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Elevated urinary F2-isoprostanes tied to age-related macular degeneration

Tristan Manalac
24 Jul 2017

Elevated level of F2-isoprostanes in the urine is independently associated with age-related macular degeneration (AMD) in Chinese adults in Singapore, a new case-control study has found.

“We demonstrated that urinary [F2-isoprostanes] were positively associated with any AMD independent of age, sex, smoking, body mass index (BMI), systolic blood pressure (BP), total and high-density lipoprotein (HDL) cholesterol, and cardiovascular disease (CVD),” said researchers.

“The positive association was not linear, with a ceiling effect observed with higher levels, which implied conversely that lower levels of [F2-isoprostanes] were protectively associated with AMD,” they added.

The study included 238 patients with AMD (mean age 66.2±9.4 years; 63.0 percent male) and 390 controls (mean age 67.1±9.2; 64.4 percent male) distributed across four quartiles of urinary F2-isoprostane concentrations.

Compared to the first quartile, those in the second (odds ratio [OR], 1.96; 95 percent CI, 1.21 to 3.19), third (OR, 1.76; 1.08 to 2.88) and fourth (OR, 1.72; 1.03 to 2.88) quartiles had significant correlations with any AMD after adjusting for age, sex, smoking, BMI and other confounders. The trend was not linear (p=0.6 for trend). [Invest Ophthalmol Vis Sci 2017;58:2538-2543]

Repeated analysis showed that those in the second (OR, 2.32; 1.40 to 3.85), third (OR, 1.98; 1.19 to 3.31) and fourth (OR, 1.81; 1.06 to 3.09) also showed significant associations with early AMD (p=0.3 for trend).

While subgroup analysis showed that those with hypertension (OR, 1.84; 1.04 to 3.27), with BMI <25 kg/m2 (OR, 2.38; 1.24 to 4.57) and females (OR, 2.45; 1.04 to 5.76) had higher risks of any AMD, none of the associations were statistically significant.

Urinary F2-isoprostane levels were associated with drusen (OR, 2.06; 1.26 to 337) but not pigmentary lesions (OR, 1.41; 0.86 to 2.33).

“Several potential mechanisms have been postulated to explain the association between [F2-isoprostanes] and AMD,” investigators explained. Previous studies have established the relationship between F2-isoprostanes and atherosclerosis and inflammation, both of which are key drivers of AMD.

”In addition, [F2-isoprostanes] have also been shown to be associated with several proatherogenic factors including smoking, diabetes and hypertension,” they said.

Participants were recruited from thee Singapore Chinese Eye Study. Those with either early or late AMD were designated as cases while age- and sex-matched individuals without any AMD were recruited as controls. AMD was confirmed through fundus photography.

Concentrations of F2-isoprostanes and creatinine were measured from frozen urine samples. Logistic regression models were used to evaluate the association between F2-isoprostanes and AMD.

“[The findings] provide further evidence of a link between oxidative stress and AMD pathogenesis. If confirmed in prospective studies and diverse populations, [F2-isoprostanes] may serve as a potential systemic biomarker for predicting AMD,” said researchers.

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