Article Date: 8/1/2001

More insights into this challenging disease.

This month, we complete the discussion we began in May about new developments in diagnosing and treating glaucoma. Read on to learn about new tomography scans, the latest thought on dietary supplements and more.

How Does It Feel?

Understanding your patients' emotional aspects of vision loss.

You know a lot about the physical effects of vision loss and about what drugs and aids can help. But have you thought about the psychological impact vision loss has on your patients? Upon becoming legally blind, Bill Chapman, Ed.D., a 30-year consultant to the visually impaired, wrote the book Coping With Vision Loss, and presents the following insights.


Marijuana Hopes Quashed


Patients who look to marijuana as an alternate therapy for treating glaucoma won't be able to do so legally. The Supreme Court recently ruled 8 to 0 that California cannabis clubs can't distribute marijuana for medical conditions because it violates federal law. People can still use the drug in states that permit it, but the ruling will make it more difficult to obtain.

Corneal thickness can interfere with diagnosis.

Researchers at the Mayo Clinic have discovered that corneal thickness can confound the diagnosis and classification of ocular hypertension.

Subjects selected from the Ocular Hypertension Treatment Study who had ocular hypertension were found to have greater average corneal thickness than age-matched controls.

"Because the major diagnostic criterion for ocular hypertension is based primarily on the clinical measurement of intraocular pressure (IOP), any variable that can affect the measure of IOP could lead to an errant diagnosis of ocular hypertension," the researchers note. It could also modify the estimated risk of patients with ocular hypertension who are progressing to glaucoma.

Filtering Surgery
Technological developments you should know about.
BY JOHN GELVIN, O.D., F.A.A.O., Kansas City, Mo.

Most of you are probably familiar with modern trends of trabeculectomies. Antimetabolites such as 5-fluorouracil and mitomycin C have successfully lowered intraocular pressure (IOP) into the low teens without the use of medications postsurgery. Releaseable or laserable sutures of the scleral flap allow IOP to be slowly reduced over a 4-week post-op period, reducing hypotony. However, you might not be aware of these newer developments in filtering surgery.

A patient's eye after undergoing filtering surgery.

Trabeculectomy still gives the best IOP-lowering results, but keep up with the research because it's changing all the time.

Dr. Gelvin is with Glaucoma Services at Hunkeler Eye Center in Kansas City, Mo.


A Vaccine for the Optic Nerve?
Multiple sclerosis drug shows promise

Professor Michal Schwartz of the Weizmann Institute in Rehovot, Israel, has demonstrated that vaccination with glatiramer acetate (Copaxone), a drug that treats multiple sclerosis, may protect the optic nerve.

Dr. Schwartz and her associates discovered that cell death resulting from increased intraocular pressure (IOP) initiates the release of chemicals such as glutamate at toxic levels that may damage neighboring healthy cells in a process called "secondary degeneration." To combat this, Dr. Schwartz tried to enlist the body's immune system using fragments of proteins from the outside covering of the nerve. Vaccinations with these proteins prevented optic nerve degeneration, but she next needed to be sure of which specific protein fragments wouldn't cause autoimmune disease.

She discovered that glatiramer acetate was a safe synthetic alternative to use in rats. Rats with high IOP showed only a 4% loss of cells when vaccinated with glatiramer acetate as opposed to a 28% loss in rats that weren't vaccinated.

Because Copaxone is already FDA-approved, scientists hope that human trials can begin soon.

How Will I Know?
When to refer a patient for filtering surgery.

There are several reasons why one of your glaucoma patients may need to undergo filtering surgery:

Over the last few years, we've seen that the acceptable level for IOP control has been reduced so that we consider surgery at an earlier point. We've begun to ask ourselves, "What will the patient's eyes look like in 20 years if he continues at the current IOP level," rather than considering only the patient's immediate future.

There's no one correct equation for calculating the proper target IOP, but most doctors consider the patient's highest IOP level, the status of his optic nerve and his visual fields to come to an acceptable figure.

Generally, the greater the nerve damage, the lower the IOP needs to be. Data from the Advanced Glaucoma Intervention Study of 2000 showed that over an 8-year period, patients with IOPs that averaged 12.3 mm Hg had stable visual fields, while higher IOPs were associated with greater decay.

It's wise to aim for IOPs in the mid-teens instead of accepting an IOP lower than 21 mm Hg. We've simply become more aggressive in our approach.

Dr. Fingeret is chief of the Optometry Section at Brooklyn/St. Albans Campus, Department of Veterans Administration New York Harbor Health Care System. He's a member of the board of directors of the Glaucoma Foundation and is chair of the glaucoma diplomate committee for the American Academy of Optometry.

A Better Mousetrap?
Why gingko biloba extract might have value in treating glaucoma.
BY ROBERT RITCH, M.D., New York, New York

 We now recognize that glaucoma damage is caused not only by elevated intraocular pressure (IOP), but also by non-pressure-dependent factors. These include systemic hypotension, cardiovascular disease, vasospasm (migraine, Raynaud's disease), defective vascular autoregulation, autoimmune disease, hemorrheologic abnormalities and cerebral microvascular ischemia. However, treatment goals for open-angle glaucoma traditionally have focused almost exclusively on lowering IOP with drugs, laser therapy or surgery.

New approaches under investigation include agents that could improve blood flow to the eye, and neuroprotective drugs. However, they pose some problems.


Measuring IOP at Home
The Proview Eye Pressure Monitor


Bausch & Lomb has introduced a new intraocular pressure (IOP)-monitoring device for use at home. Called the Proview Eye Pressure Monitor, it's the first tonometer that detects changes in IOP "off of the cornea" and "out of the office."

To use it, the patient presses the tonometer on his partly closed eyelid until he sees a pressure phosphene (a dark circle with a ring of light around it). It requires no anesthetic, tracks the impact of drug therapies and allows for insight into patient-specific diurnal IOP variations.

Proview is sold as a complete monitoring kit containing the monitor, a log book, instruction manual and more. It's available through national wholesalers, distributors and pharmacies. If a given pharmacy doesn't have it, you can request that they get it from their wholesaler. You could also order directly from Bausch & Lomb by calling 1-800-323-0000 for a minimum order of three units.

Pharmacologic limitations

Pharmacologic treatment of non-IOP-dependent mechanisms in glaucoma has been limited to calcium channel blockers, which are also used to treat systemic hypertension, coronary artery disease, stroke, arrhythmias, Raynaud's disease and migraine.

Though calcium channel blockers have been reported to improve ocular blood flow and have neuroprotective effects, eye care specialists haven't widely adopted them because of reports of increased morbidity with calcium channel blockers, and also because we still can't tell which patients these treatments will harm and which they'll help. So what's the alternative?

The gingko option

Ginkgo biloba extract (GBE) is freely available and has several biological actions that make it potentially important in treating glaucoma. These actions include: improvement of central and peripheral blood flow, reduction of vasospasm, reduction of serum viscosity and more. GBE as a potential antiglaucoma therapy deserves intensive scrutiny.

GBE contains more than 60 known bioactive compounds. Not all brands are sgltandardized for consistency of components, and some are labeled as containing flavonoids only. Caution patients that they might not have all the active ingredients.

GBE protects against free radical damage and lipid peroxidation in various tissues and experimental systems. Its antioxidant potential is comparable to water-soluble antioxidants such as ascorbic acid and glutathione, and lipid-solubles such as
alpha-tocopherol and retinol acetate. GBE inhibits oxidation of cholesterol in low-density lipoproteins. It preserves mitochondrial metabolism and adenosine triphosphate (ATP) production in tissues, and it partially prevents changes associated with mitochondrial aging. GBE can scavenge nitric oxide and possibly inhibit its production.

Experimental evidence indicates that GBE has neuroprotective properties in hypoxia/ischemia, seizure activity, cerebral edema and peripheral nerve damage. It improves peripheral and cerebral blood flow and hemorrheologic indices, decreasing blood viscosity and increasing erythrocyte deformability. Better blood flow should result.

GBE increases skin perfusion. I've noticed remarkable improvement in Raynaud's disease, which is commonly associated with normal-tension glaucoma. Patients often report improvement in cold hands and feet and also fewer migraine attacks. Interestingly, GBE prevented vasomotor changes of extremities in mountaineers in the Himalayas and inhibited acute mountain sickness.

GBE and the eye

In the eye, GBE increased end diastolic velocity in the ophthalmic artery by 23% in a double-masked, placebo-controlled study in normal volunteers. GBE reduces ischemia-reperfusion injury in rat retinas and protects against electroretinographic alterations associated with chloroquine retinopathy and diabetes. It affords protection against light-induced retinal damage and may be useful prophylactically in patients undergoing ocular surgery.

Although neuroprotective strategies and pharmaceutical agents have been used to treat disorders of the central and peripheral nervous systems (trauma, epilepsy, stroke, Huntington's disease, amyotrophic lateral sclerosis), none has yet been used to treat glaucoma. A prospective, placebo-controlled, multi-institutional trial of memantine, a potentially neuroprotective agent, is underway.

GBE has properties that should be beneficial in treating non-IOP-dependent mechanisms in glaucoma. Its beneficial actions, including increased ocular blood flow, antioxidant activity, platelet activating factor inhibitory activity, nitric oxide inhibition and neuroprotective activity, suggest that it could have major therapeutic value.

(References available upon request.)

Robert Ritch, M.D., is glaucoma service professor and chief, Glaucoma Services, and surgeon director, The New York Eye and Ear Infirmary, New York, N.Y.

Technology Revolution!
Introducing the Optical Coherence Tomography Scan.
BY J. JAMES THIMONS, O.D., Fairfield, Conn.

The last decade has seen a host of new technologies directed at improving our diagnostic and therapeutic efficacy in glaucoma management. These include: Short Wavelength Automated Perimetry (SWAP), Frequency Doubling Technology and Swedish Interactive Thresholding Algorithm for visual field testing, Laser Diagnostic Technologies' GDx Nerve Fiber Analyzer and the Heidelberg Retina Tomograph (HRT) for nerve fiber layer analysis and optic nerve imaging. Now Zeiss Humphrey Systems' Optical Coherence Tomography Scan (OCT2) will make its debut.

Understanding the OCT2

The OCT2 is a revolutionary laser-based diagnostic system that uses a noninvasive technology to assess and monitor a broad array of ophthalmic conditions such as macular edema, macular holes, optic nerve topography and nerve fiber layer thickness. OCT2 evaluates the reflectance of posterior segment structures and incorporates a mathematical algorithm that localizes the anterior and posterior limits of the retinal nerve fiber layer (NFL).

A low coherence near-infrared light (850 nm) from a super luminescent diode laser captures the retinal backscatter.

Then a fiber optic interferometer resolves this. Essentially what occurs is that the system captures 100 separate longitudinal A-scans and displays a composite image of them on the monitor. The image is captured in about 1 second and processing takes approximately 1 minute. The analysis of the signal corresponding to the nerve fiber is translated into a numeric representation of the NFL.

The OCT2 diagnostic system.

Opportunity knocked

The NFL is an important element in diagnosing glaucoma. A study in Archives of Ophthalmology shows that the NFL was thinner in the eyes of ocular hypertensives than in normal eyes. Other studies in Ophthalmology and the American Journal of Ophthalmology show similar findings in ocular hypertensive and glaucomatous patients.

For us, it's not an issue of whether NFL analysis is appropriate for glaucoma therapy, but rather, which of the systems produces the most reliable and consistent images. The two currently available units (HRT and GDx ) have been well researched and have shown to provide accurate and objective analysis of the NFL in most patients.

The HRT is a confocal scanning laser ophthalmoscope that creates 32 coronal sections of the optic nerve to a depth of approximately 3.5 mm. This produces a 3-dimensional topographic map of the optic nerve head. Additionally, it indirectly and simultaneously analyzes the NFL.

The GDx is a scanning laser polarimeter that measures NFL thickness by analyzing the amount of beam "retardation" and linearly relating it to thickness of the NFL. Because analysis of the NFL is complex, neither system has established itself as definitive, creating opportunities for systems such as the OCT2. It'll be interesting to measure the efficacy of each system as more clinical assessments determine which technology is superior.

Talia's Retinal Thickness Analyzer (RTA), also used in glaucoma diagnosis, uses a slit imaging system that scans multiple image areas and an algorithm system to analyze the data to create a retinal thickness map and comparative report. Additionally, the RTA system generates disc topography maps by applying edge detection analysis to light reflections from the optic nerve head. Like the GDx and HRT, however, it's also not definitive.

Looking ahead

The OCT2 will add a potentially significant competitor to our armamentarium in glaucoma diagnosis and could prove to be the next generation of instrumentation in the changing field of glaucoma therapy.

(References available upon request.)

Dr. Thimons is the director of Ophthalmic Consultants of Connecticut and Clinical Director of OM.

Optometric Management, Issue: August 2001