Inger Christine Munch

Incidence of Legal Blindness From Age-Related Macular Degeneration in Denmark: Year 2000 to 2010

PURPOSE To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older. DESIGN Population-based observational registry study. METHODS settings: Membership register of the Danish Association of the Blind, the primary admission criterion of which is best-corrected visual acuity 0.1 (20/200) or lower in a persons better-seeing eye. study population: A total of 11 848 incident cases of legal blindness from a population of citizens aged ≥50 years numbering 1.71 million in 2000 and 1.87 million in 2010 with free access to a single-payer public health care system. main outcome measures: Incidence rates of legal blindness from AMD from 2000 to 2010. RESULTS The incidence rate of legal blindness attributable to AMD in citizens aged ≥50 years decreased from 52.2 cases per year per 100 000 in 2000 to 25.7 cases per year per 100 000 in 2010, corresponding to a reduction of 50% (95% confidence interval [CI(95)]: 45%-56%, P < .0001, adjusted for age), the bulk of the reduction occurring after 2006. The incidence of legal blindness from causes other than AMD decreased by 33% (CI(95): 21%-44%, P < .0001), most of the reduction occurring between 2000 and 2006. CONCLUSION From 2000 to 2010 the incidence of legal blindness from AMD fell to half the baseline incidence. The bulk of the reduction occurred after the introduction of intravitreally injected inhibitors of vascular endothelial growth factor in 2006.

Mechanism of Retinal Pigment Epithelium Tear Formation Following Intravitreal Anti–Vascular Endothelial Growth Factor Therapy Revealed by Spectral-Domain Optical Coherence Tomography

PURPOSE To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT). DESIGN Retrospective observational case series. METHODS OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur in this setting. RESULTS In all eyes, pretear images revealed a vascularized pigment epithelial detachment (PED) containing hyperreflective material consistent with choroidal neovascularization (CNV). This CNV was adherent to the undersurface of the RPE and created contractile folds in the RPE contour. In 6 eyes, contractile neovascular tissue spanned the PED, causing outward bowing of the Bruch membrane and a peaked appearance to the overlying RPE monolayer. RPE tears occurred after the first anti-VEGF injection in 6 of 8 eyes. The posttear OCT images showed a discontinuity in the RPE with the CNV adherent to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution and contraction of neovascular tissue adherent to the undersurface of the RPE may impart a substantial contractile force that tears this already-strained tissue layer.

Retinal Oxygen Saturation in Patients with Systemic Hypoxemia

PURPOSE To assess spectrophotometric oximetry across a broad range of arterial saturation levels and to study the effect of chronic systemic hypoxemia on retinal oxygen extraction. METHODS The study included 16 patients with Eisenmenger syndrome, a cyanotic cardiac defect, and 17 healthy volunteers. Oxygen saturation in selected major retinal arteries and veins was assessed using noninvasive spectrophotometric oximetry. Arterial blood gases were determined within 1 day of the ophthalmic examination in blood samples from the femoral artery. RESULTS The retinal arterial oxygen saturation of 81% ± 9% (mean ± SD) in patients with Eisenmenger syndrome was subnormal and demonstrated more interindividual variation than the 93% ± 3% observed in healthy subjects (P < 0.001). A comparable difference was found for the respective retinal venous oxygen saturations of 44% ± 12% and 59% ± 5% (P < 0.001). Fractional arteriovenous oxygen extraction was comparable between the two groups (37% ± 6% and 34% ± 5%, respectively; P = 0.29). Retinal and femoral artery oxygen saturation were correlated (ρ = 0.82; P < 0.001), the former approximating the latter at least as well as fingertip oximetry. CONCLUSIONS When compared to arterial blood gas analysis of blood samples drawn by arterial puncture, the gold standard in the field, fundus oximetry was found to be in good overall agreement with the arterial blood samples. Blood flow measurements will be needed to determine whether the systemic hypoxia is completely compensated, as suggested by oxygen extraction being comparable between the two groups.

Straight versus tortuous retinal arteries in relation to blood pressure and genetics

Background/aims: To assess the relative influence of genetic and environmental factors on retinal arterial tortuosity and the association between tortuosity and various health indices in healthy young to middle-aged persons. Methods: This cross-sectional study included 57 monozygotic and 52 dizygotic same-sex healthy twin pairs, aged 20 to 46 years, who were characterised by determination of retinal vessel diameters, arterial blood pressure, blood glucose, body mass index, smoking habits and retinal arterial tortuosity, using a three-level grading scale (straight, wavy, tortuous). Heritability of retinal arterial tortuosity was estimated using structural equation modelling. Results: Of 218 subjects, 79 (36.2%) had straight retinal arteries, 110 (50.5%) had wavy arteries, and 29 (13.3%) had tortuous arteries. Heritability of tortuosity was 82% (CI95 64, 92%), with unshared environmental factors accounting for the remaining 18% (CI95 8, 36%). Increasing values of mean arterial blood pressure and body mass index were both associated with decreasing levels of retinal arterial tortuosity. Conclusion: There was a large variation in tortuosity of retinal arteries in these healthy subjects and the predominant determinant was genetic influence, accounting for 82% of the observed variation in tortuosity.

Subfoveal choroidal thickness in 1323 children aged 11 to 12 years and association with puberty: the Copenhagen Child Cohort 2000 Eye Study.

PURPOSE To investigate subfoveal choroidal thickness and ocular- and systemic-associated factors in a population-based cohort of children. METHODS Cross-sectional, observational study where 1323 healthy 11- and 12-year-old children were examined with enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT), ocular interferometric biometry, blood pressure manometry, and measurement of height, weight, nonmydriatic refraction, and best-corrected visual acuity. Self-reported stage of pubertal development was classified as Tanner stages 1 through 4. RESULTS Mean subfoveal choroidal thickness was 369 ± 81 μm in girls and 348 ± 72 μm in boys. Longer axial length was associated with a thinner subfoveal choroid (-27.2 [95% confidence interval (CI) -32.7 to -21.7] μm/mm; P < 0.0001), adjusting for age and sex. There was no difference in choroidal thickness between sexes (P = 0.14) after adjusting for age and axial length. In girls, the choroid was thickest in participants in the more advanced stage of pubertal development (54.2 [95% CI 20.7-87.7] μm for Tanner 4 versus Tanner 1, P = 0.0015) and increased with body height (19.2 [95% CI 10.8-27.5] μm/10 cm, P < 0.0001). There was no effect of height or puberty in boys, who were less sexually mature than girls. CONCLUSIONS Choroidal thickness in girls increased with body height and sexual maturation. The results suggest that puberty promotes choroidal thickening in girls, an effect that may be mediated by the pubertal growth spurt. The lack of pubertal effect in boys may be related to a smaller proportion of boys in this study having entered puberty.

Light-induced c-Fos expression in suprachiasmatic nuclei neurons targeting the paraventricular nucleus of the hamster hypothalamus: phase dependence and immunochemical identification.

The suprachiasmatic nuclei (SCN) contain a master clock driving the majority of circadian rhythms in mammals. It is believed that the SCN confers circadian rhythmicity as well as light responsiveness to pineal melatonin secretion via a direct projection to the paraventricular nucleus of the hypothalamus (PVN). Neurons in the SCN respond to light during subjective night with an expression of the immediate early gene c‐fos. The number and distribution of c‐Fos protein‐containing neurons depend on the zeitgeber time (ZT) at which the light stimulus is presented. To investigate whether this phase‐dependent activity is present in the SCN output neurons targeting the PVN, we combined retrograde cholera toxin subunit B (ChB) tracing from the PVN with c‐Fos immunohistochemistry. Male golden hamsters were injected iontophoretically with ChB into the PVN area and 7 days later given a 1.5‐hr light stimulus at either ZT 14 or ZT 19 followed by vascular fixation. Light stimulation at ZT 19 gave rise to more c‐Fos containing neurons in the SCN than light presented at ZT 14. Double immunostaining for ChB and c‐Fos revealed that light stimulation at ZT 14 induced c‐Fos expression in 26.6% ± 2.8% of the retrogradely filled perikarya, whereas light‐stimulation at ZT 19 increased this fraction to 40.7% ± 1.9%. This demonstrates the presence of a phase‐dependent c‐Fos induction in the suprachiasmatic‐paraventricular projection system. Triple immunohistochemistry showed that light‐activated output neurons contained both gastrin‐releasing peptide and vasoactive intestinal polypeptide and to a lesser extent vasopressin. The present findings provide functional evidence of light activation of central pathways involved in the regulation of circadian output rhythms. J. Comp. Neurol. 442:48–62, 2002.

Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major cell–cell adhesion molecule in vascular endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (P = 0.0002; OR = 0.61, 95% CI [0.47–0.79]). We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.

Photoreceptor atrophy in acute zonal occult outer retinopathy

Purpose:  To assess retinal morphology in acute zonal occult outer retinopathy (AZOOR) without ophthalmoscopically visible fundus changes.

Small, Hard Macular Drusen and Peripheral Drusen: Associations with AMD Genotypes in the Inter99 Eye Study

PURPOSE To study associations of small, hard macular drusen and peripheral drusen with genotypes associated with age-related macular degeneration (AMD). METHODS Digital grayscale fundus photographs recorded in red-free illumination were graded for the presence of drusen in 1107 subjects aged 30 to 66 years. Participants were genotyped for AMD-related polymorphisms in complement factor H (CFH), in LOC387715, and in complement factor B (CFB). RESULTS The prevalence of 20 or more small, hard macular drusen per eye was 14%, with no association to the investigated polymorphisms. Peripheral drusen were associated with CFHY402H (odds ratio [OR], 4.3; 95% confidence interval [95% CI], 1.4-13, for CC versus TT genotypes) as was macular drusen >63 microm (OR, 1.9; 95% CI, 1.1-3.1, for CC versus TT genotypes). Macular drusen >63 microm were associated with the presence of 20 or more small, hard macular drusen (OR, 1.7; 95% CI, 1.1-2.6) and with peripheral drusen (OR, 2.5; 95% CI,1.2-5.4) CONCLUSIONS In this study, the presence of 20 or more small, hard macular drusen per eye was not associated with known AMD-related polymorphisms, whereas the study confirmed an association of peripheral drusen with CFHY402H. (ClinicalTrials.gov number, NCT00289237).

Precursors of Age-Related Macular Degeneration: Associations With Physical Activity, Obesity, and Serum Lipids in the Inter99 Eye Study

PURPOSE To investigate associations of small, hard macular drusen and larger macular drusen with obesity-related risk factors. METHODS Cross-sectional study of 888 subjects aged 30 to 60 years characterized using anthropometric measurements and blood sample analyses. Physical activity was assessed by questionnaire. Digital grayscale fundus photographs were recorded in red-free illumination and graded for the presence of macular drusen > 63 μm in either eye and the presence of 20 or more small, hard macular drusen as a mean of both eyes. RESULTS Macular drusen > 63 μm were associated with the level of physical activity, the age- and sex-adjusted odds ratio being 0.33 (95% confidence interval 0.13-0.82, P = 0.016) for participants who were physically active more than 7 hours/week compared with participants active 0 to 2 hours/week. In women, macular drusen > 63 μm were associated with higher serum triglycerides (P = 0.0005). A waist circumference in the top quartile increased the odds for drusen > 63 μm in men whereas in women, having a waist circumference in the middle quartiles reduced these odds. The presence of 20 or more small, hard macular drusen was associated with lower levels of serum high-density lipoprotein cholesterol (HDL; P = 0.029) and with moderately elevated triglycerides. CONCLUSIONS Precursors of AMD were associated with modifiable obesity-related risk factors; notably low physical activity with drusen > 63 μm; and lower serum HDL and moderately elevated serum triglycerides with 20 or more small, hard macular drusen per eye. These findings support that a physically active, heart-healthy lifestyle prevents the earliest manifestation of AMD. (ClinicalTrials.gov number, NCT00289237.).