Age-related macular degeneration (AMD) has a number of known risk factors for progression, many of which are modifiable, such as smoking status and weight, but the condition is also associated with inflammation. A new study into systemic inflammation’s impact on intermediate AMD points to two principal components that contribute to disease progression.

The researchers evaluated combinations of 27 circulating inflammatory markers among 99 intermediate AMD patients. Markers included complement factors, cytokines, chemokines and high-sensitivity C-reactive protein (hsCRP).

            Of the 99 subjects, 21 progressed to advanced AMD. The researchers identified two principal components that contributed to the risk of progression to advanced disease, after adjusting for age and bilateral reticular pseudodrusen: the pro-inflammatory TNFα and the anti-inflammatory IL1ra. They believe this indicates that an imbalance exists between the two opposing functions.

            Patients may have increased risk of progression due to “many different combinations of analyte levels,” the researchers noted in their paper. An increased risk for conversion may result from a combination of high IL6 values and lower-than-average CRP levels, for example. They also wrote that low and high levels of other biomarkers (CCL2 and C3, respectively) would increase risk.

“Although genetic alterations in complement regulation have been shown to be an important risk factor for AMD, our data show that there is broad participation of other pathways in the innate immune system,” they wrote.

            Age was most associated with biomarker variations suggestive of AMD. Changes in the inflammatory system related to aging, known as “inflamm-aging,” demonstrate simultaneous changes in pro- and anti-inflammatory markers, according to the study authors. “Our analyses similarly found variations in analyte levels with age not represented by a simple increase in all markers, or a change in the relative balance between pro- and anti-inflammatory markers, but rather a more complex relationship.”

            They concluded that certain combinations of biomarkers could be used to distinguish between patients who did and did not progress to future advanced AMD. Because their study indicated that increased risk may result from different combinations of analyte levels, they surmise that inflammatory biomarkers have a complex relationship with AMD. The researchers pointed out that studying systemic inflammation among intermediate AMD patients may “provide insights into early pathologic events and potentially identify patients at highest risk for the development of severe AMD.” They suggested developing inflammatory marker panels to identify high-risk populations and target therapeutic interventions.

Wagner BD, Patnaik JL, Palestine AG, et al. Association of systemic inflammatory factors with progression to advanced age-related macular degeneration. Ophthalmic Epidemiol. April 8, 2021. [Epub ahead of print].