Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - “response to fluid shear stress” and “abnormal retina morphology” - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping

Foveal contrast processing of increment and decrement targets is equivalently reduced in glaucoma

Background:&nbsp;Psychophysical measurement of the function of individual precortical visual pathways (magnocellular, parvocellular and koniocellular) has enabled the development of sensitive tests for glaucoma and has enhanced understanding of its pathophysiology. Such pathways can be further subdivided into their &ldquo;On&rdquo; and &ldquo;Off&rdquo; components, which have anatomical and physiological asymmetries. This study investigated whether On and Off subdivisions of the magnocellular (M) pathway are differentially affected by glaucoma.Methods: 20 participants with glaucoma and 20 controls underwent two psychophysical procedures that have been shown to assess the M pathway (steady pedestal task) and its On and Off subdivisions (pedestal-delta-pedestal task) respectively. Luminance discrimination thresholds were measured foveally, using both increment and decrement stimuli.Results: The steady pedestal (undifferentiated M-pathway) task separated the glaucoma and control groups (p = 0.04) with equivalent outcomes for increment and decrement targets. The pedestal-delta-pedestal task (isolated On and Off M-pathway subdivisions) also differentiated between groups (p = 0.025), but the outcome was not dependent on which subdivision was isolated.Conclusions: This study found that increment and decrement targets can be used with equal effectiveness for detecting contrast processing deficits in early glaucoma. Outcomes further suggested that glaucoma affects On and Off subdivisions of the M-pathway equivalently.</div

Lowering of intraocular pressure after phacoemulsification in primary open-angle and angle-closure glaucoma: A Bayesian analysis

Phacoemulsification as treatment for primary open-angle glaucoma (POAG) remains more controversial than for primary angle-closure glaucoma (PACG). If the objective of glaucoma surgery is an additional greater than or equal to 5 to 6 mm Hg reduction of intraocular pressure (IOP), the role of phacoemulsification should be based on the probability of achieving this. A Bayesian analysis of available data was performed to calculate the change in IOP after phacoemulsification in POAG and PACG. Standard meta-analysis formulation with prephacoemulsification and postphacoemulsification IOP—assumed to have normal distributions, with study-specific means and SDs—was used. Absolute and relative change in IOP was calculated using different priors, and sensitivity analyses were performed. The prior that just included a decrease of greater than or equal to 6 mm Hg in the 95% credible interval was identified. The probability of achieving greater than or equal to 5 to 6 mm Hg decrease in IOP (and other levels) was calculated. Depending on the prior, the probability of achieving a greater than or equal to 5 mm Hg reduction in IOP in POAG varied from 0.1% to 3%. Confidence in a greater than or equal to 6 mm Hg decrease required a prior belief that phacoemulsification produces a mean decrease of 7 mm Hg. The probability of a decrease in IOP was greater in PACG: approximately 50% probability of a greater than or equal to 5 mm Hg decrease in PACG uncontrolled on medications. Phacoemulsification in POAG has a high probability of producing a small decrease in IOP that may be useful in early, well-controlled disease. The probability of a clinically significant decrease of greater than or equal to 5 to 6 mm Hg—required for advanced/uncontrolled disease—is low. Results support the role of phacoemulsification in PACG

Impairments of contrast discrimination and contrast adaptation in glaucoma

Purpose.: Contrast detection is commonly measured clinically; however, discrimination between contrasts is also important for natural vision. Furthermore, optimal performance requires the visual system to adapt to ambient contrast conditions. Recent studies of primate neurophysiology demonstrate significant retinal involvement in contrast adaptation. This study was conducted to investigate whether glaucoma alters contrast adaptation. Both detection and discrimination task performance were examined. Methods.: Psychophysical contrast detection and discrimination thresholds were measured in central vision, for a vertically oriented D6 centered on 3 cyc/deg. Thresholds were measured with and without adaptation to low (15%)- and high (70%)-contrast, vertically oriented, 3-cyc/deg sinusoidal gratings. Fifteen people with glaucoma, and 15 age-similar control subjects participated. Full-contrast discrimination (dipper) functions were measured for a subset (three patients with glaucoma and three control subjects). Results.: On average, the glaucoma group showed elevated detection and discrimination thresholds relative to control subjects (detection: t(28) = 2.42; P = 0.02; discrimination: F 1,28 = 6.157, P = 0.02). For the subset of additionally tested participants, normalized contrast discrimination functions were similarly shaped for all observers. Glaucoma group thresholds were less influenced by contrast adaptation than were control subjects, for discrimination (F 1,28 = 10.89, P F 1,28 = 2.28; P = 0.11). Differences between groups were greatest for low-contrast stimuli (significant interaction between contrast and group: P Conclusions.: Glaucoma alters the effect of contrast adaptation on discrimination performance, particularly at low contrast. The study of suprathreshold aspects of vision may reveal new insights into the pathophysiology of glaucoma and possibly relate better to real-world visual performance than detection measures. </p