Periodontal Disease and AMD

While perhaps surprising, recent research has indicated a link between gum disease and AMD.

SUSHANT WAGLEY • JORGE G. ARROYO, MD, MPH

Age-related macular degeneration is one of the leading causes of irreversible vision loss in the elderly population.¹ Although the exact pathophysiology of AMD is not fully understood, age-associated changes and oxidative stress, resulting in cellular damage, have been suggested as the triggering factors in AMD.² This cellular damage is further aggravated by the subsequent immune and inflammatory response.

A chronic aberrant inflammatory response may result in the progression of AMD into advanced stages, indicated by retinal atrophy, angiogenesis/formation of neovascular membranes, or both — resulting in a severe decrease in vision.³

PERIODONTAL DISEASE

Periodontal disease is a common infectious and inflammatory condition that results in long-term inflammation and heightened immune response. Periodontal disease is highly prevalent (47.2% in adults 30 years old or older), and its prevalence increases with age.⁴

Ranging from inflammation of the gingiva in gingivitis (the lesser and reversible form of periodontal disease) to loss of supporting connective tissue and alveolar bone in periodontitis (the more advanced form), the accumulation of bacterial biofilm (dental plaque) adjacent to the gums in periodontal disease results in damage to the periodontal tissue from bacterially induced inflammation.⁵

Loss of tissue results in the formation of periodontal pockets that place bacterial biofilm in close proximity to the circulation. This juxtaposition alongside chronic local inflammation of the surrounding tissue results in the introduction of pathogens and their biologically active components into the circulation, which can result in systemic inflammation.⁶

PERIODONTAL DISEASE AND CARDIOVASCULAR DISEASE

Periodontal disease has been shown to be independently associated with an increased risk of developing atherosclerotic vascular disease. Periodontal bacteria and their components, including DNA, have also been demonstrated in atheromatous plaques.

Both a direct (via vascular infection by periodontal pathogen) and an indirect pathophysiological pathway (via systemic inflammation or molecular mimicry) have been proposed as potential links between periodontal disease and atherosclerotic vascular disease.⁵

Cardiovascular disease and AMD have many risk factors in common, including similarities in certain pathological presentations. For example, many compositional and histological similarities exist between the drusen seen in AMD and the atherosclerotic plaques present in cardiovascular disease.

It has been hypothesized that similar biochemical and immune processes, most importantly inflammation, are implicated in the development of both drusen and atherosclerotic plaques.⁷

While we have been aware of an association between periodontal disease and cardiovascular disease for quite some time, we are only now starting to discover and understand the relationship between periodontal disease and AMD.

INCREASED RISK OF AMD

Periodontal disease is associated with increased risk of AMD. In a cross-sectional study of 1,751 individuals in Finland, periodontal disease — as measured by alveolar bone loss — was independently associated with increased risk of AMD in males. This relationship was not noted in women.⁸

Another cross-sectional study, based on the National Health and Nutrition Examination Survey (NHANES) in the United States, found a significant independent association between periodontal disease and AMD. That study examined 5,887 individuals with periodontal data and graded retinal photographs.

Wagley et al⁹ found a significant association between periodontal disease and AMD in subjects ≤60 years old regardless of sex, after controlling for confounding factors. However, no significant relationship emerged in subjects older than 60. It has been hypothesized that increasing age results in increased influence of covariates on AMD, diluting the effects of periodontal disease.

PERIODONTAL DISEASE AND CRP

In the same study of 5,887 participants from the NHANES population, Wagley et al⁹ reported significantly higher C-reactive protein (CRP) levels in adults with periodontal disease vs those without. Again, this relationship was significant only in those 60 years of age or younger, indicating effect dilution by covariates as age increased.

C-reactive protein is an acute-phase reactant protein used as a clinical biomarker for inflammation.¹⁰ Previous reports have already demonstrated increased levels of CRP in patients with periodontal disease.^11,12

Increased levels of CRP have also been associated with an increased risk of developing AMD, providing support for an inflammatory component behind the pathogenesis of AMD.¹³

THE INFECTIOUS/INFLAMMATORY HYPOTHESIS

Studies have already identified associations between infections/chronic systemic inflammation and AMD.^14,15 Cytomegalovirus, Helicobacter pylori, and Chlamydia pneumoniae have been reported as potential pathogens associated with AMD.^16,17

One study reported on the detection of C. pneumoniae in choroidal neovascular membranes excised from patients with AMD and found that this microbe was capable of inducing the production of VEGF by macrophages and inducing increased production of IL-8 and MCP-1.¹⁸ Persistent infection and a subsequent inflammatory response may promote the progression of other inflammatory age-related conditions such as AMD.

More than 500 distinct microorganisms exist in the human oral cavity, and periodontal disease increases the risk of introducing these pathogens into the systemic circulation.¹⁹

Because periodontal disease was associated with AMD even after controlling for systemic CRP levels in the study by Wagley et al, alternate mechanisms to CRP-mediated complement activation and tissue destruction model have been hypothesized.

A pathophysiological pathway of pathogen-associated molecular pattern (PAMP) recognition and the subsequent triggering of the immune response constitute another pathway hypothesized in this infectious/inflammatory model.

Finally, as also seen in cardiovascular disease,⁵ tissue destruction via molecular mimicry could also be an additional mechanism supporting the infectious/inflammatory hypothesis for the association of periodontal disease with AMD.

NEXT STEPS

While extensive research has examined the association between periodontal disease and cardiovascular disease, few studies to date have investigated the association between periodontal disease and AMD.⁸

We are already aware of the similarities in risk factors, mechanisms, and pathological findings seen between cardiovascular disease and AMD. Further work is necessary to better understand the connections between periodontal disease and AMD.

Good oral health is beneficial regardless of its connection to systemic disease, so even as we continue to study the relationship between periodontal disease and AMD, it is important to consider the periodontal status of the patient and encouraging proper oral health. RP

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