To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe. Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-015-0010-0) contains supplementary material, which is available to authorized users.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide and their prevalence is rising, largely due to cultural and environmental changes. Genetic investigation is a valuable tool to better understand the molecular mechanisms underlying abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies involving 542,934 European participants and identified 336 novel genetic loci associated with refractive error that explain an additional 4.6% of spherical equivalent heritability, or an improvement by a third over the previous estimates. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (AUC=0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes participating in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may make possible predicting refractive error and the development of personalized myopia prevention strategies in the future.

Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.

Purpose In a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with disease attributable to causative variants in each gene. Design Retrospective study of electronic patient records. Participants Patients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified. Methods Genetic screening used a combination of single-gene testing, gene panel testing, whole exome sequencing, and more recently, whole genome sequencing. For this study, genes listed in the Retinal Information Network online resource ( https://sph.uth.edu/retnet/ ) were included. Transcript length was extracted for each gene (Ensembl, release 94). Main Outcome Measures We calculated proportions of families with IRD attributable to variants in each gene in the entire cohort, a cohort younger than 18 years, and a current cohort (at least 1 patient encounter between January 1, 2017, and August 2, 2019). Additionally, we explored correlation between numbers of families and gene transcript length. Results We identified 3195 families with a molecular diagnosis (variants in 135 genes), including 4236 affected individuals. The pediatric cohort comprised 452 individuals from 411 families (66 genes). The current cohort comprised 2614 families (131 genes; 3130 affected individuals). The 20 most frequently implicated genes overall (with prevalence rates per families) were as follows: ABCA4 (20.8%), USH2A (9.1%), RPGR (5.1%), PRPH2 (4.6%), BEST1 (3.9%), RS1 (3.5%), RP1 (3.3%), RHO (3.3%), CHM (2.7%), CRB1 (2.1%), PRPF31 (1.8%), MY07A (1.7%), OPA1 (1.6%), CNGB3 (1.4%), RPE65 (1.2%), EYS (1.2%), GUCY2D (1.2%), PROM1 (1.2%), CNGA3 (1.1%), and RDH12 (1.1%). These accounted for 71.8% of all molecularly diagnosed families. Spearman coefficients for correlation between numbers of families and transcript length were 0.20 ( P = 0.025) overall and 0.27 ( P = 0.017), –0.17 ( P = 0.46), and 0.71 ( P = 0.047) for genes in which variants exclusively cause recessive, dominant, or X-linked disease, respectively. Conclusions Our findings help to quantify the burden of IRD attributable to each gene. More than ...

We used a fibre electrode in the lower conjunctival sac of the human eye to record the a-wave of the photopic electroretinogram elicited in response to dim red flashes, delivered in the presence of a rod-saturating blue background, before and after exposure of the eye to bright white illumination that bleached a significant fraction of cone photopigment. Responses were recorded from two normal subjects whose pupils were maximally dilated. A range of intensities of bleaching light were used, from 500 to 3000 photopic cd m −2 , and exposures were made sufficiently long in duration to achieve a steady-state bleach. In addition, responses were also recorded following shorter durations of exposures to the highest intensity (3000 cd m −2 ); these durations ranged from 5 to 60 s. The amplitude of the a-wave response to dim flashes was reduced following the exposures, with brighter or longer exposures causing greater reduction. The amplitude then recovered within about 4 min to the prebleach level. The amplitudes measured at ca 15 ms after the flash were used to derive the effective intensity of the flashes, thereby quantifying the fraction of photopigment available at the time of delivery of each flash. Recovery from all exposures in both subjects followed a common time course, which could be described well by a model of pigment kinetics based on rate-limited regeneration, where the initial rate of recovery following a total bleach was ca 50% of the total pigment per minute, and the residual pigment level for half the maximal rate was ca 20% of the total pigment. The same parameters, together with a fixed photosensitivity, could account for the steady-state pigment levels seen at each bleaching intensity, and also for the fraction of pigment bleached following exposures of different duration at the highest intensity. The dim-flash ERG thus provides a novel method for assessing pigment regeneration in vivo. Our finding that pigment regeneration follows rate-limited kinetics may explain previous reports of pigment regeneration deviating from first order kinetics. We present a model of regeneration in which the rate limit arises from a limitation in the delivery of 11-cisretinoid to the photoreceptor outer segments.

Modern cataract surgery is safe in more than 95 per cent of patients. In the small number of cases where a serious complication occurs, the most common is an intra-operative posterior capsular rupture. This can lead to vitreous loss or a dropped nucleus and can increase the risk of post-operative cystoid macular oedema or retinal detachment. Postoperatively, posterior capsular opacification is the most common complication and can be readily treated with a YAG capsulotomy. The most devastating complication is endophthalmitis, the rate of which is now significantly decreased through the use of intracameral antibiotics. As a clinician, the most important step is to assess the patient pre-operatively to predict higher risk individuals and to counsel them appropriately. In these patients, various pre-or intra-operative management steps can be taken in addition to routine phacoemulsification to optimise their visual outcome.

We recorded the a‐wave of the electroretinogram from human subjects with normal vision, using a corneal fibre electrode and ganzfeld stimulation under photopic conditions, so as to extract the parameters of cone phototransduction. The amplitude of bright flash responses provided a measure of the massed circulating current of the cones, while the amplitude of dim flash responses provided a measure of the product of the fraction of cone photopigment present, and the amplification constant of transduction within the cones. In the presence of steady background illumination, the cone circulating current declined to half at 3000 photopic trolands, and to a quarter at 20 000 photopic trolands. At very early times after the delivery of a near‐total bleach, we could not determine the level of circulating current as our bright flashes did not appear to saturate the a‐wave (presumably because so little pigment was present). However, by 20–30 s after a total bleach, the cone circulating current had returned to its dark‐adapted level. Following smaller bleaches (when ca 50 % of the pigment remained present) the bright flashes were able to saturate the a‐wave even at very early times. Within 3 s of extinction of the illumination, the cone circulating current had returned to its dark‐adapted level. This is at least a factor of 300 times faster than the period of ca 15 min required for full recovery of rods exposed to the same level of bleach, and indicates a major difference between rods and cones in the way that they cope with the photoproducts of bleaching. Despite the very rapid recovery of circulating current after bleaches, the recovery of dim‐flash sensitivity was much slower, with a time constant of ca 1.5 min after a near‐total bleach. This time course is very similar to previous measurements of the regeneration of cone photopigment, and it seems highly probable that the reduction in dim‐flash sensitivity results from pigment depletion.

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