Ping Fei

A Genetic Variant in the SKIV2L Gene Is Significantly Associated With Age-Related Macular Degeneration in a Han Chinese Population

PURPOSE Previous studies have shown that genetic variants in the complement component 2 (C2)/complement factor B (BF) gene are associated with AMD in Caucasians, but not in Han Chinese. Recent studies have indicated that genetic variants in the neighboring superkiller viralicidic activity 2-like (SKIV2L) gene showed significant association with AMD. We conducted this study to investigate whether genetic variants in the SKIV2L gene are associated with AMD in a Han Chinese population. METHODS Thirteen single nucleotide polymorphisms (SNPs) in the C2-BF-RDBP-SKIV2L-STK19 region were genotyped by the SNaPshot method in a cohort composed of 449 patients with choriodal neovascularization (CNV) AMD and 1025 healthy controls of Han Chinese descent. RESULTS Among the SNPs genotyped, P values of seven SNPs were less than 0.05; however, only rs429608 was found to be significantly associated with AMD after correction for multiple testing. The minor allele (A) frequency of rs429608 was 0.050 in cases and 0.089 in controls, and the P value was 3.76 × 10(-4) (0.00489 after Bonferroni correction), with an odds ratio of 0.55 (95% confidence interval, 0.40-0.77). The SKIV2L gene was expressed in the human RPE, retina, and D407 (human RPE) cells, and in mouse retinas and RPE. CONCLUSIONS We demonstrated that the rs429608 genetic variant in the SKIV2L gene was significantly associated with AMD in a Han Chinese population. SKIV2L may play an important role in the development of AMD.

Clinical characteristics and treatment of 22 eyes of morning glory syndrome associated with persistent hyperplastic primary vitreous

Purpose To describe the clinical manifestations and treatment outcomes in a retrospective case series of morning glory syndrome (MGS) associated with persistent hyperplastic primary vitreous (PHPV). Methods The medical records of 85 eyes/74 patients referred for ophthalmology consultation diagnosed as MGS in our clinic were reviewed retrospectively. All patients underwent thorough ophthalmological examinations. 22 eyes of 19 patients diagnosed as having MGS associated with PHPV were included, accounting for 25.88% of all the MGS eyes. Clinical manifestations and management of these patients were documented. Results 15 patients (78.95%) were younger than 1 year old at the first diagnosis. Six eyes were associated with microphthalmia. 19 of 22 eyes (86.36%) had complications, including cataract (10 eyes), secondary glaucoma (8 eyes), corneal leucoma or oedema (8 eyes), retinal detachment (8 eyes), strabismus (3 eyes) and nystagmus (2 eyes). Treatment methods varied depending on the severity of the complications. Nine eyes with secondary glaucoma or cataract got lensectomy; three eyes underwent combined vitrectomy and lensectomy. Eight patients underwent cranial MRI/MR angiography or CT examination. Widened cerebral fissures of bilateral temporal lobes, abnormal dilated branch of middle cerebral artery in the left hemisphere and abnormal signal in the grey matter of frontal and occipital lobes were revealed respectively in three patients. Conclusions Our study revealed the coexistence of PHPV in a significant percentage of patients with MGS, suggesting a potential common genetic link. Compared with MGS and PHPV alone, the combination of the two conditions manifested with higher incidence and more severe complications in younger patients. Close follow-up was recommended. Lensectomy and vitrectomy were beneficial in the management of the complications.

Identification of novel KIF11 mutations in patients with familial exudative vitreoretinopathy and a phenotypic analysis.

KIF11 gene mutations cause a rare autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR). Recently, such mutations were also found to be associated with familial exudative vitreoretinopathy (FEVR). Here, we report 7 novel KIF11 mutations identified by targeted gene capture in a cohort of 142 probands with FEVR who were diagnosed in our clinic between March 2015 and November 2015. These mutations were: p.L171V, c.790-2A>C, p.Q525*, p.Q842*, p.S936*, p.L983fs and p.R1025G. Phenotypic analysis revealed that all of the affected probands had advanced FEVR (stage 4 or above). Three had microcephaly, and one had chorioretinopathy, which indicated a phenotypic overlap with MCLMR. Two mutations were also found in the families of the affected probands. One parent with a p.R1025G mutation had an avascular peripheral retina and abnormal looping vessels. However, one parent with p.L983fs had normal retina, which indicated incomplete penetration of the genotype. Our results further confirmed that KIF11 is causative of FEVR in an autosomal dominant manner. We also suggest the examination of MCLMR-like features, such as microcephaly, chorioretinopathy, for patients with FEVR and wide-field fundus photography for patients with MCLMR in future practice.

SURGICAL MANAGEMENT OF ADVANCED FAMILIAL EXUDATIVE VITREORETINOPATHY WITH COMPLICATIONS.

Purpose: To report the management of complicated advanced familial exudative vitreoretinopathy in a predominantly young population. Methods: This retrospective study was performed on 34 eyes of 25 patients with severe complications of advanced familial exudative vitreoretinopathy, including retinal detachment, corneal opacity, shallow or flat anterior chamber, cataract, posterior pupillary adhesion, secondary glaucoma, vitreous hemorrhage, and preretinal hemorrhage. Preoperative and postoperative clinical information was reviewed. Results: The average age of the patients was 3.52 ± 5.94 years. Of the 34 eyes, 22 underwent lensectomy, 9 underwent lensectomy combined with vitrectomy, 2 underwent staged lensectomy and vitrectomy, and 1 underwent lens-sparing vitrectomy. After surgery, the shallow or flat anterior chamber became normal in 26/28 eyes; corneal opacity disappeared or improved in 10/22 eyes; and secondary glaucoma was controlled in 22/24 eyes. Among the 12 eyes operated by vitrectomy, the retina was attached in 5 eyes and partly attached in 7. Final visual acuity ranged from no light perception to 30/200 (n = 17). All 5 eyes with preoperative and postoperative visual acuity records showed improvement. Conclusion: Surgical intervention is recommended to resolve complications of advanced familial exudative vitreoretinopathy and to preserve visual function. Staged lensectomy and vitrectomy is an alternative for advanced familial exudative vitreoretinopathy with corneal complications and/or vascularly active fibrovascular proliferation.

Peripheral Retinal Nonperfusion in Pediatric Patients With Morning Glory Syndrome

BACKGROUND AND OBJECTIVE To report the association of morning glory syndrome (MGS) with peripheral retinal nonperfusion in pediatric patients with MGS. PATIENTS AND METHODS The authors retrospectively analyzed the records of pediatric patients with MGS using fundus fluorescein angiography. The peripheral retinal vascular architecture was recorded and graded according to the severity of peripheral retinal nonperfusion. RESULTS Eighty-six eyes of 74 patients were enrolled. Seventy-three of 86 eyes (84.88%) had peripheral retinal nonperfusion, in which mild severity was found in 31 of 86 eyes (36.05%), moderate in 17 of 86 eyes (19.77%), severe in 18 of 86 eyes (20.93%), and extreme in seven of 86 eyes (8.14%). Secondary complications of nonperfusion included leakage in six of 73 eyes (8.22%), fibrovascular proliferation in two of 73 eyes (2.74%), and tractional retinal detachment in one of 73 eyes (1.34%). CONCLUSION There is a high prevalence of peripheral retinal nonperfusion in pediatric MGS eyes, with secondary complications in some, suggesting that more attention should be paid to the peripheral retina in MGS. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:674-679.].

The characteristics of digenic familial exudative vitreoretinopathy

AimTo describe and analyse the clinical and genetic characteristics of digenic familial exudative vitreoretinopathy (FEVR).MethodsThe study cohort consisted of patients with FEVR (n = 13) to identify patients with two mutations in two different genes. A genetic analysis of the LRP5, FZD4, TSPAN12, and ZNF408 genes was performed with next-generation sequencing (NGS). The genotype data obtained from the patients with FEVR were analysed and correlated with their clinical manifestations. They were then further evaluated in conjunction with other data that were available for these genes. The probands and parents/relatives underwent comprehensive age-appropriate ophthalmic examinations.ResultsThe medical history and genetic reports of 487 patients with FEVR were reviewed. In all, we identified 13 probands (2.67%, 13/487) with simultaneous mutations in two disease-causing genes. A total of 25 of mutations were found, including10 in FZD4, 8 in LRP5, 3 in ZNF408, 2 in NDP, and 2 in TSPAN12. The most frequent mutations were those in FZD4 and LRP5. We identified 8 mutations that had previously been identified and 17 novel variants. Among 26 eyes, 65.38% exhibited a phenotype, and 10 (38.46%) were stage 4, while 7 (26.92%) were stage 5.ConclusionsThis is the first study to report a group of patients with digenic FEVR. In most affected eyes, the stage was more severe than stage 3. We speculate that the phenotype of FEVR is more severe in patients with digenic rather than monogenic variants of FEVR-related genes.

A Modified Technique for the Transconjunctival and Sutureless External Drainage of Subretinal Fluid in Bullous Exudative Retinal Detachment Using a 24-G i.v. Catheter.

Purpose: To present the use of a 24-G Optiva® i.v. catheter for external drainage of subretinal fluid (SRF) in bullous exudative retinal detachment (RD). Methods: Thirteen eyes with bullous exudative RD were included in our study. SRF drainage was accomplished via a transconjunctival scleral incision with a 24-G catheter followed by laser treatment, vitrectomy, or anti-VEGF treatment, as needed. Data on age, indications, visual acuities, the number of drainage times, drainage duration, complications, and fundoscopy were collected. Results: Two females and 11 males, with a mean age of 4.2 ± 2.7 years, were included. Surgical indications included exudative RD caused by Coats disease (12 eyes) and Sturge- Weber syndrome (1 eye). Successful drainage was achieved in all cases. The mean duration of the SRF drainage procedure was 63.5 ± 16.9 s. Except for 1 case of localized subretinal haemorrhage, no complications were noted. Conclusions: External drainage of SRF using a 24-G Optiva® i.v. catheter is safe, efficient, and useful.

Asymmetric Outcomes of Type 1 Retinopathy of Prematurity after Bilateral Intravitreal Ranibizumab Treatment

Purpose. To present cases with retinopathy of prematurity (ROP), who were treated with intravitreal injection of ranibizumab (IVR) and had unpredictable asymmetric outcomes. Methods. A retrospective review was performed in infants with type 1 ROP and had bilateral IVR (0.25 mg/0.025 mL) as initial treatment. Patients were classified into the asymmetric outcome group and the symmetric outcome group. Results. Eighty-four patients (168 eyes) were included. There were 18 eyes of 9 patients (10.7%) in the asymmetric outcome group and 150 eyes of 75 patients (89.3%) in the symmetric outcome group. In the symmetric outcome group, 86 eyes (57.3%) had ROP regression, 60 eyes (40%) had reactivation requiring laser treatment, and 4 eyes (2.7%) progressed to retinal detachment requiring vitrectomy. In the asymmetric outcome group, one of the eyes of the 9 patients had ROP regression with/without reactivation after IVR, while the contralateral eyes had negative response, including remarkable posterior fibrosis, partial or total retinal detachment, and vitreous hemorrhage. There was statistically significant difference between the birth weight of the two groups. Conclusion. Contralateral eyes with ROP can take a different clinical course after ranibizumab treatment. High rate of reactivation after IVR is another concern that ophthalmologists should pay attention to.

Identification and functional analysis of novel FZD4 mutations in Han Chinese with familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease characterized by defects in the development of retinal vessels. However, known genetic mutations can only explain approximately 50% of FEVR patients. To assess the mutation frequency of Frizzled 4 (FZD4) in Chinese patients, we analysed patients with FEVR from 61 families from China to identify mutations in FZD4 and to study the effects of identified mutations on FZD4 function. All coding exons and adjacent intronic regions of FZD4 were amplified by polymerase chain reaction and subjected to Sanger sequencing analysis. Three mutations in the FZD4 gene were identified in these families. Of these, two were novel mutations: p.E134* and p.T503fs. Both mutations involve highly conserved residues and were not present in 800 normal individuals. Each of these two novel FZD4 mutations was introduced into wild-type FZD4 cDNA by site-directed mutagenesis. Wild-type and mutant FZD4 DNAs were introduced into HEK293 cells to analyse the function of FZD4 in Norrin-dependent activation of the Norrin/β-catenin pathway using luciferase reporter assays. Both the p.E134* and p.T503fs mutants failed to induce luciferase reporter activity in response to Norrin. Our study identified two novel FZD4 mutations in Chinese patients with FEVR.