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Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

Introduction: This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. Methods: We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. Results: A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. Conclusion: During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if retinal vascular calibers and systemic risk factors in patients with no or minimal diabetic retinopathy (DR) can predict risk of long‐term progression to proliferative diabetic retinopathy (PDR). Methods: This was a matched case–control study of patients with diabetes having no or minimal DR at baseline with (cases) or without (controls) subsequent development of PDR. We collected six‐field, 45‐degree retinal images, demographic and clinical data from the Funen Diabetes Database. Results: We included 52 eyes from 39 cases and 107 eyes from 89 controls matched on sex, age, type of diabetes, time from first to last screening episode and baseline DR level. Cases had higher HbA1c (73 vs. 55 mmoL/moL; p < 0.001), triglycerides (1.32 vs. 1.16 mmoL/L; p = 0.02) and longer duration of diabetes (19 vs. 14 years; p = 0.01), but the groups did not differ in calibers of retinal arterioles (229 vs. 227 μm; p = 0.49), venules (289 vs. 290 μm; p = 0.83) or the arterio‐to‐venule ratio (0.78 vs. 0.77; p = 0.86).In a multivariable logistic regression model with cluster robust standard error, HbA1c (OR 1.54 per 10 mmoL/moL; 95%‐CI: 1.15–2.07; p = 0.004), triglyceride (OR 1.39 per 1 mmoL/L; 95%‐CI: 1.03–1.86; p = 0.03) and duration of diabetes (OR 1.09 per year; 95%‐CI: 1.03–1.16; p = 0.003) were independent risk factors for PDR. Conclusion: Retinal vascular calibers did not predict long‐term development of PDR in contrast to well‐established risk factors like HbA1c, triglyceride and duration of diabetes. [ABSTRACT FROM AUTHOR]

Background/aims To determine agreement of one-field (1F, macula-centred), two-field (2F, disc-macula) and five-field (5F, macula, disc, superior, inferior and nasal) mydriatic handheld retinal imaging protocols for the assessment of diabetic retinopathy (DR) as compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photography. Methods Prospective, comparative instrument validation study. Mydriatic retinal images were taken using three handheld retinal cameras: Aurora (AU; 50° field of view (FOV), 5F), Smartscope (SS; 40° FOV, 5F), and RetinaVue (RV; 60° FOV, 2F) followed by ETDRS photography. Images were evaluated at a centralised reading centre using the international DR classification. Each field protocol (1F, 2F and 5F) was graded independently by masked graders. Weighted kappa (Kw) statistics assessed agreement for DR. Sensitivity (SN) and specificity (SP) for referable diabetic retinopathy (refDR; moderate non-proliferative diabetic retinopathy (NPDR) or worse, or ungradable images) were calculated. Results Images from 225 eyes of 116 patients with diabetes were evaluated. Severity by ETDRS photography: no DR, 33.3%; mild NPDR, 20.4%; moderate, 14.2%; severe, 11.6%; proliferative, 20.4%. Ungradable rate for DR: ETDRS, 0%; AU: 1F 2.23%, 2F 1.79%, 5F 0%; SS: 1F 7.6%, 2F 4.0%, 5F 3.6%; RV: 1F 6.7%, 2F 5.8%. Agreement rates of DR grading between handheld retinal imaging and ETDRS photography were (Kw, SN/SP refDR) AU: 1F 0.54, 0.72/0.92; 2F 0.59, 0.74/0.92; 5F 0.75, 0.86/0.97; SS: 1F 0.51, 0.72/0.92; 2F 0.60, 0.75/0.92; 5F 0.73, 0.88/0.92; RV: 1F 0.77, 0.91/0.95; 2F 0.75, 0.87/0.95. Conclusion When using handheld devices, the addition of peripheral fields decreased the ungradable rate and increased SN and SP for refDR. These data suggest the benefit of additional peripheral fields in DR screening programmes that use handheld retinal imaging. [ABSTRACT FROM AUTHOR]

This study formed part of a diagnostic test accuracy study to quantify the ability of three index home monitoring (HM) tests (one paper-based and two digital tests) to identify reactivation in Neovascular age-related macular degeneration (nAMD). The aim of the study was to investigate views about acceptability and explore adherence to weekly HM. Semi-structured interviews were held with 98 patients, family members, and healthcare professionals. A thematic approach was used which was informed by theories of technology acceptance. Various factors influenced acceptability including a patient's understanding about the purpose of monitoring. Training and ongoing support were regarded as essential for overcoming unfamiliarity with digital technology. Findings have implications for implementation of digital HM in the care of older people with nAMD and other long-term conditions. [ABSTRACT FROM AUTHOR]

Background Data on population-based self-reported dual vision and hearing impairment are sparse in Europe. We aimed to investigate self-reported dual sensory impairment (DSI) in European population. Methods A standardised questionnaire was used to collect medical and socio-economic data among individuals aged 15 years or more in 29 European countries. Individuals living in collective households or in institutions were excluded from the survey. Results Among 296 677 individuals, the survey included 153 866 respondents aged 50 years old or more. The crude prevalence of DSI was of 7.54% (7.36-7.72). Among individuals aged 60 or more, 9.23% of men and 10.94% of women had DSI. Eastern and southern countries had a higher prevalence of DSI. Multivariable analyses showed that social isolation and poor self-rated health status were associated with DSI with ORs of 2.01 (1.77-2.29) and 2.33 (2.15-2.52), while higher income was associated with lower risk of DSI (OR of 0.83 (0.78-0.89). Considering country-level socioeconomic factors, Human Development Index explained almost 38% of the variance of age-adjusted prevalence of DSI. Conclusion There are important differences in terms of prevalence of DSI in Europe, depending on socioeconomic and medical factors. Prevention of DSI does represent an important challenge for maintaining quality of life in elderly population. [ABSTRACT FROM AUTHOR]

Purpose: Prediction of the early treatment response is important in neovascular age‐related macular degeneration (nAMD). Hence, we aimed to test if non‐invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. Methods: In 58 eyes of 58 patients with treatment‐naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra‐ or subretinal fluid or macular haemorrhage. Results: Of 54 eyes attending follow‐up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length‐diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82–0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68–1.00, p = 0.05, for each 0.01 unit increment). Conclusion: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long‐term, prospective studies, this might help to guide treatment. [ABSTRACT FROM AUTHOR]

Background/aims To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. Methods We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. Results Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. Conclusion Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is associated with cognitive impairment and a twofold increased risk of dementia compared with age-matched individuals without diabetes. Given that the eye and the brain share similar embryologic origin and anatomical features, the retina offers a unique window to the brain. In this study, we wanted to determine whether there was a difference in retinal imaging–based neuronal and vascular markers in individuals with type 2 diabetes with or without mild cognitive impairment (MCI). We included 134 persons with type 2 diabetes. Based on neuropsychological tests, the prevalence of MCI was 28%. We performed seven-field color fundus photos, optical coherence tomography (OCT), OCT-angiography (OCT-A), and retinal oximetry to analyze retinal markers. In a multivariable cluster analysis, persons with MCI had a significantly thinner macular retinal nerve fiber layer and macular ganglion cell layer, and less venular oxygen saturation in the nasal quadrant compared with those without MCI. There were no differences in retinal vessel density, fractal dimension, width, tortuosity, or OCT-A markers. People with type 2 diabetes and MCI demonstrate alterations in retinal structure and metabolism, suggesting noninvasive retinal markers may be useful to detect people with type 2 diabetes at risk for cognitive dysfunction. Article Highlights: Type 2 diabetes is associated with mild cognitive impairment (MCI). Therefore, retinal and cerebral neurodegeneration may run in parallel. To assess whether there was a difference in retinal structure, vessel, and metabolic parameters in individuals with MCI. We found those with MCI had a thinner macular retinal nerve fiber layer, macular ganglion cell layer, and less venular oxygen saturation. We suggest noninvasive retinal markers may be useful to detect those at risk of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: To determine the extent to which diabetic retinopathy severity stage may be classified using machine learning (ML) and commonly used clinical measures of visual function together with age and sex. Methods: We measured the visual function of 1901 eyes from 1032 participants in the Northern Ireland Sensory Ageing Study, deriving 12 variables from nine visual function tests. Missing values were imputed using chained equations. Participants were divided into four groups using clinical measures and grading of ophthalmic images: no diabetes mellitus (no DM), diabetes but no diabetic retinopathy (DM no DR), diabetic retinopathy without diabetic macular oedema (DR no DMO) and diabetic retinopathy with DMO (DR with DMO). Ensemble ML models were fitted to classify group membership for three tasks, distinguishing (A) the DM no DR group from the no DM group; (B) the DR no DMO group from the DM no DR group; and (C) the DR with DMO group from the DR no DMO group. More conventional multiple logistic regression models were also fitted for comparison. An interpretable ML technique was used to rank the contribution of visual function variables to predictions and to disentangle associations between diabetic eye disease and visual function from artefacts of the data collection process. Results: The performance of the ensemble ML models was good across all three classification tasks, with accuracies of 0.92, 1.00 and 0.84, respectively, for tasks A–C, substantially exceeding the accuracies for logistic regression (0.84, 0.61 and 0.80, respectively). Reading index was highly ranked for tasks A and B, whereas near visual acuity and Moorfields chart acuity were important for task C. Microperimetry variables ranked highly for all three tasks, but this was partly due to a data artefact (a large proportion of missing values). Conclusions/interpretation: Ensemble ML models predicted status of diabetic eye disease with high accuracy using just age, sex and measures of visual function. Interpretable ML methods enabled us to identify profiles of visual function associated with different stages of diabetic eye disease, and to disentangle associations from artefacts of the data collection process. Together, these two techniques have great potential for developing prediction models using untidy real-world clinical data. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate qualitative and quantitative differences in vascular density analysis of an established and a novel alternative for post-processing on optical coherence tomography angiography (OCTA) images in healthy individuals. OCTA examinations of 38 subjects were performed. After extracting the images, two semi-manual post-processing techniques, the already established Mexican hat filtering (MHF) and an alternative, the Shanbhag thresholding (ST) were applied. We assessed Vessel Density (VD), Skeleton Density (SkD) and Vessel Diameter Index (VDI). We analyzed the results in order to establish similarities or potentially relevant differences. Regarding SkD and VD, MHF generally gave higher values than ST. Simultaneously, mean values were also predominantly higher by MHF; however, standard deviations (SD) were higher by ST (range [mean ± SD]: 0.054 ± 0.038 to 0.134 ± 0.01 and 0.134 ± 0.095 to 0.362 ± 0.028 vs 0.012 ± 0.014 to 0.087 ± 0.03 and 0.039 ± 0.047 to 0.4 ± 0.095 for SkD and VD with MHF vs SkD and VD with ST, respectively). Values of VDI were considerably higher with ST than with MHF, while standard deviation was still significantly higher with ST (range [mean ± SD]: 2.459 ± 0.144 to 2.71 ± 0.084 and 2.983 ± 0.929 to 5.19 ± 1.064 for VDI with MHF and ST, respectively). The noise level reduction of the two methods were almost identical (noise levels: 65.8% with MHT and 65.24% with ST). Using MHF, the vascular network gets more fragmented by an average of 40% compared to ST. Both methods allow the segmentation of the vascular network and the examination of vascular density parameters, but they produce largely inconsistent results. To determine if these inconsistent results are clinically meaningful, and which method is more suitable for clinical use, our results provide further evidence that detailed understanding of the image analysis method is essential for reliable decision making for patients with retinal pathology. For longitudinal monitoring, use of the same image processing method is recommended. [ABSTRACT FROM AUTHOR]

Purpose: The Danish Registry of Diabetic Retinopathy includes information from >200 000 patients who attends diabetic retinopathy (DR) screening in Denmark. Screening of patients with uncomplicated type 2 diabetes is often performed by practicing ophthalmologists, while patients with type 1 and complicated type 2 diabetes attends screening at hospitals. We performed a clinical reliability study of retinal images from Danish screening facilities to explore the inter‐grader agreement between the primary screening ophthalmologist and a blinded, certified grader. Methods: Invitations to participate were sent to screening facilities across Denmark. The primary grader uploaded fundus photographs with information on estimated level of DR (International Clinical Diabetic Retinopathy scale as 0 [no DR], 1–3 [mild, moderate or severe nonproliferative DR {NPDR}], or 4 [proliferative DR {PDR}]), region of screening, image style, and screening facility. Images were then regraded by a blinded, certified, secondary grader. Weighted kappa analysis was performed to evaluate agreement. Results: Fundus photographs from 230 patients (458 eyes) were received from practicing ophthalmologists (52.6%) and hospital‐based grading centres (47.4%) from all Danish regions. Reported levels of DR by the primary graders were 66.8%, 12.2%, 13.1%, 1.3% and 5.5% for DR levels 0–4. The overall agreement between primary and secondary graders was 93% (κ = 0.83). Based on screening facility agreement was 96% (κ = 0.89) and 90% (κ = 0.76) for practicing ophthalmologists and hospital‐based graders. Conclusion: In this nationwide study, we observed a high overall inter‐grader agreement and based on this, it is reasonable to assume that reported DR gradings in the screening programme in Denmark, accurately reflect the truth. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate qualitative and quantitative differences in vascular density analysis of an established and a novel alternative for post-processing on optical coherence tomography angiography (OCTA) images in healthy individuals. OCTA examinations of 38 subjects were performed. After extracting the images, two semi-manual post-processing techniques, the already established Mexican hat filtering (MHF) and an alternative, the Shanbhag thresholding (ST) were applied. We assessed Vessel Density (VD), Skeleton Density (SkD) and Vessel Diameter Index (VDI). We analyzed the results in order to establish similarities or potentially relevant differences. Regarding SkD and VD, MHF generally gave higher values than ST. Simultaneously, mean values were also predominantly higher by MHF; however, standard deviations (SD) were higher by ST (range [mean ± SD]: 0.054 ± 0.038 to 0.134 ± 0.01 and 0.134 ± 0.095 to 0.362 ± 0.028 vs 0.012 ± 0.014 to 0.087 ± 0.03 and 0.039 ± 0.047 to 0.4 ± 0.095 for SkD and VD with MHF vs SkD and VD with ST, respectively). Values of VDI were considerably higher with ST than with MHF, while standard deviation was still significantly higher with ST (range [mean ± SD]: 2.459 ± 0.144 to 2.71 ± 0.084 and 2.983 ± 0.929 to 5.19 ± 1.064 for VDI with MHF and ST, respectively). The noise level reduction of the two methods were almost identical (noise levels: 65.8% with MHT and 65.24% with ST). Using MHF, the vascular network gets more fragmented by an average of 40% compared to ST. Both methods allow the segmentation of the vascular network and the examination of vascular density parameters, but they produce largely inconsistent results. To determine if these inconsistent results are clinically meaningful, and which method is more suitable for clinical use, our results provide further evidence that detailed understanding of the image analysis method is essential for reliable decision making for patients with retinal pathology. For longitudinal monitoring, use of the same image processing method is recommended. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) appears capable of detecting diabetic retinopathy (DR) with a high degree of accuracy in adults; however, there are few studies in children and young adults. Methods: Children and young adults (3-26 years) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were screened at the Dhaka BIRDEM-2 hospital, Bangladesh. All gradable fundus images were uploaded to Cybersight AI for interpretation. Two main outcomes were considered at a patient level: 1) Any DR, defined as mild non-proliferative diabetic retinopathy (NPDR or more severe; and 2) Referable DR, defined as moderate NPDR or more severe. Diagnostic test performance comparing Orbis International's Cybersight AI with the reference standard, a fully qualified optometrist certified in DR grading, was assessed using the Matthews correlation coefficient (MCC), area under the receiver operating characteristic curve (AUC-ROC), area under the precision-recall curve (AUC-PR), sensitivity, specificity, positive and negative predictive values. Results: Among 1274 participants (53.1% female, mean age 16.7 years), 19.4% (n = 247) had any DR according to AI. For referable DR, 2.35% (n = 30) were detected by AI. The sensitivity and specificity of AI for any DR were 75.5% (CI 69.7-81.3%) and 91.8% (CI 90.2-93.5%) respectively, and for referable DR, these values were 84.2% (CI 67.8-100%) and 98.9% (CI 98.3%-99.5%). The MCC, AUC-ROC and the AUC-PR for referable DR were 63.4, 91.2 and 76.2% respectively. AI was most successful in accurately classifying younger children with shorter duration of diabetes. Conclusions: Cybersight AI accurately detected any DR and referable DR among children and young adults, despite its algorithms having been trained on adults. The observed high specificity is particularly important to avoid over-referral in low-resource settings. AI may be an effective tool to reduce demands on scarce physician resources for the care of children with diabetes in low-resource settings. [ABSTRACT FROM AUTHOR]

Background The ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe. Methods The study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOPlowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation. Results Six hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seventythree eyes (64.6% of 113 phakic) required cataract surgery during follow-up. Mean VA increased from a baseline of 52.2 letters to 57.1 letters at month 36, with improvement observed up to month 48. Supplementary therapies were given in 43.7% of eyes. When classified by length of cDMO less than or greater than the median duration those with a shorter history experienced greater VA gains than those with a longer history. Conclusion This study confirms the favourable, longterm benefit-to-risk profile of the FAc implant in eyes with cDMO, with an additional benefit in patients when this therapy is administered earlier. [ABSTRACT FROM AUTHOR]

Background/aims Associations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment of the condition. We aimed to evaluate overall and subtype-stratified risk of CVD and all-cause mortality following RVO and assess any alterations after the introduction of angiostatic therapy in Denmark in 2011. Methods This nationwide, registry-based cohort study from 1998 to 2018 evaluated 4 194 781 individuals. Hazard ratios (HRs) were reported for RVO as an overall measure and subclassified as branch and central RVO. Results Patients with RVO (n=15 665) were median 71.8 years old at the time of exposure and 50.7% were women. RVO associated with incident CVD (adjusted HR 1.13, 95%CI 1.09 to 1.17) but not mortality (adjusted HR 1.00, 95%CI 0.97 to 1.03). Almost similar risks of CVD were found for patients with branch and central RVO (adjusted HRs 1.14, 95%CI 1.03 to 1.25, and 1.12, 95%CI 1.00 to 1.25, respectively), but only patients with central RVO exhibited increased mortality (adjusted HR 1.12, 95%CI 1.04 to 1.21). Risk of CVD, especially non-ischaemic, was higher for patients diagnosed after 2011 (adjusted HRs 1.24, 95%CI 1.15 to 1.33 vs 1.06, 95%CI 1.01 to 1.12). Conclusion In a cohort of the Danish population aged 40 years or more, patients with RVO had a 13% increased risk of incident CVD compared with unexposed individuals. Risk of CVD was increased after 2011, when intravitreal angiostatic treatment was introduced and referral practices altered. [ABSTRACT FROM AUTHOR]

Purpose: To compare diabetic retinopathy (DR) severity identified on handheld retinal imaging with ultrawide field (UWF) images. Methods: Mydriatic images of 225 eyes of 118 diabetic patients were prospectively imaged with the Aurora (AU) handheld retinal camera [5‐field protocol (macula‐centred, disc‐centred, temporal, superior, inferior)] and compared with UWF images. Images were classified based on the international classification for DR. Sensitivity, specificity, kappa statistics (K/Kw) were calculated on an eye and person‐level. Results: Distribution of DR severity by AU/UWF images (%) by eye was no DR 41.3/36.0, mild non‐proliferative DR (NPDR) 18.7/17.8, moderate 10.2/10.7, severe 16.4/15.1, proliferative DR (PDR) 13.3/20.4. Agreement between UWF and AU was exact in 64.4%, within 1‐step 90.7%, k = 0.55 (95% CI:0.45–0.65), and kw = 0.79 (95% CI:0.73–0.85) by eye, and exact in 68%, within 1‐step 92.9%, k = 0.58 (95% CI:0.50–0.66), and kw = 0.76 (95% CI:0.70–0.81) by person. Sensitivity/specificity for any DR, refDR, vtDR and PDR were as follows: 0.90/0.83, 0.90/0.97, 0.82/0.95 and 0.69/1.00 by person and 0.86/0.90, 0.84/0.98, 0.75/0.95 and 0.63/0.99 by eye. Handheld imaging missed 37% (17/46) eyes and 30.8% (8/26) persons with PDR. Only 3.9% (1/26) persons or 6.5% (3/46) eyes with PDR were missed if a referral threshold of moderate NPDR was used. Conclusions: Data from this study show that comparing UWF and handheld images, when PDR was the referral threshold for handheld devices, 37.0% of eyes or 30.8% of patients with PDR were missed. Due to the identification of neovascular lesions outside of the handheld fields, lower referral thresholds are needed if handheld devices are used. [ABSTRACT FROM AUTHOR]

Developments in retinal imaging technologies have enabled the quantitative evaluation of the retinal vasculature. Changes in retinal calibre and/or geometry have been reported in systemic vascular diseases, including diabetes mellitus (DM), cardiovascular disease (CVD), and more recently in neurodegenerative diseases, such as dementia. Several retinal vessel analysis softwares exist, some being disease-specific, others for a broader context. In the research setting, retinal vasculature analysis using semi-automated software has identified associations between retinal vessel calibre and geometry and the presence of or risk of DM and its chronic complications, and of CVD and dementia, including in the general population. In this article, we review and compare the most widely used semi-automated retinal vessel analysis softwares and their associations with ocular imaging findings in common systemic diseases, including DM and its chronic complications, CVD, and dementia. We also provide original data comparing retinal calibre grading in people with Type 1 DM using two softwares, with good concordance. [ABSTRACT FROM AUTHOR]

Background/aim To assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD). Methods This pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD receiving intravitreal ranibizumab from 24 UK hospitals. Participants were randomised to either pars plana vitrectomy with 24 Gray EMB and pro re nata (PRN) ranibizumab (n=224) or PRN ranibizumab monotherapy (n=119). Although masking was not possible, masked clinicians assessed best-corrected visual acuity (BCVA) and imaging. After month 24, participants reverted to standard care, with either ranibizumab or aflibercept, returning for a month 36 study visit. Results Of 363 participants, 309 (85.1%) completed month 36. The number of injections was 12.1±8.1 in the EMB group versus 11.4±6.1 in the ranibizumab group (difference 0.7, 95% CI of difference −0.9 to 2.3, p=0.41) between months 1 and 36, and 3.6±3.3 (n=200) versus 3.9±2.7 (n=102) (difference −0.3, 95% CI of difference −1.0 to 0.4, p=0.43) between months 25 and 36 (standard care). Over 36 months, BCVA change was −19.7±18.5 letters in the EMB group and −4.8±12.5 in the ranibizumab group (difference −14.9, 95% CI of difference −18.5 to −11.2, p<0.0001). The month 36 BCVA of 20 EMB-treated participants with microvascular abnormalities (MVAs) at month 24 was similar to EMB-treated participants without MVAs (−21.8 vs −19.4 letters, p=0.65). Conclusion EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor inhibitors have substantially improved the visual outcomes in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), but treatment outcomes are highly variable and early prediction of expected clinical outcome would be important for individualized treatment. As non-invasive metabolic, structural and functional retinal markers might act as early predictors of clinical outcomes, we performed a 12-month, prospective study aimed to evaluate if baseline retinal oximetry, optical coherence tomography angiography (OCT-A) or microperimetry were able to predict need of treatment, structural or functional outcome in patients with ME caused by treatment-näive BRVO. We evaluated 41 eyes of 41 patients with a mean age of 69.6 years and 56% females. We found a strong tendency towards a higher retinal arteriolar oxygen saturation in patients without a need of additional aflibercept treatment after the loading phase (99.8% vs. 92.3%, adjusted odds ratio 0.80 (95% confidence interval 0.64-1.00), adjusted p = 0.058), but otherwise, retinal oximetry, OCT-A or microperimetry were not able to predict need of treatment, structural nor functional outcomes. (Trial registration: clinicaltrials.gov, S-20,170,084. Registered 24 August 2014, https://clinicaltrials.gov/ct2/show/NCT03651011) [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare 2-field (2F) and 5-field (5F) mydriatic handheld retinal imaging for the assessment of diabetic retinopathy (DR) severity in a community-based DR screening program (DRSP). Methods: This was a prospective, cross-sectional diagnostic study, evaluating images of 805 eyes from 407 consecutive patients with diabetes acquired from a community-based DRSP. Mydriatic standardized 5F imaging (macula, disc, superior, inferior, temporal) with handheld retinal camera was performed. 2F (disc, macula), and 5F images were independently assessed using the International DR classification at a centralized reading center. Simple (K) and weighted (Kw) kappa statistics were calculated for DR. Sensitivity and specificity for referable DR ([refDR] moderate nonproliferative DR [NPDR] or worse) and vision-threatening DR ([vtDR] severe NPDR or worse) for 2F compared to 5F imaging were calculated. Results: Distribution of DR severity by 2F/5F images (%): no DR 66.0/61.7, mild NPDR 10.7/14.4, moderate NPDR 7.9/8.1, severe NPDR 3.3/5.6, proliferative DR 5.6/4.6, ungradable 6.5/5.6. Exact agreement of DR grading between 2F and 5F was 81.7%, within 1-step 97.1% (K = 0.64, Kw = 0.78). Sensitivity/specificity for 2F compared 5F was refDR 0.80/0.97, vtDR 0.73/0.98. The ungradable images rate with 2F was 16.1% higher than with 5F (6.5 vs. 5.6%, p < 0.001). Conclusions: Mydriatic 2F and 5F handheld imaging have substantial agreement in assessing severity of DR. However, the use of mydriatic 2F handheld imaging only meets the minimum standards for sensitivity and specificity for refDR but not for vtDR. When using handheld cameras, the addition of peripheral fields in 5F imaging further refines the referral approach by decreasing ungradable rate and increasing sensitivity for vtDR. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the structural changes in choroidal vessels and to observe choroid microstructural changes in different age and sex groups in a healthy Chinese population. Methods: Enhanced depth imaging optical coherence tomography (EDI-OCT) was employed to analyze the luminal area, stromal area, total choroidal area, subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), large choroidal vessel layer (LCVL), choriocapillaris–medium choroidal vessel layer, and LCVL/SFCT of the choroid in the subfoveal macular area within 1500 μm of the macula. We analyzed the age- and sex-related changes in the subfoveal choroidal structure. Results: A total of 1566 eyes from 1566 healthy individuals were included. The mean age of the participants was 43.62 ± 23.29 years, the mean SFCT of healthy individuals was 269.30 ± 66.43 μm, LCVL/SFCT percentage was 77.21 ± 5.84%, and the mean macular CVI was 68.39 ± 3.15%. CVI was maximum in the 0–10 years group, decreasing with age, and the lowest values occurred in the >80 years group; LCVL/SFCT was the lowest in the 0–10 years group, increasing with age and reaching a maximum in the >80 years group. CVI showed a significant negative correlation with age, and LCVL/SFCT showed a significant positive correlation with age. There was no statistically significant difference between males and females. Interrater and intrarater reliability was less variable with CVI than with SFCT. Conclusions: The choroidal vascular area and CVI decreased with age in the healthy Chinese population, of which the age-related decrease in vascular components maybe dominated by the decrease in choriocapillaris and medium choroidal vessels. Sex had no effect on CVI. The CVI of healthy populations showed better consistency and reproducibility when compared with SFCT. [ABSTRACT FROM AUTHOR]

Purpose: To determine the number of people being certified as either severely sight impaired or sight impaired due to diabetic eye disease (DED) in Northern Ireland (NI). Methods: Sight impairment data have been collected for the 6-year period of 2014–2019, these data included age, gender, certification status, visual acuity, and type of eye disease. All data were entered into an Excel database and analyzed using Stata to ascertain the number of total certifications and diabetic eye disease certifications per year. Results: The number of total certifications in NI increased year on year as has the number of diabetic eye disease certifications. The number of diabetic eye disease certifications rose from 12.6 per million in 2014 to 17.4 per million in 2019, with a peak of 27 per million in 2018. There were more males than females registered due to diabetic eye disease. Diabetic eye disease's proportional representation of total certifications of visual impairment remained relatively stable during the 6-year period. Conclusions: In the 6-year period, the overall number of certifications has increased from 2014 to 2019, as have the number of certifications due to DED. This may be attributed to the improvement of certification and diabetic eye care pathways. People with diabetes who are certified are more likely to be younger and male. More research with medical data needs to be conducted in the future. [ABSTRACT FROM AUTHOR]

Purpose: Within a population-based follow-up study, to examine the 10-year incidence of pseudoexfoliation syndrome (PEX), possible risk factors for PEX and its association with ocular aging of the cornea, lens and retina. Methods: The baseline examination was conducted in 2006 on a random sample of 1,033 adult participants from Kaunas city (Lithuania) population of whom 631 had ophthalmic examination data at attendance of the 10-year follow-up in 2016. Detailed examination of the anterior and posterior segment of the eye was carried out. After diagnostic mydriasis PEX was diagnosed by the presence of typical grayish-white exfoliation material on the anterior capsule surface of the lens. The participants were divided to PEX and non-PEX groups. Results: PEX prevalence increased from 9.8 to 34.2% from baseline to 10-year follow-up. Nuclear cataract was common both in the PEX group (66.7%) and in those without PEX (72.2%), but this difference did not reach statistically significantly increased risk of developing cataract in those with PEX (OR 1.2; p = 0.61). Central corneal thickness (CCT) was thinner in the PEX group (529 ± 34 μm) and in the oldest group (525 ± 36 μm) (p < 0.001). Compared to baseline, corneal curvature (CC) became flatter in both groups (7.6 ± 0.27 vs 7.7 ± 0.26 mm; p < 0.001) during the follow-up, but the difference did not reach significance between groups. Corneal astigmatism was most commonly with-the-rule in both groups (37 (50.0%) vs 148 (68.5%); p > 0.05). Age, sex and PEX had no influence on age-related macular degeneration distribution. Conclusion: The prevalence of PEX increased significantly with age in our population, with those with PEX having thinner and flatter corneae, but no difference in cataract and age-related macular degeneration characteristics. [ABSTRACT FROM AUTHOR]

The visually impaired community often finds the built environment difficult to navigate. Elements of street design such as street furniture, bollards and shared space are some of the problems that contribute to a hostile built environment. This article aims to investigate how the built environment affects people with a visual impairment through questionnaires, focus groups and interviews conducted with visually impaired people and built-environment professionals. A majority of visually impaired respondents stated the built environment was difficult to navigate, with several issues identified. These issues need to be addressed to create more inclusive spaces and places for all. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a major public health concern, with approximately 80% of the burden falling on low- and middle-income countries (LMICs). Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and early detection through diabetic eye screening programmes is essential to prevent visual impairment and blindness. Careful planning at a national level is crucial for effective implementation of such programmes. Methods: A scoping review was conducted, and the protocol was published previously to explain the methods in detail. Data were collected from databases and searches, including grey literature. Furthermore, consultations were conducted with key informants from LMICs. Results: Lower-middle-income countries (29/50, 58%) and upper-middle-income countries (27/59, 45.8%) are making more progress than low-income countries (4/29, 13.8%) in terms of DR policy planning. However, no identified data for published policies have actually implemented national DR policies. Compared to low-income and lower-middle-income countries, upper-middle-income countries are making the most progress in implementing national diabetic eye screening programmes; however, their progress is still slow, with only 5/59 (8.5%) having such programmes. Conclusion: There are significant gaps in the literature, with no data reported for 78/138 (56.5%) LMICs. Further research is clearly needed to support and document DR policy development in LMICs. [ABSTRACT FROM AUTHOR]

Aims: To characterise continuous glucose monitor and flash glucose monitor use and related issues (both positive and negative) in the population of children and young people living with type 1 diabetes in the Southern Health and Social Care Trust (SHSCT), Northern Ireland. Methods: Four focus groups were conducted in the SHSCT with people with type 1 diabetes and their families, to assess opinions of diabetes technology. In addition, questionnaires were distributed to diabetes specialist nurses (DSNs), young people and their families about use and access to diabetes technology. Results: Questionnaires were completed by 68 children, young people (0–18 years) and their parents/guardians. Nearly all (98.5%) had access to their own diabetes related data, and 70.6% used diabetes data systems, for example, Libreview. Most of those using these systems found them beneficial and easy for daily use and clinical review. Most DSNs (83.9%) agreed that the systems were easy to use, and 82.3% were confident in interpreting the data accurately. DSNs felt virtual review was beneficial in over half of young people with 62.9% advising changes to diabetes management based on the data. Focus groups participants deemed diabetes technology a 'gamechanger' and 'lifechanging'. Some drawbacks included 'disruptive' alarms, self‐confidence issues, visible diabetes technology and problems in school. Conclusions: Most young people, their families and healthcare professionals reported they were confident in interpreting diabetes data and technology was easy to use. Diabetes technology could improve access to care through virtual clinics, improve clinical outcomes and enhance quality of life. [ABSTRACT FROM AUTHOR]

Background and aim Undiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG). Design Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK. Participants 314 study participants with POAG in either eye. Methods Logistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access. Results 217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, p<0.0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p<0.0001). Conclusions The risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate treatment efficacy in diabetic macular oedema (DME) comparing a study population receiving combined intravitreal vascular endothelial growth factor (VEGF) inhibition and focal/grid photocoagulation with a matched, real‐world population receiving standard of care treatment. Methods: In an exploratory study, we included 43 eyes from 32 patients from a previously published study as well as 46 eyes from 38 standard‐of‐care patients. The study population had received a loading dose of three monthly aflibercept injections followed by focal/grid photocoagulation and additional aflibercept pro re nata. Principal measurements at 12 months were numbers of intravitreal injections, best corrected visual acuity (BCVA) and central retinal thickness (CRT). Results: At baseline, there were no differences between groups regarding age, sex, body mass index, haemoglobin A1C, systolic pressure or type of diabetes, but the study population had a higher diastolic pressure (81.6 versus 72.1 mmHg, p = 0.03) and a lower duration of diabetes (12.3 versus 23.2 years, p = 0.03). At month 12, patients in the study group had a higher visual acuity (79.6 versus 74.3 ETDRS letters, p = 0.03), despite having received fewer aflibercept injections (4.4 versus 5.9, p < 0.01) with a higher likelihood of having only received the three mandatory injections in the loading phase (39.5% versus 13.0%, p = 0.01). Conclusion: In comparison to a matched, real‐world DME‐population, patients in combined treatment with intravitreal aflibercept and postloading focal/grid photocoagulation obtained a better functional outcome despite having received fewer intravitreal injections. Future randomized studies are needed to evaluate the long‐term efficacy of this combined treatment regimen. [ABSTRACT FROM AUTHOR]

Purpose: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients. Methods: Treatment‐naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re‐treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry. Results: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best‐corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 μm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re‐treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (−195 versus −181 μm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67). Conclusion: In treatment‐naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a sight‐threatening complication of diabetes mellitus (DM) and it contributes substantially to the burden of disease globally. During the last decades, the development of multiple imaging modalities to evaluate DR, combined with emerging treatment possibilities, has led to the implementation of large‐scale screening programmes resulting in improved prevention of vision loss. However, not all patients are able to participate in such programmes and not all are at equal risk of DR development and progression. In this review, we discuss the relevance of the currently available imaging modalities for the evaluation of DR: colour fundus photography (CFP), ultrawide‐field photography (UWFP), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), OCT angiography (OCTA) and functional testing. Furthermore, we suggest where a particular imaging technique of DR may aid the evaluation of the disease in different clinical settings. Combining information from various imaging modalities may enable the design of more personalized care including the initiation of treatment and understanding the progression of disease more adequately. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to evaluate the feasibility of ultra-widefield (UWF) imaging to identify ocular pathologies amongst in- and out-patients in a tertiary university hospital. Methods: We followed a prospective double-blinded multicenter clinical study. In total, 634 patients from a university hospital with pulmonary, cardiovascular, and endocrine diseases were examined by two teams by conventional slit-lamp biomicroscopy (CBM). UWF images with Optos Tx200 were taken and subsequently graded independently by two retina specialists and graders from two reading centers for the presence of pre-defined pathologies. Interrater reliability was calculated using Fleiss statistical software. An independent, trained and certified ophthalmologist with retinal subspecialty (BL) classified all UWF images with retinal hemorrhages by severity and interrater agreement. Results: Complete data were available for 502 patients. The Moorfields Eye Hospital Reading Center, London, UK (RM), reported the highest number of cases with retinal pathologies (378), and the Reading Center GRADE Bonn, Germany (RB), did so for cases with optic disc cupping (466). Two retinal consultants (R1 and R2) from the Department of Ophthalmology, University Hospital Giessen and Marburg GmbH, Campus Giessen, Germany, noted optic disc pathologies. R1 reported 151 cases with optic disc pallor, while R2 reported only 39 disc pathologies. Both for clinical and for image readers, the early changes had equally low interrater reliability. The presence of at least 3 retinal hemorrhages had the highest interrater reliability (0.59). Conclusions: UWF imaging is convenient to identify overt retinal pathologies in patients at risk of ocular complications of their systemic disease who are attending hospital clinics. Imaging the eye allows for remote retinal assessment and for placing the patient into the appropriate clinical pathway for ophthalmology. Precis: UWF-imaging in a population of in- and out-patients at a university hospital who are at risk of retinal complications is effective to detect overt retinal pathologies and allows for tele-ophthalmology approaches to be enabled for placing the patients into the appropriate clinical pathways. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible vision loss that gradually damages the optic nerve. In ophthalmic fundus images, measurements of the cup to optic disc (CD) ratio, CD area ratio, neuroretinal rim to optic disc (RD) area ratio, and rim thickness are key measures to screen for potential glaucomatous damage. We propose an automatic method using deep learning algorithms to segment the optic disc and cup and to estimate the key measures. The proposed method comprises three steps: The Region of Interest (ROI) (location of the optic disc) detection from a fundus image using Mask R-CNN, the optic disc and cup segmentation from the ROI using the proposed Multiscale Average Pooling Net (MAPNet), and the estimation of the key measures. Our segmentation results using 1099 fundus images show 0.9381 Jaccard Index (JI) and 0.9679 Dice Coefficient (DC) for the optic disc and 0.8222 JI and 0.8996 DC for the cup. The average CD, CD area, and RD ratio errors are 0.0451, 0.0376, and 0.0376, respectively. The average disc, cup, and rim radius ratio errors are 0.0500, 0.2257, and 0.2166, respectively. Our method performs well in estimating the key measures and shows potential to work within clinical pathways once fully implemented. [ABSTRACT FROM AUTHOR]

Aim To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses. Methods We included 115 954 UK Biobank participants aged 40-69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Participants with self-reported ocular conditions, high refractive error (< -6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses. Results After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 μm (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=-0.16 μm, p=2.0 × 10-5), thicker photoreceptor inner segment layer (β=0.04 μm, p=0.001) and thinner RPE (β=-0.13 μm, p=0.002). Higher levels of PM2.5 absorbance and NO2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10 (PM with an aerodynamic diameter <10 μm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOx was associated with thinner photoreceptor synaptic region. Conclusion Greater exposure to PM2.5 was associated with self-reported AMD, while PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were all associated with differences in retinal layer thickness. [ABSTRACT FROM AUTHOR]

Introduction: Anti‐vascular endothelial growth factors (anti‐VEGFs) are considered standard of care therapy for diabetic macular oedema (DME). This study examined treatment patterns and outcomes in patients with DME treated with anti‐VEGF therapy. Methods: Using anonymized electronic medical record data collected from three UK sites, this retrospective cohort study assessed rates of anti‐VEGF intravitreal injections in adults with treatment‐naïve DME who received their first treatment between 1 September 2010 and 31 July 2018. The proportion of patients with at least one interval of at least 12 weeks between injections; the distribution of injection intervals; the discontinuation rates; and the number of anti‐VEGF injection‐, injection‐free‐ and total visits were assessed during the first and second years of treatment. Results: Overall, 1606 patient eyes with DME were included, with no minimum follow‐up. During the first and second year of treatment, 63.2% and 73.1% of eyes had at least one anti‐VEGF injection interval of at least 12 weeks, respectively. In the first and second years of treatment, the mean (standard deviation) numbers of injections were 7.7 (1.9) and 5.6 (2.2), with 14.2 (5.7) and 13.4 (6.4) total clinic visits, and 6.6 (5.0) and 7.8 (5.8) injection‐free visits, respectively. In total, 27.8% of patient eyes discontinued treatment during the first 2 years. Conclusions: The high number of clinic visits and high discontinuation rates demonstrate a significant unmet need for a treatment to enable sustainable extended injection intervals, while maintaining visual acuity. This could improve patient adherence and health‐related quality of life for patients with DME. [ABSTRACT FROM AUTHOR]

Background: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD).Objective: To investigate diabetes and DR as a risk marker of present and incident AD.Methods: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes.Results: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59-0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81-0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18-1.53).Conclusion: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR. [ABSTRACT FROM AUTHOR]

Purpose: Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) patients treated with intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) monotherapies achieve lower vision improvements compared with patients in clinical trials. This qualitative research study aimed to better understand the real-world anti-VEGF treatment experience from nAMD and DME patients', caregivers', and retina specialists' perspectives. Methods: One-time, semi-structured, individual interviews were conducted with adult patients with nAMD or DME treated with anti-VEGF injections for ≥ 12 months, their caregivers, and experienced retina specialists. Interview transcripts were analyzed qualitatively using a thematic analysis approach. Results: A total of 49 nAMD and 46 DME patients, 47 nAMD and 33 DME caregivers, and 62 retina specialists were interviewed in the USA, Canada, France, Germany, Italy and Spain. Most (79%) patients and caregivers reported disruptions to their routine on the day before, the day of, or the day after anti-VEGF injection. Seven nAMD patients (14%) and 14 DME patients (30%) reported having missed an injection visit. The most frequently reported driver for adherence for patients was the doctor–patient relationship (n=66, 70%), whereas for caregivers, it was the ease of booking an appointment (n=25, 32%). Retina specialists reported patient education on the treatment (n=28, 45%) as the most important driver. Treatment barriers could be grouped into four categories: tolerability, clinical factors, logistical parameters and human factors. The most frequently reported barrier to adherence for patients and caregivers was related to side effects (pain/discomfort/irritation: n=63, 67% of patients; n=52, 66% of caregivers), whereas for retina specialists it was logistical parameters (travel logistics: n=44, 71%). Conclusion: This study highlights the importance of the doctor–patient relationship and patient education as key drivers, and treatment tolerability and logistics as key barriers to treatment adherence. Improved doctor–patient relationship/communication and patient education together with new therapies offering convenience, long-acting effectiveness, and better tolerability may improve treatment adherence. [ABSTRACT FROM AUTHOR]

Background: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options.Methods: TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 μg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms.Discussion: The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy.Trial Registration: ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10. [ABSTRACT FROM AUTHOR]

Purpose: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort. Methods: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age. The baseline examination, including fundus photography, was conducted between 2007 and 2012, and the 5-year follow-up examination was performed between 2012 and 2017. AMD grading of fundus photographs was performed according to the Rotterdam Eye Study classification. The 5-year cumulative incidence and progression of AMD were calculated. Poisson regression analysis was conducted to investigate factors associated with the cumulative incidence and progression of AMD. Results: Six-thousand-eight-hundred-eighty-eight participants (49.8%, n = 3427 female) were included in the analysis. AMD prevalence was 8.5% [95% CI: 7.9–9.2%] at baseline and 10.3% [95% CI: 9.6–11.1%] at follow-up. The cumulative 5-year-incidence was 2.0% [1.7–2.4%]. AMD progression within 5 years was seen in 18.1% [95% CI: 15.1–21.5%] of the participants. AMD incidence and AMD progression were associated with higher age, for each 10-year increase in age, the risk of AMD doubles (RR = 2.30), and the risk of progression of the disease is increased by 1.6. while AMD incidence also with pseudophakic status. Conclusions: In summary, this population-based sample provides substantial epidemiologic data from a large German cohort, including data on progression and cumulative incidence of macular degeneration in younger age groups. AMD progression over 5 years is common in the German population, 18.1% of subjects with AMD showed progression in at least one eye in this time frame and is associated with higher age. Nevertheless, although usually defined to occur over the age of 50, in this cohort AMD occurred in 0.5% and AMD progression occurred in 5.4% of those already affected in the youngest age group before 50 years of age. [ABSTRACT FROM AUTHOR]

Background Choroidal naevi are a common incidental finding prompting specialist referrals to ocular oncology. Rarely, such lesions have sufficient suspicious features to diagnose a small melanoma. The aim of the study is to show that 'virtual' imaging-based pathways are a safe and efficient option to manage such referrals. Methods A prospective cohort study at the Manchester Royal Eye Hospital and Moorfields Eye Hospital between June 2016 and July 2017 of the management decision of 400 patients reviewed by an ophthalmologist in a face-toface consultation (gold standard) supported by fundus photography, optical coherence tomography, autofluorescence (AF) and B-mode ultrasound. The images were also read independently by blinded graders (non-medical) and blinded ophthalmologists, and a management decision was made based on image review alone (virtual pathway). The two pathways were compared for safety. Results The agreement for management decisions between face-to-face and virtual pathways was 83.1% (non-medical) and 82.6% (medical). There were more over-referrals in the virtual pathway (non-medical 24.3%, medical 23.3% of gold standard discharge) and only two under-referrals (10.5% of gold standard referrals), both borderline cases with minimal clinical risk. The agreement for risk factors of growth (orange pigment, subretinal fluid, hyper-AF) ranged between 82.3% and 97.3%. Conclusions We prospectively validated a virtual clinic model for the safe management of choroidal naevi. Such a model of care is feasible with low rate of under-referral. An over-referral rate of almost 24% from the vitrual pathway needs to be factored into designing such pathways in conjunction with evidence on their costeffectiveness. [ABSTRACT FROM AUTHOR]