A UNIFICATION HYPOTHESIS OF PIGMENT DISPERSION
BY Robert Ritch, MD
Purpose: To synthesize recent findings regarding pigment dispersion syn-
drome in order to arrive at a hypothesis concerning the nature of an
underlying genetic predisposition.
Methods: The literature on the subject was reviewed and analyzed.
Results: Eyes with pigment dispersion syndrome differ from normal in that
theyhave a larger iris, a midperipheral posterior iris concavity that increas-
es with accommodation, a more posterior iris insertion, increased irido-
lenticular contact that is reversed by inhibition of blinking, possibly an
inherent weakness of the iris pigment epithelium, and an increased inci-
dence of lattice degeneration of the retina.
Conclusion: A gene affecting some aspect ofthe development ofthe mid-
dle third ofthe eye early in the third trimester appears at the present time
to be the most likely cause.
Pigment dispersion syndrome (PDS) is a unique and fascinating entity. Far
more prevalent than previously suspected,' it is the first common disease
leading to glaucoma for which we are on the verge of a coherent overall
explanation ofpathogenesis and pathophysiology. This paper is an attempt
to tie together many interesting and sometimes disparate and/or appar-
ently anomalous findings in order to synthesize a coherent portrait of the
PDS and pigmentary glaucoma (PG) are characterized by disruption
of the iris pigment epithelium (IPE) and deposition of the dispersed pig-
ment granules throughout the anterior segment. The classic diagnostic
'From the Departments ofOphthalmology, NewYork Eye and Ear Infirmary, NewYork, and
New York Medical College, Valhalla. Supported by the New York Glaucoma Research
Institute and an unrestricted grant from Allergan.
TR. AM. OPHTH. SOC. VOL. XCIV, 1996
triad consists of corneal pigmentation (Krukenberg spindle); slitlike, radi-
al, midperipheral iris transillumination defects, and dense trabecular pig-
mentation. The iris insertion is typically posterior, and the peripheral iris
tends to have a concave configuration. The basic abnormality in this
hereditary disorder remains unknown.
In 1899, Krukenberg' described spindle-shaped pigment deposition on
the cornea. In 1901, von Hippel3 suggested that pigment obstructing the
aqueous outflow system could lead to elevated intraocular pressure (IOP).
Levinsohn4 first suggested that pigment in the anterior chamber angle of
patients with glaucoma originated from the IPE. A cause-and-effect rela-
tionship between pigment and glaucoma found both support56 and oppo-
In 1949, Sugar and Barbour"° described 2 young, myopic men with
Krukenberg spindles, trabecular hyperpigmentation, and open angles,
whose IOP increased with mydriasis and decreased with pilocarpine. The
investigators identified the disorder as a rare, distinct form of glaucoma,
which they termed pigmentary glaucoma. More patients were subse-
quently reported, and in 1966 Sugar" reviewed 147 cases in the world lit-
erature, mentioning several additional features, including bilaterality, fre-
quent association with myopia, greater incidence in men than in women,
and a relatively young age at onset. These features were confirmed by
Scheie and Cameron."
In the 1950s, the discovery of iris transillumination defects led to the
concept that the trabecular pigment originated from the IPE and perhaps
the ciliary body.'3"4 Congenital atrophy or degeneration of the IPE was
suggested as a cause of loss of iris pigment."5"6
In 1979, Campbell'7 proposed the pathogenesis to involve mechanical
damage to the IPE during rubbing ofthe posterior iris against the anteri-
or zonular bundles during physiologic pupillary movement. Subsequently,
the autosomal dominant inheritance, natural history, reversibility, and
more precise therapeutic approaches have become increasingly delineat-
ed. Ultrasound biomicroscopic studies are presently revealing new insights
into the pathophysiology ofPDS.
Loss of iris pigment appears clinically as a midperipheral, radial, slitlike
pattern oftransillumination defects seen most commonly inferonasally and
Pigment Dispersion Syndrome
more easily in blue eyes than in brown ones (Fig 1). Although the defects
can sometimes be seen by retroillumination, they are more easily detect-
ed by a dark-adapted examiner using a fiberoptic transilluminator in a
darkened room. Infrared videography provides the most sensitive method
of detection.'8 Pigment particles deposited on the iris surface tend to
aggregate in the furrows.""9 Rarely, this pigment can be dense enough to
darken the iris or to cause heterochromia when involvement is asymmet-
ric."'20 Iris vascular hypoperfusion on fluorescein angiography has been
reported,2' a finding which awaits verification.
Iris transillumination defects. Typical defect is midperipheral, radial, and slit-like. Some
defects, especially inferiorly, have peripheral clublike endings, giving them the appearance of
an exclamation point. These peripheral transillumination dots might result from iridociliary
Anisocoria may occur with asymmetric involvement, the larger pupil
corresponding to the eye with greater pigment loss from the iriS.22-24
Alward and Haynes22 suggested the presence of an efferent defect in the
eye with the larger pupil. The pupil may be distorted in the direction of
maximal iris transillumination.'5 This would be consistent with the pres-
ence of hyperplasia of the iris dilator muscle (see below).26
Corneal endothelial pigment generally appears as a central, vertical,
brown band (Krukenberg spindle), the shape being attributed to aqueous
convection currents (Fig 2). The pigment is phagocytosed by endothelial
cells,27,28 but endothelial cell density and corneal thickness remain
unchanged compared with controls.'9 Coincident PDS and megalocornea
have been reported,12162930as have subluxated lenses.'2'3'
The anterior chamber is deeper both centrally and peripherally than
can be accounted for by sex, age, and refractive error. Davidson and asso-
ciates32 compared the central and peripheral anterior chamber depths of
patients with PDS to statistical controls. The anterior chamber was signif-
icantly deeper, and the anterior chamber volume was significantly greater
in the PDS group, the difference being greatest inferiorly.
The angle is characteristically widely open, with a homogeneous,
dense hyperpigmented band on the trabecular meshwork (Fig 3). Pigment
may also be deposited on Schwalbe's line. The iris insertion is posterior,
and the peripheral iris approach is often concave. The iris is most concave
in the midperiphery. In younger patients, the scleral spur may be poorly
Pigment Dispersion Syndrome
Pigment reversal sign in 48-year-old man. A. Inferior angle. B. Superior angle. Pigment is
denser in superior angle. Note that pigment band has sharp anterior and posterior margins
and appears smooth, indicating that pigment was deposited in past and is now localized to
region of filtering portion oftrabecular meshwork. Iris is inserted posteriorly.