Jonathan S. Myers

BASICS

DESCRIPTION

• Pigment dispersion syndrome (PDS) is a disorder characterized by the release of pigment particles from the pigment epithelium of the iris. These pigment particles are carried by the aqueous humor and deposited on the structures of the anterior segment.

• Pigmentary glaucoma (PG) is a secondary open-angle glaucoma, occurring in one third of patients with PDS. Released iris pigment interferes with trabecular meshwork function, leading to elevated intraocular pressure (IOP) and an optic neuropathy.

EPIDEMIOLOGY

Incidence

• Approximately one third of patients with PDS will go on to develop PG over 15 years.

• Conversion from the syndrome to glaucoma is less frequent as age increases into the 40s and 50s, and in some cases, the glaucoma may regress over time.

Prevalence

• Constitutes 1–2.5% of all glaucoma seen in most Western countries

• Can be detected as early as the mid-teen years of life

• Peak prevalence 3rd and 4th decades of life

RISK FACTORS

• Most often seen in young adults—can be diagnosed in adolescents and in older individuals

• Caucasians—rarely seen in Asians and African Americans

• Male gender—possibly due to increased chamber depth as compared with females

• Myopia—present in 80% of individuals with PDS

Genetics

PDS is thought to be autosomal dominant with incomplete penetrance. At least one genetic locus has been identified on chromosome 7q.

PATHOPHYSIOLOGY

• Mechanical:

– A posterior bowing of the peripheral iris induces recurrent contact between the iris pigment epithelium and the lens zonules, leading to a dispersion of pigment.

– Posterior iris bowing may be from a posterior iris insertion to the sclera, a concave profile in the setting of a deeper than normal anterior chamber, and/or a floppy iris stroma.

– A posteriorly directed pressure gradient can trigger this phenomenon, such as blinking or reverse pupillary block seen with iris–lens contact, accommodation, and exercise.

– Long anterior zonular fibers inserted onto the central lens capsule may also cause mechanical disruption of the pigment epithelium at the central iris, leading to pigment dispersion.

• Genetic and environmental conditions leading to weakness of the iris pigment epithelium.

• As affected individuals age, many patients experience a decrease in pigment dispersion.

– Increased pupillary miosis and cataract formation cause an increase in relative pupillary block. This permits accumulation of aqueous within the posterior chamber and increases the distance between the zonule fibers and the iris.

ETIOLOGY

• Certain conditions have been found to exacerbate the dispersion of pigment:

– Accommodation, jarring physical exercise, emotional stress, and naturally occurring or drug-induced mydriasis

COMMONLY ASSOCIATED CONDITIONS

• PDS

• Myopia

DIAGNOSIS

HISTORY

• Like many open-angle glaucomas, PG is usually asymptomatic. Thus, diagnosis is often made on routine exam.

• Most often bilateral in nature

• Conditions triggering an acute dispersion of pigment (exercise, accommodation, prolonged dark environment, etc.), can lead to an acute rise in IOP, with resultant symptoms.

– Haloes around lights, ocular pain, and blurred vision from corneal edema

PHYSICAL EXAM

• On slit lamp exam, pigment may be seen on numerous structures throughout the anterior ocular segment.

– Increased anterior chamber depth with visible melanin granules in the aqueous

– Aqueous convection currents cause released pigment to deposit in a vertical fashion, slightly decentered inferiorly, on the corneal endothelium (Krukenberg spindle). The pigment is then phagocytized by corneal endothelial cells. This spindle is neither pathognomonic nor invariably present.

– Radial midperipheral slit-like iris defects seen on retroillumination or transillumination—corresponds to location of iris–zonule contact (best seen using a small slit beam, in a dark room, prior to patient dilation)

– Open anterior chamber angle with increased pigmentation of the trabecular meshwork 360^∘ and pigment deposition anterior to Schwalbe’s line (Sampaolesi’s line), in the inferior 180^∘

– Pigment inside a glaucoma filtering bleb

– Pigment deposition in circumferential iris furrows. This can lead to iris heterochromia if the disease is asymmetric between the two eyes (with the darker iris being the more affected side).

– Anisocoria—larger pupil is on the side with the greater iris transillumination.

– Combination of iris heterochromia and anisocoria may mimic Horner syndrome.

– Pigment deposition on the posterior lens surface at the site of zonular attachments (Zentmayer’s ring or Scheie’s line)

– Pigment granules on the lens zonular fibers and equatorial region seen in mydriasis

In contrast to pseudoexfoliation glaucoma, this pigment deposition does not seem to lead to zonular weakness.

• A concave appearance of the peripheral iris seen on slit lamp exam and gonioscopy.

• On peripheral retinal examination, lattice degeneration or retinal breaks may be seen.

DIAGNOSTIC TESTS & INTERPRETATION

Imaging

Initial approach

• Ultrasound biomicroscopy (UBM) analysis (optional)—provides high-resolution imaging of anterior and posterior chamber anatomy.

– Concave profile of the peripheral iris with iridozonular contact

– Reverse pupillary block

– Longer than usual radial iris length leading to iris flattening on the anterior lens surface (iridolenticular contact)

– Increased anterior chamber depth

– Posterior iris insertion

• Slit lamp optical coherence tomography (optional)—may be used to assess the parameters of the anterior chamber and angle dimensions.

Diagnostic Procedures/Other

• Gonioscopy—increased pigmentation of the anterior chamber angle 360^∘

• Transillumination/retroillumination—visualize midperipheral iris defects

• Diurnal curve measurements—diurnal curve fluctuations are thought to occur more often in PG and can lead to acute symptomatic elevations in IOP.

Pathological Findings

• Pigment and debris in the trabecular meshwork cells.

– Trabecular meshwork cells engulf the pigment and eventually detach from the trabecular beams, leading to sclerosis and eventual fusion of the intratrabecular spaces.

• The cul-de-sacs, which normally terminate in aqueous channels, are reduced, contributing to increased resistance to aqueous outflow.

• Atrophy and hypopigmentation of the iris pigment epithelium

• Hyperplasia of the iris dilator muscle

DIFFERENTIAL DIAGNOSIS

• Pseudoexfoliation glaucoma—differs by pseudoexfoliative material on the anterior lens and pupillary border. No myopic predilection, older age, and 50% of cases are unilateral. Iris transillumination characteristically begins at the pupillary border rather than the midperiphery. Darker and less homogenous pigment deposition in meshwork.

• Primary open-angle glaucoma with increased trabecular meshwork pigmentation. Often see patchy pigment band in angle, older age.

• Cysts of the iris and ciliary body, typically unilateral

• Pigmented neoplasms of the iris–ciliary body complex—will not see Krukenberg spindle or midperipheral transillumination defects. May see narrowing of the angle at the area of neoplasm.

• Iris chafing syndrome—misplacement of posterior chamber intraocular lens leading to haptics rubbing the posterior iris

• Uveitis—careful examination for keratic precipitates on corneal endothelium and lack of pigment deposition on other anterior segment tissues, greater pigmentation inferiorly

• Previous surgery or trauma—obtain thorough history. Iris transillumination, if present, usually more confluent and/or segmental.

TREATMENT

MEDICATION

First Line

• Medical therapy directed at lowering IOP:

– Aqueous suppressant drops—beta-blockers, α-agonist, carbonic anhydrase inhibitors

– Aqueous outflow enhancing drops—prostaglandin analogues

Iris surface color change seen with the use of prostaglandin analogues is due to increased melanin production by iris melanocytes. This is not known to affect the iris pigment epithelium or result in increased pigment dispersion.

Second Line

• Cholinergic agents (pilocarpine)—lowers IOP by both increasing aqueous outflow at the trabecular meshwork and by pulling the iris away from zonular fibers, leading to reduced pigment release.

– Pilocarpine has been found to be effective in inhibiting exercise-induced pigment dispersion and resultant increase in IOP.

– Especially in young patients, miotics may induce headaches, blurred vision, or increase the risk of retinal detachment.

– In this setting, thymoxamine, an α-adrenergic antagonist that constricts the pupil without inducing a myopic shift, may be considered. Note: Thymoxamine is not available in all parts of the world.

– Ocusert, a low-dose pilocarpine, has also been found to provide enough miosis to create pupillary block, without the disabling adverse effects.

– Note: Headaches, myopic shift, and the risk of retinal detachment limit the use of pilocarpine in this condition.

• Laser trabeculoplasty

– Laser treatment is effective but not always lasting. Treatment effect may be reduced in degree or duration in younger patients. Energy must be reduced as high TM pigment absorption of laser energy may lead to IOP spikes.

ADDITIONAL TREATMENT

Issues for Referral

• In cases of uncertain diagnosis, referral to a glaucoma specialist is indicated.

• Consider referral to a retinal specialist for dilated peripheral retinal exam if concerns arise for retinal degeneration or retinal detachment.

SURGERY/OTHER PROCEDURES

• Surgery is indicated when maximal medical therapy fails and there is concern for optic nerve damage.

– Laser trabeculoplasty—often requires lower laser power (ALT: 200–600 mW, SLT: 0.4–0.7 mJ), as the increased trabecular meshwork pigment absorbs energy readily.

– Laser peripheral iridotomy—relieves reverse pupillary block and may reduce iris chafe and pigment release (remains controversial).

• Incisional surgery is indicated when both medications and laser fail to control IOP.

– Filtering surgery—use antimetabolites cautiously as patients may be young and myopic, thus more prone to hypotony maculopathy.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• PDS—periodic evaluation for the development of PG

• PG—follow-up is similar to other types of open-angle glaucoma.

– IOP measurement before and after dilation

– Visual field testing

– Evaluation of optic nerve appearance

– Pachymetry—to measure central corneal thickness

– Gonioscopy—to access the degree and progression of trabecular pigmentation

• Dilated exam of peripheral retina—increased incidence of myopia, peripheral retinal degeneration, and risk of retinal detachment

• Visual field and optic nerve status evaluation or imaging yearly

Patient Monitoring

• Annually in pigment dispersion; every 3–6 months in PG. Increased frequency depending on the severity of the disease.

• Frequency of follow-up may decrease with aging if pigment liberation ceases or trabecular pigmentation begins to diminish.

PATIENT EDUCATION

• Educate patients on the importance of long-term follow-up and treatment to prevent irreversible optic neuropathy and associated vision loss.

• Signs and symptoms of acute IOP elevation–haloes around lights, blurry vision, ocular pain

• Warning signs and symptoms of retinal detachment, including flashes, floaters, and decrease in vision

PROGNOSIS

• Prognosis is good with regular follow-up and careful control of IOP.

• Uncontrolled disease can lead to elevated IOP, optic nerve cupping, and visual field loss.

• Success rates of filtering surgery are similar to other forms of open-angle glaucoma at comparable age levels.

• Over time, a “burn out,” phase often occurs—pigment begins clearing from the iris surface, trabecular meshwork, corneal endothelium, iris defects disappear, and IOP decreases. Visual field and optic nerve appearance stabilize.

– As the pigment clears from the trabecular meshwork, the pigment band is darker superiorly more than inferiorly (pigment reversal sign).

– May be attributable to age-related increase in axial length of the lens, which pulls the peripheral iris away from the zonules

– This phase does not occur invariably, most patients require lifelong therapy.

COMPLICATIONS

Patients have a higher incidence of lattice degeneration, retinal breaks, and rhegmatogenous retinal detachment. Retinal detachment may occur in as many as 6–7% of individuals.

Geriatric Considerations

This condition most typically manifests in early to mid adulthood.

Pediatric Considerations

This condition is very uncommon at ages below 20 years.

Pregnancy Considerations

Most medications used to treat PG are pregnancy class C: studies have shown risks to the fetus in animal models.

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