Early diagnosis, diurnal IOP control among hot topics in glaucoma

In a report from the OSN Section Editor Summit, Richard A. Lewis, MD, also discusses combination drugs, drug delivery options and new devices.

First, I would like to point out the changes implemented this year by our new OSN Glaucoma Section Editor, Thomas W. Samuelson, MD.

The “Glaucoma Home Page,” which appears in every issue, was started this year in the Jan. 15 issue. It contains a number of features, such as regularly appearing columnists who cover glaucoma news and commentary, an Industry Pipeline and Glaucoma News Notes.

In the new columns in our section, Douglas J. Rhee, MD, will be discussing the clinical applications of basic research in a column entitled “From the Lab to the Clinic.” Nathan G. Congdon, MD, MPH, will address global issues in glaucoma, epidemiology and mission surgery. George L. Spaeth, MD, will write about the glaucoma community. James D. Brandt, MD, will be discussing new technologies. And Dr. Samuelson himself is going to write about glaucoma in relation to the anterior segment.

Structure before function

The theme “structure before function” is a hot issue in glaucoma right now in terms of treatment. The pendulum has lately swung toward structure. For a long time the feeling was that visual field loss could be seen before we saw optic nerve cupping. Clearly that has changed, and with the new imaging systems that are available we definitely see optic nerve change before we see visual field loss. Imaging systems have completely changed the paradigm regarding when to initiate treatment.

The retinal imaging systems that are available include the GDx/VCC and the Stratus OCT from Carl Zeiss Meditec and the HRT II from Heidelberg Engineering. Of those three, the most useful for glaucoma specialists are the GDx and HRT II. The OCT seems to be more useful in retinal diseases than in glaucoma. The GDx and HRT II are easier to interpret, easier to perform and a little more specific in early diagnosis. I think OCT will play a bigger role later in the disease in terms of progression and long-standing damage.

In terms of picking up visual field loss, Carl Zeiss Meditec has now included the SITA SWAP test as an additional feature on the Humphrey Field Analyzer. There is also the Humphrey Matrix frequency doubling technology, which is also useful. The combination of all of these different systems allows us to identify glaucoma patients much earlier and initiate treatment before damage occurs.

Diurnal fluctuations

Regarding medical therapy, there has been interest in the issue of preventing diurnal fluctuation. As clinicians, we check pressure only when patients are upright in the office, but studies are showing that if we check pressures when patients are lying down, or particularly when they’re sleeping, their pressures are much higher. This part of the diurnal pressure curve has been missed because the diurnal pressure checks that we have done in the past tended to be between 8 a.m. and 5 p.m. The key in treating glaucoma is to flatten that curve by providing either medications or surgery.

The discussion in the office now has to do with how we check pressure and whether we really believe we’re getting an accurate measurement. The role of corneal pachymetry has completely altered the way we interpret IOP. The Pascal Dynamic Contour Tonometer is a new device that incorporates information on corneal rigidity.

Another diagnostic tool that has generated interest in the past year is the glaucoma risk calculator. This calculator, modeled on risk calculators for cardiovascular disease, takes into account risk factors including age, IOP, pattern of standard deviation and corneal thickness to give you and the patient an assessment of the long-term risk of developing glaucoma. You can tell the patient that he or she has a 5% risk or a 50% risk of getting glaucoma within 5 years, and that can influence whether or not you want to initiate treatment.

Combination therapies

Richard A. Lewis

Physicians and patients both like the concept of combination therapies, but there are several in the pipeline that the Food and Drug Administration has not yet approved. Some day there will be a study that will validate the fact that 40% of patients taking prostaglandins are also taking a beta-blocker. There’s an obvious need in the marketplace for a combination product, but it can’t seem to get past our FDA. In Europe it’s already a popular drug.

The combination products that are currently under investigation include prostaglandins plus timolol, prostaglandins plus a carbonic anhydrase inhibitor, and timolol plus brimonidine.

This topic was brought up at the American Glaucoma Society meeting this year, and some of the concerns that were raised have to do with the dosing of these drugs. Because timolol is a once-a-day drug and brimonidine is a twice-a-day drug, this creates some systemic issues. But the efficacy results were impressive.

Drug delivery

There is still a great need for better drug delivery in glaucoma, and a variety of different mechanisms are being discussed. One issue that has been raised is the possibility of intravitreal delivery — not only that it play a role in IOP reduction, but also that it might play a role in neuroprotection. There has been a lot of discussion about the possibility of neuroprotection if we can get drug delivery back to the optic nerve and retina.

Intravitreal injection is not thought of as negatively as it used to be. The recent increase in the use of intravitreal triamcinolone and the intravitreal injection of several drugs for macular degeneration have changed the mentality of how to deliver drugs to the posterior segment. This raises some interesting options also in glaucoma, particularly as we await the results of clinical trials of memantine, a potential neuroprotective drug.

Medication compliance, cost difficulties

Patients are saddled with tremendous cost problems in glaucoma because of their need for chronic medication, and that leads to problems with compliance. The arguments continue among glaucoma specialists as to which prostaglandin is the best and has the fewest side effects.

Managed care formulary issues drive some of this argument. The formularies dictate what drugs we can use, so many times our choices are narrowed by what the managed care formularies are allowing us to use.

Medicare Part D has also created issues for patients. Patients are confused by the range of plans and options, and many cannot make sense of it.

In an attempt to boost compliance, several companies are coming up with different types of dosing aids. Alcon’s Travatan (travoprost) dosing aid is an interesting device. When the patient uses the medication, that is registered by a device which is linked to your computer, and from that information you can actually determine if the patient complies with the medication dosing. I think it’s a useful adjunct. Each of the companies has a slightly different version of a compliance aid.

Investigational procedures

There’s a huge market for glaucoma surgery, a tremendous opportunity for device developers. As the cost of medications goes up, patients are requesting surgical options because they can’t afford their medications.

Currently under investigation, there is the iStent from Glaukos, which is a trabecular bypass device.

And then there’s the NeoMedix Trabectome, an electrosurgical device developed by George Baerveldt to open up the canal system.

An alternative to using Schlemm’s canal is to augment uveoscleral outflow, an approach used with the Solx Gold MicroShunt implant. The gold implant is placed in the suprachoroidal space, and the outflow channels in the shunt are activated using a laser. You can activate as many channels as you like to get the pressure to a desired level. The interesting thing about this is that it’s using a space that no one has ever used before, the suprachoroidal space.

Another technique, being developed by iScience, is canal expansion, which utilizes the entire outflow system. It’s a fascinating procedure. Robert Stegmann was crucial in helping us move this thing along, and now we’ve enrolled more than 100 patients in the study.

What we’ve been doing historically in trabeculectomy is creating an artificial outflow channel. We created a bleb and allowed the fluid to drain from inside the eye through this hole. With the iScience technique we are using the existing canal. We make a scleral flap, a secondary flap into the canal. We then pass a cannula, which has a lumen and a beacon of light, through the entire canal. As we do that we’re injecting a viscoelastic, Healon GV (sodium hyaluronate, Advanced Medical Optics). We’re dilating the canal as we pass this cannula through it, and then we pull it out the other side.

We then tie a 10-0 polypropylene suture to the cannula, and we bring the cannula back out, leaving the suture in the canal as a stent, which keeps the canal open. We have shown with ultrasound that the canal is closed in glaucoma, and by doing this we can keep the canal open. We also tie off the suture, which provides some tension to bring the meshwork forward. Then we close down the flap tightly so there’s no bleb, and we’ve eliminated 90% of our postop glaucoma problem, which is the bleb.

For more information:

• Richard A. Lewis, MD, can be reached at 1515 River Park Drive, Sacramento, CA 95815; 916-649-1515; fax: 916-649-1516; e-mail: rlewiseyemd@yahoo.com.