Clinical characteristics, rates of blindness, and geographic features of PACD in China.

OBJECTIVE: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China. METHODS: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed. RESULTS: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes. CONCLUSION: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.

Association of Single-Nucleotide Polymorphisms in ABCC5 Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population.

BACKGROUND: The rs1401999 gene in ABCC5 gene was the first locus confirmed by a genome-wide association study (GWAS) to be associated with both anterior chamber depth (ACD) and primary angle closure glaucoma (PACG); however, this locus was of obvious heterogeneity among different populations in the GWAS, and the conclusion has not been further verified by other studies. Therefore, this study was carried out to investigate whether the single-nucleotide polymorphisms (SNPs) in ABCC5 gene are associated with PACG and the ocular biometric parameters ACD and axial length (AL) in samples from northern China. METHODS: Case-control association study included 500 PACG patients and 720 unrelated controls from northern China, and genotyping was performed for ten SNPs in ABCC5 gene using an improved multiplex ligation detection reaction technique. The association between these SNPs and risk of PACG was estimated by PLINK using a logistic regression model, while the association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. RESULTS: An SNP rs4148568 (p = 0.046) and a haplotype TCGGAG (p = 0.0364) in ABCC5 were associated with PACG, and rs4148568 was nominally associated with AL (ß = 0.092, p = 0.08). CONCLUSIONS: The SNP rs4148568 and a haplotype TCGGAG in ABCC5 contribute to PACG in northern Chinese people. In addition, rs4148568 might be associated with the AL, the variant allele of which may have effect of making the AL longer. Further studies are needed to elucidate the exact mechanism of ABCC5 in the progress of PACG.

Evaluating correlation between the ocular biometry and genetic variants of MYOC and ABCA1 with primary angle-closure glaucoma in a cohort from northern China.

AIM: To investigate whether the gene variants in MYOC and ABCA1 are associated with primary angle-closure glaucoma (PACG) and anterior chamber depth (ACD) and axial length (AL) in samples from northern China. METHODS: The present case-control association study consisted of 500 PACG patients and 720 unrelated controls. Each participant was genotyped for eleven single nucleotide polymorphisms (SNPs) in MYOC and ABCA1 genes (rs12076134, rs183532, rs235875 and rs235913 in MYOC, rs2422493, rs2487042, rs2472496, rs2472493, rs2487032, rs2472459 and rs2472519 near ABCA1) using an improved multiplex ligation detection reaction (iMLDR) technique. The genetic association analyses were performed by PLINK using a logistic regression model. The association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. Bonferroni corrections were implemented and the statistical power was calculated by the Power and Sample Size Calculation. RESULTS: Two SNPs rs183532 and rs235875 as well as a haplotype TTC in MYOC were nominally associated with PACG despite the significance was lost after Bonferroni correction. No association was observed between ABCA1 and PACG, neither did the association between these variants and ACD as well as AL. CONCLUSION: The present study suggests MYOC and ABCA1 do not play a part in the pathogenesis of PACG as well as the regulation of ocular biometric parameters in a northern Chinese population. Further investigations with large sample size are needed to verify this consequence.

Genotype-ocular biometry correlation analysis of eight primary angle closure glaucoma susceptibility loci in a cohort from Northern China.

PURPOSE: Recent genome-wide association studies (GWAS) have verified eight genetic loci that were significantly associated with primary angle-closure glaucoma (PACG). The present study investigated whether these variants are associated with the ocular biometric parameters of anterior chamber depth (ACD) and axial length (AL) in a northern Chinese population, as well as whether there were differences in the association of genetic markers in our cohort based on ethnicity. METHODS: A case-control association study of 500 patients and 720 controls was undertaken. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) (rs11024102 in PLEKHA7, rs3753841 in COL11A1, rs1015213 located between PCMTD1 and ST18, rs3816415 in EPDR1, rs1258267 in CHAT, rs736893 in GLIS3, rs7494379 in FERMT2, and rs3739821 mapping between DPM2 and FAM102A) using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic and genotypic frequency differences were evaluated using a logistic regression model. Generalized estimation equation (GEE) analysis was conducted for association testing between genotypes and ocular biometric parameters. False discovery rate (FDR) correction for multiple comparisons was employed, and the statistical power was calculated via power and sample size calculation. RESULTS: Four of the eight SNPs, rs3753841, rs1258267, rs736893 and rs7494379, were associated with PACG (p = 0.007, 0.0016, 0.0045, 0.045, respectively), and only rs3753841, rs1258267 and rs736893 surpassed the FDR correction. For subgroup analysis, only rs1258267 could withstand multiple testing correction in the Han nationality (p = 0.00571). In the GEE tests, rs3753841, rs1258267 and rs736893 were found to be nominally associated with ACD (p = 0.023, 0.016, 0.01, respectively). However, these associations could not survive FDR correction. CONCLUSIONS: The SNP rs3753841 in COL11A1, rs1258267 in CHAT and rs736893 in GLIS3 are associated with PACG in northern Chinese people, and the association of genetic markers manifests a tendency of ethnic diversity. Larger population-based studies are warranted to reveal additional PACG loci and ethnic aspects of PACG.

Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population.

BACKGROUND: The membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; also, the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL. The present study investigated the association of single nucleotide polymorphisms (SNPs) in ZNRF3, HGF and MFRP with PACG in a northern Chinese population, as well as the association of these SNPs with the ocular biometric parameters of anterior chamber depth (ACD) and AL. METHODS: A total of 500 PACG patients and 720 controls were recruited. All individuals were genotyped for 12 SNPs in three genes (rs7290117, rs2179129, rs4823006 and rs3178915 in ZNRF3; rs5745718, rs12536657, rs12540393, rs17427817 and rs3735520 in HGF, rs2510143, rs36015759 and rs3814762 in MFRP) using an improved multiplex ligation detection reaction (iMLDR) technique. Genotypic distribution was analyzed for Hardy-Weinberg equilibrium. Differences in the allelic and genotypic frequencies were evaluated and adjusted by age and sex. Linkage disequilibrium (LD) patterns were tested and haplotype analysis was conducted by a logistic regression model. Generalized estimation equation (GEE) analysis was conducted using SPSS for primary association testing between genotypes and ocular biometric parameters. Bonferroni corrections for multiple comparisons were performed, and the statistical power was calculated by power and sample size calculations. RESULTS: The rs7290117 SNP in ZNRF3 was significantly associated with the AL, with a p-value of 0.002. We did not observe any significant associations between the SNPs and PACG or ACD. In a stratification analysis by ethnicity, rs12540393 and rs17427817 in HGF showed a nominal association with PACG in the Hui cohort, although significance was lost after correction. CONCLUSIONS: The present study suggests rs7290117 in ZNRF3 may be involved in the regulation of AL, though our results do not support a contribution of the SNPs we tested in ZNRF3, HGF and MFRP to PACG in northern Chinese people. Further studies in a larger population are warranted to confirm this conclusion.

Cause of the lacrimal duct obstruction reoccured after lacrimal duct stent operation / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To discuss the cause of lacrimal duct obstruction relapsed after lacrimal duct stent operation.·METHODS:A total of 523 patients(523 eyes) of lacrimal duct obstruction were enrolled. They were given regular examination of the eyes and nose before lacrimal duct stent operation. We analyzed the correlation between the lacrimal duct obstruction and the relevant disease. And 280 cases reoccurred lacrimal duct obstruction during the average 2a follow-up. The causes correlated with the relapsed obstruction were assessed.·RESULTS: Lacrimal duct obstruction mostly occurred secondary to the inflammation of conjunctiva or nasal mucosa. The upper site obstruction correlated with the chronic conjunctivitis, while the lower site obstruction related to the hypertrophy of inferior turbinate. Outcome of some cases were discouraging after the stents removed. The removal of the ring silicone tube usually leaded to the upper site obstruction, while the lower site obstruction usually caused by the removal of spherical silicone tube.· CONCLUSION: Lacrimal duct stent operation is a simple, safe and outpatient treatment. But the long-term effectiveness is not encouraging. We should make personal treatment according to the etiological factor, the site of the obstruction, age, and the procedure of treatment.

Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis.

USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS) was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants (c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C) were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have also demonstrated that a targeted NGS approach is a valuable tool for the genetic diagnosis of USH2 and RP.

Association of specific genetic polymorphisms with age-related macular degeneration in a northern Chinese population.

PURPOSE: The associations between genetic variants located in CFH, CFB, ARMS2 and HTRA1 and the risk of age-related macular degeneration (AMD) in a northern Chinese population were investigated. METHODS: A case-control association study of 150 AMD patients and 145 ethnicity- and gender-matched controls were recruited. Genomic DNA was prepared from peripheral blood after the participants underwent comprehensive eye examinations. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) in four specific genes. Genotypic distribution was tested for Hardy-Weinberg equilibrium. Statistical analysis was performed for genotype, allele and haplotype frequencies along with their p values and corresponding odds ratios (OR), 95% confidence intervals (95% CI) and measures of linkage disequilibrium (LD). Bonferroni corrections for multiple comparisons were performed. RESULTS: Among the SNPs genotyped, p values of seven SNPs were less than 0.05 in the genotypic distributions and allele frequencies between AMD and control subjects. However, after Bonferroni correction, the genotype and allele distributions of two SNPs in CFH (rs10737680, rs1410996), one SNP (rs10490924) in ARMS2 and one SNP (rs11200638) in HTRA1 differed significantly between the controls and AMD patients. Two SNPs were significantly associated with AMD in the allele distributions. They were rs800292 (p(allele) = 0.006, OR [CI] = 1.643[1.155-2.336]) in CFH and rs641153 (p(allele) = 0.002, OR [CI] = 0.273[0.120-0.620]) in CFB. Five haplotypes in CFH significantly predisposed patients to AMD after 50,000 permutations (p = 0.0099, p = 0.0099, p = 0.0013, p = 0.0414 and p = 0.0327). CONCLUSIONS: Gene variants in CFH, ARMS2 and HTRA1 are related to an increased risk of AMD in a northern Chinese population.

Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2.

Usher syndrome (USH) is a group of disorders manifested as retinitis pigmentosa and bilateral sensorineural hearing loss, with or without vestibular dysfunction. Here, we recruited three Chinese families affected with autosomal recessive USH for detailed clinical evaluations and for mutation screening in the genes associated with inherited retinal diseases. Using targeted next-generation sequencing (NGS) approach, three new alleles and one known mutation in MYO7A gene were identified in the three families. In two families with USH type 1, novel homozygous frameshift variant p.Pro194Hisfs*13 and recurrent missense variant p.Thr165Met were demonstrated as the causative mutations respectively. Crystal structural analysis denoted that p.Thr165Met would very likely change the tertiary structure of the protein encoded by MYO7A. In another family affected with USH type 2, novel biallelic mutations in MYO7A, c.[1343+1G>A];[2837T>G] or p.[?];[Met946Arg], were identified with clinical significance. Because MYO7A, to our knowledge, has rarely been correlated with USH type 2, our findings therefore reveal distinguished clinical phenotypes associated with MYO7A. We also conclude that targeted NGS is an effective approach for genetic diagnosis for USH, which can further provide better understanding of genotype-phenotype relationship of the disease.

[A comparison of master eye operation with slave eye operation on patients with large-angle exotropia].

OBJECTIVE: To search for an excellent therapy for patients with large-angle exotropia. METHODS: Strabotomy was performed on the master eyes in the 41 cases (master eye group) and slave eyes in the other 41 cases (slave eye group) with large-angle exotropia (>/= 60(Delta)). The post-operative visual acuity, ocular position, visual function and fixation, the average surgical amount and the frequency of strabotomy were statistically compared between the two groups. RESULTS: Post-operatively, orthophoria occurred in 39 cases and mild exotropia remained in 2 cases in each group. The statistic analyses showed that the surgical results were better in the master eye group in the visual acuity (P < 0.05), visual function (P < 0.05), average surgical amount and frequency (P < 0.01). CONCLUSIONS: The surgical results of strabotomy performed on the master eye in cases with large-angle exotropia are better than that on the slave eye, and the surgical damage in the master eye is less. Thus, the master eye strabotomy is especially suitable for children with large-angle exotropia under general anesthesia.