Objective To observe the alterations of macular vascular density and the area of foveal avascular zone (FAZ) in branch retinal vein occlusion (BRVO) eyes. Methods A retrospective case-control study. Forty-five patients with unilateral BRVO and macular edema were enrolled in this study. Optical coherence tomography angiography (OCTA) was performed on the BRVO and fellow eyes. The scanning region in the macular area was 3 mm×3 mm. Macular vascular density and FAZ area in the superficial and deep retinal capillary plexi were measured in all eyes. The values of macular vascular density and FAZ area between BRVO eyes and fellow eyes, affected sector and unaffected sector were compared. Results The mean overall vascular density measured in the entire scan was lower in BRVO eyes compared with fellow eyes in both the superficial and deep capillary plexus (t=14.186, 9.468; P＜0.05). The reduce degree of vascular density in the deep capillary plexus (7.65%) was higher than that in the superficial plexus (7.27%). In the superficial plexus, the vascular density was lower in the affected sector and the unaffected sector of the BRVO eyes compared with the corresponding sector in the fellow eyes (t=15.386, 9.435; P＜0.05). The FAZ area enlarged in the BRVO eyes compared with the fellow eyes in the superficial capillary plexus and in the deep capillary plexus (t=3.216, 5.119; P＜0.05). The degree of enlargement of FAZ area in the deep capillary plexus (0.19 mm2) was higher than that in the superficial plexus (0.11 mm2). Conclusions In eyes with BRVO, quantitative OCTA measurements confirm that vascular density decreased and FAZ area enlarged in the superficial and deep capillary plexi. The reduce degree of vascular density and enlargement degree of FAZ area in the deep capillary plexus are higher than those in the superficial plexus.
ObjectiveTo observe the macular capillary morphology in diabetic patients.MethodsA total of 61 patients (104 eyes) with diabetes mellitus (DM group) and 31 healthy controls (41 eyes) were enrolled in the study. According to the degree of diabetic retinopathy (DR), the DM group was divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. There were 13 patients (23 eyes), 21 patients (34 eyes) and 27 patients (47 eyes) in each group, respectively. According to whether there was diabetic macular edema (DME), the DM patients were divided into DME group and non-DME group, each had 20 patients (28 eyes) and 41 patients (76 eyes), respectively. The age (F=2.045) and sex (χ2=2.589) between the control group, the NDR group, the NPDR group and PDR group were not statistically significant (P=0.908, 0.374). The 3 mm × 3 mm region in macula was scanned by optical coherence tomography angiography (OCTA), and the retinal capillary morphological changes of superficial capillary layer (SCL) and deep capillary layer (DCL) were observed. Chi-square test and t test were used to compare data among different groups.ResultsThere was no abnormal change of retinal capillary morphology in control group. Microaneurysms and foveal avascular zone (FAZ) integrity erosion can be found in NDR group. There were microaneurysms, FAZ integrity erosion, vascular tortuosity bending, capillary non-perfusion and venous beading in NPDR and PDR groups. The microaneurysms of DCL were significantly more than that of the SCL (t=4.759, P＜0.001). The eyes with microaneurysms in NDR group, NPDR group, and PDR group showed significant differences (χ2=44.071, P＜0.001), and the eyes with FAZ integrity erosion among these three groups also showed significant differences (χ2=30.759, P＜0.001). Compared with NPDR group and PDR group, there were significant differences in vascular tortuosity bending and capillary non-perfusion (vascular tortuosity bending: OR=0.213, 95%CI 0.070−0.648, P=0.004; capillary non-perfusion: OR=0.073, 95%CI 0.022−0.251, P＜0.001), and there was no significant difference in venous beading (OR=0.415, 95%CI 0.143−1.208, P=0.102). SCL blood flow density in the 4 groups (control, NDR, NPDR and PDR group) was 49.233±1.694, 48.453±2.581, 45.020±4.685 and 40.667±4.516, respectively. While the difference between the control and NDR group was not significant, the differences between other pairs (control vs NPDR/PDR, NDR vs NPDR/PDR, NPDR vs PDR) were significant. The ratio of FAZ integrity erosion and non-perfusion of DME group was significantly higher than those of non-DME group (vascular tortuosity bending: OR=7.719, 95%CI 1.645−36.228, P=0.004; capillary non-perfusion: OR=14.560, 95%CI 3.134−67.646, P＜0.001).ConclusionsOCTA can distinctively detect the abnormal retinal capillary changes of SCL and DCL in diabetic patients. Even in DM patients without diabetic retinopathy, OCTA can detect abnormal blood vessels.
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.
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.