The progress of the gene editing therapy of inherited retinal diseases based on CRISPR/Cas9 / 中华眼底病杂志

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.

Analysis of ocular clinical features and gene mutations of Waardenburg syndrome / 中华眼底病杂志

Objective:To deeply explore the clinical features and gene mutations of Waardenburg syndrome (WS) by tested of the eyes and genes of three patients.Methods:A 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.Results:All 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. Conclusions:The 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.

Applying optical coherence tomography and optical coherence tomography angiography to improve the diagnosis and treatment of neuro-ophthalmic diseases / 中华眼底病杂志

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.

The status and progress of morning glory syndrome / 中华眼底病杂志

Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.

The status and progress of morning glory syndrome / 中华眼底病杂志

Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.