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 investigate the therapeutic effect of different wavelength krypton lasers on diabetic retinopathy. Methods A total of 55 eyes (35 cases) with diabetic retinopathy underwent different wavelength k rypton lasers photocoagulation treatment, according to the different manifestati on of the affected eyes. The visual acuity, intraocular pressure，visual field,visual evoked potential were examined, and slit-lamp, ophthalmoscopy, Bultraso nography, and fundus fluorescein angiography were performed preoperatively. The patients were followed up for at least 12 months after krypton laser treatment. Results The resulting effect on visual acuity after 12 months of photocoagulation in this series revealed that, 20 eyes (36.4%) i mproved, 34 eyes (61.8%) remained no change, and one eye (1.8%) decreased. Conclusions Different wavelength krypton lasers photoco agulation can be used in treatment of diabetic retinopathy and can improve the visual acuity at certain extent. (Chin J Ocul Fundus Dis, 2001,17:178-180)
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.
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 To evaluate the visual prognostic factors in vitreoretinal surgery for diabetic tractional retinal detachment (DTRD). Methods 102 eyes of 86 consecutive patients with DTRD underwent vitreoretinal surgery were analyzed retrospectively. All cases diagnosed via indirect ophthalmoscope and B ultrasonic scan after mydriasis. Followup duration varied from 12 to 56 months (mean: 23 months). Best corrected visual acuity (BCVA) and anatomic success were observed postoperatively. The patients were divided into visual acuity improved group and didn't improved group. Ttest, Chisquare test and Multivariate Logistic regression analysis were performed to predict the prognosis of visual acuity. Results After primary vitreoretinal surgery, 87 eyes (85.3%) were anatomically reattached, 15 eyes (14.71%) needed reoperation because of the recurrence of retinal detachment (RD). Postoperative BCVA improved and better than 0.05 in 49 eyes (48.04%), reduced or increased but less than 0.05 in 53 eyes (51.96%). Comparing natural factors between these two groups, only combined cataract surgery and optic nerve atrophy were significant different (chi;2=5.266,9.274;P=0.022,0.002). Among post-operative complications only the RD recurrence was significant different (chi;2=12.059，P=0.000). Multivariate Logistic regression revealed recurrence of RD and optic nerve atrophy were two independent risk factors in the final BCVA (P=0.003,0.041;OR=33.518、4.079). Preoperative PRP was identified as the only protecting variable in the final BCVA(P=0.034，OR=0.270).Conclusion This study revealed recurrence of RD and optic nerve atrophy were two independent risk factors in final BCVA of DTRD patients.
Objective To compare the therapeutic effects of 577 nm laser and 532 nm laser panretinal photocoagulation (PRP) in the treatment of non-proliferative diabetic retinopathy (NPDR). Methods This is a prospective controlled study. A total of 23 patients (41 eyes) with clinically diagnosed severe NPDR were randomly divided into two groups including 577 nm group (11 patients, 20 eyes) and the 532 nm group (12 patients, 21 eyes). 577 nm group and 532 nm group received 3 - 4 times PRP with single-point mode. The laser energy and the number of laser spots were compared, and the laser energy density was calculated. Before treatment and 1 day, 1, 3, 6 and 12 months after treatment, the changes of best corrected visual acuity (BCVA), average threshold sensitivity, a/b-wave amplitude of flash ERG (F-ERG) in the 30° - 60° visual field, and fundus fluorescein angiography (FFA) were compared between two groups. Results The response rate was 85.0% and 23.8%, respectively in the 577 nm and 532 nm group, the difference was statistically significant (χ2=15.43，P < 0.05).Compare to the pre-treatment measurement, the average threshold sensitivity, a/b wave amplitude of F-ERG and the 30° - 60°visual field were reduced at 1 day after treatment both in the 577 nm and 532 nm group, the difference were statistically significant (F=8.68, 7.57, 4.52; P < 0.05). The average threshold sensitivity (t=2.41, 3.48, 1.23), a/b wave amplitude (a wave: t=5.82, 4.45, 7.83；b wave: t=5.40, 3.23, 4.67) of F-ERG were different between 577 nm and 532 nm group at 3 , 6 and 12 months after treatment (P < 0.05). There was no retinal neovascularization and non-perfusion region in two groups at 6 months after treatment. The average laser power were (436.25±54.65) and (446.43±35.61) mW, number of laser spots were (1952.95±299.09) and (2119.05±302.69) spots, energy density were (7.60±1.30) and (7.60±3.00) mW×ms/μm2 in the 577 nm group and 532 nm group, respectively. There was no difference in average laser power (t=1.35), number of laser spots (t=2.85) and energy density (t=1.99) between two groups (P > 0.05). Conclusion Compared with the 532 nm laser, 577 nm laser treatment has better visual outcomes for NPDR patients.
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.
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.
ObjectiveTo observe the concentration of the inflammatory cytokines in vitreous of severe proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab injection (IVR). MethodsA total of 80 PDR patients (80 eyes) were enrolled in this study. The patients were randomly divided into vitrectomy group (group A) and IVR combined with vitrectomy group (group B), 40 eyes in each group. The differences of sex (χ2=0.05), age (t=0.59), duration of diabetes (t=0.36), HbA1c (t=0.13) and intraocular pressure (F=0.81) between two groups were not significant (P>0.05). The eyes in group B received 0.5 mg (0.05 ml) ranibizumab injection at 7 days before operation. The vitreous samples (0.4 ml) were obtained before operation. The concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF) were measured by enzyme-linked immunosorbent assays. ResultsThe concentration of VEGF and ICAM-1 were (10.70±3.60), (224.64±90.32) pg/L in group B and (72.38±23.59), (665.61±203.34) pg/L in group A. The differences of VEGF and ICAM-1 concentration between two groups was significant (t=16.34, 12.53; P<0.001). The concentration of IL-6 and IL-8 were (210.64±80.27), (156.00±57.74) pg/L in group B and (45.78±33.82), (41.07±13.82) pg/L in group A. The differences of IL-6 and IL-8 concentration between two groups was significant (t=11.97, 12.24; P<0.001). There was no difference of CTGF concentration between two groups (t=1.39, P=0.17). The CTGF/VEGF in group B was higher than that in group A (t=14.75, P<0.001). ConclusionsOne week after IVR, the concentration of VEGF and ICAM-1 are decreased, while IL-6 and IL-8 increased. There is no obvious change in CTGF, but CTGF/VEGF is increased.
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.