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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) 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 for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Purpose: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Design: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. Participants: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. Methods: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Main Outcome Measures: Corneal-compensated IOP. Results: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). Conclusions: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Purpose To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design Cross-sectional study. Participants We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures Thicknesses of mRNFL, GCC, and GCIPL. Results We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Retinal detachment is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank dataset, where retinal detachment was ascertained by self-report or hospital records, genetic correlations between retinal detachment and high myopia or cataract operation were respectively 0.46 (SE=0.08) and 0.44 (SE=0.07). These correlations are consistent with known epidemiological associations. Through meta-analysis of genome-wide association studies using UK Biobank retinal detachment cases (N=3977) and two cohorts, each comprising ~1000 clinically-ascertained rhegmatogenous retinal detachment patients, we uncovered 11 genome-wide significant association signals. These are near or within ZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1 and LOXL1. Replication in the 23andMe dataset, where retinal detachment is self-reported by participants, firmly establishes six retinal detachment risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits described to date, the first two specifically impact risk of a retinal detachment, while the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritised the lead common missense variant (TYR S192Y) as causal variant at the TYR locus and a small set of credible causal variants at the FAT3 locus. The larger study size presented here, enabled by resources linked to health records or self-report, provides novel insights into retinal detachment aetiology and underlying pathological pathways.

Purpose\ud To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH).\ud \ud Design\ud Multicenter, national cohort study.\ud \ud Methods\ud Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity.\ud \ud Results\ud Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25–2.49, P = .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39–10.62, P = .0095).\ud \ud Conclusions\ud Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.

PurposeThe purpose of the study was to investigate the role of ethnicity on idiopathic macular holes (IMH) structure and surgical outcome. This was a retrospective review.Patients and methodsConsecutive patients undergoing primary IMH surgery at two surgical sites of Moorfields Eye Hospital (London, UK) between April 2012 and June 2013. The main outcome measure was post surgical anatomical closure of IMH.ResultsTwo hundred and twenty two primary IMH surgeries were undertaken. A standard procedure including pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade was undertaken for all cases. 61.3% of patients were Caucasian, 21.2% were South Asian, and 16% were Afro-Caribbean. The mean minimum linear diameter (MLD) for our cohort was 434.6 mcm. Mean MLD was 395.3 mcm in Caucasian patients, 490.0 mcm in South Asians (P=0.006), and 491.4 mcm in Afro-Caribbeans (P=0.007). Regression analysis demonstrated that MLD and Afro-Caribbean ethnicity were independent significant risk factors for surgical failure (OR: 1.01, P0.001 and OR: 5.73, P=0.008, respectively).ConclusionSouth Asian and Afro-Caribbean patients present with larger IMH than Caucasians. In addition to IMH diameter, Afro-Caribbean ethnicity is an independent risk factor for surgical failure.

AIM: Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images.METHODS: Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC).RESULTS: Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62-0.66) and in trial 2 it was 0.63(0.61-0.65). There were no significant differences between study design or trials conducted.CONCLUSIONS: Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.

Objective To compare key characteristics of ophthalmology training programs in 6 different English-speaking countries: Australia, New Zealand, Canada, Ireland, the United Kingdom, and the United States. Participants Seven ophthalmologists with personal knowledge of all 6 systems contributed. Methods The main features examined were career pathway, duration of training, surgical training, governing bodies, and examination structure. Data were collected from the literature, online resources, and personal experience. Results Several differences were highlighted, including length of training (ranging from 4 to 9 years after medical school), number of surgical procedures such as cataracts (ranging from minimum 86 to approximately 600), and structure of fellowship training. Conclusions As trainees increasingly seek international experience to enhance their knowledge and skills, the similarities and differences between training programs in different countries have become more relevant. Some of these differences may reflect differing needs of different patient populations and different healthcare delivery systems across the globe. However, these differences should also prompt educators to more carefully scrutinize their own training system and search for potential improvements.

Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions.

Cerebral palsy (CP) is the most common cause of motor disability in children and is often accompanied by sensory and/or cognitive impairment. The aim of this study was to characterise visual acuity impairment, perceptual visual dysfunction (PVD) and physical disability in a community-based sample of Bangladeshi children with CP and to assess the impact of these factors on the quality of life of the children.A key informant study was used to recruit children with CP from Sirajganj district. Gross Motor Function Classification System (GMFCS) levels and visual impairment were assessed by a physiotherapist and an optometrist, respectively. Assessments of visual perception were performed and standardised questionnaires were administered to each child's main carer to elicit indicators of PVD and parent-reported health-related quality of life. A generalised linear regression analysis was conducted to assess the determinants of the quality of life scores.180 children were recruited. The median age was 8 years (IQR: 6-11 years); 112 (62%) were male; 57 (32%) had visual acuity impairment and 95 (53%) had some parent-reported PVD. In analyses adjusted for age, sex, GMFCS and acuity impairment, visual attention (p0.001) and recognition/navigation (p0.001) were associated with total health-related quality of life, and there were similar trends for total PVD score (p=0.006) and visual search (p=0.020).PVD is an important contributor in reducing quality of life in children with CP, independent of motor disability and acuity impairment. Better characterisation of PVD is important to help design interventions for affected children, which may improve their quality of life.

Aims: To describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database.\ud \ud Methods: Structured clinical data were anonymised and extracted from an electronic medical record from 19 participating UK centres: age at first injection, ETDRS visual acuity (VA), number of injections, ETDRS diabetic retinopathy (DR) and maculopathy grade at baseline and visits. The main outcomes were change in mean VA from baseline, number of injections and clinic visits and characteristics affecting VA change and DR grade.\ud \ud Results: Data from 12 989 clinic visits was collated from baseline and follow-up for 3103 eyes. Mean age at first treatment was 66 years. Mean VA (letters) for eyes followed at least 2 years was 51.1 (SD=19.3) at baseline, 54.2 (SD: 18.6) and 52.5 (SD: 19.4) at 1 and 2 years, respectively. Mean visual gain was five letters. The proportion of eyes with VA of 72 letters or better was 25% (baseline) and 33% (1 year) for treatment naïve eyes. Eyes followed for at least 6 months received a mean of 3.3 injections over a mean of 6.9 outpatient visits in 1 year.\ud \ud Conclusions: In a large cohort of eyes with DMO treated with ranibizumab injections in the UK, 33% of patients achieved better than or equal to 6/12 in the treated eye at 12 months compared with 25% at baseline. The mean visual gain was five letters. Eyes with excellent VA at baseline maintain good vision at 18 months.

Since 2000, endothelial keratoplasty (EK) in its various forms has largely eclipsed penetrating keratoplasty (PK) as the procedure of choice in the primary treatment for corneal endothelial failure secondary to Fuchs dystrophy [1]. Advantages include safer surgery under local anaesthetic and early functional visual rehabilitation – both of particular benefit in the older age group comprising the majority of patients with endothelial failure. Additional advantages include preservation of eye wall strength, refractive shape, and freedom from suture-related complications. Although primary transplantation for Fuchs dystrophy is now predominantly by EK, a sizeable cohort of Fuchs dystrophy cases treated initially with PK remains. The advantages of primary EK mostly hold true for EK surgery after failed PK, but a number of additional considerations apply in surgical planning [1–5]. Here we will explore results for EK after PK, surgical variations, and an algorithm for procedure choice.

Aim To report the long-term visual outcome of a multicentre prospectively recruited cohort of macula-off rhegmatogenous retinal detachments (RRD) Methods The Scottish retinal detachment study was a prospectively recruited study that recruited all incident cases of primary RRD in Scotland over a 2-year period (2007–2009). All patients with a macula-off RRD from four participating sites were invited for clinical examination at 6 weeks, 3 months, 6 months and 1 year after the initial surgery. Using a joinpoint model we estimated the effect of duration of macular detachment on final visual outcome. Results In total, there were 291 patients with macula-off RRD without pre-existing retinal disease who had successful repair after one operation. 65.9% achieved a final visual acuity (VA) of 0.48 logMAR(6/18). Our model identified two time points (day 8 (95% CI 3 to 15 days) and (day 21 (95% CI 6 to 26 days)) after which there was a statistically significant worsening in final VA. Conclusions Our study suggests that the majority of patients with macula-off RRD successfully repaired with one operation will achieve a VA of 6/18 or better at final follow-up. After 8 days of macular detachment, the final visual outcome may be adversely affected and, thus, operative repair within this period is desirable. Duration of macular detachment of ≤8 days demonstrated a continuing improvement in VA for up to 1 year, a finding which was not found in macula detachments of longer duration.

Objectives To report the early surgical outcome, risk of failure and predictive value of rhegmatogenous retinal detachment (RRD) classification based on all participants in the Scottish Retinal Detachment study. Methods Over 2 years, all incident cases of RRD in Scotland were approached for recruitment. Early postoperative success was defined as an attached retina following one procedure with a minimum follow-up of 6–8 weeks. Using a regression model, the influence of clinical factors on the failure risk was estimated and the sensitivity and specificity of the Royal College of Ophthalmologists (RCOphth) grading for RRD and the vitrectomy in retinal detachment stratification risk formula (VR-SRF) in predicting operative failure were assessed. Results Primary outcome data were available for 86.2% (975/1130) of patients. The overall primary success rate was 80.8% (95% CI 78.1 to 83.3%). The presence of preoperative proliferative vitreoretinopathy of any degree and each additional clock hour of detachment increased the risk of failure by an OR of 2.4 and 1.13 respectively (p 95% in predicting early surgical failure was noted for highly complex RRDs according to the VR-SRF formula and the RCOphth classification. Conclusions Consistent with previous series, the overall early success rate of RRD repair was 80% after one operation. The type of surgical repair did not influence overall success rates. Significant predictors of failure are the presence of preoperative proliferative vitreoretinopathy of any grade and the extent of detachment. The analytical value of current classification systems in predicting failure is most useful in complex RRDs.

Purpose To describe the predisposing pathology and clinical features of all incident cases of rhegmatogenous retinal detachment (RRD) recruited in Scotland during a 2-year period. Design Prospective surveillance study of incident cases of RRD. Participants All incident cases of RRD recruited as part of the Scottish Retinal Detachment Study. Methods During a 2-year period, we coordinated a comprehensive system in which every case of primary RRD presenting to 1 of 6 vitreoretinal surgical sites in Scotland was examined and approached for study inclusion. Main Outcome Measures Rhegmatogenous retinal detachment incidence, predisposing features, and clinical characteristics. Results A total of 1202 cases were recruited. Detailed clinical information was available on 1130 (94%) of cases. By causative break, the proportions of RRD were horseshoe tear (HST) associated with posterior vitreous detachment (PVD) in 86.2%, giant retinal tear (GRT) and PVD in 1.3%, non-PVD round hole (RH) in 4.9%, retinal dialysis in 5.9%, and retinoschisis RRD in 1.6%. One in 10 cases reported significant ocular trauma. One in 5 cases were pseudophakic. Round hole RRD more frequently presented with multiple retinal breaks compared with HST RRD (67.8% vs. 48.7%; P = 0.003). In PVD-associated RRD, 56.1% (95% confidence interval [CI], 53.8–58.3) of breaks were identified in the superotemporal retina. In non-PVD RRD, 54.6% (95% CI, 47.9–61.1) of breaks were inferotemporal, followed by superotemporal in 34.9% (95% CI, 28.7–41.5). Lattice degeneration was present in 18.7% of affected eyes and more common in RH RRD (35.7%) than in HST RRD (19.3%) ( P = 0.003). Seven percent reported an affected first-degree relative, and these cases were significantly more myopic than nonfamilial cases. Conclusions More than 85% of RRD cases are associated with PVD and related tractional tears. Non-PVD RH RRD occurred in younger and more myopic individuals. The majority of cases are caused by more than 1 retinal break, and the macula is affected in more than 50% at presentation. Ocular trauma, previous cataract surgery, family history, and lattice degeneration are important predisposing features. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background The pathogenesis of rhegmatogenous retinal detachment is complex, and our knowledge of the exact mechanism of vitreoretinal attachment and detachment remains incomplete. Methods We performed a Medline, Ovid, and EMBASE search using search words rhegmatogenous, retinal detachment, vitreous, and retinal adhesion. All appropriate articles were reviewed, and the evidence was compiled. Results Cortical vitreous contains fibrillar collagens type II, V/XI, and IX. The inner limiting membrane of the retina contains collagens type I, IV, VI, and XVIII as well as numerous other glycoproteins and potential adhesion molecules. The distribution and age-related changes in the structure of these molecules play an important role in the formation of a retinal break, which may compromise and disrupt the normal mechanisms of neurosensory retinal adhesion. Conclusion Rhegmatogenous retinal detachment development is intimately related to changes in the fibrillar structure of the aging vitreous culminating in posterior vitreous detachment with regions of persistent and tangential vitreoretinal traction predisposing to retinal tear formation. A complex interplay of factors such as weakening of vitreoretinal adhesion, posterior migration of the vitreous base, and molecular changes at the vitreoretinal interface are important in predisposing to focal areas of vitreoretinal traction precipitating rhegmatogenous retinal detachment. Once formed, the passage of liquefied vitreous through a retinal break may overwhelm normal neurosensory-retinal pigment epithelium adhesion perpetuating and extending detachment and causing visual loss. To understand the molecular events underlying rhegmatogenous retinal detachment so that new therapies can be developed, it is important to appreciate the structural organization of the vitreous, the biology underlying vitreous liquefaction and posterior vitreous detachment, and the mechanisms of vitreoretinal attachment and detachment.

Socio-economic deprivation plays a major role in health and disease, but its role in retinal detachment has not been studied. Data from the Scottish Retinal Detachment Study were used to investigate any association between retinal detachment, macular status at presentation and deprivation.Prospective multicentre population-based observational study. Data were collected on all patients with primary retinal detachment presenting in Scotland between 1 November 2007 and 31 October 2008. Every patient was allocated a validated deprivation ranking according to their postcodes based on the Scottish Index of Multiple Deprivation (SIMD), which takes into account income, employment, health, education, housing, geographic accessibility and crime in 6505 postcode-based datazones. The patients were divided into four quartiles according to their SIMD ranking.572 patients were included. The annual incidence of detachment declined from 15.4/100,000 in the most affluent quartile to 13.6/100,000 in the second, 9.3/100,000 in the third and 6.9/100,000 in the most deprived (chi(2) for trend = 50.2, p0.0001). The trend was more marked for men than for women but was present in both sexes. There were no differences in the rate of macula-off detachments or the number of quadrants detached. Rates of pseudophakic and myopic detachment were evenly distributed across all quartiles.Retinal detachment appears to be associated with affluence. This has not been previously reported and may be partly responsible for the variation in estimates of the incidence of retinal detachment. It may also have implications for service planning. The reason for this association is unknown.

Aim To explore and describe trends in the principal disorders/conditions (‘cause’) for severe sight impairment (SSI) (blind) and sight impairment (SI) (partial sight) certification in children in England and Wales since 1999. Methods We obtained certification data for SI and SSI from a national database for all individuals aged 16 years or less at the time of certification in England and Wales for the years 1999/2000 and for the years 2007/2008–2009/2010. Results In total, there were 861 certifications in the year 1999/2000, rising to 1040 certifications in 2009/2010. The commonest single causes of SSI certification in 1999/2000 were cerebral visual impairment (23.2%) and optic nerve disorders (23.2%). The commonest single causes of SI certification in the same year comprised nystagmus (16.7%) and optic nerve disorders (15.5%). Cerebral visual impairment was the commonest single cause of SSI in children in England and Wales annually between 2007/2008 and 2009/2010 accounting for 21%–31% of certifications. The commonest causes of SI certification in 2009/2010 were congenital globe anomalies (18.4%) and retinal dystrophy (16.6%). The proportion of SI and SSI due to optic nerve disorders has decreased since 1999/2000. Conclusions Our findings suggest that in England and Wales, cerebral visual impairment is now the commonest cause of paediatric SSI certification and hereditary retinal dystrophy and congenital globe anomalies are the commonest causes of SI certification.

Genome-wide association studies (GWAS) use high-throughput genotyping technologies to genotype thousands of single-nucleotide polymorphisms (SNPs) and relate them to the development of clinical and quantitative traits. Their use has been highly successful in the field of ophthalmology, and since the advent of GWAS in 2005, many genes not previously suspected of having a role in disease have been identified and the findings replicated. We conducted an extensive literature review and describe the concept, design, advantages, and limitations of GWAS and provide a detailed description of the applications and discoveries of GWAS in the field of eye disease to date. There have been many novel findings revealing previously unknown biological insights in a diverse range of common ocular conditions. GWAS have been a highly successful modality for investigating the pathogenesis of a wide variety of ophthalmic conditions. The insights gained into the pathogenesis of disease provide not only a better understanding of underlying disease mechanism but also offer a rationale for targeted treatment and preventative strategies. Expansive international collaboration and standardised phenotyping will permit the continued success of this investigative technique.

Item does not contain fulltext Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss and can potentially lead to blindness. The underlying pathogenesis is complex and incompletely understood. We applied a two-stage genetic association discovery phase followed by a replication phase in a combined total of 2833 RRD cases and 7871 controls. The discovery phase involved a genome-wide association scan of 867 affected individuals and 1953 controls from Scotland, followed by genotyping and testing 4347 highest ranking or candidate single nucleotide polymorphisms (SNPs) in independent sets of cases (1000) and controls (2912) of Dutch and British origin. None of the SNPs selected reached a Bonferroni-corrected threshold for significance (P < 1.27 x 10(-7)). The strongest association, for rs12960119 (P = 1.58 x 10(-7)) located within an intron of the SS18 gene. Further testing was carried out in independent case-control series from London (846 cases) and Croatia (120 cases). The combined meta-analysis identified one association reaching genome-wide significance for rs267738 (OR = 1.29, P = 2.11 x 10(-8)), a missense coding SNP and eQTL for CERS2 encoding the protein ceramide synthase 2. Several of the top signals showing suggestive significance in the combined meta-analysis encompassed genes with a documented role in cell adhesion or migration, including SS18, TIAM1, TSTA3 and LDB2, which warrant further investigation. This first genetic association study of RRD supports a polygenic component underlying RRD risk since 27.4% of the underlying RRD liability could be explained by the collective additive effects of the genotyped SNP from the discovery genome-wide scan.

AIM: To explore temporal trends in the incidence of childhood blindness and partial-sight registration in England between 1982 and 2011. METHODS: We obtained blind and partial-sight registration data for all new individuals registered annually in England. We calculated the age-specific incidence of new registrations for childhood blind and partial sight. RESULTS: The incidence of new registration for blindness of all ages has decreased from 2.6 per 10 000 in 1982 to 1.7 per 10 000 in 2011, however the annual incidence of new paediatric blind registration has increased, with an incidence of 0.17 per 10 000 in 1982, doubling to 0.41 per 10 000 in 2011. The annual incidence of new paediatric partial-sight registration showed a comparable trend. CONCLUSIONS: Over 30 years, there has been a greater than twofold increase in blind and partial-sight registration in children in England. Better awareness of this is needed to ensure adequate resources are available to help these children.

Purpose. The study aim is to describe the clinical outcomes of patients with polypoidal choroidal vasculopathy (PCV) treated with focal argon laser photocoagulation and ranibizumab combination therapy. Methods. This study is a retrospective case series of 6 patients (6 eyes) diagnosed with PCV who received combination therapy with argon laser photocoagulation and ranibizumab and have at least 12 months follow-up. Argon laser photocoagulation was applied directly to the polypoidal lesions as identified on indocyanine green angiography and followed by a course of intravitreal ranibizumab injections. The primary outcome measures were the mean change in logMAR visual acuity and the mean change in central macular thickness (CMT) at final follow-up. Results. The mean (SD) duration of follow-up was 1.09 (0.22) years. At the final follow-up the difference (95% confidence interval [CI]) in logMAR acuity was 0.48 (0.10-0.74) (p=0.01) and the difference (95% CI) in CMT was 207 μm (35-490) (p=0.02) on optical coherence tomography. The mean (SD) number of ranibizumab injections per eye was 4.83 (3.6). The mean (SD) number of laser treatments per eye was 1.16 (0.4). Conclusions. In this study, combination therapy with focal argon laser photocoagulation and intravitreal ranibizumab resulted in improved visual acuity and clinical outcomes for patients with PCV for up to 1 year.

Aim To characterise the predisposing pathology and clinical features in the fellow eyes of patients recruited as part of the Scottish Retinal Detachment Study. Methods The Scottish Retinal Detachment Study was a 2-year prospectively recruited population-based epidemiology study that sought to recruit all incident cases of primary rhegmatogenous retinal detachment (RRD) in Scotland. Results A total of 1202 incident cases of primary RRD were recruited in Scotland, over a 2-year period and in 94% (1130 cases) detailed data on the clinical features of fellow eyes with RRD were available. Full-thickness retinal breaks were found in 8.4% (95/1130) of fellow eyes on presentation. Lattice degeneration was present in 14.5% (164/1130) of fellow eyes. Thirteen per cent (148/1130) of affected fellow eyes had a best corrected visual acuity of 6/18 or worse with previous RRD, the second most common cause of poor vision. Overall, 7.3% (88/1202) of cases had RRD in both eyes; 60% of cases with consecutive bilateral RRD presented before the macula were affected. Conclusions Rhegmatogenous pathology in the fellow eye represents an important threat to vision. Fellow-eye detachments are more common in pseudophakic individuals and those with a more myopic refractive error. Fellow-eye RRD has a greater likelihood of prompt presentation.

Purpose The influence of genetic predisposition on nonsyndromic primary rhegmatogenous retinal detachment (RRD) is poorly characterized. The purpose of this study was to investigate the magnitude of genetic risk for RRD. Methods All participants (probands) in the Scottish Retinal Detachment Study (N = 922) with known postal addresses were contacted by questionnaire to assess the personal and family history of RRD. Sibling affection status was modeled by logistic regression and generalizing estimating equations accounting for the effect of proband covariates of age, sex, spherical equivalent refraction, index birth order, and body mass index (BMI). Sibling-sibling recurrence risk ratios (λs) and parent-offspring recurrence risk ratios were calculated. Results Sixty-five percent of probands returned completed questionnaires. Of these, 602 families (parents, siblings, offspring), 7.8% (47) had one affected member, and 0.5% (3) had two affected members. A total of 501 sibships were included in the regression analysis. The odds ratio (OR) that a sibling would be affected, given another affected sibling, was 1.91 (95% confidence interval [CI], 1.18-3.05). With adjustment for age and sex, the OR that a sibling would be affected increased by 9.8% for each additional diopter of spherical equivalent refractive error (SER) toward myopia in the proband. The λs and the parent-offspring recurrence risk ratio of RRD were 2.1 (95% CI, 1.3-3.2) and 2.9 (95% CI, 1.9-4.2), respectively. Conclusions Genetic factors are important in the etiology of myopic and nonmyopic RRD. The risk of having an affected sibling with RRD increases twofold, given that a sibling has had the condition. The sibling risk increases with the level of spherical equivalent myopia in the proband.

International audience; Abstract Aim Rhegmatogenous retinal detachment (RRD) is a common and sight threatening condition. RRD incidence has varied considerably in published literature and few studies have examined the temporal trends in incidence rate over a long time period. Our aim is to examine the time trends of primary RRD in Scotland. Methods We obtained linked hospital episode statistics data for all patients admitted with a primary diagnostic code of RRD in Scotland between 1987 to 2006. Using this database as an estimate of RRD incidence, we calculated the annual age and sex specific incidence rates of RRD in Scotland. Loglinear Poisson regression analysis was used to explore age, period and cohort trends. Results The overall age standardised incidence of RRD in Scotland has steadily increased from 9.36 per 100,000 (95%CI:8.19-10.53) in 1987 to 13.61 per 100,000 (95%CI:12.25-14.97) in 2006 with an average annual increase of 1.9% (p

Rhegmatogenous retinal detachment (RRD) is a common ophthalmic emergency. Population-based data on primary RRD incidence has been variable, with large differences reported. This study is the first large-scale prospective examination of the incidence of primary RRD in the United Kingdom.The authors established a two-year prospective, population-based observational study recruiting all cases of primary RRD in Scotland. The annual incidence was calculated and analyzed in relation to age, sex, refractive error, and lens status. A national, population-based tool, the Scottish Index of Multiple Deprivation (SIMD), was used to examine the socioeconomic distribution of all incident cases.A total of 1244 cases were identified during the study period from a population of 5,168,500 yielding an annual incidence of 12.05 per 100,000 population (95% confidence interval, 11.35-12.70). The age-specific incidence increased to a peak in both sexes in the 60- to 69-year age group. RRD was significantly more frequent in males than in females (14.70 vs. 8.75 per 100,000; P0.001). Of the cases without previous intraocular surgery, 53.2% were myopic, with a spherical equivalent refractive error-1 D, 23.4% had undergone cataract surgery, and 10.4% had sustained traumatic injury. A strong association was found between RRD incidence and affluence, with a significant rising trend across quintiles of deprivation.The estimated annual incidence of primary RRD in Scotland is 12.05 per 100,000. Based on this estimate, there are approximately 7300 new cases annually in the United Kingdom. RRD incidence increases with age, is more common in men and right eyes, and is strongly associated with affluence.

Acute toxic serous macular detachment after cataract surgery is very rare, and has been described previously with the use of high concentrations of intra-cameral cefuroxime. We report a case of serous macular detachment and cystoid macular edema 1 day after uncomplicated phacoemulsification using standard dose subconjunctival cefuroxime at the end of surgery. Our case demonstrates that subconjunctival cefuroxime may cause retinal toxicity in a similar fashion to intra-cameral cefuroxime, possibly due to entry of the drug into the anterior chamber through the section or trans-scleral absorption. To our knowledge, this is the first report of this complication with subconjunctival administration of cefuroxime.

Aims/Background Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. Methods A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. Results RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100 000 population. For studies with a sample size >300 the median annual incidence per 100 000 population was 10.5 (IQR 8.1–13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7±20.3% and myopia was 47.28±12.59%. Conclusions Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.

Background Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition and a common cause of ocular morbidity. Establishing an accurate estimate of disease incidence and distribution is an important first step in assessing the healthcare burden related to this condition and in subsequent planning and provision of treatment strategies. The aim of this study is to obtain a first estimate incidence of RRD in Scotland, to estimate the incidence of familial RRD and to describe the known associations of RRD within the study population. Methods/Design We have established a national prospective observational study seeking to identify and recruit all incident cases of RRD in the Scottish population over a 2 year period. After fully informed consent, all participants will have a blood sample taken and a full medical history and clinical examination performed including visual acuity, refraction, slit-lamp examination, intra-ocular pressure measurement and detailed fundal examination. We describe the study design and protocol. Conclusion This study will provide the first estimate of the annual incidence of RRD in Scotland. The findings of this study will be important in estimating the burden of disease and in the planning of future health care policy related to this condition. This study will also establish a genetic resource for a genome wide association study to investigate if certain genetic variants predispose to RRD.

Importance Descemet stripping automated endothelial keratoplasty (DSAEK) for isolated endothelial dysfunction has become the preferred surgical option for many corneal surgeons. However, there are limited large-scale reports on DSAEK survival and clinical variables affecting the risk of rejection and failure after failed penetrating keratoplasty (PK). Objective To report the survival, risk factors for graft rejection and failure, and visual outcome of DSAEK after failed PK. Design, Setting, and Participants A multicenter retrospective interventional case series included patients recruited from 6 tertiary referral surgical centers: 3 in the United States, 2 in Europe, and 1 in Asia. A total of 246 consecutive eyes (246 patients) that underwent DSAEK after failed PK, with a minimum follow-up period of 1 month, was included. Data comprising demographic details, preoperative and postoperative risk factors, time to rejection, time to failure, and corrected distance visual acuity were collected. Main Outcomes and Measures Cumulative probability of graft survival, hazard ratio estimates for survival, and corrected distance visual acuity were determined. Results The mean (SD) recipient age was 63.2 (16.6) years and the median follow-up period was 17 months (interquartile range, 6-30 months). One-third of the grafts (n = 82) had follow-up data for more than 2 years; 18.3% had more than 1 failed PK before DSAEK. In total, 19.1% (47 of 246) of DSAEK grafts failed. The cumulative probability of DSAEK survival after a failed PK was 0.89 (95% CI, 0.84-0.92), 0.74 (95% CI, 0.64-0.81), and 0.47 (95% CI, 0.29-0.61) at 1 year, 3 years, and 5 years, respectively. Based on multivariate analysis, significant preoperative risk factors for failure were young recipient age (hazard ratio [HR], 5.18 [95% CI, 1.57-17.18]), previous tube filtration surgery (HR, 5.23 [95% CI, 1.47-7.33]), and rejection episodes before PK failure (HR, 3.28 [95% CI, 1.47-7.33]); single-surgeon centers had a protective effect. Any rejection episode prior to PK failure was a significant predictor of post-DSAEK rejection, which in turn was a significant predictor of DSAEK failure. After a median follow-up of 17 months, 33.3% of the grafts achieved 0.3 or greater logMAR (20/40) corrected distance visual acuity. Conclusions and Relevance Descemet stripping automated endothelial keratoplasty after failed PK combines greater wound stability and reduced suture-related complications, with visual outcomes and graft survival rates comparable to those of a second PK.

Use of pegaptanib in the treatment of vitreous haemorrhage in idiopathic retinal vasculitis

Thank you for your interest in our case and your insightful comments. Reaching a diagnosis of Eale’s disease involves systematic exclusion of known causes of retinal vasculitis. Although baseline investigations are important in all cases, individually tailored diagnostic testing based on patient symptoms and signs is recommended. Furthermore, in cases of diagnostic doubt, infection may be considered more likely if, after an initial improvement with therapy, the patient’s disease rapidly becomes refractory to treatment. Our case did in fact undergo an extensive systemic work-up, which was not emphasised in the study. We also referred our patient to the physicians given the unusual nature of his presenting symptoms. A complete physical examination as well as medical, contact, and travel history did not reveal any abnormalities or risk factors. In addition to routine blood and urine testing, other investigations performed included fasting glucose and lipid profile, thyroid function tests, renal and liver function tests, serum homocysteine levels, coagulation screen, vitamin B12 and folate levels, serum ACE, CRP, ESR, full autoantibody screen, serum protein electrophoresis, and 72-h Mantoux testing. Radiological investigations performed comprised a chest X-ray, abdominal ultrasound, and carotid Doppler. All investigations completed did not reveal any systemic abnormality. We agree that prompt referral to the physicians and a full contact and travel history are important in ruling out other causes of retinal vasculitis, especially in cases with systemic features (eg, fever, weight loss, and altered bowel habit). In our case, the clinical effect of adjunctive treatment with pegaptanib was evidenced by the rapid regression of disc and retinal neovascularisation with no recurrence of vitreous haemorrhage for up to 9 months.