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Assessment of capillary dropout in the superficial retinal capillary plexus by optical coherence tomography angiography in the early stage of diabetic retinopathy.
Shen, C, Yan, S, Du, M, Zhao, H, Shao, L, Hu, Y
BMC ophthalmology. 2018;(1):113
Abstract
BACKGROUND To assess capillary dropout in the superficial retinal capillary plexus (SCP) by optical coherence tomography angiography (OCTA) in the early stage of diabetic retinopathy (DR). METHODS This study was a cross-sectional observational study. Patients that underwent OCTA examinations in our hospital between November 2015 and May 2016 were included in the study. The subjects were divided into two groups: A) normal controls (41 eyes of 41 subjects) and B) the DR patients (49 eyes of 49 patients with mild non-proliferative DR (NPDR)). The retinal thickness and SCP vessel density were analyzed using built-in software in nine sections of the macular area; whole scan area; fovea; parafovea; and sub-sections of the parafovea, superior-hemi, inferior-hemi, temporal, superior, nasal, and inferior. The correlation between vessel density and retinal thickness was also analyzed. RESULTS The SCP density was significantly lower (P < 0.05) in mild NPDR patients than in normal controls in all areas, with the exception of the fovea (P > 0.05). In the parafovea, superior-hemi, inferior-hemi, temporal, and nasal sectors of group B, the SCP density was negatively correlated with the corresponding retinal thickness (P < 0.05). Specifically, as the SCP density decreased, retinal thickness increased. CONCLUSIONS In the early stage of NPDR, retinal capillary dropout and retinal thickness changes can be clearly captured and analyzed by OCTA. The results confirm a negative correlation between vessel density and retinal thickness in diabetic patients. This noninvasive technique could be applied for DR detection and monitoring. Further study with a larger sample size is warranted.
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Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.
Wielders, LHP, Schouten, JSAG, Winkens, B, van den Biggelaar, FJHM, Veldhuizen, CA, Murta, JCN, Goslings, WRO, Kohnen, T, Tassignon, MJ, Joosse, MV, et al
Journal of cataract and refractive surgery. 2018;(7):836-847
Abstract
PURPOSE To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING Twelve European study centers. DESIGN Randomized clinical trial. METHODS Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 μm and 9.7 μm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.
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Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.
Virgili, G, Parravano, M, Evans, JR, Gordon, I, Lucenteforte, E
The Cochrane database of systematic reviews. 2018;(10):CD007419
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Abstract
BACKGROUND Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. OBJECTIVES The 2014 update of this review found high-quality evidence of benefit with anti-VEGF modalities, compared to laser photocoagulation, for the treatment of DMO. The objective of this updated review is to compare the effectiveness and safety of the different anti-VEGF drugs using network meta-analysis methods. SEARCH METHODS We searched various electronic databases on 26 April 2017. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham or no treatment in people with DMO. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods for pair-wise meta-analysis and we augmented this evidence using network meta-analysis methods. We focused on the relative efficacy and safety of the three most commonly used drugs as interventions of direct interest for practice: aflibercept and ranibizumab, used on-label; and off-label bevacizumab.We collected data on three efficacy outcomes (gain of 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean change in best-corrected visual acuity (BCVA); mean change in central retinal thickness (CRT)), three safety outcomes (all severe systemic adverse events (SSAEs); all-cause death; arterial thromboembolic events) and quality of life.We used Stata 'network' meta-analysis package for all analyses. We investigated the risk of bias of mixed comparisons based on the variance contribution of each study, having assigned an overall risk of bias to each study. MAIN RESULTS Twenty-four studies included 6007 participants with DMO and moderate vision loss, of which two studies randomised 265 eyes of 230 participants and one was a cross-over study on 56 participants (62 eyes) that was treated as a parallel-arm trial. Data were collected on drugs of direct interest from three studies on aflibercept (975 eyes), eight studies on bevacizumab (515 eyes), and 14 studies on ranibizumab (1518 eyes). As treatments of indirect interest or legacy treatment we included three studies on pegaptanib (541 eyes), five studies on ranibizumab plus prompt laser (557 eyes), one study on ranibizumab plus deferred laser (188 eyes), 13 studies on laser photocoagulation (936 eyes) and six studies on sham treatment (793 eyes).Aflibercept, bevacizumab and ranibizumab were all more effective than laser for improving vision by 3 or more lines after one year (high-certainty evidence). Approximately one in 10 people improve vision with laser, and about three in 10 people improve with anti-VEGF treatment: risk ratio (RR) versus laser 3.66 (95% confidence interval (CI) 2.79 to 4.79) for aflibercept; RR 2.47 (95% CI 1.81 to 3.37) for bevacizumab; RR 2.76 (95% CI 2.12 to 3.59) for ranibizumab. On average there was no change in visual acuity (VA) with laser after one year, compared with a gain of 1 or 2 lines with anti-VEGF treatment: laser versus aflibercept mean difference (MD) -0.20 (95% CI -0.22 to -0.17) logMAR; versus bevacizumab MD -0.12 (95% CI -0.15 to -0.09) logMAR; versus ranibizumab MD -0.12 (95% CI -0.14 to -0.10) logMAR. The certainty of the evidence was high for the comparison of aflibercept and ranibizumab with laser and moderate for bevacizumab comparison with laser due to inconsistency between the indirect and direct evidence.People receiving ranibizumab were less likely to gain 3 or more lines of VA at one year compared with aflibercept: RR 0.75 (95% CI 0.60 to 0.94), moderate-certainty evidence. For every 1000 people treated with aflibercept, 92 fewer would gain 3 or more lines of VA at one year if treated with ranibizumab (22 to 148 fewer). On average people receiving ranibizumab had worse VA at one year (MD 0.08 logMAR units, 95% CI 0.05 to 0.11), moderate-certainty evidence; and higher CRT (MD 39 µm, 95% CI 2 µm to 76 µm; low-certainty evidence). Ranibizumab and bevacizumab were comparable with respect to aflibercept and did not differ in terms of VA: RR of gain of 3 or more lines of VA at one year 1.11 (95% CI 0.87 to 1.43), moderate-certainty evidence, and difference in change in VA was 0.00 (95% CI -0.02 to 0.03) logMAR, moderate-certainty evidence. CRT reduction favoured ranibizumab by -29 µm (95% CI -58 µm to -1 µm, low-certainty evidence). There was no evidence of overall statistical inconsistency in our analyses.The previous version of this review found moderate-certainty evidence of good safety of antiangiogenic drugs versus control. This update used data at the longest available follow-up (one or two years) and found that aflibercept, ranibizumab and bevacizumab do not differ regarding systemic serious adverse events (SSAEs) (moderate- or high-certainty evidence). However, risk of bias was variable, loop inconsistency could be found and estimates were not precise enough on relative safety regarding less frequent events such as arterial thromboembolic events or death (low- or very low-certainty evidence).Two-year data were available and reported in only four RCTs in this review. Most industry-sponsored studies were open-label after one year. One large publicly-funded study compared the three drugs at two years and found no difference. AUTHORS' CONCLUSIONS Anti-VEGF drugs are effective at improving vision in people with DMO with three to four in every 10 people likely to experience an improvement of 3 or more lines VA at one year. Aflibercept may confer some advantage over ranibizumab and bevacizumab in people with DMO at one year in visual and anatomic terms but it is unclear whether this applies to the long-term. There is a need for more evidence on the long-term (greater than two years) comparative effects of these anti-VEGF agents. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated and under-monitored.We found no signals of differences in overall safety between the three antiangiogenic drugs that are currently available to treat DMO, but our estimates are imprecise for cardiovascular events and death.
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Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis.
Song, P, Yu, J, Chan, KY, Theodoratou, E, Rudan, I
Journal of global health. 2018;(1):010803
Abstract
BACKGROUND Diabetic retinopathy (DR), the primary retinal vascular complication of diabetes mellitus (DM), is a leading cause of vision impairment and blindness in working-age population globally. Despite mounting concerns about the emergence of DM as a major public health problem in the largest developing country, China, much remains to be understood about the epidemiology of DR. We aimed to investigate the prevalence of and risk factors for DR, and estimate the burden of DR in China in 2010. METHODS China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline were searched for studies that reported the prevalence of and risk factors for DR in Chinese population between 1990 and 2017. A random-effects meta-analysis model was adopted to pool the overall prevalence of DR. Variations in the prevalence of DR in different age groups, DM duration groups and settings were assessed by subgroup meta-analysis and meta-regression. Odds ratios (ORs) of major risk factors were pooled using random-effects meta-analysis. The number of people with DR in 2010 was estimated by multiplying the age-specific prevalence of DR in people with DM with the corresponding number of people with DM in China. Finally, the national number of people with DR was distributed into six geographic regions using a risk factor-based model. RESULTS A total of 31 studies provided information on the prevalence of DR and 21 explored potential risk factors for DR. The pooled prevalence of any DR, nonproliferative DR (NPDR) and proliferative DR (PDR) was 1.14% (95% CI = 0.80-1.52), 0.90% (95% CI = 0.56-1.31) and 0.07% (95% CI = 0.02-0.14) in general population; In people with DM, the pooled prevalence rates were 18.45% (95% CI = 14.77-22.43), 15.06% (95% CI = 11.59-18.88) and 0.99% (95% CI = 0.40-1.80) for any DR, NPDR and PDR, respectively. The prevalence of any DR in DM patients peaked between 60 and 69 years of age, and increased steeply with the duration of DM. DM patients residing in rural China were at a higher risk to have DR than those in urban areas. In addition, insulin treatment, elevated FBG level and higher HbA1c concentration were confirmed to be associated with a higher prevalence of DR in people with DM, with meta-ORs of 1.99 (95% CI = 1.34-2.95), 1.33 (95% CI = 1.12-1.59) and 1.15 (95% CI = 1.09-1.20) respectively. In 2010, a total of 13.16 million (95% CI = 8.95-18.00) Chinese aged 45 years and above were living with DR, among whom the most were in South Central China and the least were in Northwest China. CONCLUSIONS DR has become a serious public health problem in China. Optimal screening of and interventions on DR should be implemented. Improved epidemiological studies on DR are still required.
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Systematic review and meta-analysis of diagnostic accuracy of detection of any level of diabetic retinopathy using digital retinal imaging.
Piyasena, MMPN, Murthy, GVS, Yip, JLY, Gilbert, C, Peto, T, Gordon, I, Hewage, S, Kamalakannan, S
Systematic reviews. 2018;(1):182
Abstract
BACKGROUND Visual impairment from diabetic retinopathy (DR) is an increasing global public health concern, which is preventable with screening and early treatment. Digital retinal imaging has become a preferred choice as it enables higher coverage of screening. The aim of this review is to evaluate how different characteristics of the DR screening (DRS) test impact on diagnostic test accuracy (DTA) and its relevance to a low-income setting. METHODS We conducted a systematic literature search to identify clinic-based studies on DRS using digital retinal imaging of people with DM (PwDM). Summary estimates of different sub-groups were calculated using DTA values weighted according to the sample size. The DTA of each screening method was derived after exclusion of ungradable images and considering the eye as the unit of analysis. The meta-analysis included studies which measured DTA of detecting any level of DR. We also examined the effect on detection from using different combinations of retinal fields, pupil status, index test graders and setting. RESULTS Six thousand six hundred forty-six titles and abstracts were retrieved, and data were extracted from 122 potentially eligible full reports. Twenty-six studies were included in the review, and 21 studies, mostly from high-income settings (18/21, 85.7%), were included in the meta-analysis. The highest sensitivity was observed in the mydriatic greater than two field strategy (92%, 95% CI 90-94%). The highest specificity was observed in greater than two field methods (94%, 95% CI 93-96%) where mydriasis did not affect specificity. Overall, there was no difference in sensitivity between non-mydriatic and mydriatic methods (86%, 95% CI 85-87) after exclusion of ungradable images. The highest DTA (sensitivity 90%, 95% CI 88-91%; specificity 95%, 95% CI 94-96%) was observed when screening was delivered at secondary/tertiary level clinics. CONCLUSIONS Non-mydriatic two-field strategy could be a more pragmatic approach in starting DRS programmes for facility-based PwDM in low-income settings, with dilatation of the pupils of those who have ungradable images. There was insufficient evidence in primary studies to draw firm conclusions on how graders' background influences DTA. Conducting more context-specific DRS validation studies in low-income and non-ophthalmic settings can be recommended.
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New insights into diabetic retinopathy by OCT angiography.
Liu, G, Xu, D, Wang, F
Diabetes research and clinical practice. 2018;:243-253
Abstract
Diabetic retinopathy (DR) is one of the most common diabetic complications, which has become a leading cause for vision loss, mainly because of macular edema and vitreous hemorrhage. Optical coherence tomography (OCT) angiography is a novel technique to visualize vascular changes including microaneurysm, non-perfusion area, intraretinal microvascular abnormalities, and neovascularization. Recently, it is possible to quantify vascular density, foveal avascular zone area, non-perfusion area objectively using OCT angiography. In addition, OCT angiography also provides an alternative method to evaluate the effect of anti-vascular endothelial growth factor (VEGF) treatments by providing high resolution images of macular microcirculatory abnormalities. Thus OCT angiography is an effective method to investigate the vascular changes of the disease, and can also be potentially applied in the diagnosis, treatment, and follow up of DR.
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A tailored intervention to promote uptake of retinal screening among young adults with type 2 diabetes - an intervention mapping approach.
Lake, AJ, Browne, JL, Abraham, C, Tumino, D, Hines, C, Rees, G, Speight, J
BMC health services research. 2018;(1):396
Abstract
BACKGROUND Young adults (18-39 years) with type 2 diabetes are at risk of early development and rapid progression of diabetic retinopathy, a leading cause of vision loss and blindness in working-age adults. Retinal screening is key to the early detection of diabetic retinopathy, with risk of vision loss significantly reduced by timely treatment thereafter. Despite this, retinal screening rates are low among this at-risk group. The objective of this study was to develop a theoretically-grounded, evidence-based retinal screening promotion leaflet, tailored to young adults with type 2 diabetes. METHODS Utilising the six steps of Intervention Mapping, our multidisciplinary planning team conducted a mixed-methods needs assessment (Step 1); identified modifiable behavioural determinants of screening behaviour and constructed a matrix of change objectives (Step 2); designed, reviewed and debriefed leaflet content with stakeholders (Steps 3 and 4); and developed program implementation and evaluation plans (Steps 5 and 6). RESULTS Step 1 included in-depth qualitative interviews (N = 10) and an online survey that recruited a nationally-representative sample (N = 227), both informed by literature review. The needs assessment highlighted the crucial roles of knowledge (about diabetic retinopathy and screening), perception of personal risk, awareness of the approval of significant others and engagement with healthcare team, on retinal screening intentions and uptake. In Step 2, we selected five modifiable behavioural determinants to be targeted: knowledge, attitudes, normative beliefs, intention, and behavioural skills. In Steps 3 and 4, the "Who is looking after your eyes?" leaflet was developed, containing persuasive messages targeting each determinant and utilising engaging, cohort-appropriate imagery. In Steps 5 and 6, we planned Statewide implementation and designed a randomised controlled trial to evaluate the leaflet. CONCLUSIONS This research provides an example of a systematic, evidence-based approach to the development of a simple health intervention designed to promote uptake of screening in accordance with national guidelines. The methods and findings illustrate how Intervention Mapping can be employed to develop tailored retinal screening promotion materials for specific priority populations. This paper has implications for future program planners and is intended to assist those wishing to use Intervention Mapping to create similar theoretically-driven, tailored resources.
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Genetic association of AKR1B1 gene polymorphism rs759853 with diabetic retinopathy risk: A meta-analysis.
Cao, M, Tian, Z, Zhang, L, Liu, R, Guan, Q, Jiang, J
Gene. 2018;:73-78
Abstract
OBJECTIVE The study aimed to ascertain the correlation between AKR1B1 polymorphism rs759853 and the risk of diabetic retinopathy (DR) through a meta-analysis. METHODS Crude odds ratios (ORs) and the corresponding 95% confidence interval (95% CIs) were calculated to assess the association of AKR1B1 rs759853 polymorphism with DR risk. Stratification analyses were further conducted based on ethnicity, diabetes mellitus (DM) type, Hardy-Weinberg equilibrium (HWE) status, and genotyping method. Heterogeneity was detected by Q test. Sensitivity analysis was implemented to check the robustness of final results. Additionally, Begg's funnel plot and Egger's test were used to evaluate underlying publication bias. RESULTS Our meta-analysis ultimately incorporated 21 eligible publications with 22 independent case-control studies. The overall results demonstrated that AKR1B1 rs759853 polymorphism had no association with DR risk under all genetic models. However, after subgroup analysis by DM type, the rs759853 polymorphism was a protective factor against the DR onset in patients with type 1 DM (TT vs. CC: OR = 0.33, 95% CI = 0.17-0.67; TT + CT vs. CC: OR = 0.49, 95% CI = 0.36-0.68; TT vs. CC + CT: OR = 0.48, 95% CI = 0.28-0.83; allele T vs. allele C: OR = 0.56, 95% CI = 0.44-0.72; CT vs. CC: OR = 0.52, 95% CI = 0.37-0.74). Furthermore, subgroup analysis by genotyping method suggested that rs759853 genotyped using MassARRAY assay was significantly correlated with decreased risk of DR under dominate model (TT + CT vs. CC: OR = 0.71, 95%CI = 0.52-0.96). CONCLUSION AKR1B1 polymorphism rs759853 may inhibit the occurrence of DR in patients with type 1 DM.
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The FTO variant is associated with chronic complications of diabetes mellitus in Czech population.
Hubacek, JA, Dlouha, D, Klementova, M, Lanska, V, Neskudla, T, Pelikanova, T
Gene. 2018;:220-224
Abstract
BACKGROUND Genome-wide association studies have resulted in the identification of the FTO gene as an important genetic determinant of diabetes mellitus. The aim of this study was to confirm the role of this gene in the development of DM in the Czech-Slavonic population and to analyse whether this gene is associated with common DM complications. METHODS Two groups of patients (814 with T1DM and 848 with T2DM) and a group of healthy controls (2339 individuals) - both of Czech origin - were genotyped for the FTO rs17817449 SNP. ANOVA and logistic regression were used for the statistical evaluations. RESULTS The frequency of the GG genotype was significantly higher in T2DM (25.4% vs. 16.7%, P<0.0005) but not in T1DM patients (19.3% vs. 16.7%, P=0.20) than in controls. The increased risk of development of diabetic nephropathy was observed both for T1DM patients (GG vs. TT homozygotes, P<0.01) and T2DM patients (G carriers vs. TT homozygotes, P<0.05). FTO genotype predicted the development of diabetic neuropathy (GG vs. TT comparison; P<0.01) in the T2DM patients only. No association between FTO genotype and development of retinopathy was detected. All presented values are after adjustment for age, sex, BMI and duration of diabetes. CONCLUSIONS We confirm the association between the FTO rs17817449 SNP and susceptibility to T2DM in the Czech-Slavonic population. The same variant is associated with a spectrum of chronic complications in both types of diabetes.
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Multimodal imaging of diabetic retinopathy.
Tran, K, Pakzad-Vaezi, K
Current opinion in ophthalmology. 2018;(6):566-575
Abstract
PURPOSE OF REVIEW Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and a leading cause of blindness throughout the world. Ocular imaging continues to play a vital role in the diagnosis, management and monitoring of diabetic retinopathy. Major technological advancements in imaging over the past decade have improved our understanding and knowledge of diabetic retinopathy and therefore a multimodal approach to imaging has become the standard of care. RECENT FINDINGS Updates to traditional technologies such as digital fundus photography along with recent advancements in optical coherence tomography (OCT) and OCT angiography (OCTA) have provided clinicians with new information and improved efficiency. SUMMARY In this review, we describe the benefits and clinical applications of several imaging techniques in diabetic retinopathy including color photography, fluorescein angiography, OCT, OCTA and adaptive optics. Understanding the indications and limitations of each technology allows clinicians to gain the most information from each modality and thereby optimize patient care.