Hyaluronic Acid for the Ocular Surface

Hyaluronic Acid for the Ocular Surface

Hyaluronic Acid for the Ocular Surface
Gary N. Foulks, MD, FACS

Considerable enthusiasm has developed for the ability of hyaluronic acid to lubricate, moisturize, and protect the ocular surface.

Found naturally in the vitreous humor, synovial fluid, and many other locations in the body, hyaluronic acid functions primarily as a lubricant and volumizer. In recent years, considerable enthusiasm has developed for this natural polymer’s ability to lubricate, moisturize, and protect the ocular surface.

Ocular Surface Applications

Within ophthalmology, hyaluronic acid was initially developed as an intraocular viscoelastic. Surgeons using it for cataract and other intraocular surgery found that a drop on the ocular surface after surgery protected the cornea. It was a short logical jump from there to using hyaluronic acid to relieve the symptoms of dry eye disease.

Subsequent studies demonstrated that long-term use of hyaluronic acid relieves dry eye symptoms and reduces ocular surface damage without triggering allergic reactions. This molecule is known to both bind water and weakly adsorb to the eye’s epithelial layer (so that it is retained on the ocular surface). In theory, then, its benefits derive from its ability to remain on the ocular surface and to hold moisture there.
  
Regulatory Roadblocks

To date, hyaluronic acid’s application as an ocular surface lubricant has been greatest in Japan, where it is the active ingredient in the most commonly prescribed and recommended artificial tears. It is also available in Europe, but in the United States, the FDA placed restrictions on the original commercial product, which was derived from rooster combs—the FDA has long looked unfavorably on such biological extracts due to the risks of contamination and the transmission of infectious disease.

More recently, advances in recombinant DNA technology have enabled production of hyaluronic acid using microbial fermentation. These safer, biotechnological sources supply all the hyaluronic acid found in artificial tears today.

Several artificial tears and contact lens rewetting drops that are marketed in the US contain hyaluronic acid. In these products, however, the hyaluronic acid is technically an excipient, ie, an “inactive” ingredient. As a result, the companies that make these products don’t advertise its presence, although it is listed on packaging and package inserts.

Versatile Drop

Using biotechnology to produce hyaluronate not only increases safety, it allows for the manufacture of ophthalmic-grade hyaluronic acid polymers of various chain lengths and molecular weights. This, in turn, allows the production of ophthalmic solutions in varying viscosities.3

The thicker drop afforded by a heavier-weight molecule and higher concentration provides longer retention time. But on a practical level, increased thickness produces increased blurring. As a result, the concentrations used in artificial tear preparations are relatively low—less than 0.5%. (By contrast, we use a considerably high concentration intraocularly and to coat the cornea after surgery.)

Other than blurring vision when used in a high-concentration, viscous solution, there are few downsides to hyaluronic acid. Today, several manufacturers remain interested in winning FDA approval for claims of hyaluronic acid’s therapeutic effects on the ocular surface. Yet it remains unclear how and when this interest will translate into regulatory change. Meanwhile, look for increasing use of hyaluronic acid in lubricating eye drops as an excipient with benefits.
 

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Gary N. Foulks, MD, FACS, is the Arthur and Virginia Keeney professor of ophthalmology, University of Louisville, Louisville, KY,  and is editor-in-chief of The Ocular Surface.

References

1.     Condon Pl, McEwen CG, Wright M, et al. Double blind, randomized, placebo controlled crossover, multicentre study to determine the efficacy of a 0.1% sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome. Br J Ophthalmol. 1999;83(10)1121-4.
2.     Aragona P, Papa V, Micali A, et al. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol. 2001;86(2)181-4.
3.     Guillaumie F, Furrer P, Felt-Baeyens O, et al. Comparative studies of various hyaluronic acids produced by microbial fermentation for potential topical ophthalmic applications. J Biomed Mater Res A. 2010;92(4):1421-30.