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The indicating physician and ophthalmologist must be aware of the possible side effects of Topamax therapy to determine the correct diagnosis and to administer treatment appropriately. To evaluate the results of 3 cases with persistent macular holes (MH) treated by 23-gauge vitrectomy, extension of internal limiting membrane peeling, a human amniotic membrane (hAM) plug insertion into the subretinal space through MH and expanding gas endotamponade. The diagnosis of persistent MH in three patients was unilaterally confirmed using SD-OCT.