Publications

2020

Haque M, Lei F, Xiong X, Ren Y, Kumar A, Das JK, Ren X, Fang D, Figueiredo P, Yang JM, Song J. Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺. iScience. 2020;23(7):101333.
The viral antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed HBV replication and prevented HBV surface Ag expression. We further demonstrate that the adoptive transfer significantly increased T cell accumulation and production of antiviral cytokines. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the liver and suppress HBV replication through producing antiviral cytokines.
Liebman D, McKay KM, Haviland M, Moustafa G, Borkar D, Kloek C. Quantifying the educational benefit of additional cataract surgery cases in ophthalmology residency. J Cataract Refract Surg. 2020;46(11):1495–1500.
PURPOSE: To quantify the resident learning curve for cataract surgery using operative time as an indicator of surgical competency, to identify the case threshold at which marginal additional educational benefit became equivocal, and to characterize heterogeneity in residents' pathways to surgical competency. SETTING: Academic medical center. DESIGN: Large-scale retrospective consecutive case series. METHODS: All cataract surgery cases performed by resident physicians as primary surgeon at Massachusetts Eye and Ear from July 1, 2010, through June 30, 2015, were reviewed. Data were abstracted from Accreditation Council for Graduate Medical Education case logs and operative time measurements. A linear mixed-methods analysis was conducted to model changes in residents' cataract surgery operative times as a function of sequential case number, with resident identity included as a random effect in the model to normalize between-resident variability. RESULTS: A total of 2096 cases were analyzed. A marked progressive decrease in operative time was noted for resident cases 1 to 39 (mean change -0.17 minutes per additional case, 95% CI, -0.21 to -0.12; P < .001). A modest, steady reduction in operative time was subsequently noted for case numbers 40 to 149 (mean change -0.05 minutes per additional case, 95% CI, -0.07 to -0.04; P < .001). No statistically significant improvement was found in operative times beyond the 150th case. CONCLUSIONS: Residents derived educational benefit from performing a greater number of cataract procedures than current minimum requirements. However, cases far in excess of this threshold might have diminishing educational return in residency. Educational resources currently used for these cases might be more appropriately devoted to other training priorities.
McKay T, Schlötzer-Schrehardt U, Pal-Ghosh S, Stepp MA. Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells. Exp Eye Res. 2020;:108138.
Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet's membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and endothelial cells in vitro for transplantation in the clinic thereby transforming clinical practice and quality of life for patients. Current knowledge on the expression and function of the integrins that mediate adhesion to the basement membrane expressed by corneal epithelial and endothelial cells in health and disease is summarized. This is the first review to discuss similarities and differences in the integrins expressed by both cell types.
FCRS AM, MBBS B, MD T, MBBS M, MS A, MD GD, PhD R, MS A, DNB MS, FRCSOphth W, FRCSEd CS, MD M, FRCSGlasg HS, FRCSEd T, MD C, MS B, MD N, MS A, DNB M, MD K, FRCSOphth J, MD TT, DNB B, MS B, MD C, PhD L, MD AD, MD B, MD I, MD GD, MD HC, PhD BA, PhD GLJ, MD A, MS B, MS M, MD E, MD T, MD N, DNB A, MD A, MD V, MS S, MD S, PhD S, PhD Z, MRCP KO, PhD CE, PhD KJ, PhD NQ, FRCSOphth P, MS G. The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis. Ocul Immunol Inflamm. 2020;:1–10.
Agrawal R MD F, MBBS GD, MS A, MD T, MD C, FRCOphth W, MBBS M, PhD R, MS A, DNB MS, FRCSEd CS, MD M, FRCSGlasg HS, FRCSEd T, MD C, MS B, MD N, MS A, DNB M, MD K, FRCSOphth J, MD TT, DNB B, MS B, PhD L, MD AD, MD B, MD I, MD GD, MD HC, PhD BA, PhD GLJ, MD A, MS B, MS M, MD ES, MD T, MD N, DNB A, MD A, MD V, MS S, MD S, PhD S, PhD Z, MRCP KO, PhD CE, PhD KJ, PhD NQ, FRCSOphth P, MS G. Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report #6. Ocul Immunol Inflamm. 2020;:1–9.
Hamad A, Moinuddin O, Blair M, Schechet S, Shapiro M, Quiram P, Mammo D, Berrocal A, Prakhunhungsit S, Cernichiaro-Espinosa L, Mukai S, Yonekawa Y, Ung C, Holz E, Harper A, Young R, Besirli C, Nagiel A, Lee T, Gupta M, Walsh M, Khawly J, Campbell P, Kychenthal A, Nudleman E, Robinson J, Hartnett ME, Calvo C, Chang E. Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity. Ophthalmol Retina. 2020;4(6):602–612.
PURPOSE: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy. DESIGN: Retrospective, nonconsecutive, noncomparative, multicenter case series. PARTICIPANTS: Three hundred sixty-three eyes of 186 patients. METHODS: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings. MAIN OUTCOME MEASURES: Rate of RDs and factors conferring a higher risk of RDs. RESULTS: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009). CONCLUSIONS: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.
Li LH, Lee JCY, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients. 2020;12(6).
Lutein is one of the few xanthophyll carotenoids that is found in high concentration in the macula of human retina. As synthesis of lutein within the human body is impossible, lutein can only be obtained from diet. It is a natural substance abundant in egg yolk and dark green leafy vegetables. Many basic and clinical studies have reported lutein's anti-oxidative and anti-inflammatory properties in the eye, suggesting its beneficial effects on protection and alleviation of ocular diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, myopia, and cataract. Most importantly, lutein is categorized as Generally Regarded as Safe (GRAS), posing minimal side-effects upon long term consumption. In this review, we will discuss the chemical structure and properties of lutein as well as its application and safety as a nutritional supplement. Finally, the effects of lutein consumption on the aforementioned eye diseases will be reviewed.
Elhusseiny A, Jamerson E, Menshawey R, Tam E, El Sayed Y. Collector Channels: Role and Evaluation in Schlemm’s Canal Surgery. Curr Eye Res. 2020;45(10):1181–1187.
OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.
Douglas KA, Douglas VP, Moschos M. Ocular Manifestations of COVID-19 (SARS-CoV-2): A Critical Review of Current Literature. In Vivo. 2020;34(3 Suppl):1619–1628.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.