Dx and Tx of Pigment Dispersion Syndrome and Pigmentary Glaucoma

This article is from January 2009 and may contain outdated material.

Pigment dispersion syndrome (PDS), a bilateral disorder, occurs when pigment is lost from the posterior surface of the iris and is redistributed to the structures of the anterior and posterior chambers. Released pigment can deposit in the trabecular meshwork to cause increased intraocular pressure and pigmentary glaucoma. Since onset of PDS can occur as early as the second decade of life, significant glaucomatous damage may occur before the patient presents to the ophthalmologist. 

Pathophysiology

In eyes with PDS, a concave posterior iris surface mechanically rubs against anteriorly oriented zonular fibers to release iris pigment granules into the anterior chamber. This concave iris position is thought to occur as a result of reverse pupillary block where higher pressure in the anterior chamber leads to posterior iris bowing, contact with anterior lens zonules and pigment release. Aqueous convection currents then disperse these pigment granules to structures of the anterior chamber, including the corneal endothelium, iris surface and trabecular meshwork. When liberated pigment accumulates in the trabecular meshwork and limits aqueous humor outflow, increased intraocular pressure and pigmentary glaucoma may develop.

Cases of PDS are most often sporadic although genetic studies suggest an autosomal dominant inheritance pattern with linkage to chromosome 7.¹

Clinical Findings

Often the first sign of PDS, a Krukenberg spindle represents the vertical collection of pigment granules along the corneal endothelium. The spindle is usually oriented nasally with a wider base inferiorly. This finding is best exam ined by using the slit-lamp biomicroscope to focus a broad beam of light on the corneal endo thelium. It is important to note that a Krukenberg spindle is neither sensitive nor specific for PDS, as it may be found in other conditions associated with pigment liberation, such as uveitis and trauma.

Unlike other causes of pigment liberation, however, pigment deposition in PDS can occur at the insertion of lens zonular fibers into the posterior lens capsule and cause a pattern known as a Zentmayer ring or Scheie stripe. To appreciate this pattern of pigment deposition, the examiner must focus the slit lamp on the posterior chamber while the patient assumes extreme gaze in any direction. Pigment granules in PDS also have been reported to deposit on the anterior hyaloid-capsular ligament (Egger’s line) and in filtering blebs.

In eyes with PDS, the posteriorly bowed iris mechanically rubs against radially oriented lens zonules to create the midperipheral slitlike iris transillumination defects characteristic of the disease. Iris transillumination defects are best examined prior to pupillary dilation by directing a small slit beam perpendicular to the plane of the iris in a darkened room.

Gonioscopic examination reveals increased trabecular pigmentation that is uniform and distributed diffusely along the entire 360 degrees of a wideopen anterior chamber angle. Pigment deposition along Schwalbe’s line is referred to as Sampaolesi’s line. Gonioscopy of the peripheral iris reveals a concave iris configuration.

Careful examination of the posterior segment is crucial in patients with PDS. The frequency of lattice degeneration is higher in these patients than in age and refraction-matched controls,² and retinal detachment has been reported to occur in approximately 6.4 percent of PDS patients.³

Differential Diagnosis

Several ocular conditions result in pigment release into the anterior chamber and may be associated with glaucoma. Most of these conditions occur unilaterally and are, therefore, easily distinguished from PDS. Unlike PDS, the trabecular pigmentation is less dense and is unevenly distributed throughout the anterior chamber angle in most of these conditions.

Pseudoexfoliative glaucoma. Pseudo-exfoliative glaucoma is similar to PDS and shares many clinical features: iris transillumination defects, a Krukenberg spindle, trabecular pigmentation and increased IOP. However, the iris transillumination defects in pseudoexfoliative glaucoma are typically at the pupillary border, in contrast to the characteristic midperipheral spokelike iris defects in PDS. Pseudoexfoliative glaucoma generally affects patients older than 60 years of age and becomes more severe with increasing age. PDS typically afflicts a younger demographic in the third and fourth decades of life and becomes less severe with increasing age. The presence of whitish-gray flakes of exfoliation material at the pupillary margin of the iris and anterior lens capsule is diagnostic for pseudoexfoliative glaucoma and lacking in PDS. The clinical features of PDS and pseudoexfoliative syndrome are summarized in the table titled “Pigment Dispersion vs. Pseudoexfoliation.”

Anterior uveitis. Anterior uveitis is a common cause of pigment liberation into the anterior chamber and should be considered in the differential diagnosis of PDS. However, pigmentation of the trabecular meshwork in uveitis is irregularly distributed, mostly in the inferior angle and in clumps. Other features of anterior uveitis such as peripheral anterior synechiae, aqueous flare and keratic precipitates are absent in PDS.

Primary open-angle glaucoma. The trabecular meshwork in patients with primary-open angle glaucoma may be variably pigmented, but this pigmentation tends to be more segmental and less diffuse than in PDS. As with pseudoexfoliative glaucoma, patients with primary open-angle glaucoma are older and lack the other characteristic findings of PDS.

Ocular tumors. Johnson and colleagues recently reported a case of uveal melanoma masquerading as pigmentary glaucoma.⁴ Indeed, many ocular tumors cause both pigment liberation and secondary glaucoma. However, these cases are most often unilateral and associated with other clinical features such as corectopia and tumor mass effect.

Other conditions. Additional causes of pigment dispersion such as trauma, rhegmatogenous retinal detachment and pigment liberation due to intraocular lens placement should also be considered in the differential diagnosis of PDS.

Clinical Course

Approximately 35 percent of patients with PDS will develop ocular hypertension or glaucoma. Therefore, all patients with PDS should undergo periodic eye examinations to ensure early diagnosis and management of pigmentary glaucoma. The ophthalmologist may examine these patients on an annual basis if they demonstrate normal visual fields, optic nerve head examination and intraocular pressures. However, more frequent follow-up is warranted if any of these clinical indicators are suspicious for glaucomatous damage.

Generally, IOP in pigmentary glaucoma is more difficult to control than in primary open-angle glaucoma. Typically, though, as the patient ages and pigment release slows, the disease becomes less severe. This phenomenon occurs as the lens naturally enlarges and increases physiologic relative pupillary block, pushing the peripheral iris forward and relieving the iris-zonular contact.

Some patients with pigmentary glaucoma may develop a rapid, transient intraocular pressure spike due to increased pigment release, with pharmacologic pupillary dilation or vigorous physical activity. Prophylactic antihypertensive treatment of these patients prior to participation in heavy exercise or competitive sporting should be considered. 

Management

Patients with PDS generally are at an increased risk of developing ocular hypertension and glaucoma and should therefore be followed closely for early initiation of treatment. One should consider initiating treatment in patients with PDS and persistently high IOPs. Patients with PDS who develop pigmentary glaucoma have greater fluctuation in their IOPs than patients with POAG and may not be as responsive to standard medical, laser and surgical therapies.

Medication. Medical therapy for pigmentary glaucoma does not differ greatly from other types of open-angle glaucoma. Miotics, beta-blockers, prostaglandin analogs, carbonic anhydrase inhibitors and alpha-adrenergic compounds all can lower IOP.

Miotics, such as pilocarpine, are believed to have a twofold advantage in treating pigmentary glaucoma by: 1) decreasing IOP by allowing greater aqueous outflow and 2) shifting the iris forward to increase pupillary block and decrease iris-zonular apposition and pigment release. However, most patients with pigmentary glaucoma are young, high myopes and do not tolerate miotic therapy secondary to increased myopia, headaches and accommodative spasm. Also, the physician needs to be cautious when initiating miotic therapy in the myopic patient with pigmentary glaucoma because of the increased risk of retinal detachment associated with pilocarpine use.

Iridotomy. Ultrasound biomicroscopic studies have demonstrated that laser iridotomy eliminates the iris concavity in PDS by equalizing the pressure between the anterior and posterior chambers. Theoretically, this procedure should eliminate iridozonular contact and pigment shedding. However, there is conflicting evidence regarding the efficacy of the procedure in reducing IOP in eyes with PDS. Furthermore, laser iridotomy prevents the natural relative pupillary block that occurs with age, and this theoretically results in decreased severity of disease in patients with pigmentary glaucoma. Currently, laser iridotomy is controversial in the management of pigmentary glaucoma.⁵

Laser trabeculoplasty. Laser trabeculoplasty has been demonstrated to lower IOP effectively in eyes with pigmentary glaucoma. Caution must be exercised when setting the laser energy in this procedure, as the heavily pigmented trabecular meshwork in eyes with pigmentary glaucoma absorbs greater energy. A lower energy setting should be used to lessen tissue damage and prevent an IOP spike after the procedure. Pretreatment with topical alpha2-adrenergic agonists also can help blunt laser-induced pressure spikes.

Filtering surgery. Filtering surgery is often successful in pigmentary glaucoma. However, the surgeon should be aware that the use of antifibrotic agents in young myopes increases the risk of hypotony maculopathy. Implantation of seton devices also has been successful in controlling IOP in pigmentary glaucoma. Unlike pseudoexfoliative glaucoma, there is no increased risk of complications after cataract surgery in eyes with pigmentary glaucoma. 

Conclusion

Frequently underdiagnosed, PDS afflicts a relatively young patient population that is at risk for development of pigmentary glaucoma. The disease is bilateral and presents with characteristic clinical features. Intraocular pressure is more difficult to control than in primary open-angle glaucoma, and this necessitates early screening, diagnosis and treatment of PDS patients.

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1 Andersen, J. S. et al. Arch Ophthalmol 1997;115:384–388.

2 Liebmann, J. M. Focal Points 1998;16(2):1–14.

3 Scheie, H. G. et al. Br J Ophthalmol 1981;65:264–269.

4 Johnson, D. L. et al. Arch Ophthalmol 2008;126:868–869.

5 Yang, J. W. et al. J Glaucoma 2001;10:S30–S32.

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Dr. Aref is a resident in ophthalmology and Dr. Scott is a professor of ophthalmology and public health sciences. Both are at Penn State University. Dr. Callahan is an assistant professor of ophthalmology at the University of South Florida.