Vitreous Substitutes and Tamponades

Quiz: Pretests on Vitreous Substitutes and Tamponades

 

Vitreous substitutes and tamponades are essential tools in modern vitreoretinal surgery, occupying the vitreous cavity following vitrectomy for conditions such as retinal detachment, macular hole, and proliferative diabetic retinopathy. Depending on the indication, these agents may serve as:

• Short-term tamponades: expansile gases such as sulfur hexafluoride (SF₆) and perfluoropropane (C₃F₈).
• Long-term tamponades: silicone oils of varying viscosities, including heavy silicone oils for inferior pathology.
• Intraoperative adjuncts: perfluorocarbon liquids, used transiently as a “third hand” to stabilize the retina or occasionally retained for a few days postoperatively.

Emerging materials such as hydrogels and hyaluronan derivatives are under active investigation. These biomimetic polymers aim to replicate the viscoelastic and optical properties of the native vitreous, with potential advantages in biocompatibility, biodegradability, and drug delivery.

Despite their utility, vitreous substitutes are not without complications. Cataract progression, secondary glaucoma, emulsification, inflammation, and migration remain significant concerns, underscoring the need for careful patient selection and timely removal when indicated.

This review synthesizes the current literature on vitreous substitutes and tamponades, detailing their composition, physical properties, surgical applications, and limitations, while also highlighting future directions in the development of next-generation vitreous replacements.

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The vitreous body constitutes nearly 80% of the ocular volume and is composed of ~99% water. The remaining 1% consists of a complex extracellular matrix of collagens (predominantly type II), hyaluronic acid, structural glycoproteins (fibrillin, laminin, fibronectin), salts, and small amounts of glucose, ascorbic acid, and other metabolites.

• Collagen network: Provides the scaffold that maintains vitreous structure and viscoelasticity.
• Hyaluronic acid: Binds to collagen fibrils, spacing them apart and preserving transparency.
• Electrolytes and nutrients: Support metabolic homeostasis and antioxidative defense.

Functionally, the vitreous contributes to:

• Structural support (maintaining globe shape, elasticity, and ocular growth)
• Nutritional/metabolic support for adjacent tissues
• Optical clarity for unhindered light transmission
• Biomechanical roles in accommodation and shock absorption

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🔹 Vitreous Substitutes in Surgery

In modern vitreoretinal surgery, removal of the native vitreous necessitates replacement with vitreous substitutes. These agents restore intraocular volume and, in some cases, provide tamponade—a mechanical barrier across retinal breaks to prevent fluid ingress into the subretinal space.

• Vitreous substitute: Any material used to occupy the vitreous cavity (e.g., balanced salt solution, hydrogels, silicone oil, gases).
• Vitreous tamponade: A subset of substitutes (gases, silicone oils, heavy liquids) that exert surface tension and buoyancy, sealing retinal breaks until chorioretinal adhesion forms.

Key distinction: Balanced salt solution and hydrogels can replace volume but lack buoyancy, so they are not true tamponades.

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🔹 Classification of Vitreous Substitutes

Category	Examples	Typical Use
Gases	Air, SF₆, C₂F₆, C₃F₈	Short- to medium-term tamponade; macular hole, RD
Liquids	Balanced salt solution, perfluorocarbon liquids, semi-fluorinated alkanes, silicone oil	Intraoperative manipulation (PFCL), long-term tamponade (silicone oil)
Polymers	Natural (hyaluronic acid, chitosan), synthetic (PEG, smart hydrogels)	Experimental substitutes aiming to mimic native vitreous properties

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Quiz: Pretests on Physical Properties of Intravitreal Gases

 

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Intraocular Gases as Vitreous Tamponades

🔹 Historical Perspective

• 1911 – Ohm: First reported the use of sterile air injection for retinal detachment repair.
• 1973 – Norton: Introduced sulfur hexafluoride (SF₆), noting its longer tamponade duration compared to air.

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🔹 Types of Intravitreal Gases

• Non-expansile: Air
• Expansile: SF₆, C₂F₆, C₃F₈

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🔹 Physical Properties

• Surface tension: Maintains bubble integrity and seals retinal breaks.
• Buoyancy: Gas rises, exerting upward tamponade; positioning is critical.

• Contact angle:

  • Air/gas bubbles: ~38.8° → larger retinal contact area.

  • Silicone oil: ~16° → smaller contact area, but persists until removed.

• Duration:
  • Air: absorbed in days.
  • SF₆: ~1–2 weeks.
  • C₂F₆: ~3–4 weeks.
  • C₃F₈: ~6–8 weeks.

 

 

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🔹 Clinical Indications

• Retinal detachment (RD)
  • Pneumatic retinopexy for superior breaks (isolated, ≤1 clock hour, no PVR).
  • Persistent detachment after scleral buckle.
  • Inferior breaks (fishmouth tears) → expansile C₃F₈.
• Macular hole (MH)
  • SF₆ and C₃F₈ both effective; air inferior for holes ≤400 µm.
  • C₃F₈ useful for persistent MHs post-vitrectomy.
• Optic pit maculopathy
• Displacement of submacular hemorrhage
  • Gas bubble displaces blood away from fovea; requires careful case selection.

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🔹 Advantages

• Air
  • Short duration → faster visual rehabilitation.
  • Safer for patients at high altitude or requiring early air travel.
  • Lower risk of cataract progression.
• Expansile gases
  • Longer tamponade duration → higher success in complex RDs and MHs.
  • Enable outpatient pneumatic retinopexy with high reattachment rates.

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🔹 Disadvantages

• Positioning: Requires strict postoperative head positioning, challenging for elderly/frail patients.
• Visual impairment: Temporary due to refractive index mismatch.
• Lens changes: Vacuoles, posterior capsular opacities, posterior subcapsular cataracts.
• IOP rise: From overfill, expansile concentration, or anterior chamber migration.
• Gas migration: Into subconjunctival space (hypotony) or subretinal space (optic pit/coloboma).
• Air travel risk: Expansion with altitude → IOP spikes, CRAO risk.
  • Avoid flying for ~2 weeks after SF₆, ~6 weeks after C₃F₈.

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🔹 Recent Advances

• Shaving vitreous under air: Improves peripheral vitreous removal without scleral indentation (challenging for novices).
• Pneumatic vitreolysis (PVL): Gas injection to release focal vitreomacular traction or close small stage 2 MHs (~⅓ closure rate).

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Quiz: Pretests on Silicone Oils

 

🔹  Silicone Oil as Vitreous Substitute

Historical Background

• Introduced in 1962 by Armaly and Cibis.
• Chemical: Polydimethylsiloxane (PDMS).
• Specific gravity: 0.97 g/mL (lighter than water).
• Refractive index: similar to vitreous.

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Physical Properties

• Types and viscosities: The most widely used are 1000, 1500, and 5000 centistokes (cSt).

  • 1000 cSt: lower viscosity, easier and faster to inject and remove, but more prone to emulsification.

  • 5000 cSt: higher viscosity, more resistant to emulsification, but harder to handle surgically and associated with more corneal abnormalities.

  • Both have similar specific gravity (~0.97 g/mL, lighter than water) and surface tension, but differ in molecular weight (37 kDa vs 65 kDa).

• Other variants: Commercially available oils include Oxane 1300 and Oxane 5700.

• Heavy silicone oils (HSOs): e.g., Densiron 68, Densiron Xtra, Oxane HD. These are mixtures of silicone oil with semifluorinated alkanes, making them denser than water and particularly useful for tamponading inferior retinal detachments.

  • • Inflammation: HSOs are associated with a higher inflammatory response compared to conventional silicone oil.

    • Intraocular pressure (IOP): They carry a greater risk of IOP elevation.

    • These complications limit their routine use, reserving them for selected complex cases.

• General properties:

  • On injection, silicone oil forms a single continuous bubble with high interfacial tension, which helps the aqueous humor tamponade retinal breaks.

Highly purified silicone oils are stable, long‑term substitutes with constant volume.

 

Comparison of Various Silicone Oils

Type / Variant	Viscosity (cSt)	Molecular Weight	Specific Gravity	Handling Characteristics	Emulsification Tendency	Clinical Notes
Standard Silicone Oil	1000	~37 kDa	0.97 g/mL (lighter than water)	Easier and faster to inject and remove; flows readily through cannulas	Higher risk of emulsification	Widely used; convenient for surgery but less stable long-term
Standard Silicone Oil	1500	Intermediate	0.97 g/mL	Handling between 1000 and 5000 cSt	Moderate emulsification risk	Less commonly used than 1000 or 5000 cSt
Standard Silicone Oil	5000	~65 kDa	0.97 g/mL	More difficult to inject/remove; slower egress at sclerotomy	Lower risk of emulsification	More stable in eye; associated with more corneal abnormalities
Commercial Variants	Oxane 1300, Oxane 5700	Varies	0.97 g/mL	Highly purified, stable	Low emulsification	Long-term vitreous substitute with constant volume
Heavy Silicone Oils (HSO)	e.g., Densiron 68, Densiron Xtra, Oxane HD	Higher viscosity blends	>1.0 g/mL (denser than water)	More viscous, stable, tolerated	Lower emulsification than older HSOs, but higher inflammation/IOP risk	Useful for inferior retinal detachments and complex cases

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🔹 Key Takeaways

• Viscosity trade-off:
  • Lower viscosity (1000 cSt) → easier handling, higher emulsification.
  • Higher viscosity (5000 cSt) → more stable, harder to handle, more corneal issues.
• Heavy silicone oils: Designed for inferior pathology, but carry higher risks of inflammation and IOP rise.
• All standard oils share similar specific gravity (~0.97 g/mL) and surface tension, differing mainly in viscosity and stability.

 

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Clinical Indications

• Rhegmatogenous RD with severe PVR, retinotomies, or poor positioning compliance.
• Tractional RD (esp. monocular patients, NVG, phthisis risk).
• Trauma: reduces risk of PVR, hemorrhage, endophthalmitis.
• Endophthalmitis: antimicrobial and fungistatic properties.
• Myopic macular hole RD, coloboma-related RD, viral retinitis, chronic uveitis with hypotony.
• Heavy silicone oils: inferior RD, complex detachments.

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• Efficacy in severe PVR

  • Silicone oil and C₃F₈ are both effective in reattaching the retina and improving visual function.

  • Both have relatively low complication rates.

  • Silicone oil is superior to SF₆ in these challenging cases.

• Special scenarios favoring silicone oil

  • Retinotomies: In eyes requiring retinotomy to flatten the retina, silicone oil increased the chance of visual recovery and reduced hypotony at 6 months.

  • Severe anterior PVR: Silicone oil provides more stable outcomes.

  • Poor compliance with postoperative positioning: Oil is advantageous because it does not rely on strict head positioning like gases.

  • Patients needing to fly or travel to high altitudes: Silicone oil is safer since it does not expand with pressure changes, unlike gases.

• Scenarios favoring C₃F₈

  • Breaks at the edge of a scleral buckle

  • Abnormal iris diaphragm

  • Superior retinal breaks In these cases, the buoyancy and distribution of C₃F₈ gas make it more effective than silicone oil.

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🔹 Why Silicone Oil in TRD?

• Indications:

  • Monocular patients (where preserving the only seeing eye is critical).

  • Eyes with neovascular glaucoma (NVG) or high risk of phthisis.

  • Cases where all vitreoretinal traction cannot be removed or the retina cannot be fully reattached during pars plana vitrectomy.

• Mechanism beyond tamponade:

  • Silicone oil acts as a barrier preventing the migration of vasoproliferative factors (VEGF and others) from the posterior to the anterior segment.

  • This reduces the risk of anterior segment neovascularization, which is a major cause of secondary glaucoma and poor prognosis in TRD.

🔹 Evidence (McCuen et al.)

• In a landmark study:

  • 83% of eyes with anterior proliferation and neovascularization had stabilization of neovascularization under long‑term silicone oil.

  • 56% achieved retinal attachment.

• This shows silicone oil is not only a mechanical tamponade but also has a biological protective effect in ischemic, proliferative eyes.

🔹 Clinical Takeaway

Silicone oil is particularly valuable in TRD with ischemic drive (e.g., proliferative diabetic retinopathy, NVG). It provides both:

1. Mechanical support when complete traction relief is not possible.

2. Biological benefit by limiting anterior migration of angiogenic factors, thereby reducing neovascular complications.

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🔹 Antimicrobial Properties

• In vitro studies show that silicone oil itself has bactericidal and fungistatic activity.

  • 1000 cSt oil: complete bactericidal effect by day 21.

  • 5000 cSt oil: complete bactericidal effect by day 30.

• Both viscosities inhibit multidrug-resistant organisms.

• They also demonstrate fungistatic properties, preventing fungal proliferation and enhancing the efficacy of intravitreal antifungal drugs.

• This makes silicone oil a useful adjunct in infectious endophthalmitis, especially fungal cases.

🔹 Myopic Macular Hole (MH) and Retinal Detachment

• Silicone oil is effective in myopic macular holes and retinal detachments secondary to MHs in highly myopic eyes.

• An additional benefit: the refractive index of silicone oil induces a hyperopic shift, which can sometimes be advantageous in high myopia.

🔹 Complex Retinal Cases

• Preferred tamponade in:

  • Coloboma-related retinal detachment

  • Breaks associated with viral retinitis

• These eyes often require long-term tamponade, especially in monocular patients where preserving the globe is critical.

🔹 Chronic Uveitis with Hypotony

• Silicone oil can serve as a long-term vitreous substitute in eyes with chronic uveitis and hypotony, helping to maintain intraocular pressure and prevent progression to phthisis bulbi.

 

 

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🔹 Clinical Takeaway

• Silicone oil is the tamponade of choice in complex RRD with severe PVR, retinotomies, poor positioning compliance, or when air travel is anticipated.

• C₃F₈ is preferred in superior pathology or anatomical configurations (edge buckle breaks, iris diaphragm abnormalities).

• SF₆ is less effective in severe PVR compared to both silicone oil and C₃F₈.

Advantages

• Long-term tamponade (only accepted long-term substitute).
• High surface tension, transparency, low toxicity.
• Rapid visual rehabilitation, clear fundus visualization.
• Shorter prone positioning required.
• Suitable for patients unable to posture or needing to travel by air.

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Disadvantages / Complications

• Emulsification → cataract, keratopathy, glaucoma, inflammation.
• Anterior migration in aphakic eyes → corneal decompensation.
• Ocular hypertension/glaucoma (esp. with overfill or 5000 cSt).
• Keratopathy (band-shaped, vascularization).
• Unexplained visual loss (possibly DCP ischemia).
• Intracranial migration (rare, in anomalous discs).
• Need for timely removal once retina is stable to reduce complications.

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Quiz: Pretests on PFCL

 

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🔹 What PFCLs Are

• First described: Chang et al., 1987, for giant retinal tears and proliferative vitreoretinopathy.
• Chemistry: Synthetic fluorinated hydrocarbons (C–F bonds).
• Physical properties:
  • High specific gravity → heavier than water, so they sink and flatten the retina.
  • High viscosity → stable intraocular bubble.
  • Transparent, immiscible with aqueous/blood, refractive index different from saline.
• Examples: Perfluoro‑n‑octane (PFO), perfluorodecalin (PFD), perfluoroethylcyclohexane, perfluorotributylamide, perfluorooctylbromide (PFOB).

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🔹 Indications

• Giant retinal tears (GRTs): Prevents flap slippage, unfolds folded retina.
• Proliferative vitreoretinopathy (PVR): Opens closed funnels, stabilizes retina, reduces iatrogenic retinotomies.
• Diabetic vitrectomy: Stabilizes retina for membrane peeling, flattens folds.
• Macular surgery: Stabilizes ILM flap, treats macular holes, myopic foveoschisis, MH‑related RD.
• Suprachoroidal hemorrhage: Helps extrude liquefied blood.
• Intraocular foreign body removal: Protects posterior pole, stabilizes retina.
• Pediatric eyes: Induces posterior vitreous detachment.
• Medium‑term tamponade: Recent studies (e.g., Shukla et al.) show PFO tamponade can be viable in very complex RDs with high risk of redetachment or prolonged silicone oil use.

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🔹 Advantages

• High density: Flattens retina, unrolls folds, displaces subretinal fluid (sometimes avoids retinotomy).
• Transparency: Allows precise surgical maneuvers.
• Immiscibility: Maintains clear field despite bleeding.
• Interface visibility: PFCL–BSS interface aids intraocular maneuvers.
• Laser compatibility: Endolaser can be performed under PFCL.
• Direct PFCL–silicone oil exchange: Reduces risk of slippage in GRTs.
• Low viscosity: Easy injection/aspiration, even with small‑gauge vitrectomy.

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🔹 Disadvantages

• Must be removed at end of surgery (unless used as medium‑term tamponade in select cases).
• Intraoperative IOP spikes if injected too quickly (prevented with dual‑bore cannula).
• Contaminants: Linked to necrotizing inflammation, vascular occlusion, optic atrophy.
• Intrinsic risks:
  • Mechanical/chemical damage to cornea and trabecular meshwork → ↑ IOP.
  • Inflammatory reaction (worse with longer tamponade).
  • Migration into anterior chamber (visual axis obstruction) or subretinal space (especially under fovea).
  • Secondary glaucoma, retinotoxicity.
• Comparative toxicity: Perfluorodecalin (PFD) less toxic than perfluorooctane (PFO).

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🔹 Future Directions

• Oxygenated PFCL perfusion: May improve outcomes in ischemic retina and diabetic vitrectomy by reducing bleeding and stabilizing retina.
• Hydrogenated hydrofluorocarbon liquids (HFCLs): Alternatives with lower specific gravity and higher lipophilicity, potentially safer.
• “Double fill” techniques: Combining PFCL with silicone oil or semifluorinated alkanes to tamponade both superior and inferior retina simultaneously.

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🔹 Clinical Takeaway

PFCLs are indispensable intraoperative tools in vitreoretinal surgery, especially for giant retinal tears, PVR, and complex detachments. While traditionally removed at the end of surgery, medium‑term tamponade with PFO is emerging as an option in select, high‑risk cases. Their unique physical properties make them invaluable, but their toxicity and inflammatory risks demand careful handling and complete removal unless specifically indicated.

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Reference: Shettigar, Manoj P.; Dave, Vivek Pravin; Chou, Hung‑Da; Fung, Adrian; Iguban, Eleonore; March de Ribot, Francesc; Zabala, Camille; Hsieh, Yi‑Ting; Lalwani, Geeta. Vitreous substitutes and tamponades – A review of types, applications, and future directions. Indian Journal of Ophthalmology. 2024 Aug; 72(8):1102‑1111. DOI: 10.4103/IJO.IJO_2417_23