Publications

2019

Moustafa G, Borkar D, Borboli-Gerogiannis S, Greenstein S, Lorch A, Vasan R, Kloek C. Optimization of cataract surgery follow-up: A standard set of questions can predict unexpected management changes at postoperative week one. PLoS One. 2019;14(9):e0221243.
PURPOSE: There is limited evidence to inform the optimal follow-up schedule after cataract surgery. This study aims to determine whether a standardized question set can predict unexpected management changes (UMCs) at the postoperative week one (POW1) timepoint. SETTING: Massachusetts Eye and Ear, Harvard Medical School. DESIGN: Prospective cohort study. METHODS: Two-hundred-and-fifty-four consecutive phacoemulsification cases having attended an examination between postoperative days 5-14. A set of 7 'Yes' or 'No' questions were administered to all participants by a technician at the POW1 visit. Patient answers along with perioperative patient information were recorded and analyzed. Outcomes were the incidence of UMCs at POW1. RESULTS: The incidence of UMCs was zero in uneventful cataract cases with unremarkable history and normal postoperative day one exam if no positive answers were given with the question set demonstrating 100% sensitivity (p<0.0001). A test version with 5 questions was equally sensitive in detecting UMCs at POW1 after cataract surgery. CONCLUSION: In routine cataract cases with no positive answers to the current set of clinical questions, a POW1 visit is unlikely to result in a management change. This result offers the opportunity for eye care providers to risk-stratify patients who have had cataract surgery and individualize follow-up.
Subramanian S, Maurer A, Bator C, Makhov A, Conway J, Turner K, Marden J, Vandenberghe L, Hafenstein S. Filling Adeno-Associated Virus Capsids: Estimating Success by Cryo-Electron Microscopy. Hum Gene Ther. 2019;30(12):1449–1460.
Adeno-associated viruses (AAVs) have been employed successfully as gene therapy vectors in treating various genetic diseases for almost two decades. However, transgene packaging is usually imperfect, and developing a rapid and accurate method for measuring the proportion of DNA encapsidation is an important step for improving the downstream process of large scale vector production. In this study, we used two-dimensional class averages and three-dimensional classes, intermediate outputs in the single particle cryo-electron microscopy (cryo-EM) image reconstruction pipeline, to determine the proportion of DNA-packaged and empty capsid populations. Two different preparations of AAV3 were analyzed to estimate the minimum number of particles required to be sampled by cryo-EM in order for robust calculation of the proportion of the full versus empty capsids in any given sample. Cost analysis applied to the minimum amount of data required for a valid ratio suggests that cryo-EM is an effective approach to analyze vector preparations.
Achillea species and in particular Achillea tenuifolia Lam. is generally used as a food flavor and traditional remedies, especially in the initial developmental stage for medical conditions in the Mediterranean part of Iran. In this report, we extracted the essential oil from the aerial parts of A. tenuifolia (collected from Khoy), at various developmental stages (i. e., vegetative, flowering and fruiting), characterized them and studied their antibacterial activities. Of 46, 51 and 38 components found in the vegetative, flowering, and fruiting stages, respectively, 35 were present in all three stages, including oxygenated terpenes such as carvacrol (30.85-34.11), germacrene C (16.21-17.87), spathulenol (7.26-8.96), β-sesquiphellandrene (4.11-4.25), τ-muurolol (2.27-3.25) and α-cadinol (2.01-3.29). We witnessed that the composition of the essential oils varies with phenological stages and geographic regions. The essential oil demonstrated substantial antibacterial properties against both Gram-positive and Gram-negative bacteria, indicated by disk method, Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays. Except Pseudomonas aeruginosa, the essential oils of various phenological stages showed higher antibacterial activity against tested bacteria, with Bacillus anthracis as the most sensitive strain. Moreover, although antibacterial characteristics of the essential oil from the vegetative and flowering stages were similar (p=0.91), they were significantly different from those of fruiting stage (p<0.005 in both MIC and MBC tests). This emphasizes the importance of the developmental stage of the plant in the biological properties of its essential oil and justifies the widespread application of this plant in the vegetative stage.
Neurodegenerative diseases demonstrate the progressive decline of brain functions resulting in a significant deterioration in the quality of patient's life. With increasing life expectancy, there has been a significant increase in the incidence of these diseases. Neurodegenerative diseases like Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis are devastating and afflicts a large world population. Eye, given the similar neural and vascular similarity to the brain, demonstrates many pathological hallmarks of some of these neurological diseases. Moreover, these diseases create an economic and social burden to society. Despite tremendous efforts made in the drug discovery, there is no cure for these fatal diseases. Thus, there is an unmet need to understand cellular and molecular pathophysiology of these diseases. All these diseases demonstrate damage to a large number of seemingly disparate cellular processes and functions such as Ca homeostasis, lipid metabolism, axonal transport, unfolded protein response, autophagy and inflammatory responses. Mitochondria are closely associated with Endoplasmic reticulum (ER) and ER-mitochondrial cross-talk regulates many of these cellular processes and functions damaged in neurodegenerative and eye diseases. Several studies have implicated the disruption of ER-mitochondria contacts in these diseases. This review is aimed at understanding and summarizing the role of ER-mitochondria interacting proteins in major neurodegenerative and eye diseases studied so far.
We analyzed clinical and histopathologic data of 97 pediatric patients who underwent excision of dermoid cysts. On review, 16.5% of the sample population demonstrated localized chronic inflammatory changes, including the presence of giant cells and epithelial disruption. These features were considered indicative of prior cyst rupture. Age at time of initial presentation was significantly older and cyst size was significantly larger in patients with histopathologic signs of previous rupture. Longer time to presentation and time to excision were associated with increased odds of spontaneous rupture.
Deng S, Borderie V, Chan C, Dana R, Figueiredo F, Gomes J, Pellegrini G, Shimmura S, Kruse F. Reply. Cornea. 2019;38(12):e56-e57.
Ing E, Pagnoux C, Torun N. Advances in the diagnosis of giant cell arteritis. Curr Opin Ophthalmol. 2019;30(6):407–411.
PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.
Sabeti S, Kheirkhah A, Yin J, Dana R. Management of Meibomian Gland Dysfunction: A Review. Surv Ophthalmol. 2019;
Meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye disease and is one of the most common conditions encountered by eye care providers. MGD is characterized by obstruction of the meibomian gland terminal ducts and/or changes in their glandular secretion, resulting in changes in tear film stability, inflammation, and symptoms of irritation. There is no gold standard treatment for MGD, but rather a diversity of options. Conservative measures include warm compresses and lid hygiene, but there is growing interest and need for medical treatments and procedures. Potential medical treatments include antibiotics, non-steroidal and steroidal anti-inflammatory agents, essential fatty acid supplementation, hormone therapy, and control of Demodex infestation. Procedures include intraductal meibomian gland probing, the use of electronic heating devices, intense pulsed light therapy, and intranasal neurostimulation. We provide an update on MGD treatments based on recent studies.
Fini E, Jeong S, Gong H, Martínez-Carrasco R, Laver N, Hijikata M, Keicho N, Argüeso P. Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse. Prog Retin Eye Res. 2019;:100777.
The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.