Safety of sodium fluorescein for in vivo study of skin

Abstract

Background/purpose: Epicutaneous labeling or intradermal injection of the fluorescent sodium fluorescein is being used increasingly to investigate skin conditions in vivo when using non‐invasive devices such as confocal scanning laser microscopy. Sodium fluorescein was used intravenously for decades for the examination of the vasculature of the ocular fundus (fluorescein angiography) and as eye drops for diagnosis of corneal erosions. The objective of this article is to systematically review the literature on fluorescein and conclude its safety in cutaneous research to support research planning and evaluations by ethics committees. Methods: A number of databases and the literature about safety and toxicity of fluorescein in animal and human studies were searched and analyzed. Results: Side effects or adverse events reported in the literature were related to intravenous bolus injection. Transient nausea and vomiting may occur. Other adverse events such as vasovagal reaction, cardiac or respiratory effects and anaphylaxes are extremely rare but may be fatal. Intradermal injection may cause mild itch or pain; systemic adverse event was reported. Epicutaneous labeling is associated with no reported problem. A typical local dose is several magnitudes of order smaller than a typical intravenous dose. Conclusion: Fluorescein has been used for many years in medicine for diagnostic purposes and is widely safe, albeit intravenous bolus injection may cause serious adverse reactions. In the literature, we could not trace reports of local or systemic side effects of topical sodium fluorescein except itch and pain on intradermal injection, however, dependent on the fluorescein preparation used. Local dermal application of fluorescein for in vivo study of skin may be considered widely safe.

Combining in vivo reflectance with fluorescence confocal microscopy provides additive information on skin morphology

“…in our study we used SFl, which has been applied safely for decades as a contrast agent for ophthalmic angiography [17]. after intradermal injection the rapid extracellular distribution of the dye enabled an immediate evaluation.…”

Spectral imaging reveals microvessel physiology and function from anastomoses to thromboses

“…11,12 Several optical techniques are useful for direct imaging of microvascular morphology and function either clinically or in preclinical animal models. Intravascular fluorescence contrast agents can be used for imaging of microvessel morphology in some tissues with wide-field fluorescence imaging ͑e.g., retinal angiography with sodium fluorescein 13 ͒ or multiphoton microscopy using dyes or quantum dots.…”

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

“…25 This dye can be safely administered intravenously in humans and has been used clinically in multiple applications. 20 The use of fluorescein as a tumor marker for resection has been widely investigated for multiple tumor types, including skull base tumors, 6 metastatic brain tumors, 21 and high-grade gliomas. 10,11,16,23,24 Fluorescein has not been previously demonstrated as an agent that bioaccumulates in a glioblastoma flank xenograft model.…”