Focal choroidal excavation in eyes with central serous chorioretinopathy.

[Purpose]To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). [Design]Prospective, cross-sectional study. [Methods]We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm2, were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). [Results]The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (−4.42 ± 2.92 diopters) than eyes without excavations (−0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). [Conclusions]Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue

Association between the SERPING1 Gene and Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Japanese

PURPOSE: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups--336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chi-square test for trend. Age and gender were adjusted using logistic regression analysis. RESULTS: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. CONCLUSIONS: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium

Purpose To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). Methods A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE -0.5 D); and (2) second set included 898 highly myopic subjects (SE -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). Results In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. Conclusions Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.</p

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

Macular choroidal thickness and volume in eyes with angioid streaks measured by swept source optical coherence tomography.

[Purpose]: To study the mean choroidal thickness and volume of the macula in eyes with angioid streaks using swept source optical coherence tomography (OCT) in the 1050-nm wavelength range. [Design]: Prospective case series. [Methods]: The macular area of 39 eyes of 23 patients with angioid streaks and of 20 normal eyes of 20 matched controls (Group 1) was studied with a swept source OCT prototype system. Eyes with angioid streaks were classified into 1 of 4 groups: those without choroidal neovascularization (CNV) (Group 2); those with CNV that had no history of treatment (Group 3); those with CNV that had previously received only anti–vascular endothelial growth factor treatments (Group 4); and those with CNV that had previously received photodynamic therapy (Group 5). Using a raster scan protocol with 512 × 128 A-scans, we produced a macular choroidal thickness map (6 × 6 mm2). [Results]: There were no significant differences in age, axial length, or refractive error among the 5 groups. Mean choroidal thickness of the macula in Group 2 (218.9 ± 46.8 μm) was as great as that in Group 1 (218.8 ± 69.2 μm). However, the macular choroidal thickness in Group 3 (119.7 ± 49.2 μm), Group 4 (140.1 ± 64.9 μm), and Group 5 (144.0 ± 52.6 μm) was significantly less than that of Group 1 (P < .05). There were no statistical differences between Groups 3 through 5. In each group, the choroid of the nasal quadrant was significantly thinner compared to that in other quadrants (P < .05). [Conclusions]: The choroid in eyes with angioid streaks without CNV was as thick as that in normal controls, but was significantly thinner in eyes with angioid streaks that had developed CNV

Multimodal evaluation of macular function in age-related macular degeneration.

[Objective] To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages. [Methods] Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography. [Results] Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region. [Conclusion] Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD