Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form.

This study showed that SNPs rs3753394 (P = 0.0276), rs800292 (P = 0.0266), rs1061170 (P = 0.00514), and rs1329428 (P = 0.0089), but not rs7535263, rs1410996, or rs2274700, in CFH were significantly associated with wet AMD in a mainland Han Chinese population. This study showed that CFH was more likely to be AMD susceptibility gene at Chr.1q31 based on the finding that the CFHR1 and CFHR3 deletion was not polymorphic in the cohort of this study, and none of the SNPs that were significantly associated with AMD in a white population in C2, CFB, and C3 genes showed a significant association with AMD.

High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.

ABSTRACT.Purpose: To evaluate the effect of early vitreoretinal surgery on vascularly active stage 4 ROP through the preoperative use of intravitreal bevacizumab. Methods: This was a retrospective study. Eighteen patients with vascularly active stage 4 ROP who underwent primary vitrectomy from April 2007 to March 2010 were enrolled. Twelve eyes from eight patients received one-time intravitreal injection of 0.625 mg bevacizumab 7 days prior to vitrectomy (bevacizumab group), and 11 eyes from 10 patients underwent the surgical procedure without bevacizumab (control group). Demographical information of all patients was recorded. The patients were followed up for 12-36 months after the surgery. The postmenstrual age at vitrectomy, surgical procedure, anatomical and visual outcome, adverse effects and surgical complications were compared. Results: There was no statistically significant difference between the two groups in gender, birthweight and gestational age. The bevacizumab group showed remarkable regression of vascular activity after the injection. The mean postmenstrual age at the time of vitrectomy was significantly earlier in the bevacizumab group (40 versus 47 weeks, p = 0.002) compared with the controls. The mean surgery time was shorter in the bevacizumab group (74.81 versus 101.70 min, bevacizumab group versus control, p = 0.002). At the final follow-up, all patients in the bevacizumab group achieved anatomical retinal attachment, compared with 70% in the control group. Eighty-eight per cent patients in the bevacizumab group obtained pattern vision, while it was 30% in the control group (p = 0.015). Conclusion: Intravitreal bevacizumab administrated prior to vitrectomy effectively reduced active neovascularization in vascularly active stage 4 ROP patients, thus advancing the timing of vitrectomy and facilitating pars plicata vitrectomy (PPV).