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Acta Ophthalmologica Dec 2022Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring... (Review)
Review
Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.
Topics: Humans; Lubricant Eye Drops; Hyaluronic Acid; Dry Eye Syndromes; Tears
PubMed: 35514082
DOI: 10.1111/aos.15159 -
Climacteric : the Journal of the... Apr 2016Vaginal dryness is a common condition that is particularly prevalent during and after the menopause, and is one of the symptoms of vulvovaginal atrophy/genitourinary... (Review)
Review
Vaginal dryness is a common condition that is particularly prevalent during and after the menopause, and is one of the symptoms of vulvovaginal atrophy/genitourinary syndrome of menopause. The impact of vaginal dryness on interpersonal relationships, quality of life, daily activities, and sexual function can be significant, but is frequently underestimated. Furthermore, barriers exist to treatment-seeking, and this condition is often underreported and undertreated. Greater education about vaginal dryness and the range of available treatments is essential to encourage more women to seek help for this condition. Personal lubricants and moisturizers are effective at relieving discomfort and pain during sexual intercourse for women with mild to moderate vaginal dryness, particularly those who have a genuine contraindication to estrogen, or who choose not to use estrogen. However, there is a distinction between lubricants and moisturizers, and notable differences between commercially available products. Women should be advised to choose a product that is optimally balanced in terms of both osmolality and pH, and is physiologically most similar to natural vaginal secretions. A series of recommendations for the use of vaginal lubricants and moisturizers, either on their own or in combination with systemic or topical hormone replacement therapy, is presented.
Topics: Administration, Intravaginal; Atrophy; Dyspareunia; Estrogen Replacement Therapy; Female; Humans; Lubricants; Menopause; Quality of Life; Vagina; Vaginal Diseases; Vulva; Women's Health
PubMed: 26707589
DOI: 10.3109/13697137.2015.1124259 -
International Journal of Molecular... Feb 2022Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are... (Review)
Review
Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.
Topics: Drug Compounding; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Viscosity
PubMed: 35269576
DOI: 10.3390/ijms23052434 -
International Journal of Environmental... Mar 2021Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops,... (Meta-Analysis)
Meta-Analysis Review
Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops, including saline and conventional artificial tears (ATs), for the treatment of dry eye disease. Eight databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, DBpia, KoreaMed, KMBASE, RISS, KISS) were searched for studies comparing the efficacies of HA- and non-HA-based ATs in patients with DES published up to September 2020. Two independent reviewers assessed the quality and extracted the relevant data. The mean differences of Schirmer's (SH) test scores, tear breakup times (TBUT), corneal fluorescein staining scores (Oxford scale, 0-4), and ocular surface disease indexes were calculated. The standard mean difference and 95% confidence interval were calculated using a random effect model. Nineteen studies, including 2078 cases, were included. HA eye drops significantly improved tear production compared with non-HA-based eye drops (standard mean difference (SMD) 0.18; 95% confidence interval (CI) 0.03, 0.33). In a subgroup analysis, the SH test scores and TBUT values after using HA significantly increased compared to those measured after using saline (SMD 0.27; 95% CI 0.05, 0.49 and SMD 0.28; 95% CI 0.03, 0.52, respectively). Based on these results, HA eye drops may be superior to non-HA eye drops including normal saline and ATs. Further research is needed to assess the efficacies stratified by age, treatment duration, the severity of dry eye, and optimal dosages.
Topics: Dry Eye Syndromes; Humans; Hyaluronic Acid; Lubricant Eye Drops; Tears
PubMed: 33804439
DOI: 10.3390/ijerph18052383 -
Scientific Reports Aug 2022Cross-contamination of biological samples during handling and preparation, is a major issue in laboratory setups, leading to false-positives or false-negatives. Sample...
Cross-contamination of biological samples during handling and preparation, is a major issue in laboratory setups, leading to false-positives or false-negatives. Sample carryover residue in pipette tips contributes greatly to this issue. Most pipette tips on the market are manufactured with hydrophobic polymers that are able to repel high surface tension liquids, yet they lack in performance when low surface tension liquids and viscous fluids are involved. Moreover, hydrophobicity of pipette tips can result in hydrophobic adsorption of biomolecules, causing inaccuracies and loss in precision during pipetting. Here we propose the use of lubricant-infused surface (LIS) technology to achieve omniphobic properties in pipette tips. Using a versatile and simple design, the inner lumen of commercially available pipette tips was coated with a fluorosilane (FS) layer using chemical vapor deposition (CVD). The presence of FS groups on the tips is confirmed by x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) tests. After lubrication of the tips through a fluorinated lubricant, the omniphobicity and repellent behaviour of the tips drastically enhanced which are revealed via static and hysteresis contact angle measurements. The repellency of the lubricant-infused pipette tips against physical adsorption is investigated through pipetting a food coloring dye as well as human blood samples and are compared to the untreated tips. The results show significantly less amount carryover residue when the lubricant-infused tips are utilized compared to commercially available ones. We also demonstrate the lubricant-infused tips reduce bacteria contamination of the inner lumen by 3 to 6-log (over 99%, depending on the tip size) after pipetting up and down the bacteria solution.
Topics: Humans; Adsorption; Hydrophobic and Hydrophilic Interactions; Lubricants; Lubrication; Surface Properties; Complex Mixtures
PubMed: 36008518
DOI: 10.1038/s41598-022-18756-x -
European Review For Medical and... Sep 2020The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear... (Review)
Review
OBJECTIVE
The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes.
MATERIALS AND METHODS
A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting.
RESULTS
The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology.
CONCLUSIONS
Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.
Topics: Animals; Dry Eye Syndromes; European Union; Humans; Lubricant Eye Drops; Medical Device Legislation
PubMed: 32964952
DOI: 10.26355/eurrev_202009_22801 -
Nature Communications Apr 2023PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of...
PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase β cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, -4, and -5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase β and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase β and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase β as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4.
Topics: Humans; Male; Animals; Rats; Tryptases; Proteoglycans; Lubrication; NF-kappa B; Osteoarthritis; Inflammation; Cartilage, Articular
PubMed: 37024468
DOI: 10.1038/s41467-023-37598-3 -
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2 -
Tidsskrift For Den Norske Laegeforening... Aug 2023In Norway, approximately 360 000 cervical screening samples were taken in 2020, of which 11 000 were registered as inadequate. We therefore wished to investigate...
BACKGROUND
In Norway, approximately 360 000 cervical screening samples were taken in 2020, of which 11 000 were registered as inadequate. We therefore wished to investigate doctors' knowledge of cervical sample-taking in the primary health service.
MATERIAL AND METHOD
An anonymous survey on cervical sample-taking was sent by email to around 4 700 members of the Norwegian College of General Practice in September 2021.
RESULTS
Of the 1 039 doctors who responded to the survey, 820 (79 %) reported that they always indicate the reason for taking the sample in the requisition form, and 898 (86 %) reported that they avoid taking a sample during menstruation. Only one in three doctors (343) correctly indicated the location of the squamocolumnar junction in postmenopausal women. In response to a question aimed at users of the ThinPrep method, which is particularly sensitive to sampling errors, 426 out of 697 (61 %) answered that they either avoid using a lubricant or use a water-based lubricant, while only 35 % of the doctors responded that they stop taking the sample if bleeding occurs.
INTERPRETATION
The results show that although many doctors have satisfactory knowledge, a continuous focus on cervical sample-taking is essential. Correct sampling and knowledge of anatomical factors in postmenopausal women may be significant for reducing the number of inadequate samples.
Topics: Female; Humans; Early Detection of Cancer; General Practice; Lubricants; Primary Health Care; Uterine Cervical Neoplasms; Specimen Handling; Health Knowledge, Attitudes, Practice; Norway; Physicians, Primary Care
PubMed: 37589352
DOI: 10.4045/tidsskr.23.0066 -
Medicina (Kaunas, Lithuania) Sep 2019The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of... (Review)
Review
The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman's quality of life. Epidemiology, signs, symptoms, diagnostic criteria of VVA and target treatments for restoring vaginal health are discussed in light of the most recent literature. Issues related to this condition in menopausal women are under-diagnosed, lack objective diagnostic criteria, and consequently under-treated. Over the years, many treatments have been developed but their long-term effectiveness and safety have yet to be clearly defined. Patients are often dissatisfied and stop treatment, suggesting the need for a more personalized and tailored approach to achieve better compliance and thereby effectiveness. The aim of this paper is to provide an overview of the most recent literature on VVA in order to help the gynecologist in the management of this condition.
Topics: Administration, Intravaginal; Atrophy; Emollients; Female; Hormone Replacement Therapy; Humans; Laser Therapy; Lubricants; Perimenopause; Postmenopause; Vagina; Vaginal Diseases
PubMed: 31547180
DOI: 10.3390/medicina55100615