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Silpa-Archa S, Dejkong A, Kumsiang K, Chotcomwongse P, Preble JM, Foster SC. Poor prognostic factors in post-traumatic endophthalmitis following open globe injury. Int J Ophthalmol 2020;13(12):1968-1975.Abstract
AIM: To demonstrate prognostic factors for poor visual outcome in patients with post-traumatic endophthalmitis (PTE) following open globe injury. METHODS: A retrospective study was conducted on 66 patients (66 eyes) with PTE following open globe injury from 2005 to 2015. Potential factors accounting for good and poor visual outcome were statistically analyzed by Chi-square test and Logistic regression model. RESULTS: In 66 cases, 39 cases (59%) had a poor visual outcome. Univariate and multivariate Logistic regression analysis identified retained intraocular foreign body (IOFB) as the only factor significantly associated with poor visual outcome [adjusted odds ratio, 4.62; 95% confidence interval (1.04-20.53); =0.04]. The most common causative agents were gram-positive organisms (83%), of which (33%), was the most common pathogen. All cases received intravitreal antibiotic injections. Oral ciprofloxacin was the most used systemic antibiotic (33%). Pars plana vitrectomy was performed in 83% (55/66) of cases. At 6mo follow-up, mean BCVA was 1.74±0.72 logMAR units. CONCLUSION: In patients with PTE following open globe injury, the only predictor of poor visual outcome is the presence of IOFB. is the most isolated microorganism.
Singh T, Ichhpujani P, Singh RB. First Line of Defense in COVID-19: Masks in Clinical Practice. Asia Pac J Public Health 2020;:1010539520979928.Abstract
The current evidence suggests that masks are efficacious in limiting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Although cloth masks are effective in outdoor environments, there is a consensus about the requirement of N95 masks or respirators when working in close proximity to patients who may be asymptomatic carriers, specifically in ophthalmology clinics, where slit-lamp examinations, noncontact tonometry, and other procedures place the physicians and patients in close proximity with each other. In this report, we review the available evidence regarding the efficacy of different types of masks in clinical practice in ophthalmology.
Tripathy K, Ying H, Maldonado Cerda A, Filipowicz A, Kaya M, Seymen Z, Anesi SD, Chang PY, Foster CS. Widefield Fundus Fluorescein Angiography Features of Uveitis Associated with Juvenile Idiopathic Arthritis. Ocul Immunol Inflamm 2020;:1-10.Abstract
PURPOSE: To evaluate the wide-field fundus fluorescein angiography (WFA) characteristics of uveitis associated with juvenile idiopathic arthritis (JIA-uveitis). METHODS: Retrospective review of records. WFA with Spectralis (Heidelberg) of JIA-uveitis patients were analyzed using the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Thirty-seven eyes of 20 patients were studied. A total score of at least 1 was noted in 27 eyes (72.97%). WFA features included optic disc hyperfluorescence (51.35%), macular leakage (27.03%), retinal vascular staining/leakage at posterior pole (27.03%) and peripheral retina (64.86%), capillary leakage at the posterior pole (37.84%), and peripheral retina (59.46%). A decision to change the management plan was made in 8 of 9 patients with bilateral quiet anterior chambers after WFA results. CONCLUSION: More than 70% of JIA-uveitis eyes showed some WFA-evidence of posterior segment inflammation, which changed the course of therapy for a major proportion of patients with no clinically active anterior chamber inflammation.
Efstathiou NE, Moustafa GA, Maidana DE, Konstantinou EK, Notomi S, Barbisan PRT, Georgakopoulos CD, Miller JW, Vavvas DG. Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells. PLoS One 2020;15(12):e0244307.Abstract
RATIONALE: Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-α) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-α induced C3 in RPE cells. METHODS: ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-α was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis. RESULTS: Acadesine suppresses TNF-α induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine's effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it's action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn't prevent acadesine from decreasing TNF-α induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK α catalytic subunit did not affect the inhibitory effect of acadesine on TNF-α upregulation of C3. CONCLUSIONS: Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.
Marmamula S, Mitchell W, Zebardast N, Locascio J, Barrenkala NR, Kumbham TR, Modepalli SB, Khanna RC, Friedman DS. Impact of Vision Loss on Visual Function Among Elderly Residents in the "Home for the Aged" in India: The Hyderabad Ocular Morbidity in Elderly Study. Transl Vis Sci Technol 2020;9(13):11.Abstract
Purpose: The purpose of this study was to report the association between visual impairment (VI) and self-reported visual difficulty among the elderly in residential care using the Indian Vision Functioning Questionnaire (IND-VFQ-33) psychometrically validated questionnaire. Methods: Participants aged ≥ 60 years were recruited from 41 homes in Hyderabad in South India. All participants underwent detailed eye examination and interviews. Self-reported visual function was assessed using the IND-VFQ-33 questionnaire. Factor Analysis and Item Response Theory (IRT) models were used for analysis. Multivariable regression models were used to investigate associations between derived global difficulty scores versus severity and causes of VI. Presenting visual acuity worse than 6/18 in the better eye was considered as VI. Results: In total, 867 elderly participants completed the INDVFQ-33. Two latent traits ("daily activities" and "visual symptoms") were identified on factor analysis, each with uniquely loading questions. Participants with VI reported significantly higher daily activities difficulty (6 points higher) and visual symptoms difficulty (1.7 points higher) than those without VI ( < 0.05). Those with cataract reported the highest daily activities and visual symptoms difficulty (7.6 points and 2.2 points higher, respectively, < 0.05). Greater severity of VI was associated with increased self-reported difficulty for both factors, and for all causes of VI. Conclusions: We present a psychometrically validated visual questionnaire particularly suited to older adults in residential homes. We show a significant association between cause/severity of VI and difficulty with daily activities and visual symptoms after adjusting for sociodemographic and medical factors. Translational Relevance: Understanding the impact of vision loss on visual functions in the elderly will help in planning and resource allocation for developing early intervention programs for the elderly.
Webb LM, Chen JJ, Aksamit AJ, Bhattacharyya S, Chwalisz BK, Balaban D, Manzano GS, Ali AS, Lord J, Clardy SL, Samudralwar RD, Mao-Draayer Y, Garrity JA, Bhatti TM, Turner LE, Flanagan EP. A multi-center case series of sarcoid optic neuropathy. J Neurol Sci 2020;:117282.Abstract
OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.
Ludwig CA, Perera C, Myung D, Greven MA, Smith SJ, Chang RT, Leng T. Automatic Identification of Referral-Warranted Diabetic Retinopathy Using Deep Learning on Mobile Phone Images. Transl Vis Sci Technol 2020;9(2):60.Abstract
Purpose: To evaluate the performance of a deep learning algorithm in the detection of referral-warranted diabetic retinopathy (RDR) on low-resolution fundus images acquired with a smartphone and indirect ophthalmoscope lens adapter. Methods: An automated deep learning algorithm trained on 92,364 traditional fundus camera images was tested on a dataset of smartphone fundus images from 103 eyes acquired from two previously published studies. Images were extracted from live video screenshots from fundus examinations using a commercially available lens adapter and exported as a screenshot from live video clips filmed at 1080p resolution. Each image was graded twice by a board-certified ophthalmologist and compared to the output of the algorithm, which classified each image as having RDR (moderate nonproliferative DR or worse) or no RDR. Results: In spite of the presence of multiple artifacts (lens glare, lens particulates/smudging, user hands over the objective lens) and low-resolution images achieved by users of various levels of medical training, the algorithm achieved a 0.89 (95% confidence interval [CI] 0.83-0.95) area under the curve with an 89% sensitivity (95% CI 81%-100%) and 83% specificity (95% CI 77%-89%) for detecting RDR on mobile phone acquired fundus photos. Conclusions: The fully data-driven artificial intelligence-based grading algorithm herein can be used to screen fundus photos taken from mobile devices and identify with high reliability which cases should be referred to an ophthalmologist for further evaluation and treatment. Translational Relevance: The implementation of this algorithm on a global basis could drastically reduce the rate of vision loss attributed to DR.
Ning K, Song E, Sendayen BE, Prosseda PP, Chang K-C, Ghaffarieh A, Alvarado JA, Wang B, Haider KM, Berbari NF, Hu Y, Sun Y. Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome. Mol Genet Genomic Med 2020;:e1566.Abstract
BACKGROUND: Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia. METHODS: We report a 9-year-old Senior-Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H&E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1. RESULTS: Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5-phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. CONCLUSION: The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.
Gonzalez-Andrades M, Jalimarada SS, Rodriguez-Benavente M, Feeley MN, Woodward AM, AbuSamra DB, Argüeso P. Golgi α1,2-mannosidase I induces clustering and compartmentalization of CD147 during epithelial cell migration. Cell Adh Migr 2020;14(1):96-105.Abstract
CD147 is a widely expressed matrix metalloproteinase inducer involved in the regulation of cell migration. The high glycosylation and ability to undergo oligomerization have been linked to CD147 function, yet there is limited understanding on the molecular mechanisms behind these processes. The current study demonstrates that the expression of Golgi α1,2-mannosidase I is key to maintaining the cell surface organization of CD147 during cell migration. Using an in vitro model of stratified human corneal epithelial wound healing, we show that CD147 is clustered within lateral plasma membranes at the leading edge of adjacent migrating cells. This localization correlates with a surge in matrix metalloproteinase activity and an increase in the expression of α1,2-mannosidase subtype IC (MAN1C1). Global inhibition of α1,2-mannosidase I activity with deoxymannojirimycin markedly attenuates the glycosylation of CD147 and disrupts its surface distribution at the leading edge, concomitantly reducing the expression of matrix metalloproteinase-9. Likewise, treatment with deoxymannojirimycin or siRNA-mediated knockdown of MAN1C1 impairs the ability of the carbohydrate-binding protein galectin-3 to stimulate CD147 clustering in unwounded cells. We conclude that the mannose-trimming activity of α1,2-mannosidase I coordinates the clustering and compartmentalization of CD147 that follows an epithelial injury.
Neerukonda VK, Jakobiec FA, Freitag SK, Stagner AM, Wolkow N. Lacrimal Gland Intravascular Micrometastasis From a Human Papillomavirus-Driven Anorectal Squamous Cell Carcinoma With a Review of Metastatic Disease to the Lacrimal Gland. Ophthalmic Plast Reconstr Surg 2020;Abstract
PURPOSE: To document a unique case of anorectal squamous cell carcinoma that was metastatic to the microvasculature of the lacrimal gland in a patient with human immunodeficiency virus and to review previously reported cases of metastases to the lacrimal gland. METHODS: Both a retrospective chart review and comprehensive literature review were performed. The unusual histopathologic pattern of the current case was illustrated with immunohistochemical studies (CD31, D2-40, pancytokeratin, p16, and p63) and in situ hybridization studies for high-risk human papillomavirus types 16 and 18. RESULTS: The authors describe the first case of metastatic anorectal squamous cell carcinoma to the lacrimal gland. Only 24 cases of metastatic disease to the lacrimal gland have been reported, the majority from breast carcinomas. The metastasis did not form a macroscopic lesions, instead was composed of microscopic intravascular and intraparenchymal tumor deposits, a subtle phenomena. Immunohistochemistry confirmed the presence of the intravascular neoplastic cells. p16 served as a surrogate marker for human papillomavirus-associated squamous cell carcinoma and was confirmed with in situ hybridization for human papillomavirus 16 and 18. This testing, combined with the clinical history, defined the diagnosis and confirmed human papillomavirus as the tumor driver. CONCLUSIONS: Metastases to the lacrimal gland remain rare, but clinicians and pathologists alike must be attuned to the possibility of subtle microscopic foci of tumor as a pattern of metastasis in scenarios without a discrete mass-forming lesion, as this may portend a poor prognosis.
Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang J-H, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature 2020;588(7836):124-129.Abstract
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to DNA methylation patterns over time form the basis of ageing clocks, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.
Tecilazich F, Phan TA, Simeoni F, Scotti GM, Dagher Z, Lorenzi M. Patrolling Monocytes Are Recruited and Activated by Diabetes to Protect Retinal Microvessels. Diabetes 2020;69(12):2709-2719.Abstract
In diabetes there is a long latency between the onset of hyperglycemia and the appearance of structural microangiopathy. Because Ly6C patrolling monocytes (PMo) behave as housekeepers of the vasculature, we tested whether PMo protect microvessels against diabetes. We found that in wild-type mice, diabetes reduced PMo in the general circulation but increased by fourfold the absolute number of PMo adherent to retinal vessels (leukostasis). Conversely, in diabetic NR4A1 mice, a model of absence of PMo, there was no increase in leukostasis, and at 6 months of diabetes, the number of retinal acellular capillaries almost doubled compared with diabetic wild-type mice. Circulating PMo showed gene expression changes indicative of enhanced migratory, vasculoprotective, and housekeeping activities, as well as profound suppression of genes related to inflammation and apoptosis. Promigratory CXCR4 was no longer upregulated at longer duration when retinal acellular capillaries begin to increase. Thus, after a short diabetes duration, PMo are the cells preferentially recruited to the retinal vessels and protect vessels from diabetic damage. These observations support the need for reinterpretation of the functional meaning of leukostasis in diabetes and document within the natural history of diabetic retinopathy processes of protection and repair that can provide novel paradigms for prevention.
Moharrer M, Tang X, Luo G. With Motion Perception, Good Visual Acuity May Not Be Necessary for Driving Hazard Detection. Transl Vis Sci Technol 2020;9(13):18.Abstract
Purpose: To investigate the roles of motion perception and visual acuity in driving hazard detection. Methods: Detection of driving hazard was tested based on video and still-frames of real-world road scenes. In the experiment using videos, 20 normally sighted participants were tested under four conditions: with or without motion interruption by interframe mask, and with or without simulated low visual acuity (20/120 on average) by using a diffusing filter. Videos were down-sampled to 2.5 Hz, to allow the addition of motion interrupting masks between the frames to maintain video durations. In addition, single still frames extracted from the videos were shown in random order to eight normally sighted participants, who judged whether the frames were during ongoing hazards, with or without the diffuser. Sensitivity index d-prime (d') was compared between unmasked motion ( = 20) and still frame conditions ( = 8). Results: In the experiment using videos, there was a significant reduction in a combined performance score (taking account of reaction time and detection rate) when the motion was disrupted ( = 0.016). The diffuser did not affect the scores ( = 0.419). The score reduction was mostly due to a decrease in the detection rate ( = 0.002), not the response time ( = 0.148). The d' of participants significantly decreased ( < 0.001) from 2.24 with unmasked videos to 0.68 with still frames. Low visual acuity also had a significant effect on the d' ( = 0.004), but the change was relatively small, from 2.03 without to 1.56 with the diffuser. Conclusions: Motion perception plays a more important role than visual acuity for detecting driving hazards. Translational Relevance: Motion perception may be a relevant criterion for fitness to drive.
Mitchell W, Hassall M, Henderson T. Updating the model of eye care for Aboriginal populations in remote Central Australia. Clin Exp Ophthalmol 2020;48(9):1299-1306.Abstract
Eye disease is the third-highest contributor towards health inequality for Aboriginal Australians. Understanding how the Central Australian ophthalmology service addresses complexities of remote eye care is crucial in understanding how expansion can meet current and future needs. The present study analyses findings from the MEDLINE database and Governmental reports, and descriptive information from stakeholders in Central Australia and the Australian Department of Health. We describe the current Central Australian ophthalmology model at three levels; (a) the healthcare service level (specialized primary care, local/outreach optometry and ophthalmology services, and intensive extended surgical weeks), (b) the community level (local community staff, clinics and initiatives, and eye "champions" and mutual support), and (c) the healthcare system level (federal and state government, and private funding). We conclude that building full-time specialist availability, and system-wide approaches to increase patient utilisation, will facilitate overcoming barriers of remoteness, and create enduring improvements in Central Australian eye care and health-inequality.

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