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1.
Exosomes, extracellular vesicles and the eye.
Rudraprasad, D, Rawat, A, Joseph, J
Experimental eye research. 2022;:108892
Abstract
Exosomes are a subset of extracellular vesicles which accommodate a cargo of bioactive biomolecules that generally includes proteins, nucleic acids, lipids, sugars, and related conjugates depicting the cellular environment and are known to mediate a wide array of biological functions, like cellular communication, cellular differentiation, immunomodulation, neovascularization, and cellular waste management. The exponential implication of exosomes in the pathological development and progression of various disorders including neurodegenerative diseases, cardiovascular diseases, and cancer has offered a tremendous opportunity for exploring their role in ocular conditions. Ocular diseases such as age-related macular disease, glaucoma, infectious endophthalmitis, diabetic retinopathy, autoimmune uveitis etc face various challenges in their early diagnosis and treatments due to contributing factors such as delay in the onset of symptoms, microbial identification, difficulty in obtaining samples for biopsy or being diagnosed as masquerade syndromes. Studies have reported unique exosomal cargos that are involved in successful delivery of miRNA or proteins to recipient cells to express desired expression or exploited as a diagnostic marker for various diseases. Furthermore, engineered exosomes can be used for targeted delivery of therapeutics and exosomes being natural nanoparticles found in all types of cells, host may not elicit an immune response against it. With the rapid advancement of opting personalized therapeutics, extending exosomal research to sight-threatening ocular infections can possibly advance the current diagnostic and therapeutic approaches. This review briefs about the current knowledge of exosomes in visual systems, advancements in exosomal and ophthalmic research, participation of exosomes in the pathogenesis of common ocular diseases, the challenges for exosomal therapies along with the future of this promising domain of research for diseases that fatally threaten billions of people worldwide.
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Use of erythropoietin in ophthalmology: a review.
Feizi, S, Alemzadeh-Ansari, M, Karimian, F, Esfandiari, H
Survey of ophthalmology. 2022;(2):427-439
Abstract
Erythropoietin (EPO) is a glycoprotein hormone that regulates hematopoiesis in the human body. The presence of EPO and its receptors in different tissues indicates that this hormone has extramedullary effects in other tissues, including the eye. We focus on the biological roles of this hormone in the development and normal physiologic functions of the eye. Furthermore, we explore the role of EPO in the management of different ocular diseases - including diabetic retinopathy, retinopathy of prematurity, inherited retinal degeneration, branch and central retinal vein occlusion, retinal detachment, traumatic optic neuropathy, optic neuritis, methanol optic neuropathy, nonarteritic anterior ischemic optic neuropathy, glaucoma, and scleral necrosis.
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3.
Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study.
, , ,
The Lancet. Global health. 2021;(2):e144-e160
Abstract
BACKGROUND Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. METHODS We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. FINDINGS Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change -0·2% [95% UI -1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by -15·4% [-16·8 to -14·3], while avoidable MSVI showed no change (0·5% [-0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7-18·0]), followed by glaucoma (3·6 million cases [2·8-4·4]), undercorrected refractive error (2·3 million cases [1·8-2·8]), age-related macular degeneration (1·8 million cases [1·3-2·4]), and diabetic retinopathy (0·86 million cases [0·59-1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2-101·0]) and cataract (78·8 million cases [67·2-91·4]). INTERPRETATION Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached. FUNDING Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.
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4.
A Review of Topical and Systemic Vitamin Supplementation in Ocular Surface Diseases.
Fogagnolo, P, De Cilla', S, Alkabes, M, Sabella, P, Rossetti, L
Nutrients. 2021;(6)
Abstract
In the homeostasis of the ocular surface, vitamins play a critical role in regulating inflammatory responses and promoting cell differentiation, development and correct function. Systemic vitamin supplementation has been available for many decades; in recent years, thanks to pharmacological advancements, topical vitamin delivery has also become available in an attempt to better treat ocular surface disease (OSD) and dry eye disease (DED). In this paper, we reviewed the current evidence on the role of vitamin supplementation in OSD and DED. We originally searched the PubMed archive, inspected the references and restricted the search to pertinent papers. The body of evidence was evaluated using the amelioration of both signs and symptoms as the outcome, when available. We found that in patients with vitamin deficiency, systemic supplementation of Vitamin A is effective in treating OSD, reducing both DED signs and symptoms. Additionally, systemic supplementation of vitamin D is useful in reducing DED symptoms and increasing tear volume. Vitamin A is also effective in reducing DED signs and symptoms when administered locally. The efficacy of supplementation with other vitamins is still not fully proven. In conclusion, the inclusion of vitamins into the treatment strategies for OSD and DED allows for better treatment customization and better outcomes in these patients.
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5.
COVID-19 and the Unfinished Agenda of VISION 2020.
Ung, L, Jonas, JB, Lietman, TM, Chodosh, J
American journal of ophthalmology. 2021;:30-35
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Abstract
PURPOSE To critically evaluate the potential impact of the coronavirus disease (COVID-19) pandemic on global ophthalmology and VISION 2020. DESIGN Perspective supplemented with epidemiologic insights from available online databases. METHODS We extracted data from the Global Vision Database (2017) and Global Burden of Disease Study (2017) to highlight temporal trends in global blindness since 1990, and provide a narrative overview of how COVID-19 may derail progress toward the goals of VISION 2020. RESULTS Over 2 decades of VISION 2020 advocacy and program implementation have culminated in a universal reduction of combined age-standardized prevalence of moderate-to-severe vision impairment (MSVI) across all world regions since 1990. Between 1990 and 2017, low-income countries observed large reductions in the age-standardized prevalence per 100,000 persons of vitamin A deficiency (25,155 to 19,187), undercorrected refractive disorders (2,286 to 2,040), cataract (1,846 to 1,690), onchocerciasis (5,577 to 2,871), trachoma (506 to 159), and leprosy (36 to 26). Despite these reductions, crude projections suggest that more than 700 million persons will experience MSVI or blindness by 2050, principally owing to our growing and ageing global population. CONCLUSIONS Despite the many resounding successes of VISION 2020, the burden of global blindness and vision impairment is set to reach historic levels in the coming years. The impact of COVID-19, while yet to be fully determined, now threatens the hard-fought gains of global ophthalmology. The postpandemic years will require renewed effort and focus on vision advocacy and expanding eye care services worldwide.
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6.
Ocular manifestations of dermatological diseases part I: infectious and inflammatory disorders.
Al Akrash, LS, Al Semari, MA, Al Harithy, R
International journal of dermatology. 2021;(1):5-11
Abstract
Skin and eyes share a common embryological origin from the embryonic surface ectoderm. Ocular manifestations are one of the most important and common associations of dermatological diseases. Currently, there are few comprehensive reviews of the ocular manifestations of dermatological diseases. We have reviewed more than 40 published articles related to the ocular manifestations of the most important dermatological diseases. The search included Pubmed, Google Scholar, and Cochrane databases from 2014 to 2019. This review was divided into three parts including infections, inflammatory, genetics, connective tissue, autoimmune, neoplasms, and drug-related disorders. We excluded metabolic, endocrine, and nutrition-related dermatological diseases. The relationship of ocular manifestations and dermatological diseases is important to recognize for appropriate management since many dermatological diseases can manifest initially with ocular findings. In this part, we summarized the most common and significant ocular findings in infectious and inflammatory dermatological disorders with appropriate referral recommendations to ophthalmology.
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Factors Associated With a Patient's Decision to Select a Cost-effective vs the Most Effective Therapy for Their Own Eye Disease.
Malik, D, Cao, X, Sanchez, JC, Gao, T, Qian, J, Montaner, S, Sodhi, A
JAMA network open. 2021;(2):e2037880
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Abstract
IMPORTANCE Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease. OBJECTIVE To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020. INTERVENTIONS Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism). MAIN OUTCOMES AND MEASURES Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study. RESULTS A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy. CONCLUSIONS AND RELEVANCE These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.
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Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis.
Iturriaga-Goyon, E, Buentello-Volante, B, Magaña-Guerrero, FS, Garfias, Y
Cells. 2021;(6)
Abstract
Aptamers are single-stranded DNA or RNA oligonucleotides that are currently used in clinical trials due to their selectivity and specificity to bind small molecules such as proteins, peptides, viral particles, vitamins, metal ions and even whole cells. Aptamers are highly specific to their targets, they are smaller than antibodies and fragment antibodies, they can be easily conjugated to multiple surfaces and ions and controllable post-production modifications can be performed. Aptamers have been therapeutically used for age-related macular degeneration, cancer, thrombosis and inflammatory diseases. The aim of this review is to highlight the therapeutic, diagnostic and prognostic possibilities associated with aptamers, focusing on eye pathological angiogenesis.
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A global review of publicly available datasets for ophthalmological imaging: barriers to access, usability, and generalisability.
Khan, SM, Liu, X, Nath, S, Korot, E, Faes, L, Wagner, SK, Keane, PA, Sebire, NJ, Burton, MJ, Denniston, AK
The Lancet. Digital health. 2021;(1):e51-e66
Abstract
Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.
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Protein Microarrays for Ocular Diseases.
Solís-Fernández, G, Montero-Calle, A, Alonso-Navarro, M, Fernandez-Torres, MÁ, Lledó, VE, Garranzo-Asensio, M, Barderas, R, Guzman-Aranguez, A
Methods in molecular biology (Clifton, N.J.). 2021;:239-265
Abstract
The eye is a multifaceted organ organized in several compartments with particular properties that reflect their diverse functions. The prevalence of ocular diseases is increasing, mainly because of its relationship with aging and of generalized lifestyle changes. However, the pathogenic molecular mechanisms of many common eye pathologies remain poorly understood. Considering the unquestionable importance of proteins in cellular processes and disease progression, proteomic techniques, such as protein microarrays, represent a valuable approach to analyze pathophysiological protein changes in the ocular environment. This technology enables to perform multiplex high-throughput protein expression profiling with minimal sample volume requirements broadening our knowledge of ocular proteome network in eye diseases.In this review, we present a brief summary of the main types of protein microarrays (antibody microarrays, reverse-phase protein microarrays, and protein microarrays) and their application for protein change detection in chronic ocular diseases such as dry eye, age-related macular degeneration, diabetic retinopathy, and glaucoma. The validation of these specific protein changes in eye pathologies may lead to the identification of new biomarkers, depiction of ocular disease pathways, and assistance in the diagnosis, prognosis, and development of new therapeutic options for eye pathologies.