PIGMENT DISPERSION SYNDROME AND PIGMENTARY GLAUCOMA

Signs and Symptoms

Pigment dispersion syndrome (PDS) is an asymptomatic disorder typically discovered upon routine evaluation.1 Pigmentary glaucoma (PG), a sequela of pigment dispersion syndrome, is also asymptomatic. Patients rarely present with complaints related to episodic rises in intraocular pressure secondary to exercise, such as colored haloes around lights, blurred vision or subtle ocular pain.2,3 Both conditions are typically encountered in young, typically myopic, Caucasian males between the ages of 20 and 40.4 One population-based study observed pigment dispersion syndrome in 2.45% of Caucasians undergoing glaucoma screening.4 Pigment dispersion syndrome and pigmentary glaucoma also occur in African American patients, though less commonly than in Caucasians.5-7 The majority of patients in this category are older, female and hyperopic.5-7

Patients with pigment dispersion syndrome and pigmentary glaucoma demonstrate liberation of iris pigment within the anterior chamber. Often, this is seen as diffuse accumulation or possibly a granular brown vertical band along the corneal endothelium known as a Krukenberg’s spindle.8-10 Pigment accumulation may also be evident on the lens and the surface of the iris.

Dense pigmentation is seen gonioscopically, often covering the trabecular meshwork for 360 degrees; it is most prominent in the inferior quadrant due to gravity.8,11 When pigment accumulates on Schwalbe’s line, it is referred to as Sampaolesi’s line.5 The angle recess remains unchanged and open. Radial, spoke-like transillumination defects of the mid-peripheral iris are common.5,7,8

There seem to be some differences in the appearance of pigment dispersion syndrome and pigmentary glaucoma in African American patients. Here, the degree of corneal endothelial pigmentation is quite mild, and Krukenberg’s spindles are not usually present. The degree of corneal endothelial pigmentation is not predictive of the amount of trabecular meshwork pigment that may have accumulated. Iris transillumination defects are rarely present, possibly due to a thicker iris stroma.5,6,9

While the intraocular pressure (IOP) is not altered in pigment dispersion syndrome, it may rise sharply in cases of pigmentary glaucoma. Likewise, pigment dispersion syndrome presents with a normal optic nerve appearance, while patients with pigmentary glaucoma manifest evidence of glaucomatous optic atrophy and associated field loss.

Pathophysiology

The pathophysiology of pigmentary glaucoma must be considered in two parts: mechanism of pigment release and mechanism of pressure elevation. Pigment dispersion occurs as a result of the proximity between the posterior iris pigment epithelium and the zonular fibers of the lens. The abrasive nature of this physical contact leads to mechanical disruption of the iris surface and release of pigment granules into the posterior chamber, which follows the flow of the aqueous convection currents into the anterior chamber angle.13-15

Many patients with pigment dispersion syndrome and pigmentary glaucoma demonstrate a concave approach of the iris as it inserts into the anterior chamber angle, giving the iris a “backward bowed” appearance on gonioscopy.15 This posterior bowing of the iris places the posterior iris into apposition with the lens zonules. As the iris responds to light, iridozonular friction results in pigment liberation from the posterior iris. Sometimes the degree of pigment loss in the mid-peripheral areas produces visible transillumination defects corresponding to packets of iris zonular fibers.14 While the majority of these patients have a concave iris approach, others may have a flat or planar approach.15

It has been theorized that in cases with a markedly concave iris insertion, the iris functions as a flap valve lying against the anterior lens surface. When a pressure gradient develops that is greater in the anterior chamber, the iris is forced backwards, closing the valve and stopping the aqueous from moving into the anterior chamber. This increased anterior chamber pressure subsequently forces the iris into the concave approach of the iris and has been termed “reverse pupillary block.” The blocked flow increases IOP and over time produces the expected neural damage.16,17 This phenomenon has been found to increase with patient blinking.14,18,19

When excessively released pigment accumulates in the trabecular meshwork, there are two possible consequences. First, pigment may reside benignly in the trabecular meshwork. Here, IOP is unaffected and the condition remains pigment dispersion syndrome. Alternatively, when the pigment causes a rise in IOP and the nerve and function suffer, the patient develops pigmentary glaucoma.14

Interestingly, physical blockage of the trabecular meshwork by pigment granules is not the likely cause of the pressure rise.20 Endothelial cells lining the trabecular beams of the trabecular meshwork quickly phagocytize small amounts of accumulated pigment, preserving the normal architecture of the trabecular meshwork.21-23 However, in chronic cases of pigment dispersion, greater amounts of pigment are more difficult for the cells to phagocytize. When this occurs, the endothelial cells that line the trabecular meshwork beams disintegrate. The resultant degeneration of the trabecular meshwork with the accumulation of debris, collapsed beams and loss of intratrabecular spaces is what produces the rise in IOP.23 The IOP rise in pigmentary glaucoma mostly occurs due to a breakdown of normal phagocytic activity of the endothelial cells and subsequent loss of normal trabecular architecture and function.23

Management

As pigment dispersion syndrome has no direct ramifications on ocular health or vision, other than potential future development of pigmentary glaucoma, these patients should be treated as glaucoma suspects. Patients should be monitored for IOP spikes and optic nerve changes three to four times a year, with threshold visual fields, diagnostic imaging and gonioscopy performed annually. One study noted the conversion rate from pigment dispersion syndrome to pigmentary glaucoma to be 20%, with the vast majority converting within 10 years from the diagnosis of pigment dispersion syndrome.24 However, patients with pigment dispersion syndrome who were followed for greater than 10 years without developing pigmentary glaucoma had a low risk of developing pigmentary glaucoma subsequently.24 Another study noted the risk of developing pigmentary glaucoma from pigment dispersion syndrome was 10% at five years and 15% at 15 years. Young, myopic men were more likely to convert to pigmentary glaucoma, and an IOP greater than 21mm Hg at initial examination was associated with an increased risk of conversion.25

Medical treatment of pigmentary glaucoma involves reduction of IOP with aqueous suppressants.8 There has been conjecture that prostaglandin medications should be avoided in glaucoma patients where pigment liberation is involved in the etiology, as these medications increase the amount of melanin in stromal melanocytes and could potentially impair drainage further. However, this fear is unfounded as the melanocyte size has only been confirmed to increase within the iris stroma. Prostaglandin medications have been seen to successfully lower IOP in eyes with pigment dispersion from pseudoexfoliative glaucoma. Thus, prostaglandin medications are a good therapeutic option for pigmentary glaucoma.26-28

Laser peripheral iridotomy (LPI) has intermittently been performed for patients with pigment dispersion syndrome and pigmentary glaucoma where there is significant iris concavity.14-16 It has been well reported that the iris can convert from a concave to a planar approach following LPI.14-16 However, there is very little information available regarding the effect of LPI on IOP in pigmentary glaucoma. In a retrospective study, data was analyzed on patients with bilateral pigmentary glaucoma who received uniocular LPI.29 The main outcome measure was the post-laser intraocular pressure course of the treated eyes, compared with the fellow, untreated eyes. The conclusion of this study did not show a benefit in long-term IOP control in eyes with pigmentary glaucoma undergoing LPI.29

A prospective, controlled, randomized study looked at 166 eyes with pigment dispersion syndrome and elevated IOP, but no glaucomatous damage, and randomized eyes to either LPI or no LPI with a primary outcome of conversion to pigmentary glaucoma at three years. Analyses showed no evidence of any difference in time to visual field progression or commencement of topical therapy between the two groups. This study concluded that there was no benefit of LPI in preventing progression from PDS with associated ocular hypertension to pigmentary glaucoma within three years of follow up.30

Patients with pigmentary glaucoma tend to respond well to argon laser trabeculoplasty, presumably due to the improved thermal effects on trabecular tightening, secondary to the increased meshwork pigmentation.31-35 There appears to be little published data regarding the efficacy of selective laser trabeculoplasty (SLT) in pigmentary glaucoma. However, because SLT works by creating inflammation where the immune system effectively cleans the spaces between the trabecular beams and the mechanism of pigmentary glaucoma is secondary to beam damage, it would seem logical that SLT would not be effective. In one series involving four patients, researchers found that post-SLT IOP elevation was a serious adverse event.36 Trabeculectomy remains an option for patients with recalcitrant pigmentary glaucoma.

Clinical Pearls

Pigmentary glaucoma should be strongly considered when encountering glaucoma in younger patients.

Pigmentary glaucoma is often under-diagnosed in African American patients due to the lack of corneal endothelial pigment and iris transillumination defects. Often, the trabecular hyperpigmentation is incorrectly attributed to overall racial pigmentation.

Diurnal IOP variations can be quite extreme in pigmentary glaucoma.

There appears to be no role for LPI in the management of PG.

The issue of exercise-induced liberation of pigment with resultant IOP spike arises from a single published case. Attempts at experimental induction of this phenomenon have met with little success. There is no reason to discourage young patients with pigment dispersion syndrome from exercise.

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