The mineralocorticoid receptor (MR) belongs to the nuclear receptor superfamily and is expressed in the retina and choroid. MR antagonist (MRA) has a long history of application in non-ophthalmic clinical practice. Various cellular and animal models indicated that inappropriate activation of MR participated in pathological angiogenesis, oxidative stress, inflammation, disturbance of ion/water homeostasis and neurodegenerative changes, while the application of MRA can reduce or reverse these pathological processes. After using MRA in central serous chorioretinopathy (CSC) patients, improved visual function, less subretinal fluid and reduced sub-foveal choroidal thickness were observed. Single nucleotide polymorphisms in MR and plasma aldosterone levels were significantly different between chronic CSC patients and CSC patients with spontaneous remission. Novel formulation for sustained-release MRA and the mechanisms involving inflammation may become the new focus of MR study. This review summarizes the research status of MR and MRA in order to provide a reference for future basic research and clinical treatment.
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.
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）
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 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.
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.
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.
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.
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.
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.