New Mechanisms of Angle Closure Glaucoma

Harry A. Quigley, MD

We think of angle closure and those eyes with optic nerve damage through this series of mechanisms (angle closure glaucoma, ACG) as fairly well understood. The simple explanation is: aqueous is blocked from entering the anterior chamber at the pupil (1) and making a laser hole fixes the problem.

Small eyes are more likely to get angle closure, having a variety of smaller dimensions in the anterior chamber structure. Another risk factor is being Chinese, as the rate of ACG is up to 5 times higher for them compared to Europeans and Africans. (2)

Chinese persons are proportionately more likely to get ACG, but they do not have proportionately more persons with small eyes compared to European populations. Therefore, there must be more to ACG mechanisms than we have been assuming. Anatomy can’t explain what’s going on.

In addition, gonioscopy, which is our gold standard for clinical detection of AC, fails to separate those with iridotrabecular contact from those with AC and ACG. (3) There are 10 persons with narrow looking angles for every person who will get ACG. So gonioscopy is a vital first step in recognizing potential AC but it is an anatomic method in a disorder that occurs for physiological reasons.

The angle changes dramatically from moment to moment, as lighting conditions change, for example. By observing the change in angle depth using the ultrasonic biomicroscope, we see that those narrow angle eyes that will suffer AC (the one in ten) become narrower in the dark than do eyes that are just as narrow in the light but will not develop AC. (4) Future investigations must delineate these physiological responses and produce predictive tests that allow us to know who will most likely benefit from iridotomy. (5)

One mechanism of AC that adds to pupil block is plateau iris syndrome, a relatively uncommon disorder in European-derived persons. Here, after iridotomy, the angle not only does not open, but high pressure reoccurs on pupil dilation. The additional mechanisms that cause this condition probably relate to differences in anatomy and physiology of the iris insertion into the limbal sclera, including possible juxtaposition of the ciliary body behind the iris.

Another physiological behavior of the eye that is relevant to AC is the ability of the vitreous humor to transmit fluid through its gel. Water moves through the vitreous in both directions under constraints produced by its macromolecular structure. In some persons, it is conceivable that the fluid conductivity of vitreous is abnormally low. In these eyes, when a transient difference in pressure across the vitreous happens, say higher pressure in the posterior fluid vitreous compartment, the vitreous cannot equilibrate the difference. Experiments show that the vitreous will collapse and develop even poorer conductivity for water under this condition, leading to a vicious cycle. (6) The vitreous would move forward in the eye, carrying the lens and iris with it, flattening the anterior chamber. This is the mechanism of the form of AC called malignant glaucoma. The previously proposed mechanism known as “misdirection of aqueous” is not correct—in fact, the idea is physiologically impossible, since if aqueous could move posteriorly behind the vitreous cavity, it would move right back just as easily.

It is likely that many eyes with typical AC have a component of poor vitreous conductivity as a contributing feature to their disease. This would intensify resistance to fluid movement through the pupil, and cause worse pupil block in these eyes, providing the compounding factor that made some narrow angles close while others did not.

A final mechanism that is well-known to participate in secondary forms of AC is expansion of the choroid. A variety of drugs, vascular occlusions, and treatments (retinal surgery and PRP) lead to choroidal swelling and shallowing of the anterior chamber. It takes very little expansion of the choroid overall to raise IOP (7) and rapidly to produce a posterior to anterior internal pressure gradient. Surgeons experience this occasionally in the operating room performing lens surgery—the phenomenon known as positive pressure. It is likely that another feature of the eye that contributes to increased pupil resistance and AC disease in narrow eyes is a greater than average tendency for the choroid to expand. Choroidal expansion has been documented in malignant glaucoma. (8)

In summary, there are multiple physiological and anatomical features of the eye that probably explain why some smaller eyes develop AC and ACG, while others do not. These mechanisms will hopefully be delineated more fully soon and predictive tests developed to measure them. Potentially, treatments that would shrink the choroid or increase vitreous fluid conductivity would be excellent adjuncts in primary AC and secondary AC.

1) Silver DM, Quigley HA. Aqueous flow through the iris—lens channel: estimates of differential pressure between the anterior and posterior chambers. J Glaucoma, 2004;13:100-107.

2) Quigley HA, Broman A. The number of persons with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006;90:151-156.

3) Wilensky JT, Kaufman PL, Frohlichstein D, Gieser DK, Kass MA, Ritch R, Anderson R. Follow-up of angle-closure glaucoma suspects. Am J Ophthalmol. 1993;115:338-46.

4) Friedman DS, Gazzard G, Foster P, Devereux J, Broman A, Quigley HA. Ultrasonographic biomicroscopy, Scheimpflug photography, and novel provocative tests in contralateral eyes of Chinese patients initially seen with acute angle closure. Arch Ophthalmol, 2003;121: 633-642.

5) Quigley HA, Friedman DS, Congdon NG. Possible mechanisms of primary angle-closure and malignant glaucoma. J Glaucoma, 2003;12:167-180.

6) Fatt I. Hydraulic flow conductivity of the vitreous gel. Invest Ophthalmol Vis Sci, 1977;16:565-8.

7) Silver D, Geyer O. Pressure-volume relation for the living human eye. Curr Eye Res, 2000;20:115-20.

8) Liebmann JM, Weinreb RN, Ritch R. Angle-closure glaucoma associated with occult annular ciliary body detachment. Arch Ophthalmol, 1998;116;731-5.