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Clinical Therapeutics Nov 2017While corticosteroids are relatively inexpensive and commonly used as treatment for a variety of conditions, long-term use is known to be associated with certain... (Review)
Review
PURPOSE
While corticosteroids are relatively inexpensive and commonly used as treatment for a variety of conditions, long-term use is known to be associated with certain toxicities. Prior systematic reviews have revealed an increased risk for costly adverse events (AEs), including bone fracture, infection, and gastrointestinal bleeding. The objective of this study was to conduct a systematic literature review of recent publications on the burden of long-term corticosteroid exposure, specifically, to summarize the AEs and economic impact of long-term corticosteroid use and to reveal data gaps for additional research.
METHODS
The Ovid search platform was used to access scientific literature databases. The search strategy targeted the use of corticosteroids and economic outcomes research. Articles were restricted to those published between 2007 and 2016 to cover publications since prior reviews; conference abstracts and articles assessing pediatrics were excluded. Titles and abstracts resulting from inclusion criteria were screened, and reviewers independently extracted relevant information from the relevant full-text articles.
FINDINGS
The literature review included 32 articles, with 75% focusing on autoimmune diseases, asthma, or lung diseases. Included articles were 14 database analyses, 6 simulations, 6 clinical trials, 3 systematic literature reviews, 2 patient surveys, and 1 chart review. Commonly-cited AEs associated with long-term corticosteroid exposure included hypertension (prevalence >30%); bone fracture (21%-30%); cataract (1%-3%); nausea, vomiting, and other gastrointestinal conditions (1%-5%); and metabolic issues (eg, weight gain, hyperglycemia, and type 2 diabetes; cases had 4-fold the risk of controls). Association of dose and duration with increased AE risk is not well-quantified. AEs like peptic ulcer and myocardial infarction are particularly costly to payers (1-year cost of $21,825 and $26,472, respectively, in year-2009 USD). The few articles assessing the economic impact of corticosteroid use have found dose-related increases in health care resource utilization and costs, with per-annum incremental costs relative to nonusers ranging from $5700 in low-dose users (<7.5 mg/d) to $29,000 in high-dose users (>15 mg/d). Adherence to treatment guidelines on avoiding AEs (eg, prescribing of oral bisphosphonates, calcium, and vitamin D) remains low.
IMPLICATIONS
Although doses of long-term corticosteroids have fallen over the past several decades in response to AEs, dose reduction may not be a sufficient solution. Numerous AEs, some very costly, persist among long-term corticosteroid users, suggesting a need for further research to fill current data gaps, as well as a potential need for alternative treatment options.
Topics: Adrenal Cortex Hormones; Asthma; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Gastrointestinal Diseases; Humans; Outcome Assessment, Health Care; Time Factors
PubMed: 29055500
DOI: 10.1016/j.clinthera.2017.09.011 -
Eye (London, England) Aug 2020The aim of our study was to estimate regional and global cataract prevalence, its prevalence in different age groups, and the determinants of heterogeneity and its... (Meta-Analysis)
Meta-Analysis Review
The aim of our study was to estimate regional and global cataract prevalence, its prevalence in different age groups, and the determinants of heterogeneity and its prevalence. For that, we used international databases such as PubMed, Web of Science, Scopus, Embase, and other sources of information to conduct a systematic search for all articles concerning the prevalence of age-related cataract and its types in different age groups. Of the 9922 identified articles, 45 studies with a sample size of 161,947 were included in the analysis, and most of them were from the Office for the Western Pacific Region (19 studies). Age- standardized pooled prevalence estimate (ASPPE) and 95% confidence interval (95% CI) of any cataract, cortical cataract, nuclear cataract, and posterior subcapsular (PSC) cataract were 17.20% (13.39-21.01), 8.05% (4.79-11.31), 8.22% (4.93-11.52), and 2.24% (1.41-3.07), respectively. Significant effects on heterogeneity were observed for the WHO region in the prevalence of any cataract (b: 6.30; p: 0.005) and study year in the prevalence of nuclear cataract (b: -0.66, p: 0.042). In general, the prevalence of cataract not only varies by region but also by age group, and most cases are over the age of 60 years. We examined the sources of variance in the prevalence of cataract and its different types, and identified age as a responsible factor in the prevalence of any cataract, cortical cataract, nuclear cataract, and PSC of cataract, WHO region in the prevalence of any cataract, and study year in the prevalence of nuclear cataract.
Topics: Cataract; Databases, Factual; Humans; Middle Aged; Prevalence
PubMed: 32055021
DOI: 10.1038/s41433-020-0806-3 -
The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
PloS One 2014Changes in lens may reflect the status of systemic health of human beings but the supporting evidences are not well summarized yet. We aimed to determine the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Changes in lens may reflect the status of systemic health of human beings but the supporting evidences are not well summarized yet. We aimed to determine the relationship of age-related cataract, cataract surgery and long-term mortality by pooling the results of published population-based studies.
METHODS
We searched PubMed and Embase from their inception till March, 2014 for population-based studies reporting the associations of any subtypes of age-related cataract, cataract surgery with all-cause mortality. We pooled the effect estimates (hazards ratios [HRs]) under a random effects model.
RESULTS
Totally, we identified 10 unique population-based studies including 39,659 individuals at baseline reporting the associations of any subtypes of cataract with all-cause mortality from 6 countries. The presence of any cataract including cataract surgery was significantly associated with a higher risk of death (pooled HR: 1.43, 95% CI, 1.21, 2.02; P<0.001; I(2) = 64.2%). In the meta-analysis of 9 study findings, adults with nuclear cataract were at higher risks of mortality (pooled HR: 1.55, 95% CI, 1.17, 2.05; P = 0.002; I(2) = 89.2%). In the meta-analysis of 8 study findings, cortical cataract was associated with higher risks of mortality (pooled HR: 1.26, 95% CI, 1.12, 1.42; P<0.001, I(2) = 29.7%). In the meta-analysis of 6 study findings, PSC cataract was associated with higher risks of mortality (pooled HR: 1.37, 95% CI, 1.04, 1.80; P = 0.03; I(2) = 67.3%). The association between cataract surgery and mortality was marginally non-significant by pooling 8 study findings (pooled HR: 1.27, 95% CI, 0.97, 1.66; P = 0.08; I(2)= 76.6%).
CONCLUSIONS
All subtypes of age-related cataract were associated with an increased mortality with nuclear cataract having the strongest association among the 3 cataract subtypes. However, cataract surgery was not significantly related to mortality. These findings indicated that changes in lens may serve as markers for ageing and systemic health in general population.
Topics: Aging; Cataract; Cataract Extraction; Humans; Proportional Hazards Models; Treatment Outcome
PubMed: 25369040
DOI: 10.1371/journal.pone.0112054 -
Philosophical Transactions of the Royal... Apr 2011Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a... (Review)
Review
Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.
Topics: Aging; Cataract; Crystallins; Free Radical Scavengers; Humans; Lens, Crystalline; Models, Biological; Optical Phenomena; Oxidative Stress; Presbyopia; Protein Processing, Post-Translational
PubMed: 21402586
DOI: 10.1098/rstb.2010.0300 -
Investigative Ophthalmology & Visual... Jan 2021Human cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus-cortex interface. Cortex and...
PURPOSE
Human cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus-cortex interface. Cortex and nucleus have different elastic properties, which change with age. We therefore subjected ex vivo lenses to simulated accommodation and studied the internal deformations to better understand the mechanism of cortical cataract formation.
METHODS
Nine human donor lenses (33-88 years old) were tested using a bespoke radial stretching device for anterior eye segments. Seven of the lenses exhibited cortical cataracts. The other two lenses, without cataract, were used as controls. Frontal and cross-sectional images of the lens obtained during stretching facilitated measurements on equatorial lens diameter and central lens thickness in the stretched and unstretched states.
RESULTS
Stretching caused the lens equatorial diameter to increase in all cases. Conversely, the lens central thickness showed no systematic variation during stretching. For four of the lenses with cortical cataract, ruptures were observed during stretching at the nucleus-cortex boundary adjacent to the cortical cataracts. Ruptures were not observed in the control lenses or in the three other lenses with cortical cataract.
CONCLUSIONS
Internal ruptures can occur in aged ex vivo lenses subjected to simulated disaccommodation. These ruptures occur at the nucleus-cortex interface; at this location, a significant stiffness discontinuity is expected to develop with age. It is hypothesized that ruptures occur in in vivo lenses during accommodation-or attempted accommodation.
Topics: Accommodation, Ocular; Adult; Aged; Aged, 80 and over; Biomechanical Phenomena; Cataract; Cross-Sectional Studies; Humans; Lens Cortex, Crystalline; Middle Aged; Photography; Rupture, Spontaneous; Stress, Physiological; Tissue Donors
PubMed: 33427852
DOI: 10.1167/iovs.62.1.12 -
Indian Journal of Ophthalmology Jul 2021The aim of this study was to evaluate visual outcomes of cataract surgery in patients with retinitis pigmentosa.
PURPOSE
The aim of this study was to evaluate visual outcomes of cataract surgery in patients with retinitis pigmentosa.
METHODS
This retrospective case series includes a review of the medical records of all patients with retinitis pigmentosa undergoing cataract surgery between 2005 and 2018. The primary outcome measure was corrected distant visual acuity and change in vision impairment after surgery.
RESULTS
Of the 103 (132) patients, 60 (58.3%) were men and 43 (41.7%) were women. The mean age of the study population was 51.3 ± 11.3 (22-74) years. The mean symptom duration was 35.4 ± 44.5 (1-300) months. The most common morphology of cataracts was a combination of nuclear sclerosis, posterior subcapsular, and cortical cataract (n = 65 eyes, 49.3%). Phacoemulsification (87 eyes, 65.9%) was the preferred surgical technique. The mean preoperative corrected distant visual acuity of 1.21 ± 0.87 log MAR units improved significantly (P < 0.001) to 0.60 ± 0.56 log MAR units after surgery. The number of blind patients reduced from 27 (26.2%) to 8 (7.8%) patients. Zonular dialysis and posterior capsule tear were seen in six (4.5%) eyes each. Good preoperative vision (odds ratio: 6.1 [95% confidence interval: 2.9-13.0], P < 0.0001) was associated with better outcome, wheras reduced central macular thickness (odds ratio: 3.5 [95% confidence interval: 1.3-9.2], P = 0.011) was associated with poor outcome.
CONCLUSION
A considerable number of patients presented with advanced cataracts and severe vision impairment. Significant improvement in visual acuity and alleviation of vision impairment was seen after surgery, with few complications. Good preoperative visual acuity predicted a good outcome, whereas macular thinning predicted a poor outcome.
Topics: Adult; Aged; Cataract; Cataract Extraction; Female; Humans; Male; Middle Aged; Phacoemulsification; Retinitis Pigmentosa; Retrospective Studies; Young Adult
PubMed: 34146021
DOI: 10.4103/ijo.IJO_2916_20 -
Ophthalmology May 2022To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs.
PURPOSE
To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs.
DESIGN
DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset.
PARTICIPANTS
A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants).
METHODS
Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students.
MAIN OUTCOME MEASURES
Mean squared error (MSE).
RESULTS
On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC.
CONCLUSIONS
DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.
Topics: Cataract; Cataract Extraction; Deep Learning; Humans; Photography
PubMed: 34990643
DOI: 10.1016/j.ophtha.2021.12.017 -
Optometry and Vision Science : Official... Oct 2014To determine normative reference ranges for higher-order wavefront error (HO-WFE), compare these values with those in common ocular pathologies, and evaluate treatments. (Review)
Review
PURPOSE
To determine normative reference ranges for higher-order wavefront error (HO-WFE), compare these values with those in common ocular pathologies, and evaluate treatments.
METHODS
A review of 17 major studies on HO-WFE was made, involving data for a total of 31,605 subjects. The upper limit of the 95% confidence interval (CI) for HO-WFE was calculated from the most comprehensive of these studies using normal healthy patients aged 20 to 80 years. There were no studies identified using the natural pupil size for subjects, and for this reason, the HO-WFE was tabulated for pupil diameters of 3 to 7 mm. Effects of keratoconus, pterygium, cataract, and dry eye on HO-WFE were reviewed and treatment efficacy was considered.
RESULTS
The calculated upper limit of the 95% CI for HO-WFE in a healthy normal 35-year-old patient with a mesopic pupil diameter of 6 mm would be 0.471 μm (471 nm) root-mean-square or less. Although the normal HO-WFE increases with age for a given pupil size, it is not yet completely clear how the concurrent influence of age-related pupillary miosis affects these findings. Abnormal ocular conditions such as keratoconus can induce a large HO-WFE, often in excess of 3.0 μm, particularly attributed to coma. For pterygium or cortical cataract, a combination of coma and trefoil was more commonly induced. Nuclear cataract can induce a negative spherical HO-WFE, usually in excess of 1.0 μm.
CONCLUSIONS
The upper limit of the 95% CI for HO-WFE root-mean-square is about 0.5 μm with normal physiological pupil sizes. With ocular pathologies, HO-WFE can be in excess of 1.0 μm, although many devices and therapeutic and surgical treatments are reported to be highly effective at minimizing HO-WFE. More accurate normative reference ranges for HO-WFE will require future studies using the subjects' natural pupil size.
Topics: Adult; Aged; Aged, 80 and over; Cataract; Contact Lenses; Corneal Wavefront Aberration; Female; Humans; Keratoconus; Male; Middle Aged; Refraction, Ocular; Young Adult
PubMed: 25216319
DOI: 10.1097/OPX.0000000000000377 -
Indian Journal of Ophthalmology Nov 2020In the present study, we describe a step-by-step technique for cortex aspiration during cataract surgery- POPS (positioning, occlusion, posterior displacement, and...
In the present study, we describe a step-by-step technique for cortex aspiration during cataract surgery- POPS (positioning, occlusion, posterior displacement, and swiping). Firstly, the aspiration probe is positioned under the bulk of cortical fibers beyond the capsulorhexis margin. Subsequently, the aspiration port is occluded with minimal vacuum, and the occluded port is displaced posteriorly to detach the cortical fibers off the anterior capsule. Now, tangential, arc-like swiping movements are performed while gradually increasing vacuum at the same time. The fibers are brought to the center and finally aspirated. This allows complete removal of the equatorial fibers and lens epithelial cells (LEC) with the least stress to the capsulozonular complex. Unlike the conventional technique, which involves the radial pull of cortical fibers, in this technique, there is swiping and posterior displacement of the cortical fibers before pulling towards the center and aspirating. We believe this technique will ensure safer, more effective cortical and LEC removal, reducing zonular stress.
Topics: Capsulorhexis; Cataract; Cataract Extraction; Epithelial Cells; Humans; Lens, Crystalline; Vacuum
PubMed: 33120645
DOI: 10.4103/ijo.IJO_2384_19