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation. METHODS: A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45 years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC). RESULTS: Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76 months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm to 1436 cells/mm at the conclusion of postoperative follow-up. CONCLUSION: Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely 'mature' corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.
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Gagrani M, Garg I, Ghate D. Surgical interventions for primary congenital glaucoma. Cochrane Database Syst Rev 2020;8:CD008213.Abstract
BACKGROUND: Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries. OBJECTIVES: To compare the effectiveness and safety of different surgical techniques for PCG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months. The interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95% confidence interval (CI) -0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I = 83%). Two trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD -1.64, 95% CI -5.94 to 2.66) and surgical success (RR 1.11, 95% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38% in viscotrabeculotomy and 28% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95% CI 0.63 to 2.83). Two trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD -2.44, 95% CI -3.69 to -1.19; 100 eyes) and at 12 months (MD -1.77, 95% CI -2.92 to -0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40% in the microcatheter group and 17% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (-1). Of the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data. Many of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear. AUTHORS' CONCLUSIONS: The evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.
Gaier ED, Tarabishy S, Bayers C, Wolkow N, Gardiner M, Lefebvre DR, Grob S. Poor prognoses of open globe injuries with concomitant orbital fractures. Orbit 2020;39(4):241-250.Abstract
PURPOSE: Orbital trauma, particularly with open globe injury, can have a wide range of visual outcomes, which can be difficult to predict at presentation. Clinical features on presentation may provide insight into visual prognosis. We hypothesized that patients with open globe injuries and concomitant orbital fractures have poorer visual outcomes than patients without orbital fractures. METHODS: We reviewed the charts of 77 patients with isolated open globe injuries (OG) and 76 patients with open globe injuries and concomitant orbital fractures (OGOF). Multivariate regression analysis was performed to assess the relative influence of individual presenting historical and clinical features on visual outcome. RESULTS: OGOF patients were more likely to have sustained blunt trauma than a sharp, penetrating injury compared to OG patients. Ocular wound locations were more posterior and likely to involve multiple zones in OGOF compared to OG patients. Among OGOF patients, orbital floor fractures were the most common and roof fractures were the least common, but the latter was associated with presenting NLP vision and multiple zone involvement. The presence of an orbital fracture independently increased the odds of subsequent evisceration/enucleation (OR: 4.6, 95% CI 1.3-20.1, = .0246) and NLP vision (OR: 6.81, 95% CI 2.42-21.85, = .0005) when controlling for zone, mechanism of injury, uveal prolapse and demographic variables. CONCLUSIONS: The presence of an orbital fracture independently confers a worse visual and ocular prognosis in patients with open globe injuries. Patients with open globe injuries in this category should be appropriately counseled.
Geffrey AL, Geenen KR, Abati E, Greenstein SH, VanderVeen DK, Levy RL, Davidson SL, McGarrey MP, Thiele EA, Aronow ME. Juvenile cataract in association with tuberous sclerosis complex. Ophthalmic Genet 2020;41(4):345-349.Abstract
BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas occurring in multiple organ systems including the brain, kidneys, heart, lungs, liver, skin, and the eyes. Typical retinal findings associated with TSC include astrocytic hamartoma and achromic patch. While rare cases of cataract occurring in the setting of TSC have been reported, this is the first analysis of a large series of individuals with TSC that aims to quantify the frequency of this finding and to describe its clinical and genetic associations. MATERIALS AND METHODS: This is a retrospective chart review of 244 patients from the Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital who underwent complete ophthalmic examination. We describe the clinical and genetic findings in five individuals with TSC and juvenile cataract. RESULTS: Four of five cases (80%) were unilateral. The cataract was described as having an anterior subcapsular component in 3 of 5 cases (60%). Three individuals (60%) underwent lensectomy with intraocular lens (IOL) implant and two individuals (40%) were observed. Genetic testing revealed a known disease-causing mutation in in 100% of cases. CONCLUSIONS: Recent evidence suggests that mTOR signaling may play a role in cataract formation which could explain the relatively high incidence of juvenile cataract in this population. Juvenile cataract is a potentially under-recognized ocular manifestation of TSC.
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Hanyuda A, Rosner BA, Wiggs JL, Willett WC, Tsubota K, Pasquale LR, Kang JH. Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts. Eye (Lond) 2020;34(8):1465-1475.Abstract
BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976-2016, 1986-2016 and 1991-2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91-1.39; P = 0.40) for the overall score; 1.10 (95% CI, 0.89-1.35; P = 0.38) for the animal score and 0.96 (95% CI, 0.79-1.18; P = 0.88) for the vegetable score. No differential associations by IOP level was found (P ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55-1.10]; P = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83-1.44]; P = 0.14; P = 0.03). CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.
Hu A, Gu SZ, Friedman DS, Cao K, Wang N. Six-Year Incidence and Causes of Low Vision and Blindness in a Rural Chinese Adult Population: The Handan Eye Study. Ophthalmic Epidemiol 2020;:1-9.Abstract
PURPOSE: To determine the six-year incidence, risk factors, and causes of visual impairment in a Chinese population. METHODS: This was a population-based study of eye disease in Chinese adults in a rural district of Handan in China. 6,830 individuals were invited to participate in 2006 and 5,394 returned for follow-up in 2012. All participants underwent standardized eye examinations. Visual impairment was defined according to WHO criteria. The incidence of visual impairment was age- and gender-standardized to the 2010 China Census. Multivariable logistic regression analysis was used to determine risk factors for visual impairment. RESULTS: The leading causes of visual impairment were cataract and refractive error. Based on (PVA), the six-year incidence rates of low vision and blindness were 5.2% and 0.5%, respectively. Incidence of low vision was associated with older age ( < .001), less education ( < .001), diabetes ( < .05), and lower BMI ( < .001). The incidence of blindness was associated with diabetes ( < .05). Based on (BCVA), the six-year incidence rates of low vision and blindness were 0.8% and 0.1%, respectively. Incidence of low vision was associated with older age ( < .001) and lower BMI ( < .05). None of these factors were associated with the incidence of blindness. CONCLUSION: In Handan, the incidence of visual impairment was high and associated with older age, less education, diabetes, and lower BMI. The majority of cases were due to unoperated cataract and uncorrected refractive error, reflecting the need for improved eye care in this region.
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Inomata T, Kitazawa K, Kuno T, Sung J, Nakamura M, Iwagami M, Takagi H, Midorikawa-Inomata A, Zhu J, Fujimoto K, Okumura Y, Miura M, Fujio K, Hirosawa K, Akasaki Y, Kuwahara M, Dana R, Murakami A. Clinical and Prodromal Ocular Symptoms in Coronavirus Disease: A Systematic Review and Meta-Analysis. Invest Ophthalmol Vis Sci 2020;61(10):29.Abstract
Purpose: This systematic review aimed to determine currently reported clinical and prodromal ocular symptoms in patients with coronavirus disease 2019 (COVID-19). Methods: An online article search was performed in PubMed and EMBASE. Altogether 15 studies (retrospective, prospective, or case studies) involving 1533 patients with COVID-19, reporting on ocular symptoms, and with outcome data available were identified. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Study-specific estimates (incidence rates of ocular symptoms in patients with COVID-19) of cases were combined using one-group meta-analysis in a random-effects model. Results: Of all included studies, 11.2% (95% confidence interval, 5.5-16.9; 78/1526 cases) reported ocular symptoms. The most common ocular finding was conjunctivitis. Prodromal ocular symptoms occurred in 12.5% (13/104 cases) of patients with COVID-19. Positive real-time polymerase chain reaction results were obtained for 16.7% (10/60 cases) of conjunctival samples and 0% (0/17 cases) of tear samples. Twelve ocular conjunctival swab samples tested positive for SARS-CoV-2. Ten cases were from subjects showing ocular symptoms (16.7%, 10/60 cases), and the remaining two cases were from subjects without ocular manifestation (1.8%, 2/113 cases). Limitations included the short study period, small sample size, findings were limited to the Asian population, only seven articles included ophthalmologic examination details, and there is currently no consensus on COVID-19 management. Conclusions: Ocular symptoms may occur in the presymptomatic phase as a prodromal symptom (12.5%, 13/104 cases), suggesting the possibility of viral transmission from the conjunctiva.
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Kang J, Cho SS, Kim HY, Lee BH, Cho HJ, Gwak YS. Regional Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury. Cell Mol Neurobiol 2020;40(6):861-878.Abstract
Spinal cord injury (SCI) causes maladaptive changes to nociceptive synaptic circuits within the injured spinal cord. Changes also occur at remote regions including the brain stem, limbic system, cortex, and dorsal root ganglia. These maladaptive nociceptive synaptic circuits frequently cause neuronal hyperexcitability in the entire nervous system and enhance nociceptive transmission, resulting in chronic central neuropathic pain following SCI. The underlying mechanism of chronic neuropathic pain depends on the neuroanatomical structures and electrochemical communication between pre- and postsynaptic neuronal membranes, and propagation of synaptic transmission in the ascending pain pathways. In the nervous system, neurons are the only cell type that transmits nociceptive signals from peripheral receptors to supraspinal systems due to their neuroanatomical and electrophysiological properties. However, the entire range of nociceptive signaling is not mediated by any single neuron. Current literature describes regional studies of electrophysiological or neurochemical mechanisms for enhanced nociceptive transmission post-SCI, but few studies report the electrophysiological, neurochemical, and neuroanatomical changes across the entire nervous system following a regional SCI. We, along with others, have continuously described the enhanced nociceptive transmission in the spinal dorsal horn, brain stem, thalamus, and cortex in SCI-induced chronic central neuropathic pain condition, respectively. Thus, this review summarizes the current understanding of SCI-induced neuronal hyperexcitability and maladaptive nociceptive transmission in the entire nervous system that contributes to chronic central neuropathic pain.
Keel S, Evans JR, Block S, Bourne R, Calonge M, Cheng C-Y, Friedman DS, Furtado JM, Khanna RC, Mathenge W, Mariotti S, Matoto E, Müller A, Rabiu MM, Rasengane T, Zhao J, Wormald R, Cieza A. Strengthening the integration of eye care into the health system: methodology for the development of the WHO package of eye care interventions. BMJ Open Ophthalmol 2020;5(1):e000533.Abstract
Objective: To describe the rational for, and the methods that will be employed to develop, the WHO package of eye care interventions (PECI). Methods and analysis: The development of the package will be conducted in four steps: (1) selection of eye conditions (for which interventions will be included in the package) based on epidemiological data on the causes of vision impairment and blindness, prevalence estimates of eye conditions and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from clinical practice guidelines and high-quality systematic reviews by a technical working group; (3) expert agreement on the inclusion of eye care interventions in the package and the description of resources required for the provision of the selected interventions; and (4) peer review. The project will be led by the WHO Vision Programme in collaboration with Cochrane Eyes and Vision. A Technical Advisory Group, comprised of public health and clinical experts in the field, will provide technical input throughout all stages of development. Results: After considering the feedback of Technical Advisory Group members and reviewing-related evidence, a final list of eye conditions for which interventions will be included in the package has been collated. Conclusion: The PECI will support Ministries of Health in prioritising, planning, budgeting and integrating eye care interventions into health systems. It is anticipated that the PECI will be available for use in 2021.
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Lee JS, Mukherjee S, Lee JY, Saha A, Chodosh J, Painter DF, Rajaiya J. Entry of Epidemic Keratoconjunctivitis-Associated Human Adenovirus Type 37 in Human Corneal Epithelial Cells. Invest Ophthalmol Vis Sci 2020;61(10):50.Abstract
Purpose: Ocular infection by human adenovirus species D type 37 (HAdV-D37) causes epidemic keratoconjunctivitis, a severe, hyperacute condition. The corneal component of epidemic keratoconjunctivitis begins upon infection of corneal epithelium, and the mechanism of viral entry dictates subsequent proinflammatory gene expression. Therefore, it is important to understand the specific pathways of adenoviral entry in these cells. Methods: Transmission electron microscopy of primary and tert-immortalized human corneal epithelial cells infected with HAdV-D37 was performed to identify the means of viral entry. Confocal microscopy was used to determine intracellular trafficking. The results of targeted small interfering RNA and specific chemical inhibitors were analyzed by quantitative PCR, and Western blot. Results: By transmission electron microscopy, HAdV-D37 was seen to enter by both clathrin-coated pits and macropinocytosis; however, entry was both pH and dynamin 2 independent. Small interfering RNA against clathrin, AP2A1, and lysosome-associated membrane protein 1, but not early endosome antigen 1, decreased early viral gene expression. Ethyl-isopropyl amiloride, which blocks micropinocytosis, did not affect HAdV-D37 entry, but IPA, an inhibitor of p21-activated kinase, and important to actin polymerization, decreased viral entry in a dose-dependent manner. Conclusions: HAdV-D37 enters human corneal epithelial cells by a noncanonical clathrin-mediated pathway involving lysosome-associated membrane protein 1 and PAK1, independent of pH, dynamin, and early endosome antigen 1. We showed earlier that HAdV-D37 enters human keratocytes through caveolae. Therefore, epidemic keratoconjunctivitis-associated viruses enter different corneal cell types via disparate pathways, which could account for a relative paucity of proinflammatory gene expression upon infection of corneal epithelial cells compared with keratocytes, as seen in prior studies.
Liu Z, Xu J, Ma Q, Zhang X, Yang Q, Wang L, Cao Y, Xu Z, Tawfik A, Sun Y, Weintraub NL, Fulton DJ, Hong M, Dong Z, Smith LEH, Caldwell RB, Sodhi A, Huo Y. Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche. Sci Transl Med 2020;12(555)Abstract
The coordination of metabolic signals among different cellular components in pathological retinal angiogenesis is poorly understood. Here, we showed that in the pathological angiogenic vascular niche, retinal myeloid cells, particularly macrophages/microglia that are spatially adjacent to endothelial cells (ECs), are highly glycolytic. We refer to these macrophages/microglia that exhibit a unique angiogenic phenotype with increased expression of both M1 and M2 markers and enhanced production of both proinflammatory and proangiogenic cytokines as pathological retinal angiogenesis-associated glycolytic macrophages/microglia (PRAGMs). The phenotype of PRAGMs was recapitulated in bone marrow-derived macrophages or retinal microglia stimulated by lactate that was produced by hypoxic retinal ECs. Knockout of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (; for rodents), a glycolytic activator in myeloid cells, impaired the ability of macrophages/microglia to acquire an angiogenic phenotype, rendering them unable to promote EC proliferation and sprouting and pathological neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Mechanistically, hyperglycolytic macrophages/microglia produced large amount of acetyl-coenzyme A, leading to histone acetylation and PRAGM-related gene induction, thus reprogramming macrophages/microglia into an angiogenic phenotype. These findings reveal a critical role of glycolytic metabolites as initiators of reciprocal activation of macrophages/microglia and ECs in the retinal angiogenic niche and suggest that strategies targeting the metabolic communication between these cell types may be efficacious in the treatment of pathological retinal angiogenesis.
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M A, K S, A C, O A-Q, J R, PS S, LP A, JK S. Vascular Density of Deep, Intermediate and Superficial Vascular Plexuses Are Differentially Affected by Diabetic Retinopathy Severity. Invest Ophthalmol Vis Sci 2020;61(10):53.
Maleki A, Ueberroth JA, Manhapra A, Walsh M, Asgari S, Chang PY, Anesi SD, Foster SC. Fixed-Luminance and Multi-Luminance Flicker Electroretinography Parameters in Patients with Early Active Birdshot Chorioretinopathy. Ocul Immunol Inflamm 2020;:1-7.Abstract
Purpose To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. Methods Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. Results There was no statistically significant difference between the Fixed-Luminance flicker magnitude ( = .6), the Fixed-Luminance flicker phase ( = .9), and the Multi-Luminance flicker phase area under the curve ( = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. ( = .003) Conclusions Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. Abbreviations BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.
Marmamula S, Barrenkala NR, Challa R, Kumbham TR, Modepalli SB, Yellapragada R, Bhakki M, Friedman DS, Khanna RC. Falls and visual impairment among elderly residents in 'homes for the aged' in India. Sci Rep 2020;10(1):13389.Abstract
We evaluated the prevalence of falls and their association with visual impairment (VI) in elderly residents in 'homes for the aged' in Hyderabad, India. Participants aged ≥ 60 years were recruited from 41 homes, and a comprehensive eye examination was conducted. Interviews were conducted to collect personal and demographic information, systemic health status, fear of falling, depression, and history of falls in the last year. VI categories included low vision (presenting visual acuity worse than 6/18 to 3/60) and blindness (presenting visual acuity worse than 3/60). The data of 1,074 participants were analysed. The mean age was 74.4 years (standard deviation:8.7 years); 63.9% were women, 19.4% had no formal education, 28.1% were diabetic and 56.9% were hypertensive. The annual prevalence of falls was 29.1% (95% CI: 26.4-32.0). Multivariable analysis showed those with VI had significantly higher odds of falls (Odds Ratio:1.47; p = 0.043). The prevalence of falls was higher among those with VI due to uncorrected refractive errors. We found a very high prevalence of falls in elderly individuals living in 'homes for the aged' in Hyderabad, India. Addressing VI can result in fewer falls and contribute to healthy aging in India.
McKay TB, Hutcheon AEK, Guo X, Zieske JD, Karamichos D. Modeling the cornea in 3-dimensions: Current and future perspectives. Exp Eye Res 2020;197:108127.Abstract
The cornea is an avascular, transparent ocular tissue that serves as a refractive and protective structure for the eye. Over 90% of the cornea is composed of a collagenous-rich extracellular matrix within the stroma with the other 10% composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers (e.g., Bowman's and Descemet's membranes) at the anterior and posterior cornea, respectively. Due to its prominent role in corneal structure, tissue engineering approaches to model the human cornea in vitro have focused heavily on the cellular and functional properties of the corneal stroma. In this review, we discuss model development in the context of culture dimensionality (e.g., 2-dimensional versus 3-dimensional) and expand on the optical, biomechanical, and cellular functions promoted by the culture microenvironment. We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration.
Molinaro A, Micheletti S, Rossi A, Gitti F, Galli J, Merabet LB, Fazzi EM. Autistic-Like Features in Visually Impaired Children: A Review of Literature and Directions for Future Research. Brain Sci 2020;10(8)Abstract
There remains great interest in understanding the relationship between visual impairment (VI) and autism spectrum disorder (ASD) due to the extraordinarily high prevalence of ASD in blind and visually impaired children. The broad variability across individuals and assessment methodologies have made it difficult to understand whether autistic-like symptoms shown by some children with VI might reflect the influence of the visual deficit, or represent a primary neurodevelopmental condition that occurs independently of the VI itself. In the absence of a valid methodology adapted for the visually impaired population, diagnosis of ASD in children with VI is often based on non-objective clinical impression, with inconclusive prevalence data. In this review, we discuss the current state of knowledge and suggest directions for future research.
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Savage SW, Zhang L, Swan G, Bowers AR. The effects of age on the contributions of head and eye movements to scanning behavior at intersections. Transp Res Part F Traffic Psychol Behav 2020;73:128-142.Abstract
The current study was aimed at evaluating the effects of age on the contributions of head and eye movements to scanning behavior at intersections. When approaching intersections, a wide area has to be scanned requiring large lateral head rotations as well as eye movements. Prior research suggests older drivers scan less extensively. However, due to the wide-ranging differences in methodologies and measures used in prior research, the extent to which age-related changes in eye or head movements contribute to these deficits is unclear. Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. Scans, analyzed for 15 four-way intersections in city drives, were split into two categories: (consisting only of eye movements) and (containing both head and eye movements). Older drivers made smaller scans than younger drivers (46.6° vs. 53°), as well as smaller scans (9.2° vs. 10.1°), resulting in overall smaller scans. For scans, older drivers had both a smaller head and a smaller eye movement component. Older drivers made more scans than younger drivers (7 vs. 6) but fewer scans (2.1 vs. 2.7). This resulted in no age effects when considering scans. Our results clarify the contributions of eye and head movements to age-related deficits in scanning at intersections, highlight the importance of analyzing both eye and head movements, and suggest the need for older driver training programs that emphasize the importance of making large scans before entering intersections.

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