Hyaluronic acid (Figure 1) (ie, a linear polysaccharide molecule of sodium glycuronate and N-acetyl glucosamine) is commonly used in eye drops and contact lens rewetters because of its high wetting and water binding properties. This article reviews the development and usage of hyaluronic acid in cataract surgery.
Ophthalmic viscosurgical devices (OVDs),1 formerly called viscoelastics or viscoelastic substances, are a class of nonactive, clear, gel-like chemical compounds with viscous and elastic properties.2 Its physical properties make OVDs useful for ophthalmic—mainly cataract—surgery.3 OVDs create and maintain anterior chamber depth and visibility as well as protect the corneal endothelium and other intraocular tissues during surgery. They minimize interaction between tissues and instruments and, therefore, ensure high tissue integrity.4,5
ESSENTIAL FOR CATARACT SURGERY
Today, OVDs are essential in ophthalmic surgery; they have become increasingly popular for cataract, cornea, glaucoma, trauma, and vitreoretinal surgery.6,7 Since the introduction of viscoelastics in the 1970s, the properties of these agents have improved the quality of anterior segment surgery. Based on these properties, OVDs may be divided into two groups:8
• Cohesive agents. These show high viscosity, adhere to themselves, and act like a gel. Its molecules are long chains, have a high molecular weight, and show high pseudoplasticity and surface tension.
• Dispersive agents. These show low viscosity, the molecules behave separately, and they build up a solution. They show low pseudoplasticity and surface tension with short chains and low molecular weight.
In 1934, Meyer and Palmer isolated hyaluronic acid from the vitreous cortex.9,10 In that same year, Endre Balazs purified hyaluronic acid from umbilical cord and rooster combs.11 In 1958, he first suggested using hyaluronic acid as a possible vitreous substitute during complicated retinal detachment surgery.12 Fourteen years later, he performed the first intravitreous injection of hyaluronic acid.13
Miller and Stegman first suggested hyaluronic acid for use during IOL implantation.14 In 1977, Miller used sodium hyaluronate to perform experimental IOL implantation in rabbit eyes.15 That same year, Fechner used a 1% methylcellulose to maintain the volume of the anterior chamber.16 Other surgeons also described methylcellulose as an inexpensive alternative to hyaluronic acid.17,18
During a symposium on ocular surgery, Balazs (1) developed and coined the procedure viscosurgery, and (2) presented the patent of viscoelastic material with high molecular weight,19 consisting of purified hyaluronic acid, that was used in an IOL implantation procedure. In the same year, he sold his patent to Pharmacia (Peapack, New Jersey; now Pfizer Inc., New York, New York), and the company developed Healon (sodium hyaluronate, 1%), the first viscoelastic product. Today, Healon is distributed by Advanced Medical Optics, Inc. (Santa Ana, California).
FDA APPROVAL
In 1976, Healon gained a US Investigational New Drug application. The following year, new drug applications were filed for use with IOLs, cataracts, glaucoma, and corneal transplants. In 1979, 510k permission to market Healon was granted, and the substance was first presented during the American Academy of Ophthalmology congress. The product launch occurred in 1980, during the American Society of Cataract and Refractive Surgery congress, followed by its FDA approval in January 1983.
Since the introduction of Healon, OVDs have become essential tools in ophthalmic surgery, particularly in the anterior segment.20 Eisner was the first to show space and surface tactical aspects of OVD application.21 He described techniques including viscoblockade, viscotamponade, and viscospatula.22 OVDs had—and still have—a great impact on the success of cataract surgery and IOL implantation.23-28
From 1995 to 2000, the International Organization for Standardization developed international standards for viscoelastic safety, performance, and approval requirements, under a new designation of OVDs.29 Additionally, the development of new viscoelastics modalities accompanied new cataract extraction procedures (ie, phacoemulsification) and foldable IOL implantation.
SYNERGISTIC ACTION
Viscoelastics have a range of features with rheologic-related properties including viscosity, elasticity, pseudoplasticity, and cohesiveness.30-32 Although the properties exist independently, they act synergistically. The same viscoelastic may be used according to specific needs, such as to separate or join tissues, maintain space, or protect surfaces (ie, corneal endothelium, lens capsule or anterior hyaloid) from mechanical trauma or fluid infusion.
Viscosurgery procedures are not limited to cataract surgery. They are now routinely used in antiglaucoma filtering surgery, combined surgical interventions, keratoplasty, and anterior vitrectomy.33,34 In corneal surgery, Alpar observed reduced endothelial cell loss in various keratoplasty procedures performed with Healon.35 Findings of reduced complication rate with OVDs were confirmed by other studies. After removal of a recipient cornea, an OVD depot (ie, dome) supports and stabilizes the donor cornea (ie, cushion) and facilitates positioning. Healon 5 (Advanced Medical Optics, Inc.), a high concentration viscoadaptive OVD is popular for this procedure.
Sodium hyaluronate was the first substance used as an OVD, and it is now the most widely used material and the gold standard to which all other viscoelastics are compared.36
The molecular weight of hyaluronic acid may range from 100,000 to 7 million daltons; the molecule consists of nearly 10,000 disaccharide units.37-43 This natural biological substance is found in all vertebrates, humans, and also some bacteria. High concentrations are found in human connective tissue and in the eye (ie, vitreous, cortex, trabecular meshwork). Low concentrations are found in the aqueous humor and corneal endothelium.
OVDs
Chondroitin sulfate. Like hyaluronic acid, chondroitin sulfate (Figure 2) is a biological substance found in the extracellular matrix, mainly in solid tissue parts (eg, cartilage or corneal stroma).37,44 For use as an OVD, this polysaccharide is mainly extracted from shark fin cartilage. The molecular weight is about 20,000 daltons; a chain length of 50 nm gives the molecule a lower viscosity and negative charge.
Methylcellulose. This substance is widely distributed in cotton and wood, but not in humans or animals (Figure 3).44-46 It is a disaccharide with side chains that make the molecule more hydrophilic. In ophthalmology, methylcellulose is used as a lubricant, because of its wetting and coating capacity. In the human body, methylcellulose shows a significant inflammatory potential, and it is not metabolized completely.
Polyacrylamide. This synthetic polymer has a high molecular weight derived from acrylamide, consisting of long carbon chains. The product was withdrawn from the market in 1991, after IOP elevation was observed with its use. Today, poyacrylamid is only of historical interest.7
Collagen. Type IV collagen may be extracted from human as well as pig tissue. There is little information about the origin of collagen use for an OVD.7
Further substances have been suggested and attained as a basis for OVD, however, they do not show any clinical relevance.47 Development, production, and use of OVD require ongoing research to evaluate the biocompatibility, purity, and ocular structure protection of the materials in question.48-59 In vivo studies have proven that the molecular and chemical structure of hyaluronic acid is ideal, and interactions between molecules and receptor tissue60 and inflammatory and immunogenic reaction61 have also been studied extensively.
Sibylle Scholtz, PhD, is employed by Advanced Medical Optics, Inc. in an administrative function. She states that she is a paid consultant for Advanced Medical Optics, Inc. Dr. Scholtz may be reached at sibylle.scholtz@gmx.de.
Up Front | Jan 2007
History of Ophthalmic Viscosurgical Devices
OVDs create and maintain anterior chamber depth and visibility and protect intraocular tissues during surgery.
Sibylle Scholtz, PhD
