Several age-associated changes can include progressive relative pupillary block from a combination of increasing lens thickness, more anterior positioning of the lens, and pupillary miosis. It should be emphasized, however, that PACG with pupillary block can occur in patients of any age, and rarely even in children –

though the etiologies among the young are almost always developmental or secondary.152–155

Gender

Older studies have reported that PACG with pupillary block occurs 2–3 times more commonly in women than in men.36,117,156–159 The

increased prevalence of angle closure in women probably reflects the fact that women have shallower anterior chambers;96,160 with

some 10% less ocular volume than men.19 One exception to this observation may be in those of black African ancestry, in whom

the occurrence of angle-closure glaucoma is apparently comparable among men and women.118

Heredity

Most cases of PACG with pupillary block are sporadic in nature –

that is, there is no family history of glaucoma. However, several pedigrees are reported to have a high prevalence of PACG,161,162

some with autosomal-dominant and some with autosomal-recessive patterns of inheritance. Shallow anterior chambers and narrow angles have been reported as more common in relatives of patients

with PACG than in individuals whose relatives do not have the disorder.163–165 Similarly, a recent report observed that plateau iris

configuration may aggregate in familial patterns.166

Fifty years ago, Tornquist91,163 suggested that the configuration of the anterior chamber was inherited under polygenic influence, explaining the variable familial occurrence of PACG rather than a specific gene linked to the disease. The intricate developmental details now available regarding the growth of the anterior chamber167 and the explosive field of molecular genetics may soon elaborate upon these clinical perceptions.

Refractive error

The prevalence of PACG with pupillary block is much higher in

individuals with hyperopic eyes, which typically have shallow anterior chambers and short axial lengths.96,143 Although rare, angle-

closure glaucoma can occur in myopic eyes.168

Miscellaneous factors

Older reports have suggested that PACG with pupillary block occurs more commonly in the winter months.169–171 This was vari-

ously attributed to low levels of illumination, increased cloudiness, changeable weather, and low sunspot activity.172 Central corneal thickness – a recently recognized risk factor for POAG – does not seem to have an association with PACG.173

Ocular risk factors and mechanisms

Ocular risk factors cluster around a variety of findings, each of which reflects smaller ocular dimensions:19,20,143

1.Shallow anterior chamber both centrally81–83 and peripherally.82,84,85 Both Lowe81 and Alsbirk86 found angleclosure glaucoma to be uncommon in eyes with central anterior chamber depths of 2.5 mm or greater (Table 15-1).

2.Decreased anterior chamber volume.77

3.Short axial length of the globe.76,82

4.Small corneal diameter.84,88

5.Increased posterior corneal curvature (i.e., decreased radius of posterior corneal curvature).89–91

6.Decreased corneal height.83

Table 15-1  Central anterior chamber depth and angle-closure glaucoma in a group of Eskimos

Modified from Alsbirk PH: Acta Ophthalmol (Copenh) 53:89, 1975.86

 7. Anterior position of the lens with respect to the ciliary body.83

 8. Increased curvature of the anterior lens surface.92

 9. Increased thickness of the lens.76,83,92,93,174

10.More anterior insertion of the iris into the ciliary body,

giving a narrower approach to the angle recess, and possible anomalies of iris histology.175

11.Thinning of the ciliary body is reportedly associated with

anterior movement of the lens, increased lens thickness and decreased anterior chamber depth.176

Three measures in particular show particularly high correlations with angle-closure disease: (1) reduced axial anterior chamber depth and volume; (2) thicker lens; and (3) steeper radii of corneal curvature.177,178 The biometric peculiarities of eyes predisposed to

angle-closure glaucoma are accentuated by three trends associated with aging. First, the lens grows in thickness throughout life.95,96

Second, the lens assumes a more anterior position with age.95 Third, the pupil becomes increasingly miotic with age. All of these age-associated changes increase the contact between the iris and lens, potentiate pupillary block, and reduce anterior chamber depth and volume. It is estimated that central anterior chamber depth decreases 0.01 mm/year.96

Despite the elaboration of the specific ocular risk factors associated with PACG, the ‘fit’ with the demographic data is not completely congruent: to wit, population studies do not support the

generalization that ethnic groupings have smaller eyes or ocular dimensions than others.19,177,179 Another way of integrating the

data in light, for example, of the excessive burden of devastating PACG among Chinese populations, is to state that, statistically, Chinese don’t have smaller eyes – but those with small eyes (e.g., elderly women) are at greater risk for angle-closure disease. This anomaly has generated new hypotheses as to what other specific factors may be at play, such as the possible role of choroidal expan-

sion in both angle-closure glaucoma and in ciliary block (malignant) glaucoma.19,180

Iris bowing and lens–iris channel

Somehow the junction of the lens and iris at the pupillary plane modulates the flow of aqueous from the posterior to the anterior chamber, but it apparently is not a simple matter of direct contact between lens and iris. Part of this mechanism is thought to be due to iris structures: the iris sphincter muscle exerts a posterior vector of force that causes the central iris to ‘hug’ the anterior lens surface,78 with a possible contributory interplay with the dilator musculature. Preliminary studies of intra-iris collagen in acute PACG eyes suggest morphological changes may also contribute to abnormal iris mechanics.175 The flow capacity may also depend on the viscosity and other properties of the aqueous.

Fig. 15-6  Relative pupillary block.

This important interface has been described as the iris–lens channel: an extremely thin ( 5 microns), fluid-filled, flat, doughnutshaped passage between the posterior iris surface and the anterior lens, circumferentially extending beyond the edges of the pupil.181 This dynamic and pulsatile182 fluid ‘structure’ provides normal resistance to aqueous flow from the posterior to anterior chambers. This thus functions as a relative one-way valve to sustain a minimally higher pressure in the posterior chamber than in the anterior chamber, hence directing anterior flow forward. Though the iris–lens channel is currently below the level of UBM resolution, the lens itself is not thought to directly contact the posterior iris, but remains a major variable in determining the configuration of the lens–iris channel, and hence its flow capacity.

The resistance to flow has classically been referred to as relative pupillary block (Fig. 15-6). Under normal circumstances, this pressure differential is of little significance; however, if the pupillary block were to increase, the pressure posterior to the iris could force the peripheral iris to billow forward into the angle. (‘Like a sail full of wind’ is how this is often described to patients in explaining the salutory effect of a peripheral iridotomy’s perforation of the iris.) The increasing anterior bowing of the peripheral iris is maximized both when the anterior lens surface is progressively more anterior relative to the iris root, and when the pupil is in a mid-dilated position. A thicker iris has reduced flexibility which could increase

the pressure difference between posterior and anterior chambers through the lens–iris channel.19,175,183

If the peripheral iris bows forward slightly or if the anterior chamber is relatively large, the effect on IOP and anterior chamber dynamics would be inconsequential. However, if the peripheral iris bows forward enough to cover the trabecular meshwork, the normal outflow of aqueous humor from the anterior chamber would be blocked and the IOP could increase79 (Fig. 15-7).Angle- closure disease typically occurs in eyes with small anterior segments in which even a relatively small forward bow of the peripheral iris may contact the trabecular meshwork.

Intraocular pressure and outflow facility are normal in eyes with shallow but open angles, no matter how narrow the angle appears. In contrast, when the iris is in contact with the trabecular

(A)

(B)

Fig. 15-7  (A) Pupillary block leading to angle closure. (B) Ultrasound biomicroscopic photograph illustrating central posterior iris apposition causing the iris to bow forward and occlude the anterior chamber angle.

(Courtesy of Robert Ritch, MD.)

meshwork, IOP rises and outflow facility falls in proportion to the extent of the angle closed; the resultant IOP would depend on the function (outflow facility) of the remaining unobstructed and undamaged angle.

Moderate pupillary dilation is historically the most recognizable cause of increased pupillary block, frequently due to pharmacologic dilation. It is thought that the posterior vector of force of the

iris sphincter muscle reaches its maximum when the pupil is moderately dilated to a diameter of 3.0–4.5 mm.78,97,183 Furthermore,

when the pupil is moderately dilated, the peripheral iris is under less tension and is more easily pushed forward into contact with the trabecular meshwork. Lastly, dilation may also thicken and bunch the peripheral iris in the angle. In contrast, when the pupil is widely dilated, there is little or no contact between the lens and the iris and minimum pupillary block. This fact explains why acute angle-closure glaucoma rarely occurs while the pupil is in the actual process of dilating due to mydriatic eye drops: the dilation occurs rapidly enough that pupillary block does not have time to develop. Rather, pupillary block ‘classically’ occurs as the pupil constricts over hours following dilation, presumably because the mid-dilation is prolonged as the mydriatic effect slowly reverses.