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Purpose: To study characteristics and associations of Gunn dots in a cohort of healthy children aged 11 to 12 years., Methods: As part of the Copenhagen Child Cohort 2000 Study, red-free fundus photographs were taken on 761 healthy children aged 11 to 12 years. The photographs were centered on the optic disk. Gunn dots were annotated and counted within a disk-centered circular grid of 6 mm diameter. Data were analyzed in relation to age, sex, axial length, and retinal nerve fiber layer thickness., Results: Gunn dots were found in 716 of the 761 participants (94%). The majority of dots were located both inferior and superior to the optic disk, situated within a distance of 3 mm from its center. The median number of Gunn dots was 64 (range 0-574) in right eyes and 68 (range 0-532) in left eyes. Having more than the median number of Gunn dots in the right eye was associated with older age (odds ratio 2.12, 95% CI 1.56 to 2.89, P < 0.0001, adjusted for sex, axial length, and retinal nerve fiber layer thickness) and was less common among the children with a thinner retinal nerve fiber layer (odds ratio 0.40, 95% CI 0.26-0.60, P < 0.0001 comparing bottom and top quartiles)., Conclusion: Gunn dots were visible in the majority of healthy children aged 11 to 12 years, and large numbers of dots were associated with a thicker nerve fiber layer and with older age, within the limited age range of 1 year. The clinical significance of Gunn dots is unknown. Their location at the vitreoretinal interface makes them a parameter of interest in the study of aging, epiretinal fibrosis, macular pucker and retinal detachment.

Purpose: We aimed to explore the effect of multiple pre- and postnatal exposures on optic nerve status in young adults due to this critical period for development., Methods: We analysed peripapillary retinal nerve fibre layer (RNFL) status and macular thickness at age 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) cohort in relation to several exposures., Results: Of the 269 participants (median (IQR) age, 17.6 (0.6) years; 124 boys), 60 participants whose mothers had smoked during pregnancy had a thinner RNFL: adjusted mean difference -4.6 μm (95% CI -7.7; -1.5 μm, p = 0.004) compared with participants whose mothers had not smoked during pregnancy. A total of 30 participants who were exposed to tobacco smoke both during foetal life and childhood had thinner RNFL: -9.6 μm (-13.4; -5.8 μm, p < 0.001). Smoking during pregnancy was also associated with a macular thickness deficit: -4.7 μm (-9.0; -0.4 μm, p = 0.03). Higher indoor concentrations of particulate matter 2.5 (PM2.5) was associated with thinner RNFL: -3.6 μm (-5.6; -1.6 μm, p < 0.001) and a macular deficit: -2.7 μm (-5.3; -0.1 μm, p = 0.04) in the crude analyses, but not in the adjusted analyses. No difference was found among participants who smoked at age 18 years compared with non-smokers on RNFL or macular thickness., Conclusions: We found that exposure to smoking during early life was associated with a thinner RNFL and macula at age 18 years. The absence of an association between active smoking at 18 years suggests that the vulnerability of the optic nerve is highest during prenatal life and early childhood., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To determine the prevalence of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a population-based child cohort and to study their association with other optic nerve head features and myopia., Design: Observational, population-based cohort study of 1407 children aged 11-12 years., Methods: Optical coherence tomography scans of optic nerve heads were graded for PHOMS, disc tilt, prelaminar hyperreflective lines, and scleral canal diameter and investigated for associated prenatal and ocular parameters. Children with optic disc drusen or optic disc edema were excluded., Results: PHOMS were found in 8.9% of children. The location of PHOMS was predominantly in the superonasal section of the optic disc. Myopia and optic nerve head tilt were more common in children with PHOMS than in children without PHOMS (P < .001 and P < .001, respectively). Prelaminar hyperreflective lines were found in 17.9% of children with PHOMS compared to 7.3% of children without PHOMS (P < .001). Prelaminar hyperreflective lines with and without PHOMS were associated with a shorter axial length of the eye (P < .001). There were no prenatal factors associated with PHOMS. Prelaminar hyperreflective lines were associated with higher birth weight and continued maternal smoking during pregnancy (P = .01 and P = .02, respectively)., Conclusions: PHOMS had a prevalence of 8.9% in healthy children without optic disc drusen or optic disc edema and was associated with increasing myopic refraction and the presence of a tilted optic nerve head and prelaminar hyperreflective lines. Given the high prevalence of PHOMS, they should not unreservedly be taken as evidence of optic neuropathy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between prenatal exposures and anthropometric data and cardiovascular risk factors including retinal arteriolar wall-to-lumen ratio in adolescence., Methods: This longitudinal observational study included all 1445 adolescents from the Copenhagen Child Cohort 2000 who attended the 2016-2017 examination. Outcome measures included retinal arteriolar wall-to-lumen ratio, height, body mass index, waist-to-hip ratio, body composition measured by bioimpedance, and blood pressure. Information on prenatal exposures (birth weight, gestational age, maternal smoking during pregnancy) as well as sex, parental age, household income and parental educational levels were obtained from national registries. Associations between exposures and outcome measures were analyzed using general linear models., Results: Maternal smoking during pregnancy was associated with a higher retinal arteriolar wall-to-lumen ratio (0.004 or 1.9%, P = 0.009) at age 16/17 years, an association driven exclusively by the female participants (0.008 or 3.7%, P < 0.0001). Maternal smoking during pregnancy was also associated to higher body-mass index (1.43 kg/m 2 , P < 0.0001), waist-to-hip ratio (0.02, P < 0.0001) and fat mass index (0.93 kg/m 2 , P < 0.0001). Birth weight, gestational age, and parental age had no detectable impact on retinal arteriolar wall-to-lumen ratios., Conclusion: Prenatal exposure to tobacco smoking is associated with a higher risk of obesity and, predominantly in girls, to a greater retinal arteriolar wall thickness, which suggests that maternal smoking may induce an unfavorable cardiovascular and metabolic risk profile in the child., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 μm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort., Methods: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 μm, or (4) ≥20 small hard drusen combined with drusen ≥63 μm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects., Results: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 μm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 μm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 μm at follow-up (p = 0.02). Development of drusen ≥63 μm was attributable to 49% genetic effects and 51% environmental effects., Conclusion: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 μm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 μm at baseline was associated with incident drusen ≥63 μm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To estimate the incidence of cilioretinal arteries in a Danish child cohort and associations with birth parameters., Methods: The population-based Copenhagen Child Cohort 2000 Eye Study examined 1406 children aged 11-12 years. Colour fundus images of both eyes were graded for cilioretinal arteries in the three categories large temporal (defined as supplying the central macula), small temporal and nasal. Data on maternal smoking during pregnancy, gestational ageand birth weight were obtained from the Danish Medical Birth Registry., Results: A total of 463/1338 (35%) children were found to have one or more cilioretinal arteries per child. Large temporal cilioretinal arteries were present in 280/1338 (21%) of children and were associated with tobacco smoking during pregnancy, being present in 70/246 (28%) of children with mothers who were smoking during pregnancy, but only in 191/990 (19%) of children whose mothers did not smoke during pregnancy (p = 0.0022). After adjustments for potential confounders, the odds ratio of having one or more large temporal cilioretinal arteries was 1.72 (CI95% 1.19-2.47; p = 0.0035) in the smoking versus none smoking category. No other associations with birth parameters were found., Conclusion: Cilioretinal arteries were present in more than one third of 11- to 12-year-old Danish children. Large temporal cilioretinal arteries were found in one fifth of children and were associated with maternal smoking during pregnancy. This finding suggests that the intrauterine environment may have an impact on the development of retinal vessels during foetal life., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To examine cone density in relation to gestational and morphological parameters in the Copenhagen Child Cohort (CCC2000)., Methods: The macula was imaged using adaptive optics in 1,296 adolescents aged 16-17 years. Axial length and distance visual acuity were determined. Absolute and angular cone photoreceptor density were analysed for an 80 × 80-pixel area, 2 degrees temporal to the fovea. Association with axial length was analysed with linear regression. Correlation with visual acuity was described with a Pearson correlation coefficient. Associations of cone density with gestational parameters, maternal smoking, sex and age were analysed using multiple regression adjusted for axial length., Results: Mean absolute cone density was 30,007 cones/mm 2 (SD ± 3,802) and mean angular cone density was 2,383 cones/deg 2 (SD ± 231). Peri- and postnatal parameters, sex and age had no statistically significant effect on cone density (p > 0.05). Absolute cone density decreased with longer axial length (-2,855 cones/mm 2 per mm or -9.7% per mm, p < 0.0001). For angular density, which included a correction for the geometrical enlargement of the eye with axial length, a decrease with axial length was detectable, but it was small (-20 cones/deg 2 per mm or -0.84% per mm, p = 0.009)., Conclusions: The decrease in cone density per unit solid angle with increasing axial length was small, less than 1 percent per mm, indicating that expansion of the posterior pole during the development of refraction takes place without a clinically significant loss of cones. Perinatal parameters, within the spectrum presented by the study population, had no detectable effect on cone density., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Background: The purpose of the study was to examine 5-year changes in eyes with optic disc drusen at baseline on optical coherence tomography (OCT) scans and the relation of incident drusen to hyperreflective prelaminar lines., Methods: The study included children who presented at baseline, when participants were aged 11-12 years, and again 5 years later. Grading for optic disc drusen was made in all. Grading for prelaminar lines was made in all children at follow-up and in eyes with optic disc drusen at baseline. Analyses included associations with scleral canal diameter at baseline in all children with optic disc drusen and a nested control group of 115 children without optic disc drusen. Data are reported as the number of children having at least one drusen or at least one hyperreflective line per person., Results: The analysis included 724 children who attended both rounds of the study. Of these, 11 (1.5%) had optic disc drusen at baseline. Five additional children had developed optic disc drusen at follow-up, whereas optic disc drusen had disappeared in none, so that 16 (2.2%) children had optic disc drusen in one or both eyes at follow-up. Children with optic disc drusen at the 5-year follow-up had had a mean scleral canal diameter of 1,364 µm (interquartile range [IQR] 81 µm), compared with 1,457 µm (IQR 197) µm in 115 nested controls without optic disc drusen (P < 0.001). Optic disc drusen at follow-up were associated with more hypermetropic refraction. All children who had optic disc drusen at follow-up also had prelaminar hyperreflective lines. In addition, such lines were found at follow-up in 24 of the remaining 708 children without optic disc drusen (P < 0.001). Prelaminar hyperreflective lines with or without optic disc drusen were associated with a narrower scleral canal (diameter 1,364 µm, IQR 119 µm) compared with absence of prelaminar lines (1,486 µm, IQR 206 µm; P < 0.0001)., Conclusion: This study provides the first evidence from a prospective study that small optic discs and prelaminar hyperreflective lines on OCT are risk factors for the development of optic disc drusen. The association between prelaminar hyperreflective lines, hypermetropia, and a narrow scleral canal supports that a crowded disc is an essential predisposing factor for the development of optic disc drusen.

Purpose: To determine the myopia prevalence in a Danish cohort aged 16-17 years and its relation to physical activity and use of screen-based electronic devices., Methods: The Copenhagen Child Cohort 2000 Eye Study is a prospective, population-based, observational study. Information about use of screen devices and physical activity was obtained using questionnaires. Myopia was defined as non-cycloplegic subjective spherical equivalent refraction ≤-0.50 D in right eye., Results: We included 1443 participants (45% boys) with a median age (±IQR) of 16.6 years (±0.3). The prevalence of myopia was 25% (CI95% 23-28, n = 360) with no differences between sexes (p = 0.10). The odds ratio (OR) for myopia was 0.57 (CI95% 0.42-0.76, p = 0.0002) in participants physically active 3-6 hr/week (n = 502) and 0.56 (CI95% 0.42-0.76, p = 0.0002) if active >6 hr/week (n = 506), both compared with participants physically active <3 hr/week (n = 396). The use of screen devices >6 hr/day was associated with increased OR for myopia compared with screen device use <2 hr/day in both weekdays (OR = 1.95, CI95% 1.16-3.30, p = 0.012) and weekends (OR = 2.10, CI95% 1.17-3.77, p = 0.013)., Conclusion: In this cohort of healthy 16-17-year olds, lower physical activity and more use of screen devices contributed significantly to the observed 25% prevalence of myopia with a roughly doubled risk of having myopia if physically active <3 hr/week or if using screen devices >6 hr/day. Our results support physical activity being a protective factor and near work a risk factor for myopia in adolescents., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Myopic eyes are longer than nonmyopic eyes and have thinner choroids. The purpose of present study was to investigate whether a thinner subfoveal choroid at 11 years of age predicted axial eye elongation and myopia during adolescence., Methods: Longitudinal, population-based observational study. Axial length was measured using an interferometric device and choroidal thickness was measured by spectral-domain optical coherence tomography. Myopia was defined as non-cycloplegic subjective spherical equivalent refraction ≤ - 0.50 diopters., Results: Right eyes of 714 children (317 boys) were examined at age (median (IQR)) 11.5 (0.6) years and 16.6 (0.3) years during which axial length (median (IQR)) increased by 243 (202) μm in eyes without myopia (n = 630) at baseline compared with 454 (549) μm in eyes with myopia (n = 84) at baseline, p < 0.0001. A thicker baseline subfoveal choroid was associated with increased five-year axial elongation after adjustment for baseline axial length in nonmyopic eyes (β = 27 μm/100 μm, 95%CI 6 to 48, p = 0.011) but not in myopic eyes (p = 0.34). Subfoveal choroidal thickness at 11 years of age did not predict incident myopia at 16 years of age (p = 0.11). Longer baseline axial length was associated with greater five-year axial elongation in both myopic (β = 196 μm/mm, 95%CI 127 to 265, p < 0.0001) and nonmyopic eyes (β = 28 μm/mm, 95%CI 7 to 49, p = 0.0085) and the odds for incident myopia increased with 1.57 (95%CI 1.18 to 2.09, p = 0.0020) per mm longer axial length at baseline., Conclusion: A thin subfoveal choroid at age 11 years did not predict axial eye elongation and incident myopia from age 11 to 16 years. A longer eye at age 11 years was associated with greater subsequent axial eye elongation and with increased risk of incident myopia at age 16 years.

Purpose: To study the thickness of retinal arteriolar walls in a population-based cohort of adolescents., Methods: This cross-sectional, observational study included 1217 participants aged 16-17 years from the Copenhagen Child Cohort 2000 Study. The wall thickness and lumen diameter of a major branch retinal arteriole were measured using adaptive optics imaging. The wall-to-lumen ratio was analyzed in relation to blood pressure and body composition variables using a general linear model. Overall in the study population, wall-to-lumen ratio was found to decrease by 0.49% per μm increase in arteriole diameter (P < 0.0001) and all subsequent analyzes were adjusted accordingly., Results: The average outer and inner arteriole diameters were 117 ± 19 and 96.6 ± 18 μm (mean ± SD), corresponding to a wall-to-lumen ratio of 0.21 ± 0.024. There was no detectable difference between sexes. A higher wall-to-lumen ratio was associated with a higher BMI (+0.21% per kg/m, P = 0.0018), higher body fat percentage (+0.097% per 1% increase, P = 0.0052), wider hip circumference (+1.1% per 10 cm increase, P = 0.0006), wider waist circumference (+0.92% per 10 cm increase, P = 0.0009), higher SBP in girls (+1.1% per 10 mmHg increase, P = 0.0005), longer axial length (+0.70% per mm increase, P = 0.013), and younger age (+4.9% per year younger, P < 0.0001), adjusted for arteriole diameter, age, sex, and height., Conclusion: A higher retinal arteriolar wall-to-lumen ratio was associated with all registered indices of body fat proportion.

Purpose: To report 10-year, real-world experiences with intravitreal therapy (IVT) using vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration (nAMD)., Methods: Retrospective single-centre review of IVT-log 2007-2019 with a treatment-as-needed regimen and ETDRS visual acuity charts., Results: The 4,678 treatment-naïve eyes of 3,668 patients received a mean of 5.4 IVT in the first year and 4.0-4.3 IVT yearly thereafter. Baseline mean best corrected visual acuity (BCVA) was 57.9 (±16.4) letters (6/18) that improved a mean +2.1 (±0.2) letters at the first follow-up visit and gradually declined to -5.0 (±2.2) letters after 10 years. At baseline, there were 29% with BCVA ≥6/12. This proportion increased to 31-37% until year 9. There were 8% with BCVA loss of ≥3 lines at the first follow-up visit increasing to 34% after 10 years. Poorer baseline BCVA was associated with larger increase in BCVA (p < 0.0001, multiple linear regression). The 2,566 (55%) discontinued eyes had a mean baseline BCVA of 56.9 (±16.4) letters compared with 61.5 (±15.9) letters for eyes remaining in treatment. In year 0-7, the discontinued eyes lost an additional mean 2-4 letters (last observation carried forward) but were similar thereafter. There were 12.6% (74 of 585 eligible eyes) that were still in treatment after 10 years. At baseline, 10% had bilateral nAMD. Of patients with unilateral presentation, 17% had received fellow-eye IVT after 5 years., Conclusion: A treatment-as-needed regimen stabilized BCVA in active nAMD up to 10 years in most eyes. Baseline BCVA was the most important prognostic factor., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To image retinal blood vessels in patients with Waldenström's macroglobulinemia using optical coherence tomography (OCT)., Methods: Retrospective case series examining fundus photographs and OCT scans of 16 eyes in eight patients with Waldenström's macroglobulinemia. Analyses included intravascular OCT reflectivity profiles and vessel diameters, and their relation to total immunoglobulin M (IgM) levels., Results: In six out of eight patients, cross-sectional OCT scans of larger retinal vessels (diameter > 100 μm) showed normal intravascular reflectivity and retrovascular shadowing. In two patients with the highest total IgM > 60 g/l, altered intravascular reflectivity, distinct anterior and posterior vessel wall reflexes, and retrovascular hyposhadowing were seen. Normalization of the OCT reflectivity in these patients occurred after reduction of total IgM to < 17 g/l and was accompanied by decreasing venous tortuosity and disappearance of retinal haemorrhages and cotton wool spots., Conclusion: This study found that Waldenström's macroglobulinemia and total IgM > 60 g/l were associated with abnormal intravascular reflectivity and retrovascular shadowing on OCT. Awareness of these signs of hyperviscosity could potentially enable earlier detection of critical conditions in patients with Waldenström's macroglobulinemia and improve the assessment of severity and treatment effect., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To determine the prevalence of strabismus among Danish adults and to find the frequency of history of strabismus and strabismus surgery. Furthermore, to evaluate the prevalence of strabismus-associated amblyopia among participants with strabismus and to relate the results to the current national vision screening programme., Methods: In total, 3785 adults in the Danish Rural Eye Study underwent an interview regarding eye health, visual acuity measurement, Hirschberg test and retinal photography. Participants were categorized into groups based on their birth date in relation to the introduction of the national vision screening programme., Results: In total, the prevalence of strabismus was 1.1% (41/3785; 95% CI: 0.8-1.5); no differences were found in relation to gender or screening status. The prevalence of exotropia (XT) was 0.3% (12/3785; 95% CI: 0.2-0.6) and of esotropia (ET) 0.8% (29/3785; 95% CI: 0.5-1.1), resulting in an XT:ET ratio of 1:2.7. A history of strabismus was present in 4.6% (174/3785; 95% CI: 4.0-5.3), and a history of strabismus surgery was present in 0.8% (32/3785; 95% CI: 0.6-1.2) of the participants. Among participants with manifest strabismus, 24% had strabismus-associated amblyopia., Conclusion: In this first European population-based study of strabismus prevalence in adults, the prevalence was similar to three out of five previous studies using cover test. The use of Hirschberg test may have led to an underestimation of the true prevalence. The prevalence was neither related to screening status nor gender. Our results are the first to display a predominance of ET among Caucasian Scandinavian adults., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: We describe changes in choroidal thickness from age 11 to 16 years and its association with ocular biometrics and body development., Method: In this longitudinal, population-based observational study, choroidal thickness was measured subfoveally and 1- and 3-mm temporal thereof using enhanced depth imaging spectral domain optical coherence tomography. Analyses were stratified by sex and adjusted for age and the time of day that the scan was performed., Results: The study included 687 participants (304 boys). Median (interquartile range [IQR]) age was 11.5 (0.6) years at baseline and 16.6 (0.3) years at follow-up. Mean increase in choroidal thickness was 33, 27, and 11 μm at the three respective locations. The subfoveal choroid thickened less in eyes whose axial length increased more (boys, β = -85 μm/mm; 95% confidence interval [CI], -104 to -66, P < 0.0001; girls, β = -105 μm/mm; 95% CI, -121 to -89, P < 0.0001) and in eyes with a more negative refractive development (boys, 11 μm/diopters [D]; 95% CI, 4.0 to 18, P = 0.0022; girls, 22 μm/D; 95% CI, 16 to 27, P < 0.0001). Subfoveal choroidal thickness increased less in girls who underwent early puberty (Tanner stage 4 vs. 1; -39 μm' 95% CI, -72 to -5.9, P = 0.021) and who had a longer baseline axial length (β = -8.6 μm/mm; 95% CI, -15 to -2.7, P = 0.0043), and more in girls who grew taller (β = 0.9 μm/cm; 95% CI, 0.1 to 1.7, P = 0.026)., Conclusions: The choroid increased in thickness from age 11 to 16 years. The increase was greater in girls with later sexual maturation and smaller in eyes that added more axial length and had a relatively negative refractive development.

Purpose: To assess the prevalence and associations of small hard drusen in a child cohort., Methods: Cross-sectional study of 11- to 12-year-old Danish children from the population-based Copenhagen Child Cohort 2000 Eye Study. Fovea-centered, 45° color images of both eyes were graded for macular drusen (within one optic-disc-rim-to-fovea distance of the foveal center) and for extramacular drusen. Analyses tested for associations between drusen and anthropometric measures including choroidal thickness., Results: Gradable fundus images from both eyes were available for 1333 children (640 boys, 693 girls) with a mean (SD) age of 11.7 (0.40) years. One or more small hard macular drusen (diameter <63 μm) were present in 82 (6.2%) right eyes and 82 (6.2%) left eyes and in 147 (11.0%) subjects. Four children (0.30%) had 20 or more small hard macular drusen in one or both eyes. Extramacular small hard drusen were present in 10.7% of children, and 19% of children had such drusen anywhere. The odds for having one or more small hard macular drusen increased with subfoveal choroidal thickness with an odds ratio of 1.15 (95% confidence interval, 1.03-1.28; P = 0.013) per 50-μm thicker choroid, adjusted for age and sex. The association with choroidal thickness was also present for extramacular drusen., Conclusions: Having one or more small hard macular drusen was common in 11- to 12-year old children and it was associated with a thicker subfoveal choroid. Few children had many small hard drusen. There is no apparent clinical impact of small hard drusen in childhood.

Purpose: To evaluate the prevalence of amblyopia and associated biometric factors in Danish children., Methods: Determination of best-corrected visual acuity (BCVA) using ETDRS charts, non-cycloplegic subjective refractioning guided by automated refractometry, axial length and corneal curvature, fundus photography and optical coherence tomography (OCT) in 1335 children from the population-based Copenhagen Child Cohort 2000 (CCC2000) Eye Study. Birth data were obtained from the Danish Medical Birth Registry., Results: The mean (±SD) age of children was 11.7 (±0.4) years, and 47% were boys. Amblyopia prevalence was 1.5 (95% CL 0.8-2.2) %. Unilateral amblyopic eyes [BCVA < 80 ETDRS letters (0.8 snellen) and ≥2 lines difference between the eyes] was 0.6 (95% CL 0.3-1.0) mm shorter, 1.34 (95% CL 0.30-2.37) D more hyperopic and had 0.79 (95% CL 0.14-1.44) D more astigmatism compared with fellow eyes. Compared with the right eyes of the non-amblyopic children, unilateral amblyopic eyes were 1.0 (95% CL 0.5-1.6) mm shorter, 2.48 (95% CL 1.11-3.86) D more hyperopic, 1.09 (95% CL 0.43-1.75) D more astigmatic and had a 47 (95% CL 13-81) μm thicker subfoveal choroid., Conclusion: Amblyopia was found in 1.5% of Danish children born 22 years after the inception of the nationwide preschool visual screening programme. Amblyopia was associated with anisometropia, astigmatism, a thicker subfoveal choroid and a history of childhood strabismus., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To examine retinal blood flow at arteriovenous crossings using spectral-domain optical coherence tomography (SD-OCT)., Methods: Retrospective observational case series of 11 arteriovenous crossings in 10 eyes examined by SD-OCT and fluorescein angiography on suspicion of manifest or imminent branch retinal vein occlusion., Results: Fluorescein angiographic evidence of turbulence was seen at 5 of 11 arteriovenous crossings, whereas laminar angiographic flow was intact at the crossing and downstream thereof at the remaining 6 crossings. On SD-OCT, chaotic reflectivity patterns were seen at the point of crossing and downstream thereof in all 5 cases with angiographic turbulence, whereas an intravascular trilayer SD-OCT pattern consistent with laminar flow was seen throughout the examined course of the vein in the eyes with laminar angiographic flow., Conclusion: We examined retinal blood flow at and near arteriovenous crossings and found that SD-OCT may rival fluorescein angiography in the ability to demonstrate turbulent venous blood flow.

Background: Optic disc drusen (ODD) are seen in up to 2.4% of the general population, but the etiology and pathophysiology of the condition is still unknown. The purpose of this study was to determine the prevalence of ODD in a population-based child cohort and to determine if scleral canal diameter and fetal birth and pubertal parameters are associated with the presence of ODD., Methods: This observational, longitudinal population-based birth cohort study, with a nested case-control, included 1,406 children. Eye examinations were performed when the children were between 11 and 12 years of age. Assessment was performed of optical coherence tomography (OCT) scans from 1,304 children with gradable enhanced depth imaging scans of the optic disc., Results: ODD in one or both eyes were found in 13 (1.0%) of all children. All but one of the cases were found in children with scleral canal diameter in the lowest quartile (1,182-1,399 μm) in the nested case-control study. Children with ODD had a mean disc diameter of 1,339 μm (interquartile range, 30 μm), whereas it was 1,508 μm (interquartile range, 196 μm) in the 130 controls without ODD (P < 0.001). No differences in sex, birth weight, refractive error, and Tanner stages (of puberty) were found between children with and without ODD., Conclusions: The prevalence of ODD was 1% in a large child cohort examined by OCT. ODD was found only in eyes with a narrow scleral canal, which is consistent with the hypothesis that ODD might arise as a consequence of retinal nerve fiber congestion in the scleral canal.

Background: Small hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen., Methods: Retinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised., Results: Small hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22-61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex., Conclusion: High lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1-4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To assess the effect of elevated core body temperature on temporal and spatial contrast sensitivity and retinal vessel diameters., Methods: The study included 13 healthy volunteers aged 20-37 years. Core body temperature elevation (target +1.1°C) was induced by wrapping the participants in cling film, tinfoil and warming blankets. Subsequent cooling was achieved by undressing. Flicker sensitivity (critical flicker fusion frequency) was chosen to assess temporal resolution, while the Freiburg Vision Test was used to determine spatial contrast sensitivity at 1.5 cycles per degree. Scanning laser ophthalmoscopy was used to measure retinal trunk vessel diameters. Assessment was made at baseline, during hyperthermia and after cooling., Results: The induction of a mean increase in core body temperature of 1.02°C was associated with a 7.15-mmHg mean reduction in systolic blood pressure (p < 0.01), a 10.6-mmHg mean reduction in diastolic blood pressure (p < 0.01), a mean increase in pulse rate of 36.3 bpm (p < 0.0001), a 2.66% improvement in flicker sensitivity (CI 95 1.37-3.94, p < 0.001), a 2.80% increase in retinal artery diameters (CI 95 1.09-4.51, p < 0.01) and a 2.95% increase in retinal vein diameters (CI 95 0.96-4.94, p < 0.01). There was no detectable effect of temperature on spatial contrast sensitivity. All ocular test parameters returned to baseline levels after cooling., Conclusion: Increased core body temperature was accompanied by improved temporal visual resolution and retinal trunk vessel dilation. The results suggest that hyperthermia is associated with enhanced retinal function and increased retinal metabolism., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension., Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation., Results: The mean fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined., Conclusions: In young adult twins, the branching pattern of the retinal vessels demonstrated a higher structural similarity in monozygotic than in dizygotic twin pairs. The retinal vascular fractal dimension was mainly determined by genetic factors, which accounted for 54% of the variation. The genetically predetermination of the retinal vasculature may affect the retinal response to potential vascular disease in later life.

Background: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers., Methods: Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA)., Results: Ten patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71-87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch's membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion., Conclusions: Beside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

Importance: Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina., Objective: To investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer (RNFL) thickness in preadolescent children., Design, Setting, Participants: The Copenhagen Child Cohort 2000 Eye Study is a prospective, population-based, birth cohort study that included all children (n = 6090) born in 2000 in Copenhagen, Denmark. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the study performed eye examinations on 1406 of these children from May 1, 2011, to October 31, 2012, when the children were aged 11 or 12 years. The participants were predominantly (1296 [92.4%]) of European descent. Study data were analyzed from June 1, 2016, to October 1, 2016., Main Outcomes and Measures: Peripapillary RNFL thickness measured using optical coherence tomography at the 11- or 12-year examination., Results: Of the 1406 children in the study, 1323 were included in the analysis (mean [SD] age was 11.7 [0.4] years; 633 [47.8%] were boys and 690 [52.2%] were girls). The mean (SD) RNFL thickness was 104 (9.6) μm. In 227 children whose mothers had smoked during pregnancy, the peripapillary RNFL was 5.7 μm (95% CI, 4.3-7.1 μm; P < .001) thinner than in children whose mothers had not smoked after correction for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In low-birth-weight children (<2500 g), the RNFL was 3.5 μm (95% CI, 0.6-6.3 μm; P = .02) thinner than in normal-birth-weight children after adjustment for all variables., Conclusions and Relevance: Exposure to maternal smoking during uterine life and low birth weight were independently associated with having a thinner RNFL at age 11 or 12 years. These observations support previous findings that intrauterine and perinatal factors can have long-lasting effects on the retina and the optic nerve. The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health.

Purpose: To examine the association between retinal vessel diameters and retinopathy in participants with and without type 2 diabetes in a Danish population-based cohort., Methods: The study included 878 persons aged 30 to 60 years from the Inter99 Eye Study. Retinopathy was defined as a presence of one or more retinal hemorrhages or one or more microaneurysms. Vessel diameters were expressed as central retinal artery equivalent diameter (CRAE) and central retinal vein equivalent diameter (CRVE). Multiple linear regression analyses were performed., Results: Among participants with diabetes, CRAE was 6.3 µm (CI 95%: 1.0 to 11.6, p = 0.020) wider and CRVE was 7.9 µm (CI 95%: 0.7 to 15.2, p = 0.030) wider in those with retinopathy compared to those without retinopathy, after adjusting for age, gender, HbA1c, blood pressure, smoking, serum total and HDL cholesterol. In all participants, CRAE increased with presence of retinopathy (p = 0.005) and with smoking (p = 0.001), and CRAE decreased with hypertension (p < 0.001), high HDL cholesterol (p = 0.016) and age (p < 0.001). Central retinal vein equivalent diameter increased with presence of retinopathy (p = 0.022) and with smoking (p < 0.001), and decreased with higher HDL cholesterol (p < 0.001) and age (p = 0.015). Female gender was associated with wider CRVE (p = 0.029)., Conclusions: Wider retinal vessel diameters were associated with the presence of retinopathy in participants with diabetes, but not in participants without diabetes. The associations between retinal vessel diameters and known retinopathy risk factors were confirmed. These results suggest that information obtained by non-invasive imaging of the interior of the eye can contribute to a better understanding of systemic disease processes.

Purpose: To study the circulation in the retinal vessels in patients with blood dyscrasia due to myeloproliferative neoplasms using non-invasive retinal imaging., Methods: Prospective consecutive case series of seven treatment-naïve patients with chronic myeloid leukaemia (n = 2), polycythemia vera (n = 4), essential thrombocytosis (n = 1) examined before and after cytoreductive treatment. We investigated retinal circulation with motion-contrast imaging, retinal oximetry and spectral-domain optical coherence tomography., Results: Retinal venous blood velocity increased by 8.14% (CI 95 3.67% to 12.6%, p = 0.004) and retinal arterial oxygen saturation increased by 7.23% (CI 95 2.9% to 11.6%, p = 0.010) at follow-up (mean 12 weeks, range 5-14 weeks) where complete haematological remission had been achieved by cytoreductive treatment. Abnormal optical coherence tomography reflectivity patterns were present at baseline in patients with chronic myeloid leukaemia and were replaced by normal patterns at follow-up. Retinopathy, in the form of cotton-wool spots and retinal haemorrhages, was found at presentation in the two patients with chronic myeloid leukaemia and in one patient with polycythemia vera. The retinopathy had resolved at follow-up in all patients., Conclusion: With non-invasive retinal imaging, we were able to demonstrate increased retinal venous blood velocity, increased retinal arterial blood oxygenation and normalization of intravascular reflectivity patterns after successful treatment of myeloproliferative neoplasms. Larger prospective studies are needed to assess the prognostic value of these non-invasive imaging methods in predicting circulatory complications in myeloproliferative neoplasms., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the epidemiology of Gunn's dots and their associations in a population-based cohort of children., Methods: Red-free fundus photographs from 2,286 children aged 11 years to 14 years from the Sydney Myopia Study were graded. Gunn's dots were manually marked and counted within a 6 mm grid centered on the optic disc., Results: One or more Gunn's dots were seen in at least one eye in 82.6% of children. The median number of Gunn's dots per eye was 46 (range 0-482). Most Gunn's dots were found inferior and superior of the optic disc (49.3% and 45.8%, respectively, of the total number of Gunn's dots in the population). The odds for having 1 or more Gunn's dots were 3-fold greater in children with dark brown irides compared with children with blue irides (odds ratio 2.99, 95% CI 1.81 to 4.94, P < 0.0001 adjusted for age, sex, retinal nerve fiber layer thickness, refraction, ethnicity, and axial length). In the same analysis, the presence of 1 or more Gunn's dots was less frequent in children with thin retinal nerve fiber layers (first quartile) compared with children with thick retinal nerve fiber layers (fourth quartile) (odds ratio 0.68, 95% CI 0.49-0.93, P = 0.016). No disease or disease-marker associations were identified., Conclusion: Gunn's dots were visible on fundus photographs in most of the school children, most of the dots being located inferiorly and superiorly to the optic disc. Fundus photographically visible Gunn's dots were associated with darker irides and thicker retinal nerve fiber layers. Gunn's dots are a common and apparently harmless finding in children. Assessment of their clinical significance will require long-term follow-up.

Purpose: To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice., Methods: We extracted information about patients recorded in electronic databases managing anti-VEGF injections and cataract surgery. We compared Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and frequency of anti-VEGF injections before and after cataract surgery., Results: We identified 89 eyes from 89 patients who had cataract surgery after being treated with a median of 10 (range 3-36) anti-VEGF injections for neovascular AMD. Visual acuity improved by a mean of 7.1 [95% confidence interval (CI) 4.6-9.6] ETDRS letters in the first 6 months after cataract surgery. The need of anti-VEGF injections did not change after cataract surgery with an average of 1.5 in the 6 months before surgery versus 1.7 in the 6 months after surgery (p = 0.25). Visual improvement was greater in patients when the time from latest injection to cataract surgery was lower., Conclusions: Cataract surgery improves vision in patients undergoing treatment for neovascular AMD. Cataract surgery was not associated with an increased need for anti-VEGF treatment and patients who were in active anti-VEGF treatment had better visual outcomes than patients who had cataract surgery after long injection-free periods., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715., Methods: Cross-sectional study of 848 subjects aged 30-60 years from the Inter99 Eye Study. Daily intake of vitamins and minerals was estimated from a 198-item food frequency questionnaire. Digital fundus photographs were recorded in red-free illumination and graded for macular drusen >63 μm and numerous (>20) small hard macular drusen as a mean of both eyes., Results: Higher intake of vitamin A increased the risk of having macular drusen >63 μm with odds ratio = 1.82 (CI 95 1.02-3.24, p = 0.042) comparing participants in the highest quartile of vitamin A intake with participants in the lowest quartile, adjusted for recruitment group, age and sex. There was a significant interaction with CFHY402H (p = 0.038). Among 504 participants with CFHY402H, the relative risk of having macular drusen >63 μm was increased in participants in the highest quartile of vitamin A intake (odds ratio = 2.58; CI 95 1.16-5.73, p = 0.020) and in the second highest quartile (odds ratio = 3.27; CI 95 1.50-7.13, p = 0.0029) compared with the lowest quartile. Further adjusting for total fat intake, energy intake, plasma cholesterol, body mass index (BMI), smoking, alcohol intake, education and physical activity strengthened the association., Conclusions: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate changes in retinal metabolism, function, structure and morphology in relation to initiation of insulin pump therapy (continuous subcutaneous insulin infusion, CSII)., Methods: Visual acuity, retinopathy level, dark adaptation kinetics, retinal and subfoveal choroidal thickness, macular perfusion velocities, retinal vessel diameters and blood oxygen saturations were measured at baseline and after 1, 4, 16, 32 and 52 weeks in 31 patients with type 1 diabetes who started CSII and 20 patients who continued multiple daily insulin injections (MDI)., Results: One year of CSII reduced haemoglobin A1c (HbA1c ) by 1.6% (17.8 mmol/mol) compared with 0.3% (3.1 mmol/mol) in the MDI group (p < 0.0001). Central retinal thickness increased by 1.5% in the CSII group (within-group p = 0.0098; between-group p = 0.063) without producing macular oedema. No detectable change was found in any other primary outcome measure. The proportion of patients with retinopathy worsening did not differ between groups. At baseline, longer disease duration was associated with higher retinal artery oxygen saturation (p = 0.014) and lower macular venous perfusion velocity (p = 0.045)., Conclusion: One year of CSII led to an HbA1c reduction relative to continued MDI and a small increase in retinal thickness but not to early retinopathy worsening or to changes in retinal vascular, structural or functional characteristics. Longer duration of type 1 diabetes appears to be associated with lower macular venous perfusion velocity and higher retinal artery oxygen saturation. The latter could potentially reflect cumulative glycaemia., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Dark adaptation is an energy-requiring process in the outer retina nourished by the profusely perfused choroid. We hypothesized that variations in choroidal thickness might affect the rate of dark adaptation., Method: Cross-sectional, observational study of 42 healthy university students (mean age 25 ± 2.0 years, 29 % men) who were examined using an abbreviated automated dark adaptometry protocol with a 2° diameter stimulus centered 5° above the point of fixation. The early, linear part of the rod-mediated dark adaptation curve was analyzed to extract the time required to reach a sensitivity of 5.0 × 10(-3) cd/m2 (time to rod intercept) and the slope (rod adaptation rate). The choroid was imaged using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT)., Results: The time to the rod intercept was 7.3 ± 0.94 (range 5.1 - 10.2) min. Choroidal thickness 2.5° above the fovea was 348 ± 104 (range 153-534) μm. There was no significant correlation between any of the two measures of rod-mediated dark adaptation and choroidal thickness (time to rod intercept versus choroidal thickness 0.072 (CI95 -0.23 to 0.38) min/100 μm, P = 0.64, adjusted for age and sex). There was no association between the time-to-rod-intercept or the dark adaptation rate and axial length, refraction, gender or age., Conclusion: Choroidal thickness, refraction and ocular axial length had no detectable effect on rod-mediated dark adaptation in healthy young subjects. Our results do not support that variations in dark adaptation can be attributed to variations in choroidal thickness.

Purpose: This study compared in vivo enhanced-depth imaging optical coherence tomography (EDI-OCT) with ex vivo histology of the choroid in human eyes., Methods: Three eyes in three patients with advanced iris melanoma without posterior segment involvement underwent EDI-OCT less than 24 hours prior to enucleation and, in one eye, immediately after enucleation. Following fixation in 4% buffered formaldehyde and paraffin embedding, serial sections of the whole eye were cut horizontally, mounted, stained with hematoxylin-eosin and digitized. Alignment between histology and EDI-OCT was made on landmarks such as retinal vessel, the foveal depression, ciliary arteries, drusen, and nevi., Results: Intra- and interindividual variations in relative choroidal thickness were comparable between the two modalities. After histologic fixation of the three melanoma eyes, the fullness of the choroidal vessels was reduced and subfoveal choroid thickness reduced to 56%, 45%, and 56%, respectively, of its in vivo thickness on EDI-OCT., Conclusions: There were no identifiable discrepancies in choroidal structural patterns between clinical EDI-OCT and histologic sections except that after enucleation and histologic fixation choroidal thickness was reduced to roughly half of its in vivo value, a phenomenon that may reflect the high content of blood vessels in the choroid.

Introduction: Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing demand for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases, e.g. age-related macular degeneration and diabetic retinopathy. We systematically reviewed the existing literature to provide an overview of the experiences in this transformational process., Methods: We searched for literature on 22 September 2015 using PubMed, Embase, the Cochrane Library, CINAHL and the Web of Science. Eligible studies had to address any outcome based on non-physician delivered intravitreal therapy regardless of the study design. Being non-physician was defined as the injecting personnel not being a physician, but no further restrictions were made., Results: Five studies were included with a total of 31,303 injections having been performed by 16 nurses. The studies found that having nurses perform the intravitreal injections produced to a short-term capacity improvement and liberated physicians for other clinical work. Training was provided through courses and direct supervision. The rates of endophthalmitis were 0-0.40‰, which is comparable to reported rates when the intravitreal therapy is given by physicians., Conclusion: Non-physician delivered intravitreal therapy seems feasible and safe.

Introduction: The demand for intravitreal therapy has increased dramatically with the introduction of vascular endo-thelial growth factor inhibitors. Improved utilisation of existing resources is crucial to meeting the increased future demand. We investigated time spent preparing intravitreal injection treatment using either prefilled syringes or vials in routine clinical practice., Methods: We video-recorded preparations of intravitreal injections (n = 172) for each preparation type (ranibizumab prefilled syringe (n = 56), ranibizumab vial (n = 56) and aflibercept vial (n = 60)) in a multi-centre time and motion study. The preparation times for each step were extracted from videos and the three preparation types were compared., Results: Prefilled syringes eliminated several steps in the preparation process. Total preparation time was 40.3-45.1 sec. using vials, and the use of prefilled syringes saved 25.5 sec. (95% confidence interval (CI): 23.3-27.6 sec., p < 0.0001). The preparation time when aflibercept vials were used was 3.7 sec. (95% CI: 1.45-5.96 sec., p = 0.0014) longer than when ranibizumab vials were used., Conclusions: Prefilled syringes for intravitreal injections reduce preparation time by eliminating preparation steps that both entail a risk of contamination and are subject to variation. The amount of time saved may enable increased utilisation of existing resources and outsourcing to non-ophthalmologists., Funding: This study was supported by a grant from Novartis. The funders had no influence on the design of the study, analysis of the data, preparation of the manuscript or the decision to publish., Trial Registration: not relevant.

Purpose: To develop 28 short texts to be used as sentence optotypes in a Danish version of the Radner Reading Chart for the measurement of reading acuity and speed., Method: Forty-six short texts of comparable lexical and grammatical difficulty were constructed. The short texts were tested together with two longer reference texts in 100 persons with visual acuity 6/6, of which 50 were university students (age: 24.7 ± 3.1 years, 36% males) and 50 were blue-collar workers (37.2 ± 13.4 years, 54% males). Study parameters were mean reading speed and error rate per participant, and mean reading time, variance and number of errors per short text., Results: The students read the short texts faster than the blue-collar workers (184 ± 21.4 words per minute (wpm) versus 163 ± 26.3 wpm, p < 0.0001). There was a high correlation between the reference texts and the short texts [Pearson's correlation coefficient = 0.89 (95% CI 0.83-0.92)]. The mean reading time for each of the short texts ranged from 4.4 s to 5.8 s with a mean of 4.96 ± 0.35 s, and the median number of errors was eight. Twenty-eight short texts were selected for sentence optotypes with mean reading times between 4.6 s and 5.2 s, a mean standard deviation of 1.2 s or less and a number of errors of 17 per 100 persons or less., Conclusion: Reading time uniformity in the Danish version of the Radner Reading Chart was comparable to that of the original German version. Education had an influence on reading performance that may warrant stratification for this parameter when reading tests are used in clinical trials., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose . To describe associations between retinal vessel diameters and cardiovascular risk markers and mortality. Methods . The present study included 908 persons aged 30 to 60 years. Vessel diameters were expressed as central retinal venular equivalent (CRVE) and central retinal arteriolar equivalent (CRAE). Multiple linear regression analyses and Cox regression models were used. Results . Multiple linear regression analyses showed that narrower CRAE was associated with higher systolic blood pressure, age, and higher HDL cholesterol, whereas wider CRAE and CRVE were associated with smoking. Narrower CRVE was associated with higher HDL cholesterol. In an age-adjusted model, associations between wider CRVE and risk of ischemic heart disease were found ( P < 0.001). Wider CRVE was associated with all-cause mortality (HR = 2.02, P = 0.033) in a model adjusted for age, gender, and blood pressure. However, the association was not statistically significant after additional adjustment for smoking. Conclusions . The associations between retinal vessel diameters and known cardiovascular risk factors were confirmed. All-cause mortality was not associated with retinal vessel diameters when adjusting for relevant confounders., Competing Interests: The authors declare that they have no competing interests.

We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease.

Purpose: To examine choroidal thickness in a population-based child cohort in relation to birth parameters., Methods: The Copenhagen Child Cohort 2000 Eye Study examined 1406 children aged 11 to 12 years using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT), ocular biometry and measurement of height, weight, refraction, and self-reported pubertal development status. Birth parameters were obtained from the Danish Medical Birth Registry., Results: The subfoveal choroid in low birth weight children (<2500 g, n = 51, mean 324 ± 76 μm) was thinner than in normal birth weight children (2500-4500 g, n = 1194, mean 361 ± 78 μm), the difference being -37 (CI95 -60 to -15) μm, P = 0.001 after adjusting for age, sex, height, Tanner stage by sex, axial length, anterior chamber depth, and spherical equivalent refractive error. The subfoveal choroid in high birth weight children (>4500 g, n = 48, mean 351 ± 63 μm) was comparable with normal birth weight children, P = 0.44. The subfoveal choroid was thinner in preterm children, however the difference was not significant (-18 [-37 to 2] μm, P = 0.08). Small for gestation children had thinner subfoveal choroid (-19 [-37 to -1] μm, P = 0.04) compared with appropriate for gestation children. Longer birth length was associated with a thicker subfoveal choroid (2 [1-4] μm/cm, P = 0.005). Macular choroidal thickness at 16 extrafoveal locations was measured in a subset of children and found to have the same associations with birth weight as the subfoveal choroidal thickness., Conclusions: In 11- to 12-year-old children, thinner choroids were associated with lower birth weight, lower birth length, and being small for the gestational age., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease.

Purpose:   To study intravascular characteristics of flowing blood in retinal vessels using spectral-domain optical coherence tomography (SD-OCT)., Methods:   Examination of selected arterial bifurcations and venous sites of confluence in 25 healthy 11-year-old children recruited as an ad hoc subsample from the population-based, observational Copenhagen Child Cohort 2000 study., Results:   The blood stream in retinal arteries maintains a figure-of-8 SD-OCT profile consistent with a laminar flow in concentric sheets and a parabolic velocity distribution up to the point of divergence at arterial bifurcations. In contrast, the blood stream at the site of confluence of two retinal veins remains divided into two parallel sets of sheets with separate velocity distribution for a downstream distance of at least four trunk vessel diameters. Consequently, retinal trunk vessels near bifurcations/confluences have distinctly different internal SD-OCT profiles, a figure-of-8 pattern in arteries and a figure figure-of-88 in veins that can be used to distinguish between the two vessel types., Conclusion:   This study verified the hypothesis that directions of blood flow at dichotomous vascular branchings can be determined using SD-OCT. This feature may assist the identification of flow reversal near sites of vascular occlusion, the analysis of blood flow near vascular malformations and the segmentation of retinal SD-OCT images., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy., Methods: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome., Results: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid., Conclusion: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.