International Journal of Ophthalmic PathologyISSN: 2324-8599

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Review Article, Int J Ophthalmic Pathol Vol: 5 Issue: 3

Vitreous Substitutes in Vitreoretinal Surgeries

Shalu Gupta*, Rajeev Tuli and Sharma RK
Department of Ophthalmology, Dr. Rajendra Prasad Government Medical College, Kangra at Tanda 176 001, Himachal Pradesh, India
Corresponding author : Dr. Shalu Gupta
MS (Resident), Department of Ophthalmology, Dr. Rajendra Prasad Government Medical College, Kangra at Tanda 176 001, Himachal Pradesh, India
Tel: +91 89882 26026
Fax: +91 1892 224906
E-mail: [email protected]
Received: August 22, 2016 Accepted: September 07, 2016 Published: September 13, 2016
Citation: Gupta S Tuli R, Sharma RK (2016) Vitreous Substitutes in Vitreoretinal Surgeries. Int J Ophthalmic Pathol 5:3. doi:10.4172/2324-8599.1000186


The vitreous is an inert, transparent, colorless, hydrophilic gelatinous structure that fills the space between the lens and the retina. It maintains the intra ocular pressure and is important in maintaining transparency of the media for maximum photon transmission to the retina. With advancing age the vitreous undergoes liquefaction resulting in its transformation from a formed gel form to fluid form. Vitreous substitutes or the so called tamponading agents are used in vitreo-retinal surgery to restore intraocular pressure and provide intraocular tamponed. The type of substitute used is dependent on the individual clinical situation. The proper vitreous substitute for long-term drug delivery system should either reduce or eliminate the need for multiple intravitreal injections.

Keywords: Vitreous substitutes; Tamponade; Intravitreal; Retinal detachments; Vitreo-retinal surgery; Emulsification


Vitreous substitutes; Tamponade; Intravitreal; Retinal detachments; Vitreo-retinal surgery; Emulsification


Vitreous substitutes or the so called tamponading agents are used in vitreo-retinal surgery to restore intraocular pressure and provide intraocular tamponade. With advancing age the vitreous undergoes liquefaction resulting in its transformation from a formed gel form to fluid form. In case of Retinal Detachments (RD), the vitreous undergoes inflammatory changes and acts as a source of traction resulting in non-resolution of RD. In such cases there is need for removal of vitreous & vitreous substitutes are required.
The vitreous is an inert, transparent, colorless, hydrophilic gelatinous structure that fills the space between the lens and the retina. It occupies 2/3rd of the eye by volume (4 ml). It is composed of 98-99% water, rod like collagen and inter-fibrillary hyaluronic acid, pH of 7.0-7.4, viscosity 4.200 cm3/g & refractive index 1.3345-1.3348. The vitreous can be divided into two parts, the cortex and the nucleus (the main vitreous body). The part of the vitreous about 4 mm across the ora serrata is called as vitreous base, where the attachment of the vitreous is strongest.

Functions of Vitreous

It is a hydrophilic gel that mainly serves the optical functions. It maintains the intra ocular pressure and mechanically stabilizes the volume of the globe. It is a pathway for nutrients to reach the lens & retina and also helps as a shock absorber.
Ideal vitreous substitute
Ideal Vitreous Substitute would mimic the native vitreous in both form and function (easily manipulable during surgery) [1]. It should have similar viscoelastic properties and be able to maintain the intraocular pressure and support the intraocular tissues. The ideal vitreous substitute should not induce any toxic reactions and should remain biocompatible for long-term use. For practical reasons, the ideal substitute should be easily available, stable during storage, injectable through a small syringe and available at a reasonable cost.
Classification of Vitreous Substitutes
Based on physical properties
i. Aqueous miscible e.g. balanced salt solution (BSS), hyaluronic acid solutions
ii. Aqueous immiscible:
a. Gases : air, sulfur hexafluoride (SF6), perfluoro-propane (C3F8)
b. Liquids:
• Those that are lighter than water : polydimethylsiloxane (PDMS) [silicon oil]
• Those that are heavier than water : fluorinated silicone oils, perfluorocarbon liquids (PFCL) and semifluorinated alkanes (SFA)
The relative specific gravity for each of these tamponades is: air ~ gas << silicone oil > water ~ saline < PFC liquids. The type of substitute used is dependent on the individual clinical situation.

Currently used Vitreous Substitutes

Physiological solutions
Physiological solutions such as Ringer’s lactate or balanced salt solution (BSS) can be used as substitute after vitrectomy for endophthalmitis or uncomplicated vitreous hemorrhage.
Air: The use of intraocular gases for the treatment of retinal detachment was reported as early as 1911 by Ohm [2], by injecting air into the vitreous cavity after drainage of sub-retinal fluid. Air is commonly used internal tamponade in uncomplicated cases. It is absorbed within 3 days & is useful in pneumatic retinopexy.
Expansile gas-based substitute
Expansile Gas-Based Substitute is preferred over air in complex cases requiring prolonged intraocular tamponade. The indications for the use of intraocular gas in retinal detachment surgery have not changed since originally described by Norton in 1973 [3,4]. Recent interest is in treating uncomplicated rhegmatogenous retinal detachment without permanent sclera buckling stimulated Hilton and Grizzard [5] to modify Rosengren’s technique by injecting a small expanding gas bubble without drainage of sub-retinal fluid.
Intraocular gases are the most commonly used temporary vitreous replacement [6,7]. The type of intraocular gas used should be selected to solve the retinal problem in each individual case. Gases of shorter intraocular longevity are recommended for use in non-vitrectomized eyes. The versatility of gases with variable expansile capability and longevity is not available with other vitreous substitutes. The high surface-tension characteristics and high buoyant force of these gases provide the best internal flattening ability. Techniques of fluidgas exchange are safe and effective methods for treating recurrent retinal detachment without reoperation. The most commonly used intraocular gases are Sulphur hexafluoride, perfluoro-propane etc. with surface tension of 70 dynes/ cm2 [8,9]. Sulphur hexafluoride (SF6) [5 times heavier than air] doubles its volume at 100% and lasts 10-14 days, perfluoro-ethane (C2F6) triples its volume and lasts 30-35 days, perfluoro-propane (C3F8) [6 times heavier than air] quadruples its volume and lasts 55-65 days & also is used in isovolumetric concentration (20-30% SF6 and 12-16% for perfluoropropane). However, post-oppositioning of patient is required. There can be unpredictable rise of IOP in the immediate post-opperiod which can result in retinal vascular occlusion and if the patient rapidly ascends to a higher altitude, gas expansion to dangerous levels can occur. Cataract formation and corneal endothelial damage are other disadvantages.
Perfluorocarbon Liquids (PFCLs)
Perfluorocarbon Liquids (PFCLs) are fluorinated, synthetic, carbon containing compounds with 1.6 to 2.1 specific gravity and low viscosity. Perfluorocarbon liquids (PFCLs) were initially developed as blood substitutes because of their large capacity for transporting oxygen and biological inertness. In the 1980s, perfluorocarbon liquids were investigated for tamponade of inferior retinal tears and reattachment of the retina. Chang et al. [10,11] were the first to study PFCL use in humans. The use of PFCLs as an instrument for manipulating complicated retinal detachments represents an important development in vitreoretinal surgery. The most commonly used PFCLs are perfluorodecalin (PFD), perfluorohexyloctane (F6C8), perfluoroper hydrophenanthrene, and octafluoropropane and perfluoro-n-octane. The various perfluorocarbon liquids currently used in vitreous surgery have different physical and optical properties. Perfluoro-n-octane, because of the better visibility it allows, low viscosity, and high vapor pressure, is most commonly used.
The high specific gravity of PFCLs makes them effective for the intraoperative repair of complex retinal detachments, acts as surgical third hand during removal of proliferative membranes and stabilizes macula while dissecting the anterior PVR membranes [12,13]. These are also useful in repair of giant retinal tears, retinal detachments caused by ocular trauma, dislocated crystalline and intraocular lenses & rhegmatogenous retinal detachments without PVR. In case of suprachoroidal hemorrhage PFCLs produce a posterior tamponade effect pushing the suprachoroidal hemorrhage out through anterior sclerotomies & in submacular hemorrhage, may facilitate the removal of liquefied submacular hemorrhage by displacing the hemorrhage away from the fovea. PFCLs allow for easy intraoperative tissue manipulation, injection and removal. Anterior and posterior segment complications are uncommon. However, their use is limited to intraoperative period due to toxicity & iatrogenic retinal breaks and subretinal migration of PFCLs are known to occur by forced injection.
Silicone Oils (SO)
Silicone Oils (SO) are hydrophobic substances with a specific gravity slightly less than water (0.97 g/mL) and a refractive index of 1.4, currently accepted for long-term vitreous replacement with lesser complication rates. SO’s have high surface tension, easy removal, low toxicity and transparency. It creates a tamponade effect on the superior retina, with a 70% success rate in preserving anatomical integrity.
SO is useful in case of retinal detachment complicated by severe proliferative vitreoretinopathy, in the complications of severe proliferative diabetic retinopathy & in the repair of macular holes. In case of repair of giant retinal tears, it acts in two ways, first as an instrument to facilitate unfolding and flattening of the retinal detachment and tear, and secondly as a long-term tamponade. It is also useful in retinal detachment associated with choroidal coloboma, chronic uveitis with profound hypotony, infectious retinitis, trauma, complicated pediatric retinal detachment and endophthalmitis. However, because of low specific gravity, tamponade of the inferior retina is difficult. Emulsified droplets can adhere to a silicone IOL [14]. Post-operative cataracts, anterior chamber migration, corneal decompensation, band keratopathy, glaucoma from pupillary block or overfilling and hypotony from underfilling can occur.
As a general principle, silicone oil should be removed once the objectives of the tamponade have been achieved and the retinal status is stable in order to minimize the long-term complications associated with its use. In most cases, silicone oil should be removed between 6 weeks and 6 months, if the retina remains attached and the intraocular pressure is normal. However, oil can be left in place in case of partial recurrent retinal detachment, if the anatomic or visual prognosis is very poor, if the eye is chronically hypotonous and in cases associated with trauma. The Silicone Study [15,16] was conducted to evaluate the use of various methods of retinal tamponade, together with pars plana vitrectomy techniques on eyes with complex retinal detachment and advanced PVR. The results of the study showed no significant differences between perfluoropropane gas and silicone oil in achieving visual acuity of 5/200 or better (43% versus 45% for Group 1, 38% versus 33% for group 2) for 6 months following the surgical procedure.
Ultimately, surgical technique and constant attention to the relief of retinal traction are far more important determinants of the likelihood of the success of vitreoretinal surgery in the management of complicated retinal detachment than is the decision as to whether to use silicone oil or a long acting gas.
Semifluorinated Alkanes (SFA)
Semifluorinated Alkanes (SFA) also known as partially fluorinated alkanes (PFAs), are the first internal tamponade agents with specific gravity of 1.35 g/ml and a refractive index of 1.3. These can be used beyond the intraoperative setting, produce less retinal damage, can be left in situ for longer duration to tamponade the inferior retina and provides a better chance for bridging giant retinal tears. Disadvantages are emulsification and cataract formation.
Silicone oil/SFA combinations
Silicone Oil/SFA Combinations are double fill (DF) and heavy silicon oil (HSO). Double Fill is combination of Silicone oil and SFAs, with the goal of having the light silicone oil support the superior retina while the heavier SFA supports the inferior retina, keeping the percentage of oil as low as possible to avoid toxicity. In case of heavy silicone oil, it is a combination of SO and a PFA, in such a way as to create a homogenous solution. It is more viscous, more stable & better tolerated.
Natural polymers (short term vitreous substitutes) such as hyaluronic acid, collagen, modified collagen and chitosan causes mild, transient inflammatory reaction, no cataract formation but rapid biodegradation. These are not useful as inferior retinal tamponades.

Newer Vitreous Substitutes

Hydrogels (‘‘swell gels’’) swell in aqueous solutions without dissolving. These act as retinal tamponade with drug delivery systems, e.g. polyvinyl alcohol-methacrylate (PVA-MA), modified poly (acrylamide) gel. Although causes intravitreal inflammation, fragmentation and phagocytosis. Smart Hydrogels are new class that can respond to a variety of stimuli, i.e. PH, temperature, light, pressure, electric fields or chemicals [e.g. WTG-127 (Wakamoto Pharmaceutical, Tokyo, Japan)]. It is developed as a vehicle for improving bioavailability of ophthalmic solutions.
Finally the various clinical situations in which internal tamponade is required, with the best possible option are Gas for primary vitreoretinal surgery for a detachment and macular hole surgery, Gas/liquid for retinal detachment with PVR, giant retinal tear and infectious retinitis and Liquid for severe proliferative diabetic retinopathy, chronic uveitis with hypotony and complicated paediatric detachment.
In future, there is possibility of artificial generation of vitreous in vitro by using ascorbic acid (0.1-3 mg/mL) which enhances hyalocyte proliferation by increasing collagen production and mRNA expression of cells in vitro.

Conflicts of interest

There are no conflicts of interest.


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