rx perspective
New Hyaluronidase Coming Soon
Once a key factor in many surgeries, an improved formulation is poised to make an impact.
By Richard A. Lewis, M.D.

In early 2001, the widely used spreading agent hyaluronidase (Wydase, manufactured by Wyeth) was pulled from the market because of manufacturing issues. At the time, the American Academy of Ophthalmology estimated that it was used in 750,000 ophthalmic surgical procedures a year, mainly cataract surgery.

It's been said that the disappearance of hyaluronidase sent shock waves through ophthalmology. A 2001 Academy Rapid Clinical Report noted that its absence re-sulted in longer anesthetic dissemination time, greater orbital swelling, even strabismus. Members of an expert panel agreed unanimously that injectable anesthetics couldn't be administered as safely and effectively without hyaluronidase.

These observations mirrored my experience performing cataract and glaucoma surgery. A good retrobulbar block applied with hyaluroni-dase leaves the patient pain-free, with anesthesia lasting 3 to 4 hours (well into the post-op recovery period), and the eye is very still. Without hyaluronidase, a retrobulbar block keeps the eye still, but patients experience more pain. I've found ways to compensate, such as adding a subconjunctival injection to topical anesthesia, but I miss the full efficacy of my local blocks.

The Academy conducted a Web poll of members last summer to evaluate how surgeons were compensating for the lack of hyaluronidase. About 41% of respondents were using compounded hyaluronidase, although more than half of them had difficulty obtaining it. Nearly 60%, like me, weren't using it at all.

New and Improved

All of this may soon be a thing of the past. ISTA Pharmaceuticals has received FDA approval to market its highly-purified preservative-free ovine hyaluronidase, Vitrase, which is indicated as a spreading agent for use in ophthalmic surgery. For now, the approval covers a 6,200 unit/ml vial. But the company submitted a supplemental NDA in August for a 150 unit/ml vial, and hopes to receive that approval by the end of this year.

This new version of hyaluroni-dase differs from Wydase:

► Wydase contained thimerosol; Vitrase is nonpreserved.

► Vitrase's source is ovine (sheep) which addresses concerns raised about the theoretical potential of bovine (cow) source material to transmit the human form of "mad cow" disease. This isn't necessarily a clinical advantage, but it does provide added piece of mind.

► Vitrase is under investigation as an aid for treating vitreous hemorrhage. This research actually predates interest in the product as a spreading agent, and presumably gave the product its name.

The biochemical mechanism that makes hyaluronidase useful for clearing a vitreous hemorrhage is the same one that makes it an effective spreading agent: It modifies the permeability of the vitreous humor, essentially liquefying it. This helps to disperse an anesthetic, and also allows a hemorrhage to dissipate rapidly. (Vitrase doesn't treat the hemorrhage per se. Instead, it clears the vitreous more quickly, letting the surgeon determine the cause of the problem sooner. It also restores visual acuity while patients are waiting for surgery.)

ISTA received an approvable letter for the hemorrhage indication last year and continues to work with the FDA toward full approval.

A Welcome Return

Like most of us, I haven't had an opportunity to use Vitrase yet, but I'll certainly consider using it when I need to create a retrobulbar block, particularly when procedures would be painful for the patient.

It's unlikely that Vitrase will revolutionize my practice the way it might for my retina colleagues if it's approved for vitreous hemorrhage. But it should contribute to my relentless pursuit of better surgical outcomes by letting me once again provide the full advantages of local blockade to my patients who need it. And that's no small thing.

Dr. Lewis is in private practice in Sacramento, Calif. He is a clinical investigator for ISTA Pharmaceuticals, Allergan, Alcon and Pfizer, but has no financial interest in ISTA or Vitrase. He can be reached at (916) 455-9938 or rlewismd@pacbell.net.