A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

Toric intraocular lenses for correction of astigmatism in keratoconus and after corneal surgery

PURPOSE: To describe the results of cataract extraction with toric intraocular lens (IOL) implantation in patients with preexisting astigmatism from three corneal conditions (keratoconus, postkeratoplasty, and postpterygium surgery). METHODS: Cataract patients with topographically stable, fairly regular (although sometimes very high) corneal astigmatism underwent phacoemulsification with implantation of a toric IOL (Zeiss AT TORBI 709, Alcon Acrysof IQ toric SN6AT, AMO Tecnis ZCT). Postoperative astigmatism and refractive outcomes, as well as visual acuities, vector reduction, and complications were recorded for all eyes. RESULTS: This study evaluated 17 eyes of 16 patients with a mean age of 60 years at the time of surgery. Mean follow-up in this study was 12 months. The corrected distance Snellen visual acuity (with spectacles or contact lenses) 12 months postoperatively was 20/32 or better in 82% of eyes. The mean corneal astigmatism was 6.7 diopters (D) preoperatively, and 1.5 D of refractive cylinder at 1-year follow-up. No vision-compromising intra- or postoperative complications occurred and decentration or off-axis alignment of toric IOLs were not observed. CONCLUSION: Phacoemulsification with toric IOL implantation was a safe and effective procedure in the three mentioned corneal conditions. Patient selection, counseling, and IOL placement with optimal astigmatism correction are crucial

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

Genome sequence of the human malaria parasite Plasmodium falciparum

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria