The Angle

The true nature of angle-closure glaucoma

Harry A. Quigley

Glaucoma Service and Dana Center for Preventive Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Introduction

It is only during the last 100 years that we have begun to differentiate the various types of glaucoma. Important insights into angle-closure glaucoma came from E.J. Curran, a Kansas eye physician, who proposed the concept that pupillary block led to high eye pressure, and described how small holes in the iris would alleviate it.1 In 1931, Rosengren noted that there were two populations among those with glaucoma: one group had high intraocular pressure (IOP), pain, and shallow anterior chambers; the second had normal chamber depth, what was considered normal IOP, and were asymptomatic.2 Through his development of gonioscopic observation, Otto Barkan supported the idea that narrowness of anatomical structure predisposes to outflow obstruction in angle closure.3 Most ophthalmologists have a sense of confidence that we understand angle-closure glaucoma, and, with laser iridotomy, we have a rapid cure.

So, what is the problem?

This essay questions our understanding of the pathogenesis of primary angleclosure glaucoma (PACG). In the simplest terms, I propose that the events leading to pupillary block include forces that move the vitreous and lens forward, and that are additive to relative pupillary block. Observations of the behavior of angleclosure eyes at later cataract surgery show that these forces are still present after iridotomy, but most often they fail to cause a recurrence of acute angle closure. The nature and contribution of this ‘extra-pupillary’ mechanism requires further research. Study of PACG is timely, since it has recently been recognized to represent as much as half the glaucoma in the world4 – and, it causes proportionately more visual disability than its open-angle cousin.5,6

Address for correspondence: Harry A. Quigley, MD, Wilmer 122, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, USA. e-mail: hquigley@jhmi.edu

Glaucoma in the New Millennium, pp. 51–63

Proceedings of the 50th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, April 6-8, 2001

edited by Jonathan Nussdorf

© 2003 Kugler Publications, The Hague, The Netherlands

Definitions for angle closure

Here, I will use some newer definitions for angle closure that were recently suggested at Worldwide Glaucoma 2000, a meeting co-sponsored by the World Health Organization (Baltimore, MD; May, 2000). The meeting summary is available on the Wilmer web site (www.wilmerinstitute.net). In the formulation proposed, there are three categories of angle-closure: narrow-angle, primary angleclosure, and primary angle-closure glaucoma.

Narrow-angle (NA) is defined as a bilateral condition in which the gonioscopic view of the angle with a Goldmann-type lens shows no view of the posterior (pigmented) trabecular meshwork through three-fourths or more of the angle. The gonioscopy is conducted with the eye in the primary position and without any attempted indentation of the cornea artificially to deepen the angle. In order to be classified as narrow-angle only, the person must not have an abnormality of the IOP, optic disc, visual field, or have peripheral anterior synechiae or other signs of past acute attacks (iris atrophy, iris spiralling of vessels, or anterior lens opacity).

For this definition, abnormality in IOP or cup/disc is defined as the value that exceeds the 97.5th percentile value for the population to which the person belongs. For European-derived people, this would be 21 mmHg, or a cup of 0.7. Visual field abnormality is defined by the Zeiss-Humphrey threshold test with ‘outside normal limits’ on the glaucoma hemifield test (GHT) or a pattern standard deviation (PSD) probability < 5%.

Primary angle-closure (PAC) is defined as a person with bilateral narrow angle (as above) and at least one of the following:

CIOP above the 97.5th percentile for the population

Cperipheral anterior synechiae for at least one clock hour

Chistory of, or observed past, acute attacks, defined as bilateral narrow-angle with an episode of documented IOP more than twice as high as the 97.5th percentile value for the population in one eye, often but not necessarily associated with ocular pain, decrease in vision, and conjunctival redness

Csigns of past acute attacks (iris atrophy, spiralling, anterior lens opacity)

Ccup/disc ratio exceeding the 97.5th percentile for the population, but a normal visual field

Primary angle-closure glaucoma (PACG) is defined as a person with bilateral narrow angle and glaucomatous optic nerve damage in at least one eye, which is defined as a cup/disc exceeding the 97.5th percentile and the presence of a ZeissHumphrey visual field defect as described above.

These definitions adhere to two basic ideas. Firstly, that primary glaucoma is a term only applied to eyes with damage to the optic nerve (field loss with a compatible disc change). Secondly, that qualifying terms for PACG such as intermittent, chronic, plateau iris, creeping, or subacute, imply more knowledge of the natural history than we have at this time; hence, they are not to be used.

The tyranny of gonioscopy

While gonioscopy confirmed the dichotomy between PACG and open-angle glaucoma, we have become slaves to angle observation, which has limited clinical predictive value and provided almost no pathogenic information. When the angle

is closed by peripheral anterior synechiae, higher IOP can be expected. But, none of our present clinical tools allows the differentiation of persons who will develop a disease from persons who will not, among all those with NA. There are ten persons with narrow angles for every one with PACG.5 Gonioscopy is only moderately successful in specifying the angle associated with a future disease, regardless of which grading system is used.

Shaffer’s gonioscopic grades give a single value for angle width, while Spaeth’s system separately describes the position of iris insertion, the angle width, and the shape of the peripheral iris. How likely is it that a Shaffer Grade 1 angle will occlude? Does it matter whether we describe the position of iris insertion as in Spaeth’s system? This might be determined by longitudinal follow-up of a large number of persons thought to be at risk for PAC or PACG, who could be followed without therapy after gonioscopic grading. There have been few prospective studies of the power of gonioscopy to predict the development of PACG.7,8

Gonioscopy is all we have, but it is inherently anatomical and static, when we need to predict the physiological behavior of the eye. As an analogy, imagine that someone you cannot see is pushing a car over a cliff. You are down below trying to determine if it will fall, but all you are measuring is the amount of car hanging over the edge at that time. To be sure, the more car you can see, the more likely disaster is to strike, but it is the unseen force pushing the car that will determine the outcome. It is the unseen forces that are behind the angle that we should be attempting to estimate, and gonioscopy does not provide that information.

The risk factors for PACG include smaller axial length, smaller cornea, shallower anterior chamber, larger lens diameter, and hyperopia. These all logically fit with a predisposition for crowding of the anterior ocular structures. Some investigators have tried to improve on gonioscopy with newer technology to measure critical anatomical features. These include ultrasonic biomicrosopy, Scheimpflug photography, and pachymetry of the anterior chamber by ultrasound and optical methods. To date, these are only fancier methods to measure how much of the car is hanging over the cliff. In his lecture to the Worldwide Glaucoma 2000 meeting, the noted observer of angle closure, Poul Helge Alsbirk quoted Ronald Lowe, one of those who spent his life on this disorder, as saying: “I believe that the big remaining problems of angle-closure glaucoma will be little assisted by further biometry, as they have a disturbed physiological basis.”

It isn’t all acute attacks

An acute attack of angle closure is impressive, with its pain, vision loss, corneal edema, and high IOP. Yet, in population-based studies, acute angle-closure attacks are far less common than asymptomatic PACG.5,8,10 But, these surveys looked at a group at one point in time. It could be that there are more acute attacks that are missed in population surveys. How might these unrecognized acute cases of PACG have been missed? Firstly, if the attacks were associated with some fatal condition, persons who suffered attacks might be ‘missing’ from the population due to selective death. However, a selectively greater mortality than the general rate is not found among those with glaucoma. Secondly, acute attacks could go undetected. But, attacks typically leave visible scarring and atrophy. If attacks occur without symptoms, and resolve without detectable iris or lens damage, the eye would

have asymptomatic peripheral anterior synechiae and, ultimate nerve damage in a quiet eye. This merely describes the mechanism of PACG, and becomes a circular argument.

Since there are many more persons with PACG than there are those who have had an acute attack (considered here a form of PAC), screening for PACG could be effectively carried out by looking for optic nerve damage. This means that methods being tested to screen for open-angle glaucoma will identify many of those with PACG as well – a welcome bonus.

There is more to PACG than meets the eye-ridotomy

We were taught that pupillary block explains all the important aspects of PAC and PACG. After all, a hole in the iris has some benefit in these conditions. Laser iridotomy is relatively easy to perform and has few long-term complications. But, if all persons with NA were given iridotomy, and the relative proportion of NA to PACG is really 10:1, then iridotomy would look as if it had a 90% cure rate, even if it were totally worthless. As described above, a longitudinal study of at-risk eyes is needed to determine who will benefit from iridotomy.

It is interesting to speculate on how many iridotomies are needed for the USA, based on a population at the last census of 76.7 million persons over the age of 50 years. A recent population study in Europeans can be used to calculate the incidence of PACG from its prevalence.9 The estimate of 29 new cases/100,000/year leads to the suggestion that 44,000 iridotomies would be appropriate to cover all those with PACG (two eyes per person). Additional iridotomies might be appropriate for those whose risk was sufficiently high. Medicare data suggest an estimated 57,000 iridotomies in 1999 among those over the age of 65 years in the USA (unpublished data kindly provided by Anne Coleman, MD, PhD).

Yet, as we evaluate those who have been ‘cured’ by iridotomy, there are bothersome observations that indicate that everything is not normalized. These observations can be placed in three groups:

C1. some eyes continue to get worse, despite iridotomy;

C2. some eyes still have acute attacks with a patent iris hole;

C3. some eyes, particularly PAC eyes, even those that have had iridotomy, have a tendency for forward iris-lens movement during cataract removal.

A progressive course after iridotomy could result from a variety of circumstances. The diagnosis could have been incorrect, and the subject has open-angle glaucoma, or the subject could have both types of glaucoma. Secondly, many of those who have iridotomy for an acute attack need subsequent trabeculectomy.11 Most likely, these eyes had permanent angle damage and iridotomy came too late. But, some observers propose that the angle continues to form permanent, new synechiae despite iridotomy, referred to as ‘creeping’ angle closure.

There are no well-documented gonioscopic follow-ups of PAC patients that show what proportion have increasing synechiae after iridotomy. Since the same IOP control problem could arise from damage sustained prior to iridotomy, specific evidence for progressively more synechiae is needed to support this mechanism. It is not enough to cite that there is sometimes poor IOP control or the perceived need for trabeculectomy. The impetus leading to more angle closure

could be forces leading the iris and lens to move anteriorly, despite elimination of relative pupillary block (see below).

I examined 140 consecutive eyes that underwent iridotomy and found that the angle grade had widened in 68% of eyes.12 Subsequently, with much better quantification, Lee et al.13 found that the peripheral chamber deepens after iridectomy, i.e., the peripheral iris convexity flattens. But, they and others14 have conclusively shown that the position of the lens relative to the cornea does not change with iridotomy. In other words, the central chamber depth is unchanged by iridotomy. While 30 of the eyes in my follow-up study had had past acute attacks, and others had had positive mydriatic provocative testing, none had IOP elevations when the pupil was dilated after iridotomy. So, iridotomy did eliminate the component of their disease related to the iris, without changing the lens position. As we will see, the position of the lens in the antero-posterior axis is very important in generating critical pupil block.

The flattening of the peripheral iris does not happen in every NA, PAC, or PACG eye after iridotomy. In my experience, most eyes that retain a narrow appearance after iridotomy do not have recurrent acute attacks. Some refer to such eyes as having a plateau iris configuration. One possible explanation for this appearance is ciliary processes that are more anterior than normal, and this has been observed by ultrasound biomicroscopy.15 Among those with plateau iris configuration after iridotomy, an even smaller number develops repeat attacks of high IOP with pupil dilation. These are referred to as plateau iris syndrome. No detailed study of these eyes compared to other plateau iris eyes has demonstrated risk factors that explain this behavioral difference. While some claim that plateau iris syndrome is common, my experience is that it is not. In general, iridotomy prevents sudden, episodic IOP increase in eyes that have NA. How does it do this?

Tiedeman16 wrote a most lucid description of the reasons that the iris assumes a convex shape. He assumed that the forces acting on the iris derived from five basic structural/physiologic facts: 1. the iris is fixed at its root; 2. the iris sphincter produces a force acting inward (perpendicular to the optical axis and toward it); 3. the iris dilator produces a force acting outward (opposite the sphincter); 4. there is a hydrostatic pressure both in front and behind the iris; and 5. position of the lens antero-posteriorly determines the corresponding position of the pupil. By using fairly elementary physics, he modeled the likely shape of the iris in two and three dimensions. He stated that the pressure in the posterior chamber would be higher than that in the anterior chamber (otherwise no fluid would move through the pupil from back to front). This pressure differential combined with the resistance to flow through the pupil would determine the aqueous flow rate.

His model for iris shape led to several important facts. Under nearly every condition in which there is a lens in the eye and in which the iris has only the pupil opening (no iridectomy), the iris assumes a convex shape. Using the imaging method called Scheimpflug photography, Anderson et al.17 found that the predictions of Tiedeman’s model fit the actual shape of the iris under a variety of conditions in real eyes. Furthermore, Tiedeman predicted that the more anterior the position of the pupil relative to the iris root, the more convex its shape. The most convex profile would occur at mid-dilation, with flatter shapes at both a smaller and a larger pupil diameter. He stated some facts that are clearly true, but which may surprise many ophthalmologists. We frequently hear that the iris ‘rests on the

lens’. In fact, the lack of exfoliative deposits on the middle of the lens (compared to its central polar area or its periphery, where the deposits do collect) is often cited as evidence that the iris rubs off the deposits here. Certainly, the iris could, and probably does, come into contact with the lens at some time. A further illustration of this is the transillumination defects seen in pigment dispersion syndrome, which result from iris contact with the zonule in eyes predisposed to this phenomenon. But, under normal conditions and even in angle-closure glaucoma eyes, there is always flow through the pupil and no iris lens contact. The narrow zone between the iris and lens contributes to the resistance to aqueous flow through the normal pupil. If there were no resistance to flow, or if the pressure in the anterior and posterior chambers were equal, the iris would not be bowed forward (convex).

Under what conditions might the pressure in the anterior and posterior chambers be equal? With an iris hole somewhere away from the pupil, this would occur. Clinical experience cited above confirms that this is true, and Jin and Anderson showed it to be the case photographically.18 Interestingly, we might consider what happens during an acute attack of angle closure. In this setting, the iris configuration becomes convex forward to such an extent that the iris contacts the trabecular meshwork, obstructing it to varying degrees. The degree of contact needed to produce a significant IOP rise must differ among eyes, but there is not reason to think that all the meshwork must be occluded, or that flow stops completely. In fact, if flow did stop, pressure in the posterior and anterior chamber would become equal, the iris would assume a flat configuration, and the attack would be broken. Hence, in the middle of a continuing attack, it is quite likely that flow does not stop completely, and that some outflow is ongoing (not 100% angle closure).

One prediction of Tiedeman’s model that is not intuitively obvious is that the shape of the iris is not dependent upon the actual tension in the iris dilator and sphincter, nor, probably, is it dependent upon the thickness of the iris stroma. Tiedeman assumed for the model that the iris stroma exerted no relevant force to determine iris shape, and only the iris musculature contributed. This seems to be a reasonable judgment, considering how loose the iris connective tissue is. In reality, the model predicts that, if the iris components of the model are strengthened (e.g., if the stroma is thicker and exerts itself into the equation), the convex shape of the iris is unaffected, but the pressure differential between posterior and anterior chamber increases proportionately. While this has not been measured in vivo in an eye, a laboratory model of iris, pupil and lens was studied by Wyatt and Ghosh,19 using a latex membrane simulating the iris and a ball for the lens. The behavior of this model fits in every way with the Tiedeman equations. Moreover, they tried doubling the thickness of the latex membrane and found that, as predicted, the shape of the convexity did not change, but that the measured difference in pressure from posterior to anterior did. This may have relevance to the differences among human eyes of various thicknesses, relative to angle-closure glaucoma. It has been a frequently expressed anecdote that angle closure and acute attacks are less frequent in black persons. Population-based data do not support this idea,4,10 indicating that Africanand European-derived persons have similar rates of PACG. In addition, if thicker irises made PACG less likely to happen because the iris did not bow forward as readily, then why would Chinese persons, with thicker brown irises, have so much PACG?5

It is interesting to speculate on the behavior of the lens at the pupil, given the

Tiedeman model. Moses20 may have been the first to realize that the lens has forces acting on it that would move its position more anteriorly. Firstly, he recognized that, in the area of the pupil, the lens has a lower hydrostatic pressure on its anterior surface (the ambient anterior chamber pressure), but on its posterior surface, it has the higher posterior chamber pressure. This would tend to move the lens toward a more anterior position. In addition, there might be a Venturi-like effect moving the lens forward, which would be induced by the flow of aqueous through the pupil. We cannot measure these forces in total, but their combined effects must be relatively small in the living human eye. I base this conclusion on the fact that the resting position of the anterior surface of the lens does not move posteriorly when iridotomy is performed.13 Iridotomy not only equalizes anterior and posterior chamber pressure, but also decreases flow through the pupil to at least some degree. Despite the removal of both forces that would lead to anterior lens position, there is no net posterior lens movement. It is not true that the lens cannot move forward in the angle-closure eye; on the contrary, as we discuss below, it is all too common to see it move forward when the anterior chamber is opened. But, the resting anterior position of the lens in PACG eyes is unaffected when an iris hole is made. Then, what forces do lead the lens to assume a more anterior position in the resting state of eyes with PACG?

Every cataract surgeon has observed that some eyes have a disturbing tendency for the iris and lens to move toward the cornea when a corneal or limbal incision is made. This dramatic ‘positive pressure’ phenomenon results from equating the hydrostatic pressure in the anterior chamber with that ambient in the operating room. In this condition, the pressure in the vitreous cavity behind the iris and lens is equal to the prevailing IOP just prior to the incision (say 15 mmHg higher than atmospheric). It would be expected that movement of the lens toward the cornea would always occur, and it is interesting that this is not the case in most eyes. Working to keep the iris and lens from moving forward is their resistance to movement, which must be higher in the supine position (in the operating room) than in the sitting position. Not only does forward lens movement occur in PAC eyes with an iridotomy, but also it seems (anecdotally) to be more frequent than in other eyes.

When large incision cataract surgery was the norm, eyes with positive pressure caused the iris to prolapse continuously and the nucleus practically delivered itself (sometimes followed by vitreous). This would continue to occur during the entire procedure, despite an existing iridotomy (and the production of new iris holes). Obviously, positive pressure does not result from pupillary block. It occurs even during ‘small incision’ phacoemulsification lens removal. Those who try to remove the lens in angle-closure eyes cannot fail to be impressed that some residual force is attempting to move the iris and lens forward. A second clinical observation indicates that PAC eyes have a tendency for forward lens movement when there is an increased pressure differential between the anterior and posterior lens surfaces. Most glaucoma surgeons would agree that PAC eyes have a greater tendency to develop flat anterior chambers after trabeculectomy. Since they always have an iridotomy performed at the time of trabeculectomy, pupillary block cannot be a factor. The tendency toward forward lens movement seems to be a regular feature of the angle-closure eye. This could be part of the explanation for the PAC

58 H.A. Quigley

eye developing abnormal IOP and trabecular obstruction. As Tiedeman pointed out, the more anterior the lens, the more the forward bowing of the iris (convexity). Many eyes may have the same small dimensions of cornea, axial length, and the same larger than average lens size. But, only a minority develop full-blown PAC or PACG. I propose that, in these eyes, there is an additional feature or features causing anterior lens position in the resting state (further bowing these irises forward to the point of meshwork obstruction).

Surgeons have discovered that preoperative digital or instrumented pressure on the closed lid for a period of minutes decreased the problems of positive pressure. These techniques reduce the prevailing IOP by removing aqueous humor from the anterior and posterior chamber, as well as by removing volume from the fluid in the vitreous cavity, via the retinal and choroidal vasculature. Reducing the IOP would make the instantaneous pressure differential across the lens smaller, reducing the tendency for it to move forward.

It is quite remarkable that more eyes do not develop positive pressure. Seemingly, they rapidly equilibrate the anterio-posterior pressure differential by loss of vitreous volume. To do so, fluid might exit the vitreous cavity, either going forward into the anterior chamber or exiting through the retina/choroid. Anteriorly, the vitreous gel is in direct contact with the lens. The area through which water could diffuse to leave the gel is shaped like a doughnut with the lens occluding the central area (Fig. 1). In PAC eyes, there are two reasons why this anterior fluid diffusion would be slower. Their axial length is smaller, making the outer diameter of the doughnut smaller, and the lens is larger, making the inner, blocked area bigger. In the illustration in Figure 1, the dimensions of a typical PACG eye lead to the anterior diffusional area decreasing by nearly one half. This could contribute to forward movement of the iris and lens within the eye, not only in the extreme case of paracentesis, but also in the closed eye with various other situations (e.g., the prone position). A second region for fluid to exit from the vitreous cavity (to minimize positive pressure) is across the surface of the retina. In a smaller eye with an axial length of 21 mm, the retinal surface area is 25% less than in an eye of 24 mm. Thus, for both exit pathways for fluid from the vitreous cavity, the small eye is at a disadvantage.

If as described above, water must diffuse from the vitreous cavity into the anterior chamber to equilibrate the induced pressure differential with paracentesis, water molecules are passing through the vitreous body to do so. The vitreous has a high water content, but there are hydrogen bonds and other chemical interactions that limit water diffusion through vitreous. Fatt21 measured the fluid conductivity of the vitreous in vitro. He determined that the fluid conductivity decreases as a pressure differential is induced across the vitreous gel. This suggests the intriguing idea that a risk factor for positive pressure is poor vitreous fluid conductivity. This could be either high baseline resistance, or a more than average rise in resistance with induced pressure differential. Hence, a risk factor for positive pressure would be a vitreous with a greater collapsibility under pressure (similar to poor outflow facility). Note that the eye with highly collapsible and compressible vitreous would be prone to a disequilibrium (vicious cycle), with initial higher pressure behind the vitreous gel leading to greater compression and higher resistance, further decreasing diffusional flow. The extreme case of severe positive pressure on opening the anterior chamber is identical to what has been called malignant glaucoma (Fig. 2). The clinical observations of this condition describe

Fig. 1. In an eye with an axial length of 24 mm and a lens diameter of 9 mm, the anterior area for fluid to diffuse from the vitreous cavity to the posterior chamber is a doughnut-shaped zone, with an area of 113.1 mm2. A typical PACG eye has an axial length of 21 mm and the lens is slightly larger, say 9.5 mm in diameter. These changes alone would lead the diffusional dough- nut-shaped area of the PACG eye to decrease to 64.3 mm2, nearly twice as small.

lakes of fluid behind a forward, compressed appearing vitreous gel,22 which flattens the anterior chamber. In my view, the eye with malignant glaucoma results from high resistance to vitreous fluid diffusion and/or highly collapsible vitreous. This is more logical than the idea of ‘misdirected aqueous’, a proposed mechanism, that appears to violate the laws of physics. If aqueous humor could move in a so-called misdirected way from the ciliary body through the vitreous gel to the fluid compartment behind it, it would be able to move back the opposite way. A functional ball valve would somehow need to be invented to propose a one-way movement of aqueous humor, and none has ever been documented. Shaffer and Hoskins suggested the possibility that the vitreous was detached at its base in a way that allowed such a ball valve or one-way flow. Instead, I propose that the inciting event for malignant glaucoma is a transiently higher hydrostatic pressure in the fluid vitreous cavity than that in front of the gel. Most commonly, this happens iatrogenically during ocular surgery when the anterior chamber is opened to the air. It can happen spontaneously if there was a higher IOP behind the vitreous. With Jonathan Pederson, I made observations in aphakic eyebank eyes in which such differential pressures were induced using two needles inserted into the eye, one through the optic nerve and the other in the anterior chamber. It takes less than a 5 mmHg difference in pressure to cause forward vitreous movement, as in malignant glaucoma, even in normal eyebank eyes.

The therapies for malignant glaucoma all fit in well with this hypothesis. Cycloplegia widens the ciliary body diameter, increasing forward diffusional area for fluid to leave the eye. Osmotic agents remove fluid from the entire eye, but have a disproportionately greater effect on the vitreous cavity, thereby lowering the pressure differential across the vitreous body. Vitrectomy as a definitive therapy logically removes the resistance to fluid movement entirely, though if only partial vitrectomy is performed, the flow may not be fully sufficient to allow normal intraocular fluid dynamics (not enough collapsible vitreous removed).

In addition to vitreous block of aqueous flow, a second additional feature that may lead to positive pressure is expansion of choroidal volume. The choroid is a highly vascular structure whose choriocapillaries are permeable to a variety of proteins. The choroid has one of the highest ratios of blood flow to tissue volume in the body. The thickness of the choroid is about 400 m in the human eye when measured histologically; however, its volume in vivo would seem to be determined by a group of variables. These include arterial and venous pressure in choroidal vessels and colloid osmotic pressure of the choroidal extracellular space. The choroidal venous pressure would have to be higher than IOP in order to keep the vessels open to carry blood out of the vortex vein outlets. Consider what would happen to the choroid’s extracellular space if the eye pressure were quickly to fall from 15 mmHg to zero. The hydrostatic force driving water into choroidal veins would fall by that amount, leading to an expansion of the choroidal volume. The same would result from increase in choroidal venous pressure (or increased pressure in any distal drainage site, the orbital or jugular veins). There was an empirical demonstration of this expansion in a recent report by Schumann and colleagues. They documented increased choroidal thickness with the higher venous pressure generated by the vigorous playing of a wind instrument.23 A 20% increase in choroidal thickness was measured. Presumably, the degree to which a given change in IOP or choroidal venous pressure leads to a change in choroidal thickness would vary among eyes, based on various features of the choroidal tissue, such as its elasticity,

vascular permeability, and protein concentration. If this feature were called choroidal elasticity, it might be proposed that some persons have greater choroidal elasticity than others, so that their choroid expanded more for a given change in hydrostatic forces. At one extreme, a change in IOP might lead the vortex veins to collapse completely at their exit from the eye. This has been proposed as a mechanism in nanophthalmos, a condition in which small eye size leads to a disorder of fluid movements in the eye.

Increases in choroidal volume have potentially dramatic effects on anterior ocular structural positions. The estimated vitreous cavity volume of an eye with axial diameter of 23 mm can be calculated as about 5000 l. The choroidal volume in this eye is about 480 l and the anterior chamber volume about 150 l. If an incision opens the anterior chamber, and the choroid expands by 20%, its increase is equal to two-thirds of the anterior chamber volume. In an eye with a relatively smaller chamber, all aqueous would exit, with the iris forced against the cornea (positive pressure). Since the IOP changes during these events, the alteration in the sclera that would occur are predictable.24 If the IOP fell, the sclera would contract somewhat, accentuating the flattening of the anterior chamber. If the choroid expanded and the incision in the eye were closed temporarily, then the IOP might rise, even higher than the original IOP. In this case, some of the expansion of the choroid would generate an expansion of the scleral diameter and the rise in IOP would be mitigated, though there would still be an impressive loss of anterior chamber volume.

There have been past attempts to codify the entities that comprise pupillary block or angle-closure glaucoma. In large part, these consisted of efforts to divide cases into specific types of mechanisms that were considered to be separate from each other and not occurring simultaneously. I have referred above to the observations that comprise the scenario of malignant glaucoma or nanophthalmos as they are typically seen. However, in more recent investigations, the coexistence of a picture identical to malignant glaucoma with annular uveal swelling has been observed by ultrasonic biomicroscopy.25 This seems illogical, since IOP is typically high in malignant glaucoma, and ciliary detachment by serous fluid is more often a sign of low IOP. It appears more likely that the so-called choroidal detachments seen in this setting represent relative expansions of the choroidal thickness (whether ‘serous’ or not), and are examples of high choroidal elasticity.

In summary, past analysis stressed two major elements in angle-closure glaucoma: an anatomically small eye and blockade of aqueous movement at the pupil. I propose that there is more to the mechanism of angle closure than these two elements. These additional features are evident after relative pupil block has been eliminated by iridotomy. They could include forces generated by poor exchange of fluid or collapsibility of the vitreous body and over-vigorous expansion of the choroid. These elements unify the concepts of malignant glaucoma and nanophthalmos with angle closure, suggesting that features that dominate one condition could be contributory to the others.

References

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11.Aung T, Ang LP, Chan S-P, Chew PTK: Acute primary angle-closure: long-term intraocular pressure outcome in Asian eyes. Am J Ophthalmol 131:7-12, 2001

12.Quigley HA: Long term follow-up of laser iridotomy. Ophthalmology 88:218-224, 1981

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