Sodium fluorescein and indocyanine green are currently used as indicators for angiography of the retinal and choroidal vasculatures. This study was conducted to suggest additional indicator substances for this technique. Fifty-three dyes and biological stains were evaluated by the following criteria: intravenous LD50, histopathological damage from intravenous administration, binding properties in blood, in vivo metabolism of the substances, fluorescent and absorption spectra, and impurities detected with thin-layer chromatography. Male Swiss-Webster mice were used for the intravenous toxicity studies and for the metabolism and LD50 determinations. Several cyanines were modified by recrystallization with sodium iodide and an oxazine was sulfonated to improve their solubility and biocompatibility. Both techniques were successful in improving the intravenous toxicity and the solubility of the dyes in water. Iodination was not successful on the merocyanines. Patent blue VF and 8-hydroxy-1,3,6-pyrene trisulfonic acid trisodium salt were promising since both had impurities yet their LD50s exceeded 1000 mg/kg. Fluorones with two salt sites (NaO and COONa) were soluble at 10% or more in water. Nonhalogenated fluorones were excreted totally in the urine, while those with eight halogen atoms were removed via the biliary system. Those fluorones with six or less halogen atoms were excreted by both systems. Twenty-three of the fifty-three dyes were tolerated well enough for use in angiography of the ocular fundus. The majority of the substances had at least one impurity. In general, the cationic dyes were poorly tolerated; only 2 of the 23 acceptable substances were cationic. Those dyes that were anionic or dipolar were the best tolerated, with the dipolar molecules being cleared, at least partially, by the liver.
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