825 resultados para Degeneração macular
Resumo:
Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.
Resumo:
BACKGROUND:
Age-related macular degeneration (AMD) and Alzheimer's disease (AD) share several features, including the presence of extracellular abnormal deposits associated with neuronal degeneration, drusen, and plaques, respectively. Investigation of any association of AMD and specifically AD is worthwhile but has rarely been done.
OBJECTIVES:
The aim of this study was to determine the prevalence of AMD in subjects with AD in comparison with an age-matched cognitively normal cohort.
METHODS:
Cases were defined as those diagnosed with AD using standardized criteria as part of their clinical care, while controls were cognitively intact individuals aged 65 years or more. Dilated retinal photographs were taken, and a range of potentially confounding factors measured including APOE genotype. AMD features were recorded and AMD grades given.
RESULTS:
Data was collected on 322 controls and 258 cases. While AMD was associated with AD, and the proportion of cases of advanced AMD in AD cases was twice that of controls, when corrected the association was lost. AD was associated with age, the presence of an APOE allele, and smoking, while being 'generally unwell recently' was associated with a reduced risk of AD.
CONCLUSION:
AD and AMD are both associated with age, but our study does not find evidence they are associated with each other. However the retina offers an opportunity to non-invasively image neuronal tissue, and more sophisticated imaging techniques may shed light on ocular biomarkers of AD.
Resumo:
Purpose:The Signal Transducer and Activator of Transcription 3 (STAT3) pathway is known to play an important role in inflammation and angiogenesis. STAT3 can be activated by IL-6 family cytokines through the receptor IL-6R/gp130. Increased IL-6 has been detected in the plasma and vitreous in neovascular age-related macular degeneration (nAMD) patients. The aim of this study was to investigate the role of the STAT3 pathway in the pathogenesis of nAMD.
Methods:Blood cells from nAMD patients (n = 11) and age-, gender-matched healthy controls (n = 13) were stimulated with IL-6 for 20 minutes. The expression of the activated form of STAT3 (p-STAT3) was examined by flow cytometry. The mRNA levels of gp130, IL-6R and the suppressor of cytokine signalling 3 (SOCS3, a negative regulator of p-STAT3) were evaluated by real-time RT-PCR. Laser-induced choroidal neovascularisation (CNV) was performed in WT C57BL/6J mice as well as in the myeloid cell specific SOCS3 deficiency mice i.e., the LysMCre-SOCS3fl/fl mice. STAT3 activation in CNV lesions was examined by western blot. The size of CNV at different times after laser treatment was measured by confocal microscopy of RPE/choroidal flatmounts.
Results:The expression of p-STAT3 in CD11b+ monocytes was significantly increased in nAMD patients compared to healthy controls, although mRNA expression of gp130, IL-6R and SOCS3 did not differ between patients and controls. The expression of p-STAT3 in the retinal and RPE/choroidal tissues was increased at 1 and 3 days after laser treatment. The administration of a STAT3 inhibitor LLL12 significantly suppressed CNV. CD11b+ monocytes from LysMCre-SOCS3fl/fl mice expressed higher levels of p-STAT3 compared to the cells from WT mice. Laser induced CNV developed earlier and were larger in LysMCre-SOCS3fl/fl mice compared to WT C57BL/6J mice.
Conclusions:Our results suggest that STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD, and targeting the STAT3 pathway may have therapeutic potential in nAMD.
Resumo:
Objective
To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA).
Design
NMA.
Data sources
The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science.
Eligibility criteria for selecting studies
Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions.
Results
Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections.
Conclusions
We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections.
Resumo:
The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; Index test: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46–98%) and 78% (64–88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.
Resumo:
PURPOSE: To evaluate serum soluble Flt-1 (sFlt-1) in age-related degeneration (AMD) patients.
DESIGN: Case control study.
METHODS: Fifty-six non-AMD participants, fifty-three early AMD patients and ninety-seven neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS.
RESULTS: Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8±2.9 pg/mL (±SEM), 88.2±2.6 pg/mL and 79.9±2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, p<0.01). For each 10 point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decreases by 27.8% OR=0.722 (95% CI: 0.588-0.888, p=0.002) and 27.0% OR=0.730 (95% CI: 0.594-0.898, p=0.003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD.
CONCLUSIONS: Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD.
Resumo:
Topic
To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.
Clinical RelevanceTraditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.
MethodsSystematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.
ResultsWe included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.
ConclusionsThere is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.
Resumo:
BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.
OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.
DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).
REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.
INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).
COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.
RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£44,649; QALYs 10.575; incremental cost-effectiveness ratio £47,768). The least costly strategy had a 46.4% probability of being cost-effective at £30,000 willingness-to-pay threshold.
LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.
CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.
STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.
FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Resumo:
Pupose. To evaluate the relationship between retinal vascular caliber (RVC), iris color and age-related macular degeneration (AMD) in elderly Irish nuns. Methods. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin age-related maculopathy grading system. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction and fellow RVC. Results. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range: 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P<0.05) but this was no longer significant after adjustment. AMD status was categorized as no AMD, any AMD and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis but this was no longer significant after adjustment. A non-significant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Conclusions. RVC was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but non-significant AMD risk was observed in those with brown compared to blue iris color.
Resumo:
Background
Diabetic macular oedema (DMO) is a thickening of the central retina, or the macula, and is associated with long-term visual loss in people with diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic fundus photography, leads to moderate visual loss in one of four people within three years. It also showed that grid or focal laser photocoagulation to the macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs has also been used to try to improve vision in people with macular oedema due to DR.Optical coherence tomography (OCT) is based on optical reflectivity and is able to image retinal thickness and structure producing cross-sectional and three-dimensional images of the central retina. It is widely used because it provides objective and quantitative assessment of macular oedema, unlike the subjectivity of fundus biomicroscopic assessment which is routinely used by ophthalmologists instead of photography. Optical coherence tomography is also used for quantitative follow-up of the effects of treatment of CSMO.
Objectives
To determine the diagnostic accuracy of OCT for detecting DMO and CSMO, defined according to ETDRS in 1985, in patients referred to ophthalmologists after DR is detected. In the update of this review we also aimed to assess whether OCT might be considered the new reference standard for detecting DMO.
Search methods
We searched the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1950 to June 2013), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to June 2013), BIOSIS Previews (January 1969 to June 2013), MEDION and the Aggressive Research Intelligence Facility database (ARIF). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 June 2013. We checked bibliographies of relevant studies for additional references.
Selection Criteria
We selected studies that assessed the diagnostic accuracy of any OCT model for detecting DMO or CSMO in patients with DR who were referred to eye clinics. Diabetic macular oedema and CSMO were diagnosed by means of fundus biomicroscopy by ophthalmologists or stereophotography by ophthalmologists or other trained personnel.
Data collection and analysis
Three authors independently extracted data on study characteristics and measures of accuracy. We assessed data using random-effects hierarchical sROC meta-analysis models.
Main results
We included 10 studies (830 participants, 1387 eyes), published between 1998 and 2012. Prevalence of CSMO was 19% to 65% (median 50%) in nine studies with CSMO as the target condition. Study quality was often unclear or at high risk of bias for QUADAS 2 items, specifically regarding study population selection and the exclusion of participants with poor quality images. Applicablity was unclear in all studies since professionals referring patients and results of prior testing were not reported. There was a specific 'unit of analysis' issue because both eyes of the majority of participants were included in the analyses as if they were independent.In nine studies providing data on CSMO (759 participants, 1303 eyes), pooled sensitivity was 0.78 (95% confidence interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to 0.93). The median central retinal thickness cut-off we selected for data extraction was 250 µm (range 230 µm to 300 µm). Central CSMO was the target condition in all but two studies and thus our results cannot be applied to non-central CSMO.Data from three studies reporting accuracy for detection of DMO (180 participants, 343 eyes) were not pooled. Sensitivities and specificities were about 0.80 in two studies and were both 1.00 in the third study.Since this review was conceived, the role of OCT has changed and has become a key ingredient of decision-making at all levels of ophthalmic care in this field. Moreover, disagreements between OCT and fundus examination are informative, especially false positives which are referred to as subclinical DMO and are at higher risk of developing clinical CSMO.
Authors' conclusions
Using retinal thickness thresholds lower than 300 µm and ophthalmologist's fundus assessment as reference standard, central retinal thickness measured with OCT was not sufficiently accurate to diagnose the central type of CSMO in patients with DR referred to retina clinics. However, at least OCT false positives are generally cases of subclinical DMO that cannot be detected clinically but still suffer from increased risk of disease progression. Therefore, the increasing availability of OCT devices, together with their precision and the ability to inform on retinal layer structure, now make OCT widely recognised as the new reference standard for assessment of DMO, even in some screening settings. Thus, this review will not be updated further.
Resumo:
Purpose:To determine the optimal role of OCT in diagnosing and monitoring nAMD (detecting disease activity and the need for further anti-VEGF treatment).
Methods:Systematic review. Major electronic databases and websites were searched. Studies were included if they reported the diagnostic performance of time domain or spectral domain OCT (or selected other tests) against a reference standard of ophthalmologist-interpreted fluorescein angiography in people with newly suspected or previously diagnosed nAMD. Risk of bias was assessed by two independent investigators using QUADAS-2. Summary receiver operating characteristic (SROC) curves were produced for each test given sufficient data.
Results:3700 titles/abstracts were screened, and 120 (3.2%) were selected for full-text assessment. A total of 22 studies were included (17 on diagnosis, 7 monitoring, and 3 both). From 15 studies reporting OCT data, sensitivity and specificity ranged from 59% to 100% and 27% to 100%, respectively.
Conclusions:The reported diagnostic performance of OCT showed large variability. The methodological quality of most studies was sub-optimal.
Resumo:
Age-related macular degeneration (AMD) is the leading cause of blindness among white caucasians over the age of 50 years with a prevalence rate expected to increase markedly with an anticipated increase in the life span of the world population. To further expand our knowledge of the genetic architecture of the disease, we pursued a candidate gene approach assessing 25 genes and a total of 109 variants. Of these, synonymous single nucleotide polymorphism (SNP) rs17810398 located in death-associated protein-like 1 (DAPL1) was found to be associated with AMD in a joint analysis of 3,229 cases and 2,835 controls from five studies [combined P ADJ = 1.15 × 10(-6), OR 1.332 (1.187-1.496)]. This association was characterized by a highly significant sex difference (P diff = 0.0032) in that it was clearly confined to females with genome-wide significance [P ADJ = 2.62 × 10(-8), OR 1.541 (1.324-1.796); males: P ADJ = 0.382, OR 1.084 (0.905-1.298)]. By targeted resequencing of risk and non-risk associated haplotypes in the DAPL1 locus, we identified additional potentially functional risk variants, namely a common 897-bp deletion and a SNP predicted to affect a putative binding site of an exonic splicing enhancer. We show that the risk haplotype correlates with a reduced retinal transcript level of two, less frequent, non-canonical DAPL1 isoforms. DAPL1 plays a role in epithelial differentiation and may be involved in apoptotic processes thereby suggesting a possible novel pathway in AMSaveD pathogenesis.
