Abstract: Different genetic loci reported to contribute to the susceptibility of eyes to primary open angle glaucoma/normal transient glaucoma have been identified, and at least 15 loci, from juvenile open angle glaucoma gene to glaucoma 1opoen angle gene, have been linked to primary open angle glaucoma. Thus, it is reasonable to examine the association between primary open angle glaucoma and insulin like growth factor II gene polymorphisms and to investigate effect of polymorphism on the type of treatment. The present study included 80 cases with primary open angle glaucoma and 40 age and sex-matched controls. Cases subdivided into two equal groups: the first included 40 cases who were medically controlled; and the second included 40 cases who were surgically treated. All subjects had full ophthalmologic examination and were investigated for IGF-II polymorphism. AA was reported in 10%, 7.5.0% and 45.0% in subgroup A, B and control groups respectively; while GA was reported in 50.0%, 57.5%, and 32.5% in the same order and finally, GG was reported in 40%, 35.0% and 22.5% in subgroup in the same order with significant increase of GG and decrease of both AA and GA in study group when compared to control group. At the same time, there was no significant difference between subgroups A or B as regard Genotyping. The odds ratio was significantly different between study and control groups when comparing the frequency of GG to AA and GA to AA genotype. The odds ratio of G/G homozygote is 2.74 (95% confidence interval = 1.43-5.27). IGF-II gene polymorphism is associated with POAG. The most reasonable mechanism may be linked to oxidative stress. No effect of IGF-II polymorphism on treatment was observed.