PURPOSE: To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. METHODS: A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. RESULTS: Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. CONCLUSIONS: IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.
Aged ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/*therapeutic use ; Diabetic Retinopathy/*drug therapy/physiopathology ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Intravitreal Injections ; Macular Edema/*drug therapy/physiopathology ; Male ; Middle Aged ; Nephelometry and Turbidimetry ; Retina/pathology ; *Subretinal Fluid ; Tomography, Optical Coherence ; Treatment Outcome ; Triamcinolone Acetonide/*therapeutic use ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/physiology

BACKGROUNDPoly(ADP-ribose) polymerase (PARP) plays an important role in the death of retinal capillary cells in diabetic retinopathy (DR) partly via its regulation of nuclear factor kappa B (NF-κB). The current study investigated the effect of the regimen of Gaoshan Hongjingtian (RG) on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian (Rhodiola sachalinensis, RS) on diabetic retinopathy.

METHODSWistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 (ICAM-1) in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction (PCR). In addition, the basement membranes of capillaries in the rats' retinas were observed using electron microscopy, and diabetes-induced capillary degeneration (ghost pericytes and acellular capillaries) were quantitated.

RESULTSFrom the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-κB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries (ghost pericytes and acellular capillaries) was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-κB, and ICAM-1 in the retinas of diabetic rats at the end of 5-month diabetic duration. Treatment using RG and RS significantly inhibited increases in the number of acellular capillaries and pericyte ghosts and suppressed the basement membrane thickening in the retinas of rats with diabetes for 8 months compared with the control diabetic rats.

CONCLUSIONSThese results indicate that PARP plays an important role in the pathogenesis of diabetic retinopathy. RS and RG may have acted on the mechanism of PARP regulation of NF-κB, which suppressed the expression of NF-κB and ICAM-1, and led to the inhibition of retinal capillary degeneration.

Animals ; Basement Membrane ; drug effects ; pathology ; Diabetes Mellitus, Experimental ; drug therapy ; pathology ; Diabetic Retinopathy ; drug therapy ; pathology ; Intercellular Adhesion Molecule-1 ; genetics ; Male ; Medicine, Chinese Traditional ; NF-kappa B ; genetics ; physiology ; Poly(ADP-ribose) Polymerases ; physiology ; Rats ; Rats, Wistar ; Rhodiola ; Streptozocin

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

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

PURPOSE: To evaluate the effect of intravitreal bevacizumab on visual function and retinal thickness in patients with diabetic macular edema (DME). METHODS: Thirty eyes of twenty-eight patients (mean age, 57.9+/-13.8 years) with DME were included in this study. Complete ophthalmic examination, including determination of best-corrected visual acuity (BCVA), stereoscopic biomicroscopy, and retinal thickness measurement by optical coherence tomography (OCT), was done at baseline and at each follow-up visit. All patients were treated with a 0.05 mL intravitreal injection containing 1.25 mg of bevacizumab. RESULTS: All patients completed 3 months of follow-up with a mean follow-up period of 5.26+/-2.39 months. The mean BCVA at baseline was 0.73+/-0.36 logMAR, which significantly improved to 0.63+/-0.41 (p=0.02), 0.58+/-0.36 (p=0.003), and 0.61+/-0.40 logMAR (p=0.006) at 1 week, 1 month, and 3 months. Final BCVA analysis demonstrated that 15 eyes (50%) remained stable and 12 (40%) improved > or =2 lines on BCVA. The mean central retinal thickness was 498.96+/-123.99 microm at baseline and decreased to 359.06+/-105.97 (p<0.001), 334.40+/-121.76 (p<0.001), 421.40+/-192.76 microm (p=0.035) at 1 week, 1 month, and 3 months. No ocular toxicity or adverse effects were observed. CONCLUSIONS: Intravitreal bevacizumab injection resulted in significant improvement in BCVA and central retinal thickness as early as 1 week after injection in patients with DME, and this beneficial effect persisted for up to 3 months. However, the slight reduction in this improvement at 3 months suggests that repeated bevacizumab injections might be necessary. To evaluate the long-term safety and efficacy, further prospective randomized controlled clinical trials will be needed.
Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal/*administration & dosage ; Diabetic Retinopathy/*drug therapy/pathology ; Female ; Follow-Up Studies ; Humans ; Injections ; Laser Therapy/methods ; Macular Edema/*drug therapy/pathology ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity ; Vitrectomy/methods ; Vitreous Body

PURPOSE: To compare the efficacy between macular laser grid (MLG) photocoagulation and MLG plus intravitreal triamcinolone acetonide (IVTA; MLG+IVTA) therapy in diabetic macular edema (DME) patients. METHODS: A prospective, randomized, clinical trial was conducted of DME patients. A total of 60 eyes (54 patients) affected by DME were observed for a minimum of 6 months. Thirty eyes of 28 patients who received MLG treatment and 30 eyes of 26 patients who received the combined MLG+IVTA treatment were included in the study. Main outcome measures were BCVA and central macular thickness (CMT) as measured by optical coherence tomography (OCT) at 1, 3, and 6 months after treatment. Additionally, the authors examined retrospectively 20 eyes of 20 patients who were treated with only IVTA and compared with the 2 groups (MLG group and MLG+IVTA group). RESULTS: Baseline BCVA was 0.53+/-0.32 and CMT was 513.9+/-55.1 microm in the MLG group. At 1 and 3 months after treatment, the MLG group showed no significant improvement of BCVA and CMT, although there was significant improvement after 6 months. In the MLG+IVTA group, the baseline BCVA was 0.59+/-0.29 and CMT was 498.2+/-19.8 microm. After treatment, significant improvement of BCVA and CMT was observed at all follow-up time periods. When comparing the MLG group with the MLG+IVTA group, the latter had better results after 1 and 3 months, although at 6 months, there was no significant difference of BCVA and CMT between the 2 groups. Additionally, the IVTA group showed more improvement than the MLG group at 1 and 3 months but showed no significant difference at 6 months. In addition, the IVTA group showed no significant difference with the MLG+IVTA group at all follow-up time periods. CONCLUSIONS: For DME patients, the combined MLG+IVTA treatment had a better therapeutic effect than the MLG treatment for improving BCVA and CMT at the early follow-up time periods. IVTA treatment alone could be an additional alternative therapeutic option to combined therapy.
Aged ; Diabetic Retinopathy/*drug therapy/pathology/physiopathology/*surgery ; Follow-Up Studies ; Glucocorticoids/*administration & dosage ; Humans ; Injections ; *Laser Coagulation ; Macular Edema/*drug therapy/pathology/physiopathology/*surgery ; Middle Aged ; Postoperative Period ; Tomography, Optical Coherence ; Triamcinolone Acetonide/*administration & dosage ; Visual Acuity ; Vitreous Body

PURPOSE: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular edema. METHODS: In a retrospective study, 44 eyes with diffuse diabetic macular edema were treated with an intravitreal injection of 4 mg (n=12 eyes), 8 mg (n=17) or 25 mg (n=15) of triamcinolone acetonide (TA). Optical coherence tomography, best-corrected logMAR visual acuity and Goldmann tonometry were performed at baseline, 1 week, and 1, 3, 6, 9 and 12 months after treatment. Mean follow-up was 9.8 months (standard deviation=2.3) with a range of 5-12 months. RESULTS: The duration of intravitreal TA effects on macular thickness and visual acuity increased with increasing dosage. An observed increase in intraocular pressure induced by TA was not significantly associated with dosage. CONCLUSIONS: In patients with diffuse diabetic macular edema who receive intravitreal TA, effects may last longer after a dosage of 25 mg, than after lower doses of 8 mg or 4 mg.
Adult ; Aged ; Aged, 80 and over ; Diabetic Retinopathy/*complications/drug therapy/pathology ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Glucocorticoids/*administration & dosage ; Humans ; Injections ; Intraocular Pressure ; Macular Edema/diagnosis/*drug therapy/etiology ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Treatment Outcome ; Triamcinolone Acetonide/*administration & dosage ; Visual Acuity ; Vitreous Body

BACKGROUNDDiabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes.

METHODSWe used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats.

RESULTSGSPE significantly reduced the AGEs of diabetic rats (P < 0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism.

CONCLUSIONSThese findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

Animals ; Blood Glucose ; drug effects ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; complications ; metabolism ; pathology ; Diabetic Retinopathy ; drug therapy ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Glycated Hemoglobin A ; metabolism ; Glycation End Products, Advanced ; metabolism ; Grape Seed Extract ; Male ; Plant Extracts ; pharmacology ; Proanthocyanidins ; pharmacology ; Proteomics ; methods ; Rats ; Rats, Wistar

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

PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE-I) in retarding progression of severe non-proliferative diabetic retinopathy (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a retrospective case control study of 128 patients with normotensive type 2 diabetes with lower than +1 dipstick proteinuria and severe NPDR who were classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 , Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b) development of proteinuria of higher than +1 level requiring medication of ACE-I. RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and 99 ACE-I untreated patients. There were no differences in the average age, duration of diabetes, body mass indices, blood pressure and levels of hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in both groups remained unchanged during the study. The mean follow-up period was 41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6 developed proteinuria of greater than +1 over the follow-up period. In the control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I did not yield any beneficial effects in retarding the progression of severe NPDR.
Treatment Failure ; Severity of Illness Index ; Retrospective Studies ; Ramipril/administration & dosage/*therapeutic use ; Middle Aged ; Male ; Humans ; Fundus Oculi ; Female ; Enalapril/administration & dosage/*therapeutic use ; Dose-Response Relationship, Drug ; Disease Progression ; Diabetic Retinopathy/*drug therapy/pathology ; Diabetes Mellitus, Type 2 ; Case-Control Studies ; Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*therapeutic use ; Aged