New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a highly heritable disease (h2 = 0.42 ± 0.09). Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG ris

A history of visual acuity testing and optotypes

After going into the etymology of the word “optotype”, this article covers some tasks in ancient times that required good visual acuity (VA). Around 300 BCE, Euclid formulated the existence of a visual cone with a minimal visual angle at its tip. Trials to test VA appeared AD 1754. Around that time, texts were introduced by opticians in order to be able to prescribe more reliably. In the early nineteenth century, the need for VA tests in ophthalmology resulted in German and English test charts. Numerous variants emerged after the first edition of Snellen’s optotypes in 1862 in The Netherlands. However, 100 years later there was still no standard optotype to reliably test VA. Multidisciplinary approaches between ophthalmology, linguistics, psychology and psychophysics improved optotypes and VA testing, which led to the more reliable LogMAR charts. Recent advances in aids and therapies for the blind and severely visually handicapped, necessitate further development of new and standardized VA tests