Epidemiology of age-related maculopathy

In 1875, Pagenstecher and Gentll provided the first description of age-related maculopathy (ARM). Nowadays, hundred and twenty years after the first description, ARM is one of the major causes of severe irreversible visual loss in the elderly in western countries. It has been estimated that there are 640000 people aged 75 years or older in the United States who have signs of the endstage of this disease. Still, Olll' knowledge about the etiology of ARM is very limited and treatment is only possible in a minority of patients. The Framingham Eye Study was the first population-based study that provided information about prevalence and risk factors for ARM. Since then, several epidemiologic studies on the disease have been performed, most of them in the USA. A review of the epidemiological knowledge obtained in these studies is given in chapter 2 of this thesis. Since until recently a uniform classification of ARM has not been available, comparison of the results of different studies has for years been a problem. Chapter 3 presents the results of several international meetings of six research groups with the aim to develop a uniform classification system for ARM. Little information was available on the prevalence of ARM in the Netherlands. The Rotterdam Study, however, provided an excellent opportunity to answer several research questions into the epidemiology of the disease. The results of the prevalence study are presented in chapter 4. The remainder of this thesis focuses on risk factors of the late stages of the disease, atrophic and neovascular agerelated macular degeneration (AMD). In chapter 5, the associations of various indicators of atherosclerosis and the late stages of the disease are described. Chapter 6 presents the association between smoking and AMD and in chapter 7 the relation with age of menopause and is described. Methodological issues related to the presented studies are discussed in chapter 8, together with a review of the results of these studies and suggestions for future research

Patient-reported outcomes in patients with vitreous floaters:A systematic literature review

Seeking treatment for bothersome vitreous floaters is patient driven. To measure the impact of floaters and treatment on an individual's quality of life, patient-reported outcome measurements (PROMs) are essential. We review all studies using a PROM for patients with floaters. We evaluated content coverage against quality-of-life domains previously identified in other ophthalmic disorders, and against a qualitative study investigating quality-of-life issues in patients with floaters. We assessed measurement properties of PROMs using an extensive range of psychometric quality criteria. We identified 59 studies using 28 different PROMs. Many PROMs were not specifically developed for patients with floaters. Floater-specific PROMs were mostly based on content validation from an ophthalmologist or researcher perspective; two included a patient perspective. Using the outcomes of the qualitative study, we found that the floater-specific PROMs were narrow in their content coverage, with most items relating to visual symptoms and activity limitations. Testing the psychometric quality of PROMs was rare, and when employed mostly limited to responsiveness and known group validity. The remarkable high number of floater-specific PROMs reveals a need for such measurements in ophthalmology. Unfortunately, reporting on psychometric quality is limited, and content development is most often done without patient involvement.</p

Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study

PURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlands. A total of 4822 subjects who at baseline were aged 55 years more, were free of ARM, and participated in at least one of two follow-up examinations after a mean of 2 and 6.5 years, were included in the study. At baseline, blood pressure and the presence of atherosclerosis were determined. ARM was assessed according to the International Classification and Grading System and defined as large, soft drusen with pigmentary changes; indistinct drusen; or atrophic or neovascular age-related macular degeneration. RESULTS: After a mean follow-up of 5.2 years, incident ARM was diagnosed in 417 subjects. Increased systolic blood pressure or pulse pressure was associated with a higher risk of ARM. Adjusted for age, gender, smoking, total and high-density lipoprotein cholesterol, body mass index, and diabetes mellitus, odds ratios (OR) per 10-mm Hg increase were 1.08 (95% confidence interval [CI]: 1.03-1.14) and 1.11 (95% CI: 1.04-1.18), respectively. Moreover, different measures of atherosclerosis were associated with the risk of ARM. An increase in carotid wall thickness (OR per 1 SD, 1.15; 95% CI: 1.03-1.28) increased the risk of ARM. The lowest compared with the highest tertile of ankle-arm index had an OR of 1.32 (95% CI: 1.00-1.75). A weak association was found between aortic calcifications and the risk of ARM. CONCLUSIONS: Elevated systolic blood or pulse pressure or the presence of atherosclerosis may increase the risk of development of ARM

Incidence of glaucomatous visual field loss after two decades of follow-up: the Rotterdam Study

To determine the incidence of glaucomatous visual field loss (GVFL) two decades after the start of the Rotterdam Study, and to compare known risk factors for open-angle glaucoma (OAG) between different clinical manifestations of OAG. Of 6806 participants aged 55 years and older from the population-based Rotterdam Study, 3939 underwent visual field testing at baseline and at least one follow-up round. The ophthalmic examinations included optic disc assessment and measurements of intraocular pressure (IOP), refractive error, diastolic blood pressure (DBP), and height and weight. The incidence rate of GVFL was calculated. Associations with the risk factors age, gender, baseline IOP, family history, myopia, DBP, and body-mass index [BMI] were assessed using Cox regression, with different clinical manifestations of OAG as outcome measure (glaucomatous optic neuropathy (GON), GVFL, GVFL and GON, GVFL without GON, and GON without GVFL). Median follow-up was 11.1 (IQR 6.8–17.2; range 5.0–20.3) years. The incidence rate of GVFL was 2.9 (95% confidence interval 2.4–3.4) per 1000 person years (140 cas

Comparison of retinal regions-of-interest imaged by OCT for the classification of intermediate AMD

To study whether it is possible to differentiate intermediate age-related macular degeneration (AMD) from healthy controls using partial optical coherence tomography (OCT) data, that is, restricting the input B-scans to certain pre-defined regions of interest (ROIs). A total of 15744 B-scans from 269 intermediate AMD patients and 115 normal subjects were used in this study (split on subject level in 80% train, 10% validation and 10% test). From each OCT B-scan, three ROIs were extracted: retina, complex between retinal pigment epithelium (RPE) and Bruch membrane (BM), and choroid (CHO). These ROIs were obtained using two different methods: masking and cropping. In addition to the six ROIs, the whole OCT B-scan and the binary mask corresponding to the segmentation of the RPE-BM complex were used. For each subset, a convolutional neural network (based on VGG16 architecture and pre-trained on ImageNet) was trained and tested. The performance of the models was evaluated using the area under the receiver operating characteristic (AUROC), accuracy, sensitivity, and specificity. All trained models presented an AUROC, accuracy, sensitivity, and specificity equal to or higher than 0.884, 0.816, 0.685, and 0.644, respectively. The model trained on the whole OCT B-scan presented the best performance (AUROC = 0.983, accuracy = 0.927, sensitivity = 0.862, specificity = 0.913). The models trained on the ROIs obtained with the cropping method led to significantly higher outcomes than those obtained with masking, with the exception of the retinal tissue, where no statistically significant difference was observed between cropping and masking (p = 0.47). This study demonstrated that while using the complete OCT B-scan provided the highest accuracy in classifying intermediate AMD, models trained on specific ROIs such as the RPE-BM complex or the choroid can still achieve high performance