To observe the efficacy of intravitreal injection of conbercept (IVC) combined with panretinal laser photocoagulation (PRP) in the treatment of diabetic retinopathy (DR) combined with stage I and II neovascular glaucoma (NVG).MethodsA clinical case-control study. From October 2013 to March 2019, 50 eyes (50 patients) with DR and stage Ⅰ to Ⅱ NVG diagnosed in the Department of Ophthalmology, Peoples's Hospital of Xianghe were were included in the study. There were 27 eyes (27 males) and 23 eyes (23 females); all patients were monocular with the average age of 53.5±7.13 years old. Stage Ⅰ and Ⅱ NVG were 11 and 39 eyes, respectively. All patients underwent BCVA, intraocular pressure, and fundus angiography. The BCVA examination adopted the international standard visual acuity chart, which was converted to logMAR BCVA visual acuity in statistics. The patients were divided into the Conbercept+laser therapy (combination therapy) group and the laser therapy group by random number table, with 25 eyes. The age of the two groups of patients (t=0.058), gender composition ratio (χ2=0.081), logMAR BCVA (t=0.294), intraocular pressure (t=－0.070), the number of eyes with different grades of angle and iris neovascularization（χ2=1.683, 0.854）were compared, the difference was not statistically significant (P＞0.05). The changes of BCVA, intraocular pressure, iris neovascularization, and angular neovascularization were compared and observed between the two groups one week after the completion of PRP treatment, 1, 3, 6, and 9 months. Independent sample t test was used for continuous variables. Between the combination treatment group and the laser treatment group, at different time points within the two groups and the interaction of the two factors, a single-factor repeated analysis of variance was used.ResultsCompared with the results before treatment, the combined treatment group and laser treatment group had statistically significant differences in the number of angle and iris neovascularization, intraocular pressure and logMAR BCVA at different times after treatment in the combined treatment group and laser treatment group (F=124.211, 65.153, 69.249, 26.848; P＜0.001). After treatment, the combined treatment group was better than the laser treatment group in terms of the regression of eye angle and iris neovascularization, intraocular pressure and logMAR BCVA, and the difference was statistically significant (F=47.543, 25.051, 12.265, 9.994; P=0.001, 0.001, 0.001, 0.003). At different times after treatment, compared with the laser treatment group, the number of neovascularization in the iris and angle of the eye in the combined treatment group was less, the intraocular pressure was significantly decreased, and the BCVA was increased. The difference was statistically significant (P＜0.05).ConclusionThe efficacy of Kang IVC combined with PRP in the treatment of DR with stage Ⅰ and Ⅱ NVG is better than that of PRP alone.
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.
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）
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.
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
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 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.
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.
ObjectivesTo evaluate the effect of peeling of internal limiting membrane (ILM) on the postoperative visual acuity in patients with diabetic macular edema, and to detect the role indocyanine green (ICG) plays in the surgery of peeling of ILM. MethodsThirty patients (31 eyes) with diabetic retinopathy at proliferative stage with macular edema underwent vitrectomy. The patients were randomly divided into two groups: 16 eyes in group A underwent single vitrectomy with panretinal photocoagulation and ocular filling with 20% SF6; 15 eyes in group B underwent vitrectomy and peeling of ILM after the posterior pole was stained with ICG. All of the patients were asked to keep the posture of facing down for 10-14 days. The follow-up lasted 3-12 months.ResultsIn 16 eyes in group A, the visual acuity increase of 2 or more lines in 10 (62.5%) and alleviation of macular edema in 9 (56.2%) were found; the postoperative average macular retinal thickness examined by optic coherence tomography (OCT) was 393 μm. In 15 eyes in group B, the visual acuity increase of 2 or more lines in 14 (93.3%) and alleviation of macular edema in 14 (93.3%) were found; the postoperative average macular retinal thickness was 319 μm. The postoperative improvement of visual acuity in group B was much better than that in group A (X2=4.210, P=0.05), while the postoperative macular retinal thickness in group B was obviously lower than that in group A (P＜0.01). The operative sample was proved to be the ILM.
ConclusionsVitrectomy is effective for diabetic macular edema and the curative effect may be improved by peeling of ILM; ICG can dye ILM well, which ensures the safe and accurate peeling of ILM.(Chin J Ocul Fundus Dis, 2005,21:138-141)
