Cone photoreceptor density in the Copenhagen Child Cohort at age 16-17 years.

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/mm2 (SD ± 3,802) and mean angular cone density was 2,383 cones/deg2 (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/mm2 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/deg2 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.

Myopia prevalence in Denmark - a review of 140 years of myopia research.

PURPOSE: To evaluate potential changes in myopia prevalence in Denmark by revising more than 100 years of myopia research. METHODS: A systematic literature search was performed in the PubMed, Embase and Cochrane Library databases. Only studies reporting a myopia prevalence in Denmark were included. Myopia was defined using the definition in individual references. We did not restrict inclusion of studies to specific methods of measuring or evaluating refraction. As refraction changes throughout life, information from available studies was divided in relevant age groups. Chi-squared test was used when analysing the effect of sex and education on myopia prevalence except when the expected values were beneath 5, where Fisher's exact test was used. To further compare the effect of sex, we calculated the odds ratio of being myopic for females compared to males. RESULTS: We identified 29 Danish studies reporting on prevalence of myopia. The studies were performed between year 1882 and 2018. We found no strong evidence of an increase in myopia prevalence in Denmark. Increasing age was associated with an increased myopia prevalence up to the age of 60 years where after the prevalence decreased. Longer education and more intensive educational load were associated with myopia. Fourteen studies compared the prevalence of myopia between males and females and two of these studies found a significant higher prevalence in females. CONCLUSION: We evaluated nearly 140 years of myopia research in Denmark and did not find a convincing change in prevalence of myopia which is in contrast to the high prevalence of myopia reported in some parts of the world and the expected rise in myopia as predicted by WHO.

Axial length change and its relationship with baseline choroidal thickness - a five-year longitudinal study in Danish adolescents: the CCC2000 eye study.

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 (ß = 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 (ß = 196 µm/mm, 95%CI 127 to 265, p < 0.0001) and nonmyopic eyes (ß = 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.

Low physical activity and higher use of screen devices are associated with myopia at the age of 16-17 years in the CCC2000 Eye Study.

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.

Five-Year Change in Choroidal Thickness in Relation to Body Development and Axial Eye Elongation: The CCC2000 Eye Study.

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, ß = -85 µm/mm; 95% confidence interval [CI], -104 to -66, P < 0.0001; girls, ß = -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 (ß = -8.6 µm/mm; 95% CI, -15 to -2.7, P = 0.0043), and more in girls who grew taller (ß = 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.

Visual acuity and amblyopia prevalence in 11- to 12-year-old Danish children from the Copenhagen Child Cohort 2000.

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.

Sleep-wake stability in narcolepsy patients with normal, low and unmeasurable hypocretin levels.

OBJECTIVE: To compare diurnal and nocturnal electrophysiological data from narcolepsy patients with undetectable (<20 pg/mL), low (20-110 pg/mL) and normal (>110 pg/mL) cerebrospinal fluid (CSF) hypocretin-1 levels. PATIENTS/METHODS: A total of 109 narcolepsy patients and 37 controls were studied; all had available CSF hypocretin-1 measurements. The sleep laboratory studies were conducted between 2008 and 2014. The study retrospectively examined measurements of sleep stage transitions in diurnal and nocturnal continuous polysomnography. The percentage distribution of time awake and rapid eye movement (REM) sleep, and the occurrence of sleep onset REM (SOREM) in the nocturnal polysomnography were also measured. RESULTS: Participants with undetectable hypocretin-1 levels had significantly higher frequencies of transitions than controls and those with normal hypocretin-1 levels. Participants with low hypocretin-1 levels showed more transitions than controls and, in some cases, also more than those with normal hypocretin-1. Participants with normal hypocretin-1 failed to show any significant difference from the controls, except in the overall diurnal transitions. CONCLUSION: Undetectable hypocretin-1 levels in particular, but also low hypocretin-1 levels, were associated with a less stable phenotype featuring more sleep state transitions and SOREM episodes. In addition, there was a distinction between nocturnal and diurnal REM sleep in hypocretin-deficient participants, expressed as increased diurnal REM sleep, which was not reflected in nocturnal sleep.

Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length.

The hypocretin/orexin neuropeptides (hcrt) are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF) from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June-July). The amplitude was 19.9 pg hcrt/mL [12.8-26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation.