From The British Journal of Ophthalmology

Age-related Macular Degeneration

The Importance of Family History as a Risk Factor

Humma Shahid; Jane C Khan; Valentina Cipriani; Tiina Sepp; Baljinder K Matharu; Catey Bunce; Simon P Harding; David G Clayton; Anthony T Moore; John R W Yates

Authors and Disclosures

Abstract and Introduction

Abstract

Background Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case–control study of reported family history and, second, by examining the siblings of AMD cases.
Methods The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype.
Results 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8).
Conclusion The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

Introduction

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and the most common cause of registered blindness in the developed world.^[1] In the early stages of the disease, deposits called drusen develop between the retinal pigment epithelium and the underlying choroid in the macular region of the retina. In the advanced stages of the disease, there is atrophy of the retinal pigment epithelium and overlying photoreceptor cells (geographic atrophy, GA) and/or aberrant choroidal neovascularisation (CNV; exudative AMD, also called wet AMD). Both can lead to loss of central vision. Susceptibility to AMD is influenced by age, ethnic background, and genetic and environmental factors, notably smoking.^[1] Several genetic variants that influence susceptibility to AMD have recently been identified.^[2]
With the advent of effective therapy for the neovascular form of AMD, early diagnosis and treatment is recommended and there is increased emphasis on patient self-screening for the early symptoms of disease.^[3] Family history is a known risk factor for AMD but it is not currently routine practice to alert those with a family history to the increased risk or advise them of the importance of recognising early symptoms. This is partly because estimates of the risk vary in different studies and the reliability of self-reported family history is unclear.^[4–16]
The aim of this study was to accurately quantify the risk associated with a family history of AMD in the UK population, first, by a case–control study of reported family history and, second, by examining the siblings of cases with advanced AMD.

Section 1 of 4

Next: Methods »