Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25/696). Among 25 KIF11 mutations, 80% (20/25) carried variants of loss of function and 48% (12/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1/70) of eyes with FEVR with mutations in other genes (p < 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12/70) of eyes with KIF11-associated retinopathy, and in 50% (39/78) of eyes with FEVR with mutations in other genes (p < 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.

Stickler syndrome is a connective tissue disorder that affects multiple systems, including the visual system. Seven genes were reported to cause Stickler syndrome in patients with different phenotypes. In this study, we aimed to evaluate the mutation features of the phenotypes of high myopia and retinal detachment. Forty-two probands diagnosed with Stickler syndrome were included. Comprehensive ocular examinations were performed. A targeted gene panel test or whole exome sequencing was used to detect the mutations, and Sanger sequencing was conducted for verification and segregation analysis. Among the 42 probands, 32 (76%) presented with high myopia and 29 (69%), with retinal detachment. Pathogenic mutations were detected in 35 (83%) probands: 27 (64%) probands had COL2A1 mutations, and eight (19%) probands had COL11A1 mutations. Truncational mutations in COL2A1 were present in 21 (78%) probands. Missense mutations in COL2A1 were present in six probands, five of which presented with retinal detachment. De novo COL2A1 mutations were detected in 10 (37%) probands, with a mean paternal childbearing age of 29.64 ± 4.97 years old. The mutation features of probands with high myopia or retinal detachment showed that the probands had a high prevalence of COL2A1 mutations, truncational mutations, and de novo mutations.

Knobloch syndrome is an inherited disorder characterized by high myopia, retinal detachment, and occipital defects. Disease-causing mutations have been identified in the COL18A1 gene. This study aimed to investigate novel variants of COL18A1 in Knobloch syndrome and describe the associated phenotypes in Chinese patients. We reported six patients with Knobloch syndrome from four unrelated families in whom we identified five novel COL18A1 mutations. Clinical examination showed that all probands presented with high myopia, chorioretinal atrophy, and macular defects; one exhibited rhegmatogenous retinal detachment in one eye. Occipital defects were detected in one patient.

Aims: To investigate the success rate of oral fluorescein angiography (oral FA) in children with ultrawide scanning laser ophthalmoscopy (SLO) system and whether it can provide images of sufficient quality compared with intravenous FA (IVFA). Methods: In this comparative case series study, a series of 40 consecutive pediatric patients of the age of 3–18 with retinal vascular diseases, in whom FA was needed for the diagnosis or treatment, were enrolled in this study. IVFA and oral FA were performed within one week and images were obtained with the SLO system. The image quality was scored blindly and compared based on: (I) visualization of the branch retinal vessel, (II) the foveal avascular zone (FAZ), and (III) clinically important findings, such as the presence of microaneurysms, neovascularization, leakage, or significant nonperfusion. All these were scored using a three-point scale. Results: In preschoolers (three to six years), all 19 children complete oral FA (100%), while only 7 (36.84%) complete IVFA (p < 0.0001). With the SLO system, the branch retinal vessels were well visualized both in oral and IV FA (all images were two scores). The visualization of FAZ was similar between oral and IV FA (p = 0.8972). The clinically important findings were well visualized in both groups (p > 0.9999). The overall image quality was similar between the two groups (p = 0.2500). Conclusion: Oral FA is more acceptable to preschoolers than IVFA owing to the needle-free procedure. With the SLO system, oral FA provided high-quality angiograms similar to IVFA. Oral FA is an effective alternative to IVFA and may be considered the first option for FA in pediatric patients, especially in preschoolers.

Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by abnormalities in the retinal vasculature. The FZD4 gene is associated with FEVR, but the prevalence and impact of FZD4 copy number variation (CNV) on FEVR patients are unknown. The aim of this study was to better understand the genetic features and clinical manifestations of patients with FZD4 CNVs. A total of 651 FEVR families were recruited. Families negative for mutations in FEVR-associated genes were selected for CNV analysis using SeqCNV. Semiquantitative multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification were conducted to verify the CNVs. Four probands were found to carry whole-gene deletions of FZD4, accounting for 5% (4/80) of probands with FZD4 mutations and 0.6% (4/651) of all FEVR probands. The four probands exhibited similar phenotypes of unilateral retinal folds. FEVR in probands with CNVs was not more severe than in probands with FZD4 missense mutations (p = 1.000). Although this is the first report of FZD4 CNVs and the associated phenotypes, the interpretation of FZD4 CNVs should be emphasized when analyzing the next-generation sequencing data of FEVR patients because of their high prevalence.

The VCAN/versican gene encodes an important component of the extracellular matrix, the chondroitin sulfate proteoglycan 2 (CSPG2/versican). Heterozygous variants targeting exon 8 of VCAN have been shown to cause Wagner disease, a rare autosomal dominant non-syndromic vitreoretinopathy that induces retinal detachment, cataracts and permanent visual loss. In this study, we report on six patients from three unrelated families with Wagner disease in whom we identified three novel copy number variations of VCAN. Quantitative real-time polymerase chain reaction analysis identified deletions, including one exon–intron boundary of exon 8 or both exons 8 and 9, causing the haploinsufficiency of VCAN mRNAs.