OBSERVATIONS Relationship Between Periodontal Disease and Diabetic Retinopathy

R ecently, various studies have reported that periodontal disease adversely affects diabetes (1). The control of periodontal disease in elderly individuals has been reported to improve the control of blood glucose (2). Severe periodontal disease is associated with elevated blood lipopolysaccharide levels as a result of periodontogenic bacteria, which induce higher levels of interleukin-6 (IL-6) and tumor necrosis factor(TNF) (3,4). Control of periodontal disease is now considered not only a dental problem but also an issue affecting the patient’s overall quality of life. Proinflammatory cytokines such as IL-6 have been shown to be involved in the pathogenesis of diabetic retinopathy (DR) (5), while the relationship between diabetic retinopathy and periodontal disease remains unclear. We investigated whether periodontal disease is correlated with diabetic retinopathy. The study was based on a prospective review of 73 eyes in 73 consecutive diabetic patients. The mean duration of diabetes was 14.3 7.1 years (range 2–33), and the mean HbA1c was 7.5 1.6% (5.2–13.7). IL-6 and TNFlevels in the vitreous fluid samples from 32 eyes obtained during vitrectomy and in paired plasma samples were measured by enzyme-linked immunosorbent assay. Nondiabetic patients included 10 with macular hole and 2 with epiretinal membrane. Institutional ethics committee approval was obtained, and all participants gave informed consent. The severity of diabetic retinopathy was quantified according to the modified Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy severity scale (6). The severity of periodontal disease was quantified according to bone loss and then graded and evaluated (7). Patients with periodontal disease were classified as positive or negative based on median values. Diabetic patients were classified as having nonproliferative or proliferative diabetic retinopathy. Data are presented as means SD. The Mann-Whitney U test was used to compare IL-6 and TNFlevels. To determine the relationship between the severity of periodontal disease and ETDRS, retinopathy severity, or angiogenic factors, as well as between X and Y parameters, Spearman’s rank-order correlation coefficient and logistic regression model were applied. The severity of periodontal disease was significantly correlated with the severity of diabetic retinopathy (P 0.0012), and the risk of proliferative diabetic retinopathy was significantly higher in the presence of periodontal disease (odds ratio 2.80, P 0.036). There was no significant relationship between the severity of periodontal disease and HbA1c or duration of diabetes (P 0.098 and 0.295, respectively). There was a significant relationship between the severity of diabetic retinopathy and duration of diabetes (P 0.002). The vitreous fluid level of IL-6 (mean 154.2 164.6 pg/ml [range 0.993–597.0]) was significantly elevated in patients with diabetic retinopathy compared with that in nondiabetic patients (mean 1.34 0.91 pg/ml [0.6– 3.68]) (P 0.0001). Furthermore, the vitreous fluid level of IL-6 was significantly correlated with the severity of periodontal disease (P 0.012). There was no significant relationship between the vitreous fluid level of IL-6 and HbA1c or duration of diabetes (P 0.293 and 0.705, respectively). In contrast, the vitreous fluid level of TNFwas not significantly correlated with the severity of periodontal disease. The IL-6 concentration in vitreous fluid (mean 154.2 164.6 pg/ml [0.993–597.0]) was significantly higher than that in plasma (mean 1.89 3.47 pg/ml [0.156–18.8]) (P 0.0001). There was a significant relationship between periodontal disease and severity of diabetic retinopathy, but it was unclear whether periodontal disease directly affects the progression of diabetic retinopathy because this was a cross-sectional study. Further prospective studies, including evaluation of systemic factors, are necessary.