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      Modern approach to the treatment of dry eye, a complex multifactorial disease: a P.I.C.A.S.S.O. board review

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          Abstract

          Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient’s clinical presentation have to be considered and possibly treated simultaneously. The treatment should be long-lasting and personalised since it has to be adapted to the different clinical conditions observed along the course of the disease. Since DED treatment is frequently unable to provide fast and complete relief from symptoms, empathy with patients and willingness to explain to them the natural history of the disease are mandatory to improve patients’ compliance. Furthermore, patients should be instructed about the possible need to increase the frequency and/or change the type of treatment according to the fluctuation of symptoms, following a preplanned rescue regimen.

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          Most cited references112

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          TFOS DEWS II Epidemiology Report

          The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.
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            TFOS DEWS II Diagnostic Methodology report

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              Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein.

              Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR-independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.
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                Author and article information

                Journal
                Br J Ophthalmol
                Br J Ophthalmol
                bjophthalmol
                bjo
                The British Journal of Ophthalmology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0007-1161
                1468-2079
                April 2021
                23 July 2020
                : 105
                : 4
                : 446-453
                Affiliations
                [1 ] departmentDepartment of Biomedical Sciences, Ophthalmology Clinic, University of Messina , Messina, Italy
                [2 ] departmentOphthalmology, Magna Graecia University of Catanzaro , Catanzaro, Italy
                [3 ] Institute of Ophthalmology , Florence, Italy
                [4 ] departmentOphthalmology, University of Parma , Parma, Italy
                [5 ] departmentOphthalmology, Israelitic Hospital , Rome, Italy
                [6 ] departmentOcular Surface Unit, ISPRE , Genoa, Italy
                Author notes
                [Correspondence to ] Maurizio Rolando, Ocular Surface Unit, ISPRE Genova, Genoa, Italy; maurizio.rolando@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-9582-9799
                http://orcid.org/0000-0003-2617-0289
                http://orcid.org/0000-0002-4982-1462
                Article
                bjophthalmol-2019-315747
                10.1136/bjophthalmol-2019-315747
                8005804
                32703782
                659a1a58-accf-4603-b1d4-2e67e8c11568
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 December 2019
                : 01 June 2020
                : 18 March 2020
                Categories
                Review
                1506
                Custom metadata
                unlocked

                Ophthalmology & Optometry
                cornea,conjunctiva,eye lids,ocular surface,tears
                Ophthalmology & Optometry
                cornea, conjunctiva, eye lids, ocular surface, tears

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