The Health Outcome

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world.
(1, 2, 3) Most people affected with AMD are elderly but this degenerative disease can manifest itself as early as the 5 th decade of life. AMD is characterized by the progressive loss of central vision. Diagnostic features include drusen (yellowish deposits that form under the retina), atrophy of the retina or the retinal pigment epithelium, and choroidal neovascularization (the formation of small blood vessels under the retina). (4) An estimated 11 million people in the United States are affected with AMD and an additional 7 million more, exhibiting drusen, are at risk of developing AMD. (5)

The Finding

This study was intended to assess the association of fibulin gene family variants with age-related macular degeneration. The fibulins are a group of extracellular matrix proteins that have various roles in the structure and function of tissues, including specialized binding and vascular development and remodeling. Variation in other members of the fibulin gene family has been implicated in the pathology of other degenerative eye diseases, including Doyne honeycomb retinal dystrophy, a rare Mendelian form of macular degeneration. (6)

In this study, peripheral blood was extracted from 831 patients (402 cases; 263 “general-population” controls; and 166 “other” controls). Retinal specialists at the University of Iowa Retina Clinic and elsewhere in the United States diagnosed the cases with AMD according to standard criteria. Two control groups were selected from the University of Iowa . The “general population” controls displayed no history of AMD (although not confirmed by eye exam) and the “other” control group, characterized by the absence of AMD (confirmed by eye exam) and a negative family history of AMD. Fibulin genes 1, 2, 4 and 6 were sequenced for all cases and the “general-population” controls; the fibulin 5 gene was sequenced for all cases and both control groups. Although 114 variants were found in the fibulin genes among patients with AMD, neither a single variation nor variations in a single gene demonstrated a strong association with the AMD phenotype. The authors suggested that while variations in the fibulin genes are probably not causative factors for AMD, they may play a role in the pathophysiology of AMD.

As the population of the United States and other countries ages, the increasing prevalence of AMD will have important public health implications. Given that reading is the leading leisure activity for retired persons, progressive degenerative vision loss will greatly impact quality of life for the elderly. Secondary conditions such as depression could result when people with AMD lose the ability to do many daily tasks independently, (removed such as). It is also anticipated that there will be an economic impact as persons affected by early onset AMD may need to stop working before retirement age and may need to rely on disability insurance and other social security benefits. As frequent visits to ophthalmologists and retinologists are necessary to monitor the progression of the disease, there is a significant cost of care for those inflicted with AMD. Additionally, expensive interventions, such as special glasses, reading machines, and other assisted-living devices may be needed for a patient to continue productive living.

The results of this study do not have any direct implications for public health prevention or intervention but may point to areas of future study for understanding AMD pathology. The authors suggest that the fibulins may play a role in the natural history of AMD, but not enough is known about either the fibulins or AMD itself. Future studies of AMD biology are warranted to understand how various risk factors, including genes, environmental influences, and a combination of the two, impact the occurrence and severity of the disease.

References

1. Fong DA. Age-Related Macular Degeneration: Update for Primary Care. American Family Physician. 2000 May;61(10):3035-42.
2. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmol. 1992;99:933-43.
3. Jonasson F, Arnarsson A, Peto T, Sasaki H, Sasaki K, Bird AC. 5-year incidence of age-related maculopathy in the Reykjavik Eye Study. Ophthalmol. 2005 Jan;112(1):132-8.
4. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Survey of Ophthalmology. 2003 May;48(3):257-93.
5. Friedman DS, O'Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J; Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004 Apr;122:567-72.
6. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University , Baltimore , MD. MIM Number: 135820: 2/22/2005: World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/.
7. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, Sangiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J. Complement Factor H Polymorphism in Age-Related Macular Degeneration. Science. 2005 Apr 15;308(5720):385-9. Epub 2005 Mar 10.