Principles of Primary Angle-Closure Glaucoma

Principles of Primary Angle-Closure Glaucoma

Jeffrey R. SooHoo, MD; David L. Epstein, MD, MMM; and George Ulrich, MD, FACS

GENERAL CONSIDERATIONS

The classic teachings about the diagnosis and management of primary angle-closure glaucoma remain relevant. Nevertheless, our understanding of angle closure continues to evolve with the introduction of new diagnostic techniques other than gonioscopy that aid in the evaluation of the chamber angle and the angle’s potential to become occluded. These technologies include anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicrosopy (UBM). Because of the affordability and wide availability and utility of gonioscopy, primary angle-closure glaucoma is usually discussed in the context of gonioscopy. AS-OCT and UBM are important adjuncts in understanding the dynamics of angle closure, but they are relatively costly and therefore not universally available.

In the various forms of angle-closure glaucoma, the trabecular meshwork (TM) may have intrinsically normal function, but the position of the peripheral iris in front of the TM blocks flow of aqueous humor to this outflow pathway. Because there is very limited circumferential flow of aqueous humor once in Schlemm’s canal,¹ each portion of the TM circumference functions as if it were a relatively independent outflow segment. Thus, the full blockage of a limited segment of the TM circumference by the peripheral iris results in a proportional decrease in outflow facility.^2,3

Aqueous humor normally exits through the posterior half of the TM, closest to the scleral spur. This is illustrated by the common observation of relatively increased pigmentation of this posterior half of the TM. Thus, when only the anterior half of the TM is visualized by gonioscopy, and if the unseen posterior half of TM is blocked by iris apposition, there may be limited aqueous outflow occurring through this segment of the angle circumference. This observation may be misinterpreted by inexperienced gonioscopists who report that they “see some TM.” Stated another way, the full width of the TM needs to be visualized to the scleral spur, without indentation, to know that the angle is functionally open. Thus, the term partial angle closure does not mean that part of the TM is visible in one area. Rather, the term refers to the fact that the angle is functionally closed by iris apposed to at least the posterior half of the TM in a portion of the 12–clock-hour angle circumference (Figure 23-1).

The peripheral iris that functionally blocks access to the draining posterior-half of the TM either for a limited number of clock hours or for the full circumference may be apposed without permanent adhesion or with a semipermanent or permanent adhesion. These adhesions are called peripheral anterior synechiae (PAS). The terms chronic appositional angle closure and chronic synechial angle closure are sometimes, respectively, used to describe these 2 clinical situations. In the former situation, in which there is no permanent adhesion, relief of the factors causing the movement of the peripheral iris over the TM can theoretically restore normal outflow. Nevertheless, even in this circumstance of nonpermanent adhesion, some have argued that chronic iris touch can cause permanent TM dysfunction without apparent synechiae formation. Likewise, in the latter situation where PAS have formed, altering in some way the factors causing movement of the peripheral iris over the TM will not by itself restore normal TM function.

Figure 23-1. Iris apposed to posterior half of trabecular meshwork occludes outflow, despite anterior trabecular meshwork (which is nonfiltering) being visible. (A) Appearance in cross-section. (B) Appearance in gonioscopy.

When the angle is closed in only a part of its circumference, intraocular pressure (IOP) may or may not rise in proportion to the extent of closure. With the angle closed in only a portion of its circumference, the level of IOP may vary in different eyes depending not only on the amount of angle closed but also on the efficiency of the remaining open angle. Thus, in an eye that has an unusually good facility of outflow, such as 0.40 μL/min/mm Hg, when the angle is entirely open, closure of half the angle may still allow a normal or near-normal IOP. The facility of outflow may still be within the normal range (eg, 0.20 μL/min/mm Hg). In another eye, starting with a borderline facility of outflow of 0.16 μL/min/mm Hg when the angle is open, closure of half of this angle may result in a facility of outflow well below normal (eg, 0.08 μL/min/mm Hg), causing a considerable elevation in IOP.

A lack of proportion between the extent of closure and the level of IOP in some eyes may also be related to a temporary diminution in the rate of aqueous production. This might happen after a severe attack of acute angle-closure glaucoma. In this case, the angle closure may have resolved spontaneously, but there still may be residual permanent outflow obstruction. Yet, because of temporarily reduced aqueous production, IOP may still be normal or even subnormal for hours, days, or weeks despite extensive residual synechial closure of the angle and reduced outflow. However, as the eye recovers from the acute insult, aqueous production resumes. The IOP again rises to a level consistent with the extent of residual closure.

The onset and course of angle-closure glaucoma in most cases is episodic. When the angle closes rapidly in an acute episode, the IOP rises rapidly, causing symptoms of blurred vision, pain, and sometimes an appearance of colored haloes around lights. In subacute angle-closure glaucoma, however, there may be a rapid rise in IOP but not to such a level as in the acute form, because, generally, only a part of the angle is involved in subacute closure. Nevertheless, during an episode of partial or subacute closure, the patient may still note blurring of vision and seeing haloes around lights. In chronic angle-closure glaucoma, the closure is gradual, and the patient may be asymptomatic until the glaucoma is in an advanced state with significant permanent visual field loss from optic nerve compromise. This mimics primary open-angle glaucoma (POAG) and is often misdiagnosed as such.

In its early stages, angle-closure glaucoma is reversible and curable. If the angle reopens throughout the full circumference either spontaneously or as a result of pharmacologic intervention, the eye again has a narrow but open angle, yet it remains predisposed to further attacks of closure. Repeated episodes often occur and result eventually in synechial angle closure, elevated IOP, and permanent optic nerve compromise. The tendency toward synechial closure varies greatly among eyes. In some eyes, a single severe episode of closure of the angle, especially if prolonged, may result in extensive synechiae formation. In other eyes, repeated episodes of closure over a period of a year or more may cause little or no formation of synechiae. With treatment by laser iridotomy, such an angle may be stabilized and maintain a capability of opening throughout its circumference.

NARROW-ANGLED EYES: EVALUATING THE STATUS AND THE RISK FOR GLAUCOMA

In narrow-angled eyes, there are 2 common clinical situations. Each of these 2 situations has different questions that must be addressed to understand the condition and how it should be approached and treated.

Situation 1

The angle is narrow but the IOP is normal. The question is whether the angle is sufficiently narrow such that there is a significant risk of spontaneous (or perhaps pharmacologically induced) angle closure. This situation is referred to as the occludable angle. While the definition of what is considered occludable varies among practitioners, many will perform prophylactic laser peripheral iridotomy on these patients with the goal of deepening the angle and reducing the risk of chronic or acute angle closure.

Situation 2

The angle is narrow, and the IOP is elevated. In this case, the question is different: Is there sufficient functional angle closure around the circumference to explain the IOP elevation? That is, is the IOP elevation due to a form of angle-closure glaucoma with or without synechiae formation, or does the patient really have POAG but with a narrow yet functionally open angle? In fact, it may be some degree of both. The angle may be narrow yet remain functionally open in some portion of the circumference, contributing to an elevated pressure by an open-angle mechanism. At the same time, the angle may be apposed either with or without synechiae formation in other areas with a corresponding decrease in outflow facility. Such a condition is often referred to as mixed mechanism glaucoma. The need for such discrimination is not rare in clinical practice. For example, exfoliative eyes (a form of open-angle glaucoma) commonly have narrow angles and may have an angle-closure component contributing to elevated IOP.

TERMINOLOGY

Angle-closure glaucoma may be acute, wherein there are usually symptoms of pain and blurred vision with signs of ocular injection and a fixed mid-dilated pupil. The angle in most, if not all, of the circumference has gone suddenly from a narrow but open and functional status to that of dramatic appositional closure.

Angle-closure glaucoma may be termed subacute with milder symptoms and signs because only a portion of the 360-degree circumference is functionally closed. This may happen intermittently and repetitively with episodes resolving or without permanent PAS formation.

Finally, angle closure may be termed chronic. This usually implies an asymptomatic long-term condition that mimics POAG. In fact, misinterpreting and erroneously treating chronic angle-closure glaucoma as POAG is among the most common diagnostic and interventional errors in glaucoma.

In most patients with chronic angle-closure glaucoma, there is a progressive though gradual increase in the extent of the circumference of the angle involved and progressive synechial closure. This usually begins in the superior angle. Because of the gradual nature of this process, the IOP slowly elevates, and no acute or subacute-type symptoms occur. The term chronic silent angle closure is the name for this condition.

Figure 23-2. Aqueous humor is formed by the ciliary epithelium and moves across the posterior chamber between the posterior iris surface and lens, through the pupil, and into the anterior chamber. Especially in the smaller hyperopic eye, some resistance is present to flow through the pupil (relative pupillary block) that results in a slightly greater pressure in the posterior chamber than in the anterior. The result is forward iris convexity. Most emmetropic eyes demonstrate a slight iris convexity (forward) due to slight relative pupillary block. When a high degree of relative pupillary block is present, angle-closure glaucoma can ensue from the resulting forward movement of the iris into the angle.

THE CONCEPT OF PUPILLARY BLOCK

Aqueous humor is an ultrafiltrate of plasma produced by the ciliary body. Aqueous is secreted into the posterior chamber behind the iris and then flows forward through the pupil into the anterior chamber (Figure 23-2). In most eyes, there is some resistance to flow through the pupillary space due to the close proximity of the pupil to the anterior surface of the crystalline lens. This phenomenon is termed relative pupillary block.

The iris functions in some ways as a valve between the posterior and anterior chambers. The iris contour, whether convex toward the cornea, planar, or concave away from the cornea, reflects the pressure differential between the posterior chamber and anterior chamber. In normal eyes, the iris is in contact with the crystalline lens only in the immediate vicinity of the pupillary border, hence the normal slight iris convexity due to a small amount of relative pupillary block. In most clinical situations, it is believed that the pressure differential that results from relative pupillary block is small in magnitude, probably less than 1 mm.

Relative pupillary block is, in general, more marked in hyperopic eyes, which conceptually are smaller eyes with less room in the middle segment for structures such as the lens. Because of this relatively crowded anatomy, there is more potential for pupillary block. The lens may push the iris forward and there is a greater-than-usual area of contact between the iris and the anterior surface of the lens. This produces a relatively increased resistance to forward flow of aqueous through the pupil. The resulting relatively greater pressure in the posterior chamber produces a greater forward convexity in iris contour.

Forward iris convexity is also a very common occurrence in aged eyes and may or may not by itself produce a functionally narrow angle. A functionally narrow angle depends on additional factors and vectors that will be described. Thus, iris convexity by itself is not an indication for iridotomy to prevent angle closure. Rather, the status and appearance of the angle itself is the indication for laser iridotomy.

In young emmetropic eyes, the iris position is commonly planar, indicating an absence of relative pupillary block and free flow of aqueous through the pupil. Interestingly, in some myopic eyes and in many eyes with pigment dispersion syndrome, the iris contour is concave, indicating a higher pressure in the anterior chamber relative to the posterior chamber. Aqueous humor still flows forward from the posterior chamber to the anterior chamber in the conventional manner in such eyes. How this paradoxical and hypothetical pressure differential exists is a subject of debate. One hypothesis is that in such eyes, in addition to conventional aqueous flow from the ciliary body into the posterior chamber and then through the pupil to the anterior chamber, there is also movement of fluid into the peripheral anterior chamber directly through the base of the iris. Such a phenomenon has been noted in the study of aqueous dynamics in certain primates.4 This might be accentuated in myopic human eyes in which there is relative thinning of the base of the iris.

It is also a matter of debate whether iris concavity is fairly specific for pigment dispersion syndrome or whether it is related more to myopic anatomy. Regardless, one must keep in mind that the iris contour relates very directly to the relative pressure differential across the iris surface. An interesting corollary is that, when there is posterior segment pathology such as retinal tears with egress of fluid posteriorly through the retinal break,⁵ the iris contour may assume a somewhat concave or retracted contour (iris retraction syndrome), especially when there is a condition of pupil sequestration.^6,7

As the eye ages, the crystalline lens increases in size and thickness, producing some iris convexity, even when there was no preexisting hyperopia. This iris convexity is due to relative pupillary block. With aging there is increasing lens size. This allows greater contact of the relatively enlarged lens with the posterior iris surface. Thus, some relative pupillary block is a normal finding in older eyes and does not, by itself, require intervention. The word relative is stressed because normally with iris convexity, there continues to be fluid movement through the pupil into the anterior chamber. There is mildly increased resistance to transpupillary flow at the level of the pupil that results in only a slightly higher pressure in the posterior chamber.

The pupil in acute angle-closure glaucoma may move into a position where there is total or near-total pupillary block (ie, no movement of aqueous into the anterior chamber). The iris bows forward from a build-up of pressure in the posterior chamber to the extent that peripheral iris obstructs the TM outflow system. The presentation is usually dramatic with an iris bombé configuration.

An alternate presentation of pupillary block occurs when there are 360 degrees of posterior synechiae between the iris and the anterior surface of the lens. In this scenario, pupillary block does not occur because of physiologic movement of the pupil into a mid-dilated position. Rather, there is a total adhesion between the border of the pupil and the lens. This condition of total circumferential adhesion is referred to as pupillary seclusion or total pupillary block. It is usually the sequela of inflammation.

Relative pupillary block causes forward iris convexity that results in the movement of the peripheral iris toward the TM. This narrows the approach to the angle. If the approach to the angle becomes sufficiently narrow, progressive forward movement of the peripheral iris may occlude the TM or a portion of the TM. This might happen spontaneously as the pupil changes in diameter in response to illumination. Relative pupillary block is maximized at one particular size of the pupil—usually mid-dilated. The same dynamic might be precipitated pharmacologically.

Laser iridotomy is the definitive treatment for pupillary block. This intervention will equalize the pressure differential between the posterior chamber and the anterior chamber. The iridotomy allows free communication of fluid between the 2 chambers without requiring flow through the pupil. The iridotomy opening must be large enough (50 to 60 μm is sufficient) to allow free flow of aqueous across the iris from the posterior to the anterior chamber. The opening must also be full thickness through the substance of the iris.

It should be noted that a convex iris caused by relative pupillary block can usually be converted to a planar contour by creating an iridotomy. This physical change is based on the equalization of pressure between the anterior and posterior chambers. Nevertheless, the loss of iris convexity does not, by itself, indicate that iridotomy was justified. The indication for iridotomy depends on the assessment of the angle, and not iris contour alone. Most older eyes have iris convexity, but only a minority have a corresponding angle narrow enough to warrant prophylactic iridotomy.

If there is relative pupillary block and iris convexity to the extent that the peripheral iris comes forward to appose the TM, there is limited access of aqueous humor to the TM face. Depending on the extent of nonfunctional angle thus created, the IOP will increase. One should keep in mind that outflow facility and the rate of aqueous production are separate terms in the Goldmann equation that determines IOP. Accordingly, the magnitude of the IOP increase, whether subclinical (ie, still in the normal range under 22 mm Hg) or abnormally higher, depends not only on the extent of the closure but also on the inherent filterability (outflow facility) of the part of the angle that remains open. It should be kept in mind that the IOP also remains affected by the rate of aqueous humor production.

In the presence of functional angle closure, an iridotomy relieves the pressure differential that had caused the iris movement over the TM. Whether there is a beneficial effect on IOP depends on whether the previous angle-closure configuration was simply appositional or if it was synechial. Prior to intervention, indentation gonioscopy of a narrow-angle eye may differentiate potentially reversible apposition from synechial closure. In the former case, the angle opens with pressure applied by the contact goniolens. In the latter case, the angle may open when pressure is applied, revealing the presence of synechiae. This maneuver of applying pressure with the goniolens and observing the angle is more predictive of the benefit of iridotomy than is assessment of the iris contour.

FACTORS THAT MAY INCREASE RELATIVE PUPILLARY BLOCK OR MAY OTHERWISE INFLUENCE THE OCCURRENCE OF ANGLE CLOSURE

Why do some narrow angles close and others do not? Why do some eyes develop chronic angle closure in only a portion of the circumference? Although there is still much that we do not know about angle closure, we do have knowledge of some factors that influence the process. Mapstone 8 has described factors that are involved using the concept of vector forces (Table 23-1). Each of these factors is discussed below.

The Pupil

The size of the pupil can influence pupillary block. In mid-dilation, relative pupillary block increases due to greater contact between the posterior surface of the iris and the anterior surface of the lens. This results in a relative increase in pressure in the posterior chamber and increase in iris convexity (Figure 23-3). Progressively, there may be apposition of the peripheral iris over the TM face and sudden ballooning of the peripheral iris over the angle.

This is classic acute angle-closure glaucoma. The pupil is observed to be fixed in a mid-dilated position, presumably from the ischemia of the iris sphincter that results from very high IOP elevation and impairment of blood flow within the iris. In addition to dilation of the pupil to 5 or 6 mm, the peripheral iris may lose rigidity to the extent that the pressure in the posterior chamber can more easily push the iris forward. The iris is pushed forward a critical amount needed to close the angle.

This event of angle closure was initiated by the normal physiologic movement of the pupil. The individual experiences illumination conditions that result in a mid-dilated position (eg, going into a darkened movie theater). The resulting ischemia from high IOP and impaired blood flow then fixes the pupil in this position.

IRIS RETRACTION SYNDROME

David L. Epstein, MD, MMM

An appreciation of vectors affecting iris contour helps in understanding a peculiar condition, termed by Campbell¹ as iris retraction syndrome. From a clinical point of view, the presence of this iris retraction syndrome^1,2 should suggest an occult rhegmatogenous retinal detachment. In this syndrome, which is usually associated with pupillary seclusion, the peripheral iris demonstrates a retracted appearance. Some have termed this the iris suck sign. Because of the pupillary seclusion, the patients initially might present in pupillary block associated with iris bombé, but after initiation of aqueous humor suppressant therapy, the peripheral iris surprisingly demonstrates this retracted appearance.

The explanation for this phenomenon is that aqueous humor is exiting the eye posteriorly through the retinal hole, presumably by the pumping mechanism of the retinal pigment epithelium. With reduced rates of aqueous humor formation that may be due to uveitis combined with the effect of aqueous humor suppressants, the rate of aqueous humor production might become less than the posterior outflow rate through the retinal hole. Further, the retinal pigment epithelial pump may be stimulated by the use of carbonic anhydrase inhibitors.³ The net posterior movement of fluid results in the retracted appearance of the peripheral iris. In this unusual condition, the secluded pupil acts to keep aqueous humor in the posterior chamber from moving into the anterior chamber.

It must also be remembered that, in the normal physiological state, there is some portion of aqueous humor fluid moving posteriorly through the vitreous chamber and likely being pumped^3,4 out of the eye by the retinal pigment epithelium. In fact, interference with such pumping is one possible explanation for the sudden vitreous expansion that may occur in malignant glaucoma.

REFERENCES

1. Campbell DG. Iris retraction associated with rhegmatogenous retinal detachment syndrome and hypotony. A new explanation. Arch Ophthalmol. 1984;102:1457-1463.

2. Greenfield DS, Bellows AR, Asdourian GK, et al. Iris retraction syndrome after intraocular surgery. Ophthalmology. 1995;102:98-100.

3. Kawano S, Marmor MF. Metabolic influences on the absorption of serous subretinal fluid. Invest Ophthalmol Vis Sci. 1988;29(8):1255-1257.

4. Tsuboi S, Pederson JE. Volume flow across the isolated retinal pigment epithelium of cynomolgus monkey eyes. Invest Ophthalmol Vis Sci. 1988;29:1652-1655.

Physiologic dilation of the pupil is probably the factor most often responsible in instances of angle-closure glaucoma. Onset is associated with dim light or darkness, emotional disturbances, shock, physical illness, or stress experienced in an accident. Angle-closure glaucoma may also be precipitated in anatomically predisposed eyes by systemic medications, such as gastrointestinal or muscle relaxants, antihistamines, or sedatives. Such drugs have atropine-like, anticholinergic properties and induce a slight mydriasis, predisposing to pupillary block.