Ophthalmic viscosurgical devices (OVDs) are surgical auxiliary solutions used in intraocular surgery to maintain space, protect the corneal endothelium, prevent corneal drying, and assist with staining. Initially treated merely as surgical aids, they have evolved with the development of formulations with various properties to be regarded as surgical instruments, and are now collectively referred to as viscosurgical devices.
The history of ophthalmic use of hyaluronic acid began in 1934 when Karl Meyer and John Palmer isolated hyaluronic acid from bovine vitreous humor 1). In 1979, Drs. Robert Stegmann and David Miller first clinically used 1% sodium hyaluronate during cataract surgery 1). From 1980 to 1983, Pharmacia received FDA approval and launched it on the global market, revolutionizing modern cataract surgery 1).
Currently, in Japan, sodium hyaluronate is mainly used as a viscosurgical device, with sodium chondroitin sulfate as a combination agent. Sodium hyaluronate is a type of glycosaminoglycan with a long-chain structure of repeating disaccharides of N-acetylglucosamine and glucuronic acid. It is a natural substance also found in connective tissues, skin, vitreous humor, cartilage, and synovial fluid in the body.
Due to the importance of its role, the viscosurgical device has shifted from being a mere surgical auxiliary solution to being positioned as a surgical instrument. Since it greatly affects the safety and efficacy of cataract surgery, surgeons are required to select an OVD with a thorough understanding of its properties.
The surgical use of viscoelastic substances is determined by their physical properties. The following four properties are directly related to their use in surgery.
Viscosity
Viscosity: Indicates the resistance to flow. Higher molecular weight and concentration result in higher viscosity. High-viscosity viscoelastic substances are more effective at moving tissue and are less likely to be expelled from the anterior chamber.
Pseudoplasticity
Pseudoplasticity: The property of changing viscosity in response to shear rate. At rest, it exhibits high viscosity, but under high shear rates such as instrument manipulation, viscosity decreases, making injection and removal easier. Sodium hyaluronate has non-Newtonian fluid properties, and the longer the molecular chain, the greater the pseudoplastic change.
Elasticity
Elasticity: The ability to return to original shape after deformation. Higher elasticity provides better space-maintaining ability. All viscoelastic substances restore corneal shape and the anterior chamber after instrument insertion and removal.
Coatability
Coatability: Determined by surface tension and contact angle. Lower surface tension and smaller contact angle result in higher coatability, providing better tissue protection but making removal from the eye more difficult.
Viscoelastic substances are classified into four categories based on the cohesion dispersion index (CDI).
| Classification | Cohesion Dispersion Index | Viscosity | Representative Products (Japan) |
|---|---|---|---|
| Cohesive type | ≥30%asp/mmHg | High (high molecular weight) | Opegan® Hi, Healon® |
| Dispersive type | <30%asp/mmHg | Low (low molecular weight) | Viscoat®, Shellgan® |
| High viscosity dispersive type | Intermediate | Medium to high | DisCoVisc® |
| Viscoadaptive type | ≥30%asp/mmHg | Very high | Healon V® |
The main component is 1% sodium hyaluronate. The molecular chains are long and intertwine with each other, providing high elasticity and cohesiveness. As aspiration pressure increases, they tend to be expelled as a mass (likened to spaghetti). They are classified into low molecular weight, intermediate molecular weight, and high molecular weight types based on molecular weight, each with different characteristics.
A representative product is a combination of 3% sodium hyaluronate and 4% sodium chondroitin sulfate. These have short-chain molecules, low viscosity, and high coating ability. Under high shear rates, they disperse and thinly coat the corneal endothelium (likened to macaroni). The cohesion-dispersion index is very low, about 1/10 that of cohesive types, making them difficult to remove even when aspiration pressure increases. Due to sulfate groups, they are negatively charged and tend to adhere to the positively charged corneal endothelial cells. However, because they adhere to intraocular tissues, complete removal is difficult, and residual material poses a risk of increased intraocular pressure 1).
Representative product: Healon V® (2.3% high molecular weight sodium hyaluronate). The cohesion-dispersion index is very high, over 70, and the molecular chains are even more intertwined than in high molecular weight cohesive types, providing high elasticity and cohesiveness. A characteristic feature is the property of being rapidly removed when aspiration pressure exceeds a threshold (pseudo-dispersive). At irrigation flow rates below 25 mL/min, they exhibit high cohesiveness and high space maintenance; at flow rates above 25 mL/min, they are easily aspirated and removed 1).
Representative product: DisCoVisc® (1.65% low molecular weight sodium hyaluronate + 4% sodium chondroitin sulfate). It has an intermediate cohesion-dispersion index between cohesive and dispersive types, providing ease of removal from the anterior chamber similar to cohesive viscoelastics and corneal endothelial protection similar to dispersive types.
The roles of viscoelastic substances in each stage of cataract surgery (phacoemulsification) are as follows.
After creating the incision, the aqueous humor is completely replaced with a viscoelastic substance to form the anterior chamber. During anterior capsulotomy, the viscoelastic substance maintains the dome shape of the cornea and the depth of the anterior chamber, providing stability to the anterior capsule surface, thereby reducing the probability of the capsulotomy extending peripherally. High viscosity and high elasticity viscoelastics under low shear rates are ideal.
During phacoemulsification, the anterior chamber depth is maintained by infusion pressure, but the corneal endothelium is susceptible to damage from ultrasonic energy and fluid turbulence. Viscoelastic substances with high coating ability (endothelial protection) and high elasticity (vibration absorption) are required, and dispersive viscoelastic substances are suitable.
Before removing the ultrasonic tip from the anterior chamber, simultaneous injection of viscoelastic substance through the side port prevents sudden anterior chamber collapse and protects against posterior capsule rupture, iris, and corneal tissue damage. In cases with low corneal endothelial cell density, viscoelastic substances prevent direct contact of nuclear fragments with the corneal endothelium (soft-shell technique).
After sufficiently depressing the posterior capsule to expand the capsular bag, the intraocular lens is inserted. Under low shear rates where the intraocular lens is stationary, high-viscosity agents protect the endothelium from compression by the intraocular lens and provide cushioning for folding and unfolding of the intraocular lens. High molecular weight cohesive viscoelastic substances are suitable.
After intraocular lens insertion, the viscoelastic substance remaining in the anterior chamber is removed using irrigation and aspiration. In particular, if viscoelastic substance remains on the posterior surface of the intraocular lens, bacteria can easily colonize, leading to postoperative endophthalmitis. It is necessary to directly wash the posterior surface using the “behind-the-lens technique,” where the irrigation/aspiration tip is inserted behind the intraocular lens.
The rate of corneal endothelial cell loss after cataract surgery is reported to be 4–25%, and the main cause is mechanical trauma from surgical instruments, nuclear fragments, and intraocular lenses 2). Viscoelastic substances are a primary means of reducing this trauma.
Hsiao et al. (2023) conducted a systematic review and meta-analysis of 12 randomized controlled trials from 2000 to 2020, comparing viscoelastic substances containing chondroitin sulfate and hyaluronic acid (VISCOAT®, DuoVisc®, DisCoVisc®) with hyaluronic acid alone or hydroxypropyl methylcellulose products 2).
A meta-analysis using a random-effects model showed that the combination of chondroitin sulfate and hyaluronic acid viscoelastic significantly reduced the rate of corneal endothelial cell loss at 3 months postoperatively compared to hyaluronic acid alone (mean difference: -4.10%; 95% CI: -5.81 to -2.40; p<0.0001; 9 studies)2). A significant difference was also observed compared to hydroxypropyl methylcellulose products (mean difference: -6.47%; 95% CI: -10.41 to -2.52; p=0.001; 2 studies)2).
Regarding changes in corneal thickness (24 hours postoperatively), the combination of chondroitin sulfate and hyaluronic acid viscoelastic showed significantly less corneal swelling compared to hyaluronic acid alone (mean difference: -3.22%; 95% CI: -6.24 to -0.20%; p=0.04; 4 studies)2).
It is thought that sodium chondroitin sulfate forms a triple negative charge with hyaluronic acid-chondroitin sulfate, promoting molecular attraction to the corneal endothelium, which is the mechanism for its superior endothelial coating and protective effect2).
Basically, cohesive viscoelastics are chosen for space maintenance, and dispersive viscoelastics for corneal endothelial protection. In high-risk cases such as hard cataracts or corneal endothelial dystrophy, the soft shell technique combining both is particularly effective. In glaucoma surgery, cohesive viscoelastics are considered advantageous for ease of removal during anterior chamber irrigation.
This is a representative combination technique described by Steve Arshinoff in 19991). At the start of surgery, a dispersive viscoelastic is injected into the anterior chamber to form a mass on the anterior lens surface, then a cohesive viscoelastic is injected into the center behind the dispersive mass. This pushes the dispersive viscoelastic upward and outward, forming a smooth layer against the corneal endothelium. During phacoemulsification and irrigation/aspiration, the high-viscosity cohesive viscoelastic is quickly removed, while the low-viscosity dispersive viscoelastic remains as a protective layer for the endothelium.
Especially in cases with hard nuclei, this technique has been shown to reduce postoperative corneal endothelial cell loss compared to using cohesive or dispersive viscoelastics alone1).
Intraoperative floppy iris syndrome (IFIS) is a well-known complication associated with the use of alpha-blockers (such as tamsulosin) for prostate treatment1). Decreased iris muscle tone leads to miosis and iris prolapse. Viscoadaptive viscoelastics (e.g., Healon V®) help mechanically dilate the pupil (viscoelastic mydriasis) and stabilize the iris to prevent prolapse through the wound1).
In more difficult cases, a combination of soft-shell, ultimate soft-shell, and tri-soft-shell techniques is used 1).
Hard brown cataracts and mature cataracts carry high risks of corneal endothelial damage, nucleus drop, and posterior capsule rupture 1). Because longer surgical manipulation and higher ultrasound energy affect the corneal endothelium, the use of dispersive ophthalmic viscosurgical devices (OVDs) or a combination product (soft-shell technique) is appropriate 1).
A flat anterior chamber after glaucoma surgery is a common complication of posterior chamber surgery, and injecting an OVD into the anterior chamber is one treatment option 1). Viscous adaptive OVDs have been reported to be effective 1).
When using a wide-angle viewing system for fundus observation, the pre-corneal lens must be brought to about 1 cm above the cornea, so a wet shell using an OVD is useful for preventing corneal drying. In addition, mixing an OVD with internal limiting membrane stains (indocyanine green, brilliant blue G) allows control of the staining area and concentration.
The following complications related to OVDs are known.
VisThesia (2% lidocaine + 0.3% sodium hyaluronate, Carl Zeiss Meditec), which combines an ophthalmic viscosurgical device with lidocaine, was developed to provide anesthetic effect and viscosurgical device function in one step 1). While improvement in intraoperative pain control has been reported, some studies have reported a greater decrease in corneal endothelial cell density compared to conventional ophthalmic viscosurgical devices, and results are inconsistent 1). This is an area requiring further research.
Pe-Ha-Blue® PLUS (Albomed), which combines sodium hyaluronate with trypan blue (anterior capsule stain), aims to facilitate capsulorhexis while protecting the corneal endothelium 1). In cases with poor pupil dilation such as pseudoexfoliation syndrome, significant reduction in surgical time and improvement in surgeon satisfaction have been reported 1). It also has the advantage of allowing visual confirmation of residual blue ophthalmic viscosurgical device for easier removal.
