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

Electrodes for multifocal electroretinography (mfERG): a comparison of four electrodes types

The purpose of this study was to compare the performance of four different electrode types in detecting the multifocal electroretinogram (mfERG) using the visual evoked response imaging system (VERIS). Multifocal ERG of 30 healthy subjects aged 17-50 years was recorded. Four different types of electrodes were used (JET contact lens, gold foil, DTL thread and c-glide carbon fiber electrodes) and the trough to peak amplitude response densities of the first order kernels (which approximated to the a and b wave of the full field electroretinogram) were compared. The JET contact lens electrode produced the highest amplitude response which was significantly different from the gold foil, DTL thread and the c-glide electrodes, but there was no significant difference between the gold foil and DTL or between DTL and the c-glide electrodes. In conclusion, contact lens electrode produced the highest response density followed by the gold foil and the DTL thread. There was no significant difference in amplitude response between the gold foil and DTL thread, therefore these two electrodes provide for viable alternatives for recording mfERG especially when there are concerns that contact lens electrode may be uncomfortable for recording periods that may take a long time

Retinal stretching limits peripheral visual acuity in myopia

AbstractAxial elongation of the myopic eye has the potential to stretch the retina, thereby reducing the sampling density of retinal neurons. Resolution acuity in the peripheral field of normal eyes is known to be sampling-limited, which suggests that retinal stretching in the myopic eye should have a direct effect on resolution acuity everywhere in the visual field except perhaps the fovea, which is usually optically limited. We tested this prediction that neural sampling density is reduced in myopic eyes by measuring resolution acuity for sinusoidal gratings in the fovea plus five peripheral locations in 60 myopic subjects exhibiting a wide range of refractive errors. Control experiments using a detection paradigm to provoke spatial aliasing verified that peripheral resolution was sampling limited. Retinal spatial frequencies of the grating stimulus were computed assuming Knapps’ Law of visual optics, which ensures that retinal image size (in mm) is independent of refractive error when axial myopia is corrected by a spectacle lens located in the anterior focal plane of the eye. Results obtained at every retinal locus showed that resolution acuity declined linearly with magnitude of refractive error. Regression of the population data indicated that approximately 15D of refractive error doubles the spacing between retinal neurons, thereby halving peripheral resolution acuity relative to the emmetropic eye. Several subjects also demonstrated sampling-limited performance in the fovea, which indicated that optical filtering by the eye’s optical system failed to protect the fovea from aliasing artifacts of neural undersampling in these eyes. We conclude that stretching of the retina is a primary cause of reduced spatial resolution of the peripheral field, and occasionally of the fovea, in myopic eyes. Stretching appears to be locally uniform over the central ±15° of visual field but is globally non-uniform since the foveal region appears to stretch more than the globe itself

Corneal changes following near work in myopic anisometropia

Purpose: To examine the symmetry of corneal changes following near work in the fellow eyes of non-amblyopic myopic anisometropes.\ud \ud Methods: Thirty-four non-amblyopic, myopic anisometropes (minimum 1 D spherical equivalent anisometropia) had corneal topography measured before and after a controlled near work task. Subjects were positioned in a headrest to minimise head movements and read continuous text on a computer monitor for 10 minutes at an angle of 25 degrees downward gaze and an accommodation demand of 2.5 D. Measures of the morphology of the palpebral aperture during primary and downward gaze were also obtained.\ud \ud Results: The more and less myopic eyes exhibited a high degree of interocular symmetry for measures of palpebral aperture morphology during both primary and downward gaze. Following the near work task, fellow eyes also displayed a symmetrical change in superior corneal topography (hyperopic defocus) which correlated with the position of the upper eyelid during downward gaze. Greater changes in the spherical corneal power vector (M) following reading were associated with narrower palpebral aperture during downward gaze (p = 0.07 for more myopic and p = 0.03 for less myopic eyes). A significantly greater change in J0 (an increase in against the rule astigmatism) was observed in the more myopic eyes (-0.04 ± 0.04 D) compared to the less myopic eyes (-0.02 ± 0.06 D) over a 6 mm corneal diameter (p = 0.01).\ud \ud Conclusions: Changes in corneal topography following near work are highly symmetrical between the fellow eyes of myopic anisometropes due to the interocular symmetry of the palpebral aperture. However, the more myopic eye exhibits changes in corneal astigmatism of greater magnitude compared to the less myopic eye

Evaluation of shared genetic susceptibility to high and low myopia and hyperopia

Importance Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. Objective To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. Design, Setting, and Participants This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Exposures Four refractive error groups were defined: HM, −6.00 diopters (D) or less; LM, −3.00 to −1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. Main Outcomes and Measures Odds ratios (ORs) of polygenic risk scores in replication samples. Results A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10−15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10−5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10−7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10−16). Conclusions and Relevance Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

10.1016/j.ajhg.2013.06.016American Journal of Human Genetics932264-277AJHG