Chromovitrectomy

Definition and Concept

1. Posterior hyaloid face (vitreous cortex)
2. Epiretinal membranes (ERM)
3. Internal limiting membrane (ILM)

Why Chromovitrectomy Matters

Vital Dyes Used in Chromovitrectomy

1. Indocyanine Green (ICG)

• First dye used in chromovitrectomy (Kadonosono et al., 2000)
• Selectively stains the ILM (bright green color)
• ICG binds strongly to collagen type IV in the ILM
• Concerns: Significant retinal toxicity - causes retinal pigment epithelium (RPE) damage, increased apoptosis of ganglion cells, visual field defects. Toxicity related to osmolarity, light exposure, concentration, and prolonged contact time
• Most surgeons have now moved away from ICG due to its toxicity profile

2. Brilliant Blue G (BBG) - the current preferred ILM dye

• Approved for clinical use in many countries (marketed as Membrane Blue-Dual and ILM Blue)
• Selectively stains the ILM with high affinity (blue color)
• Significantly lower toxicity profile than ICG
• Reduces apoptosis compared to ICG
• Preferred dye for ILM peeling in macular hole surgery, macular pucker, and vitreomacular traction syndrome
• Recent safety concern (2025 systematic review, PMID 39566564): Phototoxicity has been reported with BBG and trypan blue; characteristic finding is macular pigmentary change with hypo- and hyper-autofluorescence, often sparing the fovea. Risk factors include prolonged surgery and repeat staining.

3. Trypan Blue (TB)

• FDA-approved for ERM removal
• Primarily stains epiretinal membranes (blue color); stains ILM less selectively than BBG
• Also stains the anterior lens capsule (used in cataract surgery as well)
• Lower ILM affinity compared to BBG - can be used for ERM visualization but may stain both ERM and ILM
• Toxicity: Generally considered safe at standard concentrations; phototoxicity risk at higher concentrations (see PMID 39566564)

4. Triamcinolone Acetonide (TA)

• A corticosteroid, not a traditional "dye" but functions as a vitreous stain
• Crystalline particles deposit on the vitreous cortex/posterior hyaloid, making it visible as white flakes
• FDA-approved (preservative-free formulation) for intraocular use
• Most useful for: visualizing the posterior hyaloid, confirming posterior vitreous detachment (PVD) induction, and checking for residual vitreous on the retinal surface
• No significant retinal toxicity at standard doses; IOP elevation is a known complication

5. Infracyanine Green (IFCG)

• An analogue of ICG dissolved in 5% glucose rather than water (adjusts osmolarity)
• Better osmotic compatibility with vitreous; less toxic than original ICG
• Still has some phototoxicity concerns

6. Sodium Fluorescein

• Used less commonly; stains the vitreous and posterior hyaloid
• Requires blue-light illumination (fluorescence)
• Concerns about toxicity limit widespread use

7. Patent Blue (PB)

• Stains ERM and ILM
• Less selective than BBG for ILM; used in some European centers
• Relatively low toxicity profile

8. Newer/Experimental Agents

• Lutein and anthocyanin from açaí fruit: natural dyes explored as potentially biocompatible alternatives
• Dye-stained perfluorocarbon liquids (PFCL): A recent application - adding dye to PFCL to enhance visualization of these intraoperative tools during complex retinal surgery

Summary of Dye-Tissue Selectivity

Clinical Indications

1. Macular hole surgery - ILM peeling (BBG preferred)
2. Epiretinal membrane peeling - ERM identification (trypan blue or BBG)
3. Diabetic tractional retinal detachment - vitreous base shaving, ERM/ILM dissection
4. Vitreomacular traction syndrome - posterior hyaloid and ILM identification
5. Pediatric vitrectomy - in very young eyes where PVD induction is difficult; TA for vitreous visualization
6. Proliferative vitreoretinopathy (PVR) - complex ERM/ILM removal
7. Giant retinal tears and complex retinal detachment - with PFCL staining

Injection Technique - Key Points

• Slow injection of dye into the vitreous cavity
• Keep injection away from the retinal surface (inject mid-vitreous or just above surface)
• Protect the macular hole when injecting - avoid direct contact with exposed retinal pigment epithelium
• Allow brief contact time, then wash out with balanced salt solution (BSS)
• Use the lowest effective concentration
• Avoid repeat staining (increases phototoxicity risk)
• Use air-assisted technique: fill the eye with air first, then apply dye in an air-fluid interface for more targeted staining (reduces spread, increases concentration at the target)

Complications and Toxicity

The "Ideal" Chromovitrectomy Dye

• High selectivity for the target tissue (ILM, ERM, or vitreous)
• Intense visible color for easy identification
• No retinal toxicity (cellular, mitochondrial, or phototoxic)
• Rapid washout from the eye
• No systemic toxicity following intraocular injection
• Stable shelf life, easy to prepare and use

Evidence Base (Key References)

• Bergamo VC et al. "Role of Vital Dyes in Chromovitrectomy." Asia Pac J Ophthalmol. 2020. [PMID 33252365]
• Farah ME et al. "The Use of Vital Dyes during Vitreoretinal Surgery - Chromovitrectomy." Dev Ophthalmol. 2016. [PMID 26502062]
• Bracha P, Ciulla TA, Baumal CR. "Vital Dyes in Vitreomacular Surgery." Ophthalmic Surg Lasers Imaging Retina. 2018. [PMID 30395665]
• Hernandez F et al. "Chromovitrectomy: an update." J Ophthalmic Vis Res. 2014. [PMID 25279128] (free PMC text)
• Neffendorf JE, Jackson TL. "Presumed phototoxicity from macular vital staining with BBG and Trypan Blue." Surv Ophthalmol. 2025. [PMID 39566564] (most recent systematic review - phototoxicity signal)