Pigment dispersion syndrome

PIGMENT DISPERSION SYNDROME

1. PIGMENT DISPERSION SYNDROME DR ARPITA

2. INTRODUCTION A form of secondary open-angle glaucoma characterized by dispersion of pigment granules from the iris pigment epithelium, with deposition throughout the anterior segment

3. ANATOMY

4. HISTORY In 1940, Sugar briefly described one such case with marked pigment dispersion and glaucoma 1 In 1949, Sugar and Barbour reported the details of this entity, which differed from other forms of pigment dispersion by typical clinical and histopathologic features. They referred to the condition as pigmentary glaucoma 2 1.Sugar HS. Concerning the chamber angle. I. Gonioscopy. Am J Ophthalmol 1940;23:853-866. 2. Sugar HS, Barbour FA. Pigmentary glaucoma: a rare clinical entity. Am J Ophthalmol. 1949;32(1):90-92.

5. The mechanism of the pigment dispersion was suggested by Campbell in 1979 to be a rubbing of iris pigment epithelium against packets of lens zonules, which results from a posterior bowing of the peripheral iris. [3] 3.. Campbell D.G.: Pigmentary dispersion and glaucoma: a new theory.   Arch Ophthalmol   1979;  97:1667-1672

6. TERMINOLOGY : Pigment dispersion syndrome (PDS): Dispersion of iris pigment throughout the eye. PDS can lead to ocular hypertension (OHTN) or glaucoma and is usually bilateral. Pigmentary glaucoma (PG ): defined as glaucomatous optic neuropathy attributable to elevated intraocular pressure (IOP) from PDS

7. EPIDEMIOLOGY Pigmentary glaucoma roughly constitutes 1% to 1.5% of all glaucomas Onset usually occurs before age 40 years The disease preferentially involves men (M:F=2:1) and the women affected usually are a decade older than the men Pigmentary glaucoma occurs most often in white individuals: it is diagnosed rarely in blacks and Asians S trong association between pigmentary glaucoma and myopia Typical patient is a young white myopic male

8. The diagnosis of elevated IOP at a young age should prompt the examiner to search for a cause. Usually bilateral No typical hereditary pattern is known in PDS. Most of the patients are sporadic in nature. However autosomal dominant and autosomal recessive patterns are also reported There is a significant linkage between the disease phenotype and genetic markers located on 7q 35-36 P robability of converting to pigmentary glaucoma is 10% at 5 years and 15 % at 15 years * Siddiqui Y., Hulzen R.D.T., Cameron J.D., et al: What is the risk of developing pigmentary glaucoma from pigment dispersion syndrome?.   Am J Ophthalmol   2003; 135:794-799

9. PATHOGENESIS Anatomical predisposition Myopia Deep AC P osterior insertion of the iris into the ciliary body R elatively larger iris contributing to its concavity P atients with pigment dispersion syndrome and pigmentary glaucoma have revealed focal atrophy, hypopigmentation, and apparent delayed melanogenesis of the iris pigment epithelium - inherent weakness in the iris pigment epithelium Scheie HG, Fleischhauer HW. Idiopathic atrophy of the epithelial layers of the iris and ciliary body: a clinical study. Arch Ophthalmol. 1958; 59(2):216-228 .

10. The configuration of the eye in these patients, as described above, appears to favor a “ pumping” action of the iris, in which eye movement, as with blinking, causes the peripheral iris to act as a bellows in forcing aqueous from the posterior to the anterior chamber. This results in a reverse pressure gradient , i.e., higher in the anterior than posterior chamber. The iris then acts as a one-way valve against the lens, preventing aqueous from returning to the posterior chamber. The increased pressure in the anterior chamber leads to posterior bowing of the mid-peripheral iris and consequently to the rubbing of the iris pigment epithelium against packets of lens zonules, with liberation of pigment granules into the aqueous .

11. REVERSE PUPILLARY BLOCK

12. Accommodation in patients with PDS It has been observed that accommodation in patients with PDS leads to increased posterior bowing of the iris, which the investigators explain by the forward movement of the lens, which reduces the volume, thereby increasing the pressure in the anterior chamber. Iridotomy abolishes the change in patients with PDS. Blinking Campbell proposed that blinking initially deforms the cornea, transiently increasing IOP and pushing the iris posteriorly against the lens

13. Once the pigment granules are released from the iris pigment epithelium into the aqueous, some of them find their way to the trabecular meshwork, where the remainder of the mechanism leading to elevated IOP occurs. The trabecular endothelial cells engulf the pigment, which eventually leads to cell injury and death from phagocytic overload. Macrophages carry off the pigment and debris, leaving the denuded collagen beams to collapse and fuse, with obliteration of the outflow channels . This may explain why treatments directed at trabecular outflow, such as laser trabeculoplasty, are more effective in the earlier stages of pigmentary glaucoma

14. CLINICAL FEATURES SYMPTOMS Early: asymptomatic Later: loss of peripheral vision Advanced: loss of central vision Episodes of pain/blurred vision with haloes following strenuous exercise

15. SIGNS 1) CORNEA P igment deposition on the endothelium, in a vertical spindle-shaped distribution (Krukenberg spindle)

16. KRUKENBERGS SPINDLE : Neither universal nor pathognomonic of PDS ( can also occur in trauma ,uveitis ) T ends to be slightly decentered inferiorly and wider at its base than its apex. G enerally appears as a central, vertical, brown band up to 6 mm long and up to 3 mm wide. With time, it becomes smaller and lighter and often requires careful examination to identify it. Common in women May have a hormonal relationship Normal central corneal thickness

17. Studies of fluid dynamics show that there is a vertical circulation current of aqueous humor in the anterior chamber. This is hypothesized to result from a temperature gradient from the posterior portion of the anterior chamber (warmer, causing fluid to rise) to the anterior portion of the anterior chamber (cooler, causing fluid to fall).  Deposition of circulating pigment onto the corneal epithelium gives rise to the vertical Krukenberg spindle. The spindle consists of extracellular as well as intracellular pigment granules phago-cytized by the corneal endothelium

18. 2) ANTERIOR CHAMBER Anterior chamber is very deep and melanin granules may be seen floating in the aqueous P osterior bowing of the peripheral iris .

19. IRIS Pigment epithelial atrophy due to shedding of pigment from the mid-periphery gives rise to characteristic radial slit-like/spoke like transillumination defects

20. In black patients , signs of PDS may be overlooked because dark, thick iris stroma may obscure transillumination defects and pigment granules on the stroma; corneal endothelial pigmentation may be minimal or absent; and greater degrees of trabecular meshwork pigmentation may be interpreted as normal in black patients . It has been suggested that pigment accumulation on the lens zonules and equatorial or posterior lens regions may be particularly helpful in making the diagnosis of PDS in black patients Frequent dispersion of pigments on the stroma of iris may give the iris a progressively darker appearance and create heterochromia in asymmetric cases

21. Fine surface pigment granules that may extend onto the lens; partial loss of the pupillary ruff (frill) Patients with PDS may also have anisocoria , in which the eye with the larger pupil is on the side with the greater iris transillumination. The iris heterochromia and anisocoria of PDS may mimic Horner syndrome Jack J Kanski, Brad Bowling, Seventh Edition

22. GONIOSCOPY The angle is wide open and there is a characteristic mid-peripheral iris concavity that may increase with accommodation S ometimes reveals more posterior iris insertion along with greater than expected iris processes

23. Trabecular hyperpigmentation is most marked over the posterior trabeculum The pigment is finer than in PXF Appears to lie both on and within the TM In older patients, in whom the trabecular meshwork begins to recover and the pigment gradually clears, the pigment band may become darker superiorly more than inferiorly, a pattern referred to as the pigment reversal sign

24. LENS May occassionally show a line or an annular ring of pigment on the peripheral posterior surface - Scheie stripe or Zentamayer ring Gonioscopy with pupillary dilatation will demonstrate this interrupted line of pigment which is otherwise difficult to see on routine slit lamp examination . As lens thickness increases with age, “ burnout " can occur, because the iris is displaced sufficiently to prevent further release of pigment from zonular abrasion .

25. FUNDUS FINDINGS I ncreased risk for retinal detachment , which may occur in as many as 6-7% of individuals Retinal breaks and lattice degeneration (20%) may occur twice as frequently in these eyes

26. CLASSIC DIAGNOSTIC TRIAD Krukenberg spindle M idperipheral iris transillumination defects D ense trabecular pigmentation

27. NATURAL HISTORY Active phase The mean age at onset of PDS remains unknown but is probably in the mid 20s. The development of PDS later in life is unlikely because of gradual lens enlargement and loss of accommodation . Regression phase : The severity of involvement of both PDS and PG decreases in middle age, when pigment liberation ceases , at least in the majority of patients.

28. D/D

29. 1 )    POAG May be associated with a hyperpigmented trabeculum. However, the pigment tends to be concentrated in the inferior sector of the angle, in contrast to the homogeneous distribution in PDS. Patients with POAG are also usually older and lack Krukenberg spindles and iris transillumination defects.   

30. 2 )  Pseudoexfoliation M ay exhibit trabecular hyperpigmentation and pigment dispersion. However, transillumination defects are evident at the margin of the pupil rather than in the periphery Pseudoexfoliation glaucoma usually affects patients over the age of 60 years, is unilateral in 50% of cases and has no predilection for a myopic refractive error.   

31. 3)     Pseudophakic pigmentary glaucoma occurs in the context of rubbing of the haptics and optics of a posterior chamber intraocular lens against the posterior surface of the iris, with resultant pigment dispersion and outflow obstruction.    4)    Anterior uveitis may result in trabecular hyperpigmentation and iris atrophy. Clustered old pigmented keratic precipitates may be mistaken for a Krukenberg spindle on cursory examination.    5 )   Subacute angle-closure glaucoma may be associated with a heavily pigmented trabeculum where the iris root has been in contact with the angle.

32. PDS XFN DEMOGRAPHY 30-50 years (a decade younger) Men Related to myopia Pigmented race 60-70 years Common in women, glaucoma more in men Scandinavian countries LATERALITY Bilateral disease: 90% Bilateral disease: 30% PATHOLOGY Posterior bowing of iris  Constant rubbing of posterior pigment iris and zonules  Release of pigments  Trabecular block Systemic disease of abnormal basement membrane  Secretion of amyloid-like material (oxytalon) in AC  Deposit in zonules and trabeculum  Trabecular block

33. CLINICAL FEATURES Krukenberg’s spindle Deep AC, with iris bowing posteriorly (reverse pupil block) . Iris atrophy in periphery of iris Pigment deposit on lens Pseudoexfoliative material, dandruff-like appearance throughout AC Pupil difficult to dilate Iris atrophy at edge of pupil margin (Moth eaten transillumination defect) Deposit on lens is characteristic (target likeappearance, called hoarfrost ring) Len subluxation (weak zonules) GONIOSCOPY heavily pigmented over wide, open angle queer iris configuration Sampaolesi’s line (pigmented line anterior to Schwalbe’s line) Pseudoexfoliative material PROGNOSIS Glaucoma risk: 10% Good prognosis Glaucoma risk: 1% per year (5% in 5 years, 15% in 15 years) Fair prognosis

34. INVESTIGATIONS UBM shows the posterior iris insertion,iris concavity, iridozonular contact.

35. TREATMENT Medical treatment is similar to that of POAG. The treatment typically begins with medical therapy, and all ocular hypotensive medications for open-angle glaucoma are effective in these patients- PG analogues are drug of choice Miotics would theoretically be of particular benefit because they decrease iridozonular contact in addition to facilitating aqueous outflow. They have the disadvantages, however, of exacerbating the myopia common in these patients and also of a risk of precipitating retinal detachment in myopia . They are not well tolerated by young patients.         

36. Physical Activity Exercise may increase pigmentary dispersion and elevate the IOP, which can be a concern in this population of young, active individuals .One approach to dealing with this question is to measure the IOP (and observe the amount of pigment in the anterior chamber) before and 30 minutes after the patient's typical exercise routine. If a significant pressure rise is observed, the use of pilocarpine, 0.5%, during exercise may be beneficial

37. 2     Laser trabeculoplasty The heavy trabecular pigmentation allows increased absorption of laser energy, in turn allowing lower energy levels for trabeculoplasty. Ritch et al reported 80% success rate of ALT at the end of one year follow up. It causes trabecular tightening and expansion of intertrabecular spaces. It may also lead to increase in number and/or function of endothelial cells . A just visible reaction in trabecular meshwork is required for adequate treatment.

38. 3) Laser iridotomy has been proposed to retard pigment liberation by reversing iris concavity and eliminating iridozonular contact. It may have utility in patients under the age of 40 years but benefit has not been conclusively demonstrated.

39. 4  ) Trabeculectomy When medical therapy and laser trabeculoplasty have failed to adequately control the IOP, glaucoma filtering surgery is usually indicated Filtering surgery is usually successful; however, extra care is warranted, because young patients with myopia may be at increased risk of hypotony maculopathy . U se of adjunctive antimetabolites may improve surgical outcome.

40. PROGNOSIS Over time the control of IOP becomes easier and occasionally the IOP may spontaneously revert to normal; this may or may not be associated with a decrease in trabecular pigmentation. Patients with undetected previous pigmentary glaucoma may later be erroneously diagnosed as having NPG.