Proper diagnosis is critical to safe treatment.
Exfoliation syndrome is a systemic condition in which a fibrillar extracellular substance is deposited throughout the body, including various ocular structures. Since its original known description by Lindberg in 1917, clinicians’ knowledge of this disorder has vastly expanded.1 Because exfoliation syndrome is a cause of secondary open- and closed-angle glaucomas, its diagnosis is important to tailoring glaucoma treatment as well as to preparing for cataract surgery.
The prevalence of exfoliation syndrome varies significantly depending on geographic location and population. The condition’s incidence increases with age but depends on ethnic group. Classically described in Scandinavian populations,2 exfoliation syndrome is also common elsewhere in Europe as well as in the Middle East, Southeast Asia, India, South Africa, and South America. Both sexes are equally affected. Although risk factors such as high altitude, diet, and exposure to ultraviolet light have been implicated, the etiologic connections to exfoliation syndrome remain unclear. Studies suggest that approximately 40% of patients who have exfoliation syndrome will develop glaucoma.3 It is debatable whether unilateral or bilateral disease is more common, but the condition most often presents in an asymmetric manner.3
The nomenclature for this disorder has been a source of debate, but it is frequently referred to as exfoliation (as opposed to pseudoexfoliation) syndrome due to the rarity of true exfoliation syndrome. True exfoliation is a condition originally described in glassblowers in which there was a frank capsular delamination of the lens. Recent studies have implicated variants in the gene LOXL1 as a major risk factor for exfoliation syndrome and glaucoma.4
Exfoliation syndrome is characterized by the accumulation of an abnormal fibrillar substance that is eosinophilic and periodic acid-Schiff stain positive. This substance is probably closely associated with various anterior segment tissues, including trabecular meshwork and corneal endothelium, iris stroma and vessels, and lens epithelium.3
Exfoliation syndrome is often subtle and overlooked. A careful slit-lamp examination and gonioscopy can facilitate the diagnosis. The corneal endothelium may demonstrate exfoliative material on the endothelium in a fashion similar to in pigment dispersion syndrome. The material appears as white flecks on the pupillary margin of the iris, and it is accompanied by a loss of the pupillary ruff and by peripupillary iris transillumination defects (Figure 1). Scraping of the posterior surface of the iris against the lens epithelium causes a characteristic target-like lesion that is most easily viewed after pupillary dilation (Figure 2). As the exofoliative lens material rubs against the iris, pigment is liberated and deposited in anterior segment structures, including the angle.5 Gonioscopy reveals increased pigmentation of the trabecular meshwork and possibly an accumulation of pigment along Schwalbe line, known as the Sampaolesi line. Depending on the degree of zonular laxity, the angle may also appear to be occludable due to anterior lens displacement. The clinician may note phacodonesis if significant zonular dehiscence has occurred.
Although the risk of glaucoma in eyes with exfoliation syndrome varies greatly based on the population, the disease appears to have a secondary open-angle mechanism in most cases.6 Elevated IOP results from a blockage of the trabecular meshwork by pigment as well as exfoliative material in the intertrabecular spaces. Glaucoma is often associated with high IOP, which can be very difficult to control. Greater associated visual field loss, wider IOP variation, and more pronounced optic nerve damage can occur in this patient population compared with patients who have primary open-angle glaucoma (POAG); additionally, studies have shown elastosis of the lamina cribrosa, suggesting a preexisting vulnerability of the optic nerve.3,7,8
Recently, exfoliation syndrome has been implicated as a cause of acute and chronic closed-angle glaucomas. Suggested mechanisms include anterior movement of the lens from zonular weakness as well as the formation of posterior synechiae due to increased iris adhesion to the lens from exfoliative material.3 Iridotomy or lens extraction may be indicated to protect patients against chronic angle closure.
The treatment of exfoliative glaucoma is similar to that of POAG, but multiple studies have shown that medical therapy is more likely to fail in the former patient population.3 Laser trabeculoplasty can be highly effective for exfoliative glaucoma due to the increased pigmentation of the trabecular meshwork. The results of trabeculectomy in this group are comparable to or better than those for POAG.9
Studies implicate a causal relationship between exfoliation syndrome and cataract formation. Causality is hard to discern, however, because both diseases are found with increased prevalence in the elderly. What is known is that the presence of exfoliation syndrome or glaucoma should prompt the practitioner to exercise caution during cataract surgery. These patients’ pupils often dilate poorly, probably from degenerative changes in the iris sphincter and dilator muscles. The deposition of exfoliative material on the zonules also results in zonular fragility, which predisposes these patients to zonular dehiscence, lens dislocation, and capsular rupture. As a result, the risk of vitreous loss is up to 10 times higher.10 A thinner posterior capsule has also been implicated as a risk factor in these patients.11
To minimize the chance of complications in these eyes, the surgeon should consider using mechanical dilation to maintain the pupil’s size and should minimize zonular stress by creating a large capsulorhexis. Capsular tension rings or capsular hooks can help to stabilize the capsular bag. Depending on the degree of zonular dehiscence, the IOL may need to be primarily sutured to the iris or scleral wall. Unfortunately, avoiding intraoperative zonular loss may not ensure future safety, because the IOL can dislocate years after uncomplicated cataract surgery.
Exfoliation syndrome is a common cause of secondary glaucoma, and its diagnosis depends on the physician’s recognizing specific clinical signs. Prophylaxis against angle closure may be warranted. Glaucoma treatment often requires more intense long-term management than for POAG, and cataract surgery carries a higher risk of intraoperative and postoperative complications. These patients can be successfully managed, however, with vigilant follow-up and aggressive treatment.
Supported in part by National Eye Institute Vision Core Grant P30EY010608, a Challenge Grant to The University of Texas Medical School at Houston from Research to Prevent Blindness, and the Hermann Eye Fund.
Vandana Minnal, MD, is a glaucoma fellow at the Robert Cizik Eye Clinic, Ruiz Department of Ophthalmology and Visual Science, The University of Texas Medical School at Houston. Dr. Minnal may be reached at (713) 559-5200; firstname.lastname@example.org.
Nicholas P. Bell, MD, is the A. G. McNeese, Jr. professor of ophthalmology and a clinical associate professor at the Robert Cizik Eye Clinic, Ruiz Department of Ophthalmology and Visual Science, The University of Texas Medical School at Houston. Dr. Bell may be reached at (713) 559-5200; email@example.com.
- Lindberg JG. Clinical investigations on depigmentation of the pupillary border and translucency of the iris in cases of senile cataract and in normal eyes in elderly persons. Acta Ophthalmol. 1989;190(suppl):1-96.
- Forsius H. Exfoliation syndrome in various ethnic populations. Acta Ophthalmol. 1988;184(suppl):71-85.
- Ritch R, Schlotzer-Schrehardt U. Exfoliation syndrome. Surv Ophthalmol. 2001;45(4):265-315.
- Thorleifsson G, Magnusson KP, Sulum P, et al. Common sequence variants in LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397-1400.
- Prince AM, Ritch R. Clinical signs of the pseudoexfoliation syndrome. Ophthalmology. 1986;93(6):803-807.
- Ritch R. Exfoliation syndrome: the most common identifiable cause of open-angle glaucoma. J Glaucoma. 1994;3(2):176-178.
- Tezel G, Tezel TH. The comparative analysis of optic disc damage in exoliative glaucoma. Acta Ophthalmol. 1993;71(6):744-750.
- Netland PA, Ye H, Streeten BW et al. Elastosis of the lamina cribosa in exfoliation syndrome with glaucoma. Ophthalmology. 1995;102(6):878-886.
- Konstas AG, Jay JL, Marshall GE, et al. Prevalence, diagnostic features, and response to trabeculectomy in exfoliation glaucoma. Ophthalmology. 1993;100(5):619-627.
- Skuta GL, Parris RK II, Hodapp E, et al. Zonular dialysis during extracapsular cataract extraction in exfoliation syndrome. Arch Ophtahlmol. 1987;105(5):632-634.
- Ruotsalainene J, Tarkkanen A. Capsule thickness of cataractous lenses with and without exfoliation syndrome. Acta Ophthalmol. 1987;65(4):444-449.