Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats ; Animals ; Diabetic Retinopathy/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; Interleukin-1beta/metabolism* ; Methylene Blue/pharmacology* ; Phosphorylation ; Rats, Sprague-Dawley ; MAP Kinase Signaling System ; Diabetes Mellitus, Experimental/drug therapy* ; Superoxide Dismutase/metabolism*

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.
Angiogenesis Inhibitors/therapeutic use* ; Diabetes Mellitus ; Diabetic Retinopathy/drug therapy* ; Humans ; Intravitreal Injections ; Macular Edema/drug therapy* ; Pharmaceutical Preparations ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors/therapeutic use*

The aim of this paper was to investigate the preventive effects of Keluoxin Capsules(KLX) on diabetic retinopathy in db/db mice. One hundred male db/db diabetic mice(45-55 g, 8 weeks) were randomly divided into 5 groups(model, KLX low dose, KLX middle dose, KLX high dose, Dobesilate) and 20 male C57 BL/KsJdb~(+/+) were taken as control group. Body weight and fasting blood-glucose were detected every week. Mice were administrated with saline(control and model group), KLX(780, 1 560, 3 120 mg·kg~(-1)·d~(-1), ig), Dobesilate(195 mg·kg~(-1)·d~(-1), ig) for 20 weeks, respectively. At the end of the administration, optical coherence tomography, fundus fluorescein angiography and electroretinogram of the retina were measured. The eyeball was extirpated and retina was isolated to make paraffin section, followed by HE staining and glial fibrillary acidic protein(GFAP) immunohistochemistry. The results indicated that KLX has no obvious effect on body weight and fasting blood level in db/db mice. However, KLX could significantly regulate the thickness of retinal ganglion layer and inner plexiform layer. KLX was able to remarkably reduce the quantity of diabetic microvessel. Meanwhile, KLX could notably improve retinal function. Moreover, KLX could observably modulate the cell arrangement and edema in each layer. There was no markable difference in retina according to the immunochemistry assay. In the present study, KLX exert marked preventive effects on diabetic retinopathy in db/db mice, which provided an experimental evidence for clinical use.
Animals ; Capsules ; Diabetes Mellitus, Experimental ; Diabetic Retinopathy ; drug therapy ; Fluorescein Angiography ; Hypoglycemic Agents ; pharmacology ; Male ; Mice ; Random Allocation ; Retina ; drug effects

Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.
Administration, Oral ; Contrast Media ; adverse effects ; Diabetes Mellitus, Type 2 ; diagnostic imaging ; drug therapy ; Diabetic Retinopathy ; diagnostic imaging ; Fluorescein Angiography ; adverse effects ; methods ; Humans ; Hypoglycemic Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; Metformin ; therapeutic use

PURPOSE: To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection failure. METHODS: Patients with DME and central subfield thickness (CST) >300 microm who did not respond to IVB injections were retrospectively included. Specifically, we enrolled patients who were diagnosed with refractory DME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after > or =3 consecutive IVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. All patients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinations included Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. RESULTS: Forty eyes of 34 patients were included. The average baseline CST was 476 microm. The average CST decreased to 368 microm at 2 months, 374 microm at 4 months, and 427 microm at 6 months (p < 0.001 for all results, Wilcoxon signed-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 months but decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle of resolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and 0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. CONCLUSIONS: Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CST in DME refractory to IVB.
Aged ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/*therapeutic use ; Diabetic Retinopathy/diagnostic imaging/*drug therapy/physiopathology ; Female ; Glucocorticoids/*administration & dosage ; Humans ; Injections, Intraocular ; Intraocular Pressure/physiology ; Intravitreal Injections ; Macular Edema/diagnostic imaging/*drug therapy/physiopathology ; Male ; Middle Aged ; Retrospective Studies ; Tenon Capsule/*drug effects ; Tomography, Optical Coherence ; Treatment Failure ; Triamcinolone Acetonide/*administration & dosage ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/physiology

OBJECTIVETo observe the prevention and clinical efficacy of combination of Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic retinopathy (DR).

METHODSUsing randomized, double-blind, double simulation, parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM) outpatients were recruited and assigned to the treatment group and the control group, 70 in each group. All patients received basic Western medicine treatment (such as blood glucose and pressure control). Patients in the treatment group took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times per day), while those in the control group took LDP placebos and GLT placebos. All treatment lasted for 24 consecutive months. All subjects were followed-up every month. The general clinical data as sex, age, and metabolic data such as blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected and statistically analyzed.

RESULTSThere was no significant difference in levels of blood glucose, blood pressure, or blood lipid between the two groups (P > 0.05). After treatment the DR incidence rate was significantly lower in the treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P < 0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59), P < 0.05].

CONCLUSIONCombination of LDP and GLT could effectively prevent and treat the development of DR in T2DM patients.

Blood Glucose ; analysis ; Blood Pressure ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Humans ; Phytotherapy ; Tablets

The Korean Society of Nephrology (KSN) launched a nationwide end-stage renal disease (ESRD) patient registry in 1985 called the Insan Prof. Byung-Suk Min Memorial ESRD Patient Registry. KSN members voluntarily participate in this registry, which has been collecting data through the Internet since 2000. The KSN ESRD patient registry data were reviewed to elucidate the major changes and improvements in dialysis therapy in Korea. The data review revealed: a rapid increase in the number of patients with ESRD; an increase in the number of patients with diabetic nephropathy; a decrease in the proportion of patients undergoing peritoneal dialysis; an increase in the role of private dialysis clinics; an increase in the number of elderly patients undergoing dialysis and the number of patients undergoing long-term dialysis; a decrease in mean blood pressure and an increase in pulse pressure; improvement in anemia treatment; improvement in dialysis adequacy; and improvement in the survival of patients undergoing dialysis. In conclusion, improvements have been made in blood pressure control, anemia treatment, and dialysis adequacy despite increases in the number of elderly patients, diabetic patients, and patients on long-term dialysis during the last two decades in Korea.
Diabetic Retinopathy/diagnosis/mortality/*therapy ; Humans ; Kidney Failure, Chronic/diagnosis/mortality/*therapy ; Peritoneal Dialysis/trends ; Private Sector/trends ; Quality Improvement/trends ; Quality Indicators, Health Care/trends ; Registries ; Renal Dialysis/adverse effects/mortality/standards/*trends ; Republic of Korea/epidemiology ; Risk Factors ; Time Factors ; Treatment Outcome

This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable.
Adult ; Aged ; Aged, 80 and over ; *Cost-Benefit Analysis ; Diabetic Retinopathy/*diagnosis/economics/*therapy ; Diagnostic Techniques, Ophthalmological/economics ; Early Diagnosis ; Female ; Fluorescein Angiography/economics ; Health Care Costs ; Humans ; Male ; Markov Chains ; Mass Screening/*economics/methods/statistics & numerical data ; Middle Aged ; Models, Economic ; National Health Programs/economics ; Quality-Adjusted Life Years ; Republic of Korea

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology