Diabetic retinopathy is a serious complication of diabetes and is the leading cause of blindness in people with diabetes. At present, there are many views on the pathogenesis of diabetic retinopathy, including the changes of retinal microenvironment caused by high glucose, the formation of advanced glycation end products, oxidative stress injury, inflammatory reaction and angiogenesis factor. These mechanisms produce a common pathway that leads to retinal degeneration and microvascular injury in the retina. In recent years, cell regeneration therapy plays an increasingly important role in the process of repairing diseases. Different types of stem cells have neurological and vascular protection for the retina, but the focus of the target is different. It has been reported that stem cells can regulate the retinal microenvironment and protect the retinal nerve cells by paracrine production, and can also reduce immune damage through potential immunoregulation, and can also differentiate into damaged cells by regenerative function. Combined with the above characteristics, stem cells show the potential for the repair of diabetic retinopathy, this stem cell-based regenerative therapy for clinical application provides a pre-based evident. However, in the process of stem cell transplantation, homogeneity of stem cells, cell delivery, effective homing and transplantation to damaged tissue is still a problem of cell therapy.
Objective To observe the functional and morphological changes of macular after panretinal photocoagulation（PRP）in the patients with diabetic retinopathy（DR）.Methods A total of 57 eyes of 34 patients with DR undergoing PRP were enrolled in this prospective and self-reflection study. Comparatively analyze the changes of the best visual acuity（BCVA）, optical coherence tomography (OCT) and multi-focal electroretinography (mfERG) before PRP,20 days, 3 months and more than 9 months after PRP. Statistical analyses were performed by wilcoxon, chisquare, Dunnett-t, LSD-t tests and spearman related analyses. The changes of macular function and foveal retinal thickness before and after PRP were comparatively analyzed.Results BCVA of all patients reduced at 9 months after PRP（P=0.022）.The amplitude density of mfERG P1 of ring 2 decreased at 20 days after PRP（P=0.039）,then recovered at 3 months and decreased again at 9 months（P=0.014）.The amplitude density of mfERG P1 of ring 3-5 decreased at 20 days,3 months and more than 9 months after PRP（20 days: ring 3: P=0.000,ring 4: P=0.001, ring 5: P=0.000；3 months: ring 3:P=0.000, ring 4: P=0.006, ring 5: P=0.001; more than 9 months: ring 3: P=0.000,ring 4: P=0.000, ring 5: P=0.000）. The amplitude density of mfERG P1 of ring 1 was significantly lower at 9 months after PRP（P=0.050）. The foveal retinal thickness increased at 20 days after PRP(P=0.007), then recovered at 3 months or later. Cystoid macular degeneration was found in 6 eyes(10.5%) at 20 days after PRP.Conclusions After the treatment of PRP, there were some extend reduction of the macular function, a transient increase on foveal retinal thickness. Combined mfERG and OCT can be a comprehensively and objectively assessment of macular function and morphology.
Objective Methods Ninety male Wister rats were randomly divided into normal control group, diabetic group and FTY720 group, thirty rats in each group. Diabetes was induced by giving a single intraperitoneal injection of streptozocin. FTY720 group was administered with FTY720 at a dose of 0.3 mg/kg by oral gavage daily for 3 months after establishment of diabetes. All rats were used for experiments following intervention for 3 months in FTY720 group. Immunohistochemical staining was used to observe the expression and distribution of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and the positive cells were counted. Real-time reverse transcription PCR was used to measure mRNA expression of ICAM-1 and VCAM-1. Fluorescein isothiocyanate-Concanavalin A perfusion was used to detect retinal leukocytes adhesion. Evans blue (EB) perfusion was used to analyze retinal vascular permeability. Immunofluorescence staining was used to detect retinal inflammatory cells infiltration. Results In diabetic group, both ICAM-1(t=12.81) and VCAM-1 (t=11.75) positive cells as well as their mRNA expression (t=16.14, 9.59) were increased compared with normal control group, with statistical significance (P < 0.05). In FTY720 group, both ICAM-1(t=-9.93) and VCAM-1 (t=-6.61) positive cells as well as their mRNA expression (t=-15.28, -6.10) were decreased compared with diabetic group, with statistical significance (P < 0.05). Retinal leukocytes adhesion (t=16.32) and EB permeability (t=17.83) were increased in diabetic group compared with normal control group, while they were decreased in FTY720 group compared with diabetic group(t=-9.93, -11.82),with statistical significance (P < 0.05). There were many CD45 positive leukocytes infiltration in retina of diabetic group, including CD11b positive macrophage/activated microglia, while both of them were little in FTY720 group. Conclusions FTY720 can decrease retinal leukocytes adhesion, reduce retinal vascular permeability and inflammatory cells infiltration, which is associated with down-regulation of ICAM-1 and VCAM-1.
ObjectiveTo observe the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on blood glucose levels and diabetic retinopathy in diabetes mellitus (DM) rats. MethodA total of 45 healthy male Sprague-Dawley rats were randomly divided into normal control group (group A, 10 rats) and DM group (33 rats). Diabetic model was established in DM group by tail vein injection of streptozotocin.The DM group was further randomly divided into 3 groups (11 rats in each group), including group B (no transplantation), group C (hUCMSC was injected through tail vein) and group D (hUCMSC was injected into the vitreous). Blood glucose, retina wholemont staining and expression of brain derived neurotrophic factor (BDNF) in the retina were measured at 2, 4, 6, 8 weeks after hUCMSC injection. The blood glucose was significantly different between A-D groups before injection (t=-64.400, -60.601, -44.065, -43.872; P=0.000) BDNF expression was studied by real time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry staining. ResultsThe blood glucose was significantly different between A-D groups after hUCMSC injection (F=400.017, 404.410, 422.043, 344.109; P=0.000), and between group C and group B/D (t=4.447, 4.990; P < 0.01). Immuno-staining shown that BDNF was positive in ganglion cell layer (RGC) of group A, weak in group B while BDNF expression increased in group C/D. BDNF mRNA expression was significantly different between group B, C and D at 4, 6 and 8 weeks after hUCMSC injection (F=29.372, 188.492, 421.537; P=0.000), and between group B and C/D (t=66.781, 72.401, 63.880, 88.423, 75.120, 83.002; P < 0.01) by RT-PCR analysis. The BDNF mRNA expression was significantly different between C and D groups only at 8 weeks after hUCMSC injection (t=127.321, P=0.005). ConclusionsTail vein injection of hUCMSCs can significantly reduce the blood glucose levels of rats. Intravenous and intravitreal injection of hUCMSCs can increase the expression of BDNF.
ObjectiveTo analyze the expression of VEGF, IL-33 and NO concentration after laser photocoagulation and subthreshold micropulse laser photocoagulation conventional in proliferative diabetic retinopathy (PDR) patients.MethodsA case control study. The clinical data of 39 patients of PDR and 11 patients of idiopathic macular pucker (IMP) from Department of Ophthalmology, Central Theater General Hospital during November 2015 were collected in this study. PDR patients were assigned randomly into three groups. Fifteen PDR patients with 15 eyes were treated with conventional laser as group A. Thirteen PDR patients with 13 eyes were treated with subthreshold micropulse laser as group B. Eleven PDR patients with 11 eyes without any laser therapy were grouped as C. Eleven IMP patients were grouped as D. There was no difference of age (F=0.53, P=0.23), gender ratio (χ2=0.55, P=0.91), body mass index (F=2.62, P=0.07), duration diabetes (F=0.29, P=0.75), glycoslated hemglobin (F=1.72, P=0.19) in four groups. All PDR patients were examined with FFA. Total protein was quantified by a bicinchoninic acid assay kit. Levels of VEGF, IL-33, NO were determined using enzyme-linked immunosorbent assay kits.ResultsThere was no difference of total protein in four groups (F=1.78, P=0.17). Group C had a higher VEGF level than group A and B (F=7.84, P=0.002). Group A had a higher IL-33 level than group C (t=4.15, P=0.02). There was no difference of IL-33 level in group B and C (t=1.34, P=0.20). Group D had a lower NO level than group A, B, C (F=38.42, P＜0.001). There was no difference of NO level in group A, B and C (F=3.29, P=0.06).ConclusionsBoth conventional laser photocoagulation and subthreshold micropulse laser photocoagulation can decrease vitreous VEGF level and subthreshold micropulse laser photocoagulation can induce less IL-33 level.
The ocular fundus changes and the damage of visual function were various at different stages of diabetic retinopathy (DR). To get hold of timing and different therapic method correctly of early diagnosis, whole body treatment, laser photocoagulation and vitreous-retina surgery and adopting targeted interventions could help patients receiving the most reasonable and effective treatment at different stages, both of them are keys to reduce the damage of visual function. （Chin J Ocul Fundus Dis，2008，24：240-243）
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.
Panretinal photocoagulation (PRP) and macular photocoagulation (MPC) are the gold standard treatments for proliferative diabetic retinopathy (DR) and diabetic macular edema. With the development of equipment and technology advancement, photocoagulation has been gradually applied in many Eye Centers all over China. However, there are still several problems such as no standardized guideline and undesirable therapeutic effects. In this article we will summarize the indications and techniques of photocoagulation, and when and how to apply drug treatments for retinal diseases; aim at improving the criterion and clinical effects of photocoagulation.
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.
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.