Comparison of vertical cup-to-disc ratio estimates using stereoscopic and monoscopic cameras

Background: The use of monoscopic cameras for glaucoma screening is increasing due to their portability, lower cost, and non-mydriatic capabilities. However, it is important to compare the accuracy of such devices with stereoscopic cameras that are used clinically and are considered the gold standard in optic disc assessment. The aim of this study is to compare vertical cup-to-disc ratio (VCDR) estimates obtained using images taken with a monoscopic and stereoscopic camera. Methods: Participants were selected from the Tema Eye Survey. Eligible subjects had images of at least one eye taken with two cameras. They were classified as meeting the glaucoma threshold if an eye had a VCDR estimate >97.5th percentile, corresponding to >0.725 for this population. Hence, we used 0.725 as the cutoff to group eyes into two categories: positive and negative. We calculated sensitivity, specificity, and predictive values of VCDR assessed by expert readers at a reading center for monoscopic photos using stereoscopic photos as the gold standard. Results: Three hundred and seventy-nine eyes of 206 participants were included in the study. Most participants were female (60.2%) and the most common age group was 50–59 years (36.4%). Sixteen eyes met the glaucoma threshold (VCDR > 0.725). Of these, the VCDR estimates of 14 eyes (87.5%) disagreed on the glaucoma threshold from the two cameras. The sensitivity to detect glaucoma with the monoscopic camera was 14.3% (95% CI: 4.0, 40.3). Conclusions: The low sensitivity of monoscopic photos suggests that stereoscopic photos are more useful in the diagnosis of glaucoma

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Temporal macular ganglion‐cell inner plexiform layer thinning is a hallmark of early glaucomatous damage

Purpose To investigate the pattern of damage affecting the GCIPL and to compare it to the topographical RNFL thinning in early glaucoma (EG). Methods Total Average (Tot Avg) and quadrant (S, I, N, T) RNFL, Tot Avg and sector (ST, S, SN, IN, I, IT) GCIPL thicknesses were acquired with Cirrus SD‐OCT in 99 controls, 99 EG, and 50 severe glaucoma (SG) patients. S/I Avg and N/T Avg RNFL, T Avg and N Avg GCIPL thicknesses were also calculated. AUCs were obtained for each parameter. ANCOVA was used to study the changes occurring to couples of rNFL/GCIPL sectors according with VFMD. RNFL and GCIPL sectors were compared normalizing the raw values to their sector's dynamic range [the interval between mean sector thickness in controls (max) and minimum sector thickness in SG (floor)], using the following equation: (sector thickness–floor)/(max–floor). The relationship between VFMD and S RNFL/ST GCIPL or I RNFL/IT GCIPL normalized thicknesses was investigated with linear regression analysis. Results GCIPL and RNFL sectors were thinner in EG and SG than controls (ANOVA, p < 0.001). In the EG group T Avg GCIPL was thinner than N Avg GCIPL (p < 0.001). S/I Avg rNFL had a higher AUC compared to Tot Avg (p = 0.001) and N/T Avg rNFL (p < 0.001). Similarly, T Avg GCIPL had a higher AUC (0.936) compared to Tot Avg GCIPL (p = 0.019) or N Avg GCIPL (p < 0.001). T Avg and N Avg GCIPL slopes against VFMD were significantly different (p < 0.001) in EG (VFMD ≥–6 dB), but not in SG (VFMD <–6 dB, p = 0.79). In EG, the slopes against VFMD were not statistically different for ST GCIPL vs. S RNFL (p = 0.258) and for IT GCIPL vs. I RNFL (p = 0.164). Conclusions Temporal macular GCIPL thinning is a hallmark of early glaucomatous damage along with S/I peripapillary RNFL thinning. Conversely, nasal GCIPL sectors are relatively spared in EG, resembling a pattern of damage more typical of N/T peripapillary RNFL