Retinopathy of prematurity, familial exudative vitreoretinopathy and Coats disease are the most common neonates and infants retinal vascular diseases, which may lead to severe visual damage because of either tractional retinal detachment caused by the proliferation of pathogenic neovascularization, or exudative retinal detachment due to the extremely leakage from abnormal retinal vessels. Classic treatment is retinal laser photocoagulation which could destroy these abnormal vessels or reduce non vascular areas to diminish the growth of new vessels, however the side effects induced by laser it self such as visual field damage, hemorrhage, retinal tear, fail to control the progression of the disease make the laser treatment hard to improve the vision of these young patients. Anti-vascular endothelial growth factor (VEGF) agents have been widely applied in various adult retinal and choroidal vascular diseases, they are even possible to replace the pan retinal photocoagulation in proliferative diabetic retinopathy, while there are still many unsolved problems in the applying in neonates and infants retinal vascular diseases, like dosage, timing, retreatment and systemic side effects. We should realize the importance of selecting the laser photocoagulation and anti-VEGF for neonates and infants retinal vascular diseases.
Familial exudative vitreoretinopathy (FEVR) is a serious hereditary retinal vascular disease. The clinical manifestations vary, and the severity of the patients' condition is different. In severe cases, it may lead to bilateral blindness. The pathogenic mechanism of FEVR is also complex. At present, more than ten classical and candidate pathogenic genes have been found: NDP, FZD4, LRP5, TSPAN12, CTNNB1, KIF11, ZNF408, RCBTB1, LRP6, CTNNA1, CTNND1, JAG1, ATOH7, DLG1, DOCK6, ARHGP31 and EVR3 region. These pathogenic genes are involved in Wnt/β-catenin signaling pathway, norrin/β-catenin pathway and Notch pathway. They regulate and affect the development of retinal blood vessels, hyaloid vascular system regression, endothelial cell connections, and blood retinal barrier homeostasis, ultimately leading to the occurrence and development of FEVR disease.
With the development of ophthalmic optical coherence tomography (OCT) and OCT angiography (OCTA), including the improving of light source, resolution, scanning depth and upgrade of analysis softwares, they can more accurately display the structure of retinal layers and give accurate quantitative measurement. In neuro-ophthalmic diseases, the OCT indicators (the thickness of retinal nerve fiber layer around optic disc and plexus layer in macular gangle cells) and OCTA indicators (the blood flow density of capillaries around optic disc, superficial and deep capillaries in macular area, and the area of foveal avascualr zone) had special changes. It has important value in the differential diagnosis of central nervous system diseases and retinal diseases with visual dysfunction as the first symptom, the diagnosis and differential diagnosis of neuro-ophthalmic disease, the evaluation of progression of neurodegenerative diseases. Neuro-ophthamologists should pay more attention to the exploration and application of OCT and OCTA in the field of neuro-ophthalmology.
ObjectiveTo deeply explore the clinical features and gene mutations of Waardenburg syndrome (WS) by tested of the eyes and genes of three patients. MethodsA Case series study. From 2019 to 2021, 3 children with WS who were diagnosed at Department of Ophthalmology, West China Hospital of Sichuan University were included in the study. Among them, there were 2 males and 1 female; the ages were 3, 4, and 12 months, respectively. All children underwent external eye, anterior segment, fundus and fluorescein fundus angiography, the clinical features of the eyes were observed. The peripheral venous blood of 3 children was collected, and the whole genome DNA was extracted for whole exome sequencing to analyze the gene mutation sites. ResultsAll children had different degrees of iris heterochromia and fundus pigment abnormalities, and were accompanied by sensorineural hearing impairment. Case 1 had dystopia canthorum; case 2 had macular fovea hypoplasia. The sequencing results of case 1 showed that there were large fragments of heterozygous deletion in exons 2-8 of the Paired box 3 (PAX3) gene, who was diagnosed as WS Ⅰ type. The sequencing results of of case 2 showed heterozygous mutation in exon 9 of Microphthalmia-associated transcription factor (MITF) gene (c.1066 C＞T), combined with heterozygous mutation in exon 1 of HPS6 gene (c.1417 G＞T), who was diagnosed as WS Ⅱ type. The sequencing result of case 3 showed that the exon 3 of SOX10 gene had loss of heterozygosity (c.497_500 delAAGA), who was diagnosed as WS Ⅳ type. Both PAX3 and SOX10 gene mutations were newly discovered mutations. ConclusionsThe ocular clinical features of Waardenburg syndrome include hypopigmentation of the iris and choroid, and dystopia canthorum, etc. Early screening of the eye and hearing will help to better diagnose the disease. The large fragments of heterozygous deletion in exons 2-8 of the PAX3 gene, the heterozygous mutation in exon 9 of MITF gene (c.1066 C＞T), and the loss of heterozygosity in exon 3 of SOX10 gene are pathogenic genetic variations of 3 children.
With the rapid development of fundus imaging technology, it is of great significance to establish a new naming system for neovascular age-related macular degeneration (nAMD) based on the multi-mode imaging. In 2020, an international panel of retina specialists, imaging and image reading center experts, and ocular pathologists reached a consensus after repeated discussions, a new name for nAMD subtype and related lesions was established based on the previous knowledge of fundus fluorescein angiography and pathology, combining indocyanine green angiography, optical coherence tomography and optical coherence tomography angiography with current pathological knowledge, in order to help ophthalmologists to study nAMD. The consensus proposed the term "macular neovascularization" and classified it into type 1, type 2 and type 3. Many lesions related to macular neovascularization, such as pigment epithelial detachment, hemorrhage, fibrosis, rip of retinal pigment epithelium and so on, were named. The new designation will help improve clinical communication between different studies, establish standard definitions and terms between reading centers and researchers, and further promote the understanding and communication of nAMD among ophthalmologists.
Diabetic retinopathy (DR) is one of the most common and serious complication of diabetes mellitus, which is the main cause of vision loss in adults. Biological clock genes produce circadian rhythms and control its operation, while the disorder of the expression causes the occurrence and development of a series of diseases. It has been demonstrated that biological clock genes might take effects in the development and progression of DR. On the one hand, circadian rhythm disorder-related behavior disrupts the circadian oscillation of clock genes, and the change in its expression level is prone to unbalanced regulation of glucose metabolism, ultimately increasing the risk of type 2 diabetes mellitus and DR pathogenesis. On the other hand, DR patients exhibit symptoms of circadian rhythm disorders, and it has been suggested that the clock genes may control the development and progression of DR by affecting a variety of retinal pathophysiological processes. Therefore, maintaining normal circadian rhythm can be used as a disease prevention strategy, and studying the molecular mechanism of clock genes in DR can provide new ideas for more comprehensive elaboration of the pathogenesis of DR and search for new therapeutic targets.
Inherited retinal diseases (IRDs) are the major cause of refractory blinding eye diseases, and gene replacement therapy has already made preliminary progress in the treatment of IRDs. For IRDs that cannot be treated by gene replacement therapy, gene editing provides an alternative therapeutic method. Strategies like disruption of pathogenic variants with or without gene augmentation therapy and precise repair of pathogenic variants can be applied for IRDs with various inheritance patterns and pathogenic variants. In animal models of retinitis pigmentosa, Usher syndrome, Leber congenital amaurosis, cone rod cell dystrophy, and other disorders, CRISPR/Cas9, base editing, and prime editing showed the potential to edit pathogenic variations in vivo, indicating a promising future for gene editing therapy of IRDs.
Gene therapy is designed to introduce genetic material into the cells of a patient via virus to enhance, inhibit, edit or add a genetic sequence, results in a therapeutic or prophylactic effect. Gene therapy has brought positive influence and great potential for the treatment of retinal diseases including genetic retinal diseases and acquired retinal diseases. In addition to the constant optimization of gene vectors, the exploration of different drug delivery techniques has brought different therapeutic effects for gene therapy of retinal diseases. The main delivery methods include subretinal injection, intravitreal injection, suprachoroidal injection. Considering the transfection efficiency and safety of delivery methods, emerging sub-inner limiting membrane injection and noninvasive gene delivery are under investigation. The selection of gene delivery method is very important for the safety and effectiveness of gene therapy for retinal diseases. It is not only related to the development of equipment and technology, but also related to the modification of adeno-associated virus, the selection of promoter and the specific retinal cells that the target gene wants to be transfected. Therefore, the most appropriate method of gene delivery should be selected according to the final gene therapy agent and the specific transfected cells after taking all these factors into consideration.
ObjectiveTo explore the necessity, construction plans, and implementation methods for the establishment of a fundus disease-specific biobank are discussed. MethodsAn evidence-based medicine study. “Biobank”, “Disease-specific biobank”, “Eye diseases”, “Fundus disease” were hereby used as search terms. Literatures were retrieved related to biobank construction from PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases since their establishment until October 2023. Two researchers independently selected and analyzed literature, extracting data for further analysis. ResultsAfter screening, 23 articles were included, comprising 11 articles in Chinese and 12 articles in English, involving 23 institutions. The disease-specific biobank has been built earlier abroad than domestically. Both domestic and foreign biobank have a scale of less than 1, 1 to 10, and more than 10 thousand samples, with the eye disease-specific biobank having less than 10 thousand samples. The majority of these disease-specific biobank focued on tumor-related diseases and consist of both physical and information components. Ethical committees were required to declare and record the construction of biobank, and dedicated personnel and information management systems are established. Quality control systems have been developed with standard operating procedures from sample collection to storage. These disease-specific biobank effectively supported research projects, but there was a lack of resource sharing domestically compared to abroad. Based on practical experience, the construction of fundus disease-specific biobank at West China Hospital of Sichuan University has been improved. Separate sample collection processes have been formulated for outpatient clinics and operating rooms. Standard operating procedures have been established for unique eye samples, including vitreous fluid, proliferative membranes of the retina, aqueous humor, tears, etc., to ensure sample quality. ConclusionEstablishing a fundus disease-specific biobank can promote basic and clinical research, advance the development of translational medicine, achieve resource sharing, and foster discipline development.
ObjectiveTo observe the retinal reattachment of suprachoroidal injection with sodium hyaluronate in the treatment of rhegmatogenous retinal detachment (RRD).MethodsTwelve eyes of 12 patients with RRD diagnosed by the examinations of B-mode ultrasound, binocular indirect ophthalmoscope, OCT and scanning laser ophthalmoscope in West China Hospital of Sichuan University from October 2018 to February 2019 were included in this study. There were 7 males and 5 females, aged from 15 to 66 years, with the mean age of 32.40±14.81 years. There were 4 eyes with BCVA＜0.1, 4 eyes with BCVA 0.1-0.4, 4 eyes with BCVA＞0.4. The extent of retinal detachment involves 1 to 4 quadrants. All eyes were injected with sodium hyaluronate via suprachoroidal space under non-contact wide-angle system. Surgery was performed by the same ophthalmologist with extensive surgical experience. During the operation, the retinal hole was handled with scleral freezing and laser photocoagulation. The follow-up was 2 months. The retinal reattachment was observed.ResultsOf the 12 eyes, 6 eyes (50.00%) were anatomically reattached, 4 eyes (33.33%) ere partly anatomically reattached with subretinal fluid, 2 eyes (16.67%) were not reattached. The holes in 4 eyes of partly anatomically reattached with subretinal fluid were located on the choroidal pad and the holes were closed, in addition, the subretinal fluid gradually absorbed over time. Two eyes failed in retinal reattachment received vitrectomy with silicone oil tamponade or sclera buckling surgery. No severe complications such as endophthalmitis and choroidal hemorrhage were found at follow-up visits.ConclusionSuprachoroidal injection of sodium hyaluronate is an effective and safe treatment for RRD, which can promote retinal reattachment.