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Objective:To investigate the measurements of the ciliary body in patients with acute primary angle-closure (APAC).Methods:This was a case-control study.Subjects were admitted to Ningxia Eye Hospital from January to October 2016.Fifty-five consecutive patients diagnosed with APAC in one eye were presented as case groups, and their fellow eyes were presented as fellow groups.Fifty-five eyes from 55 age-matched normal controls were also recruited as control groups.A-scan ultrasonography and ultrasound biomicroscopy (UBM) were conducted to determine biometric measurements and ciliary body parameters.Biometric measurements included axial length (AL), lens thickness (LT), anterior chamber depth (ACD), pupil diameter (PD), anterior chamber width (ACW) and lens vault (LV). Ciliary body parameters included maximum ciliary body thickness (CBTmax), ciliary body thickness at the point of the scleral spur (CBT 0) and 1 000 μm from the scleral spur (CBT 1000), anterior placement of the ciliary body (APCB), and trabecular-ciliary process angle (TCA), respectively.Pearson correlation analysis was used to examine the correlation between the biometric measurements and the ciliary body parameters.Written informed consent was obtained from each subject before any medical examination.The study protocol was approved by the Ethics Committee of People's Hospital of Ningxia Hui Autonomous Region. Results:The ACD was smaller, while the PD and lens thickness were larger in eyes with APAC compared with their fellow eyes.The differences were statistically significant ( t=-6.805, 3.490, 2.624; all at P<0.05). Smaller AL and ACD measurements were found in the fellow eyes of APAC patients compared with normal eyes, and these differences were statistically significant ( t=-4.828, -6.947; both at P<0.001). For eyes with APAC, their fellow eyes and normal eyes, the average CBT max were (0.907±0.106), (0.960±0.098) and (1.020±0.108)mm; average TCA were (48.99±11.48)°, (51.32±10.87)° and (81.94±12.45)°, respectively.CBT max, CBT 0, CBT 1000, and TCA measukements were smaller, and APCB were larger in eyes with APAC compared with their fellow eyes, and these differences were statistically significant ( t=-5.354, -3.517, -3.407, -0.753; all at P<0.05). In addition, CBT max, CBT 0, CBT 1000, and TCA measurements were smaller, and APCB were larger in the fellow eyes compared with the normal eyes, these differences were also statistically significant ( t=-6.040, -3.132, -6.005, -13.509, 16.795; all at P<0.05). Positive correlations were found between AL and CBT 1000, and between AL and TCA ( r=0.335, P=0.012; r=0.380, P=0.004), while a negative correlation was found between intraocular pressure and CBTmax ( r=-0.289, P=0.032). Conclusions:In eyes with APAC, as well as their fellow eyes, ciliary bodies are thinner and anteriorly rotated, and this anatomical change is associated with shorter AL and high intraocular pressure.
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Objective:To describe the characteristics of genotype and phenotype in 3 families with X-linked retinoschisis (XLRS) due to RS1 mutations. Methods:A cross-sectional approach was adopted.Three XLRS families at the Ningxia Eye Hospital from October 2017 to March 2019 were included.Clinical data and peripheral blood of patients and related families were collected and clinically staged were formulated through a comprehensive eye examination.The disease-causing genes screened by panel sequencing underwent conservative analysis, pathogenicity analysis and protein structure prediction by software tools.Analysis of the mutations pathogenicity was performed according to the American College of Medical Genetics and Genomics guidelines.The research was approved by Medical Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region and followed the Declaration of Helsinki.Written informed consent was obtained from each participant.Results:Total 5 young male patients and 1 middle-aged patient in these three families.The optical coherence tomography(OCT) findings of 5 young patients showed typical macular retinoschisis, which were characterized by stage I of XLRS.One middle-aged patient (Ⅱ-9) showed a stage Ⅲ lesion of macular atrophy.The mutations of c. 668G>A, c.618G>A and exon 1 deletion in RS1 gene were found in the three families.C223 and W206 were verified to be highly conserved in mammals and were predicted to be pathogenic mutations by software and the change of protein structure.Conservation analysis and prediction of protein structure were not performed for the mutation of exon 1 deletion.All the mutations were pathogenic variants according to the ACGM guidelines. Conclusions:Mutations of c. 668G>A/p.C223Y, c.618G>A/p.W206X and exon 1 deletion in RS1 gene are pathogenic mutations in Chinese XLRS families.The combination of Panel sequencing with pathogenicity analysis and protein structure prediction have important effect to diagnosis and identify the causative genes for the hereditary retinal diseases.
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Objective@#To analysis the genotype and phenotype of hereditary retinal diseases (HRD) which are easily misdiagnosed as amblyopia.@*Methods@#A case-control study was designed.The patients with HRD who were misdiagnosed as amblyopia in Ningxia Eye Hospital from January to December, 2017 were recruited in this study.The clinical medical history and ophthalmic examinations of patients and their family members were recorded, and family maps were drawed.Peripheral venous blood (5 ml) from each patient and their family members was collected, and genomic DNA was extract.The target sequence capture sequencing technology was used to detect the genetic testing in serum of the patient, and the pathogenic mutation site was determined by Sanger sequencing and co-segregation verification.Genetic testing results with related ophthalmic examination were considered together to analyze the relationship between genotype and phenotype.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian prior to entering study cohort.This study protocol was approved by Ethic Committee of People's Hospital of Ningxia Hui Autonomous Region Hospital (No.2016018).@*Results@#Twenty-two patients with HRD were enrolled in the study, including 10 Stargardt disease (STGD), 8 cases of cone dystrophy (COD) or cone and rod dystrophy (CRD), and 5 cases of familial exudative vitreoretinopathy(FEVER). Nine patients were detected to have pathogenic mutations, and the positive rate was 40.9%, of which 4 patients with STGD carried mutation gene, including ABCA4 and PROM1 genes; mutations in RPGR, PROM1 and GUCY2D genes were detected in 3 patients with COD or CRD; TSPAN12 gene mutation were detected in 2 patients with FEVER.Eleven mutation sites were detected, 4 of which were newly discovered mutation sites.All of the patients in 9 HRD families developed symptoms during adolescence.At the early stage of the disease, there was severe damage to the eyesight, but the fundus was normal or only slightly abnormal.As the disease progressed, the fundus changes were characteristic, and there were clinical phenotypic overlap between some diseases.All family genotypes and clinical phenotypes were co-separated.@*Conclusions@#The main pathogenic gene of STGD is ABCA4 gene, and PROM1 gene can also cause partial STGD; COD and CRD have similar clinical manifestations, and the pathogenic genes also cross each other, and the genetic pattern is diverse; FEVER caused by mutation of TSPAN12 gene is autosomal dominant, and the mutation type has missense mutation and frameshift mutation.HRDs lack typical early clinical signs, and genetic diagnosis can provide pre-symptomatic diagnosis.
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Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD).Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study.The patient's medical history and family history were collected.All the patients and family members received complete ophthalmic examinations to determine the phenotype,including best corrected visual acuity,slit lamp microscope,indirect ophthalmoscopy,color fundus photography,optical coherence tomography,full-field electroretinogram,and fluorescein fundus angiography.DNA was abstracted from patients and family members.Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations.Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites.The relationship between genotype and clinical phenotype of RP and CORD was analyzed.Results Of the 37 patients with RP,13 were from 6 families,including 4 families with autosomal dominant inheritance,2 families with autosomal recessive inheritance,and 3 in 6 families were detected pathogenic gene mutations.24 cases were scattered RP.Six patients with CORD were from four families,all of which were autosomal recessive.Of the 43 patients,21 patients were detected the pathogenic gene mutation,and the positive rate was 48.8％.Among them,15 patients with RP were detected 10 pathogenic gene mutations including USH2A,RP1,MYO7A,C8orf37,RPGR,SNRNP200,CRX,PRPF31,C2orf71,IMPDH1,and the clinical phenotype included 10 typical RP,2 cases of RPSP,3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations,including 2 cases of ABCA4,2 mutations of RIMS 1 gene,1 case of CLN3 gene mutation,and 1 case of CRB 1 and RPGR double gene mutation.Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar.For patients with early RP and CORD,clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.
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Background Age-related macular degeneration (AMD) is a heritable,progressive degenerative disorder that triggers central visual impairment.Research demonstrated that the single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor 1 (VEGFR1) gene is associated with AMD in different population.However,the results varied among diversified ethnic origin composition and distinct regions.Objective This study was to investigate the associations between the SNPs of VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ningxia population in China.Methods A case-control study was conducted.Four hundreds and thirty-two AMD patients including 325 Han ethnic patients and 107 Hui ethnic patients were recruited from March 2011 to June 2015,and 906 ethnicity-and gender-matched age-related cataract patients were contemporaneously recruited as control group,including 698 Han ethnic patients and 208 Hui ethnic patients.Periphery blood sample of 5 ml was collected from the subjects and genomic DNA was prepared.Eight tagging SNPs loci were acquired to cover rs2281827,rs3936415,rs7337610,rs7981680,rs9554320,rs9554322,rs9582036 and rs9943922,and the genotypes of SNPs were detected by using MassARRAYTM time-of-flight mass spectrometry system.Chi-square test and multi-factor Logistic regression analysis were utilized to estimate the discrepancy of allele frequency and genotype distribution in Hui and Han AMD patients.Moreover,the correlation of AMD with smoking and age statue were further analyzed.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Ningxia Eye Hospital.Written informed consent was obtained before any relevant medical examination.Results There were significant differences in the age between AMD group and control group in both Han and Hui ethnicity (Han:P =0.000;Hui:P =0.009).The smoking exposure was significantly different between AMD group and control group in Han ethnicity (P =0.000),and smoking was the independent risk factor of AMD disease in Han ethnicity of N ingxia region (odds ratio [OR] =2.622,95％ confidence interval [CI]:1.899-3.619).The allele frequencies of SNPs were not significantly different in the AMD patients between Han and Hui ethnicity (all at P＞0.05).However,the allele frequencies and genotype distribution of rs7337610 and rs9554322 SNPs were significantly different between the AMD group and control group in both Han and Hui ethnicity (all at P=0.00).The genotype distribution of rs9582036 and rs9943922 SNPs was significantly different between the AMD group and control group in Han ethnicity (P=0.02,0.00).Allelic G of rs7337610 was the protective factor of AMD disease in Han and Hui ethnieity (OR=0.354,95％ CI:0.288-0.435;OR=0.446,95％ CI:0.315-0.632),while allelic C of rs9554322 was the risk factor of AMD disease in Han and Hui ethnicity (OR=1.671,95％ C1:1.234-2.262;OR=3.661,95％ CI:2.156-6.218).Allelic A of rs9582036 was the risk factor of AMD disease in Han ethnicity (OR =1.477,95％ CI:1.124-1.940).Conclusions Smoking is the independent risk component for Han population with AMD.Of the eight SNPs tagged,the genotypes and alleles of rs9554322 and rs7337610 seems to confer susceptibility to AMD in both Han and Hui ethnicity,the genotypes and alleles of rs9582036 and rs9943922 confer susceptibility to AMD in only Han ethnicity.
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Background Age-related macular degeneration (AMD) is the main cause of irreversible loss of central vision in old population.The incidence of AMD is increasing year by year,but the mechanism is not clearly understood.Objective This study was to investigate the association between genetic variants and the risk of AMD in Ningxia population.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and complied with the Helsinki Declaration.Written informed consent was obtained from each subject.One hundred and fifty patients with AMD and 145 ethnicity-and gender-matched controls were recruited in Ningxia Eye Hospital from January 2012 to March 2013.All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood.The single nucleotide polymorphisms (SNPs) of 8 susceptibility loci in four candidate genes,including complement factor H (CFH),complement factor B (CFB),age-related maculopathy susceptibility 2 (ARMS2) and high temperature required factor A1 (HTRA1),were genotyped with Mass Array and MALDI-TOF technique by Sequenom platform.The distribution of genotype was tested for Hardy-Weinberge equilibrium (HWE).The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls using chi-squared test and the P value was significant at ＜ 0.006 level after correction of age,and the relationship of genotype distribution with AMD was evaluated by Logistic regression analysis.Measures of linkage disequilibrium (LD) was carried out by Haploview.Results All the genetypes met HWE.Seven SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls (all at P＜ 0.05),however,after Bonferroni correction,the differences of only four SNPs were significant between the patients and controls in the genotype and allele distributions,including the SNPs of rs10737680 and rs1410996 in CFH gene,the SNP of rs10490924 in ARMS2 gene and SNP of rs11200638 in HTRA1 gene.The allele distributions of rs800292 (Pallele =0.006,OR =1.643,95 ％ CI:1.155-2.336) in CFH and rs641153 (Pallele =0.002,OR =0.273,95 ％ CI:0.120-0.620) in CFB were significantly associated with AMD.In addition,five SNPs in CFH gene were consisted of two blocks after analysis by Haploview.In addition,five SNPs in CFH were consisted of two blocks after analysis by Haploview.The first one SNPs (including rs551397 and rs800292) and another one SNPs (including rs12124794,rs10737680) and rs1410996 were in strong linkage disequilibrium (D'=1.00).After 50 000 permutations,the GC and AT haplotypes of the first block and the AAC,TCT and ACT haplotypes in the second block were significantly different between AMD patients and controls (P =0.010,0.010,0.001,0.041 and 0.033,respectively).The allel T of rs641153 was a protective factor of AMD (P=0.002,OR =0.273,95％ CI:0.120-0.620).Conclusions The SNPs rs10737680 and rs1410996 in CFH,rs10490924 of ARMS2 gene and rs11200638 of HTRA1 gene are associated with AMD in Ningxia population.
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Background As assessment of the peripapillary retinal nerve fiber layer (RNFL) has been an important approach for detecting structural damage in patients with glaucoma and myopia is a vital risk factor of primary open glaucoma,it is urgent to establish the correlation between RNFL thickness and myopia,not only for understanding the characteristics of RNFL with the change of the degree of myopia,but also for identifying those myopic patients with the early stage of glaucoma.Objective This study was to assess the influence of myopia for the thickness of RNFL measured by 3D optical coherence tomography (3D-OCT).Methods Two hundred and fifty-eight eyes of 258 myopic subjects from General Hospital of Ningxia Medical University were recruited.The myopic eyes were divided into low myopia group (42 eyes,-0.5 D ≤ SE ≤-3.0 D),middle myopia group (120 eyes,-3.0 D＜SE≤-6.0 D),high myopia group (58 eyes,-6.0 D＜SE≤-8.0 D) and extreme high myopia group (38 eyes,SE ＞-8.0 D).The peripapillary RNFL thickness profile including temporal,superior,nasal and inferior quadrants and each of the 12 clocks was measured by 3D-OCT.The measured values were compared among different degrees of myopia,and the correlations between spherical equivalent (SE) and axial length with RNFL thickness were analyzed using linear regression equation.Results The RNFL thickness was gradually declined with the increase of SE and elongation of axis,showing significant differences among the 4 groups in the superior,nasal and inferior quadrants and mean RNFL thickness (F=10.48,15.60,3.31,8.98,all at P＜0.05),but temporal RNFL thickness was increased with the SE rise,with markedly difference among the 4 groups (F =2.92,P =0.03) ; and RNFL thicknesses in the superior,nasal,inferior quadrants and mean RNFL thickness were evidently declined in the high and extreme high myopia group in comparison with low myopia group (all at P＜0.05).The overall RNFL parameters at 1:00,2:00,3:00,4:00,5:00,6:00,8:00,12:00 o'clock sectors were thinning as the increase of SE (all at P＜0.05) and unchanged at the 7:00,9:00,10:00,11:00 sectors in different SE groups (all at P＞ 0.05).Negative correlations were found between axial length or SE with the RNFL thicknesses at superior,nasal and inferior quadrants,average thickness as well as 1:00,2:00,3:00,4:00,5:00,6:00,11:00,12:00 o 'clock,and positive correlation was seen between the axial length or SE with the RNFL thicknesses at temporal quadrant.Conclusions The thickness of RNFL varys with the different degree of myopia and axial length.