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Pigment Dispersion and Pigmentary Glaucoma
Larissa Camejo, MD
Pigment dispersion syndrome (PDS) occurs when pigment from the posterior surface of the iris is liberated and deposited on intraocular structures of both eyes. The pigment can deposit on the corneal endothelium, the trabecular meshwork, the iris and the lens. When a patient with pigment dispersion syndrome develops glaucoma, he or she is said to have pigmentary glaucoma (PG). Approximately 50% of patients with the PDS may never develop glaucoma. Sugar and Barbour first described PDS and PG in 1949. PG is a secondary open-angle glaucoma.
Unlike most types of open-angle glaucoma, PDS and PG are common among patients between the ages of 20 and 45. PDS is more common among men than women, and most patients with PDS have deep anterior chambers and are myopic. One explanation for male predilection is the gender difference in anterior chamber depth; men have deeper chambers. Women develop PG at an older age than men in the same scenario. PDS is typically seen in white patients, but may be overlooked in black patients given that they have thick irises that may resist positive transillumination. PDS is a bilateral entity, although the findings can be asymmetric. A pseudo-Horner appearance of the less-affected eye has been described, given that the eye with more signs of PDS may have a darker iris from pigment deposition and a larger pupil. Pigmentary glaucoma portrays a rapid onset, high IOP and symptoms such as halos and blurred vision. Jarring sports such as basketball trigger sudden spikes in IOP. Usually, no pain is present.
Clinical History
Patients may be seeking an eye examination as a result of reduced or blurred vision and can also be complaining of halos. A strong family history has not been established. One locus for a PDS gene has been identified on chromosome 7q.
Slit Lamp Examination
Cornea: A Krukenberg's spindle refers to the pigment deposition on the corneal endothelium in a spindle manner (Slide 1). Its pattern is secondary to aqueous humor convection currents in the anterior chamber; aqueous is warmer closer to the iris, which makes the pigment particles travel upward, and it is colder closer to the cornea, which makes the pigment particles travel downward, depositing themselves in a vertical ellipse. The melanin pigment is mainly phagocytosed by the endothelial cells, but some of it lies loosely on the posterior surface of the cornea. Curiously, the pigment does not seem to cause corneal decompensation.
Anterior chamber: Absence of inflammatory cells is noted. Often, pigment particles can be seen in the anterior chamber and these should not be confused with inflammatory cells. The anterior chamber tends to be deep and patients tend to be myopic.
Gonioscopy: The angle is wide and open 360°, and the iris can look somewhat flat. The iris may have a concave contour promoting more contact with the intraocular structures posterior to it. Pigment can be sprinkled on iris stroma. Perhaps the most striking feature in gonioscopy is the presence of a pigmented posterior trabecular meshwork. It appears as a homogeneous band of almost black pigment covering sometimes the whole width of the trabecular meshwork in the angle (Slide 2 and Slide 3). Pigment can also accumulate along Schwalbe's line and form a Sampaolesi's line as is present in exfoliation syndrome. Repeated examinations in patients have permitted the observation of attenuation of this pigmented band in the angle with aging. This may be explained by the increase in lens convexity with age, pushing the iris anteriorly and therefore changing its concave position to a more flat iris configuration and less friction with the zonules in the mid-periphery.
Iris: Mid-peripheral iris transillumination defects (TIDs) are typically seen (Slide 4). Early on, these can be slit or wedge shaped but can later become confluent. At the slit lamp, the transillumination technique implies placing the light in a coaxial position and obtaining a narrow short beam of light to point at the pupil. The specific location for the TID seen in PDS corresponds to the area of physical contact between the posterior surface of an iris that is typically bowed backward toward the posterior chamber and the zonules and peripheral lens.
Lens: With wide dilation, a Scheie stripe might be visible at the slit lamp along the lens zonules.
Optic nerve head: As with any other form of glaucoma, glaucomatous structural and functional damage can occur in a patient with PG (Slide 5 and Slide 6).
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In 1979, Campbell noticed a pronounced backbowing of the iris in patients with PDS and PG. He also described how the iris TID corresponded to packets of zonules. He stipulated that this backbowing allowed contact between the posterior pigmented iris and the zonules, and abrasion by the zonules rubbed iris pigmented epithelial cells and freed melanosomes into the aqueous humor. With the advent of ultrasound biomicroscopy, Campbell made a series of observations (Slide 7). One interesting observation was that laser peripheral iridectomy can reverse the backbowing of the iris and therefore PDS was said to be secondary to a reverse pupillary block. It was also noticed that blinking of the eyelids caused aqueous to be pushed from the posterior chamber to the anterior chamber and the aqueous in the anterior chamber then pushed the iris back so that the pigment epithelium comes in contact with the lens zonules (Slide 8). The pigment released into the anterior chamber is engulfed by the endothelial cells of the trabecular meshwork and may be toxic to them, causing decreased trabecular outflow of aqueous fluid. The release of pigment can occur abruptly as with jarring exercise like basketball or pupillary dilation and overwhelm the trabecular meshwork causing increased IOP.
Nevertheless, some patients with PDS never develop high IOP and glaucomatous damage to the optic nerve.
Furthermore, experimentally, one can reproduce pigment dispersion findings but not chronic pigmentary glaucoma. Therefore, a component besides the pigment deposition may play a role in the pathogenesis of pigmentary glaucoma.
Following are the differential diagnoses for pigmentary glaucoma:
- Pseudoexfoliation syndrome: Both increased pigmentation of the trabecular meshwork and TIDs can be seen in this syndrome, but these findings differ from those in PDS and PG in that the trabecular meshwork is less pigmented, the pigment is more coarse, and its distribution is less homogeneous. Also, the TIDs are located closer to the pupillary border as opposed to the mid-peripheral location seen in PDS and PG.
- Pathologies causing increased pigmentation of the trabecular meshwork: Generally, pathologies other than PDS, PG and pseudoexfoliation syndrome may show a highly pigmented trabecular meshwork but not involving 360°. These pathologies include uveitis, iris and ciliary body cysts, cataract surgery with IOL implantation, trauma and acute closed-angle attacks.
- Monocular pigment dissemination from an anterior uveal malignant melanoma.
Patients with PDS should be followed up regularly to detect conversion to pigmentary glaucoma early on and patients with pigmentary glaucoma should be followed closely to avoid progression of disease. Generally, pigmentary glaucoma refers to the presence of PDS and high IOP that places patients at risk for glaucomatous damage.
The general treatment approach to pigmentary glaucoma involves medical therapy first, laser trabeculoplasty second and incisional surgery third.
Medical Therapy
Pilocarpine is an effective medication for pigmentary glaucoma given that it causes miosis, changing the iris position to a more convex one, lifting it up from the lens zonules. At the same time, it lowers IOP and may even accelerate the outflow of pigment by stretching the trabecular meshwork spaces. However, miotics can cause accommodative spasm, which makes these agents difficult to tolerate. Also, there is a high prevalence of myopia in patients with pigmentary glaucoma and pilocarpine should be used cautiously in this population already predisposed to retinal detachments. Pilocarpine may also play a role in the prevention of exercise-induced IOP spikes. Low concentration pilocarpine (0.5%) can be given 30 minutes before and after exercise.
Other pressure-lowering medications, such as beta-blockers, alpha-adrenergic agonists, carbonic anhydrase inhibitors and prostaglandin analogues, can be used. Thymoxamine and dapiprazole are alpha-blockers and can cause miosis without the less desirable cycloplegic effect of pilocarpine. Nevertheless, these medications have been shown to be less effective than diluted pilocarpine in relieving iris backbowing in patients with PDS.
Laser Therapy
Laser peripheral iridectomy (LPI). LPI can flatten the iris, reversing the backbowing of the iris and helping prevent the IOP spikes in patients with PDS. Pilocarpine has been found to be better to this effect than LPI. No evidence exists that LPI can prevent a patient's conversion of PDS to pigmentary glaucoma. One consideration would be to be cautious of an IOP spike after LPI in patients with advanced glaucoma.
Laser trabeculoplasty (LT): Either argon laser trabeculoplasty (ALT) or selective laser trabeculoplasty (SLT) works well initially in patients with pigmentary glaucoma but can be less effective in older patients with pigmentary glaucoma. Laser trabeculoplasty has the potential of producing a substantial IOP increase both acutely and sustained. Therefore, less energy than conventional surgery should be used in the treatment of these patients: 300 mW per spot in ALT and 0.4 mJ per spot in SLT.
Filtering surgery: When glaucomatous progression cannot be halted with medical and laser therapy, a trabeculectomy may be needed. Trabeculectomy has a higher rate of failure and incidence of complications such as hypotonus maculopathy in this young myopic population.
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