Since it is widely believed that the retinal nerve fiber layer and the optic nerve provide important information about the presence and progression of Glaucoma, researchers have developed a variety of innovative imaging technologies to provide feedback on the health of the human eye.
The glaucoma treatment and equipment market is expected to increase from 10% to 50% in all segments by 2002. The treatment market comprises office examination and diagnosis visits, which, according to some studies, number approximately 7 million per year, surgical procedures, and the administration/dispensation of drugs. The equipment market includes the sale of diagnostic devices, laser systems, and surgical equipment to physicians, surgical centers, and hospitals.
The Disease
Glaucoma is estimated to affect 1% to 2% of the US population and an estimated 67 million people worldwide. It is the second leading cause of blindness in Caucasians and leading cause in people of African descent. There are two broad classifications of glaucoma: open-angle and angle-closure (or closed-angle). Primary open-angle glaucoma (POAG) is the most prevalent in US and African people, while angle-closure glaucoma appears most frequently in people in Asian countries. POAG accounts for approximately 90% of the total glaucoma cases, or about 3.6 million Americans, with an estimated 63,000 new cases diagnosed annually.
The exact cause of POAG is not known. It has been postulated that, as a person ages, the trabecular meshwork loses its ability to regulate the volume of aqueous humor within the eye. Another recent theory proposes that, as a lack of nourishment begins to damage the optic nerve's ganglion cells, they send a "death signal" to other ganglion cells, thereby creating a domino effect.
Angle-closure glaucoma occurs when the iris moves over the trabecular meshwork, effectively arrowing the angle between the iris and the cornea, blocking the exit channel for the aqueous humor. Angle-closure glaucoma accounts for approximately 10% of the total glaucoma population, or about 330,000 people in the USA, with an estimated 16,500 to 17,500 new cases developing annually.
The Diagnosis
Standard Screening Techniques. Detection of elevated intraocular pressure (IOP) – more than 21 mmhg – is critical to early intervention. The most commonly used diagnostic tool is the tonometer, which is usually administered during an eye exam by sending a puff of air onto the corneal surface and measuring the resulting eye pressure.
If a patient presents with a high IOP reading, the ophthalmologist can perform an ophthalmoscopy by reflecting light off of the back of the retina, creating a picture of the optic nerve. This can be used to determine if any damage has occurred to the optic nerve due to the onset of raised IOP.
Laser-Imaging Technologies
Because some normal-tension patients account for a significant proportion of glaucoma patients, there arose a need for more-advanced diagnostic tools. Since it is widely believed that the retinal nerve fiber layer and the optic nerve provide important information about the presence and progression of the disease, several innovative imaging technologies that can provide quantitative information about the retinal nerve fiber layer and the optic nerve have been developed and are now available to the ophthalmologist. These automated technologies may help in detecting glaucoma at an earlier stage, increasing the potential for limiting irreversible damage and preserving vision. Several of the newer technologies are described below.
Scanning laser polarimetry: Laser Diagnostics Technologies has developed and is marketing its GDx Nerve Fiber Analyzer. The GDx device provides a precise measurement of the nerve fiber layer which can then be compared to a normative database and allow for very early detection of glaucoma. Image acquisition occurs in 0.7 s and provides an automated alignment of baseline images for follow-up analysis, allowing the tracking of small changes over time.
Scanning laser topography/ophthalmoscopy (SLT/SLO): At least three companies produce SLT/SLO devices: Heidelberg Engineering with its Heidelberg Retinal Tomograph, the HRT II; Rodenstock with its SLO; and Odyssey Optical Systems also with its SLO, now distributed by Keeler Ltd. These SLT/SLO devices measure the surface structure of the optic nerve in less than 2 s, using computerized axial tomography. The systems are capable of providing automated alignment of follow-up images to baseline, again, useful in detailing small changes over time.
Another SLO-based device, the Panoramic200 from Optos plc, provides a wider view of the retina and may prove useful in evaluating patients for glaucoma. This device was primarily developed for detection of retinal diseases such as diabetic retinopathy and macular degeneration. It provides an extended ultrawide (200o) single color image of the retina, without the need for pupil dilation.
Optical coherence tomography This device, introduced into the marketplace by Zeiss Humphrey Systems, can depict a dimensional-depth image (rather than a topographical view as with other imaging devices) of the retina's nerve fiber layer and/or the optic nerve for detecting very small changes from normal baseline. It is, perhaps, even more sensitive than the other devices described above.
The Treatment
For more than two decades, glaucoma-treatment protocols have called for first trying drug therapies for lowering IOP, then laser trabeculoplasty, and finally, if nothing else worked, surgical intervention. Over the past several years, some ophthalmologists have advocated using laser therapy first, in conjunction with drugs, but because of the nature of the argon-laser trabeculoplasty procedure, causing scarring of the trabecular meshwork and thus limiting retreatments, that option has had only limited acceptance. Drug therapy alone has always been limited by poor patient compliance of the usual two to three times a day medications that sometimes sting and cause irritation upon application.
Current Therapies. First-generation drugs included pilocarpine for treatment of ocular hypertension and IOP reduction, followed in the early 1970s by the introduction of the beta blockers, which quickly became the therapy of choice. In 2000, annual sales of the beta blockers alone were approximately $235 million in the USA, led by Betoptic from Alcon Labs; Timoptic and Timoptic XE from Merck; and Betagan from Allergan. Today, however, several newer approaches exist. On the pharmaceutical side, three companies, Pharmacia, Alcon, and Allergan, have introduced improved once-a-day next-generation drugs – Xalatin from Pharmacia; Travatan from Alcon; and Lumigan from Allergan. Also, a new laser-treatment option has just been introduced by Coherent Medical (Lumenis), based on selective targeting of pigment in the trabecular meshwork, which appears to offer long-term success for open-angle glaucoma, and is repeatable unlike argon-laser trabeculoplasty.
Angle-closure glaucoma, on the other hand, is primarily treated by surgical intervention, including laser iridotomy, wherein either a Nd:YAG or diode laser is used to punch holes in the iris to allow aqueous outflow from the posterior to the anterior chamber of the eye.
Surgical Alternatives. Despite the primary role of medicines in the management of glaucoma, there are circumstances in which a physician must look to more-aggressive means for controlling the disease. In some cases, a patient may present at a stage in which the risk of visual loss warrants immediate aggressive intervention or side effects where the continued use of drugs may not be tolerable. Furthermore, there are situations where surgical intervention may be more economically feasible when compared to the significant expense associated with using one or more medicines over an extended period of time.
Surgical Methods. In cases where medical or original laser intervention (argon-laser trabeculoplasty) is inadequate to lower IOP, surgical procedures may represent a patient's last chance for the prevention of loss of sight.
•Trabeculectomy – Filtering surgery is the most-common surgical intervention. Long-term studies indicate that as many as half of treated patients will eventually exhibit some loss of original pressure reduction or further progression of the disease.
•Deep sclerectomy – In order to avoid some of the complications of filtration surgery, some surgeons use nonpenetrating techniques, such as deep sclerectomies.
•Tubes/shunts – Other implantable drainage tubes/shunt devices that are used in trabeculectomy surgeries include the Molteno, Baeveldt, and Ahmed implants. Basically composed of plastics, they are implanted in the anterior chamber and drain to an external reservoir. Success rates of as high as 80% have been reported, but significant complications are possible, and, as such, these implants are usually restricted to high-risk patients or those that have failed trabeculectomies.
Laser Approaches
Laser trabeculoplasty (ALT/SLT) – Typically using an argon or diode laser, laser trabeculoplasty is the most-common laser procedure performed for treating open-angle glaucoma. A series of 50 to 100 laser coagulative burns are placed in the peripheral trabecular meshwork, creating scars that help to improve fluid flow through the shrunken tissue surrounding the scars. An estimated 250,000 to 300,000 procedures are performed annually in the USA, with the effectiveness of the procedure varying from patient to patient. Usually, an average of 7 mmHg IOP reduction occurs. However, long-term studies indicate that pressure is controlled in only 45% to 55% of treated patients after five years, and the laser treatment cannot be repeated because of the permanent scarring that occurs.
Selective laser trabeculoplasty (SLT) has recently been approved by the FDA and is being introduced into the marketplace. Using a Q-switched frequency-doubled Nd:YAG laser made specifically for the procedure by Coherent Medical, the Selecta 7000, SLT is a nonthermal, repeatable laser procedure that in international clinical trials achieved an 80% success rate in obtaining a 23% IOP reduction that lasted for up to 24 months. Minimum complications were seen, and all were easily treated.
The procedure is similar to ALT, with 45 to 55 laser spots placed along an 180o arc in the trabecular meshwork. The difference, however, is that, by selectively targeting the melanin pigment within the trabecular meshwork cells rather than creating a thermal burn, a cellular reaction occurs that enhances fluid outflow without thermal destruction of the targeted cells. This means that the procedure is repeatable. With the demonstrated efficacy in patients with primarily open-angle glaucoma, even in patients with previously failed ALTs, it is our belief that SLT could conceivably evolve as the ideal primary treatment option for patients who cannot tolerate or are noncompliant with medication.
Laser iridotomy – Some forms of angle-closure glaucoma can be treated with the laser-iridotomy procedure. Iridotomy is preformed using either an argon, diode, or Nd:YAG laser to create several holes in the iris to allow outflow of aqueous humor between the posterior and anterior chambers. Iridotomy can be viewed as a preventative measure as it minimizes the likelihood of further surgical intervention. Laser iridotomy is also useful in the management of pigmentary glaucoma.
Laser cytophotocoagulation – The primary objective of laser cytophotocoagulation is to reduce the amount of fluid produced in the eye through the selective destruction of the ciliary process, the tissue responsible for producing the aqueous. EndOptics and Iridex both produce small diode lasers and the delivery systems for performing this procedure. The EndOptics probe device is inserted into the eye and accesses/targets the ciliary process, which is located beneath the iris, while the Iridex G-Probe does not enter the eye but rather is a transcleral procedure, performed from the outside of the sclera. The laser cytophotocoagulation procedure is normally done when all other methods have failed, with the real problem being not knowing how much of the ciliary process cells to destroy to effectively control the fluid buildup and elevated IOP.
Irving J. Arons, contributing editor, Medical Laser Report
Acknowledgement:
Several sections of this report were adapted from: Glaucoma in the 21st Century: New Ideas, Novel Treatments, authored by Dave Therkelsen and William Quirk of Dain Rauscher Wessels, February 2001.