Chinese Guideline of Diabetic Retinopathy was developed by the Chinese Ocular Fundus Society and Chinese Ophthalmological Society. It is the first prevention and intervention guideline document of diabetic retinopathy (DR) in China. Clinical pathways and strategies are clearly identified and described in this document for DR screening, referral, intervention, systematic management and patient education. The new DR stage classification combines the first Chinese DR classification since 1985 and the updated international classification of DR. This guideline is based on Chinese health care system, but also reflects the tradition and innovation, and reaches international practice standard. Learning and practice the guideline will promote the prevention and reduce the occurrence and development of DR in China.
Objective Toinvestigate the influence of photocoagulation on macular function and morphous in patients with diabetic retinopathy (DR).Methods Forty eyes of thirty patients with severe nonproliferative diabetic retinopathy (NPDR) were examined by multifocal electroretinogram (mfERG) and optical coherence tomography (OCT) before and 2,7, and 14 days after photocoagulation. The results were statistically analyzed by using analysis of variance and t test; the changes of macular function and macular fovea thickness were detected and observed.Results P1 response densities of ring 1,3,and 5 were 131.79plusmn;50.92，37.50plusmn;17.27，24.07plusmn;11.49，respectively,2 days after photocoagulation; and were 212.96plusmn;53.75，46.70plusmn;15.89，and 30.91plusmn;10.78, respectively, before photocoagulation. The densities before and after photocoagulation differed much（t=7.910, 2.174, 2.205; Plt;0.05）. N1 response density of ring 4 was（60.39plusmn;20.69） and the prephotocoagulation corresponding response density was （107.11plusmn;44.63）; the difference was significant（t=5.375，Plt;0.01）. The latency of P1 of ring 4 was（41.83plusmn;3.41），which had significant statistically difference（t=-2.770，Plt;0.05) with that before photocoagulation（39.52plusmn;2.64); there was no significant changes in the latency of N1 (Pgt;0.05). The most significant changes of P1 and N1 response densities occurred in the central macular 5deg; area. Seven days after photocoagulation, the response density of P1 and N1 in the central macular 5deg; area seemed to be recoverd to some extend and increased to （179.70plusmn;47.10）and (81.11plusmn;34.18) respectively until 14 days after photocoagulation, which was still much lower than that before the photocoagulation（t=3.840, 2.746; P＜0.05）; the response densities of other areas had no significant differences (P＞0.05). Seven days after photocoagulation,the latency of P1 in ring 4 was delayed to（41.78plusmn;3.57）, which had significant difference（t=-3.144，P＜0.01）with that before the photocoagulation（39.52plusmn;2.64) ; but there was no significant difference between 14 days after photocoagulation and prephotocoagulation (t=-1.809，P＞0.05). The latency of N1 in ring 1 was（20.67plusmn;3.85）at seven days after photocoagulation, It had no significant difference (t=-1.171,P＞0.05) with that before the phtocoaguation（18.78plusmn;3.29）. Before and 2 days after photocoagulation, the macular fovea thickness were（224.42plusmn;122.88）and（274.85plusmn;108.20）respectively, and the difference was statistically significant（t=-2.420，P＜0.05）. Forteen days after photocoagulation，the macular fovea thickness was（236.29plusmn;70.45），It had no significant difference with that before the photocoagulation（t=-0.578，P＞0.05）. Before and seven days after photocoagulation, P1 response density had obvious negative correlation with corresponding macular fovea thickness（r=-0.755，Plt;0.01; r=-0.594，Plt;0.05）. Conclusions After photocoagulation in patients with DR，the macular function decreased in a certain degree，and the relationship of macular retinal function and macular morphology changes was close; combination of mfERG and OCT can evaluate macular function and macular morphology structure comprehensively and objectively.
Objective To observe the effects of dual targets intervention on the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in diabetic rat retina. Methods Forty-eight Sprague -Dawley rats were randomly divided into control group (CON1 group) and diabetes mellitus group (DM group). The rats of DM group were induced with streptozotocin injection creating a diabetic model. Retinas were obtained at eight, 10, 12 weeks after DM induction from both groups. CTGF and VEGF mRNA levels were examined by realtime reverse transcriptionpolymerase chain reaction (RT-PCR). Based on the results of above experiments, 60 rats with same conditions were selected. Fifty rats were induced with streptozotocin injection creating a diabetic model, and 10 rats comprised the control group (CON2 group). Then the 50 diabetic rats were randomly divided into ranibizumab and CTGF shRNA dual targets intervention group, ranibizumab singletarget intervention group, CTGF shRNA singletarget intervention group and nonintervention group. Retinas were obtained at one week after intervention from all the groups. CTGF and VEGF mRNA levels were examined by RT-PCR. Results The levels of CTGF mRNA were significantly higher in DM group than that in CON1 group at the 8th weeks after DM induction, and this upregulation was maintained through the 12th week (t=-2.49, -2.67, -2.42;P＜0.05). There was no difference on VEGF mRNA levels between DM group and CON1 group at the 8th weeks after DM induction(t=-0.443,P=0.669). VEGF mRNA levels of DM group started to be significantly elevated over those in the CON1 group at the 10th week, and remained to be higher at the 12th week (t=-2.35, -2.57;P＜0.05). The VEGF mRNA of ranibizumab single-target intervention group was significantly lower than that in non-intervention group (t=-3.44,P=0.014), which was similar to CON2 group (t=-1.37,P＞0.05); however, the CTGF mRNA level was significantly increased as compared to the nonintervention group (t=2.48,P＜0.05). In the CTGF shRNA single-target intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=0.23, -2.92;P＜0.05). In the ranibizumab and CTGF shRNA dual targets intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=-6.09, -5.11;P＜0.001), which was similar to CON2 group (t=-1.16, 1.139; P＞0.05). Conclusions Both CTGF and VEGF gene expression are up-regulated in early diabetic rat retina, and the level of CTGF increased earlier than VEGF. Ranibizumab combined with CTGF shRNA could simultaneously reduce the level of CTGF and VEGF mRNA in diabetic rat retina.
Diabetic retinopathy (DR) is a major and irreversible blinding eye disease in working aged adults. Diabetic macular edema (DME) is a complication of the further development of DR, and it is one of the main causes of vision loss in DR patients. The emergence of anti-VEGF drugs has changed the treatment model of DR and DME. Firstly, for the treatment of DME, the previous focal/grid-like laser photocoagulation is converted to anti-VEGF drugs as the first-line treatment. Secondly, for the treatment of proliferative DR (PDR), panretinal photocoagulation (PRP) was the gold standard in the past, and now anti-VEGF drugs have become an alternative treatment for some PDR patients. In varying degrees of DR and DME, the option of treatment, anti-VEGF drug therapy replacing PRP, and the era of anti-VEGF drug therapy on DR treatment modes are worthy questions for consideration by clinicians. In-depth study of the clinical study of PRP and anti-VEGF drugs in the treatment of DR, the changes attention in clinical guidelines and expert consensus, the gradual establishment of treatment of DR and DME suitable, and the personalized treatment of DR patients may help improve the level of DR treatment in China.
Objective To evaluate the clinical efficacy and safety of 577 nm subthreshold micropulse laser on diabetic macular edema (DME). Methods Retrospective case series study. A total of 30 patients (35 eyes) with center?involving DME were enrolled in this study. All the patients received the examinations of best corrected visual acuity (BCVA), fundus colorized photography, fluorescein fundus angiography (FFA) and optical coherence tomography (OCT). BCVA was measured by Early Treatment Diabetic Retinopathy Study charts. The average retinal thickness (ART), total macular volume (TMV) and the retinal thickness (RT) and macular volume (MV) of 9 ETDRS domains were measured by the Japanese Topcon 3D-OCT 2000 instrument. The mean BCVA was 62.4±10.5 letters. The mean ART was 327.3±41.2 μm. The mean TMV was 9.24±1.17 mm3. All patients were treated with 577 nm subthreshold micropulse laser treatment. Subthreshold micropulse laser were performed in the micropulse mode, using a 200 μm spot diameter, a 0.2 s duration with 5% duty cycle and its treatment energy was 6?7 times of threshold energy. Three months after treatment, re-treatment was performed on patients with incomplete absorption of macular edema. The treatment was the same as before. The BCVA, ART, TMV and the RT and MV of each ETDRS domain were compared and analyzed before and after treatment. The possible complications of micropulse laser treatment were also observed and the safety was evaluated. Results The difference of BCVA were statistically significant in month 3 and month 6 (t=?5.58, ?7.24; P＜0.05), but not in month 1 (t=?1.82, P＞0.05). The average CRT (t=4.11, 4.17, 5.96), CMV (t=3.92, 4.05, 5.80) significantly decreased in 1, 3 and 6 months after treatment, the difference was statistically significant (P＜0.05). At sixth months, the average retinal thickness (t=3.53, 5.07, 5.02, 4.87, 4.94, 3.48, 4.03, 3.17, 3.73) and retinal volume (t=3.54, 5.16, 4.99, 4.91, 5.05, 3.47, 4.08, 3.10, 3.70) of the 9 ETDRS subdomains significantly decreased, and the difference was statistically significant (P＜0.05). There was no visible laser spots, changes in the outer retina and complications of neovascularization and subretinal fibrosis in the fundus of all patients. Conclusion577 nm subthreshold micropulse laser can reduce the CMT, CMV and improve the BCVA of DME patients with high security.
Objective To observe the expression of the pigment epithelium derived growth factor (PEDF) in retina and the effects of PEDF for vascular endothelial growth factor (VEGF) and retinal microvascular after recombinant adeno-associated virus mediated pigment epithelium derived factor（rAAV-mediated-PEDF）transferred retina of diabetic rats. Methods Male Wister rats were induced diabetes with intraperitoneal injection of streptozocin, then divided into 1 month group (DM1), 3month group(DM3) and 6 month group randomly. In diabetic rats, right eyes were injected rAAV2CMVhPEDF into vitreum as treat group,left eyes were injected into rAAV2-CMV-GFP (1times;1011 v.g/ml) as self-control group. In normal rats, right eyes were punctured but not injected (CONf), left eyes let it be without any disposal. The levels of VEGFmRNA and hPEDFmRNA in retina were evaluated using RT-PCR in different period. The protein levels of VEGF, PEDF within the retina were determined using western blot. The change of retinal capillary were observed through retinal vascular flattening. Result The expression of hPEDFmRNA in retina was enhanced persistence after rAAV2-CMV-hPEDF injected, achieved climax until 6 months. The levels of PEDF were also incerased consecutive, the differences were statistically significant in treatment group compared with own control group （Plt;0.01）. Levels of mRNA and protein of VEGF at different time-points among therapy group were not statistically significant, all obviously higher than normal （Plt;0.05），but all lower obviously than respectively own control group at the same timepoint （Plt;0.01）. The morphology of retinal capillary was not different significant with normal rats in 1 month diabetic rats. Morphology changes of therapy groups were less than those of respective own control group in DM3 and DM6. Conclusion Intravitreous injection rAAV2-CMV-hPEDF can increase expression of mRNA and protein of PEDF，alleviate lesion of retinal microvascular in early period of diabetic rats and supress expression of VEGF in retina of diabetic rats.The regulation occur on mRNA level. （Chin J Ocul Fundus Dis，2008，24：259-264）
ObjectiveTo investigate the effect of intravitreal injection of neural stem cells (NSC) derived from human umbilical cord mesenchymal stem cells (hUCMSC) on the expression of brain-derived neurotrophic factor (BDNF) and the number of retinal ganglion cells (RGC). MethodsFifty-two adult male Sprague-Dawley rats were randomly divided into normal group (group A) and diabetes mellitus group which received intraperitoneal injection of streptozocin to make diabetic rat models. One month after the diabetic rat models were confirmed successfully, diabetic rats were randomly divided into diabetic group (group B), hUCMSC group (group C) and hUCMSC-induced NSC group (group D). And thirteen diabetic rats were included in each group. Immuno-cytochemistry was applied to observe BDNF and thymosin-1(Thy-1) staining in the retina. Then mean integrated absorbance of the staining region on the retina slices were analyzed by Image-Pro Plus 6.0. The number of Thy-1 labeled RGC was record. ResultsBDNF and Thy-1 were positive on the retina slices from group A. The staining intensity from group B became weak and the expression of BDNF and Thy-1 gradually decrease with time (P < 0.05), and those from group C and group D were positively (P < 0.05), especially in group D (P < 0.05). The BDNF expression and Thy-1 labeled RGC were the same between group B and C (P > 0.05) at 2 weeks after injection, but were significant different for other time points (P < 0.05).Significant positive correlation between the expression of BDNF and the number of RGC were found by the Pearson correlation analysis (r=0.964, P < 0.05). ConclusionIntravitreal injection of hUCMSC-derived NSC to diabetic rat may protect the retina by promoting the expression of BDNF and increasing the number of RGC.
ObjectiveTo assess the clinical efficacy of vitrectomy with intravitreal ranibizumab (IVR) at different injection time for proliferative diabeticretinopathy (PDR). MethodsThis was a prospective, comparative, and randomized study. Ninety-seven eyes of 97 patients were enrolled and randomly assigned to three different treatment groups: 30 eyes (30 patients) in the preoperative IVR group, 32 eyes (32 patients) in the intraoperative IVR group and 35 eyes (35 patients) in the no IVR injection group. The best corrected visual acuity (BCVA) (F=0.18) and the grading of vitreous hemorrhage (χ2=1.39) before surgery did not differ significantly among the 3 groups, respectively (P > 0.05). All eyes enrolled underwent conventional 23-gauge pars plana vitrectomy (PPV). The preoperative IVR group received intravitreal 0.5 mg/0.05 ml ranibizumab injection 3 to 7 days before PPV, intraoperative IVR group received intravitreal 0.5 mg/0.05 ml ranibizumab injection at the end of PPV and non-drug injection group received PPV only. Postoperative BCVA, fundus color photography, optical coherence tomography examination was performed in all eyes at 1 week and 1, 3, 6, 9, 12 months after surgery. Early RVH was defined as RVH occurred within 1 week to 1 month postoperatively; while late RVH was defined as RVH occurred 1 month later after the operation. ResultsThe mean BCVA were all improved among the 3 groups compared with the preoperative vision at 1 month after operation. At the beginning of 3 months after surgery, the average BCVA of the preoperative injection group and the intraoperative injection group tended to stable; while 3 eyes in the non-drug injection group began to decreased. There was no significant difference in average BCVA at 1, 3 and 12 months of follow-up periods among the 3 groups (F=1.42, 1.17, 0.26; P > 0.05). The incidences of early RVH were 16.7%, 9.4%, 28.6% in the preoperative injection group, intraoperative injection group, and non-drug injection group, respectively (χ2=5.12, P < 0.05). The incidence of early RVH in the intraoperative injection group reduced compared to preoperative injection group and non-drug injection group (χ2=4.04, 4.93; P < 0.05). The incidences of late RVH were 13.3%, 9.4%, 14.3% in preoperative injection group, intraoperative injection group, and non-drug injection group, respectively (χ2=0.47, P > 0.05). The average centeral foveal thickness (CFT) decreased among the 3 groups in different degrees at 1 month when compared with that of 1 week after operation and the decreasing was statistically significant (F=59.50, P < 0.05). A subgroup pairwise analysis showed no significant difference of decreasing CFT in preoperative injection group compared with that of intraoperative injection group (t=0.23, P > 0.05). The average CFT of the 3 groups had different degrees of thickening at 3, 6, 9, 12 months after surgery, and the increasingof CFT among the 3 groups were not differ significantly (F=2.92, 2.86, 3.07, 3.12; P > 0.05). ConclusionsThe adjunctive use of IVR can reduce the incidence of early postoperative RVH in vitrectomy for PDR, decrease in macular thickness and obtain favorable visual recovery. The effect of preoperative IVR injection was slightly better than that of the intraoperative IVR injection.
Objective To observe the visual acuity of different stages of proliferative diabetic retinopathy (PDR) eyes after vitrectomy and analyze the risk factors of blindness.Methods A total of 384 eyes of 300 patients underwent vitrectomy for PDR were followed up. All cases were divided into three groups according to different stage of PDR (stage Ⅳ, stageⅤ and stage Ⅵ), the effect of vitrectomy were compared among these groups．Results The final visual acuity increased in 271 eyes (70.6%), among them there were 171 eyes (85.5%) in stage Ⅳ-Ⅴ, and 100 eyes (54.3%) in stage Ⅵ, and there was statistical difference between these two groups（chi;2=44.78，P＜0.05）. 82.8% of early-treated and 64.6% of middle/late-treated stage Ⅵ patients had postoperative visual acuity above 0.05 (chi;2=4.861，P＜0.05). 39.5% (131 eyes) of 332 eyes with diabetic blindness was still blind after surgery. Conclusion Visual acuity can be improved in the majority of PDR eyes after vitrectomy, early prevention and early treatment are the keys to avoid diabetic blindness.
Mesenchymal stem cells (MSC) are considered to have important value in the treatment of various diseases because of their low immunogenicity, transferability, and strong tissue repair capacity. Stromal cell derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) pathway plays an important role in migration of MSC. The induction of homing of MSC to retina by regulating SDF-1/CXCR4 may exert the curative effect on diabetic retinopathy to greatest exent.