Diabetic retinopathy and diabetic macular edema are the results of chronic damage to retinal neurovascular structures affected by the duration of diabetes . The pathophysiology of retinal damage remains uncertain but includes antioxidant imbalances and metabolic and neuroinflammatory insults . Genetic variation in antioxidant genes such as Mn-SOD leads to defect in the enzymatic activity and alteration of ROS detoxification, which may increase the risk of disease .
In the meantime, the results of this study showed a significant association between A16V polymorphism and the development of diabetic macular edema DME among diabetic patients with DR; the VV genotype was significantly higher in patients with DME than those without DME (P 0.018). This indicates that A16V polymorphism is a susceptible genetic factor for DME . This finding is consistent with Zhang, J. et al.  who, meanwhile, revealed the association of A16V polymorphism with DME in diabetic patients; they found that the A-allele frequency among DME patients was significantly lower than that of non-DME patients (P < 0.05) .
One possible explanation was that A16V polymorphism may be related to alteration of vascular permeability that causes DME rather than vascular occlusion related to DR, and A allele may protect against DME, and gene polymorphism was a susceptible genetic factor for DME . The retina in particular is susceptible to oxidative stress due to its high proportion of polyunsaturated fatty acids, high consumption of oxygen, and exposure to visible light .
The results of the current study showed that there was no statistically significant difference between diabetic patients with retinopathy and diabetic without retinopathy for the different genotypes or allele distribution as regards Mn-SOD A16V polymorphism. (AA was 20% versus 28%, AV was 47% versus 50%, and VV was 33% versus 22%) The results also showed no significant difference for the wild A allele (47.6% versus 36.5%) and mutant V allele (52.4% versus 63.5%) for peripheral DR and non-peripheral DR groups respectively (P 0.125, OR 0.5, 95th CI 0.35–1.14). This finding was in agreement with another study, which previously revealed that A16V polymorphism in Mn-SOD was not associated with DR but with a higher frequency of AA genotype in DR group (22.6% in cases versus 19.3% in controls); also, the allele frequency was not statistically significantly different between the cases and control groups (P 0.235) .
In contrast to the result of this study, Petrovic et al. revealed a significant association of Mn SOD polymorphism and DR as the VV polymorphic genotype was higher among the DR cases than in the control group 28.3% versus 16.1% respectively (P 0.006, OR 2.1, 95th CI1.2–3.4) . Also Ye et al.’s study showed that the frequencies of VV genotype and V allele were significantly higher in the DR group than that in the diabetic without retinopathy group (P 0.001). Their study showed that the V allele was associated with a 1.96-fold higher risk of development of DR (OR 1.96, 95th CI 1.29–2.97) .
In contrast to the hypothesis that the V allele could be a high-risk allele, Tian et al. in their study found a higher frequency of AA genotypes (P 0.03) and A allele (P 0.04) in the DR group (type 1 or type 2) compared to diabetics without retinopathy in the DR group .
The discrepancy between the results of this study and the previous results could be explained by the heterogeneity of the genetic background among populations, which supports the need for replication studies among all ethnic groups, particularly those with a high degree of heterogeneity. There was also a lack of standardization of the DR phenotype in different studies (i.e., studies did not show that the cases included were either peripheral DR-only or peripheral DR-type and non-peripheral DR-type; mild or severe form and, concerning for the control group, some studies enrolling diabetics without retinopathy, while others enrolling those with mild retinopathy background).
There is a possibility of interaction between Mn-SOD A16V polymorphism, and other environmental factors not taken into account in this study, such as glucose level, smoking status, and dietary and plasma antioxidant capacity. Results of some studies have shown that this antioxidant status can have an oxidative stress effect in some patients, so the antioxidant status associated with diabetes and related diseases still needs to be clarified .