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.
Diabetic macular ischemia (DMI) is one of the manifestation of diabetic retinopathy (DR). It could be associated with diabetic macular edema (DME), which may affect the vision of DR patients. FFA is the gold standard for the diagnosis of DMI, but with the advent of OCT angiography, a more convenient and diversified method for the evaluation of DMI has been developed, which makes more and more researchers start to study DMI. Intravitreal injection of anti-VEGF has become the preferred treatment for DME. When treating with DME patients, ophthalmologists usually avoid DMI patients. But if intravitreal anti-VEGF should be the contradiction of DME is still unclear. To provide references to the research, this article summarized the risk factors, assessment methods and influence of DMI. This article also analyzed the existing studies, aiming to offer evidences to a more reasonable and effective treatment decision for DME individual.
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.
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）
bjective To observe the therapeutic effect of laser photocoagulation on diabetic retinopathy (DR)at different stages.Methods A total of 534 eyes of 304 patients with DR diagnosed by fundus fluorescein angiography (FFA) were enrolled in this study. In the 534 eyes, 92 with nonproliferative DR (NPDR) had the bestcorrected visual acuity(BCVA) of 0.52plusmn;0.32,108 with preproliferative DR (PPDR) had the BCVA of 0.49plusmn;0.23,196 with early PDR had the BCVA of 0.20plusmn;0.31,and 138 with highrisk PDR had the BCVA of 0.17plusmn;0.22． According to the rules of ETDRS, retinal photocoagu1ation,pan retinal photocoagu1ation or extrapanretinal photocoagu1ation were performed on the paitents with NPDR,PPDR,and highrisk PDR,respectivelyThe patients were followed up for 10-18 months after the operations and the results of the examinations at the last time were regarded as the criteria for judgement. The examination of BCVA and ocular fundus and FFA were performed with the time interval of 3 months．The judgement for BCVA was(1)improved:improved ge;2 lines;(2) kept still: changed within 2 lines;(3)decreased:decreased ge;2 lines.And the effect on BCVA was positve when it was improved or kept still.The judgement for the therapeutic effect on DR was:retinal edeama was alleviated,leakage of hemorrhage was obsorbed,microaneurysm disappeared or decreased, neovascularization (NV) was relieved completely or partly,nonperfusion area disappeared or narrowed, and no new NV or nonperfusion area came into being. Results After the operations, BCVA in NPDR,PPDR and early PDR groups was improved or kept still in 73(79.3%),83(76.9%)，and 146 eyes (74.5%), respectively,without any statistical difference among these three groups（P＞0.05）.BCVA in highrisk PDR group was significant lower than that in the NPDR,PPDR,and early PDR groups (P＜0.05). The positive rate of therapeutic effect on DR was 89.1%,85.2%,82.7% in NPDR,PPDR,and early PDR groups, respectively without any statistical difference among the groups(P＞0.05). The positive rate of therapeutic effect on DR in highrisk PDR group was significant lower than that in the NPDR,PPDR,and early PDR groups(P＜0.05). Conclusion The prognosis of DR at different stages after laser photocoagulation is different;timely and effective laser photocoagulation is important to prevent the development of the disease and decrease the blindness rate.
ObjectiveTo observe the different effect of 23G vitrectomy surgery assisted with intravitreal injection of ranibizumab and pan-retina photocoagulation in severe proliferative diabetic retinopathy (PDR) treatment. MethodsA total of 60 patients (78 eyes) with severe PDR diagnosed were enrolled and divided into intravitreal injection of Lucentis group (Group A, 22 patients, 28 eyes), pan-retina photocoagulation group (Group B, 18 patients, 20 eyes) and control group (Group C, 20 patients, 30 eyes), all of them received 23G vitreoretinal surgery. The average operation time, iatrogenic hiatus, the use of filler and electric coagulation, postoperative bleeding and best corrected visual acuity in three months were comparatively analyzed among the three groups. ResultsThe operation time in the three group was (67.429±11.243), (77.762±10.435), (106.839±20.724) min respectively, the differences of A vs C and B vs C were statistically significant(t=8.940, 5.928; P < 0.05). Five eyes needed electric coagulation in Group A, 6 eyes in Group B, and 24 eyes in Group C, the differences of A vs C and B vs C were all statistically significant (χ2=19.955, 10.505;P < 0.05). Four eyes used the filler in Group A, 3 eyes in Group B, and 23 eyes in Group C, the differences of A vs C and B vs C were all statistically significant (χ2=18.099, 14.083;P < 0.05). The difference of iatrogenic hiatus and postoperative bleeding was no significance among the three groups (P > 0.05). The best corrected visual acuity of 3 months after surgery in the three group is (0.383±0.122), (0.251±0.067), (0.104±0.044) respectively, the differences of A vs C and B vs C were all statistically significant(t=11.909, 13.616;P < 0.05). ConclusionThe intravitreaI injection of ranibizumab or pan-retina photocoagulation treatment before the vitrectomy surgery is very effective, both of them can shorten the operation time, reduce electric coagulation and use of filler, and improve patients' eyesight.
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 efficacy of intravitreal injection of ranibizumab (IVR) for different patterns of optical coherence tomography (OCT) of diabetic macular edema and the relationship between integrity of ellipsoidal zone and visual acuity outcomes. Methods Eighty-five IVR treated eyes were enrolled. The examination of BCVA was according to Early Treatment Diabetic Retinopathy Study, and the results were recorded as logarithm of the minimum angle of resolution (logMAR). Frequency-domain OCT was used to measure the central foveal thickness (CFT) and the integrity of ellipsoidal zone. All eyes were classified as diffuse macular edema (DRT group, 31 eyes), cystoid macular edema (CME group, 29 eyes), and serous retinal detachment (SRD group, 25 eyes). All the patients were treated with intravitreal injection of 0.05 ml (0.5 mg) ranibizumab. The mean follow-up time was (9.21+3.56) months after IVR treatment. The changes of BCVA and CFT in 3 groups were compared and analyzed after 3, 6 and 12 months. According to visual acuity at different ranges, the relationship between integrity of ellipsoidal zone and BCVA was analyzed. Results Compared with the average logMAR BCVA before treatment, except for 12 months after treatment in group SRD (t=2.104,P=0.053), the average logMAR BCVA after IVR at 3 months, 6 months and 12 months improved in DRT group (t=7.847, 6.771, 6.426;P=0.000, 0.000, 0.000), CME group (t=8.560, 6.680, 5.082;P=0.000, 0.000, 0.000) and SRD group (t=5.161, 3.968, 2.104;P=0.000, 0.001, 0.053). The average logMAR BCVA of the DRT group was lesser than that in CME and SRD group after 12 months treatment (t=–2.043, –3.434;P=0.030, 0.001). The average CFT after IVR at 3 months, 6 months and 12 months reduced significantly in DRT group (t=12.746, 10.687, 9.425;P=0.000, 0.000, 0.000), CME group (t=13.400, 11.460, 10.169;P=0.000, 0.000, 0.000), and SRD group (t=11.755, 10.100, 9.173;P=0.000, 0.000, 0.000). After 12 months of treatment, the average CFT of the SRD group was thicker than that in DRT group and CME group (t=–3.251, –1.227;P=0.003, 0.025); there was significant difference in the integrity of ellipsoidal zone among 3 groups (χ2=1.267,P=0.531). The results showed that there were significant differences in the integrity of ellipsoidal zone with different ranges of BCVA before and after 12 months treatment (χ2=20.145, 41.035;P=0.000, 0.000). Conclusions IVR could significantly improve the visual acuity of different patterns of DME, reduced the CFT, and had the best efficacy in the DRT group. There was relationship between the integrity of ellipsoidal zone and the visual acuity outcomes.
ObjectiveTo observe the influence of human umbilical cord mesenchymal stem cells (hUCMSC) transplantation into vitreous cavity of diabetic rats on the retinal morphology, and the expression of glial fibrillary acidic protein (GFAP) and rhodopsin (RHO). Methods78 male Sprague-Dawley rats were used. 70 rats were injected with streptozotocin by tail vein injection at a dose of 40 mg/kg to establish the diabetes mellitus model, and another 8 rats were injected with 0.1 mol/L pH 4.0 citric acid buffer at the same dose as the normal control group. After 6 weeks of modeling, 10 rats were taken as the control group of diabetic model. hUCMSC suspension was injected into the right eye vitreous cavity of the remaining 60 rats, and the same volume of Dulbecco's modified Eagle/F12 medium was injected into the left vitreous cavity as control eyes. 1, 2 and 4 weeks after transplantation, follow-up experiments were performed. The experimental eyes were labeled as U1, U2, and U4 groups, while the control eyes were recorded as D1, D2, D4, and each group consisted of 20 eyes. After paraffin section and hematoxylin-eosin staining, the structure of the retina was observed by optical microscopy and the thickness of the outer nuclear layer and the inner nuclear layer (INL) were measured. The distribution and migration of hUCMSC in rat retina were observed by frozen section-tissue immunofluorescence assay. The mRNA and protein expression of GFAP and RHO in the retina were detected by real-time quantitative polymerase chain reaction (PCR) and Western blot assays. ResultsThe results of optical microscope observation showed the normal structure of retina in normal control group. The retinal nerve fiber layer (NFL) was thinned and the number of retinal ganglion cells (RGC) in the control group of diabetic rats was decreased. The decreased number and disorder arrangement of RGC were observed as well in U1, D1 rats. The RGC number of U2, U4, D2, D4 rats was gradually decreased. Compared with D4 group, the thickness of INL in U4 group was significantly increased (P < 0.05). Tissue immunofluorescence assay showed that hUCMSC were distributed along the inner limiting membrane in the retina of the U1 group, while the number of hUCMSC in the U2 group was gradually decreased, mainly in the NFL and ganglion cell layers. Real-time PCR and Western blot data indicated that the relative expression of GFAP mRNA and protein in the diabetic retina was significantly increased, and the relative expression of RHO mRNA and protein decreased gradually in the diabetic model group and the D1, D2, D4 groups. Compared with D2 and D4 groups, the mRNA and protein expression of GFAP in U2 and U4 groups were decreased, and the relative expression of RHO mRNA and protein were all increased (P < 0.01). ConclusionhUCMSC could migrate and integrate into the retina, after the transplantation into the vitreous cavity of diabetic rats, which reduced the expression of GFAP, but enhanced the expression of RHO.
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.