Our previous experiments showed limited results of treatment with daunomycin when given at the inflammatory stage of proliferative vitreoretinopathy(PVR)induced by macrophages in rabbits.In the present study,we observed the inhibition of intraocular cellular proliferation in the same model by daunomycin which was injected in a dosage of 5mu;g 6 days after intravitreal macrophage injection,with 3H-thymidine autoradiography.The efficacy of daunomycin was also compared with that of triamcinolone,and combined triamcinlone and daunomycin.The retinal detachment occurred in 33.3%,16.1%,8.3%and 83.3%(P＜0.01) of the eyes treated with daunomycin,triamcinolone,combined drugs and the control groups,respectively.Autoradiography revealed a singnificantly decreased number of labelled nuclei of proliferative cells on days 7 and 14 in daunomycin-treated eyes(compared to controls,18.8plusmn;3.2 vs 35.7plusmn;3.4;52.1plusmn;8.0 vs 81.3plusmn;14.6，P＜0.01,respectively).Significantly decreased numbers of inflammatory cells and labelled cells were also noted in eyes treated with triamcinolone and combined drugs.The results suggest that daunomycin given at the proliferative stage,and triamcionlone given at the inflammatory stage of PVR,or combined drugs can prevent traction retinal detachment. （Chin J Ocul Fundus Dis,1994,10:229-231）
The stimulating effects of subretinal fluid (SRF) of 31 patients with rhegnmtoganous retinal detachment (among them 5 are recurrent) on the growth of fihroblasts were investigated. The results demonstrated that all samples of SRF showed stimulating effect in a variable degree.The range of proliferation-stimulating activity was from 86. 7% to 366.7% above the baseline.The stimulating ahility was mainly related to the degree of PVR and may be also related to the extent and clinical course of the detaehrnent. When stimulating rate was S0Y0 ,the dilution multiple of SRF was higher in recurrent patients than that in initiate ( P＜0.01). （Chin J Ocul Fundus Dis,1993,9:11-13）
ObjectiveTo observe and analyze the genotype and clinical phenotype in 34 families of familial exudative vitreoretinopathy associated with (FEVR) gene variation.MethodsCohort study. Thirty-four FEVR families, in which the patients and both of their parents were all found to have FEVR-related gene mutations (proband 34 cases, 67 eyes; parents 68 cases, 136 eyes), were included in the study. These patients were identifIed from 722 FEVR patients through genetic screening, which diagnosed in Department of Ophtalmology of Xinhua Hospital and Tianjin Medical University Eye Hospital from January 2010 to December 2018. The probands and their parents underwent a comprehensive ophthalmological examination appropriate to their age, including BCVA, intraocular pressure, axial length, slit lamp examination, indirect ophthalmoscopy, FFA or color fundus photography or wide field color fundus photography. According to the severity of the disease, the clinical manifestations were divided into severe phenotype and mild phenotype. Thirty-four normal healthy people over 40 years old were included as the control group. The peripheral blood samples of FEVR family members and control group members were collected, and the genes known to be involved in FEVR, such as FZD4, LRP5, NDP, TSPAN12, ZNF408 and KIF11, were analyzed by next generation sequencing molecular genetics. The data were statistically analyzed by SPSS. The counting data was expressed in numbers or rates, and tested by Kruskal-Wallis test and χ2 test to find out the existence of significant difference.ResultsIn 67 eyes of the 34 probands, 48 eyes (71.64%) were classified into severe phenotype and 19 eyes (28.36%) were mild phenotype. In 136 eyes of 68 parents of the proband patients, 76 eyes (55.88%) were normal, 60 eyes (44.12%) were classified into mild phenotype, and no severe phenotype was found. A total of 65 variants of FEVR-related genes were detected in the 34 probands, of which LRP5 mutation was the most common (64.61%), followed by FZD4 (12.31%), NDP (10.77%), TSPAN12 (6.15%), ZNF408 (4.62%) and KIF11 (1.54%). Missense mutations were the most common variant in FEVR-related genes. However, the results of correlation analysis indicated that there was no significant correlation between the type of mutation and the severity of clinical phenotype (H=1.775, P=0.620). Among the 65 mutation types, 21 types have been previously identified and 44 were novel in this study. Thirty-nine eyes of 20 cases had only one single pathogenic mutation gene but with multiple mutation sites, 26 eyes of 13 cases carried 2 relevant pathogenic mutation genes, and 2 eyes in one case had 3 pathogenic mutation genes. The mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in probands were significantly higher than those in control group, and the difference was statistically significant. The total mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in proband group were significantly higher than those in control group (χ2=64.702, P＜0.001).ConclusionsIn the FEVR families, the most frequent mutations were those in LRP5, followed by FZD4, NDP, TSPAN12,ZNF408 and KIF11. Missense mutation is the most common type of FEVR-related gene mutation, but there is no significant correlation between the clinical phenotype and gene variation type. Most of the probands were with severe clinical phenotype, while most of the parents with FEVR pathogenic gene mutation showed normal or mild manifestations.
Objective To evaluate the anatomical and functional results of retinotomy in treatment of complicated retinal detachment. Methods Twenty-three eyes were treated with retinectomy during vitrectomy for complicated retinal detachment with proliferative vitreoretinopathy when complete reattachment of retina was not obtained despite careful mambrane peeling. After released the peripheral vitreoretinal contraction or pulled subretinal membranes, perfluorocarbon liquid injection, laser retinopexy and silicone oil tamponade were performed. Retinotomy size ranged from 30-degree to 360-degree (average 132-degree). Results Retinal attachment were obtained in all of the operated eyes at the end of the operation. Silicone oil was removed from 15 eyes (65．0%) within 3～11 months postoperatively. After a minimum follow-up of 6 months, the retinae were completely attached in 17 eyes ( silicone oil was not removed in 4 eyes ) and visual acuity of 0.02 or better was obtained in 11 eye (48．0%). Recurrent retinal detachment occurred in 2 eyes in which the silicone oil had been removed. The major complications were recurrence of the proliferation in 6 eyes (26．0%) and hypotony in 3 eyes (13．0%). Conclusion Retinotomy is beneficial to reattach the retina for eyes with advanced proliferative vitreoretinopathy in seemin gly inoperable cases. (Chin J Ocul Fundus Dis,2001,17:87-89)
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
ObjectiveTo investigate the etiology, clinical features and treatment of familial exudative vitreoretinopathy (FEVR) secondary glaucoma. MethodsA retrospective clinical study. From January 1, 2016 to January 1, 2022, 15 patients (17 eyes) were diagnosed with FEVR secondary glaucoma in Beijing Tongren Hospital, Capital Medical University were included in the study. All patients underwent systematic ophthalmological evaluation. According to the patient's age, visual acuity, intraocular pressure, anterior segment, vitreous body and retina condition, the choice of translimbal lensectomy combined with vitrectomy, goniectomy, cyclophotocoagulation, intravitreal injection of anti-vascular endothelial growth factor (VEGF) treatment were chosen. The follow-up time was 3 to 37 months. The clinical characteristics of the affected eye, and the changes of intraocular pressure, anterior chamber depth and complications after surgery were observed. ResultsAmong the 15 patients, there were 11 males with 13 eyes, and 4 females with 4 eyes. Age was 6.14±7.37 years old. FEVR stages 2B, 3B, 4A, 4B, 5A, and 5B were 1, 1, 5, 6, 3, and 1 eye, respectively. The intraocular pressure of the affected eye was 42.74±9.06 mm Hg (1 mm Hg=0.133 kPa). All eyes had shallow anterior chamber and angle closure, anterior or posterior iris adhesions, lens opacity, retinal detachment, iris neovascularization in 4 eyes, and vitreous hemorrhage in 2 eyes. Sixteen eyes were treated with translimbal lensectomy combined with vitrectomy and goniotomy, of which 8 eyes were treated with anti-VEGF treatment; 1 eye was treated with cyclophotocoagulation combined with anti-VEGF treatment. After operation, the intraocular pressure of 16 eyes returned to normal range, and the depth of anterior chamber of 16 eyes returned to normal, and no obvious complications occurred. ConclusionsThe main etiology of secondary glaucoma in FEVR is the structural and functional abnormalities of the anterior chamber and angle, which are found in the 2B and above stages of FEVR. The lensectomy and vitrectomy via limbal approach can effectively control the intraocular pressure and restore the anterior chamber, with no serious complications.
Objective To compared the changes of macular microvascular architecture in early stage familial exudative vitreoretinopathy (FEVR) patients with inner retinal layer (IRL) persistence and without IRL persistence. MethodsA retrospective clinical study. From 2017 to 2022, 94 patients with stage 1 FEVR with or without IRL residue and 45 age- and sex-matched healthy volunteers with 45 eyes (normal control group) who were confirmed by ophthalmology examination in Hangzhou Hospital of Optometry Affiliated to Wenzhou Medical University and Zhejiang Provincial People's Hospital were included in the study. According to whether there was IRL residue, the patients were divided into IRL group and non-IRL group, with 22 patients (22 eyes) and 72 patients (72 eyes), respectively. Best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) were performed in all eyes. Superficial vessel density (SCP) and deep vessel density (DCP) of whole image, fovea and parafovea, the area and perimeter of fovea avascular area (FAZ), A-circularity index (AI, perimeter/standard circle perimeter with equal area) and vessel density around the 300 μm width of the FAZ (FD), central macular thickness (CMT) on macular 3 mm × 3 mm scan on OCTA were measured. ResultsSCP and DCP of whole image (F=10.774, 4.583) and parafovea (F=10.433, 3.912), CMT (F=171.940) in IRL group and non-IRL group on macular 3 mm × 3 mm scan on OCTA were significantly lower than that in normal persons (P＜0.05). There were significant differences among three groups of the area of FAZ (F=4.315), AI (F=3.413), FD-300 (F=13.592) (P＜0.05). BCVA were worst in IRL group (P＜0.05). ConclusionsBlood flow density decreased in macular area of FEVR patients. CMT is significantly thicker than normal population. The FAZ area of the foveal IRL residual eyes is small and irregular, with worse BCVA and lower macular blood density.