Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion.

BACKGROUND: Branch retinal vein occlusion (BRVO) is one of the most commonly occurring retinal vascular abnormalities. The most common cause of visual loss in people with BRVO is macular oedema (MO). Grid or focal laser photocoagulation has been shown to reduce the risk of visual loss. Limitations to this treatment exist, however, and newer modalities may have equal or improved efficacy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) has recently been used successfully to treat MO resulting from a variety of causes. OBJECTIVES: To investigate the efficacy and gather evidence from randomised controlled trials (RCTs) on the potential harms of anti-vascular endothelial growth factor (VEGF) agents for the treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); MEDLINE Ovid; Embase Ovid; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. The date of the last search was 12 June 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating BRVO. Eligible trials had to have at least six months' follow-up where anti-VEGF treatment was compared with another treatment, no treatment, or placebo. We excluded trials where combination treatments (anti-VEGF plus other treatments) were used; and trials that investigated the dose and duration of treatment without a comparison group (other treatment/no treatment/sham). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data using standard methodological procedures expected by Cochrane. The primary outcome was the proportion of participants with an improvement from baseline in best-corrected visual acuity of greater than or equal to 15 letters (3 lines) on the Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six months and 12 months of follow-up. The secondary outcomes were the proportion of participants who lost greater than or equal to 15 ETDRS letters (3 lines) and the mean visual acuity (VA) change at six and 12 months, as well as the change in central retinal thickness (CRT) on optical coherence tomography from baseline at six and 12 months. We also collected data on adverse events and quality of life (QoL). MAIN RESULTS: We found eight RCTs of 1631 participants that met the inclusion criteria after independent and duplicate review of the search results. These studies took place in Europe, North America, Eastern Mediterranean region and East Asia. Included participants were adults aged 18 or over with VA of 20/40 or worse. Studies varied by duration of disease but permitted previously treated eyes as long as there was sufficient treatment-free interval. All anti-VEGF agents (bevacizumab, ranibizumab and aflibercept) and steroids (triamcinolone and dexamethasone) were included. Overall, we judged the studies to be at moderate or unclear risk of bias. Four of the eight studies did not mask participants or outcome assessors, or both. One trial compared anti-VEGF to sham. At six months, eyes receiving anti-VEGF were significantly more likely to have a gain of 15 or more ETDRS letters (risk ratio (RR) 1.72, 95% confidence interval (CI) 1.19 to 2.49; 283 participants; moderate-certainty evidence). Mean VA was better in the anti-VEGF group at six months compared with control (mean difference (MD) 7.50 letters, 95% CI 5.29 to 9.71; 282 participants; moderate-certainty evidence). Anti-VEGF also proved more effective at reducing CRT at six months (MD -57.50 microns, 95% CI -108.63 to -6.37; 281 participants; lower CRT is better; moderate-certainty evidence). There was only very low-certainty evidence on adverse effects. There were no reports of endophthalmitis. Mean change in QoL (measured using the National Eye Institute Visual Functioning Questionnaire VFQ-25) was better in people treated with anti-VEGF compared with people treated with sham (MD 7.6 higher score, 95% CI 4.3 to 10.9; 281 participants; moderate-certainty evidence). Three RCTs compared anti-VEGF with macular laser (total participants = 473). The proportion of eyes gaining 15 or more letters was greater in the anti-VEGF group at six months (RR 2.09, 95% CI 1.44 to 3.05; 2 studies, 201 participants; moderate-certainty evidence). Mean VA in the anti-VEGF groups was better than the laser groups at six months (MD 9.63 letters, 95% CI 7.23 to 12.03; 3 studies, 473 participants; moderate-certainty evidence). There was a greater reduction in CRT in the anti-VEGF group compared with the laser group at six months (MD -147.47 microns, 95% CI -200.19 to -94.75; 2 studies, 201 participants; moderate-certainty evidence). There was only very low-certainty evidence on adverse events. There were no reports of endophthalmitis. QoL outcomes were not reported. Four studies compared anti-VEGF with intravitreal steroid (875 participants). The proportion of eyes gaining 15 or more ETDRS letters was greater in the anti-VEGF group at six months (RR 1.67, 95% CI 1.33 to 2.10; 2 studies, 330 participants; high-certainty evidence) and 12 months (RR 1.76, 95% CI 1.36 to 2.28; 1 study, 307 participants; high-certainty evidence). Mean VA was better in the anti-VEGF group at six months (MD 8.22 letters, 95% CI 5.69 to 10.76; 2 studies, 330 participants; high-certainty evidence) and 12 months (MD 9.15 letters, 95% CI 6.32 to 11.97; 2 studies, 343 participants; high-certainty evidence). Mean CRT also showed a greater reduction in the anti-VEGF arm at 12 months compared with intravitreal steroid (MD -26.92 microns, 95% CI -65.88 to 12.04; 2 studies, 343 participants; moderate-certainty evidence). People receiving anti-VEGF showed a greater improvement in QoL at 12 months compared to those receiving steroid (MD 3.10, 95% CI 0.22 to 5.98; 1 study, 307 participants; moderate-certainty evidence). Moderate-certainty evidence suggested increased risk of cataract and raised IOP with steroids. There was only very low-certainty evidence on APTC events. No cases of endophthalmitis were observed. AUTHORS' CONCLUSIONS: The available RCT evidence suggests that treatment of MO secondary to BRVO with anti-VEGF improves visual and anatomical outcomes at six and 12 months.

Insights into the genetic basis of retinal detachment.

Retinal detachment (RD) 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 data set, where RD was ascertained by self-report or hospital records, genetic correlations between RD 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 RD cases (N = 3 977) and two cohorts, each comprising ~1 000 clinically ascertained rhegmatogenous RD 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 data set, where RD is self-reported by participants, firmly establishes six RD 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 RD, whereas the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritized 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 RD aetiology and underlying pathological pathways.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy.

PURPOSE: To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH). DESIGN: Multicenter, national cohort study. METHODS: 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. RESULTS: 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). CONCLUSIONS: Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema.

AIMS: To describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database. 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. 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. 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.

The Accuracy and Reliability of Crowdsource Annotations of Digital Retinal Images.

PURPOSE: Crowdsourcing is based on outsourcing computationally intensive tasks to numerous individuals in the online community who have no formal training. Our aim was to develop a novel online tool designed to facilitate large-scale annotation of digital retinal images, and to assess the accuracy of crowdsource grading using this tool, comparing it to expert classification. METHODS: We used 100 retinal fundus photograph images with predetermined disease criteria selected by two experts from a large cohort study. The Amazon Mechanical Turk Web platform was used to drive traffic to our site so anonymous workers could perform a classification and annotation task of the fundus photographs in our dataset after a short training exercise. Three groups were assessed: masters only, nonmasters only and nonmasters with compulsory training. We calculated the sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) plots for all classifications compared to expert grading, and used the Dice coefficient and consensus threshold to assess annotation accuracy. RESULTS: In total, we received 5389 annotations for 84 images (excluding 16 training images) in 2 weeks. A specificity and sensitivity of 71% (95% confidence interval [CI], 69%-74%) and 87% (95% CI, 86%-88%) was achieved for all classifications. The AUC in this study for all classifications combined was 0.93 (95% CI, 0.91-0.96). For image annotation, a maximal Dice coefficient (∼0.6) was achieved with a consensus threshold of 0.25. CONCLUSIONS: This study supports the hypothesis that annotation of abnormalities in retinal images by ophthalmologically naive individuals is comparable to expert annotation. The highest AUC and agreement with expert annotation was achieved in the nonmasters with compulsory training group. TRANSLATIONAL RELEVANCE: The use of crowdsourcing as a technique for retinal image analysis may be comparable to expert graders and has the potential to deliver timely, accurate, and cost-effective image analysis.

Comparison of ophthalmic training in 6 English-speaking countries.

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.

The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening.

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.

Exploring Sex and Laterality Imbalances in Patients Undergoing Laser Retinopexy.

IMPORTANCE: Studies have consistently reported a small preponderance of rhegmatogenous retinal detachments in males and in right eyes, which might suggest interesting differences in ocular anatomy relating to sex and laterality. However, an important potential confounding factor is that epidemiologic studies do not consider retinal tears that do not lead to detachment. This study used the electronic patient records from a large eye hospital to explore whether any sex and laterality imbalances were present in patients who underwent laser retinopexy. OBSERVATIONS: Analysis was conducted from December 1, 2014, to March 1, 2015. Of 6760 patients who underwent retinopexy between May 21, 1996, and October 27, 2014, sex had been recorded for 5854 patients (3346 males and 2508 females) and laterality recorded for 3780 eyes (1990 treatments in the right eye and 1790 in the left eye). The proportion of males was 57.2% (95% CI, 55.9%-58.4%) and the proportion of right eyes was 52.6% (95% CI, 51.1%-54.2%). For sex and laterality, the 95% CIs did not overlap the 50% mark, indicating that the imbalance was likely not owing to chance. CONCLUSIONS AND RELEVANCE: Our study showed that laser retinopexy was performed more often in males and in right eyes. This imbalance is in the same direction as that seen for retinal detachments, suggesting that males and right eyes may have an anatomical predisposition toward retinal tears and detachment, possibly related to a slightly greater average axial length.

Crowdsourcing as a screening tool to detect clinical features of glaucomatous optic neuropathy from digital photography.

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.

Descemet stripping automated endothelial keratoplasty after failed penetrating keratoplasty: survival, rejection risk, and visual outcome.

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.

Macular Hole Progression following Ocriplasmin Intravitreal Injection.

Ocriplasmin is a protease which has been approved for the treatment of symptomatic vitreomacular adhesion (VMA). A 63-year-old presented with blurred vision in the left eye and a best corrected visual acuity of 6/18. Optical coherence tomography revealed VMA with an underlying macular hole and she subsequently underwent a left intravitreal ocriplasmin injection. One week after the injection, VMA had been released but with enlargement of the macular hole and a drop in her BCVA to 6/60. This persisted at 1 month after the injection. It is important to warn patients that ocriplasmin may lead to an enlargement of their macular hole with resultant loss in visual acuity.

Acute serous macular detachment and cystoid macular edema after uncomplicated phacoemulsification using standard dose subconjunctival cefuroxime.

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.

Crowdsourcing as a novel technique for retinal fundus photography classification: analysis of images in the EPIC Norfolk cohort on behalf of the UK Biobank Eye and Vision Consortium.

AIM: Crowdsourcing is the process of outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing for the classification of retinal fundus photography. METHODS: One hundred retinal fundus photograph images with pre-determined disease criteria were selected by experts from a large cohort study. After reading brief instructions and an example classification, we requested that knowledge workers (KWs) from a crowdsourcing platform classified each image as normal or abnormal with grades of severity. Each image was classified 20 times by different KWs. Four study designs were examined to assess the effect of varying incentive and KW experience in classification accuracy. All study designs were conducted twice to examine repeatability. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: Without restriction on eligible participants, two thousand classifications of 100 images were received in under 24 hours at minimal cost. In trial 1 all study designs had an AUC (95%CI) of 0.701(0.680-0.721) or greater for classification of normal/abnormal. In trial 1, the highest AUC (95%CI) for normal/abnormal classification was 0.757 (0.738-0.776) for KWs with moderate experience. Comparable results were observed in trial 2. In trial 1, between 64-86% of any abnormal image was correctly classified by over half of all KWs. In trial 2, this ranged between 74-97%. Sensitivity was ≥ 96% for normal versus severely abnormal detections across all trials. Sensitivity for normal versus mildly abnormal varied between 61-79% across trials. CONCLUSIONS: With minimal training, crowdsourcing represents an accurate, rapid and cost-effective method of retinal image analysis which demonstrates good repeatability. Larger studies with more comprehensive participant training are needed to explore the utility of this compelling technique in large scale medical image analysis.

Genome-wide association study identifies genetic risk underlying primary rhegmatogenous retinal detachment.

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 × 10(-7)). The strongest association, for rs12960119 (P = 1.58 × 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 × 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.

Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion.

BACKGROUND: Branch retinal vein occlusion (BRVO) is one of the most common occurring retinal vascular abnormalities. The pathogenesis of BRVO is thought to involve both retinal vein compression and damage to the vessel wall, possibly leading to thrombus formation at sites where retinal arterioles cross retinal veins. The most common cause of visual loss in patients with BRVO is macular oedema (MO). Grid or focal laser photocoagulation has been shown to reduce the risk of visual loss and improve visual acuity (VA) in up to two thirds of individuals with MO secondary to BRVO, however, limitations to this treatment exist and newer modalities have suggested equal or improved efficacy. Recently, antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) has been used successfully to treat MO resulting from a variety of causes. As elevated intraocular levels of VEGF have been demonstrated in patients with retinal vein occlusions there is a strong basis for the hypothesis that anti-VEGF agents may be beneficial in the treatment of vascular leakage and MO. OBJECTIVES: To investigate the efficacy and safety of intravitreal anti-VEGF agents for preserving or improving vision in the treatment of MO secondary to BRVO. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 August 2012 and the clinical trials registers on 10 September 2012. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTS of at least six months duration where anti-VEGF treatment was compared with another treatment, no treatment, or placebo. We excluded trials where combination treatments (anti-VEGF plus other treatments) were used and trials that investigated the dose and duration of treatment without a comparison group (other treatment/no treatment/sham). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data. The primary outcome was the proportion of participants with an improvement from baseline in best-corrected visual acuity (BCVA) of greater than or equal to 15 letters (3 lines) on the Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six months and at 12 months of follow-up. The secondary outcomes we report are the proportion of participants who lost greater than or equal to 15 ETDRS letters (3 lines) and the mean VA change at six months and any additional follow-up intervals as well as the change in central retinal thickness on optical coherence tomography (OCT) from baseline and final reported follow-up, the number and type of complications, the number of additional interventions administered and any adverse outcomes. Where available, the cost benefit and quality of life data reported in the primary studies is presented. MAIN RESULTS: We found one RCT and one quasi-RCT that met the inclusion criteria after independent and duplicate review of the search results. The studies used different anti-VEGF agents and different study groups which were not directly comparable.One multi-centre RCT (BRAVO) conducted in the USA randomised 397 individuals and compared monthly intravitreal ranibizumab (0.3 mg and 0.5 mg) injections with sham injection. The study only included individuals with non-ischaemic BRVO. Although repeated injections of ranibizumab appeared to have a favourable effect on the primary outcome, approximately 50% of the ranibizumab 0.3 mg group and 45% of the ranibizumab 0.5 mg group received rescue laser treatment which may have an important effect on the primary outcome. In addition, during the six-month observation period 93.5% of individuals in the sham group received intravitreal ranibizumab (0.5 mg). This cross-over design limits the ability to compare the long-term impact of ranibizumab versus a pure control group.The second trial was a small study (n = 30) from Italy with limitations in study design that reported a benefit of as-required intravitreal bevacizumab (1.25 mg) over laser photocoagulation in MO secondary to BRVO. We present the evidence from these trials and other interventional case series. AUTHORS' CONCLUSIONS: The available RCT evidence suggests that repeated treatment of non-ischaemic MO secondary to BRVO with the anti-VEGF agent ranibizumab may improve clinical and visual outcomes at six and 12 months. However, the frequency of re-treatment has not yet been determined and the impact of prior or combined treatment with laser photocoagulation on the primary outcome is unclear. Results from ongoing studies should assess not only treatment efficacy but also, the number of injections needed for maintenance and long-term safety and the effect of any prior treatment.

Childhood visual impairment in England: a rising trend.

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.

Long-term visual acuity and the duration of macular detachment: findings from a prospective population-based study.

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.