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Clinical Update: Glaucoma
The Dynamic Angle: New Concepts of Angle-Closure Glaucoma
Anatomy is no longer destiny when it comes to angle closure and angle-closure glaucoma (ACG). Recent discoveries about the abnormal physiological mechanisms underlying these conditions have revolutionized our thinking about a disease responsible for nearly half of glaucoma blindness worldwide. Angle closure and ACG involve more than static anatomy.
“The angle is a dynamic structure,” said Jeffrey M. Liebmann, MD, who worked to develop clinical applications of ultrasound biomicroscopy (UBM) in the 1990s, which yielded new information on the structural anatomy of eyes with angle closure. “UBM also led to conceptual advances regarding the dynamic functional relationships of ocular structures such as the iris, lens, ciliary body, anterior and posterior chambers, and the angle. For the first time, it was possible to view, in vivo, the response of the iris and angle to different illumination; and we learned that angle-closure detection is enhanced by performing gonioscopy in a darkened room,” Dr. Liebmann said.
High-resolution optical coherence tomography (OCT; Fig. 1) has also contributed to the emerging concepts. Not only has it improved visualization but it also allows measurement of structures that could previously be examined only through histopathology: the iris-lens relationship, iris stroma, choroid, and vitreous.
Here is a closer look at new findings about the dynamic angle—and how they may help clinicians manage their patients with narrow angles.
Anatomy Is the Start
Angle closure is defined as physical obstruction of the trabecular meshwork by the iris, said Dr. Liebmann, clinical professor of ophthalmology, New York University, and director, Glaucoma Services, Manhattan Eye, Ear and Throat Hospital. He described a typically chronic and slowly progressive process in which trabecular dysfunction may eventually lead to elevated IOP and subsequent glaucomatous damage to the optic nerve and visual field. “Acute attacks of angle closure are much less common than chronic angle-closure glaucoma,” he said.
Relative pupillary block is the main known causative mechanism of ACG. But there are multiple potential contributing features, including iris volume retention on dilation, choroidal expansion, and vitreous collapse.
Three More Pieces of the Puzzle
Harry A. Quigley, MD, director of the Glaucoma Center of Excellence at the Wilmer Eye Institute, outlined three of the major discoveries that have enhanced our understanding of the dynamic mechanisms affecting the angle.
One: The iris is a sponge. The iris acts like a sponge, wringing itself out when the pupil dilates. “It’s normal for the iris to lose water when the pupil dilates,” Dr. Quigley said. Using two-dimensional, cross-section views in anterior segment OCT, he found that the iris in open-angle eyes routinely loses half of its area when the pupil expands. But in angle closure, the iris maintains its bulk on dilation by retaining water,1 making it more likely to block the angle.
This finding was supported by a later study that used a three-dimensional method of assessing iris volume. This study showed that iris volume increases on dilation in the fellow eyes of patients who had previously experienced an episode of acute angle closure. The control subjects, who had open angles, lost a substantial amount of volume when the pupil dilated.2 Retention or increase in iris volume brings the iris into closer apposition with the meshwork and raises the risk for acute angle closure or ACG.
Two: The choroid is dynamic. “There’s a lot of suspicion that the choroid expands dramatically in angle-closure glaucoma,” Dr. Quigley said, explaining that the mechanisms controlling choroidal thickness are regulated inappropriately in these eyes, in part through altered vascular permeability. The choroid is normally about 0.25 mm thick, but in eyes with angle closure it is thicker than it ought to be, he said. IOP rises with the choroid’s increase in volume.
He outlined a sequence of events that explain how choroidal expansion may contribute to angle closure:3
He tested this hypothesis by having subjects drink 1 liter of water in 10 minutes, since it’s known that IOP rises with water intake. But only in angle-closure patients did the choroid get thicker; the choroid did not expand in normal-angle patients.
Three: Vitreous plays a role in malignant glaucoma. Patients with malignant glaucoma have abnormal vitreous gel. Poor vitreous fluid conductivity may increase iris–lens channel resistance by moving the lens forward in primary angle closure. Smaller eyes have less diffusion area available, perhaps only half as much as in normal eyes. Vitrectomy is the solution. It eliminates the pressure difference in the vitreous cavity by removing the vitreous gel.
This form of ACG has inappropriately been called “aqueous misdirection,” and residents have traditionally been taught that it is a mechanism for malignant glaucoma, Dr. Quigley said. But this theory is flawed because if fluid can move back through the vitreous, it can just as easily move forward; there is no one-way valve.
Putting New Concepts Into Action
“This [information] was certainly new to me as a comprehensive ophthalmologist and very different from what traditional teaching was during my residency,” said Preston H. Blomquist, MD, after a lecture by Dr. Quigley on the mechanisms of ACG. “I was impressed how changes in uveal thickness and decrease in vitreous fluid conductivity more elegantly explain what occurs in angle-closure glaucoma. There is certainly more going on than ‘shallow chambers predispose to angle closure’ as I was taught years ago,” said Dr. Blomquist, associate professor and ophthalmology residency program director at the University of Texas Southwestern Medical Center.
Thus far, however, clinical application lags behind these new insights. Can they shed any light on what has long been the central question in managing patients with narrow angles—which patients should have an iridotomy to avoid progression to ACG?
Dr. Quigley suggested considering iris volume retention. “We think some angle-closure patients will be more likely to have the disease because they have this feature of iris behavior,” he said. “If someone doesn’t lose [iris] volume, that speaks in favor of doing an iridotomy.” In the future, the addition to OCT systems of software that calculates iris volume change per mm of pupil dilation could help identify which suspects need iridotomy.
In time, these concepts of dynamic physiological mechanisms in uveal tissues and the vitreous may yield more refined ways of identifying which patients with narrow angles are likely to progress to angle closure and need treatment. For now, however, gonioscopy remains the most valuable tool for diagnosing ACG (see “Use the Gonioscope—Properly”), and laser iridotomy is still considered a reasonable approach for reducing risk in many angle-closure suspects.4
The Iridotomy Decision
“Ophthalmologists know they have a reasonable therapy—laser iridotomy—and a low complication rate. So when they identify someone who is a suspect, they are likely to recommend laser iridotomy,” Dr. Quigley said, adding that only 1 in 10 persons with anatomic narrow angles ever experiences angle closure or ACG. “We do not have decent methods for identifying who among all those suspicious people merit therapy and whom we should leave alone,” he said.
“We’re probably treating more people than we need to. That’s not necessarily wrong—it’s a question of how wrong.”
Dr. Quigley’s approach. Until there are better ways to identify at-risk suspects, Dr. Quigley performs laser iridotomy when he observes one or more of the following:
“The problem occurs when people have narrow angles, and everything else is normal,” Dr. Quigley said. In such cases, he recommends performing a detailed examination and family history and asking what the patient wants. If the patient is anxious about having an acute attack or travels to remote regions where appropriate emergency surgery is not available, he advises iridotomy.
Otherwise, “More often than not, I tell them not to have an iridotomy,” said Dr. Quigley, who has been following 200 suspects for years.
Dr. Liebmann’s approach. Anatomically narrow angles without iridotrabecular contact should be monitored periodically. But if there is iris apposition to the trabecular meshwork, iridotomy is usually warranted as a preventive measure, he said.
If the angle remains appositionally closed after iridotomy, he advises considering other causes of angle closure, such as plateau iris or an enlarged lens. Argon laser peripheral iridoplasty can be useful in some of these patients.
He stressed that to prevent continued damage to the trabecular meshwork, you must address the anatomic abnormality underlying the angle closure with laser surgery and not depend on medication.
Looking ahead. Dr. Quigley cited the need for better tests to predict who will benefit from iridotomy, as well as longitudinal studies of its effectiveness. “Improved treatment for angle closure and ACG represents the single most attainable way to prevent blindness worldwide in our lifetimes.”
1 Quigley HA et al. J Glaucoma. 2009;18(3):173-179.
2 Aptel F, Denis P. Ophthalmology. 2010;117(1):3-10.
3 Quigley HA. Am J Ophthalmol. 2009;148(5):657-669.
4 American Academy of Ophthalmology. Preferred Practice Pattern Guidelines. Primary Open-Angle Glaucoma. 2010. www.aao.org/ppp.
Dr. Blomquist reports no related financial interests. Dr. Liebmann is a consultant for or has received research support from Carl Zeiss Meditec, Heidelberg Engineering, Optovue, and Topcon. Dr. Quigley is a consultant for Alcon, Allergan, Carl Zeiss Meditec, Genentech, Merck, and Ono; is on the Merck advisory board; has a confidentiality agreement with Sensimed; and receives support from the NIH.