OBJECTIVETo study the effects of Huoxue Jiedu Recipe (HJR) on the hemodynamics of central retinal artery (CRA) and central retinal vena, as well as the morphology of blood vessels of diabetic rats.

METHODSSixty SD rats were selected and fasted for 12 h. Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected to induce diabetic rat models. The modeled rats were randomly divided into the model group, the high dose HJR group (15.4 g/kg), the middle dose HJR group (7.70 g/kg), the low dose HJR group (3.85 g/kg), and the Doxium Capsule group (the Western medicine group, 0. 167 g/kg), 10 in each group. Another 10 rats were recruited as the normal control group. Equal volume of distilled water was given to rats in the normal control group. The intervention was carried out once daily in each group, totally for 20 weeks. The peak systolic velocity (PSV), the end diastolic velocity (EDV), the mean velocity (MV), the pulsatile index (PI), the resistive index (RI), and the central retinal vena velocity (CRV) were detected in each group. The retinal vascular morphologies were observed and compared using trypsin digestion.

RESULTSCompared with the normal control group, the PSV, EDV, MV, and CRV decreased, PI, RI, and capillary density increased in the model group with statistical difference (P<0.01). The retinal capillaries rowed disorderly. The calibers of capillaries were not even. The hyperplasia of endothelial cells and less pericytes could be seen. Compared with the model group, PSV, EDV, MV, and CRV all increased, PI and RI decreased in the high and middle dose HJR groups with statistical difference (P<0.01). There was no statistical difference among all the medication groups (P>0.05). The distributions of capillaries in the 3 HJR groups were even. The vascular morphous was comparatively regular, without obvious twisting and dilation. The hyperplasia of endothelial cells was not obvious. Compared with the model group, the capillary density significantly decreased (P<0.01). There was no statistical difference among the 3 HJR groups. Compared with the model group, the capillary density significantly decreased in the Western medicine group (P<0.01).

CONCLUSIONHJR could obviously improve the retinal hemodynamics parameters of diabetic rats, increase the retinal capillary blood flow and reperfusion, and restrain the hyperplasia of endothelial cells in the capillary.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; pathology ; physiopathology ; Diabetic Retinopathy ; drug therapy ; pathology ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Hemodynamics ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley

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

PURPOSE: To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco, CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). MATERIALS AND METHODS: Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done. RESULTS: The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043). CONCLUSION: Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.
Adult ; Angiogenesis Inhibitors/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Diabetic Retinopathy/*drug therapy/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A/*metabolism

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

BACKGROUNDDiabetic retinopathy (DR) is one of the most common complications of diabetes. Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR. The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI, captopril) in the treatment of patients with non-proliferative DR.

METHODSThree hundred and seventeen type 2 diabetic patients (88.05% of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n = 202) and placebo group (n = 115). All subjects received 24-month follow-up. General clinical examinations, including blood pressure and glycated hemoglobin, as well as comprehensive standardized ophthalmic examinations were performed. Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.

RESULTSThe levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits, suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role. DR classification showed that 169 eyes (83.66%) remained unchanged and the DR grade of 33 eyes (16.34%) increased in captopril group, while 84 eyes (73.04%) remained unchanged and the grade of 31 eyes (26.96%) increased in placebo group (P = 0.024). Captopril treatment improved macular edema in 55.45% eyes, which was significantly higher than the 37.39% improvement in placebo group (P = 0.002). No significant difference was found in the visual acuity between the two groups (P = 0.271).

CONCLUSIONCaptopril can improve or delay the development of DR and macular edema, which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Captopril ; therapeutic use ; Diabetic Retinopathy ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

BACKGROUNDDiabetic retinopathy (DR) has emerged as a leading cause of visual impairment and blindness in the working-aged population worldwide. This study aimed to assess frequency and associated factors of progression of DR in subjects with known diabetes in a population-based setting.

METHODSThe Beijing Eye Study is a population based study performed in Greater Beijing in 2001 and 2006. The present investigation included all subjects with known diabetes mellitus in 2001, who participated in the follow-up examination in 2006. Fundus photographs were assessed.

RESULTSThe study included 170 subjects; 51 (30%) subjects showed signs of DR in 2001 and were re-examined in 2006, 36 (21.2%) subjects (18 subjects with DR present at baseline, 18 subjects with newly diagnosed DR in 2006) showed a progression of DR during follow-up. Progression of DR was associated with rural region (odds ratio (OR): 5.43, P = 0.001) and self-reported arterial hypertension (OR: 3.85, P = 0.023). In the non-progressive subgroup, presence of DR was associated with different levels of education (< middle school, middle school, college or higher, OR: 0.30, P = 0.023), treatment modes of diabetes mellitus (OR: 10.24, P = 0.003) and cataract surgery (OR: 9.14, P = 0.007).

CONCLUSIONSIn a population-based setting in Greater Beijing, progression of DR occurred in 35% of subjects with pre-existing DR and overall in 21% of subjects with known diabetes within a 5-year period. Progression of DR was significantly associated with rural region and self-reported arterial hypertension. In the stable subjects, presence of DR was significantly associated with poor educational level, insulin treatment of diabetes and cataract surgery.

Adult ; Aged ; Aged, 80 and over ; China ; Diabetes Mellitus ; drug therapy ; physiopathology ; Diabetic Retinopathy ; epidemiology ; pathology ; Female ; Humans ; Hypertension ; physiopathology ; Insulin ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis

OBJECTIVETo observe the effects of Huoxue Jiedu Recipe (HJR) on the electroretinogram (ERG) and the expression of glial fibrillary acid protein (GFAP) in the retina tissue of early diabetic rats.

METHODSThe diabetic rat model was established using one single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). Then the modeled rats were randomly divided into 5 groups, i.e., the model group, the low dose HJR group (3.85 g/kg), the middle dose HJR group (7.70 g/kg), the high dose HJR group (15.40 g/kg), and the Western medicine treatment group (Calcium Dobesilate Capsule, 0.167 g/kg), 8 in each group. A normal control group consisting of 8 rats was also set up, which was given equal volume of distilled water by gastrogavage. All rats were medicated by gastrogavage for 20 weeks. The electroretinograph (ERG) was determined. The amplitudes of wave a and b (the maximal electric reaction for dark-adapted eyes), and the amplitude sum of the oscillatory potentials (OPs) were detected. The integral optical density (IOD), the protein and mRNA expression of GFAP were detected using immunohistochemical assay, Western blot, and fluorescent quantitative PCR.

RESULTSCompared with the normal control group,the amplitudes of wave a, wave b, and OPs decreased in the model group (P<0.01). The protein and mRNA expressions of IOD and GFAP significantly increased (P<0.01). Compared with the model group, the amplitudes of wave b and OPs increased, and the protein and mRNA expressions of IOD and GFAP significantly decreased in each HJR group. The amplitude of wave a in the middle and high dose HJR groups increased. The amplitude of wave b increased and the IOD expression decreased in the Western medicine treatment group, showing statistical difference (P<0.05, P<0.01). There was no statistical difference in each index between the Western medicine treatment group and each HJR group.

CONCLUSIONHJR could attenuate the visual electrophysiological dysfunction in early diabetic rat, showing certain protection on retinal glial cells.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Diabetic Retinopathy ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Electroretinography ; Male ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects ; metabolism ; physiopathology

INTRODUCTIONAlthough laser photocoagulation is the primary treatment for diabetic macular oedema, treatment of eyes with diffuse macular oedema has been disappointing. Intravitreal injection of steroids is being investigated for the treatment of diabetic macular oedema. Preliminary results indicate that steroid injections do improve macular oedema, but it is not clear if they improve visual acuity.

CLINICAL PICTURE, TREATMENT, AND OUTCOMEIn this report, we describe a patient with a form of diffuse diabetic macular oedema that responded favourably to intravitreal steroid injections, with improvements in both foveal thickness and visual acuity.

CONCLUSIONIntravitreal steroids can be useful for the treatment of diffuse diabetic macular oedema.

Adult ; Diabetic Retinopathy ; diagnosis ; drug therapy ; Glucocorticoids ; administration & dosage ; Humans ; Injections, Intralesional ; Macular Edema ; diagnosis ; drug therapy ; Male ; Tomography, Optical Coherence ; Triamcinolone Acetonide ; administration & dosage ; Visual Acuity ; drug effects

PURPOSE: To compare the short-term effects of intravitreal triamcinolone acetonide (IVTA) with those of intravitreal bevacizumab (IVB) injection for diabetic macular edema (DME). METHODS: The present retrospective, comparative case study included 58 eyes of 35 consecutive patients (IVTA group, 20 eyes; IVB group, 38 eyes) with DME. IVTA (4 mg) or IVB (1.25 mg) injection was performed under local anesthesia. The effects of injection for DME were evaluated using best-corrected visual acuity (BCVA), central macular thickness (CMT) by optical coherence tomography and intraocular pressure (IOP) by applanation tonometer. Patients underwent eye examinations, including BCVA, CMT, and IOP at pre-injection, 2, 4, and 8 weeks after injection. RESULTS: BCVA (logarithm of the minimum angle of resolution) +/- SD at pre-injection, 2, 4, and 8 weeks after injection was 0.67 +/- 0.40, 0.56 +/- 0.35 (p = 0.033), 0.55 +/- 0.33 (p = 0.041), and 0.43 +/- 0.31 (p = 0.001) in the IVTA group and 0.51 +/- 0.31, 0.42 +/- 0.26 (p = 0.003), 0.43 +/- 0.32 (p = 0.001), and 0.43 +/- 0.27 (p = 0.015) in the IVB group, respectively. CMT (microm) +/- SD at pre-injection, 2, 4, and 8 weeks after injection was 400.4 +/- 94.9, 332.8 +/- 47.4 (p = 0.002), 287.5 +/- 49.1 (p = 0.007), and 282.5 +/- 49.6 (p = 0.043) in the IVTA group and 372.6 +/- 99.5, 323.2 +/- 72.4 (p = 0.077), 360.9 +/- 50.3 (p = 0.668), 368.2 +/- 88.6 (p = 0.830) in the IVB group, respectively. CONCLUSIONS: The effects of IVTA for BCVA were more favorable than were those of IVB and were consistent throughout the eight weeks after injection. IVTA significantly reduced CMT during the eight weeks after injection, while IVB did not.
Aged ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal/*administration & dosage ; Diabetic Retinopathy/*drug therapy ; Female ; Glucocorticoids/*administration & dosage ; Humans ; Intravitreal Injections ; Macular Edema/*drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Triamcinolone Acetonide/*administration & dosage

PURPOSE: To compare the efficacy of posterior sub-Tenon's capsule triamcinolone acetonide injection combined with modified grid macular photocoagulation (PSTI + MP) with intravitreal triamcinolone acetonide (IVTA) injection in the treatment of diffuse diabetic macular edema (DME). MATERIALS AND METHODS: Forty eyes of 33 patients with diffuse DME were randomly allocated into either PSTI + MP (20 eyes) or IVTA (20 eyes). Best corrected visual acuity (VA) and foveal thickness were measured. RESULTS: The ETDRS scores at baseline were 25.2 +/- 13.6 (mean +/- SD) letters in the PSTI + MP group, whereas 21.7 +/- 16.3 letters in the IVTA group. The ETDRS scores improved by 33.2 +/- 15.9, 34.7 +/- 16.6 and 30.9 +/- 19.0 letters in the PSTI + MP group whereas by 30.9 +/- 15.4, 30.1 +/- 17.9 and 31.5 +/- 15.0 letters in the IVTA group at 1, 3, and 6 months after the treatments, respectively. The VA improved significantly at 1 month and 3 months after both treatments (all p < 0.02, paired t-test). The VA improvements were no longer significant at 6 months in either group. There were no statistically significant differences at any time points between the 2 groups (all p > 0.05, Student's t-test). The foveal thicknesses at baseline and 1, 3, and 6 months after the treatments were 382.8 +/- 148.3, 309.1 +/- 131.3, 319.3 +/- 93.3, 340.4 +/- 123.5micrometer (mean +/- SD) in the PSTI + MP group vs. 369.1 +/- 123.1, 241.4 +/- 52.3, 277.5 +/- 137.4, 290.2 +/- 127.9micrometer in the IVTA group, respectively. Pairwise comparisons revealed significant decrease in foveal thickness at 1 month (p = 0.01, paired t-test) for the PSTI + MP group, and at both 1 month (p < 0.001) and 3 months (p = 0.016) for the IVTA group. There were no statistically significant differences at any time points between the 2 groups (all p > 0.05, Student's t-test). In contrast to the PSTI + MP group, where no complications were noted, the elevation of intra-ocular pressure in 3 of 20 eyes (15%) and a significant increase in average cataract grading were observed in the IVTA group. CONCLUSION: PSTI + MP treatment provides significant improvement of vision in patients with diffuse DME over 3 months, and achieves outcomes comparable to those after IVTA treatment, however, with fewer complications.
Adult ; Aged ; Anti-Inflammatory Agents/administration & dosage ; Diabetic Retinopathy/*drug therapy/physiopathology/*surgery ; Female ; Fovea Centralis/pathology ; Humans ; *Laser Coagulation ; Macular Edema/complications/*drug therapy/physiopathology/*surgery ; Male ; Middle Aged ; Prospective Studies ; Triamcinolone/*administration & dosage ; Visual Acuity ; Vitreous Body