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Croatian Medical Journal Oct 2014To evaluate the existing evidence on relative efficacy and tolerability of topical mono-compound intraocular pressure (IOP)-lowering drugs in treatment of primary open... (Review)
Review
Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews.
AIM
To evaluate the existing evidence on relative efficacy and tolerability of topical mono-compound intraocular pressure (IOP)-lowering drugs in treatment of primary open angle glaucoma (POAG) and ocular hypertension (OHT).
METHODS
In this systematic review of systematic reviews/meta-analyses of randomized controlled trials a thorough and sensitive search of PubMed, Embase and Cochrane Databases was performed. Individual study methodological quality and quality of evidence were assessed using the AMSTAR checklist and the GRADE system, respectively. The relationships between individual drugs were evaluated based on the best available evidence.
RESULTS
Of the 133 initial non-duplicate records, 16 studies met the inclusion criteria. Five achieved an overall "moderate" (none achieved "high") quality of evidence and evaluated prostaglandin analogues (PGAs) - latanoprost, travoprost, and bimatoprost; timolol; "other beta-blockers;" carbonic anhydrase inhibitors (CAI) as a group or dorzolamide separately; and brimonidine. "Moderate quality" refers to efficacy and incidence of conjunctival hyperemia. Quality of evidence regarding other tolerability aspects was low. PGAs should be considered equivalent regarding efficacy, but latanoprost was relevantly better tolerated than the other two. Non-PGA compounds did not relevantly differ between each other in either efficacy or safety. Timolol and brimonidine were relevantly less effective than all PGAs. The same was true for CAI vs bimatoprost. Regarding tolerability, timolol was superior to all PGAs and brimonidine and CAI were superior to bimatoprost.
CONCLUSION
No high quality evidence on relative efficacy and tolerability of the most commonly used mono-compound IOP-lowering drugs for POAG/OHT exists. Moderate quality evidence indicates latanoprost as a treatment with the most favorable trade-off between benefits and harms.
Topics: Administration, Topical; Aged; Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Treatment Outcome
PubMed: 25358880
DOI: 10.3325/cmj.2014.55.468 -
PloS One 2018Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is...
BACKGROUND
Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.
OBJECTIVE
To explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.
PATIENTS AND METHODS
Serum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints.
RESULTS
Serum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity.
CONCLUSION
Our results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.
Topics: Adult; Aged; Analysis of Variance; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic; Synovial Membrane; Synovitis; Ultrasonography, Doppler; Young Adult
PubMed: 30188942
DOI: 10.1371/journal.pone.0203607 -
Scientific Reports Jul 2022The purpose of this study was to evaluate any alterations in the tear film and ocular surface beyond the early postoperative period following penetrating keratoplasty...
The purpose of this study was to evaluate any alterations in the tear film and ocular surface beyond the early postoperative period following penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK). This cross-sectional, contralateral-eye study compared ocular surface and tear film parameters of eyes with a previous PK or DALK in one eye and no prior surgery in the contralateral eye. Overall, 14 (87.5%) participants underwent PK, and 2 (12.5%) underwent DALK using a mechanical dissection. The median time from surgery was 3.4 years (range 1.5 to 38.7 years). The indication for unilateral keratoplasty was keratoconus in 15 (94%) participants, and corneal scarring in 1 (6%) eye, secondary to microbial keratitis. Operated eyes exhibited poorer non-invasive tear film breakup time, lower corneal sensitivity, lower sub-basal nerve density and more severe fluorescein staining scores than unoperated fellow eyes (all Q < 0.05). There were no significant differences in tear film lipid layer quality, tear meniscus height, conjunctival hyperaemia, lissamine green staining score, or meibography grade between operated and fellow eyes (all Q ≥ 0.20). Higher corneal esthesiometry threshold (lower corneal sensitivity) was correlated with shorter non-invasive tear film breakup time (Spearman's rho = - 0.361, p = 0.04) and increased fluorescein staining score (Spearman's rho = 0.417, p = 0.02). Keratoplasty can induce persistent changes in the ocular surface and tear film, including: increased fluorescein staining, decreased tear film breakup time, decreased corneal sub-basal nerve plexus density, and reduced corneal sensitivity.
Topics: Corneal Transplantation; Cross-Sectional Studies; Fluoresceins; Humans; Keratoplasty, Penetrating; Tears
PubMed: 35835841
DOI: 10.1038/s41598-022-16191-6 -
Journal of Clinical Medicine Feb 2022Background: Ocular surface frequently affects glaucoma patients. In this paper we aimed at evaluating the impact of glaucoma surgery on the ocular surface of patients...
Background: Ocular surface frequently affects glaucoma patients. In this paper we aimed at evaluating the impact of glaucoma surgery on the ocular surface of patients who received unilateral trabeculectomy. Methods: 26 consecutive patients successfully treated with trabeculectomy on one eye (Trab Eye) and under control with topical treatments on the fellow eye (Med Eye) were included in this observational study. They received IDEEL and OSDI questionnaires, Tear Film Osmolarity (TFO), grading of conjunctival hyperemia, fluorescein tear break-up time (tBUT), grading of corneal staining and Schirmer test. Results: IDEEL and OSDI scores were 48 ± 38 and 11 ± 12, respectively, with moderate correlation (r = 0.50, p = 0.03). Compared with Med eyes, Trab Eyes had higher tBUT (6.5 ± 3.5 vs. 5.1 ± 2.7 s, p = 0.004), lower conjunctival hyperemia (0.8 ± 0.9 and 1.7 ± 1.1 respectively, p < 0.001) and lower corneal staining (0.3 ± 0.5 and 0.6 ± 0.5, respectively, p = 0.03). Correlation between corneal staining and conjunctival hyperemia was 0.55 in Trab Eyes (p = 0.01) and 0.44 in Med Eyes (p > 0.05). Patients with bilateral corneal staining had had threefold worse questionnaire scores (p < 0.05). The duration of treatment and the daily exposure to preservatives did not directly affect OS parameters in this cohort of patients. Conclusions: Patients receiving successful trabeculectomy showed better OS homeostasis (higher TBUT, lower grading of conjunctival hyperemia and corneal staining) than fellow medically treated eyes. Presence of corneal epithelial damage in both eyes is the factor more consistently affecting questionnaire scores.
PubMed: 35268329
DOI: 10.3390/jcm11051238 -
International Journal of Ophthalmology 2020To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system.
AIM
To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system.
METHODS
This was a retrospective, single-center clinical study. Patients with symblepharon caused by ocular burns at least six months later were assessed. Chronic ocular sequelae were classified into 3 categories (eyelid, conjunctiva, and cornea) and 9 chronic ocular sequelae [friction factors, exposure factors, conjunctival hyperemia, length of symblepharon, scope of adhesion, lacrimal area adhesion, loss of the palisades of Vogt (POV), corneal neovascularization, and corneal opacification]. Each ocular sequela was graded from 0 to 3, depending on the increasing severity. The 9 ocular sequelae were evaluated to obtain the total severity score for each eye. The total severity score was defined as Grade I (1-9), Grade II (10-18), and Grade III (19-27). Moreover, the correlation between the severity of chronic ocular sequelae and visual acuity, surgical strategy, and the prognosis was analyzed, respectively.
RESULTS
Cases of 79 eyes with symblepharon caused by ocular burns were included in this study. Of these, 20 (25.32%) were defined as Grade I, 43 (54.43%) as Grade II, and 16 (20.25%) as Grade III. Eyes with a high total severity score had reduced visual acuity, required complicated surgery strategies, and poor prognosis (<0.001). Multivariate regression analysis showed that the scope of adhesion, corneal opacification, and corneal neovascularization significantly affected visual acuity, surgical strategy, and prognosis (all <0.001).
CONCLUSION
The evaluation of chronic ocular sequelae enabled the development of an objective grading system for patients with symblepharon caused by ocular burns. This grading system can be applied to guide the treatment and predict the prognosis.
PubMed: 32685393
DOI: 10.18240/ijo.2020.07.08 -
Frontiers in Aging Neuroscience 2017Alzheimer's disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the earliest symptomatology of AD with 10%-15% of MCI patients reportedly progressing to a diagnosis of AD. Individuals with a history of vascular risk factors (VRF's) are considered high risk candidates for developing cognitive impairment in later life. Evidence suggests that vascular injury resulting from untreated VRF's promotes progression from MCI to AD and exacerbates the severity of dementia in AD, and neuroimaging studies have found that the neurodegenerative processes associated with AD are heavily driven by VRF's that promote cerebral hypoperfusion. Subsequently, common links between vascular disorders such as hypertension and neurodegenerative disorders such as AD include compromised vasculature, cerebral hypoperfusion and chronic low grade inflammation (a hallmark of both hypertension and AD). Exercise has been demonstrated to be an effective intervention for blood pressure management, chronic low grade inflammation and improvements in cognition. Data from recent analyses suggests that isometric exercise training (IET) may improve vascular integrity and elicit blood pressure reductions in hypertensives greater than those seen with dynamic aerobic and resistance exercise. IET may also play an effective role in the management of VRF's at the MCI stage of AD and may prove to be a significant strategy in the prevention, attenuation or delay of progression to AD. A plausible hypothesis is that the reactive hyperemia stimulated by IET initiates a cascade of vascular, neurotrophic and neuro-endocrine events that lead to improvements in cognitive function.
PubMed: 28316570
DOI: 10.3389/fnagi.2017.00048 -
Cardiovascular Diabetology Feb 2018No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral...
Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study.
BACKGROUND
No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes.
AIM OF THE STUDY
We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD.
MATERIALS AND METHODS
The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance.
RESULTS
80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index.
CONCLUSIONS
Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects.
Topics: Adult; Aged; Biopsy; Cardiovascular Diseases; Case-Control Studies; Cognition; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Hyperemia; Italy; Liver; Male; Manometry; Mental Status and Dementia Tests; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Pulse Wave Analysis; Risk Factors; Severity of Illness Index; Vascular Stiffness
PubMed: 29452601
DOI: 10.1186/s12933-018-0670-7 -
The Cochrane Database of Systematic... May 2017Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions.
OBJECTIVES
To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies.
SELECTION CRITERIA
RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE.
MAIN RESULTS
We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy, France and Portugal. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours.One trial (28 participants) reported on the proportion of abrasions healed after 24 and 48 hours. These outcomes were similar in both arms of the trial. (at 24 hours RR 1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence). In the control group nine out of 10 abrasions were healed within 24 hours and all were healed by 48 hours. Complications of corneal abrasions were reported in 6 studies (609 participants) and were infrequently reported (4 complications, 1 in NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible drug-related adverse events (AEs) were reported in two trials (163 participants), with the number of adverse events low (4 AEs, 3 in NSAID group, including discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria, and 1 in the control group, corneal abscess) very low-certainty evidence.
AUTHORS' CONCLUSIONS
The findings of the included studies do not provide strong evidence to support the use of topical NSAIDs in traumatic corneal abrasions. This is important, since NSAIDs are associated with a higher cost compared to oral analgesics. None of the trials addressed our primary outcome measure of participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours.
Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Corneal Injuries; Diclofenac; Flurbiprofen; Humans; Indomethacin; Ketorolac; Pain Measurement; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 28516471
DOI: 10.1002/14651858.CD009781.pub2 -
American Journal of Physiology. Heart... Mar 2022Acute heat exposure improves microvascular function in aged adults as assessed using reactive hyperemia. The cutaneous and skeletal muscle microcirculations are thought...
Acute heat exposure improves microvascular function in aged adults as assessed using reactive hyperemia. The cutaneous and skeletal muscle microcirculations are thought to contribute to this response, but this has never been confirmed due to the methodological challenges associated with differentiating blood flow between these vascular beds. We hypothesized that acute hot water immersion would improve endothelial-dependent, but not endothelial-independent vasodilation in the microcirculation of the vastus lateralis muscle in healthy aged adults. Participants (70 ± 5 yr) were immersed for 60 min in thermoneutral (36°C) or hot (40°C) water. Ninety minutes following immersion, skeletal muscle microdialysis was used to bypass the cutaneous circulation and directly assess endothelial-dependent and endothelial-independent vasodilation by measuring the local hyperemic response to graded infusions of acetylcholine (ACh, 27.5 and 55.0 mM) and sodium nitroprusside (SNP, 21 and 42 mM), respectively. The hyperemic response to 27.5 mM ACh did not differ between thermal conditions ( = 0.9). However, the hyperemic response to 55.0 mM ACh was increased with prior hot water immersion (thermoneutral immersion, 43.9 ± 23.2 mL/min/100 g vs. hot water immersion, 66.5 ± 25.5 mL/min/100 g; < 0.01). Similarly, the hyperemic response to 21 mM SNP did not differ between thermal conditions ( = 0.3) but was increased following hot water immersion with the infusion of 42 mM SNP (thermoneutral immersion, 48.8 ± 25.6 mL/min/100 g vs. hot water immersion, 90.7 ± 53.5 mL/min/100 g; < 0.01). These data suggest that acute heat exposure improves microvascular function in skeletal muscle of aged humans. Acute heat exposure improves microvascular function in aged adults as assessed using reactive hyperemia. The cutaneous and skeletal muscle microcirculations are thought to contribute to this response, but this has never been confirmed due to the methodological challenges associated with differentiating blood flow between these vascular beds. Using the microdialysis technique to bypass the cutaneous circulation, we demonstrated that heat exposure improves endothelial-dependent and endothelial-independent vasodilation in the microcirculation of skeletal muscle in aged humans.
Topics: Aged; Female; Humans; Hyperthermia, Induced; Male; Microcirculation; Microvessels; Muscle, Skeletal; Vasodilation
PubMed: 35060753
DOI: 10.1152/ajpheart.00645.2021 -
BMC Cardiovascular Disorders Aug 2020Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study... (Observational Study)
Observational Study
BACKGROUND
Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study was to investigate the association between urinary IgM, albuminuria, and vascular parameters reflecting arterial structure and function.
METHODS
Subjects of the present study were from the Malmö Offspring study (MOS) cohort, and included 1531 offspring (children and grand-children) to first-generation subjects that participated in the Malmö Diet Cancer-Cardiovascular Arm study cohort. At baseline, technical measurements of arterial stiffness (carotid-femoral pulse wave velocity; c-f PWV), carotid arterial morphology, 24-h ambulatory blood pressure recordings, ankle-brachial-index (ABI), and evaluation of endothelial function (reactive hyperemia index, RHI) were performed. Urinary (U) IgM, U-albumin, and U-creatinine were measured. Multivariate adjusted logistic regression was used to test whether U-IgM excretion and increasing urinary albumin excretion were related to vascular parameters.
RESULTS
Detectable U-IgM was independently associated with higher systolic blood pressure, odds ratio (OR) 1.021, 95% confidence interval (CI, 1.003-1.039), p = 0.025 and lower ABI; ABI dx: OR 0.026, 95% CI (0.002-0.381), p = 0.008, ABI sin: OR 0.040, 95% CI (0.003-0.496), p = 0.012. Low-grade albuminuria was independently associated with systolic and diastolic blood pressure, aortic blood pressure, the c-f PWV and the number of carotid intima plaques (p < 0.05).
CONCLUSIONS
In young to middle-aged, mostly healthy individuals, increased U-IgM excretion and low-grade albuminuria are associated with adverse vascular parameters. Increased U-IgM excretion may reflect subclinical peripheral atherosclerosis, whereas increased U-albumin excretion is associated with a wide range of cardiovascular abnormalities. This may reflect different pathophysiological mechanisms.
Topics: Adult; Age Factors; Aged; Aging; Albuminuria; Blood Pressure; Cardiovascular Diseases; Female; Glomerular Filtration Rate; Heart Disease Risk Factors; Humans; Immunoglobulin M; Kidney; Male; Middle Aged; Prognosis; Risk Assessment; Sweden; Vascular Stiffness; Young Adult
PubMed: 32758145
DOI: 10.1186/s12872-020-01638-3