康柏西普联合激光光凝治疗糖尿病黄斑水肿43 例临床分析

目的:探讨康柏西普玻璃体腔注射联合激光光凝治疗糖尿病黄斑水肿的临床疗效及安全性。方法:收取2013年6月至2015年8月间我院收治的糖尿病黄斑水肿患者87例(87眼)作为研究对象,采用随机数字表法将其分为观察组及对照组,观察组43例(43眼)给予康柏西普玻璃体腔注射联合激光光凝治疗,对照组44例(44眼)给予单纯激光光凝治疗。对两组患者治疗前后视力(best corrected visual acuilty,BCVA)、视网膜厚度(central macular thickness,CMT)、临床疗效、并发症以及生活质量进行观察与比较。结果:治疗前两组患者BCVA、CMT均无显著差异,治疗后两组BCVA、CMT均有所提高,同时间点观察组明显高于对照组,差异有统计学意义(P0.05)。观察组治疗后6个月视力提高率为81.40%,对照组为13.64%,观察组远高于对照组,差异有统计学意义(P0.05)。观察组患者共有3例出现一过性眼压升高,对照组共有2例患者出现一过性眼压增高,两组相较无统计学差异(P0.05)。观察组生活质量显著高于对照组,差异有统计学意义(P0.05)。结论:康柏西普玻璃体腔注射联合激光光凝治疗糖尿病黄斑水肿具有良好的疗效及安全性,有利于患者生活质量提高,值得临床推广应用。     

糖尿病性黄斑水肿3D-OCT与mERG检查结果的相关性研究

目的:探讨糖尿病性黄斑水肿的三维光学相干断层扫描技术(3D-OCT)与多焦视网膜电图(m ERG)检查结果的相关性。方法:随机选择糖尿病性黄斑水肿患者40人60只眼,经荧光造影检查示黄斑部有持续性的荧光渗漏、囊样水肿,3D-OCT示黄斑中心凹厚度大于170um,对黄斑中心凹旁上、下、鼻、颞约750um处视网膜神经上皮层处厚度进行OCT自带软件的分析测量。随机选择18人35只年龄相配的正常眼为对照组以同样方法行3D-OCT黄斑旁四个方位的神经上皮厚度测量。两组用同种方法行常规黄斑部m ERG检查。所有数据应用SPSS13.0统计软件进行处理,分析3D-OCT与m ERG在影像学方面的相关性。结果:两组被检查者检查结果经统计学处理后对比发现:被检查者黄斑中央5°、10°区域N1、P1波反应密度绝对值与黄斑中心凹神经上皮层厚度具有显著的相关性(P0.05)。结论:糖尿病性黄斑水肿的神经上皮厚度的改变与黄斑区m ERG的改变具有显著相关性,主要表现为黄斑中央5°和10°区域m ERG各波反应密度的改变,且有神经上皮厚度增加的越大,m ERG各波反应密度的降低的幅度也随之变大的趋势。     

Interobserver Agreement in Detecting Spectral-Domain Optical Coherence Tomography Features of Diabetic Macular Edema

PurposeTo evaluate interobserver agreement for the detection of spectral-domain optical coherence tomography (SDOCT) features of diabetic macular edema (DME).MethodCross-sectional study in which 2 retinal specialists evaluated SDOCT scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39 patients were graded for features of DME including intra-retinal fluid (IRF), diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as present or absent at zones involving the fovea, 1mm from the fovea and the whole scan of 49 line scans. Analysis was performed using cross-tabulations for percentage concordance and kappa values (κ).ResultsIn the 2950 line scans analysed, there was an increase in percentage concordance for DRE and HRF when moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88% vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with κ ranging from substantial to almost perfect. Percentage concordance for SRF was 96% at all 3 regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line-scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and whole scan with almost perfect and substantial κ respectively. κ agreement was substantial for VMT at all regions analysed.ConclusionWe report a high level of interobserver agreement in the detection of SDOCT features of DME. This finding is important as detection of macular fluid is used to guide retreatment with anti-angiogenic agents.     

Development of a Semi-Automatic Segmentation Method for Retinal OCT Images Tested in Patients with Diabetic Macular Edema

Purpose

To develop EdgeSelect, a semi-automatic method for the segmentation of retinal layers in spectral domain optical coherence tomography images, and to compare the segmentation results with a manual method.

Methods

SD-OCT (Heidelberg Spectralis) scans of 28 eyes (24 patients with diabetic macular edema and 4 normal subjects) were imported into a customized MATLAB application, and were manually segmented by three graders at the layers corresponding to the inner limiting membrane (ILM), the inner segment/ellipsoid interface (ISe), the retinal/retinal pigment epithelium interface (RPE), and the Bruch''s membrane (BM). The scans were then segmented independently by the same graders using EdgeSelect, a semi-automated method allowing the graders to guide/correct the layer segmentation interactively. The inter-grader reproducibility and agreement in locating the layer positions between the manual and EdgeSelect methods were assessed and compared using the Wilcoxon signed rank test.

Results

The inter-grader reproducibility using the EdgeSelect method for retinal layers varied from 0.15 to 1.21 µm, smaller than those using the manual method (3.36–6.43 µm). The Wilcoxon test indicated the EdgeSelect method had significantly better reproducibility than the manual method. The agreement between the manual and EdgeSelect methods in locating retinal layers ranged from 0.08 to 1.32 µm. There were small differences between the two methods in locating the ILM (p = 0.012) and BM layers (p<0.001), but these were statistically indistinguishable in locating the ISe (p = 0.896) and RPE layers (p = 0.771).

Conclusions

The EdgeSelect method resulted in better reproducibility and good agreement with a manual method in a set of eyes of normal subjects and with retinal disease, suggesting that this approach is feasible for OCT image analysis in clinical trials.     

Factors Affecting Reading Speed in Patients with Diabetic Macular Edema Treated with Laser Photocoagulation

Purpose

To study the factors that may affect reading speed in patients with diabetic macular edema previously treated with laser photocoagulation.

Methods

Consecutive patients with type II diabetes treated with laser photocoagulation for diabetic macular edema (DME) at least twelve months previously, with best corrected visual acuity of better than 65 letters (approximately 20/40) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts were included in this study. Patients previously treated with pan-retinal photocoagulation, vitrectomy, intravitreal steroid or anti-VEGF therapy were excluded. Any other ocular co-morbidities that may influence reading ability such as cataract, glaucoma or macular degeneration were also excluded. All patients were refracted by a certified examiner, the following measurements were collected: best corrected visual acuity (BCVA), contrast sensitivity with Pelli-Robson chart, reading speed with MNREAD chart, microperimetry with Nidek MP1, and central subfield thickness with Zeiss spectral domain optical coherent topography.

Results

The slow reading group had poorer contrast sensitivity (p = 0.001), reduced retinal sensitivity (p = 0.027) and less stable fixation (p = 0.013). Most interestingly the reduced retinal sensitivity findings were driven by the microperimetry value on the right subfield (p = 0.033), (nasal to the fovea in the right eye and temporal to the fovea in the left eye). Multiple linear regression analysis showed that contrast sensitivity is probably the most important factor that affects reading speed (p = 0.001).

Conclusion

Reduced retinal sensitivity after laser treatment is associated with reduced reading speed in patients with diabetic macular edema.     

糖尿病白内障术后黄斑水肿与房水细胞因子的关系

为了探讨2型糖尿病白内障术后黄斑水肿与房水中细胞因子的关系,本研究选取2016年2月至2017年7月在我院治疗的2型糖尿病白内障患者117例117眼,均行超声乳化白内障摘除术,观察术后4周黄斑水肿发生情况以及房水中多种细胞因子水平。研究结果显示:术后4周,有37眼发生黄斑水肿(观察组),未发生黄斑水肿80眼(对照组);观察组术后4周黄斑区视网膜厚度为(247.28±18.37)μm,明显高于对照组(p<0.05),且明显高于术前水平(p<0.05);观察组术后4周干扰素诱导蛋白-10 (IP-10)、巨噬细胞趋化蛋白(MCP-1)、血管内皮生长因子(VEGF)和细胞因子转化生长因子-β2 (TGF-β2)水平分别为(6.01±0.89) pg/mL、(340.03±45.39) pg/mL、(812.28±40.06) pg/mL和(40.05±10.03) pg/mL,明显高于对照组(p<0.05),且高于术前水平(p<0.05);观察组和对照组手术前后粒细胞-巨噬细胞集落刺激因子(GM-CSF)和碱性成纤维细胞生长因子(b-FGF)比较差异无统计学意义(p>0.05);术后4周IP-10、MCP-1、VEGF和TGF-β2水平与黄斑区视网膜厚度呈正相关(r=0.452, 0.501, 0.466和0.470, p<0.05)。本研究的结果初步说明,房水中IP-10、MCP-1、VEGF和TGF-2水平与2型糖尿病白内障术后黄斑水肿有一定关系,有可能成为黄斑水肿的特异性评价指标,值得进一步研究。     

Comparative Evaluation of Combined Navigated Laser Photocoagulation and Intravitreal Ranibizumab in the Treatment of Diabetic Macular Edema

Objective

To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME).

Research Design and Methods

A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12.

Results

Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88±1.23 vs. 3.88±2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001).

Conclusions

Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.     

玻璃体腔抗VEGF治疗不同光学相干层析成像技术分型下的糖尿病黄斑水肿临床疗效分析

摘要 目的：研究玻璃体腔内抗血管内皮生长因子（VEGF）抗体治疗不同光学相干层析成像技术（OCT）分型下的糖尿病黄斑水肿临床疗效。方法：选取2019年1月到2021年3月在我院进行治疗的糖尿病黄斑水肿患者60例,根据OCT检测分为分弥漫性黄斑水肿（DRT）组、囊样黄斑水肿（CME）组和浆液性视网膜脱离（SRD）组,每组20例。所有患者均接受玻璃体腔内注射抗VEGF抗体治疗,比较三组患者临床治疗疗效、黄斑水肿形态、最佳矫正视力（BCVA）、黄斑中心凹厚度（CMT）以及不良反应发生率。结果：（1）DRT、CME和SRD组患者临床治疗有效率分别为85.0 %、75.0 %和50.0 %,治疗后黄斑水肿消退率分别为55.0 %、25.0 %和10.0 %,且组间比较差异显著（P<0.05）;（2）三组患者治疗前BCVA和CMT均无差异（P>0.05）,治疗后三组患者BCVA和CMT均降低（P<0.05）,并且治疗后DRT和CME组患者BCVA和CMT均低于SRD组（P<0.05）;（3）DRT、CME和SRD组患者治疗期间不良反应发生率分别为10.0 %、10.0 %和25.0 %,但三组患者治疗期间不良反应发生率比较无差异（P>0.05）。结论：不同OCT分型的糖尿病黄斑水肿经玻璃体腔抗VEGF抗体治疗后临床疗效不同,其中DRT患者临床治疗疗效最好,而SRD患者疗效最差。     

Study of 27 Aqueous Humor Cytokines in Type 2 Diabetic Patients with or without Macular Edema

The aim of the present study was to compare the changes in the levels of 27 aqueous humor cytokines between diabetic patients with macular edema (ME) and diabetic patients without ME. Undiluted aqueous humor samples were obtained from 68 consecutive type 2 diabetic patients without ME and 56 consecutive type 2 diabetic patients with ME. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. Compared with diabetic patients without ME, diabetic patients with ME had significantly higher concentrations of IL-1β, IL-6, IL-8, IP-10, MCP-1, and VEGF in the aqueous humor. However, the concentrations of IL-10 and IL-12 were significantly lower in the diabetic patients with ME. The aqueous humor levels of IL-1β, IL-6, IL-8, MCP-1, IP-10, and VEGF were closely correlated with retinal macular thickness, retinal macular volume and the severity of ME. In addition, the aqueous humor levels of IL-10 and IL-12 decreased with increasing the severity of ME. A variety of cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of diabetic macular edema, and both anti-inflammatory and antiangiogenic agents should be included in the treatment of ME simultaneously.     

Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema: A Meta-Analysis of Randomized Controlled Trials

Objective

To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME).

Methods

A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software.

Results

Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD = 5.65, 95% confidence interval (CI), 4.44–6.87, P<0.00001; WMD  = 5.02, 95% CI, 3.83–6.20, P<0.00001, and WMD  = −57.91, 95% CI, −77.62 to −38.20, P<0.00001; WMD  = −56.63, 95% CI, −104.81 to −8.44, P = 0.02, respectively). The pooled RR comparing the proportions of patients with at least 15 letters improvement or deterioration were also in favor of RBZ and RBZ + Laser (RR = 2.94, 95% CI, 1.82–4.77, P<0.00001; RR = 2.04, 95% CI, 1.50–2.78, P<0.00001, and RR = 0.21, 95% CI, 0.06–0.71, P = 0.01; RR = 0.52, 95% CI, 0.29–0.95, P = 0.03, respectively). There were no significant differences between RBZ and RBZ + Laser for any of the parameters. There were no difference in the safety profile between RBZ and laser.

Conclusion

RBZ and RBZ + Laser had better visual and anatomic outcomes than laser monotherapy in the treatment of DME. RBZ + Laser seemed to be equivalent to RBZ.     

Efficacy of Anti-VEGF and Laser Photocoagulation in the Treatment of Visual Impairment due to Diabetic Macular Edema: A Systematic Review and Network Meta-Analysis

Objective

Compare the efficacy of ranibizumab, aflibercept, laser, and sham in the first-line treatment of diabetic macular edema (DME) to inform technology assessments such as those conducted by the UK National Institute for Health and Care Excellence (NICE).

Data sources

MEDLINE, Embase, Cochrane Library, congress abstracts, ClinicalTrials.gov registry and Novartis data on file.

Inclusion criteria

Studies reporting 6- or 12-month results of randomized controlled trials (RCTs) evaluating at least two of ranibizumab 0.5 mg pro re nata, aflibercept 2.0 mg bi-monthly, laser photocoagulation or sham. Study quality was assessed based on likelihood of bias in selection, attrition, detection and performance.

Outcome measure

Improvement in best-corrected visual acuity (BCVA) measured as the proportion of patients gaining ≥10 letters on the Early Treatment Diabetic Retinopathy Study scale. The outcome was chosen following acceptance by NICE of a Markov model with 10-letter health states in the assessment of ranibizumab for DME.

Meta-analysis

Bayesian network meta-analyses with fixed and random effects adjusted for differences in baseline BCVA or central retinal thickness.

Results

The analysis included 1,978 patients from eight RCTs. The random effects model adjusting for baseline BCVA was the best model based on total residual. The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept (odds ratio [OR] 1.59; 95% credible interval [CrI], 0.61–5.37). Ranibizumab and aflibercept were statistically superior to laser monotherapy with ORs of 5.50 (2.73–13.16) and 3.45 (1.62–6.84) respectively. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser.

Limitations

Three of the eight RCTs included are not yet published. The models did not adjust for all potential effect modifiers.

Conclusion

Ranibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser.     

Morphology and Function over a One-Year Follow Up Period after Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema

Background

To investigate changes in macular morphology and function after an intravitreal dexamethasone implant for diabetic macular edema (DME).

Methods

Twenty-seven eyes in 27 treatment-naive patients affected by DME were treated with intravitreal Ozurdex® injections (IVOI) and followed up 12 months to evaluate morphological and functional changes by means of best-corrected visual acuity (BCVA), microperimetry (MP1), multifocal electroretinography (mfERG), pattern electroretinography (PERG) and spectral domain optical coherence tomography (SD-OCT).

Results

Both BCVA and retinal sensitivity improved significantly at one month after the IVOI (p = 0.031 and p<0.0001, respectively). After five months, the improvement of BCVA remained statistically significant compared with baseline values (p = 0.022); retinal sensitivity improvement was statistically significant for up to four months after the IVOI (p = 0.059). Moreover, central macular thickness significantly decreased for up to four months. Interestingly, PERG and mfERG values did not change significantly for up to four months post-IVOI, but then began to worsen.

Conclusions

In eyes with DME, intravitreal dexamethasone implant determined morphological and functional improvement as soon as one month and for up to four months after the treatment.     

激光联合康柏西普治疗糖尿病视网膜病变伴黄斑水肿的临床效果及机制研究

目的:探讨激光联合康柏西普治疗糖尿病视网膜病变伴黄斑水肿的临床效果及可能机制。方法:选取2017年1月至2017年12月我院收治的糖尿病视网膜病变伴黄斑水肿患者92例作为研究对象,随机分为观察组46例(46眼)及对照组46例(46眼)。对照组患者实施激光治疗,观察组在注射康柏西普1周后再进行激光治疗。比较两组患者治疗后的临床疗效,治疗前后最佳矫正视力(BCVA)、黄斑中心厚度(CMT)、血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)及红细胞生成素(EPO)水平的变化。结果:治疗后,观察组的总有效率为91.30%,显著高于对照组(69.57%,P0.05);两组患者的BCVA均较治疗前明显提高(P0.05),CMT均低于治疗前(P0.05),但观察组BCVA较对照组更高(P0.05);CMT较对照组更低(P0.05)。治疗后,两组患者的VEGF、IGF-1、EPO均较治疗前明显降低,且观察组的VEGF、IGF-1、EPO均显著低于对照组(P0.05)。结论:激光联合康柏西普治疗糖尿病视网膜病变伴黄斑水肿的临床疗效显著优于单用激光治疗,并可有效改善VEGF、IGF-1、EPO水平,这可能对抑制血管新生产生积极作用。     

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04–9.22) and the incidence density was 2.03 (95% CI = 1.75–2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10–2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39–18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18–3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30–2.77), and aspirin use (HR = 1.65; 95% CI = 1.22–2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75–1.82) and being female (HR = 1.12; 95% CI = 0.84–1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use.

Conclusions

After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.     

Clinical Disorders in a Post War British Cohort Reaching Retirement: Evidence from the First National Birth Cohort Study

Background

The medical needs of older people are growing because the proportion of the older population is increasing and disease boundaries are widening. This study describes the distribution and clustering of 15 common clinical disorders requiring medical treatment or supervision in a representative British cohort approaching retirement, and how health tracked across adulthood.

Methods and Findings

The data come from a cohort of 2661 men and women, 84% of the target sample, followed since birth in England, Scotland and Wales in 1946, and assessed at 60–64 years for: cardio and cerebro-vascular disease, hypertension, raised cholesterol, renal impairment, diabetes, obesity, hypothyroidism, hyperthyroidism, anaemia, respiratory disease, liver disease, psychiatric problems, cancers, atrial fibrillation on ECG and osteoporosis. We calculated the proportions disorder-free, with one or more disorders, and the level of undiagnosed disorders; and how these disorders cluster into latent classes and relate to health assessed at 36 years. Participants had, on average, two disorders (range 0–9); only 15% were disorder-free. The commonest disorders were hypertension (54.3%, 95% CI 51.8%–56.7%), obesity (31.1%, 28.8%–33.5%), raised cholesterol (25.6%, 23.1–28.26%), and diabetes or impaired fasting glucose (25.0%, 22.6–27.5%). A cluster of one in five individuals had a high probability of cardio-metabolic disorders and were twice as likely than others to have been in the poorest health at 36 years. The main limitations are that the native born sample is entirely white, and a combination of clinical assessments and self reports were used.

Conclusions

Most British people reaching retirement already have clinical disorders requiring medical supervision. Widening disease definitions and the move from a disease-based to a risk-based medical model will increase pressure on health services. The promotion of healthy ageing should start earlier in life and consider the individual''s ability to adapt to and self manage changes in health.