Diagnostic Agents

Solutions commonly used in the examination and diagnosis of external ocular diseases include fluorescein, 2%; lissamine green, 1%; and rose bengal staining as impregnated paper strips. The first 2 stains outline defects of the conjunctival and corneal epithelium, whereas rose bengal staining indicates abnormal devitalized epithelial cells. A stinging sensation with instillation of these eyedrops is common.

Rose bengal has significant antiviral activity. Therefore, diagnostic use of rose bengal before viral culture may preclude a positive result, and its use to grade keratitis in the study of new antiviral drugs is discouraged.

For the study of retinal and choroidal circulation as well as abnormalities in the retinal pigment epithelium (RPE), sodium fluorescein solution in a concentration of 5%, 10%, or 25% is injected intravenously. Fundus fluorescein angiography is helpful in diagnosing various vascular diseases and neoplastic disorders. Adverse effects range from localized skin reactions to hypersensitivity and allergic reactions. The most common adverse effect is nausea, occurring in up to 10% of patients.

Indocyanine green (ICG), a tricarbocyanine dye, is approved for the study of choroidal vasculature in a variety of choroidal and retinal disorders. ICG angiography is particularly helpful in identifying and delineating poorly defined choroidal neovascular membranes in age-related macular degeneration (AMD). ICG angiography can also be used to evaluate patients with anterior scleritis. Typically, 25 mg of dye is injected as an intravenous solution. ICG is mildly toxic; adverse effects include localized skin reactions, sore throat, and hot flushes. Individual cases of severe adverse effects, such as anaphylactic shock, hypotension, tachycardia, dyspnea, and urticaria, have been reported.

ICG and trypan blue dye are useful for delineating the anterior capsule during phacoemulsification of mature cataracts. Although the FDA has approved trypan blue as an anterior capsule stain during surgery, administration of ICG for this purpose constitutes an off-label use.

ICG, trypan blue, brilliant blue G (BBG), and triamcinolone acetonide are also utilized to facilitate internal membrane peeling in macular-hole repair, although their use in this way is off-label. The preservative-free formulation of triamcinolone acetonide is FDA approved for intraoperative visualization of the vitreous. Despite considerable literature raising concerns about the toxicity of ICG dye in the retina and RPE, good surgical and visual results have been reported. The toxicity of ICG on cultured RPE cells may be related to the hypoosmolarity of the solvent. Short exposure of trypan blue has not had a toxic effect on cultured RPE cells. However, trypan blue does not appear to stain the internal limiting membrane as effectively as ICG does. Exposure of the retina to the dye and pooling at the macular hole should be minimized to reduce concerns about toxicity to the retina.

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Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.