Laser photocoagulation, intravitreal injection of antibody against vascular endothelial growth factor (VEGF) or corticosteroids and pars plana vitrectomy are current popular therapeutic approaches for diabetic retinopathy (DR). However, some DR patients still progress to irreversible blindness even after the above treatments which do not aim at the pathological mechanisms and influence factors for DR. Thus, with the further elucidation on the molecular pathological mechanisms and overall understanding of the factors affecting DR development, more and more potential therapeutic interventions such as neuron protection, vascular reconstruction and protection, gene therapy, non-VEGF dependent anti-neovascularization agents have been explored. Individual precise therapy based on the potential therapeutic targets would provide the promising future for DR patients.
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 investigate the clinical outcome and therapeutic efficacy of short-pulse pattern scan laser (PASCAL) photocoagulation for diabetic retinopathy (DR). MethodsForty-three DR patients (70 eyes) including 19 males (32 eyes) and 24 females (38 eyes) underwent short-pulse PASCAL pan-retinal photocoagulation (PRP). There were 24 patients (42 eyes) with proliferative diabetic retinopathy (PDR) and 19 patients (28 eyes) with severe non-proliferative diabetic retinopathy (NPDR). The best corrected visual acuity was better than or equal to 0.1 in 62 eyes, worse than 0.1 in 8 eyes. Diabetic macular edema was found in 18 eyes. Short-pulse PASCAL PRP was applied with multi-spot arrays. Macular edema was treated by PASCAL macular mode (MAC A + MAC B) and/or single spot. Visual acuity and fundus examinations were analyzed at the one-year follow-up procedure. ResultsOne year after short-pulse PASCAL treatment, the final visual acuity was improved in 10 eyes, stable in 53 eyes, decreased in 7 eyes; macular edema was relieved in 38 eyes, aggravated in 12 eyes, and stable in 20 eyes. Of 42 eyes with PDR, neovascularization were regressed in 20 eyes, uncontrolled in 11 eyes which experienced additional photocoagulation (1-2 times) during the follow-up. Among the 11 uncontrolled eyes, 3 eyes (3/11) received vitrectomy due to vitreous hemorrhage. ConclusionPASCAL might stabilize the progress of diabetic retinopathy safely and effectively.
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.
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.
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.
Macular edema is a common cause of visual loss in patients with retinal vascular diseases represented by diabetic retinopathy and retinal vein occlusion. Laser photocoagulation has been the main treatment for this kind of diseases for decades. With the advent of antagonist of vascular endothelial growth factor and dexamethasone implant, diabetic macular edema and macular edema secondary to retinal vein occlusion have been well controlled; the use of laser therapy is decreasing. However, considering possible risks and complications, lack of extended inspection of efficacy and safety of intravitreal pharmacotherapy, laser therapy cannot be replaced by now. Therefore, the efficacy and safety of laser therapy will improve by sober realization of role of photocoagulation and proper selection of treatment indication.
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.
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.