Prevalence and development of retinopathy in children and adolescents with Type I (insulin-dependent) diabetes mellitus. A longitudinal study

Summary In 231 subjects with Type 1 diabetes mellitus aged 17.6 ± 4.0 years, with a diabetes duration of 8.5 ± 4.9 years at the end of the study, the prevalence and the development of retinopathy during a period of 5 years were studied. All patients were examined between one and six times both by ophthalmoscopy and fluorescein angiography. A total of 626 fluorescein angiographies were evaluated. By the end of the study, 109 out of 231 patients (47%) had developed retinal changes, half of which were classified as minimal (<5 microaneurysms). Thirty-eight patients (35% of those affected) had background (n = 28) or proliferative (n = 10) retinopathy. In subjects less than 15 years of age and diabetic for less than 5 years, retinal lesions were rare. With increasing age and duration of diabetes, both the prevalence and severity of retinal changes increased markedly. Life-table analysis was used to calculate the median individual risk for the development of early retinal changes, which was 9.1 years of diabetes duration. This risk differed in sub-groups with different ages at onset of diabetes, i. e. 12.1, 8.9 and 6.6 years (p < 0.0001), with diabetes starting below 4, between 5 and 9, and after 10 years of age respectively. After 18 years of diabetes, every patient demonstrated at least incipient structural changes. Fluorescein angiography allowed the detection of retinopathy, on average, four years earlier than with ophthalmoscopy. The median interval between the ‘onset’ of retinopathy, as indicated by a few microaneurysms, and background retinopathy was 5 years.     

Destruction of the blood-retina barrier in diabetic retinopathy depends on angiotensin-converting enzyme-mediated TGF-β1/Smad signaling pathway activation

Diabetes mellitus (DM) is a systemic, chronic metabolic disease that is related to heredity and autoimmunity and is often accompanied by complications of retinopathy. However, the causative mechanism involved in the pathological process remains unclear. In this research, treatment with fosinopril or LY2109761 was found to be responsible for the improvement of the pathological processes, serum biochemical indexes and retinopathy in rats with streptozotocin-induced diabetes. In addition, the upregulation of angiotensin-converting enzyme (ACE) in the serum and the increased expression of TGF-β1 in the pathological outer nuclear layer (ONL) and inner nuclear layer (INL) of the retina were also reduced. In vitro experiments demonstrated that ACE enhanced cell damage and TGF-β1/Smad signaling pathway activation in retinal capillary endothelial cells (RCECs) under high glucose conditions. In addition, the activity of ACE was also considered to be related to the increasing levels of activated TGF-β1 in both rat retinal Müller cells (RMCs) and RCECs, but ACE activity had no effect on the high glucose-mediated upregulation of total TGF-β1 in RMCs. Coculture experiments with RCECs and RMCs showed that the barrier that was established under normal conditions was significantly impaired when exposed to high glucose combined with ACE, and damage of barrier can be prevented by adding fosinopril or LY2109761. Finally, a similar auxiliary effect of ACE was also observed in the activated TGF-β1-mediated barrier damage in blood-retinal barrier model in vitro. In summary, ACE-mediated TGF-β1/Smad signaling pathway activation was found to be involved in the destruction of the blood-retina barrier during diabetic retinopathy in a model of streptozotocin-induced diabetes, and these data may provide evidence to guide the treatment of the complications of diabetes mellitus.     

A platform of integrative studies from in vitro to in vivo experiments: Towards drug development for ischemic retinopathy

Pathologic angiogenesis induced by hypoxia is a hallmark of ischemic retinopathy including diabetic retinopathy and retinopathy of prematurity. These 2 diseases affect substantial number of working population and preterm babies, respectively, resulting in visual deterioration. It is essential for novel therapeutics for ischemic retinopathy to demonstrate the potency in reducing pathologic angiogenesis and the safety without definite toxicity on the retina and the whole body. In this review, we suggest a novel platform of integrative studies from in vitro to in vivo experiments on angiogenesis and toxicity with the aim of accelerating and facilitating the development of novel therapeutic agents for ischemic retinopathy. Robust in vitro and in vivo studies with bridging microfluidic and ex vivo systems help researchers to evaluate the efficacy and anticipate the toxicity of candidate drugs. We hope that novel therapeutic approach based on this platform will be developed in near future and reduce the incidence of vision loss from ischemic retinopathy.     

Development and Progression of Diabetic Retinopathy and Associated Risk Factors in Korean Patients with Type 2 Diabetes: The Experience of a Tertiary Center

The aim of this study was to evaluate the incidence of and risk factors for the development of diabetic retinopathy (DR) and progression to proliferative DR (PDR) in Korean patients. Patients diagnosed with type 2 diabetes and followed for more than 5 years at a university-based clinic since 2000 were consecutively enrolled in this retrospective cohort study. Based on the DR classification at the initial and final visits, the incidence and progression of DR was determined and patient characteristics were compared according to DR progression. Hazard ratios of each putative risk factor for DR progression were calculated with a multivariate Cox proportional hazard model. Rate of DR development and progression to PDR were 32.1/1,000 and 26.2/1,000 person-years, respectively. A longer duration of diabetes and higher mean HbA1c level were significant risk factors for the development of DR. Regarding progression to PDR, higher mean HbA1c level, higher standard deviation of HbA1c, and higher urine albumin-to-creatinine ratio were significant risk factors. The rates of development of DR and progression to PDR in Koreans with type 2 diabetes are lower than those reported over the last decade. An inadequate blood glycemic control is the common risk factor for development and progression of DR.

Graphical Abstract

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Oral glucose for pain relief during examination for retinopathy of prematurity: a masked randomized clinical trial

OBJECTIVE:

Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight ≤1,500 g and/or gestational age ≤32 weeks.

METHODS:

A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00648687","term_id":"NCT00648687"}}NCT00648687

RESULTS:

One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001).

CONCLUSIONS:

One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief.     

Retinopathy of prematurity

This review deals with retinopathy of prematurity (ROP), a disease characterized by retinovitreal neovascularization, eventually retinal detachment and blindness. Due to the increasing number of extremely premature newborns, it is becoming more frequent. ROP of all stages occurs in 25–35% of surviving premature newborns of gestational age up to approximately 35 weeks. Stages 3 or more occur in 5–10%, blindness in 3–5% of very immature babies. The incidence is inversely related to gestational age. Classification is internationally unified (ICROP) and describes 5 stages. Its pathogenesis has not yet been clarified. More or less proven risk factors are retinovascular immaturity, hyperoxia and possibly circulatory and respiratory instability. Prophylaxis consists in avoiding hyperoxia, and probably also in keeping the extremely premature newborn stable. Ophthalmologic examinations must be performed by ophthalmologists experienced in this field or under their direct responsibility and must be standardized. Treatment of ROP can be carried out at a certain stage by coagulation therapy.     

Detection of Sight-threatening Diabetic Eye Disease

Blindness due to diabetes mellitus is potentially preventable in the majority of patients. Early detection of sight-threatening changes is associated with a better outcome, indicating the need to screen for retinopathy. At least 50 % of diabetic patients do not attend a hospital, so that diabetologists and ophthalmologists are unable to screen the diabetic population comprehensively. Although in theory all patients have access to general practitioners, these may lack training or confidence to screen for retinopathy. Hospital based or community optometrists using direct ophthalmoscopy or slit lamps and technicians performing fundus photography are alternatives which may be more effective. Further studies are required to examine the effectiveness of optometry screening. Initial studies using fundus photography raised concerns about the sensitivity of the technique, but these have been partially addressed by improvements in methodology and technology. As well as technicological effectiveness, factors affecting patient uptake of screening services still need to be addressed.     

早产儿视网膜病变患儿血清谷氨酸水平变化的意义及其对预后的影响

目的探讨早产儿视网膜病变(ROP)患儿血清谷氨酸水平与病情严重程度之间的关系及其对预后的影响。方法选取2017年6月至2018年6月在河南省立眼科医院筛查并诊治的92例ROP患儿及同期河南省立眼科医院筛查的50例健康早产儿(对照组)进行临床对照研究,92例ROP患儿根据病变分期分为轻度ROP组和重度ROP组,依据病情进展与否分为自然消退组和病情进展组,通过测定各组儿童出生1周和出生6周血清谷氨酸水平,分析其与ROP病情严重程度的关系及其对预后评估的意义。结果重度ROP组患儿出生1周血清谷氨酸水平[(122.08±14.55)mmol/L]和出生6周血清谷氨酸水平[(107.13±13.20)mmol/L]最高,轻度ROP组患儿次之[分别为(98.60±14.48)mmol/L、(85.41±14.49)mmol/L],对照组患儿最低[分别为(68.52±7.69)mmol/L、(54.97±6.31)mmol/L],3组比较差异有统计学意义(均P<0.05);Pearson相关性分析提示出生1周和出生6周血清谷氨酸水平均与ROP病情严重程度均呈正相关(r=0.869、0.875,均P<0.05)。病情进展组患儿出生1周及出生6周血清谷氨酸水平[(107.18±17.62)mmol/L、(92.94±16.21)mmol/L]均显著高于自然消退组患儿[(131.53±10.22)mmol/L、(118.82±8.18)mmol/L],2组间比较差异均有统计学意义(均P<0.05)。出生1周和出生6周血清谷氨酸水平预测ROP病情进展患儿受试者工作特征曲线(ROC)下面积分别为0.855、0.936,根据ROC曲线结果,分别确定出生1周和出生6周血清谷氨酸水平最佳临界值分别为117.83 mmol/L(敏感性为0.909,特异性为0.728)、106.69 ng/L(敏感性为1.000,特异性为0.790)。结论出生1周和出生6周血清谷氨酸水平与ROP患儿病情严重程度呈正相关,同时出生1周和出生6周血清谷氨酸水平最佳临界值预测患儿疾病进展的敏感性和特异性均较高,对患儿预后评估具有较高的价值。