New Developments in Glaucoma Shape Treatment

Recent research and innovations help clinicians detect glaucoma earlier and treat it more effectively.

BY DIANE DONOFRIO ANGELUCCI, CONTRIBUTING EDITOR

Over the last 5 years, glaucoma specialists have witnessed many advances that continue to transform the way they manage the disease. Read on to learn more about what experts believe have been the most significant recent advances in detection and treatment of glaucoma and what they hope to see in the future.

Structural and Functional Assessment

Over the last several years, findings from the Ocular Hypertension Treatment Study (OHTS) have drawn increased attention to the optic nerve in managing patients with glaucoma. "I think that study emphasized the importance of the optic nerve as a way of detecting the onset of glaucoma before functional testing may reveal such," says Eve Higginbotham, M.D., dean and senior vice president for academic affairs, Morehouse School of Medicine, Atlanta.

With greater focus on the optic nerve, ophthalmologists are relying increasingly on a variety of imaging devices in clinical practice. "The benefit of those is helping clinicians to more quantitatively or objectively evaluate the optic nerve, and I think, along with that evaluation, it's helped us to be more correct in our evaluations," says Robert Noecker, M.D., M.B.A., University of Pittsburgh Medical Center Eye Center, Pittsburgh.

Dr. Higginbotham explains that Heidelberg Retinal Tomography ([HRT] Heidelberg, Vista, Calif.) technology continues to advance, including an important modification that allows doctors to avoid errors that might occur when drawing the contour of the disk. Advances in optical coherence tomography (OCT) technology also have brought greater utility to that technology, she says. She contends that the improvements in OCT and HRT will make measurement of changes in the optic nerve more precise. "However, there is no substitute for a clinical examination of the optic nerve," she explains. "These are enhancements."

Tony Realini, M.D., associate professor of ophthalmology, West Virginia University Eye Institute, Morgantown, W. Va., warns that the great popularity of imaging devices may have allowed them to take the place of a thorough clinical examination of the optic nerve. "The advantages of the imaging systems are that they give you an objective and usually highly reproducible measurement of optic nerve structure, but their ability to detect change over time accurately has not been established at this point," he says. "For example," he explains, "ophthalmologists should not assume that disease is progressing in a patient who shows progression on an imaging device but whose clinical optic nerve examination remains stable."

In monitoring visual function, short wavelength automated perimetry (SWAP) and frequency doubling technology (FDT) provide more information than previous visual function tests. "The advantage of these technologies is that they select out subpopulations of photoreceptors to be able to detect glaucoma earlier, especially in ocular hypertensive or glaucoma suspect patients," Dr. Noecker says.

Furthermore, SWAP has become faster for patients and, therefore, produces more reliable results. "In the past few years, I think it has been tremendously beneficial that the once very long SWAP test has now been made clinically more practical by incorporating the SITA testing algorithm," Dr. Realini says. "This shortens the test and makes it much easier to get quality data without a fatigue factor for most patients."

New Medical Strategies

In recent years, prostaglandins have solidified their status as first-line therapy in lowering IOP. In addition, manufacturers are introducing more medications without the preservative benzalkonium chloride (BAK), such as BAKfree travoprost (Travatan Z, Alcon) and newer versions of brimonidine tartrate (Alphagan P, Allergan). Long-term use of BAK has been associated with ocular surface inflammation. An inflamed ocular surface may make necessary glaucoma interventions more difficult.

Research also has provided important medical treatment information. "We all have many, many patients who are glaucoma suspects, and it's a challenge to figure out exactly when to start treating," Dr. Realini says. "Global risk assessment has been a helpful concept to help guide those sorts of decisions. There have been several risk calculators that have debuted rising from data based on the OHTS study and the European Glaucoma Prevention Study. These things help us to identify which of our patients are most likely to develop glaucoma in the future and are thus likely to benefit from preventative therapy now."

Additionally, there is greater emphasis on patient adherence to treatment and persistency, Dr. Higginbotham says, She claims there is a new understanding about the barriers to adherence, as well as evidence in the literature that once-daily medications are associated with greater adherence. Devices also are available to facilitate instillation of drugs, such as Xal-Ease for latanoprost (Xalatan, Pfizer), a reminder device from Allergan for bimatoprost (Lumigan), and a computer tracking system for patients taking travoprost. which is as significant as the introduction of a new drug. "Essentially, if patients don't take their medication, there's really no medical intervention," Dr. Higginbotham says.

Laser Developments

Innovations have renewed interest in laser treatments for glaucoma. Although selective laser trabeculoplasty (SLT) was introduced several years ago, Dr. Noecker believes it has matured in the last 5 years. "I think SLT has really dramatically changed how people look at laser trabeculoplasty and I'd argue it's one of the safest things that we do for therapeutic care of glaucoma," he says. "It has been proven to work well and it's really become part of the treatment algorithm." Previously, laser trabeculoplasty with argon laser trabeculoplasty (ALT) fell out of favor because ophthalmologists were limited in the number of times they could perform the treatment. It also carried a risk of permanent structural damage, he says.

Dr. Higginbotham finds SLT valuable as well. "Certainly patients who undergo laser treatment can have variable results, but I would say generally SLT has become a measure that we can use before taking the patient for incisional surgery. It's proven to be of benefit in some patients," she says.

Dr. Realini agrees that SLT has renewed interest in laser trabeculoplasty but asserts that available data suggest that SLT has equivalent safety and efficacy to ALT. "The advantage of SLT over ALT is not clear based on the existing data," he says, adding that there has been no information published in the peer-reviewed literature on the repeatability of SLT since it was approved in the United States in 2001.

A recently introduced alternative, micropulse laser trabeculoplasty (MLT), performed with the 810-m IQ 810 photocoagulator (Iridex, Mountain View, Calif.), is garnering interest. "The first advantage is there is no inflammatory response in the eye," says Anthony Economou, D.O., in private practice in Tulsa, Okla. "With MLT, we don't have to utilize anti-inflammatory medication. In essence, we're letting the laser work better on the area that it's targeting."

In addition, he explains, MLT delivers lower energy than ALT and SLT and produces less trabecular meshwork damage, minimizing post-trabeculoplasty IOP spikes. As an added advantage, he says that unlike SLT, MLT does not require a laser dedicated only to one procedure.

However, Dr. Economou believes MLT is still in the development stage and researchers and other users will manipulate the parameters when performing MLT. "I have increased my duration time from 200 ms, which is recommended, to 300 ms, and I'm noticing even better results," he says.

Surgical Advances

Among surgical alternatives for glaucoma, trabeculectomy with mitomycin C still reigns as the gold standard. However, surgical options continue to emerge.

"I think tube-shunt surgery has just really been more of an evolution of a technique. There have been small modifications made where it's an easier, kind of quicker procedure than it's been in the past," says Dr. Noecker. In some studies, he and his colleagues have used fibrin glue (Tisseel, Baxter, Deerfield, Ill.) to shorten operative time and increase patient comfort.

"Also, the Tube vs. Trabeculec tomy Study pointed out that in patients who failed primary trabeculectomy, the better option is probably to go with the tube vs. trying to do another trabeculectomy," Dr. Noecker says.

A number of devices have been introduced, such as the Trabectome system (NeoMedix, Tustin, Calif.), EyePass Glaucoma Implant (GMP Companies, Inc., Fort Lauderdale, Fla.)., and several angle-based procedures that aim to bypass the obstruction at the trabecular meshwork but preserve normal outflow from Schlemm's canal onward, Dr. Realini says. "These techniques are still undergoing refinement, and few have been compared at this point in prospective randomized trials to trabeculectomy, which remains the gold standard, so where they will fit in our surgical armamentarium hasn't yet been established."

Although a segment of the ophthalmic community believes nonpenetrating trabeculectomy may be useful, Dr. Higginbotham believes that shunts usually should not be first-line options. She favors trabeculectomy with mitomycin C as her primary surgical choice for patients. "The other procedures certainly may have their role," she says, "but I think we all have to recognize that we only have that one first-time opportunity to incise the conjunctiva where we might actually get our best success from a surgical procedure, so while I wouldn't necessarily use many of the other options as a primary procedure, I certainly recognize the role of setons and other procedures as a secondary."

Endocyclophotocoagulation (ECP) also has gained popularity. "That's placed in the treatment algorithm often in combination with cataract surgery as a way to get the pressure down by a moderate amount and reduce the patient need for medication without the risk of hypotony that you might have with some of the other procedures," Dr. Noecker says.

Dr. Higginbotham believes transscleral diode cyclophotocoagulation is an effective way of treating patients who cannot undergo surgical intervention.

Looking Ahead

Ophthalmologists also anticipate a variety of advances in the future in detecting and treating glaucoma. With the use of newer fixed-combination drugs outside the United States, such as latanoprost/timolol (Xalcom, Pfizer) and brimonidine/timolol (Combigan, Allergan), Dr. Higginbotham eagerly anticipates approval of at least one of the available candidates in the United States. These are expected to increase adherence.

Glaucoma specialists also expect drug-delivery devices to be a huge breakthrough in treating the disease. "There are several interesting and innovative ophthalmic drug delivery devices being investigated at this point," Dr. Realini says. "Perhaps one or more will be applicable to glaucoma medications and will allow us to dose glaucoma medications on a monthly or multi-monthly basis using a sustained delivery technology rather than relying on patients to remember to put their drops in regularly day in and day out."

To make treatment more effective, Dr. Economou hopes to see continuous-monitoring devices. "An internal monitoring device for IOP would be invaluable," he says, citing concerns raised by studies that measured IOP while patients were asleep. He also would like to see an IOP-measuring device that is not influenced by corneal thickness, corneal curvature or corneal hysteresis.

As for future procedures, Dr. Noecker believes laser treatments and surgery will continue to evolve to become less invasive with fewer side effects. "We've seen that already with SLT and ECP in the laser therapies, but I think there will be more refinement," he says. "We'll see what MLT does as well as a cost-effective benign treatment for that condition."

Dr. Higginbotham still hopes for a blebless procedure that effectively reduces IOP. "That's been the gold at the end of the rainbow for as long as I've been in ophthalmology, so I remain hopeful that we'll achieve that," she says. "The only way to get to there is to show that perhaps some of these emerging procedures may have the same long-term success that we see with trabeculectomy — I haven't seen that yet."

When considering diagnostic technology, Dr. Higginbotham would like to see more data on the effectiveness of current technology in monitoring patients long term. "As a clinician, I want to see some long-term validation on more of these technologies beyond HRT," she says.

Ophthalmologists also hope to see advances in genomic medicine in determining the genetic profile of patients at highest risk for glaucoma. "I definitely think that there's reason for hope given the emerging science in genomic medicine: the fact that we will ultimately have a way to determine the genetic profile of those patients who might be at highest risk," Dr. Higginbotham says. "Whether such tests will be available in the near future is not clear, but I certainly would anticipate that happening in the next 10 years." OM

Editor's note: Dr. Noecker is a speaker for Alcon, Allergan, Endo Optics, Heidelberg and Lumenis. Dr. Higginbotham is a speaker for Alcon, Allergan and Pfizer. Dr. Realini receives research funds from and is a speaker for Alcon, Merck and Pfizer. Dr. Economou has no financial interest in products discussed in this article.