肾素原受体在糖尿病视网膜病变中的作用及其机制研究

目的：观察糖尿病视网膜病变发生过程中肾素原受体（PRR）及血管紧张素Ⅱ受体2（AT2R）的表达水平及视网膜神经细胞凋亡情况,阐明 PRR 与糖尿病视网膜神经细胞凋亡的关系。方法建立链尿佐菌素诱导的糖尿病 SD 大鼠模型,建模成功后分别在4周、8周和12周用免疫组化法检测 CD14及8-羟脱氧鸟苷分子的表达,检测糖尿病及对照组视网膜 AT2R、PRR mRNA 的表达及细胞外信号调节激酶（ERK1/2）、磷酸化 ERK1/2（p-ERK1/2）蛋白的表达。结果各病程 SD 大鼠视网膜 AT2R 和 PRR 的 mRNA 表达水平较对照组明显升高（P <0.05）,随病程的延长表达量随之增多。病程越长糖尿病组大鼠视网膜组织凋亡细胞数量越多,各阶段病程 CD14染色未见明显新生血管。通过相关性分析显示,PRR 和 AT2R 表达水平与神经节细胞凋亡相关。各病程大鼠视网膜 ERK1/2、p-ERK1/2蛋白的表达量显著高于对照组。结论糖尿病视网膜病变中 PRR 和 AT2R 的表达与大鼠糖尿病视网膜病变的神经节细胞凋亡相关,可能通过增加 ERK 的磷酸化水平发挥功能作用。     

中药汤剂口服联合玻璃体内注射曲安奈德治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿30例临床观察

目的观察益气养阴、活血利水中药汤剂口服联合曲安奈德玻璃体内注射治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿的疗效及安全性。方法将60例(92眼)非增生性糖尿病视网膜病变弥漫性黄斑水肿患者随机分为治疗组(30例,47眼)和对照组(30例,45眼)。两组患者于治疗第1天均行患眼玻璃体内注射曲安奈德4 mg。治疗组同时予以益气养阴活血利水中药汤剂口服,每日1剂,服药3个月。观察治疗前和注射后3、6个月患眼视力、视网膜厚度及黄斑区渗漏情况。注射后第1、3、7天及3、6个月分别测量眼压、眼前节、眼后节。结果注射后3、6个月,治疗组临床疗效有效率分别为89.36%和87.23%,对照组分别为73.33%和62.22%,治疗组临床有效率优于对照组(P0.05或P0.01)。治疗组注射后3、6个月视力、视网膜厚度均较治疗前显著改善,且显著优于对照组(P0.05或P0.01)。治疗组未见明显不良反应,对照组1例患者6个月时发现晶状体后囊下呈锅底样混浊,严重影响视力。结论益气养阴、活血利水中药汤剂口服联合玻璃体内注射曲安奈德治疗非增生性糖尿病视网膜病变弥漫性黄斑水肿,能够明显提高患者的视功能,减轻视网膜水肿和黄斑区渗漏,疗效稳定,安全性良好。     

Longitudinal Commercial Claims–Based Cost Analysis of Diabetic Retinopathy Screening Patterns

Background

Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service.

Objective

To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes.

Methods

Truven Health MarketScan commercial databases (2000–2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001–2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001–2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1–4, 5–7, and 8–10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables.

Results

In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts’ mean incremental cost increase was $185 between the 0- and 1–4–year cohorts (P <.003) and $202 between the 0- and 5–7–year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8–10–year cohorts (P <.066), were not statistically significant.

Conclusions

Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened.     

Permanent Bilateral Vision Loss in Eclamptic Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) classically consists of reversible vasogenic oedema in the posterior circulation territories, which is reversible both clinically and radiologically in the majority of patients after the control of hypertension. The authors describe a 27-year-old eclamptic patient with PRES in accelerated hypertension who revealed permanent vision loss associated with bilateral Purtscher retinopathy. One of the two competing theories that explain vasogenic brain oedema in PRES is excessive autoregulation leading to the dilation of cerebral arterial vessels, particularly in the occipito-parietal vasculatures. Dysfunction of endothelial cells that results in constriction of vessels has also been hypothesised as a cause of PRES. The concurrence of bilateral vaso-occlusive retinopathy and PRES supports the hypothesis that vasoconstriction is a more plausible mechanism of vasogenic oedema in PRES.     

Utility Values Associated with Diabetic Retinopathy in Chennai,India

Abstract

Purpose: The aim of this study was to estimate utility values associated with different severity stages of diabetic retinopathy (DR) in India by a direct elicitation method (time-trade off, TTO) and indirectly by questionnaire.

Methods: People with diabetes aged 40 years and over were recruited from an on-going DR epidemiology study and a laser clinic in Chennai, India. Utility values were elicited using the direct TTO method and indirectly through a validated questionnaire (EQ-5D).

Results: Of 249 participants, 30 had no DR, 73 had non-proliferative DR, 114 had sight-threatening DR, and 32 were blind from DR (bilateral visual acuity <6/60). The mean TTO utility value was 0.73 (standard deviation, SD, 0.31). TTO utility values decreased with increasing severity of DR (p?<?0.001) and were significantly lower among participants with sight threatening DR (0.70, SD 0.33) and blindness (0.55, SD 0.24) compared to those with no DR (0.89, SD 0.25) after adjustment for sociodemographic and clinical factors. Blindness from DR was independently associated with a lower EQ-5D utility value. The utility value derived from EQ-5D (0.06) associated with being blind from DR was substantially lower than that of the TTO utility value (0.55).

Conclusions: This study provides estimates of utility values that can be used in economic evaluations of DR screening strategies in India. The relatively low utility values associated with blindness highlights the importance of screening programs for early detection of the sight-threatening stages to prevent vision loss from DR in this setting.     

Cost-utility Analysis of Screening for Diabetic Retinopathy in Japan: A Probabilistic Markov Modeling Study

ABSTRACT

Purpose: To evaluate the cost-effectiveness for a screening interval longer than 1 year detecting diabetic retinopathy (DR) through the estimation of incremental costs per quality-adjusted life year (QALY) based on the best available clinical data in Japan.

Methods: A Markov model with a probabilistic cohort analysis was framed to calculate incremental costs per QALY gained by implementing a screening program detecting DR in Japan. A 1-year cycle length and population size of 50,000 with a 50-year time horizon (age 40–90 years) was used. Best available clinical data from publications and national surveillance data was used, and a model was designed including current diagnosis and management of DR with corresponding visual outcomes. One-way and probabilistic sensitivity analyses were performed considering uncertainties in the parameters.

Results: In the base-case analysis, the strategy with a screening program resulted in an incremental cost of 5,147 Japanese yen (¥; US$64.6) and incremental effectiveness of 0.0054 QALYs per person screened. The incremental cost-effectiveness ratio was ¥944,981 (US$11,857) per QALY. The simulation suggested that screening would result in a significant reduction in blindness in people aged 40 years or over (?16%). Sensitivity analyses suggested that in order to achieve both reductions in blindness and cost-effectiveness in Japan, the screening program should screen those aged 53–84 years, at intervals of 3 years or less.

Conclusions: An eye screening program in Japan would be cost-effective in detecting DR and preventing blindness from DR, even allowing for the uncertainties in estimates of costs, utility, and current management of DR.     

中西医结合治疗单纯型糖尿病视网膜病变106例临床研究

目的：观察中西医结合治疗单纯型糖尿病视网膜病变临床疗效。方法将166例单纯型糖尿病视网膜病变患者随机分为2组,治疗组106例（212眼）予滋阴补肾中药口服联合卡波金吸入治疗,对照组60例（120眼）予以滋阴补肾中药口服治疗,2组均1个月为1个疗程,间隔10 d后进行下1个疗程,2个疗程后统计临床疗效,并进行血液流变学检测及血气分析。结果2组总有效率比较差异有统计学意义（P＜0．01）,治疗组疗效优于对照组。治疗组治疗后全血黏度（高切）、全血黏度（低切）、血浆黏度、红细胞沉降率及pH值均较本组治疗前明显降低（P＜0．01,P＜0．05）,氧分压升高（P＜0．01）,且全血黏度（高切）、全血黏度（低切）、血浆黏度、氧分压及pH值改善优于对照组（ P＜0．05）。结论滋阴补肾中药联合卡波金吸入治疗单纯型糖尿病视网膜病变,能明显改善血液流变学指标及血气分析指标,疗效优于单纯滋阳补肾中药治疗。     

Posterior sub-tenon’s bevacizumab injection in diabetic macular edema; a pilot study

Purpose

To evaluate the short-term results of sub-tenon’s injection of bevacizumab in patients with clinically significant macular edema (CSME).

Methods

In this prospective non-comparative interventional case series, sub-tenon’s injection of 2.5 mg/0.1 ml bevacizumab was performed for eyes with CSME. Macular thickness and best corrected visual acuity measurements were performed before and one month after injections.

Results

Nineteen eyes of twelve patients with a mean age of 59.8 ± 5.7 years were evaluated. Thirteen eyes (68.4%) had center-involving macular edema. No significant difference was observed between pre- and post-injection central subfield retinal thickness measurements (P = 0.3). Central subfield thickness measurements improved or remained unchanged in 13 eyes (68.4%). Baseline BCVA of 0.48 ± 0.35 LogMAR improved to 0.36 ± 0.26 LogMAR after injection (P = 0.01). Improvement of >2 lines in BCVA was found in 5 eyes (26.3%), and no eye lost >2 lines of BCVA. No complication associated with sub-tenon’s injection was observed.

Conclusion

Sub-tenon’s injection of bevacizumab resulted in significant short-term visual improvement in eyes with CSME. Retinal thickness changes were not significant.     

Retinal microglia: Just bystander or target for therapy?

Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.