Major reviewExfoliation Syndrome
Section snippets
Historical Aspects and Terminology
Exfoliation syndrome was first described in 1917 by Lindberg,332, 333 who, with the aid of the newly developed slit-lamp, noted the presence of bluish-gray flecks at the pupillary margin of the iris in 50% of his patients with chronic glaucoma. Vogt621, 622 thought that it originated from the lens capsule and called it senile exfoliation of the lens capsule and, having established its frequent association with open-angle glaucoma, capsular glaucoma. Others thought that it was just deposited on
Epidemiology
The reported prevalence of XFS both with and without glaucoma has varied widely. This reflects a combination of true differences due to racial, ethnic, or other as-yet-unknown factors; the age and sex distribution of the patient cohort or population group examined; the clinical criteria used to diagnose XFS; the ability of the examiner to detect early stages and/or more subtle signs; the method and thoroughness of the examination; and the awareness of the observer.8 Many cases go undetected
Lens
Deposits of white material on the anterior lens surface are the most consistent and important diagnostic feature of XFS. The classic pattern consists of three distinct zones that become visible when the pupil is fully dilated: a relatively homogeneous central disk corresponding roughly to the diameter of the pupil; a granular, often layered, peripheral zone, and a clear area separating the two (Fig. 1). Individual variations of this classical clinical picture may result from differing
Cataract
Although the nature of the relationship is still not well characterized or understood, increasing evidence has been presented in recent years for an association between XFS and cataract formation.55, 112, 215, 222, 236, 304, 309, 323, 342, 347, 361, 369, 371, 404, 428, 487, 571, 582, 588, 629, 633 Nuclear cataract is often more frequently found in eyes with XFS than in eyes without it.215, 523, 582 A higher rate of subcapsular cataract has also been reported.428 There is a higher prevalence of
Systemic Associations
No clear-cut association of XFS with a systemic disease has yet been shown. The response of patients with XFS but without glaucoma to topical steroid testing is similar to that of the normal population.177, 417, 583 However, in one study, two out of 15 patients with bilateral, nonglaucomatous XFS responded with a pressure rise of 6 mm Hg or more, and three out of 18 patients showed the same response when 0.1% betamethasone drops were administered four times a day for 6 weeks.583 In another
Structure of exfoliation material
The abnormally produced material appears by light microscopy as periodic acid–Schiff (PAS)-positive, eosinophilic, bush-like, nodular or feathery aggregates on the anterior segment surfaces, e.g., anterior lens capsule, anterior and posterior iris surfaces, ciliary processes, zonules, chamber angle, and, occasionally, the posterior corneal and anterior hyaloid surfaces (Fig. 23A).376
By scanning electron microscopy, the nodular aggregates are composed of an irregular tangle of fibrils (Fig. 23B)
Morphologic Studies
Regardless of etiology, typical exfoliation fibers have been demonstrated electron microscopically in close association with the pre-equatorial lens epithelium (Fig. 24B and C),30, 70, 72, 129, 521, 522 the nonpigmented ciliary epithelium (Fig. 16D),128, 172, 526 the iris pigment epithelium (Fig. 25C),171, 532 the corneal endothelium (Fig 26D),510 the trabecular endothelium (Fig. 27A and B),501 and with almost all cell types of the iris stroma, such as fibrocytes, melanocytes, vascular
Lens
The light and electron microscopic appearance of diagnostically important XFM on the anterior lens capsule is dependent upon the stage of the disease and the region of the lens examined. Histopathologic studies confirm the presence of a precapsular layer in early stages and the characteristic lenticular distribution of XFM in different zones (central disk, clear intermediate zone, peripheral granular zone, preequatorial zone) in manifest XFS, which can be best visualized by scanning electron
Conjunctiva
Extraocular deposits similar to XFM have been demonstrated electron microscopically in both the bulbar and palpebral conjunctiva of affected eyes, of fellow eyes in unilateral cases, and of patients with suspected XFS without any evidence of ocular XFM in either eye422, 452, 454, 482, 552, 559 and in Tenon's capsule,533 suggesting that the conjunctiva might be an independent source of XFM that precedes clinical recognition of XFM on anterior segment structures. The XFM was found in the
Chronic open-angle glaucoma
The pathogenesis of elevated IOP in XFS remains controversial, and the debate as to whether XFS is a coincidental finding in COAG5, 582, 586, 632 or actually causes glaucoma85, 139, 205, 487, 621 has not entirely been laid to rest. The glaucoma associated with XFS is a hypertensive glaucoma associated with an increase in aqueous outflow resistance.169, 246 Glaucomatous visual field damage correlates much better with untreated IOP in exfoliative glaucoma than it does in COAG.593 Johnson and
Posterior Synechiae
The iris pigment epithelium and the lens surface, both coated with XFM, tend to adhere, particularly when pupillary movement is inhibited by miotic therapy. Bartholomew53 coined the term “iridocapsular block” for this phenomenon. Because of the strength of these adhesions, the attachment of the pupillary ruff to the lens may be stronger than its attachment to the iris stroma. The vascular abnormalities affecting the iris stroma can also affect the synechiae.
Posterior synechiae predispose to
Management
The stepwise approach to the management of the patient with XFS is similar to that for COAG, and it includes beta-adrenergic antagonists, alpha-adrenergic agonists, miotics, carbonic anhydrase inhibitors, and laser and intraocular surgery. Response to these interventions, however, differs from the response of patients with COAG.
Epidemiology
Much remains to be learned about XFS, not only at the basic levels of its production and biochemical nature, but also with regard to genetics, epidemiology, and treatment. What are the real differences in prevalence between races, ethnic groups, and even at local levels within the same population group, and why do these differences exist? Although XFS is common worldwide, its prevalence in China, with one-fifth of the world's population, is said to be quite low (Dennis Lam, MD, personal
Method of Literature Search
References have been compiled for nearly 20 years and maintained on the computers of the authors. To our knowledge, the list of references from the past 30 years is virtually complete. Except for key papers, numerous older references from before 1960 and a few references deemed to be without merit have been omitted. Additional searches were made of MEDLINE from 1976 to 2000, using the search words pseudoexfoliation, exfoliation, capsular glaucoma, and fibrillopathia.
Outline
I. Historical aspects and terminology
II. Epidemiology
A. Frequency in the general population
1. Age
2. Sex
3. Heredity
B. Frequency in glaucoma populations
C. Glaucoma in eyes with XFS
D. Asymmetry of involvement
III. Clinical Findings
A. Lens
B. Iris (including exfoliation suspects)
C. Pupil
D. Cornea
E. Zonules and ciliary body
F. Anterior chamber angle
G. Vitreous and retina
H. Optic disk
I. Extraocular findings
J. Differential diagnosis
IV. Ocular associations
A. Cataract
B. Posterior synechiae
C. Blood-aqueous
Acknowledgements
Supported in part by the Joseph and Barbara Cohen and the Irving and Rena Katz Research Funds of the New York Glaucoma Research Institute, New York City, and by the Deutsche Forschungsgemeinschaft (SFB 539).
The authors have no proprietary or commercial interest in any product or concept discussed in this article.
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