Clinical tests imminent for laser glaucoma treatment

By using a specially modified laser, researchers may have found a way to slow down and even stop the advance of a form of blindness known as primary open-angle glaucoma. Although not an outright cure for the underlying vision problem, the new laser surgery compensates for its effects and prevents further visual loss. Because the technique builds upon laser/glaucoma research done a decade earlier and upon more recent human trials in Europe, it is likely to be approved by the US Food and Drug Administration (FDA) for clinical trials here as early as this summer, say its developers. If all goes well, the laser procedure may be widely available for general use as soon as the year 2004.

Primary open-angle glaucoma is the cause of one of the world’s most common forms of blindness, affecting approximately 7 million people annually. It occurs when fluid inside the eyeball cannot drain properly, causing internal pressure to build. Like a balloon filled with too much air, the eyeball gives way at its weakest point — in this case, where the optic nerve leaves the eye to ferry visual information to the brain. Individual cells in the optic nerve at this location are gradually squeezed to death, eventually causing permanent blindness.

Visual loss begins with barely perceptible “blind spots” on the patient’s peripheral field of vision, gradually moving toward the center. Because it is a painless and slow process, the patient usually does not notice it until the condition’s later stages, when damage is irreversible. About 3 million Americans have some form of glaucoma. Most are over the age of 50.

While there is no cure for primary open-angle glaucoma, doctors have tried halting its progress with a combination of up to five drugs taken in the form of eyedrops up to four times daily. These typically function by increasing the rate at which fluid flows out of the eye or decreasing the rate at which fluid is produced. But they have drawbacks: The drugs are expensive, hard to deliver accurately and contain numerous harmful side effects. They can cause patients to experience burning sensations, allergic reactions, difficulties in breathing, fluctuations in blood pressure, dizziness, fatigue and insomnia, among other effects. Hence, patients often don’t comply with the drug regimen, allowing the blindness to advance once again.

But a new treatment known as gonioscopic laser trabecular ablation promises to alleviate primary open-angle glaucoma without the need for daily medications. Under development by SOLX Inc. of Boston, this laser treatment heats and expands the “drain” of the eye, allowing backed-up internal fluid to escape more easily and thus relieve the internal pressure.

The treatment’s medical monitor, Dr. Roger Steinert, professor of ophthalmology at Massachusetts Eye & Ear Infirmary in Boston, calls himself “guardedly optimistic and excited, based on what happened in Spain.” 150 glaucoma patients in Barcelona and Madrid were treated by Dr. Gabriel Simon with a flashlamp-pumped, Q-switched Ti:sapphire laser operating in the near-IR range at 50 to 100 mJ. (Despite numerous attempts by Biophotonics International, Dr. Simon did not respond to inquiries about his test results or procedures.)

Inside the eye

Though we often don’t realize it, the human eyeball is not static, but part of a larger system in which fluids constantly circulate. The Glaucoma Foundation in New York has a simple analogy in its patient guide: “Think of your eye as a sink, in which the faucet is always running and the drain is always open.” The faucet is a tiny gland called the ciliary body, located between the iris and the lens; the drain is the trabecular meshwork, located where the iris meets the wall of the eye. The ciliary body produces a nearly clear, watery fluid called the aqueous humor, which bathes and delivers nutrients to the clear parts of the eye. The aqueous humor constantly circulates, then exits via the trabecular meshwork to the blood system.

The meshwork is an efficient way of connecting the aqueous humor to the rest of the circulatory system, but this sieve-like structure can be easily obstructed. For example, dandruff-like material that is rubbed off the lens by the movement of the iris can build up — essentially causing the drain to clog and the fluid to back up. (This material also results in the characteristic dull gray gleam of the glaucomous eyeball in its later stages.) Doctors can release the excess aqueous humor by surgically removing a small section of the trabecular meshwork. But this procedure has drawbacks as well: Patients usually need a hospital stay, do not have normal visual acuity for several weeks and are more prone to developing cataracts a few years later.

Enter laser surgery. This painless procedure takes between 10 and 20 minutes and can be performed in a doctor’s office. Patients can resume normal activities after the operation, with no increased risk for cataracts. Most patients can reduce the amount of eye medications, and some patients can discontinue drugs entirely.

Inside the laser

Previous researchers had experimented with laser surgery for treating glaucoma, using argon-ion lasers at 514 nm or frequency-doubled, Q-switched Nd:YAG lasers at 532 nm. These lasers essentially punch larger holes in the tissue of the trabecular meshwork with short, highly concentrated pulses of energy. While the treatment is effective, the meshwork usually heals itself after one to two months, and the problem recurs.

In contrast, researchers affiliated with SOLX rely upon the laser’s thermal effects. The system works by heating up the trabecular meshwork, causing some areas to shrink and others to open. This allows fluid to drain faster, similar to replacing a fine-mesh sieve with one containing larger spacing.

Steinert noted that the duration of the laser’s pulse is key — the pulse must be long enough to affect the trabecular meshwork while not causing any nearby healthy eye tissue to overheat. The researchers suspected that a 800-nm pulse that lasted for 10 microseconds would be ideal, but they needed some way to reach that pulse length, said Doug Adams, founder of SOLX. They experimented with alexandrite lasers, which are usually tunable from 700 to 820 nm, but the duration of these lasers’ typical Q-switched pulse only ranges from 20 to 200 ns.

They found the solution with a device made by Light Age of Somerset, N.J., that its designers call a “temporal pulse stretcher.” It prolongs each pulse in a manner that is continuously variable from 200 ns to 10 microseconds, using an optical feedback system. The system monitors the laser output energy during the Q-switching process to slow the rate of energy extraction from the laser resonator and thereby lengthen the pulse in a controlled and reproducible fashion.

Although the team has had success so far, human clinical trials are still in the early stages in the US. “They have to have a better understanding of the laser/tissue interaction,” averred Steinert. One problem has been that glaucoma rarely afflicts animals — which means that there are no lab animals that can be tested.

But with successful results upon humans overseas, and promising earlier laser/glaucoma studies, researchers are optimistic. In a best-case scenario, the procedure could be routinely available in the US in as little as three years. Adams said human clinical tests are tentatively scheduled to begin this summer in Boston, Chicago, New York and Miami.

One day, light may be used to preserve sight.

Biophotonics International
Dan Drollette

CAPTION: By using a pulse-stretched, Q-switched alexandrite laser, researchers can selectively heat the eyeball’s trabecular meshwork. Once this “drain” of the eye is opened, it allows more of the aqueous humor to escape, thereby stopping further damage to the optic nerve.

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