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Purpose: The association between thyroid dysfunction and exudative age‐related macular degeneration (AMD) is unknown. Methods: In this Danish longitudinal nationwide registry‐based cohort study we included all Danish residents aged 50–100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti‐thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti‐VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow‐up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10–1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13–1.34; p < 0.001) were both associated with the development of exudative AMD. The age‐stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. Conclusion: This is the first longitudinal nationwide study showing that both hypo‐ and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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). Conclusion: 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]

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: A number of algorithms have been developed to calculate screening intervals for diabetic retinopathy on the basis of individual risk factors. However, these approaches have not considered proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DME) as separate end points and death as competing risk. Methods: A multi‐state survival model with death as competing risk was used to predict the screening interval for diabetic retinopathy based on information about all 2446 patients from a well‐defined population who had started treatment for either PDR or DME during 25 years. The performance of the model was tested on the existing database and at seven screening sites on patients who had not developed a treatment requiring condition. Results: Testing on the existing database showed that at a risk level of 2% the algorithm could predict a screening interval with a success rate higher than 90% and a 1.75 times average prolongation of the screening interval without failing to detect the development of verified PDR og DME. The model was limited to a diabetes duration shorter than 40 years and depended on knowledge of relevant risk factors. At the other participating screening sites the algorithm predicted shorter intervals than the screener. Conclusions: Algorithms for individualised screening for diabetic retinopathy can prolong screening intervals without losing patients who develop a vision threatening condition. The calculation of screening intervals requires access to relevant risk factors and should be developed on large data sets that reflect the population in which the algorithm should be used. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in the incidence rate of primary rhegmatogenous retinal detachment (RRD) surgery over time and to determine to what extent these changes can be attributed to pseudophakia. Methods: This nationwide cohort study was based on national patient registries. The study population comprised individuals at risk of RRD aged 40 years and above from 2006 to 2021 in Denmark. The primary outcome was RRD incidence, and the exposure was phacoemulsification surgery. A chart review was conducted to validate and examine the lens status of the outcome. Results: The crude and age‐adjusted incidence rate of RRD in the Danish population increased significantly during the study period. The largest increase in RRD was seen in phakic RRD (phRRD) (65%), whereas pseudophakic RRD (pRRD) accounted for 35% of the total increase. A chart review revealed that 17% of phRRDs were misclassified as pseudophakic, resulting in pRRD accounting for a total of 45% of the increase in RRD. The prevalence of pseudophakia in Denmark grew significantly for all age groups and for both sexes (p = 10−6) from 2006 to 2021, but the 1‐year incidence of pRRD in the pseudophakic population was constant throughout the entire period. Conclusion: The incidence rate of RRD is continuing to increase in Denmark. The increase in phRRD remains undetermined, and while the risk of pRRD seemed to be constant during the study period, 45% of the overall increase in RRD could be attributed to the rise of a growing pseudophakic population. [ABSTRACT FROM AUTHOR]

To estimate the prevalence of convergence insufficiency (CI) in adult patients with post-concussion syndrome and determine the impact of CI on symptom load. Cross-sectional study of 103 patients with neurological symptoms 2–6 months after a concussion. Symptoms were assessed with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and CI was diagnosed using near point of convergence, vergence facility, and the Convergence Insufficiency Symptom Survey. The RPQ score for patients with and without CI was compared, and sensitivity, specificity, and area under the receiver operating characteristic curve for the two visually related RPQ questions as indicators of CI were calculated. The proportion of patients diagnosed with symptomatic CI was 20.4% (95% confidence interval: 13.1–29.5%). The RPQ score was significantly higher for patients with symptomatic CI both before (p =.01) and after removal of the two visually related questions in the RPQ-questionnaire (p =.03). The two visually related RPQ questions were unable to detect CI. In patients with post-concussion syndrome, the load of nonvisual symptoms is higher in the presence of CI. A prospective interventional study on CI is required to study the relationship between CI and other post-concussion symptoms. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of β-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR. Article Highlights: Type 2 diabetes can be subcategorized on the basis of β-cell function and insulin sensitivity, but little is known about the association of subtypes of type 2 diabetes with risk of diabetic retinopathy (DR). Do individuals with hyperinsulinemic or insulinopenic type 2 diabetes have an increased risk of DR compared with individuals with classical type 2 diabetes? Individuals with hyperinsulinemic type 2 diabetes had almost half the risk of prevalent or incident DR or progression of DR compared with individuals with classical type 2 diabetes. These results suggest that more individualized screening intervals for DR may be possible within subgroups of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. Methods: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene‐related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. Results: Bradykinin, VIP and CGRP induced significant concentration‐dependent dilatation and NPY significant concentration‐dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L‐NAME reduced bradykinin‐ and VIP‐induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. Conclusion: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): −0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: −0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression. [ABSTRACT FROM AUTHOR]

A study conducted in Denmark evaluated the risk of progression from no diabetic retinopathy (DR) to proliferative diabetic retinopathy (PDR) in individuals with diabetes. The study found that the risk of progression to PDR within 2 years was lower than expected in a national cohort. While individuals with impaired glycemic control had a higher risk of progression to PDR, this was only statistically significant in those with type 2 diabetes. The study suggests that biannual screening intervals for individuals without DR may be safely introduced in national DR screening programs. The study was supported by VELUX FONDEN. [Extracted from the article]

Aims: Bariatric surgery is used to induce weight loss and glycemic stability in type 2 diabetes (T2D). It has been a concern that this may lead to early worsening of diabetic retinopathy (DR) due to a rapid decline in HbA1c. In this study, we evaluated the risk of short and long-term DR development and need for ocular intervention in an entire nation of individuals with T2D undergoing bariatric surgery. Methods: The study comprised a national, register-based cohort of individuals with T2D screened for DR. Cases were matched by age, sex and DR level at the date of surgery (index date) with non-bariatric controls. We extracted information on DR levels, in- and outpatient treatments, pharmaceutical prescriptions and laboratory values. We evaluated worsening of DR (incident and progressive DR) at follow-up (6 and 36 months). Results: Amongst 238,967 individuals with T2D, who attended diabetic eye screening, we identified 553 that underwent bariatric surgery (0.2%) and 2677 non-bariatric controls. Median age was 49 years, and 63% were female. Cases had more comorbidities, lower HbA1c as well as more frequent use of glucose-lowering and antihypertensive medication than controls at index date. In a fully adjusted logistic regression model, the risk of DR worsening for cases was not significantly different compared to controls, neither short-term (OR 0.41 [CI 95% 0.13; 1.33], p = 0.14) nor long-term (OR 0.64 [CI 95% 0.33; 1.24], p = 0.18). Conclusions: In this nationwide study, bariatric surgery did not associate with increased risk of short- or long-term DR worsening. [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]

Background: To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children. Methods: Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat. Results: Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention. Conclusions: Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early "rebound-effect". Trial registration: this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted at www.clinicaltrials.gov (NCT03911271) 11/04/2019, prior to initiation. [ABSTRACT FROM AUTHOR]

The article "Dissecting the Neurovascular Unit in Human Diabetic Retinal Disease" published in Diabetes explores the relationship between microvascular and neurodegenerative aspects of diabetic retinal disease (DRD) in postmortem human retinas. The study found that microvascular defects in the deep capillary plexus of the retina can occur independently of other vascular lesions, and neural cell degeneration is not necessarily connected to microvascular lesions. The research, supported by various foundations, aims to develop a quantitative grading scale for DRD that reflects the overall status of the retina. [Extracted from the article]

Purpose: Knowledge of visual health in the population is necessary for designing and implementing measures to handle visual handicap. The purpose of the FORSYN (Forekomst af synshandicap og synshjælpemidler i Danmark) project was to study visual health in the Danish population 2020–2022 after implementation of the recent advances in the management of choroidal and retinal vascular disease. The present study reports visual acuity and causes of central visual loss from this study. Methods: A population‐representative sample of 10 350 citizens living within 40 kilometres from Aarhus University Hospital were invited to answer a questionnaire about quality of life related to vision, measurement of visual acuity and a non‐mydriatic examination of the eyes. The data were corrected for selection bias on the basis of demographic and socioeconomic factors so that the results could be projected to represent the adult Danish population. Results: Population‐adjusted visual acuity in ETDRS letters (mean ± SD) differed significantly (p < 0.0001) among the worse eye (84.1 ± 0.25), the better eye (88.4 ± 0.11) and binocularly (89.2 ± 0.15). Social blindness affected 0.22% (95% CI: 0.14%–0.33%) of the population and was in none of the studied persons due to exudative age‐related macular degeneration (AMD) or diabetic retinopathy. The most frequent causes of visual loss were atrophic AMD, neuro‐ophthalmic disorders and other chorioretinal diseases. Conclusions: Recent advances in the therapy of chorioretinal vascular diseases have been paralleled with a reduction in central vision loss secondary to exudative AMD and diabetic retinopathy in Denmark. The demographic development can be expected to increase the demand for treatments of vision‐threatening diseases that mainly affect older persons. [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]

Background: To investigate the relationship between risk factors for retinal artery occlusion (RAO) and retinal vein occlusion (RVO) and thereby identify similarities and differences between the two types of retinal vascular occlusions. Methods: In this case–control study, 5708 patients with RAO were included and matched with three patients with RVO each. The patients with RVO were matched on sex and age at index date. All patients, personal information, diagnoses, and prescriptions were obtained from the Danish nationwide registries. Adjusted conditional logistic regression was used to investigate the association of RAO and RVO with the included risk factors. Results: RAO was stronger associated with arterial hypertension, heart failure, ischemic heart disease, peripheral artery disease, and stroke than RVO, with effect measures ranging from 1.10 to 2.21. RVO was associated with cataract and glaucoma with effect measures of 0.80 (95% CI 0.73–0.87) and 0.65 (95% CI 0.56–0.76), respectively. Conclusion: Differences in the level of associations with the included risk factors suggests differences in the pathophysiologies of the two diseases. The main pathophysiology associated with RAO was atherosclerosis, whereas the main pathophysiology associated with RVO was changes in the pressure gradients of the eyes. [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]

Pregnancy is a risk factor for the development or aggravation of diabetic retinopathy. Here, we suggest a relationship between plasma vitamin C (vitC) status during pregnancy and into postpartum in type 1 diabetes and the possible progression of diabetic retinopathy based on data of 29 women. VitC was measured in first, second, and third trimesters and three months postpartum. The women had visual acuity testing and fundus photography performed at least twice during pregnancy and onto four months after birth. An overall retinopathy grade was assigned on a scale from 0 (no retinopathy) to four according to the International Clinical Diabetic Retinopathy scale. At baseline in 1st trimester, 12 women had no retinopathy; seventeen women had retinopathy in grade 1–3. The retinopathy grade increased in nine women; remained unchanged in 17 women, and improved in three women. No women had or developed proliferative retinopathy (grade 4). The level of vitC in 1st trimester predicted the possible progression of retinopathy—the lower the vitC, the more probable the progression (p = 0.03; OR 1.6 (95% CI:1.06–3.2); n = 29 (multiple logistic regression))—while the combined levels of 1st and 2nd trimesters and the mean vitC level of the whole pregnancy did not. The diabetes duration, retinopathy grade per se in 1st trimester, 24-h blood pressure measurements, kidney function, urinary protein, HbA1c, or lipid profile were not independent predictors of progression of retinopathy during pregnancy. Retrospectively, the women who experienced progression of their retinopathy during and into postpartum had significantly lower vitC levels in 1st trimester (p = 0.02; n = 9/20), combined level of vitC in 1st and 2nd trimester (p = 0.032; n = 7/18), and mean vitC level of the whole pregnancy (p = 0.036; n = 7/9), respectively. In conclusion, our results suggest that low vitC status in pregnancy could be associated with progression of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, randomized, double-masked, placebo-controlled, equal-allocation, multicenter study comparing 0.1% atropine loading dose (six months) followed by 0.01% atropine (18 months), 0.01% atropine (24 months), and placebo (24 months). Participants were monitored for a 12-months washout period. Outcome measures were axial length (AL), cycloplegic spherical equivalent (SE), photopic and mesopic pupil size, accommodation amplitude, visual acuity, intraocular pressure (IOP), and adverse reactions and events. We randomized 97 participants (mean [standard deviation] age, 9.4 [1.7] years; 55 girls (57%) and 42 boys (43%)). After six months, AL was 0.13 mm shorter (95% confidence interval [CI], −0.18 to −0.07 [adjusted p < 0.001]) with 0.1% atropine loading dose and 0.06 mm shorter (95% CI, −0.11 to −0.01 [adjusted p = 0.06]) with 0.01% atropine than in the placebo group. We observed similar dose-dependent changes in SE, pupil size, accommodation amplitude, and adverse reactions. No significant differences in visual acuity or IOP were found between groups, and no serious adverse reactions were reported. We found a dose-dependent effect of low-dose atropine in European children without adverse reactions requiring photochromatic or progressive spectacles. Our results are comparable to those observed in East Asia, indicating that results on myopia control with low-dose atropine are generalizable across populations with different racial backgrounds. [ABSTRACT FROM AUTHOR]

Purpose The purpose of the study was to evaluate vision‐related quality of life and visual ability in patients with OPA1 autosomal dominant optic atrophy (ADOA). Methods: This cross‐sectional, observational study included 145 participants with a mutation in the OPA1 gene associated with ADOA, 63 mutation‐free first‐degree relatives and 92 healthy subjects unrelated to the families. Participants underwent a clinical eye examination, and adult participants completed the National Eye Institute Visual Function Questionnaire (NEI‐VFQ‐39), while children completed the Cardiff Visual Ability Questionnaire for Children (CVAQC). Results: In adults with ADOA, both mean visual acuity (VA) and mean contrast sensitivity (CS) were significantly inferior to both first‐degree relatives and unrelated controls (p < 0.001). In children with ADOA, mean VA was significantly lower compared with first‐degree relatives (p = 0.0052), whereas CS was not (0.127). Adults with ADOA scored lower than both comparator groups on composite score (p < 0.001), general health subscale (p = 0.0075) and all vision‐related subscales (p < 0.001) except the ocular pain subscale (p = 0.2). In children with ADOA, the median CVAQC logit score was significantly lower compared with first‐degree relatives (p = 0.037). The science lessons subscale was significantly lower for children with ADOA compared with first‐degree relatives (p = 0.046), as well as the language lessons subscale (p = 0.038). For adults, composite score and subscale scores were significantly associated with both VA, CS and fixation status. Conclusion: OPA1 mutation is associated with lower quality of life and visual ability in patients with ADOA compared with both first‐degree relatives and unrelated controls. VA, CS and fixation status affect quality of life in patients with ADOA. [ABSTRACT FROM AUTHOR]

Purpose: Clustering of vision threatening diabetic retinopathy within specific families can be the result of similarities in life style but may also be due to a common genetic background. An evaluation of the role of heredity for the development of diabetic retinopathy may help adjusting control intervals in screening program to each patient's individual risk profile. Methods: Survival analysis was used to study whether family history of diabetes among men and women with type 1 or type 2 diabetes together with the degree of heredity could be added as risk factors to improve the prediction of the risk for developing proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). The study was conducted on data from 12,281 patients followed in the Aarhus area, Denmark, from 1 January 2003 to 1 July 2019. Results: The risk for developing PDR was significantly reduced 2–11 years after known onset of diabetes in the presence of female family members with type 1 diabetes, and the risk for developing DME significantly increased 4–24 years after onset of diabetes in the presence of family members with type 2 diabetes of any sex. These hereditary factors were independent of other studied risk factors such as previous cataract surgery, age of onset of diabetes, metabolic regulation and blood pressure. Conclusions: The presence of family members with diabetes affects the risk for developing vision threatening diabetic retinopathy and affects the risk for developing PDR and DME differently. This evidence may help individualizing the control intervals in screening programmes for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Introduction: Risk factors for retinal vein occlusion have been extensively studied, with varying population sizes. Smaller populations result in less certain measures of associations. The present review included studies with a relevant population size to identify clinically relevant risk factors for retinal vein occlusion. Understanding the risk factors of retinal vein occlusion is important for the management of these patients.Areas Covered: A comprehensive literature review was conducted through a systematic literature search in PubMed and Embase. Additional studies were selected from cross references in the assessed studies. Weighted effect measures were calculated for all included risk factors.Risk factors associated with retinal vein occlusion included cardiovascular diseases, eye diseases, systemic diseases, medical interventions, and sociodemographic factors.Expert Opinion: This review provided an extensive overview of a wide variety of risk factors increasing the risk of developing retinal vein occlusion. The severity of the identified risk factors indicated that these patients have been in contact with the health care system before their retinal vein occlusion event. Therefore, the clinical course for patients with retinal vein occlusion may benefit from a multidisciplinary collaboration between ophthalmologists and especially cardiologists. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to examine potential risk factors for the development of retinal artery occlusions (RAO). Methods: We used data obtained from Danish nationwide registries to evaluate potential risk factors for RAO present up to 5 years prior to the RAO diagnosis. The study included 5312 patients diagnosed with RAO registered in the Danish National Patient Register and 26,560 controls assessed from the general population matched on sex and age at index date. Adjusted conditional logistic regression was used to estimate the odds ratio of included risk factors for RAO diagnosis. We conducted supplementary analyses stratified on sex and age, and on RAO subtype. In addition, interaction analyses were performed between strata in the stratified analyses. Results: Risk factors associated with the development of RAO included diabetes, arterial hypertension, ischemic heart disease, peripheral artery disease, stroke, renal disease, cataract, and glaucoma, with ORs ranging from 1.33 to 4.94. Atrial fibrillation and sleep apnea yielded effect measures close to equivalence. The presence of a risk factor was generally associated with higher odds of RAO among the population ≤ 55 of age. Arterial hypertension was stronger associated with RAO in male patients than in female patients. The association with arterial hypertension was stronger for CRAO than for BRAO subtype. Conclusion: The investigated risk factors suggest that atherosclerosis and conditions changing the intraocular pressure are involved in the pathophysiology of RAO. [ABSTRACT FROM AUTHOR]

Purpose: To identify parameters that can predict the postoperative risk for progression of retinopathy to a vision‐threatening stage after cataract surgery. This may optimize the timing of surgery and the postoperative follow‐up strategy in diabetic patients. Methods: Multi‐state survival analysis with death as competing risk was used to investigate how year of onset and age of onset of diabetes, gender, body mass index, HbA1c and blood pressure had affected the risk for developing diabetic macular oedema (DME) and proliferative diabetic retinopathy (PDR) among 2540 right eyes from 2797 diabetic patients operated for cataract on one or both eyes during 25 years until July 1. 2019. Results: Cataract surgery had been performed in 98.8% of patients reaching 90 years of age. The risk for developing both DME and PDR was increased by cataract surgery. The risk was highest during the first postoperative years and increased by pre‐operative variability in HbA1c. The risk after more than 20 years postoperatively increased by increased cumulative HbA1c pre‐operatively. The other studied risk factors contributed differently to the development of the two complications. Conclusions: Decision models for the timing of cataract surgery in diabetic patients should consider that the risk for developing vision‐threatening retinopathy depends on follow‐up time. Differences in the risk profiles for developing DME and PDR after cataract surgery support that the two complications should be regarded as separate late complications. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that the retinal oxygen saturation in central retinal vein occlusion treated with anti‐VEGF compound has no predictive value for visual outcome after 12 months. It is of interest to evaluate whether this conclusion is similar for patients with branch retinal vein occlusion among whom only some patients are treated. Methods: Retinal oxygen saturation, visual acuity and central retinal thickness were studied at the time of referral and after six and 12 months in 111 patients successively referred to the Department of Ophthalmology, Aarhus University Hospital, with a venous occlusion affecting branches peripheral from the central retinal venule. The predictive value of the oxygen saturation at referral was investigated in treated and untreated patients. Results: Seventy‐three patients with visual acuity between 35 and 70 ETDRS letters at referral were treated with intravitreal injection of anti‐VEGF compound. Over 12 months, the venous oxygen saturation improved in parallel with central retinal thickness and visual acuity but had no predictive value for visual outcome. In 12 untreated patients with visual acuity >70 ETDRS letters, younger age and high oxygen saturation at the time of referral were positive predictors for the visual outcome after 12 months. Conclusion: Oxygen saturation, visual acuity and central retinal thickness improve in parallel during treatment of branch retinal vein occlusion with intravitreal anti‐VEGF medication. Retinal oximetry at referral cannot predict visual acuity after 12 months in treated patients but may perhaps become a tool for predicting the visual prognosis in a subgroup of patients where treatment is omitted because of a too high visual acuity at the time of diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Proliferative diabetic retinopathy (PDR) can be treated by retinal photocoagulation, but in some cases, the treatment is initiated too late or is insufficient so that the disease advances to a stage requiring vitrectomy. There is a need to identify risk factors that can predict if patients with PDR will develop complications in need for vitrectomy. Methods: Survival analysis with death as competing risk was used to study systemic risk factors for PDR progression to a complication in need for vitrectomy in right eyes of all 1288 diabetic patients from the Aarhus area, Denmark, who had developed proliferative retinopathy in the right eye during the 25 years period from 1 July 1994 until 1 July 2019. Results: The overall cumulative incidence of reaching a vitrectomy end point in the right eye was 24.1% (n = 311). In 9.3% (n = 120) of the patients where vitrectomy had been performed together with the first photocoagulation, the age of onset of diabetes was significantly higher (p < 0.0001), the diabetes duration longer (p < 0.035) and BMI higher (p < 0.01) than in the patients who had been vitrectomized later than the first photocoagulation. The risk for vitrectomy was significantly increased by high variability of HbA1c before the development of PDR (p < 0.0001), but not by other parameters known to increase the risk for developing PDR. Conclusion: Increasing variability of HbA1c before the development of PDR increases the risk for progression to a complication in need of vitrectomy. The need for vitrectomy is unaffected by other risk factors known to increase the risk for developing PDR. [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: Central retinal vein occlusion (CRVO) entails retinal hypoxia that often causes visual impairment. It has been shown that oxygen saturation in larger retinal vessels correlates with the visual acuity at the time of diagnosis of CRVO but has no predictive value for the visual outcome in patients treated with anti‐VEGF medication after 3 months. However, assessing the predictive value of retinal oxygen saturation after 12 months is essential because this is when the main restitution after CRVO occurs. Methods: Retinal oximetry was performed in 117 patients referred with CRVO to three European centres. The correlation between oxygen saturation and visual acuity at baseline and the predictive value of oxygen saturation in larger retinal vessels for the 12‐month visual outcome after treatment with anti‐VEGF medication were studied. Results: In the affected eye, the oxygen saturation was significantly higher in the arterioles, significantly lower in the venules, and the arterio‐venous (A‐V) significantly higher than in the unaffected eye (p < 0.001 for all comparisons). Correlations between best‐corrected visual acuity (BCVA) and oxygen saturations were moderate and negative for arterioles (p < 0.001), positive for venules (p = 0.03) and negative for the A‐V difference (p = 0.001). Best‐corrected visual acuity (BCVA), but not oxygen saturation or the other explanatory variables at baseline, contributed significantly to predicting BCVA after 12 months. Conclusion: Retinal vessel oxygen saturation is affected in CRVO, and saturation correlates with BCVA. However, retinal oximetry cannot replace measures of visual function as a predictor of visual outcome after 12 months of anti‐VEGF treatment for CRVO. [ABSTRACT FROM AUTHOR]

Purpose: According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Design: Prospective cohort study following screening in a hospital setting. Methods: Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76–6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Results: Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p<0.0001). Venular saturation increased by 1.74±0.26 percentage points per year (p<0.0001) and arteriovenous difference decreased by 0.99±0.20 percentage points per year (p<0.0001). Arteriolar diameters decreased by 2.7±8.5μm (p<0.0001) between visits and venular diameters decreased by 2.4±9.1μm (p = 0.0002). Median increase in red lesion count between visits was 2 lesions (range -128 to 212 lesions, p<0.0001). The change in red lesion count and change in diameters did not correlate with the length of follow-up (p>0.44). Conclusions: Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The purpose of screening for diabetic retinopathy is to detect either of the two sight-threatening complications: proliferative diabetic retinopathy (PDR) or clinically significant diabetic macular oedema (DME). The aim of the study was to evaluate whether systemic risk factors affect the risk of developing these two complications differently. Methods: Survival analysis with death as a competing risk was used to describe the effect of sex, age and time of onset of diabetes, systolic (SBP) and diastolic (DBP) BPs, and the weighted exposure and CV of HbA1c for the development of PDR and DME from all 2773 patients treated for diabetic retinopathy in a defined population from the Aarhus area, Denmark, between 1 July 1994 and 1 July 2019. Results: Increasing HbA1c above normal increased the risk of developing both PDR and DME (p < 0.04), and values below normal increased the risk of developing PDR (p < 0.013). Increasing DBP increased the risk of developing both PDR and DME (p < 0.0001), whereas increasing SBP increased the risk of developing DME (p < 0.0001), but not PDR (p > 0.08). The risk of developing PDR increased with decreasing age of onset of diabetes (p < 0.0001), whereas the risk of developing DME was maximal for a known onset of diabetes at about 30 years of age and decreased significantly for both lower and higher ages of onset (p < 0.0001). The risk of developing both PDR and DME was lower in women than in men (p < 0.004) and was reduced with lower variability of repeated HbA1c measurements (p < 0.0001). Conclusions/interpretation: Systemic risk factors such as metabolic regulation, arterial BP and the age of onset of diabetes contribute differently to the development of PDR and DME. The overall risk of developing treatment-requiring diabetic retinopathy should be calculated from the risks of reaching each of the two complications separately. [ABSTRACT FROM AUTHOR]

Diabetic maculopathy (DM) treated with photocoagulation may subsequently progress to proliferative diabetic retinopathy (PDR). However, there is insufficient knowledge about the incidence and risk factors for the development of PDR in patients previously treated for DM. Survival data was used to analyze prospectively collected epidemiological and clinical data to describe the incidence and risk factors for the occurrence of PDR in all 1,235 patients photocoagulation treated for DM in a defined population from the Aarhus area, Denmark, from January 1. 1993 until December 31. 2016. Among 1,204 (97.5%) of the patients in whom the subsequent clinical history was known, 536 (44.5%) had died and 131 (10.9%) had received panretinal photocoagulation for PDR. The cumulative incidence of developing PDR after photocoagulation for diabetic maculopathy increased with time to reach a plateau around 13% after approximately 15 years. Earlier age at diagnosis of diabetes and higher HbA1c at the time of macular treatment were significant risk factors for the development of PDR, whereas gender, diabetes type, body mass index, known diabetes duration at the time of macular photocoagulation and blood pressure were not significant risk factors. In patients treated with retinal photocoagulation for DM, a tight metabolic control is accompanied with a reduced risk for subsequent progression to PDR. In the treated patients who do not develop PDR, the control interval can be gradually increased with time. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. Methods: The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. Results: Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. Conclusions: The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: Coats' disease is characterized by vascular hyperpermeability, oedema and accumulation of exudates related to impairment of retinal vascular function. The background for the development of the disease is unknown, but it is likely that the study of diameter changes of retinal vessels may contribute to understanding the pathophysiology of the disease. Methods: In seven patients with unilateral Coats' disease (mean age = 34.7 years, range: 11–69 years), the baseline diameter and reactivity of retinal vessels during an increase in the arterial blood pressure by isometric exercise and in the metabolism by flicker stimulation were measured on video recordings of the retina obtained with the Dynamic Vessel Analyzer. Results: The baseline diameter of retinal vessels was larger in the affected than in the unaffected eyes which was significant for the arterioles (p = 0.02), but not for the venules (p = 0.15). During an increase in the arterial blood pressure induced by isometric exercise, the normal contraction of arterioles was absent in both eyes (p > 0.7), whereas there was a significant dilatation of the venules in the unaffected eyes (p = 0.04). Stimulation with flickering light induced normal dilatation of retinal vessels in both affected and unaffected eyes. Conclusion: Unilateral Coats' disease is accompanied by vasodilatation in the affected eye but impaired pressure autoregulation in both eyes. A further investigation of the disease should include an elucidation of the background for dilatation of retinal vessels in affected eyes and whether impaired pressure autoregulation can be found in vessels elsewhere in the body. [ABSTRACT FROM AUTHOR]

Purpose: Direct ophthalmoscopy can reveal systemic, neurologic and ophthalmic conditions, but is poorly mastered among young physicians. A theoretical test is needed to measure effect of educational interventions. We developed and gathered validity evidence for a multiple‐choice questionnaire (MCQ)‐based theoretical test in direct ophthalmoscopy. Methods: The MCQ was developed by interviewing experts. Then, validity evidence was evaluated using Messick's validity framework. Content was ensured by inviting the experts to contribute in a Delphi‐like process. Response process was ensured by piloting and by streamlining all instructions. Then, the test was taken by ophthalmologists and by medical students without experience in direct ophthalmoscopy. Results were used to evaluate internal structure (item quality analysis and internal consistency), relations to other variables (correlation of test scores to experience level) and consequences (establishment of pass–fail score and the consequences of its use). Results: The first phase of the study yielded 100 MCQs. In second phase, we identified that 60 items fulfilled predefined relevance and item quality requirements. These items demonstrated very high internal consistency (Cronbach's alpha = 0.95), significantly discriminated medical students from specialists (p < 0.001, independent samples t‐test) and the established pass–fail score of 50 (83%) correct answers resulted in no false positives (students passing) and no false negatives (specialists failing). A Decision study identified that sampling 15 items suffice for certification. Conclusion: We developed and validated an MCQ‐based theoretical test in direct ophthalmoscopy that enables an evidence‐based approach to measuring, evaluating and certifying the theoretical knowledge necessary for direct ophthalmoscopy. [ABSTRACT FROM AUTHOR]

Purpose: Remote ischemic conditioning (RIC) implies that transient ischemia in one organ can affect blood flow and protect from ischemia in another remote organ such as the retina. The purpose of the present study was to investigate the effect of RIC on the diameter of retinal arterioles in patients with diabetic retinopathy and whether this effect differs among peripheral and macular vessels. Methods: In twenty type 1 diabetes patients aged 20–31 years, the Dynamic Vessel Analyzer (DVA) was used to measure diameters of peripheral and macular arterioles during rest, isometric exercise, and flicker stimulation. Measurements were obtained before, immediately after, and 1 h after RIC, and were compared to responses obtained from normal persons. Results: The reduced baseline diameter (p < 0.009) and contraction of peripheral retinal arterioles during isometric exercise (p = 0.025) observed immediately after RIC in normal persons were absent in the studied diabetic patients. Conclusions: RIC affects the diameter of peripheral but not macular arterioles in normal persons, but the response is abolished in diabetic patients. Trial registration: NCT03906383 [ABSTRACT FROM AUTHOR]

Background The oxygen saturation in larger retinal vessels has been shown to increase with increasing diabetic retinopathy (DR) grade and to help predict the effect of antivascular endothelial growth factor treatment in patients with diabetic maculopathy. However, it is unknown to what extent the increased oxygen saturation co-varies with other risk factors and whether it is an independent risk factor for the severity of DR. Methods Seven hundred and twenty-two successive patients referred for specialist evaluation of diabetic retinopathy including retinal oximetry were studied. Multiple regression analysis was used to investigate whether oxygen saturation in the larger retinal arterioles and venules contributed to the severity of diabetic retinopathy, independently of gender, age, diabetes duration, diabetes type, body mass index, blood pressure, haemoglobin A1c, visual acuity and central retinal thickness. Results The included parameters could explain less than 15% of the variation in retinopathy grade. Approximately, one-third of the explained variation was related to the retinal oxygen saturation. Conclusions Prospective studies are needed to evaluate whether retinal oxygen saturation is predictive for the development of diabetic retinopathy and how it interacts with other biomarkers and risk factors over time. [ABSTRACT FROM AUTHOR]

The clinical presentation of the most frequent vision threatening retinal diseases is dominated by lesions indicating that disturbances in retinal blood flow are involved in the pathogenesis of these diseases. The present review describes the experience from a translational strategy pursued to investigate retinal vascular diseases with diabetic retinopathy as the main object. The normal regulation of retinal blood flow is investigated in porcine retinal vessels in vitro and ex vivo. Subsequently, the in vitro findings are translated to clinical studies in normal persons in vivo, and it is investigated whether the mechanisms are disturbed in retinal vascular disease. This is followed by clinical intervention studies on these diseases. The approach has been used to investigate pressure autoregulation, metabolic autoregulation and vasomotion in retinal vessels. The investigations have shown that retinal vascular tone can be regulated by receptor‐specific agonists and antagonists to vasoactive compounds such as purines, prostaglandins and nitric oxide synthesis and that the vasoactive effects can be modulated by the concentration and the mode of administration of these compounds. Additionally, it has been shown that retinal precapillary arterioles and capillaries not visible by ophthalmoscopy may play an important role for the pathophysiology of retinal vascular disease and its treatment. Future studies should focus on investigating normal and pathological regulation of retinal blood flow in these smaller vessels. [ABSTRACT FROM AUTHOR]

Purpose: Dual wavelength retinal oximetry allows the quantification of oxygen saturation in the larger retinal vessels. However, the technique might be refined further by identifying factors that are responsible for the different oxygen saturations in first order arterioles from the same eye shortly after their branching from the central retinal artery. The purpose of the present study is to investigate whether these factors involve rheological characteristics in the studied vessels. Materials and Methods: In fourty healthy persons the oxygen saturation was measured by dual wavelength oximetry and the blood flow by Doppler OCT in the upper and lower temporal and nasal arterioles and venules shortly after their branching from the central retinal artery and vein. The relationship of the measured oxygen saturations with age, vessel diameter, and blood linear velocity were assessed. Results: The measured oxygen saturations were (mean± SD) 97.8% ± 6.4% in the arterioles and 60.2% ± 8.8% in the venules. For both the arterioles and the venules the measured oxygen saturation (Sm) correlated significantly with the linear velocity (v) of the blood in mm/s (Sm = 101.6-0.28*v, p < 0.0001 for arterioles and Sm = 64.5-0.38*v, p = 0.002 for venules). After correction for the variation in linear velocity, the differences in saturation between first order branches from both arterioles and venules were significantly reduced and the standard deviation of the oxygen saturations were reduced to less than one third. Conclusions: Measurements of oxygen saturation in larger retinal arterioles and venules using dual wavelength oximetry can be improved by correcting for the influence of the linear velocity of the blood. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic retinopathy (DR) is among the leading causes of visual loss in the working‐age population. It is generally accepted that screening of DR is cost‐effective and can detect DR before it becomes sight‐threatening to allow timely treatment. Methods: A group of retinal specialists was formed by the Danish Ophthalmological Society with the aim to formulate contemporary evidence‐based guidelines for screening of DR in order to implement these in the Danish screening system. Results: We hereby present evidence for DR‐screening regarding (1) classification of DR, (2) examination techniques, (3) screening intervals and (4) automated screening. It is our recommendation that the International Clinical Retinopathy Disease Severity Scale should be used to classify DR. As a minimum, mydriatic two‐field disc‐ and macular‐centred images are required. In the case of suspected clinically significant diabetic macular oedema, supplementary optical coherence tomography can increase the diagnostic accuracy. There is solid evidence to support a flexible, individualized screening regimen. In particular, it is possible to prolong screening intervals to 24–48 months for patients with no or mild nonproliferative diabetic retinopathy (NPDR), but it is also possible to use extended intervals of 12–24 months for patients with moderate NPDR given that these are well‐regulated regarding glycaemic control (HbA1c ≤ 53 mmol/mol) and blood pressure (≤130/80 mmHg). Automated screening of DR is encouraging but is not ready for implementation at present. Conclusion: Danish evidenced‐based guidelines for screening of DR support high‐quality imaging and allow flexible, individualized screening intervals with a potential for extension to patients with low risk of DR progression. [ABSTRACT FROM AUTHOR]

The article offers information on screening for diabetic retinopathy (DR) is needed for identification and treatment of patients with sight-threatening stages prior to irreversible visual loss. Topics include the potential argument against extended screening intervals is the risk of rapid progression of DR, and the individualized screening with prolonged screening intervals might serve the vast majority of patients.

Purpose: Diabetic maculopathy can be treated with intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors. However, the therapy is not effective in all patients, and it would be desirable to have parameters for differentiating patients who will benefit from treatment from those who will not. Retinal fixation has been shown to be impaired in patients with low visual acuity (VA) secondary to macular disease, but the changes in fixational eye movements after anti‐VEGF treatment for diabetic maculopathy have not been investigated. Methods: Retinal fixation was studied in 29 patients with diabetic macular oedema before three monthly anti‐VEGF injections, and 1 and 4 months after the last injection. The change in VA was correlated with changes in area, frequency, amplitude and total number of fixational saccades. Results: During three monthly injections, best‐corrected visual acuity (BCVA) increased from (mean ± SD) 74.0 ± 11.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters to 78.3 ± 9.8 ETDRS letters, (p = 0.003) and central retinal thickness (CRT) decreased from (mean ± SD) 441.7 ± 107.0 μm to 339.5 ± 74.2 μm, (p = <0.0001), which was followed by the opposite changes after treatment (BCVA reduced nonsignificantly to 77.5 ± 10.4 ETDRS letters (p = 0.06), and CRT increased to 393.0 ± 9.8 μm, p = <0.0001). Both improvement and worsening of BCVA correlated with the fixation area (r2 = 0.28, p = 0.003 and r2 = 0.14, p = 0.045, respectively), but only improvement of BCVA correlated with the frequency (r2 = 0.15, p = 0.037) and total number of saccades (r2 = 0.18, p = 0.02). BCVA showed no correlation with the amplitude and most frequently occurring saccade amplitude. Conclusion: Fixational eye movements may be used to monitor short‐term effects of anti‐VEGF treatment on diabetic macular oedema. Future studies should aim at investigating a possible predictive value of fixational eye movements for visual function in the long term. [ABSTRACT FROM AUTHOR]

Purpose: The epidemiology, risk factors, and the effect of anti-VEGF treatment on neovascular age-related macular degeneration (nAMD) have primarily been studied in the first eye developing the disease. The understanding of pathophysiology and planning of follow-up examinations can be improved by knowledge of incidence and risk factors for development of the disease in the fellow eye.Methods: In a prospective observational cohort study, epidemiological and clinical risk factors for the development of nAMD in the fellow eye among 2516 patients consecutively diagnosed with the disease from a population of 0.9 million citizens during a period of more than 10 years were studied.Results: nAMD had been diagnosed in the fellow eye of 541 (21.5%) of the patients. The incidence of fellow-eye involvement increased from approximately 5% in patients initially presenting with bilateral disease to approximately 28% more than 6 years after the diagnosis in the first eye. Visual acuity (VA) was higher and central retinal thickness (CRT) was lower in fellow eyes with nAMD diagnosed later than the first eye. Male gender, increasing leakage area, and peripapillary location of the subretinal neovascular membrane in the first eye reduced the risk of developing disease in the fellow eye.Conclusions: The planning of follow-up examinations of patients diagnosed with nAMD in one eye should consider that the risk of fellow-eye involvement is higher within the first 6 years, in women, and when the leakage area in the first eye is small and not located peripapillary. [ABSTRACT FROM AUTHOR]

Purpose: Randomized clinical trials studying the effects of VEGF inhibition on wet age-related macular degeneration (wAMD) are designed so that the effects of individually varying risk factors on the treatment response are eliminated. The influence of these risk factors can be studied in large data sets from real-life experience. Patients and methods: All 2,255 patients diagnosed with wAMD requiring anti-VEGF treatment in at least one eye over more than 9 years in a defined Danish population with 0.9 million inhabitants were studied. The predictive value of eye laterality, sex, current smoking status, type of anti-VEGF compound, membrane position, membrane type, leakage area, number of injections, number of visits, age, time to follow-up, visual acuity, and central retinal thickness (CRT) at baseline on change in CRT after three monthly injections with anti-VEGF compound followed by treatment pro re nata for up to 12 months was assessed. Results: After 12 months, 67 patients had died, 903 had had stable CRT for at least 6 months, and 1,285 patients had not achieved stable CRT. The reduction in CRT was -84.8±118.3 µm, whereas the increase in visual acuity was 2.2±14.7 Early Treatment Diabetic Retinopathy Study letters. The risk factors included contributed to 64% of the variation in CRT reduction. High age and high CRT at baseline predicted high CRT reduction, whereas more injections, treatment with ranibizumab, and male sex predicted a low CRT reduction. Conclusion: Age, sex, and type of anti-VEGF medication can be used to plan treatment and inform patients about the expected response of anti-VEGF treatment in wAMD. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment—auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age‐related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype‐specific miRNA profiles for late‐stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD. [ABSTRACT FROM AUTHOR]