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Purpose: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR‐screening programme and non‐diabetes adults. Methods: In this registry‐based matched case–cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age‐ and sex‐matched by five non‐diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models. Results: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20–1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08–1.30) as compared to non‐diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72–0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR‐levels 1–4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow‐up (HR 1.23; 95% CI, 1.02–1.49). Conclusion: In a nationwide matched case–cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR. [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]

Purpose: We aimed to investigate if diabetic retinopathy (DR), glaucoma and/or ocular hypertension (OHT) are prospectively linked, as previous studies have proposed cross‐sectional associations, but longitudinal data from larger cohorts are lacking. Methods: We performed a bidirectional 5 years prospective, registry‐based cohort study. We extracted data from national registers, including the Danish Registry of Diabetic Retinopathy, the Danish Civil Registration System, the Danish National Patient Register and the Danish National Prescription Registry. DR level was defined by the highest level of the two eyes. Glaucoma and/or OHT was defined by diagnostic codes (H40*) or at least three redeemed prescriptions of glaucoma medication (S01E*) within 1 year. We included 205 970 persons with diabetes and 1 003 170 age‐ and gender‐matched non‐diabetes controls. Exposures were level‐specific DR (i) and glaucoma and/or OHT (ii), and outcomes were hazard ratios (HRs) for 5 years incident glaucoma and/or OHT (i) and DR (ii). Results: Persons with diabetes were more likely to develop glaucoma and/or OHT (multivariable adjusted HR 1.11, 95% CI 1.06–1.15), but this did not depend on the level of DR. In persons with diabetes, those with glaucoma and/or OHT were more likely to develop DR (multivariable adjusted HR 1.12, 95% CI 1.03–1.23) within 5 years. Conclusion: In a national cohort, diabetes associated with a little higher risk of upcoming glaucoma and/or OHT, and, inversely, the presence of the latter predicted a higher risk of incident DR. Nevertheless, our data do not seem to justify including glaucoma evaluation in the national Danish DR‐screening programme. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to evaluate the prevalence and incidence of diabetic retinopathy (DR) along with associated markers in patients with type 2 diabetes in the Danish DR‐screening programme. Methods: We included all persons with type 2 diabetes in the Danish Registry of Diabetic Retinopathy, who had attended at least one episode of DR screening in 2013–2018. DR was classified as levels 0–4 indicating increasing severity. Data were linked with various national health registries to retrieve information on diabetes duration, marital status, comorbidity and systemic medication. Results: Among 153 238 persons with type 2 diabetes, median age and duration of diabetes were 66.9 and 5.3 years and 56.4% were males. Prevalence and 5‐year incidences of DR, 2‐step‐or‐more progression of DR and progression to proliferative DR (PDR) were 8.8%, 3.8%, 0.7% and 0.2%, respectively. In multivariable models, leading markers of incident DR and progression to PDR were duration of diabetes (HR 1.98, 95% CI 1.87–2.09; HR 2.89, 95% CI 2.34–3.58 per 10 years of duration) and use of insulin (HR 1.88, 95% CI 1.76–2.01; HR 2.40, 95% CI 1.84–3.13), while the use of cholesterol‐lowering medicine was a protecting marker (HR 0.87, 95% CI 0.81–0.93; HR 0.70, 95% CI 0.52–0.93). From 2013 to 2015, 3‐year incidence rates of PDR decreased from 1.22 to 0.45 events per 1000 person‐years. Conclusion: Nationally, among Danish individuals with type 2 diabetes attending DR screening, we identified duration of diabetes and use of insulin as the most important predictor for the development of DR, while cholesterol‐lowering medicine was a protective factor. [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]

Purpose: The purpose of this study was to evaluate the association between retinal laser burden and vascular oxygen saturation in patients with proliferative diabetic retinopathy (PDR) treated with different extent of retinal laser. Methods: The study was a prospective, interventional study of patients with treatment‐naïve PDR. Patients were treated with navigated retinal laser (Navilas®, OD‐OS GmbH, Teltow, Germany) in different doses. Retinal oximetry was obtained at baseline (BL) prior to laser and after 6 months (M6). Patients were divided into three groups according to total laser spots applied: <1500 spots (Group 1), 1500–2000 spots (Group 2), and >2000 spots (Group 3). Results: We included 33 eyes of 28 patients with treatment‐naïve PDR. The groups did not differ according in BL characteristics. Between BL and M6, retinal arteriolar oxygen saturation did not change but retinal venular oxygen saturation (median with interquartile range) decreased in Groups 1 and 2 (1: 65.5 ± 8.8% versus 60.5 ± 9.5%, p = 0.04; 2: 65.3 ± 7.3% versus 63.0 ± 13.5%, p = 0.04). Focal retinal venular oxygen saturation, located to quadrants with retinal neovascularization, decreased in Group 2 from BL to M6 (67.5 ± 13.3% versus 61.5 ± 8.8%, p = 0.04). Retinal venular diameter decreased from BL to M6 in Group 1 (174.5 ± 15.3 μm versus 165.1 ± 28.7 μm, p = 0.01). Conclusions: In this study of patients with treatment‐naïve PDR, we showed that a less extensive laser treatment caused a reduction in retinal venular oxygen saturation and diameter 6 months after treatment. Our results suggest that less extensive laser treatment may be sufficient to improve the retinal metabolic environment conducive to PDR regression. [ABSTRACT FROM AUTHOR]

Purpose: To report a new severity grading system for Fuchs endothelial corneal dystrophy (FECD) using anterior segment optical coherence tomography (AS‐OCT). Methods: This observational case series included 75 eyes of 43 patients with FECD and 33 eyes of 33 healthy subjects. Pachymetry and posterior elevation maps were used to determine the AS‐OCT‐based grading scores. FECD severity was graded from 0–3 as follows: 0, normal; 1, guttae only; 2, stromal oedema; and 3, epithelial and stromal oedema. We further investigated the central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior and posterior best‐fit spheres (BFS), and the distance between the central cornea and the thinnest point. Results: Thirty‐three eyes were graded as 0, four as 1, thirteen as 2, fourteen as 3, twenty‐nine as 4, eleven as 5 and four as 6 by the modified Krachmer grade. Thirty‐three, 41, 30 and 4 eyes were graded as 0, 1, 2 and 3, respectively, by the AS‐OCT‐based grading system. The inter‐observer agreement was 100% for the AS‐OCT‐based grading system. The CCT, TCT, posterior BFS, and distance between the central cornea and thinnest point were significantly different between AS‐OCT‐based grades (p = 0.0001, 0.0001, 0.0036 and 0.0001, respectively). Anterior BFS was not significantly different with the AS‐OCT‐based grades (p = 0.1184). Conclusion: We devised a new severity grading using only objective evaluation and quantitatively demonstrated corneal thickening, predominant flattening of the posterior corneal surface compared with the anterior surface, and displacement of the thinnest point away from the central cornea with FECD progression. [ABSTRACT FROM AUTHOR]

Purpose: Ocular and brain microcirculation share embryological and histological similarities. The retinal vascular fractal dimension (FD) is a marker of retinal vascular complexity of the vascular tree. The purpose of this study was to explore the relationship between cerebral blood flow (CBF), retinal vascular FD and other retinal vascular markers. Methods: Cross‐sectional analysis comprising 26 individuals ≥65 years old from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) cohort of relative healthy older adults. Retinal vascular FD was measured from fundus photographs by using the semi‐automated Singapore Eye Vessel Assessment (SIVA) software. CBF was estimated using a 2D pulsed ASL MRI sequence. Associations between blood flow and retinal parameters were analysed using linear regression models adjusted for age and sex. Results: Cerebral blood flow was positively associated with venular FD (R2 = 0.32, p = 0.03). This association was stronger in the anterior versus posterior brain territories (R2 = 0.35 [p = 0.001] versus R2 = 0.16 [p = 0.07], respectively). Global CBF was correlated with arteriolar branching angle (R2 = 0.23, p = 0.01) and tortuosity (R2 = 0.20, p = 0.02). Global CBF was not correlated with other SIVA parameters. Conclusions: Retinal venular complexity summarized by the FD was associated with cerebral blood flow as well as retinal arteriolar tortuosity and branching angle. Larger prospective clinical studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To report the incidence of post‐injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF).We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti‐VEGF injection in 2007–2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post‐injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients.We identified 60 825 patients who received intravitreal anti‐VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow‐up, resulting in an incidence of 0.022% [95% CI 0.019%–0.025%]. Despite a linear growth in annual anti‐VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%–0.023%] from 2013 to 2022. Compared to patients receiving 1–3 injections, RR for patients receiving 4–20, 21–40, and >40 injections were 0.46 [95% CI 0.34–0.63], 0.32 [95% CI 0.21–0.50], and 0.54 [95% CI 0.36–0.81], respectively. Findings were similar across the different diagnoses.Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti‐VEGF injections. [ABSTRACT FROM AUTHOR]

Aims: We investigated the efficacy of AI‐based screenings in preventing blindness, specifically assessing cost‐effectiveness when two further detection opportunities are incorporated: "DR screening during national health checkups" and "DR screening during diabetes clinic visits at a physician's office", or a combination of the two. We also examined potential additional costs associated with AI screening under various conditions. Methods: We employed a Markov Model in this simulation study. We constructed the modelling of diabetes detection, treatment, and retinopathy treatment based on transition probabilities derived from epidemiological and clinical studies. These covered incidence and progression rates of diabetes and diabetic retinopathy, treatment options and their efficacy, and visual prognosis. The age range for the model was set at 40–90 years with a 1‐year cycle, assuming a population of 500 000 individuals with a discount rate of 2%. Simulations were conducted using TreeAge. Costs were calculated using the direct costs of general health examinations and insurance treatments. We assumed diabetic retinopathy would result in a consistent visual acuity following detection, progression, and treatment, providing utility values based on the severity of DR. Results: DR screening via AI in health check‐up programs proved not to be cost‐effective, as it led to a 0.9% increase in cumulative blindness and the ICERs were dominated. The addition of an annual AI screening at physicians' clinics, with referrals to ophthalmology based on the results, resulted in an ICER of 8192751JPY/QALY, which was not cost‐effective. However, assuming that 75% of patients received AI screening during medical examinations and that 75% of these underwent ophthalmological examinations per the results, AI screening proved to be dominant and cost‐effective, reducing the cumulative number of blindness by 2.8%. Conclusions: Even though automated AI diagnosis of DR is becoming a reality, our findings suggest that merely introducing AI screening in health checkups and physicians' clinics in Japan will not be cost‐effective. However, cost‐effectiveness can be improved by increasing the rate of screening and the follow‐up rate of ophthalmological examinations. If this is achieved, there might also be a possibility of incurring additional costs due to AI screening. Our study underlines the importance of a seamless link from diabetes detection to ophthalmologic care for successful DR screening with AI systems. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). Methods: Thirty‐seven eyes with PDR were included. Wide‐field fluorescein angiography (Optomap, Optos PLC., Dunfermline, Scotland, UK) was used to diagnose PDR at baseline and to assess activity at follow‐up month three and six. At each time‐point, a trained grader measured retinal vessel geometry on optic disc (OD) centred images using semiautomated software (SIVA, Singapore I Vessel Assessment, National University of Singapore, Singapore) according to a standardized protocol. Results: At baseline, the mean age and duration of diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9 mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight (22%) eyes had progression at month three and 13 (35%) progressed over six months. Baseline characteristics, including age, sex, duration of diabetes, HbA1c, blood pressure, vessel geometric variables and total amount of laser energy delivered did not differ by progression status. However, compared to patients with progression of PDR, patients with favourable treatment outcome had alterations in the retinal arteriolar structures from baseline to month six (calibre, 154.3 μm versus 159.5 μm, p = 0.04, tortuosity 1.12 versus 1.10, p = 0.04) and in venular structures from baseline to month three (fractal dimension 1.490 versus 1.499, p = 0.04, branching coefficient (BC) 1.32 versus 1.37, p = 0.01). Conclusion: In patients with PDR, successful PRP leads to alterations in the retinal vascular structure. However, baseline retinal vascular geometry characteristics did not predict treatment outcome. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the reliability and reproducibility of the Vesselmap Oximetry Module for arteriolar and venular oxygen saturation (SO2) of the same retinal area, specified by a peripapillary annulus, in healthy subjects. Methods: Fundus oximetry images were obtained, using a standardized protocol by a single observer, from the right eye of 20 healthy individuals. Age range was 19-45 years old, and images were analysed using the oximetry module of the Vesselmap System (Imedos, UG, Germany). Intra-observer reliability (assessment of two measurements of SO2 values performed 5 days apart); interobserver reliability (assessment of SO2 performed by two different trained observers); and intrasubject reproducibility (comparison of SO2 measurements of two different images of the same subject and retinal area, taken 10 min apart) were assessed. The standard deviations between the repeated measurements (SDr), together with the intraclass correlation coefficient (ICC), of these three parameters were calculated. Results: The SDr for intra-observer reliability was 0.56% and 0.55% for arteriolar and venular SO2, respectively. The results were similar for intrasubject reproducibility (0.69% and 0.79% for arteriolar and venular SO2, respectively); interobserver reliability, however, was higher (SDr 1.22% and 1.01% for arteriolar and venular SO2, respectively). The ICC values for intra-observer reliability were 0.99 for both arteriolar and venular SO2. The results were similar for both interobserver reliability (0.94 for arteriolar SO2 and 0.96 for venular SO2) and intrasubject reproducibility (0.98 for both arteriolar and venular SO2). Conclusion: Retinal oxygen saturation values taken using the oximetry module of the Vesselmap System are highly reliable and reproducible, provided the image quality is standardized, the same measurement area is analysed in each image, and the number of observers analysing the images is kept to a minimum. [ABSTRACT FROM AUTHOR]

. Purpose: To assess the relation between retinal vascular caliber and renal function. Patients and methods: Eighty apparently healthy subjects screened for cardiovascular risk factors (mean age 47 years, 51% female, 36% hypertensive, without diabetes or renal dysfunction) were recruited. Retinal vascular calibers were measured from fundus photographs and expressed as central retinal artery and venular equivalent. Renal function was assessed by measurement of glomerular filtration rate (urinary clearance of 99mTc-DTPA) and urinary albumin/creatinine ratio. Results: Mean glomerular filtration rate was 117 ml/min/1.73m2. Overall, central retinal artery and venular equivalent were positively correlated with glomerular filtration rate ( r = +0.31, p = 0.005 and r = +0.30, p = 0.006, respectively). In addition, central retinal artery equivalent was negatively correlated with urinary albumin/creatinine ratio ( r = −0.34, p = 0.002). No significant relationship was found between central retinal venular equivalent and urinary albumin/creatinine ratio ( r = +0.12, p = 0.32). The observed relations between retinal vascular calibers and renal function parameters remained significant after adjusting for potential confounding factors. Conclusion: In apparently healthy subjects with normal renal function, retinal arteriolar and venular calibers were negatively correlated with kidney function, suggesting common determinants of these preclinical target organ damages. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To evaluate the five‐year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR‐screening programme.Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013–2018. According to the worse eye at first screening, DR was classified (levels 0–4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication.At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five‐year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63–1.89, and HR 2.04, 95% CI 1.73–2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10–1.47, and HR 2.80, 95% CI 2.23–3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05–1.36, and HR 1.98, 95% CI 1.53–2.57).In a study of all patients with type 1 diabetes from the Danish DR‐screening programme, we identified duration of diabetes, systemic disease and use of anti‐hypertensive treatment as consistent risk markers for incident and progressive DR. [ABSTRACT FROM AUTHOR]

This article presents a sub-analysis of an age-related maculopathy statin study (ARMSS) data to examine the impact of statins on retinal vascular caliber changes compared to placebo treatment. The ARMSS examined the effect of simvastatin intake versus placebo in preventing the age-related macular degeneration progression. It concludes that statins may contribute to the prevention or management of retinal vascular diseases related to cardiovascular risks and inflammation.