Chicago—Douglas H. Johnson, MD, discussed several aspects of his research into aqueous outflow that could lead to a better understanding of the cause of glaucoma and ultimately contribute to a cure. He delivered the American Glaucoma Society lecture at the American Academy of Ophthalmology's glaucoma subspecialty day program.
Dr. Johnson, professor of ophthalmology, Mayo Clinic College of Medicine, Rochester, MN, has been a member of the Mayo Medical School faculty since 1983 and maintains a clinical practice in the subspecialty of glaucoma and a basic science research laboratory probing the pathogenesis of glaucoma.
He began by describing outflow resistance, which seems to begin in the interlamellar spaces of the meshwork. He noted that more than 40 years ago, W. Morton Grant, MD, performed trabeculotomies on eye bank eyes and discovered that if the trabecular meshwork was incised, half the outflow resistance in the normal eye disappeared. "But it's important to remember that half of the outflow resistance remains. That means from the sclera downstream, there is outflow resistance," Dr. Johnson added.
Trabecular meshwork details
Dr. Johnson presented images obtained through scanning electron microscopy showing that the seemingly simple, pencil-shaped beams of collagen that make up the trabecular meshwork are actually a series of flat plates similar to pages in a book. These detailed images also show that the empty spaces between lamellae are quite large and, more importantly, that a series of ciliary body tendons runs through the trabecular meshwork and is inserted into the Schlemm's canal.
"They are quite complex, probably designed by nature to tether the inner wall of the canal so that it doesn't collapse," Dr. Johnson said. "These tendons pull on the meshwork when you put pilocarpine in the eye."
With glaucoma these tendons become thicker, but the aqueous channels between them are still wide enough that significant resistance does not arise from plugged pathways. One theory suggests that if these tendons act like glue, stiffening the meshwork, then deformation of the inner wall could not happen as easily and might be a link to glaucoma, Dr. Johnson said. In that case, these tendons should appear early in the disease process.
To learn more about this process, Dr. Johnson, in conjunction with Dr. Elke Lutjen-Drecoll in Nuremberg, Germany, studied a series of whole autopsy eyes of patients who had various stages of glaucoma, from normal eyes to those with severe damage. They found no correlation between the highest pressures recorded in the patients' medical records and the thickness of tendons in the eyes. "That tells us that the tendon sheaths are not the cause of the elevated pressure," he said. "It must be something else."
The investigators also wanted to examine the juxtacanalicular meshwork. In eyes with pseudoexfoliative glaucoma, they observed material under the inner wall, but it differed from the tendon sheaths seen in glaucomatous eyes. The material appeared to be a series of small, randomly spaced fibers. Plotting pressures, they discovered a correlation between elevation and the amount of pseudoexfoliation.
"Just like you would think, pseudoexfoliation is plain old secondary glaucoma caused by a plumbing problem of junk in the way. That differs from primary open-angle glaucoma (POAG), which seems to be a tendon sheath problem. So in POAG, tendon sheaths are not the cause of glaucoma pressure, but they probably are a marker for the disease," Dr. Johnson said. "There seems to be a common factor that causes the pressure elevation as well as the increase in the amount of these tendon sheaths."