May 2020

Sohn EH, Strohbehn A, Stryjewski T, Brodowska K, Flamme-Wiese MJ, Mullins RF, Eliott D. POSTERIORLY INSERTED VITREOUS BASE: Preoperative Characteristics, Intraoperative Findings, and Outcomes After Vitrectomy. Retina 2020;40(5):943-950.Abstract
PURPOSE: To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base. METHODS: In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain. RESULTS: Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84%), 4 with macular hole (11%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24%; 54% had 360° laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm. CONCLUSION: Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.
Fan N-W, Dohlman TH, Foulsham W, McSoley M, Singh RB, Chen Y, Dana R. The role of Th17 immunity in chronic ocular surface disorders. Ocul Surf 2020;Abstract
Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.
Aminkhani A, Sharifi S, Ekhtiyari S. Achillea filipendulina Lam.: Chemical Constituents and Antimicrobial Activities of Essential Oil of Stem, Leaf, and Flower. Chem Biodivers 2020;17(5):e2000133.Abstract
In this study, we extracted the essential oils of the stem, leaf, and flower of Achillea filipendulina, analyzed them, and studied their antibacterial properties. Of 16, 53, and 35 compounds identified in the stem, leaf, and flowers, respectively, only five are present in all three segments of the plant. The essential oil of the stem was mainly composed of neryl acetate, spathulenol, carvacrol, santolina alcohol, and trans-caryophyllene oxide. However, the main identified components of leaf were 1,8-cineole, camphor, ascaridole, trans-isoascaridole, and piperitone oxide and the main components of the flower oil were ascaridole, trans-isoascaridole, 1,8-cineole, p-cymene, and camphor. The extracted oil from different segments demonstrated varying antibacterial properties against both Gram-positive and Gram-negative bacteria, demonstrated by disk, minimum inhibitory concentration, and minimum bactericidal concentration methods. These suggest that the application of all segments of aerial parts of A. filipendulina may have a better therapeutic effect in fighting pathogenic systems.
van Zyl T, Yan W, McAdams A, Peng Y-R, Shekhar K, Regev A, Juric D, Sanes JR. Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis. Proc Natl Acad Sci U S A 2020;117(19):10339-10349.Abstract
Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (), rhesus macaque (), pig (), and mouse (). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.
Almeida LM, Lebreton F, Gaca A, Bispo PM, Saavedra JT, Calumby RN, Grillo LM, Nascimento TG, Filsner PH, Moreno AM, Gilmore MS. Transferable Resistance Gene in Enterococcus faecalis from Swine in Brazil. Antimicrob Agents Chemother 2020;64(6)Abstract
OptrA is an ATP-binding cassette (ABC)-F protein that confers resistance to oxazolidinones and phenicols and can be either plasmid-encoded or chromosomally encoded. Here, we isolated 13 strains possessing a linezolid MIC of ≥4 mg/liter from nursery pigs in swine herds located across Brazil. Genome sequence comparison showed that these strains possess in different genetic contexts occurring in 5 different sequence type backgrounds. The gene invariably occurred in association with an regulator and a gene encoding a hypothetical protein. In some contexts, this genetic island was able to excise and form a covalently closed circle within the cell; this circle appeared to occur in high abundance and to be transmissible by coresident plasmids.
Vira J, Marchese A, Singh RB, Agarwal A. Swept-source optical coherence tomography imaging of the retinochoroid and beyond. Expert Rev Med Devices 2020;17(5):413-426.Abstract
: Swept-source optical coherence tomography (SS-OCT) imaging has ushered in an era of rapid and high-resolution imaging of the retinochoroid that provides detailed patho-anatomy of various layers.: In this detailed review, the technology of swept-source imaging including its principles and working has been discussed. The applications of SS-OCT in various conditions including age-related macular degeneration, diabetic retinopathy, pachychoroid spectrum of diseases, and inflammatory vitreoretinal conditions have been elaborated. For each disease, a brief review of literature along with the utility of SS-OCT and optical coherence tomography angiography has been provided with supporting figures. The advantages of SS-OCT over spectral-domain have been discussed if there is sufficient evidence in the literature. Finally, the review summarizes the technological advantages in this field of retinal imaging.: The introduction of SS-OCT in our clinics has added newer devices in our armamentarium that can provide high-quality images of the deep retina and choroid. These advances in medical devices can help in improving our knowledge relating to the pathophysiology of diseases and their evolution. In the near future, rapid and high-resolution imaging may provide real-time volumetric information of the whole retina and the choroid that can be readily used for patient care.
Corral-Serrano JC, Lamers IJC, van Reeuwijk J, Duijkers L, Hoogendoorn ADM, Yildirim A, Argyrou N, Ruigrok RAA, Letteboer SJF, Butcher R, van Essen MD, Sakami S, van Beersum SEC, Palczewski K, Cheetham ME, Liu Q, Boldt K, Wolfrum U, Ueffing M, Garanto A, Roepman R, Collin RWJ. PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation. Proc Natl Acad Sci U S A 2020;117(18):9922-9931.Abstract
The outer segments (OS) of rod and cone photoreceptor cells are specialized sensory cilia that contain hundreds of opsin-loaded stacked membrane disks that enable phototransduction. The biogenesis of these disks is initiated at the OS base, but the driving force has been debated. Here, we studied the function of the protein encoded by the photoreceptor-specific gene , which is mutated in inherited retinal dystrophy (RP54). We demonstrate that C2orf71/PCARE (photoreceptor cilium actin regulator) can interact with the Arp2/3 complex activator WASF3, and efficiently recruits it to the primary cilium. Ectopic coexpression of PCARE and WASF3 in ciliated cells results in the remarkable expansion of the ciliary tip. This process was disrupted by small interfering RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE harboring a retinal dystrophy-associated missense mutation. Using human retinal organoids and mouse retina, we observed that a similar actin dynamics-driven process is operational at the base of the photoreceptor OS where the PCARE module and actin colocalize, but which is abrogated in mice. The observation that several proteins involved in retinal ciliopathies are translocated to these expansions renders it a potential common denominator in the pathomechanisms of these hereditary disorders. Together, our work suggests that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane at the initiation of new outer segment disk formation.
Feldstein IT, Peli E. Pedestrians Accept Shorter Distances to Light Vehicles Than Dark Ones When Crossing the Street. Perception 2020;49(5):558-566.Abstract
Does the brightness of an approaching vehicle affect a pedestrian's crossing decision? Thirty participants indicated their street-crossing intentions when facing approaching light or dark vehicles. The experiment was conducted in a real daylight environment and, additionally, in a corresponding virtual one. A real road with actual cars provides high face validity, while a virtual environment ensures the scenario's precise reproducibility and repeatability for each participant. In both settings, participants judged dark vehicles to be a more imminent threat-either closer or moving faster-when compared with light ones. Secondary results showed that participants accepted a significantly shorter time-to-contact when crossing the street in the virtual setting than on the real road.
Marmamula S, Barrenkala NR, Challa R, Kumbam TR, Modepalli SB, Yellapragada R, Bhakki M, Khanna RC, Friedman DS. Uncorrected refractive errors for distance among the residents in 'homes for the aged' in South India-The Hyderabad Ocular Morbidity in Elderly Study (HOMES). Ophthalmic Physiol Opt 2020;40(3):343-349.Abstract
PURPOSE: To investigate the prevalence and risk factors of Uncorrected Refractive Errors (URE) for distance in elderly residents in 'homes for the aged' in Hyderabad, India. METHODS: Individuals aged ≥60 years and residing in 'homes for the aged' in Hyderabad, India for a minimum of 1 month and providing consent for participation were recruited. All participants underwent visual acuity assessment, refraction, slit lamp biomicroscopy, intraocular pressure measurement, fundus examination, and retinal imaging. Monocular presenting visual acuity was recorded using a logMAR chart. Objective and subjective refraction were performed, and best-corrected visual acuity was recorded. URE was defined as presenting visual acuity worse than 6/12 but improving to 6/12 or better with refraction. Univariable and multivariable logistic regression analyses were used to assess the risk factors associated with URE. RESULTS: In total, 1 513 elderly participants were enumerated from 41 homes of which 1 182 participants (78.1%) were examined. The mean age of participants was 75.0 years (standard deviation 8.8 years; range: 60-108 years). 35.4% of those examined were men and 20.3% had no formal education. The prevalence of URE was 13.5% (95% CI: 11.5-15.5; n = 159). On applying multiple logistic regression analysis, compared to those living in private homes, the odds of URE were significantly higher among the elderly living in the aided homes (OR: 1.65; 95% CI: 1.11-2.43) and free homes (OR: 1.67; 95% CI: 1.00-2.80). As compared to those who reported having an eye examination in the last 3 years, the odds of URE were higher among those who never had an eye examination in the last three years (OR: 1.51; 95% CI: 1.07-2.14). Similarly, those who had unilateral cataract surgery (OR: 1.80; 95% CI: 1.10-2.93) or bilateral cataract surgery (1.69; 95% CI: 1.10-2.56) had higher odds of URE compared to those elderly who were not operated for cataract. Gender, self-report of diabetes, and education were not associated with URE. CONCLUSIONS: A large burden of URE was found among the residents in the 'homes for the aged' in Hyderabad, India which could be addressed with a pair of glasses. Over 40% of the residents never had an eye examination in the last three years, which indicates poor utilisation of eye care services by the elderly. Regular eye examinations and provision of spectacles are needed to address needless URE for distance among the elderly in residential care in India.
Akbari A, Jabbari N, Sharifi R, Ahmadi M, Vahhabi A, Seyedzadeh SJ, Nawaz M, Szafert S, Mahmoodi M, Jabbari E, Asghari R, Rezaie J. Free and hydrogel encapsulated exosome-based therapies in regenerative medicine. Life Sci 2020;249:117447.Abstract
Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine.
Jumelle C, Gholizadeh S, Annabi N, Dana R. Advances and limitations of drug delivery systems formulated as eye drops. J Control Release 2020;321:1-22.Abstract
Topical instillation of eye drops remains the most common and easiest route of ocular drug administration, representing the treatment of choice for many ocular diseases. Nevertheless, low ocular bioavailability of topically applied drug molecules can considerably limit their efficacy. Over the last several decades, numerous drug delivery systems (DDS) have been developed in order to improve drug bioavailability on the ocular surfaces. This review systematically covers the most recent advances of DDS applicable by topical instillation, that have shown better performance in in vivo models compared to standard eye drop formulations. These delivery systems are based on in situ forming gels, nanoparticles and combinations of both. Most of the DDS have been developed using natural or synthetic polymers. Polymers offer many advantageous properties for designing advanced DDS including biocompatibility, gelation properties and/or mucoadhesiveness. However, despite the high number of studies published over the last decade, there are several limitations for clinical translation of DDS. This review article focuses on the recent advances for the development of ocular drug delivery systems. In addtion, the potential challenges for commercialization of new DDS are presented.
Freitag SK, Tanking T. A Nomenclature to Describe the Sequence of Visual Field Defects in Progressive Thyroid Eye Disease-Compressive Optic Neuropathy (An American Ophthalmological Society Thesis). Am J Ophthalmol 2020;213:293-305.Abstract
PURPOSE: To create a novel nomenclature to characterize the longitudinal sequence of visual field (VF) defects in patients with progression of thyroid eye disease-compressive optic neuropathy (TED-CON). METHODS: A retrospective review of records from 1 institution identified patients with progressive Humphrey VF defects secondary to TED-CON. The VF defects were analyzed by 2 independent reviewers and classified into 1 of 10 categories, divided into 3 stages that reflect the observed progression pattern, plus a miscellaneous category (stage X). Stage 1 VF defects are the earliest detectable and involve the inferior visual field with 3 levels of severity. Stage 2 VF defects include 2 distinguishable levels of severity and occur as the inferior defects advance above the horizontal midline to involve the superior VF. Stage 3 involves progression of stage 2 VF defects to complete loss of inferior and superior hemifields. RESULTS: Of 234 VFs in 37 eyes of 23 subjects, inferior defects were most common, including stage 1a (small inferior paracentral defect) in 22 of 234 VFs (9.4%), stage 1b (large inferior paracentral defect) in 112 of 234 VFs (47.9%), and stage 1c (inferior altitudinal defect) in 11 of 234 VFs (4.7%). Stage 2a (inferior altitudinal with superior advancement above the horizontal meridian) occurred in 41 of 234 VFs (17.5%), stage 2b (inferior altitudinal with superior arcuate) occurred in 6 of 234 VFs (2.6%), and stage 3 (total loss) occurred in 5 of 234 VFs (2.1%). The longitudinal sequence of VF defects from the 37 eyes of 23 patients was analyzed. Thirty-one of 37 eyes (83.8%) demonstrated a predictable progression pattern from least to more severe: stage 1a, stage 1b, stage 1c, stage 2a, stage 2b, and stage 3. A reverse order of VF defect progression was noted in 15 eyes with improving TED-CON. A minority of progression patterns (16.2%) originated from stage X (central/paracentral, enlarged blind spot, and scatter). CONCLUSIONS: Humphrey VF defects resulting from TED-CON are most often inferior, often have a predictable pattern of progression, and can be categorized into a novel descriptive nomenclature system. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Koo EH, Pineda R, Afshari N, Eghrari A. Learning Descemet Membrane Endothelial Keratoplasty: A Survey of U.S. Corneal Surgeons. Cornea 2020;39(5):590-593.Abstract
PURPOSE: The transition to Descemet membrane endothelial keratoplasty (DMEK) is frequently challenging, requiring the adoption of new techniques, skills, and methods. We sought to draw on surgeons' initial experiences with DMEK to characterize the learning curve associated with this procedure and identify factors that could be linked to the frequency of primary graft failure (PGF) in the first 10 cases. METHODS: We invited corneal surgeons based in the United States who started performing the DMEK procedure within the past 2 years to answer a 12-question survey using an online survey platform. We analyzed quantitative and qualitative data. A Fisher exact test was used to determine whether preoperative approaches to preparation were associated with decreased PGF rates. RESULTS: A total of 100 US-based corneal surgeons replied from 34 of 50 states. Of these, 68% reported that DMEK comprised a majority of their endothelial keratoplasty cases. Approximately half of surgeons (52%) had performed more than 20 DMEK cases by the time of the survey, and 51% felt equally comfortable performing DMEK relative to Descemet stripping endothelial keratoplasty. Among the respondents, 37% answered that they had experienced PGF in the first 10 cases. Scrubbing in with an experienced colleague before surgery was associated with a decreased likelihood of at least one case of PGF (31%, P = 0.049), but not participation in a wet lab with an experienced instructor or mentor (38%, P = 0.50), nor having an eye bank representative present in the operating room (43%, P = 0.886). CONCLUSIONS: The collective experience of 100 surgeons beginning DMEK confirms the importance of mentorship and that the accompaniment of an experienced colleague during the learning curve is associated with lower rates of PGF.

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