Ophthalmic Viscosurgical Devices
Rupal H. Trivedi
M. Edward Wilson
The aim of surgery using viscoelastic agents, or viscosurgery, is to provide greater protection to intraocular tissue from mechanical damage, while increasing the space available for surgical manipulation. The use of viscoelastic substances has become an integral part of ophthalmic surgery, particularly anterior segment surgery. Although the term viscoelastics has made its way into the ophthalmic lexicon, viscous products are not always elastic. The term ophthalmic viscosurgical devices (OVDs) was introduced in 2000.1 OVD more clearly implies the intended surgical role of these substances, which is viscosurgery. In common clinical conversations, “viscoelastic” and “OVD” terms are used interchangeably. For published medical literature, most editors will require that the OVD term be used. OVDs are classified as devices because they remain in an unaltered state when removed from the eye after intraocular usage. Many OVDs are now available, each possessing specific chemical and physical properties and leading to different intraoperative behaviors. Better understanding of this advancing area of technology can help pediatric cataract surgeons optimize the use of these devices to improve outcomes.
A GLOSSARY OF OVD TERMS AND PROPERTIES
Viscosity is defined as the internal friction caused by molecular attraction that leads to a solution’s resistance to flow. Viscosity denotes the protective and lubricating property of the material. Increasing either the concentration or the molecular weight of a solution can increase the viscosity and make the material more resistant to flow. Viscosity depends on the degree of molecular movement within a solution (also known as the shear rate), and it varies inversely with temperature. This is the reason why it is essential to state the temperature at which viscosity is being measured. Fluids that have the same viscosity at low shear rates and at high shear rates (i.e., when the viscosity is independent of shear rates) are referred to as newtonian fluids. Chondroitin sulfate is such an example. Fluids exhibiting a decrease in viscosity at high shear rates are referred to as non-newtonian fluids. Sodium hyaluronate (Na-Ha) is one such example. A fluid that is highly viscous will require greater force for its injection into the eye than would a less viscous fluid injected through a same-sized cannula, and the greater the force required, the less able the surgeon is to judge either the required force or the sufficiency of the injection.2
Very low shear rates are present when the ocular structures are stationary and an OVD is simply expanding space during the surgical procedure. Zero-shear viscosity correlates with the molecular weight of a rheologically active OVD and can be used to rank and classify these agents. High viscosity at low shear rates maintains space and protects intraocular tissues.
Medium shear rates correspond to the velocities at which the surgeon moves objects through the eye, such as during an intraocular lens (IOL) implantation. Moderate viscosity at medium shear rates allows movement of surgical instruments, thus assisting IOL implantation.
Very high shear rates are operative when an OVD is being injected through a cannula. Low viscosity at high shear rates allows for easy introduction into the eye through a small cannula. Elasticity is the tendency of a material to return to its original size and shape after having been deformed (i.e., stretched or compressed). Long-chain molecules such as Na-Ha tend to be more elastic than do short-chain molecules.
Plasticity can be defined as the initial resistance to flow. The resistance decreases once a fluid begins to move. The more plastic a substance, the less force is required to initiate this movement.
Pseudoplasticity refers to a solution’s ability to transform when under pressure from a gel-like state to a more liquid state. Pseudoplastic fluids, which all of our OVDs are, exhibit decreasing viscosity as the external stress is increased but, unlike plastics, possess a limiting viscosity as the stress is reduced, and always remain fluid.2
Cohesiveness is the degree to which a material adheres to itself. It is a function of molecular weight and elasticity.
Long-stranded OVDs with a high molecular weight become entangled and tend to remain as a single mass. To date, all cohesive OVDs are of higher zero-shear viscosity, and all dispersive OVDs are of lesser zero-shear viscosity.2 Superviscous cohesive OVDs have zero-shear viscosities exceeding 1,000,000 mPs (millipascal seconds), while viscous cohesive agents have zero-shear viscosities between 100,000 and 1,000,000 mPs. Cohesion is actually more complicated than this, and all OVDs are really cohesive at rest, but lower molecular weight OVDs behave in a dispersive fashion under the low vacuum stress imposed by irrigation and aspiration encountered during cataract surgery. Generally, given two viscoelastic substances of the same chemical family and concentration, the greater the mean molecular weight (i.e., the greater the polymeric chain length) of a substance, the greater its cohesion and zero-shear viscosity.2
Long-stranded OVDs with a high molecular weight become entangled and tend to remain as a single mass. To date, all cohesive OVDs are of higher zero-shear viscosity, and all dispersive OVDs are of lesser zero-shear viscosity.2 Superviscous cohesive OVDs have zero-shear viscosities exceeding 1,000,000 mPs (millipascal seconds), while viscous cohesive agents have zero-shear viscosities between 100,000 and 1,000,000 mPs. Cohesion is actually more complicated than this, and all OVDs are really cohesive at rest, but lower molecular weight OVDs behave in a dispersive fashion under the low vacuum stress imposed by irrigation and aspiration encountered during cataract surgery. Generally, given two viscoelastic substances of the same chemical family and concentration, the greater the mean molecular weight (i.e., the greater the polymeric chain length) of a substance, the greater its cohesion and zero-shear viscosity.2
Dispersiveness is the tendency of a material to disperse when it is injected into the anterior chamber. Dispersive agents commonly have low molecular weights and shorter molecular chains. In agents that have lower zeroshear viscosities, molecular chain entanglements become far less important and cohesion tends to be significantly weaker, resulting in a tendency to disperse when injected into the anterior chamber. Medium-viscosity dispersive OVDs possess zero-shear viscosities between 10,000 and 100,000 mPs. Very-low-viscosity dispersive agents include all of the unmodified hydroxypropyl methylcellulose (HPMC) agents.
Coatability refers to the ability of an OVD to adhere to the surface of tissues, instruments, and implants. A lower surface tension and a lower contact angle indicate a better ability to coat. In addition, the molecular charge of the viscoelastic substance may influence its coating ability. Arshinoff described desirable characteristics of an OVD as (1) low viscosity during its injection into the operative space, to facilitate rapid movement through a small-bore cannula while preserving the surgeon’s tactile feedback sensitivity; (2) high viscosity when stationary, to create and maintain surgical spaces; and (3) intermediate viscosity at intermediate shear rates, to allow the passage of an IOL or a surgical instrument as required during the operation.2
AVAILABLE MATERIALS
Balanced salt solutions (BSSs) and air, while not technically viscosurgical materials, were the first substances used as protective agents. Both are readily lost once the cornea is retracted or during difficult surgical manipulations in the anterior chamber.
HPMC is synthesized from methylcellulose as a raw wood pulp product of medical grade. Methylcellulose, in a 1% solution, was used to coat IOLs prior to implantation, and later 2% methylcellulose was used to maintain the anterior chamber.3 HPMC (2%) consists of a long chain of glucose molecules with replacement of the hydroxy groups by methoxypropyl and hydroxypropyl side chains. This polymeric backbone is cellulose, a carbohydrate that is not a natural component of animals or humans, and so its fate in the eye remains unknown. The physical properties of HPMC require that a largebore cannula with increased infusion pressure be used for injection. It is relatively difficult to completely remove HPMC from the eye. The primary advantages of HPMC are its ability to coat, availability, ease of preparation, room temperature storage, ability to withstand autoclaving, and low cost compared with other OVDs.4 Its safety and efficacy in intraocular surgery have been reported.3,5 Cellugel, OcuCoat, Visilon, and I-Cel are some of the commercially available HPMC OVDs.
Sodium hyaluronate (Na-Ha), a viscous substance, was used in animal implant experiments as early as 1977 and in human implant experiments beginning in 1979.6 It is a naturally occurring lubricant and shock absorber present in nearly all vertebrate connective tissue matrices. In the eye, Na-Ha is found at high concentrations in the vitreous and connective tissue of the trabecular angle and at low concentrations in the aqueous humor and covering the corneal endothelium.7 Importantly, the use of this product in surgical situations does not represent the introduction of a “foreign” material. All Na-Ha products require refrigeration, with subsequent acclimation to room temperature prior to use. The prime advantages of Na-Ha products are its creation and maintenance of space in the anterior chamber, its ease of insertion and removal, and the fact that it is a natural product of the eye. The disadvantages are its poor coating ability, its removal as a mass during high-turbulence situations, and the necessity to refrigerate it. Manufacturers emphasize the importance of the product’s purity, with various proprietary methods used to ensure this quality. It has been extracted from a variety of sources, including the dermis of rooster combs, umbilical cords, and cultures of streptococci.4 Although highly purified Na-Ha from each of these sources has the same structure, the molecular weight can vary. Healon, Healon GV, Healon5, Amvisc, Amvisc Plus, and Biolon are some of the available Na-Ha products.
Chondroitin sulfate at low concentrations is useful for coating tissue but poor for maintaining space because of its low viscosity. Viscoat is a 1:3 mixture of 4% chondroitin sulfate and 3% Na-Ha. The Na-Ha in Viscoat is produced by bacterial fermentation through genetic engineering techniques, and the chondroitin sulfate is obtained from shark fin cartilage. The combination of two biologic polymers creates a unique chemical structure with a relatively high viscosity and perhaps increases its coating ability and cell protection, because of the additional presence of a negative charge. Viscoat requires refrigeration, with subsequent acclimation to room
temperature prior to use. Ocugel is a combination of chondroitin sulfate and HPMC.
temperature prior to use. Ocugel is a combination of chondroitin sulfate and HPMC.
HIGH-VISCOSITY COHESIVE VISCOELASTIC AGENTS
Cohesive viscoelastic agents with high zero-shear viscosities are better for creating space compared to dispersive OVDs. This is especially important when expanding a shallow anterior chamber in an infantile eye. They are also useful when it is desirable to pressurize the anterior chamber to a level equal to the posterior pressure. This pressure equalization during cataract surgery is especially helpful for capsulorhexis, because it flattens the lens capsule. Cohesive OVDs can also be used to enlarge a small pupil, to dissect adhesions, and to aid IOL implantation. The high cohesiveness of viscous and superviscous material results in easy removal at the end of the surgical procedure. However, because of this same cohesive behavior, these agents also rapidly leave the anterior chamber during surgery.
Some surgeons find that the extremely high zero-shear viscosity of superviscous cohesive materials make them initially somewhat difficult to work with. When using these agents, surgeons should be more precise in their movements, as things moved into the wrong place tend to stay there (e.g., folds of the capsular flap when creating a capsulorhexis). However, with practice, the benefits of these materials quickly become apparent to the surgeon, and many have come to prefer them as their primary viscoelastic agents in pediatric cataract surgery, unless a dispersive material is surgically indicated.
Superviscous cohesive agents include I-Visc Plus (I-MED Pharma), Healon GV (AMO), and Eyefill C.
(Croma Pharma). Viscous cohesive includes I-Visc (I-MED Pharma), Healon (AMO), Provisc (Alcon), Amvisc Plus (B & L), Amvisc (B & L).
LOWER-VISCOSITY DISPERSIVE VISCOELASTIC AGENTS
The most useful properties of dispersive OVDs are their resistance to aspiration and their ability to partition spaces. Their dispersive nature, a negative electrical charge, and the presence of hyaluronic acid that can bind to specific binding sites on the corneal endothelium improves the retention of these agents within the anterior chamber throughout the surgery. Thus, these agents are capable of partitioning the anterior chamber into an OVD-occupied space and a surgical zone in which irrigation/aspiration can be continued, without the two areas mixing. This is referred to as surgical compartmentalization. Therefore, their use is even more beneficial in eyes in which a compromised endothelium is suspected. Dispersive OVDs can also selectively move or isolate a single intraocular structure within the anterior chamber (e.g., holding back vitreous at an area of zonule disinsertion or at a small hole in the posterior capsule).
Prevention of posterior capsule opacification remains an important goal in cataract surgery, especially pediatric cataract surgery. Posterior capsule opacification is caused mainly by the proliferation of lens epithelial cells. Budo et al.10 investigated the morphologic effects of Viscoat on lens epithelial cells. They conclude that light microscopy and transmission electron microscopy of human lens capsule suggest that Viscoat induces significant morphologic changes in lens epithelial cells during cataract surgery. The changes may underlie the improved visualization of these cells that has been reported during cataract surgery. Studies in a rabbit model suggest that the hyperosmolarity of Viscoat may play a partial role in the lens epithelial cell changes.
The major drawback of lower-viscosity dispersive OVDs is their relatively low viscosity and elasticity, which do not allow them to maintain or stabilize spaces as well as higher-viscosity cohesive OVDs (e.g., in the performance of capsulorhexis or IOL implantation). They tend to be aspirated in small fragments during irrigation/aspiration, which leads to an irregular viscoelastic-aqueous interface that partially obscures the surgeon’s view of the posterior capsule during surgery. The microbubbles that can form during surgery also tend to become trapped at this irregular interface, further obscuring visibility and making surgical maneuvers in the posterior chamber even more difficult. Because of low cohesion, lower-viscosity dispersive OVDs are more difficult to remove at the end of surgery.
As mentioned earlier, cohesive agents are best at creating and preserving space, while lower-viscosity dispersive agents are retained better in the anterior chamber and are capable of partitioning spaces. High zero-shear viscosity agents tend to leave the anterior chamber rapidly during the turbulent surgical outflow. Although zero-shear lowviscosity OVDs remain in the anterior chamber during surgery, they are not of use in pressure-equalized surgery, and they are more difficult to remove. The so-called soft-shell technique has been described in the literature; it maximizes the advantages and minimizes the disadvantages of both cohesive and dispersive OVDs by using them together.11 Healon5 is a product attempting to combine the best of the cohesive and dispersive agents into a single agent.12