Ophthalmologists Call for Retirement of ‘Cyanescence’ in Favor of Accurate ICG Fluorescence Terminology

Summary

Purpose of the Article

The authors — Nikhil Bommakanti, Jose S. Pulido, Howard F. Fine, and Yoshihiro Yonekawa — critically examine the term “cyanescence”, which has been used in ophthalmology to describe the fluorescence seen in indocyanine green (ICG) angiography. They ask whether it is a catchy shorthand or a scientifically inaccurate misnomer. Their conclusion: the term should be retired in favor of the precise and historically grounded term “fluorescence.”

Background: Naming in Ophthalmology

• Ophthalmologists have a tradition of coining memorable terms (e.g., ampiginous choroiditis — a blend of serpiginous choroiditis and APMPPE).
• “Cyanescence” refers to fluorescence from ICG dye, a member of the cyanine dye family — synthetic organic fluorophores with two nitrogen-containing heterocyclic rings, emitting in the visible to near-infrared spectrum.
• The question: does “cyanescence” help quickly identify ICG angiography, or does it introduce confusion and imprecision?

Fluorescein and ICG Angiography

• Both are invaluable diagnostic tools in retinal imaging.
• Shared principle: both rely on fluorescence — the emission of lower-energy light after absorbing higher-energy light.
• Problem: “Cyanescence” appears in educational materials like the American Academy of Ophthalmology’s Basic and Clinical Science Course, potentially perpetuating misunderstanding.

History of Fluorescence

• Definition: Rapid emission of lower-energy light after excitation by higher-energy light; a type of photoluminescence.
• Term origin: Coined in 1852 by George Gabriel Stokes after experiments on fluorspar; he noted emitted light has a longer wavelength than the excitation source (Stokes’ law).
• First recorded observation: 1565, Nicolás Monardes — blue coloration in water from Lignum nephriticum wood (later linked to natural fluorescence).
• Von Helmholtz (1855): Discovered the human fundus fluoresces, laying the groundwork for autofluorescence imaging.
• Fluorescein dye: Synthesized in 1871 by Adolf von Baeyer.
• ICG dye: Developed in 1957 by Brooker & Heseltine at Eastman Kodak.

Principles of Retinal Angiography

• Fluorescein angiography (FA):
  • Excitation: 465–490 nm
  • Emission: 520–530 nm
• ICG angiography (ICGA):
  • Excitation: ~790 nm
  • Emission: ~835 nm (near-infrared)
• Imaging systems use excitation filters to deliver only the excitation wavelength and emission filters to block reflected excitation light while capturing emitted fluorescence.

Why “Cyanescence” is Problematic

1. Incorrect wavelength implication:
   • “Cyanescence” suggests emission in the cyan range (490–520 nm).
   • Fact: ICG fluoresces in the near-infrared (~835 nm), far outside the cyan spectrum.
2. Misleading naming convention:
   • Implies naming emission after the dye (e.g., “cyanescence” from ICG).
   • This is inconsistent with scientific history — fluorescence was described before fluorescein or ICG existed.
   • Hypothetical: if rhodamine were used, would we call it “rhodaminescence”? Clearly illogical.
3. Inconsistency with other modalities:
   • Autofluorescence imaging uses no dye but is still called “fluorescence,” reinforcing that the term should describe the phenomenon, not the dye.

Evidence from Literature

• PubMed search results:
  • “Indocyanine green” + “fluorescence” → 5,876 results
  • “Indocyanine green” + “cyanescence” → 4 results (all in ophthalmology)
• Early descriptions of ICGA in ophthalmology and other medical fields consistently used “fluorescence”.

Clinical Relevance

• ICG angiography can reveal lesions invisible on color fundus photography or clinical exam.
  • Example: In sarcoid uveitis, ICGA showed numerous hypofluorescent spots not seen on initial exam, which later became clinically evident.
• The diagnostic power of ICGA is tied to its fluorescence properties, not to any “cyan” emission.

Historical Timeline (Key Milestones)

• 1565: Monardes observes blue fluorescence in Lignum nephriticum water.
• 1852: Stokes coins “fluorescence” and describes Stokes’ law.
• 1855: Von Helmholtz discovers fundus fluorescence.
• 1871: Von Baeyer synthesizes fluorescein.
• 1957: Brooker & Heseltine develop ICG.
• 1961: Novotny & Alvis describe fluorescein angiography in humans.
• 1973–1990s: ICGA techniques refined and widely adopted.

Authors’ Recommendation

• Retire “cyanescence” entirely.
• Use “fluorescence” for both fluorescein and ICG angiography.
• Rationale:
  • Scientifically accurate
  • Historically consistent
  • Avoids confusion in education and literature
  • Aligns with terminology in other medical fields

High‑Yield Takeaways

• Fluorescence = emission of lower-energy light after excitation; applies to both FA and ICGA.
• ICG emission is near-infrared (~835 nm), not cyan.
• “Cyanescence” is scientifically inaccurate and rarely used in literature.
• Terminology matters — precision improves clarity in clinical communication and education.
• Historical precedence: fluorescence described centuries before ICG existed.
• ICGA reveals pathology invisible to other imaging modalities, underscoring its diagnostic value.

Conclusion

While “cyanescence” may sound appealing, it is misleading both scientifically and historically. The authors make a strong case for terminological precision: call the phenomenon what it is — fluorescence — regardless of the dye used. This change would align ophthalmology with broader scientific usage, reduce confusion in training, and maintain clarity in research and clinical practice.

Bommakanti N, Pulido JS, Fine HF, Yonekawa Y. Time for “Cyanescence” to Become Cyanotic. It’s ICG “Fluorescence.” Ophthalmic Surgery, Lasers & Imaging Retina. 2025;56(7):394‑396. doi:10.3928/23258160-20250217-02