Article Date: 1/1/2007

glaucoma
Ocular and Systemic Pseudoexfoliation Syndrome

Our knowledge of this condition continues to expand, allowing us to identify new types of treatment.
MITCHELL W. DUL, O.D., M.S., F.A.A.O.

In 2007, the Optometric Glaucoma Society (OGS) will provide OM with expert authors who will discuss therapies, epidemiology, case studies and other current issues in glaucoma management. For additional information on the Society, contact the OGS through the Web site optometricglaucomasociety.org. The views expressed in this article are the author's and do not necessarily represent the views of the OGS.

Primary open angle glaucoma is by far the most common form of all of the glaucomas. The secondary glaucomas represent a group of disorders, which, unlike POAG, have a recognizable cause of elevation of intraocular pressure (IOP). You must recognize secondary glaucomas, the treatment and prognosis often differ from POAG.

Pseudoexfoliative glaucoma (PXG) began to appear in scientific literature in the early 1900s. Pseudoexfoliation (PEX) syndrome is known as an age-related disorder of the extracellular matrix. It is often diagnosed at the slit lamp by the presence of abnormal fibrillar deposits on ocular structures that line the aqueous-bathed surfaces of the anterior segment.1 These histologic changes are, to varying degrees, responsible for the co-morbid intraocular findings and surgical complications associated with PXG.

This condition has worldwide distribution, but is more common in certain populations. It represents more than half of all glaucoma cases in patients of Scandinavian descent .2 It's not uncom- mon in patients of Russian descent and is much less common in African-American and Eskimo populations.3 In the United States, the prevalence rate ranges from approximately 5% to 15% of all glaucoma cases.4 This condition is generally more common in women and the elderly.1

Diagnosis of Early Stages and Clinical and Surgical Complications of Pseudoexfoliation (PEX) Syndrome

TISSUE INVOLVEMENT EARLY CLINICAL SIGNS CLINICAL COMPLICATIONS SURGICAL COMPLICATIONS
Lens, ciliary body, and zonules Diffuse precapsular layer Phacodonesis
PEX deposits on zonules
Cataract (nuclear)
Phacodonesis
Lens subluxation

Angle-closure glaucoma due to pupillary and ciliary block
Zonular rupture/dialysis Vitreous loss
Posterior capsule
rupture Decentration of the lens implant
Anterior capsule fibrosis

Secondary cataract
Iris Peripapillary atrophy and iris sphincter region transillumination
Melanin dispersion associated with pupillary dilation
Poor mydriasis, asymmetric pupil sizes
Melanin dispersion
Poor mydriasis
Iris rigidity
Capillary hemorrhage
Blood-aqueous barrier defects, pseudouveitis

Anterior chamber hypoxia
Posterior synechiae
Miosis/poor
surgical access
Intra- and post-operative hyphema
Postoperative inflammation
Prolonged blood-aqueous barrier breakdown
Posterior synechiae/pupillary block
Trabecular meshwork Pigment deposition
Marked asymmetry of IOP
Marked IOP rise after pupillary dilation
Intraocular hypertension Open-angle glaucoma Postoperative IOP rise
Cornea Atypical cornea guttata  Endothelial decompensation
Endothelial migration/proliferation
Endothelial decompensation
Posterior segment   Retinal vein occlusion  

Etiology

We do not fully understand the etiology of this condition. Pseudoexfoliation syndrome is a systemic disease associated with abnormalities of the basement membrane in epithelial cells, which are found throughout the body (intraocular lens, lungs, skin, liver, heart, blood vessels, extraocular muscle, meninges, etc). Despite this distribution, its clinical manifestations are limited to the eye. Speculation remains regarding the role of genetics and the patient's environment. However, these factors have not been fully elucidated.

Some reports show patients with pseudoexfoliation have higher levels of homocysteine (a sulfur-containing amino acid), which may be a risk factor for cardiovascular disease due to its direct toxic effect on arteries, interference with clotting and oxidation of low-density lipoproteins.1,5 After adjusting for age and other variables, it's unclear whether an association between pseudoexfoli- ation syndrome and cardio/cerebrovascular morbidity exists.

Patients with PEX are much more likely to develop glaucoma when compared with age-matched groups without this condition.5 The accumulation of pseudoexfoliative material in the trabecular meshwork and the juxtacanalicular tissue next to Schlemm's canal leads to obstruction of aqueous leaving the eye and increases IOP.6

Clinical presentation

PEX typically presents unilaterally and, when high IOP is present, it is usually higher when compared with POAG. Diurnal IOP at all time intervals tends to be higher on average in patients with PXG when compared with age-similar norms.7 In addition, the range, maximum, minimum and variance of diurnal IOP all tend to be higher. In one recent study, more than half of PXG patients had diurnal fluctuations >5mm Hg, and 10% had fluctuations >10mm Hg.8

Over time, the contralateral eye has an approximately 40% chance of developing signs of pseudoexfoliation.9 This condition is more common in patients over the age of 60 and its incidence increases with age. Unlike pigmentary dispersion glaucoma, which shares some of the same clinical signs, it's uncommon in patients younger than age 40.10

PXG syndrome is diagnosed during the anterior segment ex-am with a biomicroscope. Pseudoexfoliative material is visible on the border of the pupil. The classic appearance is on the anterior capsule of the intraocular lens. This concentric circular pattern is comprised of a central circle of material (1mm to 2.5mm in diameter) surrounded by an apparently material-free band of anterior capsule, most likely produced by contact between the posterior iris and the lens during normal papillary function. This contact produces an apparently smooth surface on the anterior capsule and the potential for liberation of pigment from the posterior iris into the anterior cham- ber. Beyond this, a second zone of material appears to surround the remainder of the lens capsule.

Treatment options

There are three treatment options for PXG:

Medical. Because IOP can be high during the course of this condition, check the IOP of pseudoexfoliation syndrome patients at regular intervals. Once you establish a diagnosis of PXG, begin treatment as you would for primary open angle glaucoma. Monitor the efficacy of IOP lowering medica- tions, as PXG is typically a more aggressive form of glaucoma that can progress more rapidly than POAG despite previous control.7 Like pigmentary glaucoma, the use of miotics has some theoretical advantages in the care of these patients. However, in practice they are used less often than conventional medications due to the quality of life issues associated with miosis, the q.i.d. dosing regimen, the risk of retinal detachment, posterior synechia and the need to discontinue miotics for dilated fundus examinations and visual fields.

Laser. In general, patients with PXG respond well and often better than their POAG counterparts, to argon laser trabeculoplasty, at least during its initial application. Unfortunately, within five years, nearly half of these patients are back to baseline IOPs. In addition, as many as 20% of these patients will have a rapid sustained increase in IOP within two years following the procedure.11

Surgical Care. Due to the aggressive nature of this condition, trabeculectomy and/or combined cataract/trabeculectomy is more common in this population compared with their POAG counterparts. However, surgical complications are also more common.12

PXG patients who don't manifest high IOP or structural/functional changes still require regu- lar assessments due to the potentially rapid and high levels of IOP increases associated with this condition.

1. Ritch R., Schlotzer-Schrehardt U., Exfoliation syndrome, Surv Ophthalmol. 2001 Jan-Feb;45:265-315.

2. Ringvold A. Epidemiology of glaucoma in northern Europe. Eur J Ophthalmol. 1996 Jan-Mar;6(1):26-9.

3. Cashwell LF Jr, Shields MB. Exfoliation syndrome in the southeastern U.S. Prevalence in open-angle glaucoma and non-glaucoma populations. Acta Ophthalmol. 1988; 184:99-102.

4. Karger RA, Jeng SM, Johnson DH et al. Estimated incidence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Olmsted County, Minnesota. J Glaucoma. 2003 Jun; 12(3): 193-7.

5. Leibovitch I, Kurtz S, Shemesh G, et al. Hyperhomocystinemia in pseudoexfoliation glaucoma. J Glaucoma. 2003 Feb;12(1):36-9.

6. Ritch R. Exfoliation syndrome the most common identifiable cause of open-angle glaucoma. J Glaucoma. 1996; 3:176-178.

7. Schlotzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006 May;141(5):921-937.

8. Konstas AGP, Stewart WC, Stromann GA, et al. Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmol Surg Laser. 1997 Feb;28:111-117.

9. Altintas O, Yuksel N, Karabas VL, et al. Diurnal intraocular pressure variation in pseudoexfoliation syndrome. Eur J Ophthalmol. 2004 Nov-Dec;14(6):495-500.

10. Puska PM. Unilateral exfoliation syndrome: conversion to bilateral exfoliation and to glaucoma: a prospective 10 year follow-up study. J Glaucoma. 2002 Dec;11:517-24.

11.Threlkeld AB, Hertzmark E and Sturm RT, et al. Comparative study of efficacy of argon laser trabeculoplasty for exfoliation and primary open angle glaucoma. J Glaucoma. 1996 Oct;5:311-16.

12. Jacobi PC, Dietlein TS, Kriegl-stein GK. Comparative study of trabecular aspiration vs. trabeculectomy in glaucoma triple procedure to treat pseudoexfoliation glaucoma. Arch Ophthalmol 1999 Oct; 117(10): 1311-8.

Dr. Dul is chair of the department of clinical sciences and director of the Glaucoma Institute at the State University of New York (SUNY) Optometry. He is also a founding member of OGS and sees patients in both academic and private settings.



Optometric Management, Issue: January 2007