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To investigate the diagnostic value of elevated retinal pigment epithelium (RPE) and double-layer sign (DLS) in identifying macular neovascularization (MNV) secondary to central serous chorioretinopathy (CSCR).Retrospective, cross-sectional study.Patients with CSCR underwent optical coherence tomography (OCT) and OCT angiography (OCT-A) scanning at Moorfields Eye Hospital. OCT scans were reviewed to identify the presence/absence of an RPE elevation. The maximum length and maximum height of the elevated RPE were measured. A minimum length of 1000 µm and a maximum height of 150 µm were used to define the "double-layer sign." Other qualitative anatomical features were also graded from OCT scans. OCT-A was examined to confirm the presence/absence of MNV. Binary logistic regression analyses were used to assess the association between OCT features and the detection of MNV on OCT-A. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the diagnostic accuracy.One hundred sixty-three eyes from 132 patients were included. Elevated RPE was detected in 148 eyes (91%). OCT-A-confirmed MNV was detected in 54 eyes (33%). The sensitivity and specificity of RPE elevation were 100% and 13.8%, respectively. DLS was identified in 95 eyes (58%). The sensitivity and specificity of DLS for detecting MNV were 87% and 56%, respectively. Hyperreflectivity and nonhomogeneity of the sub-RPE space were independently associated with MNV within the DLS (odds ratio, 17.7 and 14.8, P.001 and P = .02, respectively). None of the other demographic or anatomical features were associated with MNV. The presence of nonhomogeneous hyperreflective RPE elevation had a sensitivity and specificity of 98% and 67%, with PPV and NPV of 60% and 99%, respectively.Nonhomogeneous and hyperreflective space under an elevated RPE of any length or height indicates an eye with higher risk of MNV than DLS. OCT-A should at least be performed for these eyes to confirm the presence of MNV and treat accordingly.

PURPOSE To study the time course to macular atrophy (MA) and associated risk factors in eyes with acquired vitelliform lesions (AVLs) as they vary between patients and between eyes of an individual. DESIGN Single-center, retrospective, observational cohort study. PARTICIPANTS Consecutive patients registered between January 2009 and January 2014 with first diagnosis of AVL confirmed by multimodal imaging were included. Eyes with baseline MA or choroidal neovascularization were excluded. METHODS Patient demographics were collected. Serial OCT scans and fundus autofluorescence (FAF) scans were graded and analyzed. Turnbull's estimator was used, and time was censored at 5 years. Multivariable Weibull parametric proportional hazard models were used to assess the association of risk factors with MA after adjustment for age and gender. Hazard ratios (HRs) are reported with 95% confidence interval (CI). MAIN OUTCOME MEASURES Time to the first OCT evidence of MA stratified by presenting visual acuity (VA) and AVL lesion subtypes. Secondary outcome included risk factors for incident MA. RESULTS A total of 237 eyes (132 patients) met the inclusion criteria. Incident MA was detected in 52 of 237 eyes (21.9%) by 5 years. Stratified by baseline VA, 40.3% of eyes with VA ≤70 letters developed atrophy within 5 years of first diagnosis in contrast to 10.3% eyes with VA >70 letters (P < 0.001). Based on lesion type only, 12.9% of eyes with vitelliform lesion at baseline developed MA versus 39.8% and 44.2% of eyes with pseudohypopyon or vitelliruptive lesion type, respectively. In adjusted analysis, baseline factors associated with increased risk of MA included VA ≤70 letters (hazard ratio [HR], 5.54; 95% confidence interval [CI], 2.30-13.34), base width (HR, 1.22; 95% CI, 1.16-1.28), maximum height (HR, 2.61; 95% CI, 1.82-3.74), presence of subretinal drusenoid deposits (SDDs) (HR, 2.83; 95% CI, 1.34-5.96), and disrupted external limiting membrane (ELM) (HR, 2.81; 95% CI, 1.34-5.86). CONCLUSIONS Baseline VA of ≤70 letters (Snellen ≤20/40) and pseudohypopyon or vitelliruptive lesion type attribute the highest risk for MA. Other prognostic indicators for MA include baseline presence of SDD, disrupted ELM, and larger lesion area.

Purpose Validation of a recently described central serous chorioretinopathy (CSCR) classification system and assessment of levels of agreement among 10 retina physicians. Methods This was a cross-sectional (inter-reader agreement) study. Ten retina physicians (assigned a role of masked grader) were provided with a comprehensive dataset of 61 eyes of 34 patients of presumed CSCR. Relevant clinical details and multimodal imaging (fundus autofluorescence, fluorescein and indocyanine green angiography, optical coherence tomography) of both involved and fellow eye were electronically shared. Later, only the fellow eye images were resent to understand the influence of affected eye on the grading of the fellow eye. Multiple inter-grader agreement using Fleiss Kappa was performed to determine the level of agreement among the 10 graders. p value of ≤ 0.05 was considered statistically significant. Results Sixty-one eyes of 34 patients were evaluated. There was moderate agreement for major criteria with Fleiss Kappa value of 0.50 (p Conclusion A fair-moderate inter-grader agreement among the masked graders suggests a need for further refinement of this novel classification system. Disease grading should include both eyes as lack of information on affected eye has a bearing on fellow eye grading and inter-grader agreement as shown by a significant difference in global [Formula: see text] values.

Vision-threatening diabetic retinopathy (VTDR) is one of the leading causes of impaired vision in the working-age population. Early identification, timely diagnosis, and prompt treatment of VTDR have to be tackled simultaneously to reduce the rate of blindness due to this condition. Considerable emphasis has been placed globally on establishing diabetic retinopathy screening (DRS) programs to enable early identification and referral of VTDR for treatment. However, there is an urgent need to shift from the common practice of opportunistic screening to a systematic DRS pathway to ensure that individuals with diabetes are screened at regular intervals and treated appropriately. While systematic DRS programs have been successfully established in countries such as the United Kingdom (UK), it continues to be a challenge to initiate and sustain such programs in low- and middle-income countries (LMIC), home to approximately 80% of people with diabetes. Telemedicine is widely recognized as an ideal DRS screening program. Although it has resulted in an upsurge of opportunistic screening, systematic recall of screened patients remains a challenge. In addition, the link between referred patients from the telemedicine programs to treatment centers is often not established or has failed to deliver; so, there is minimal impact of these telemedicine programs on VTDR blindness at present. This review covers the various barriers of establishing and sustaining systematic telemedicine DRS programs, especially in resource-constrained settings, and the challenges in aligning telemedicine to VTDR treatment pathways to ensure patients with VTDR are treated promptly and effectively.

Translating research findings to routine clinical practice is fraught with obstacles. The gap between the end of a research project and the implementation of its results is often termed the "valley of death." In this perspective, we highlight the barriers and potential solutions in translating research on diabetic retinopathy care pathways to implementation in the clinic. This gap analysis applies to all countries around the world, though it predominantly applies to low- and middle-income countries.

To evaluate the diagnostic accuracy of ultrawide pseudocolor retinal photography (pseudocolor UWF) compared to wide field fundus fluorescein angiography (WFFFA) in the detection of retinal neovascularization (NV) and NV of the disc (NVD) in patients with diabetic retinopathy (DR). Diagnostic accuracy observational study evaluating pseudocolor UWF as the index test. The reference standard was WFFFA. Single retinal centre in India. People with severe non-proliferative DR (sNPDR), early proliferative DR (ePDR) or high-risk proliferative DR (HR PDR). Sensitivity and specificity of pseudocolor UWF in the detection of NV. A total of 176 eyes of 94 subjects with sNPDR, ePDR or HR PDR underwent pseudocolor UWF and WFFFA. The sensitivity and specificity of pseudocolor UWF in detecting NVE were 92.5% (95% CI 86.2–96.5) and 81% (95% CI 64.8–92.0), respectively, with moderate interobserver agreement of 0.722 (p value 0.001). The positive predictive value and negative predictive value were 83.0 (71.4–90.5) and 91.5 (84.9–95.3), respectively. Compared to WFFFA as the gold standard, pseudocolor UWF has high sensitivity and specificity in detection of NV in all retinal quadrants and NVD. Therefore, pseudocolor UWF may be used as a non-invasive tool for screening and managing DR.

Objective To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes. Methods This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA1C), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho). Results Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant. Conclusion Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

OBJECTIVES To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. SUBJECTS/METHODS All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. RESULTS In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p

Background/aimsTo evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients receiving treatment for unilateral nAMD in a UK National Health Service (NHS) hospital outpatient setting.MethodsA patient-level state transition model was constructed to simulate the onset, detection, and treatment of nAMD in the second eye. Five index tests were compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity from baseline, fundus assessment by clinical examination or colour photography, and spectral domain optical coherence tomography (SD-OCT). Diagnosis of nAMD was confirmed by fundus fluorescein angiography (FFA) before prompt initiation of antivascular endothelial growth factor treatment. Quality-adjusted life-years (QALYs) and costs of health and social care were modelled over a 25-year time horizon.ResultsSD-OCT generated more QALYs (SD-OCT, 5.830; fundus assessment, 5.787; Amsler grid, 5.736, patient’s subjective assessment, 5.630; and visual acuity, 5.600) and lower health and social care costs (SD-OCT, £19 406; fundus assessment, £19 649; Amsler grid, £19 751; patient’s subjective assessment, £20 198 and visual acuity, £20 444) per patient compared with other individual monitoring tests. Probabilistic sensitivity analysis indicated a high probability (97%–99%) of SD-OCT being the preferred test across a range of cost-effectiveness thresholds (£13 000–£30 000) applied in the UK NHS.ConclusionsEarly treatment of the second eye following FFA confirmation of SD-OCT positive findings is expected to maintain better visual acuity and health-related quality of life and may reduce costs of health and social care over the lifetime of patients.

Macular telangiectasia type 2 (MacTel) is bilateral disease with characteristic alterations of the macular capillary network along with decreased macular pigment in the parafoveal area. The purpose of this study was to highlight that some eyes show microvascular changes which precede any visible neuronal changes on spectral-domain optical coherence tomography (SD-OCT). This observational study was conducted at a tertiary eye institute. From a registry of 630 patients with MacTel, we identified 4 patients with typical MacTel characteristics in only one eye with no visible changes on colour photographs or SD-OCT in the fellow eye. These 4 patients had findings of MacTel documented by colour fundus photograph, multicolour imaging (MCI), fundus autofluorescence (FAF), confocal blue reflectance (CBR), SD-OCT, and OCT-Angiography (OCT-A) in one eye. OCT-A was performed in MacTel patients using the High-resolution Spectralis (Heidelberg Engineering) module with a full-spectrum probabilistic approach and we employed a 30° x 15° (~8.8 mm × 4.4 mm) scan pattern covering the macula. MCI was done at the end so as to avoid fading the confocal blue reflectance hyperreflectivity seen in MacTel. On OCT-A, all 4 fellow eyes showed telangiectasia and foveal avascular zone changes in the superficial and deep capillary plexuses with no changes on SD-OCT. None of the eyes showed typically increased reflectance on CBR around the foveal area. These findings show that microvascular changes on OCT-A may occur before visible neurodegenerative changes on OCT, providing new insights into the course of the disease.

Objectives DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. Methods Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. Results A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of −119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA Conclusion Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.

Diabetic retinopathy (DR) is a global health burden. Screening for sight-threatening DR (STDR) is the first cost-effective step to decrease this burden. We analyzed the similarities and variations between the recent country-specific and the International Council of Ophthalmology (ICO) DR guideline to identify gaps and suggest possible solutions for future universal screening. We selected six representative national DR guidelines, one from each World Health Organization region, including Canada (North America), England (Europe), India (South- East Asia), Kenya (Africa), New Zealand (Western Pacific), and American Academy of Ophthalmology Preferred Practice Pattern (used in Latin America and East Mediterranean). We weighed the newer camera and artificial intelligence (AI) technology against the traditional screening methodologies. All guidelines agree that screening for DR and STDR in people with diabetes is currently led by an ophthalmologist; few engage non-ophthalmologists. Significant variations exist in the screening location and referral timelines. Screening with digital fundus photography has largely replaced traditional slit-lamp examination and ophthalmoscopy. The use of mydriatic digital 2-or 4-field fundus photography is the current norm; there is increasing interest in using non-mydriatic fundus cameras. The use of automated DR grading and tele-screening is currently sparse. Country-specific guidelines are necessary to align with national priorities and human resources. International guidelines such as the ICO DR guidelines remain useful in countries where no guidelines exist. Validation studies on AI and tele-screening call for urgent policy decisions to integrate DR screening into universal health coverage to reduce this global public health burden.摘要: 糖尿病视网膜病变(DR)是全球性的健康负担。筛查威胁视力的DR (STDR)是降低这一负担的第一个具有成本效益的步骤。我们分析了不同国家特有的指南和国际眼科理事会(ICO)指南之间的共同点和差异点, 以确定差距, 并为未来的普遍筛查提出可能的解决方案。我们选择了六个具有代表性国家的DR指南, 每个世界卫生组织区域各一个, 包括加拿大 (北美) 、英国 (欧洲) 、印度 (东南亚) 、肯尼亚 (非洲) 、新西兰 (西太平洋) 和美国眼科学会首选的临床模式 (拉丁美洲和东地中海) 。我们考量了较新的照相技术、人工智能 (AI) 技术与传统筛查方法之间的差别。所有指南都认为糖尿病患者的DR和STDR筛查应该由眼科医生主导进行, 仅少量主张非眼科医生参与。但筛选地点和转诊时间不同指南之间存在显著差异。数字眼底照相筛检在很大程度上取代了传统的裂隙灯检查和检眼镜。散瞳后的数字眼底照相视野2个或4个视野范围是目前的标准, 但免散瞳的眼底照相也逐渐兴起。目前很少使用自动进行DR分级和远程筛查。根据各国的重点政策和人力资源情况制定相应的具体指南必不可少。但国际指南如ICO-DR指南在没有具体指南的国家仍然可以使用。为了减轻这一全球公共卫生负担, 有关AI和远程筛查的有效性研究需要立刻进行政策决策, 以将DR筛查纳入全民健康的覆盖范围。.

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

The aim of this review was to discuss frequently encountered themes such as cataract surgery in presence of age-related macular degeneration (AMD), dementia, Immediate Sequential Bilateral Cataract Surgery (ISBCS), discussing non-standard intraocular lens (IOL) options during consultation in the National Health Services (NHS) and the choice of the biometric formulae based on axial length. Individual groups of authors worked independently on each topic. We found that cataract surgery does improve visual acuity in AMD patients but the need for cataract surgery should be individualised. In patients with dementia, cataract surgery should be considered 'sooner rather than later' as progression may prevent individuals presenting for surgery. This should be planned after discussion of patients' best interests with any carers; multifocal IOLs are not proven to be the best option in these patients. ISBCS gives comparable outcomes to delayed sequential surgeries with a low risk of bilateral endophthalmitis and it can be cost-saving and efficient. Patients are entitled to know all suitable IOL options that can improve their quality of life. Deliberately withholding this information or pressuring patients to choose a non-standard IOL is inappropriate. However, one should be mindful of the not spending inappropriate amounts of time discussing these in the NHS setting which may affect care of other NHS patients. Evidence suggests Hoffer Q, Haigis, Hill-RBF and Kane formulae for shorter eyes; Barrett Universal II (BU II), Holladay II, Haigis and Kane formulae for longer eyes and BU II, Hill-RBF and Kane formulae for medium axial length eyes.摘要: 本文旨在探讨在合并年龄相关性黄斑变性 (age-related macular degeneration, AMD)、 痴呆进行白内障手术以及即刻连续性双侧白内障手术(Immediate Sequential Bilateral Cataract Surgery, ISBCS)时存在的一些问题, 讨论在国家医疗服务制度 (National Health Services, NHS) 和基于生物轴向长度公式计算眼内人工晶体的选择。每组作者针对每个话题进行独立工作。我们发现, 白内障手术确实能提高AMD患者的视力, 但是否需要行白内障手术应因人而异。对于痴呆患者, 白内障手术应该被认为“更早而不是晚”, 因为病情进展可能会妨碍患者接受手术。这应在与医疗人员讨论病人的最大利益后进行安排和计划;尚未证明多焦IOLs是这些患者的最佳选择。与延迟连续手术相比, ISBCS双侧眼内炎的风险较低, 并且其成本更低及高效。患者有权获知所有可以改善其生活质量的合适的IOL选择方面的信息, 故意隐瞒这些信息或强迫患者选择非标准IOL是不妥的。然而, 在NHS系统中人们应该注意不要花过多的时间讨论这些, 因为这可能会影响NHS其他患者的护理。证据表明Hoffer Q、Haigis、Hill-RBF和Kane公式适用于眼轴较短的眼;较长眼轴的眼使用Barrett Universal II (BU II)、Holladay II、Haigis和Kane公式, 中等眼轴的眼使用BU II、Hill-RBF和Kane公式。.

Background We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion. Methods We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually. Results Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection. Conclusions Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.

Aims To estimate the incidence of early treatment diabetic retinopathy study (ETDRS) level 47 and 53 and progression to treatment with panretinal photocoagulation (PRP) for proliferative DR (PDR). Methods Log-linear regression was used to estimate the incidence of level 47–53 or worse for 33,009 people with diabetes (PWD) in Gloucestershire during 2013–2016 by calendar year and diabetes type, based on the first recording. Progression was analysed in Gloucestershire and Bristol with a parametric survival analysis examining the association of baseline and time-varying demographic and clinical factors on time to PRP after the first recording of level 47–53. Results Incidence decreased from 0.57 (95% confidence intervals (CI) 0.48–0.67) per 100 PWD in 2013 to 0.35 (95% CI 0.29–0.43) in 2016 (p 1c were associated with an increase in the risk of initiating PRP (hazard ratio 3.14 (95% CI: 1.60–6.15) and 1.21 (95% CI: 1.06–1.38 per 10 mmol/mol) respectively). Conclusion This study provides additional understanding of this population and shows that a high proportion of patients with ETDRS levels 47–53 need to be monitored as they are at high risk of progressing to PDR.

Aim To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight‐threatening diabetic retinopathy (STDR) among those with mild non‐proliferative diabetic retinopathy (NPDR). Materials and Methods An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010‐2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010‐2011, as well as the number of National Diabetes Audit processes completed in 2010‐2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model. Results A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow‐up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55‐0.74; p

Background In chronic central serous chorioretinopathy, fluid accumulates in the subretinal space and causes permanent vision loss in ≈ 30% of patients. There is no definitive treatment. Previous research suggests that the mineralocorticoid receptor antagonist eplerenone is effective but it is not licensed for chronic central serous chorioretinopathy. Objectives The objective was to evaluate whether or not eplerenone was safe and superior to placebo for treating chronic central serous chorioretinopathy. We also aimed to set up a biobank of DNA, serum and plasma samples from treatment-naive participants for future research. Design The trial was a parallel, randomised (1 : 1 ratio), multicentre, double-masked, placebo-controlled superiority trial comparing eplerenone plus usual care with placebo plus usual care. Participants were randomly allocated to eplerenone or placebo using a secure online system that returned a unique number corresponding to a bottle of the investigational medicinal product. Participants, clinical care teams, pharmacists, outcome assessors and the trial management group were masked. Setting The trial took place in 22 NHS hospitals in the UK. Participants Eligible participants were patients aged 18–60 years with treatment-naive chronic central serous chorioretinopathy of at least 4 months’ duration, a best corrected visual acuity score of 54–85 letters and no other conditions affecting visual acuity or contraindications to taking eplerenone or placebo. Interventions The intervention was oral eplerenone (25 mg/day for 1 week, increased to 50 mg/day for up to 12 months). Placebo was a lactose-filled capsule that appeared identical to the overencapsulated eplerenone tablets. To maintain blinding, participants in the placebo group followed the same dose escalation schedule as the eplerenone group. Usual care was included in both groups and was administered at the discretion of clinicians. Main outcome measures The primary outcome was best corrected visual acuity score at 12 months. Secondary outcomes were low-luminance visual acuity, central subfield retinal thickness, change in subretinal fluid thickness, systemic and ocular adverse events, macular atrophy of the retinal pigment epithelium, subfoveal choroidal thickness, choroidal permeability, resolution of subretinal fluid, time to recurrence of subretinal fluid, fundus fluorescein angiography phenotype, incidence of chronic central serous chorioretinopathy in the fellow eye, and patient-reported visual function. Results Between 11 January 2017 and 22 February 2018, 57 participants were randomised to eplerenone and 57 to placebo; 57 and 54 participants, respectively, were included in the analysis of the primary outcome. The modelled mean best corrected visual acuity score at 12 months in the eplerenone and placebo groups was 80.4 letters (standard deviation 4.6 letters) and 79.5 letters (standard deviation 4.5 letters), with an estimated difference between groups of 1.73 letters (95% confidence interval –1.12 to 4.57 letters; p = 0.24). Hyperkalaemia occurred in eight participants in each group (14%). No serious adverse events occurred in the eplerenone group; three unrelated serious adverse events occurred in the placebo group. Limitations Limitations included the inability to prevent co-treatments and discontinuation of the investigational medicinal product in the event of resolution or hyperkalaemia. Conclusions Eplerenone was safe but not superior to placebo in improving best corrected visual acuity in people with chronic central serous chorioretinopathy during 12 months of follow-up. In future work, ophthalmologists should investigate alternative treatments for this condition, which remains complicated to treat. Trial registration Current Controlled Trials ISRCTN92746680. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 2. See the NIHR Journals Library website for further project information.

Purpose The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. Design Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). Main Outcome Measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. Results The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%–91%] and 48% [95% CI, 41%–56%], respectively) or UWF images (83% [95% CI, 75%–89%] and 54% [95% CI, 46%–61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%–93%] and 49% [95% CI, 42%–56%], respectively, for UWF versus 80% [95% CI, 69–88%] and 40% [95% CI, 34%–47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. Conclusions The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

Purpose To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD). Design Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years. Participants Older adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD. Methods Self-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA. Main Outcome Measures Sensitivity and specificity of the 5 index tests. Results Of 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6–9.8); Amsler 33.7 (95% CI, 25.1–43.5); VA 30.0 (95% CI, 22.5–38.7); fundus examination 53.8 (95% CI, 44.8–62.5); and OCT 91.7 (95% CI, 85.2–95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6–98.5), 81.4 (95% CI, 76.4–85.5), 66.3 (95% CI, 61.0–71.1), 97.6 (95% CI, 95.3–98.9), and 87.8 (95% CI, 83.8–90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination. Conclusions Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Introduction: To report the 10-year rate of vitrectomies and the associated factors in people with proliferative diabetic retinopathy (PDR) from a multicentric cohort of people with diabetes mellitus. Methods: Ten centres in India with established vitreoretinal (VR) services for over 10 years were invited to provide long-term data on PDR. People with Type 1 or 2 diabetes with a clinical diagnosis of active PDR in 1 or both eyes were included. Baseline data collected included age, sex, duration of diabetes, source of referral and best-corrected visual acuity, and diabetic retinopathy status in both eyes. Available follow-up data included the numbers of panretinal photocoagulation (PRP) sessions, cataract surgery, treatment of diabetic macular oedema, use of anti-vascular endothelial growth factor (VEGF) therapy, vitrectomy with or without retinal surgeries over 10 years. Results: Over 10 years, 89% needed supplemental PRP after initial complete PRP. One-third required retinal surgery, 16% needed intravitreal injection. Men (74.5%) had significant higher risk for vitreous (VR) surgery. Of the group with low-risk PDR, 56.8% did not require VR surgery, p < 0.001. Of the patients who underwent cataract surgery and had intravitreal anti-VEGF injections, 78.5 and 28.2% needed subsequent vitreous (VR) surgery, p = 0.006 and

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BackgroundTo describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).MethodsRetrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections.ResultsFor our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient’s better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes).ConclusionsThe chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes.

New clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion–exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35–54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p

Diabetic retinopathy (DR) is a microvascular complication of diabetes with a prevalence of ~35%, and is one of the leading causes of visual impairment in people of working age in most developed countries. The earliest stage of DR, non-proliferative DR (NPDR), may progress to sight-threatening DR (STDR). Thus, early detection of DR and active regular screening of patients with diabetes are necessary for earlier intervention to prevent sight loss. While some countries offer systematic DR screening, most nations are reliant on opportunistic screening or do not offer any screening owing to limited healthcare resources and infrastructure. Currently, retinal imaging approaches for DR screening include those with and without mydriasis, imaging in single or multiple fields, and the use of conventional or ultra-wide-field imaging. Advances in telescreening and automated detection facilitate screening in previously hard-to-reach communities. Despite the heterogeneity in approaches to fit local needs, an evidence base must be created for each model to inform practice. In this review, we appraise different aspects of DR screening, including technological advances, identify evidence gaps, and propose several studies to improve DR screening globally, with a view to identifying patients with moderate-to-severe NPDR who would benefit if a convenient treatment option to delay progression to STDR became available.

Purpose Approximately 50% of patients receiving anti–vascular endothelial growth factor (VEGF) therapy show significant improvement in diabetic retinopathy severity score (DRSS), in particular at DRSS level 47 to 53 (moderately severe to severe nonproliferative diabetic retinopathy). Level 47 to 53 consists of 3 main features: deep hemorrhages (DH), venous beading (VB), and intraretinal microvascular abnormalities (IRMAs). It is unclear whether these features respond to anti-VEGF therapies differently. Design Post hoc analysis of Intravitreal Aflibercept versus Panretinal Photocoagulation in Patients with Proliferative Diabetic Retinopathy (CLARITY) study. Participants Treatment-naive participants randomized to intravitreal aflibercept. Methods We reanalyzed the fundus images at baseline, week 12, and week 52 to assess the changes of the 3 main features in DRSS level 47 to 53 in those patients who were treatment naive and had received aflibercept. Main Outcome Measures Changes in DH, VB, and IRMA after aflibercept therapy at weeks 12 and 52. Results Fifty-five treatment-naive eyes at baseline that received aflibercept were included in the study. Severe DH and severe IRMA improved in approximately 75% of eyes at week 12 and mostly remained improved at week 52; VB remained unchanged in all eyes at week 12. From 12 weeks, 32 eyes that had received injections showed improved or stable DH compared with 7 eyes that did not receive injections, and DH deteriorated in 6 eyes with no further injections compared with 4 eyes that had received more injections (P = 0.0072). Similarly, 15 eyes that continued to receive injections from week 12 showed improved or stable IRMA compared with 4 who did not receive injections (P = 0.006). Worsening of IRMA was seen in 5 eyes with no further injections compared with 4 eyes that continued to receive injections. The improvements in DH and IRMA are more likely to be maintained if less than 16 weeks have elapsed since the last anti-VEGF injection. Conclusions Aflibercept seems to improve DH and IRMA after just 3 injections. As soon as the frequency of injections were reduced, DH and IRMA can deteriorate again. It is unclear whether these results can be translated to patients without PDR.

The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650–>1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28–72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.

PURPOSE: To assess the short-term and long-term visual outcomes in patients with choroidal neovascularisation (CNV) secondary to angioid streaks treated with intravitreal anti-vascular endothelial growth factor (VEGF). METHODS: Retrospective, single-centre study. RESULTS: Overall 66 eyes of 52 patients were analysed. Follow-up ranged from 1 to 10 years. BCVA was 62 ETDRS letters at baseline, 68 letters at 1 year, 60 ETDRS letters at 5 years and 58 letters at 7 years. At 2 years patients gained 5.7 ETDRS letters from baseline but this gain was lost at 5 years. At 5 years there was an average loss of ETDRS letters from baseline of 3.3 letters. Sub-group analysis of subfoveal CNV showed worse outcome compared with eyes with extrafoveal and juxtafoveal CNV. In subfoveal CNV, BCVA was 53 ETDRS letters at 1 year (p

Purpose Single center, noninterventional cohort study to assess 10-year visual and anatomical outcomes following initiation of treatment with antivascular endothelial growth factor (anti-VEGF) agents in neovascular age-related macular degeneration (AMD) patients. Neovascular AMD patients initiated on intravitreal anti-VEGF injections in 2008–2009 and continued to be followed up for at least 10 years were included in this study. Methods The Moorfields OpenEyes database was searched for all patients who were initiated on anti-VEGF therapy for neovascular AMD in 2008–2009 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records were analyzed for those who have had at least 10-year follow-up. The spectral-domain optical coherence tomography (SD-OCT) scans, color fundus photos, and fundus fluorescein angiography (FA) were graded by two retinal physicians. The outcomes were also compared between those with good and poor VA outcomes based on pre-defined criteria. The primary end point was change in VA at 10 years; secondary outcomes included percentage with VA of 20/40 or better, 20/70 or better, VA gains and losses, anatomic outcomes and number of injections. Results After a mean of 10.04 years after initiation of anti-VEGF therapy, the mean decline in VA from baseline was −2.1 ETDRS letters (SD 19.9, p = 0.65). One hundred eyes (67.1%) achieved a VA threshold of 20/70 or better, 33.5% achieved a VA of 20/40 or better, and 76.5% eyes maintained VA defined as a loss of less than 15 letters. Fourteen percent of study eyes had VA of 20/200 or worse and 23.5% declined by 15 letters or more. 87.5% of eyes were switched from ranibizumab to aflibercept during the course of 10 years and the eyes received a mean of 52.2 (SD 18.1) injections over 10 years. From this cohort, 87 (58.3%) eyes are having on-going treatment. On OCT, 34.9% had persistent fluid at the last visit, 6.7% patients showed new onset atrophy compared to baseline, and 43.7% had increased area of macular atrophy. The mean area of atrophy at the final visit was 4.15 mm2. Comparison between the good and worse visual outcome groups showed lower baseline VA, fovea-involving atrophy and final area of atrophy had a statistically significant negative effect on the final visual outcome (p

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.

Purpose\ud To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR).\ud \ud Methods\ud Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log-linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses.\ud \ud Results\ud Across the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR.\ud \ud Conclusions\ud Incidence and prevalence of DR decreased between 2012 and 2016 in this well-characterized population of the UK.

OBJECTIVE To investigate treat-and-extend (T&E) regimens of anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of macular oedema secondary to retinal vein occlusions (RVOs). METHODS Ovid MEDLINE, Ovid EMBASE and CENTRAL were searched on 25 February 2021. Randomized controlled trials, cohort studies, case-control studies and case series were included. The primary outcome was the change in Early Treatment Diabetic Retinopathy Score (ETDRS) letters from baseline. Conversions from Snellen to ETDRS letters were performed utilizing a published protocol. Secondary outcomes included improvement in retinal thickness from baseline, number of anti-VEGF injections and frequency of adverse events. Outcomes were examined at 12 and 24 months. Certainty of evidence was assessed utilizing GRADE (Grading of Recommendations Assessments, Development and Evaluations) guidelines. RESULTS Seven hundred eighty-six eyes from 16 studies were included. Meta-analysis demonstrated a mean improvement of 15.7 (95% CI: 13.3-18.0) ETDRS letters at 12 months. Central retinal thickness improved 269.7 μm (95% CI: 233.64-305.90) at 12 months. Injections were performed 8.1 (95% CI: 7.4-8.7) and 13.1 (95% CI: 9.4-16.8) times at 12 and 24 months respectively. Adverse events were infrequent across all studies. Grading of Recommendations Assessments, Development and Evaluations (GRADE) certainty of evidence was very low across all outcomes. CONCLUSIONS The results support the viability of T&E regimens for the treatment of macular oedema secondary to RVOs.

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR.Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C).Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = −2.61, P = 0.009) and AI (Z = −2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49].Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.

The ORNATE India project is an interdisciplinary, multifaceted United Kingdom (UK)-India collaborative study aimed to build research capacity and capability in India and the UK to tackle the burden of diabetes-related visual impairment. For 51 months (October 2017-December 2021), this project built collaboration between six institutions in the UK and seven in India, including the Government of Kerala. Diabetic retinopathy (DR) screening models were evaluated in the public system in Kerala. An epidemiological study of diabetes and its complications was conducted through 20 centers across India covering 10 states and one union territory. The statistical analysis is not yet complete. In the UK, risk models for diabetes and its complications and artificial intelligence-aided tools are being developed. These were complemented by joint studies on various aspects of diabetes between collaborators in the UK and India. This interdisciplinary team enabled increased capability in several workstreams, resulting in an increased number of publications, development of cost-effective risk models, algorithms for risk-based screening, and policy for state-wide implementation of sustainable DR screening and treatment programs in primary care in Kerala. The increase in research capacity included multiple disciplines from field workers, administrators, project managers, project leads, screeners, graders, optometrists, nurses, general practitioners, and research associates in various disciplines. Cross-fertilization of these disciplines enabled the development of several collaborations external to this project. This collaborative project has made a significant impact on research capacity development in both India and the UK.

Purpose: To examine (i) the retinal structure and function using optical coherence tomography angiography (OCTA) and multifocal electroretinography (mfERG), respectively, in eyes with and without nonproliferative diabetic retinopathy (NPDR), (ii) and their interrelationship between retinal structure (OCTA) and function (mfERG) in the two groups independently. Methods: This was a prospective observational study. One hundred twenty-one eligible participants with type 2 diabetes with No DR (n = 89), or with mild or moderate NPDR (n = 32) underwent ophthalmic examination, ultrawide field-view fundus photography, OCTA, and mfERG. Group differences were assessed using a Mann–Whitney U test. Correlations were assessed using Spearman's rho. Results: There were no significant differences in OCTA measures between the two groups. The mfERG P1 implicit times (rings 1–6) were significantly delayed and P1 response densities in rings 5 and 6 were significantly lower in participants with NPDR compared to those with No DR. In those with No DR, P1 implicit times in almost all rings were delayed in relation to lower vessel density and perfusion (maximum variance noted was 13%). In individuals with NPDR, the P1 response density in rings 2 and 3 showed a positive nonsignificant correlation with macular perfusion. Conclusion: In those with diabetes with No DR, retinal neuronal function is influenced by lower macular vessel density and perfusion. The retinal neuronal function is abnormal in individuals with NPDR compared to those with No DR and is not correlated with OCT angiometric measures, suggesting the likelihood of a different retinal structural correlate.

Purpose: To present clinical profile and risk factors of sight-threatening diabetic retinopathy (STDR) among people with age of onset of diabetes (AOD) 25 group. There was a higher prevalence of PDR with high-risk characteristics in AOD

Purpose: There is an exponential rise in the prevalence of diabetes mellitus (DM) in India. Ideally all people with DM should be periodically screening for diabetic retinopathy (DR) but is not practical with current infrastructure. An alternate strategy is to identify high-risk individuals with vision-threatening diabetic retinopathy (VTDR) for priority screening and treatment. Methods: We reanalyzed four population-based studies, conducted in South India between 2001 and 2010, and reclassified individuals above 40 years into known and newly diagnosed diabetes. Multiple regression analysis was done to identify risk factors in people with known and new DM. Results: The prevalence of DR in 44,599 subjects aged ≥40 years was 14.8% (18.4 and 4.7% in known and new DM, respectively), and the prevalence of VTDR was 5.1%. Higher risk factors of VTDR were older age >50 years, diabetes duration >5 years, and systolic blood pressure >140 mm Hg. Targeted screening of people with diabetes using high-risk criteria obtained from this study was able to detect 93.5% of all individuals with VTDR. Conclusion: In a limited resource country like India, a high-risk group-based targeted screening of individuals with DM could be prioritized while continuing the current opportunistic screening till India adopts universal screening of all people with DM.

The aim of this study was to develop and validate a deep learning-based system to detect peripheral neuropathy (DN) from retinal colour images in people with diabetes. Retinal images from 1561 people with diabetes were used to predictDN diagnosed on vibration perception threshold. A total of 189 had diabetic retinopathy (DR), 276 had DN, and 43 had both DR and DN. 90% of the images were used for training and validation and 10% for testing. Deep neural networks, including Squeezenet, Inception, and Densenet were utilized, and the architectures were tested with and without pre-trained weights. Random transform of images was used during training. The algorithm was trained and tested using three sets of data: all retinal images, images without DR and images with DR. Area under the ROC curve (AUC) was used to evaluate performance. The AUC to predict DN on the whole cohort was 0.8013 (±0.0257) on the validation set and 0.7097 (±0.0031) on the test set. The AUC increased to 0.8673 (±0.0088) in the presence of DR. The retinal images can be used to identify individuals with DN and provides an opportunity to educate patients about their DN status when they attend DR screening.

Purpose To examine (1) the retinal structure by optical coherence tomography (OCT) and function by means of multifocal electroretinography (mfERG) in eyes with and without nonproliferative diabetic retinopathy (NPDR) (2) for correspondence between local retinal function and OCT zones with retinal lesions. Methods One hundred and thirty-two eligible participants (30 with nonproliferative DR (NPDR) and 102 with diabetes with no DR) underwent comprehensive ophthalmic examination, optical coherence tomography for retinal thickness measures, mfERG, and ultra-wide field fundus photography. OCT Early Treatment Diabetic Retinopathy Study (ETDRS) grid was overlaid on to mfERG plots. Results Those with NPDR had significantly thicker full retinal measures in the nine (ETDRS) zones compared to no DR. mfERG P1 latencies in rings 1-6 were significantly delayed, while the response densities in rings 4-6 were lower in the NPDR group. Significant negative correlation was noted between OCT thickness and mfERG P1 response densities in many ETDRS zones. Significant positive correlation was noted between P1 latencies and OCT thickness in a few zones. The combination of cystic spaces, microaneurysms, and hard exudates were present in all zones and were associated with a decrease in P1 response densities compared to no lesions. Reduced P1 response densities were associated with a sporadic delay in the mfERG latencies and vice versa. The number of lesions did not show correspondence to the mfERG measures. Conclusions In eyes with NPDR, retinal function is differentially correlated with the DR lesions on OCT and can be assessed using multimodal imaging modalities.

Background/aimsConcerns have been expressed about the relationship between reduced levels of health care utilisation and the COVID-19 pandemic. This study aimed to elicit and explore the views of patients with neovascular age-related macular degeneration (nAMD) regarding the COVID-19 pandemic and their ophthalmic care.MethodsBetween April 29th and September 4th 2020, semi-structured telephone interviews were conducted with thirty-five patients with nAMD taking part in a larger diagnostic accuracy study of home-monitoring tests. Participants were recruited using maximum variation sampling to capture a range of key characteristics including age, gender and time since initial treatment. Transcribed interview data were analysed using a deductive and inductive thematic approach.ResultsThree themes emerged from the analysis: i. access to eye clinic care. ii. COVID-19 mitigating factors and care delivery and iii. social and personal circumstances. Participants reported anxieties about cancelled or delayed appointments, limited communication from clinic-based services about appointments, and the impact of this on their ongoing care. Despite these concerns, there was apprehension about attending appointments due to infection risk and a perception that nAMD patients are a ‘high risk’ group. Views of those who attended clinics during the study period were, however, positive, with social distancing and infection control measures providing reassurance.ConclusionsThese findings contribute to our understanding about experiences of patients with nAMD during the COVID-19 pandemic and have potential implications for future planning of care services. Innovative approaches may be required to address issues related to access to care, including concerns about delayed or cancelled appointments.SynopsisPerspectives of patients with neovascular age-related macular degeneration regarding the COVID-19 pandemic identified important issues regarding access to, and experience of ophthalmic care. These findings have implications for future planning of services.

With the increasing prevalence of diabetes in developing and developed countries, the socio-economic burden of diabetic retinopathy (DR), the leading complication of diabetes, is growing. Diabetic retinopathy (DR) is currently one of the leading causes of blindness in working-age adults worldwide. Robust methodologies exist to detect and monitor DR; however, these rely on specialist imaging techniques and qualified practitioners. This makes detecting and monitoring DR expensive and time-consuming, which is particularly problematic in developing countries where many patients will be remote and have little contact with specialist medical centres. Diabetic retinopathy (DR) is largely asymptomatic until late in the pathology. Therefore, early identification and stratification of vision-threatening DR (VTDR) is highly desirable and will ameliorate the global impact of this disease. A simple, reliable and more cost-effective test would greatly assist in decreasing the burden of DR around the world. Here, we evaluate and review data on circulating protein biomarkers, which have been verified in the context of DR. We also discuss the challenges and developments necessary to translate these promising data into clinically useful assays, to detect VTDR, and their potential integration into simple point-of-care testing devices.

Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m2. The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007–2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999–1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82–0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD.

This literature review aims to address the available evidence on COVID19 related issues faced in ophthalmology practice.

Aim: To investigate the longitudinal correlation between drusen characteristics and retinal layer volumes pre conversion and subsequent type of choroidal neovascularisation (CNV). Methods: This was a single-centre retrospective study. The study participants were patients with wet age-related macular degeneration (AMD) in one eye who developed wet AMD in the contralateral eye, with at least 2 years of follow-up prior to conversion. The Moorfields Eye Hospital database was searched for eligible patients and their data were recorded. Eyes were classified as occult or classic based on fundus fluorescein angiography. Optical coherence tomography (OCT) images were analysed for drusen characteristics and retinal layer volumes were analysed over time using automated software (Topcon 3D OCT-2000 and Orion, Voxeleron LLC, respectively). All values were obtained at baseline as well as year 1 and year 2 before conversion to wet AMD. Results: Fifty-one eyes with bilateral CNV showed high correlation of type of CNV between eyes (kappa statistic 0.89). A total of 49 wet AMD eyes (29 occult, 20 classic) were analysed for drusen parameters. Two patients with retinal angiomatous proliferation were excluded. Drusen count, area, and volume did not differ by CNV type, but the rates of change of drusen area (p = 0.046) and drusen volume (0.022) were higher in the occult group in the year preceding CNV development. Of the 49 eyes, 17 (10 occult, 7 classic) with available good quality OCT were analysed for retinal layer volumes. There was a progressive reduction in outer nuclear layer (ONL) volume (p = 0.002) and an expansion in outer plexiform layer volume (p = 0.015) in eyes that developed occult CNV. Conclusion: Our study shows that rate of increase in drusen load and reduction in ONL are significant features seen in eyes developing occult CNV, highlighting new imaging markers that need to be replicated in larger studies. These markers provide insight into the pathogenesis of CNV and may serve as prognostic indicators, as classic CNV carries a poorer prognosis compared to occult CNV.