However, these agents have shown limited efficacy against the cystic forms.[11][25] Due to the efficacy of these drugs against the Acanthamoeba, as well as their low toxicity to the cornea, they are commonly used as the first line medications in the treatment of AK.[11][21] Biguanides have also been found to act synergistically when used in combination with diamidines, with propamidine isethionate and hexamidine being the most commonly used.[26] A limitation of diamidine use is relative corneal toxicity with long term use.[11] A combined regimen of propamidine, miconazole nitrate, and neomycin has also been suggested.[27][28][29] Due to the potential for negative longterm visual outcomes with AK, therapy is usually started with a combination of a biguanide and a diamidine. Early use of high dose dual therapy helps to eliminate both trophozoite and cyst forms of the organism, while also preventing deep penetration of cysts into the corneal stroma. Cysts that are not eradicated from the cornea will cause reoccurrence.[3][15][11] The treatment is often initiated by instilling drops onto the surface of the eye every hour, 24 hours a day, for at least the first 48–72 hours.