It is generally believed that oxidative mechanisms play a major etiologic role in the development of age-related macular degeneration (AMD) and cataract. The etiology is a decrease in efficiency of the body's natural antioxidative mechanisms, including enzymatic, and non-enzymatic (antioxidant micronutrients). However, ophthalmologists continue to debate both the value of, and the best method for, optimizing anti-oxidative processes in the eye. For example, critics of recommending use of supplemental antioxidants sometimes suggest, even insist, that the epidemiologically studied associations between level of intake (both dietary, supplemental, or both) of antioxidant micronutrients and risk of cataract or AMD may not be causal - that decreased risk may be due to other factors in the food. One way of evaluating the role of oxidative stress in the disease process is to measure and evaluate the serum level of antioxidant enzymes in healthy patients and those with ocular disease. High systemic levels could be indicative of an increased level of oxidative stress. Investigators from the prospective Pathologies Oculaires Liées á l'Age (POLA) Study evaluated the association of age-related ocular pathologies with two antioxidant enzymes (1).

Methods:

During 1995 through 1997, participants were recruited in the French city of Séte on the Mediterranean. At the baseline evaluation, presence of AMD was determined by fundus-photograph grading using the Wisconsin system in 2,196 patients. Classification was collapsed for analysis into: none, early, or late (neovascular) AMD. LOCSII was used to determine presence of cataract (none, mild, moderate, severe). Erythrocyte superoxide dismutase (SOD) activity and plasma level of glutathione peroxidase (GPx) were measured using accepted laboratory technique. Percentiles of SOD and GPx were determined. Logistic regression was used to obtain adjusted Odd's ratios (high vs. low percentile of antioxidant enzyme) for presence of disease. Age, sex, and potential confounders were included in the statistical models.

Results:

Cataracts: A strong association was found between plasma GPx and prevalence of severe cataract. Subjects in the highest quintile of GPx had over a 6-fold higher prevalence of cortical cataract, and about a 2-fold higher prevalence of nuclear or mixed cataract. The Odd's ratios were all significant. AMD: Subjects in the highest 4 quintiles of GPx had a 10-fold greater prevalence of late AMD compared with the lowest quintile level. Excess risk was not found for early AMD. Highest quintile level of erythrocyte SOD activity was associated with about a 2-fold increased prevalence of nuclear cataract but not other cataract types or AMD.

Adjusted Odd's Ratios (1) (Highest vs lowest quintile level)

*Odd's of increased prevalence of disease among subjects in highest vs lowest quintile level of SOD or GPx
** The 4 higher vs the lowest quintile

The authors concluded that age-related eye diseases are linked to high levels of antioxidant enzymes, particularly GPx - which reduces mainly hydrogen peroxide and organic hydroperoxides. They suggested that a high concentration of antioxidant enzymes might be a marker that oxidative stress is present.

References

1. Delcourt C, Cristol JP, Leger CL et. al. Associations of antioxidant enzymes with cataract and age-related macular degeneration: the POLA study. Ophthalmology 1999;106:215-222.