Can High Levels of Inflammation Predict Future Risk for Macular Degeneration?

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A new study, published “online first” in the February 2013 issue of JAMA Ophthalmology (formerly Archives of Ophthalmology), concludes that there is evidence that elevated levels of high-sensitivity C-reactive protein correlate with an increased future risk for age-related macular degeneration (AMD).

C-reactive protein is a substance, produced by the liver, that increases when inflammation is present throughout the body. Increasingly, inflammation is thought to be a key risk factor for AMD.

JAMA Ophthalmology is an international peer-reviewed journal published monthly by the American Medical Association (AMA), and is part of the JAMA Network of journals.

About the Research

The study, entitled C-Reactive Protein and the Incidence of Macular Degeneration, was authored by Vinod P. Mitta, MD, MPH; William G. Christen, ScD; Robert J. Glynn, PhD; Richard D. Semba, MD, MPH; Paul M. Ridker, MD, MPH; Eric B. Rimm, ScD; Susan E. Hankinson, ScD; Debra A. Schaumberg, ScD, OD, MPH. Lead author Vinod P. Mitta is from Brigham and Women’s Hospital and Harvard Medical School in Boston, MA.

The objective of this prospective study was to investigate the relationship between high-sensitivity C-reactive protein and the future risk of AMD in United States men and women. (Note: A prospective study measures and studies a group of individuals over time and follows up with study participants in the future. A retrospective study, on the other hand, has limitations because it collects data from past records and does not follow up with patients in the present.)

The study findings were based on participant data from five long-term health studies: the Women’s Health Study, the Physicians’ Health Study, the Women’s Antioxidant and Folic Acid Cardiovascular Study, the Nurses’ Health Study, and the Health Professionals Follow-up Study.

The researchers examined blood levels of C-reactive protein in the study participants and adjusted for other significant risk factors, including smoking, in order to determine the association between C-reactive protein levels (which indicate inflammation) and the risk for developing AMD.

All participants initially were free of AMD. The researchers identified 647 cases of AMD [that occurred over time] and selected age- and sex-matched controls [i.e., study participants without AMD] for each AMD case (two control subjects for each case with dry AMD or three control subjects for each case of wet AMD).

What Is C-reactive Protein?

From MedlinePlus:

C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. The CRP test is a general test to check for inflammation in the body. It is not a specific test. That means it can reveal that you have inflammation somewhere in your body, but it cannot pinpoint the exact location.

Your doctor may order this test to check for flare-ups of inflammatory diseases, such as rheumatoid arthritis, lupus, or vasculitis, or to determine if anti-inflammatory medicine is working to treat a disease or condition.

A more sensitive CRP test, called a high-sensitivity C-reactive protein (hs-CRP) test, is available to determine a person’s risk for heart disease. A positive hs-CRP test means that you have inflammation in the body, due to a variety of underlying conditions that can include cancer, connective tissue disease, heart disease, and rheumatoid arthritis.

Inflammation and Macular Degeneration

From Risk Factors for Age-Related Macular Degeneration at

Age and the environmental factors together produce an increased number of free radicals in the macula. The macula is the small sensitive area in the center of the retina that provides clear central vision. Free radicals are unstable molecules that must be neutralized to keep them from causing damage. Mother Nature has provided anti-oxidants in food to neutralize these free radicals.

However, when we have too many free radicals and not enough anti-oxidants, damage is done. The first signs of damage in the macula are small whitish or yellowish spots called drusen, which the ophthalmologist can see usually before the individual is experiencing vision loss.

This initial damage triggers inflammation, which causes more damage, exacerbated by more free radicals. This results in more inflammation and the cycle continues, eventually scarring the macula and causing central vision loss.

The Study Results

MedPage Today summarized the study results as follows:

High levels of the pro-inflammatory marker C-reactive protein (CRP) predicted an increased risk of age-related macular degeneration (AMD), including neovascular AMD, data from five large prospective cohort studies showed.

Comparison of patients with high versus low CRP demonstrated a 50% increase in the odds of AMD and almost doubled the risk of neovascular AMD. Separate analyses of the individual studies revealed AMD odds as high as 2.59 for patients with high versus low CRP.

The Study Implications

From the study summary in JAMA Ophthalmology:

Overall, these findings … add further evidence that elevated levels of hsCRP predict greater future risk of AMD. This information might shed light on underlying mechanisms and could be of clinical use in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols.

VisionAware will continue to provide updates for ongoing macular degeneration research as they become available.

Macular Degeneration Awareness Month

This February, during Macular Degeneration and Low Vision Awareness Month, visit to learn more about treatments for wet macular degeneration, emerging clinical trials for dry macular degeneration, and the low vision examination.