Pseudoexfoliation Syndrome
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Pseudoexfoliation syndrome (PXF or PEX) is an age-related systemic syndrome that targets mainly ocular tissues through the gradual deposition of fibrillary white flaky material from the lens, mainly on the lens capsule, ciliary body, zonules, corneal endothelium, iris and pupillary margin. There is a higher prevalence of open angle glaucoma in about 50% of these patients.
Disease Entity
Exfoliation/Pseudoexfoliation syndrome is a systemic disease. It is most commonly noted in older individuals, typically over 50 years of age.
Disease
Exfoliation (pseudoexfoliation) Syndrome is characterized by the fibrillar deposits in the anterior segment of the eye. The deposits have been found on and in the subconjunctival tissue, pupillary margin, ciliary epithelium, lens epithelium, lens capsule, iris pigment epithelium, trabecular meshwork, cornea, zonules, orbital soft tissues, iris stroma and iris blood vessels. These deposits have also been found elsewhere in the body, including in the skin, heart, lungs, liver, kidneys, and elsewhere.
The disease may be bilateral and asymmetric.
It has been associated with myocardial infarction, cerebrovascular events and systemic hypertension.
History
Finnish ophthalmologist John Linberg is credited with being the first doctor to describe pseudoexfoliation syndrome. He reported the classic findings of white/grey flakes on the anterior lens capsule, glaucoma in approximately 50% of eyes, and an increasing prevalence of the condition with advancement of the age. A few decades later, an American ocular pathologist named Georgiana Dvorak-Theobald suggested the term pseudoexfoliation to distinguish it from the true exfoliation syndrome. True exfoliation is caused by heat from glassblowing or infrared radiation exposure in the anterior lens capsule. It is characterized by "lamellar delamination of the lens capsule".
Etiology
Etiology is unknown. It may a generalized disorder involving abnormal production or turnover of extracellular matrix in the basement membrane.
Risk Factors
- Advance age over 70
- Possible genetic prevalence
- Its prevalence in different human populations: high prevalence in Scandinavia.
General Pathology
The deposits are composed of elastic fibers (fibrillin and α-elastin)and noncollagenous basement membrane materials (laminin) which form fibrils. They are coated with the glycosaminoglycan hyaluroni acid.
The iris pigment epithelium may show a “saw-toothed” configuration. There could appear abnormal material like iron filings on the edge of a magnet on the anterior lens capsule.
Pathophysiology
Unclear, but there is a gentic link to the gene LOXL1. In March 2008 of the American Glaucoma Society in Washington, D.C. Dr. Allingham. described a LOXL1 is a member of a family of enzymes that are active in the cross-linking of collagen and elastin in the extracellular matrix, he explained. “Because pseudoexfoliation syndrome is associated with abnormalities of the extracellular matrix and the basement membrane, this gene could reasonably play a role in the pathophysiology of the condition.”
Primary prevention
- Routine annual eye exam by an ophthalmologist for patients over age 50.
- Biomicroscopic examination (slit lamp) by an eye doctor to examine the anterior lens capsule, pupillary dilation, intraocular pressure and optic nerve.
- Treatment of elevated eye pressure with eye drops, laser or surgery.
- Special precaution and awareness is essential prior and during cataract surgery.
- Anterior chamber depth less than 2.5mm centrally could be an indication of zonular instability
- Poor pupillary dilation
- Zonular dialysis
- Phacodonesis
All of the above may pose a significantly higher risk for intraoperative complications.
Diagnosis
Diagnosis is made using slit lamp biomicroscopy and intraocular pressure measurement. Deposition of white fluffy material on the anterior lens capsule and pupillary margin and iris transillumination defects can be visualized in many cases. Gonioscopy may show increased pigment deposit on the trabecular meshwork.
Physical examination
Signs
- Increased intraocular pressure
- Possible glaucomatous damage to optic nerve
- Poor dilation with peripupillary transillumination defect
- Fibrillar white flaky deposits on the anterior lens capsule (Hoarfrost Ring)
- Fibrillar white flaky deposits on/at pupillary border
- Hyperpigmentation of the trabecular meshwork (TM) with an open angle on gonioscopy
- Sampaolesi line, abundance of linear pigment anterior to the TM at or anterior to Schwalbe's line (not pathogonomic; also seen in pigment dispersion syndrome)
Symptoms
No associated symptoms aside from possibly with significantly increased intraocular pressure
Laboratory test
- Genetic test for a single mutation in the LOXL1
- Check for Homocysteine level in tear film and plasma. Scientists believe that elevated levels of plasma homocysteine are a risk factor for cardiovascular disease, and two studies have found higher levels of plasma and tear fluids homocysteine level in psuedoexfoliation patients.
Differential diagnosis
- Lens capsule deposite: true exfoliation syndrome
- Trabecular meshwork hyperpigmentation/glaucoma: Pigment dispersion syndrome
- Iris transillumination defects: Pigment dispersion syndrome, trauma, prior herpes infection
Management
- Routine regular eye exam
- Glaucoma monitoring and treatment if warranted
- Special surgical considerations for cataract surgery pre-operatively, intra-operatively and post-operatively
Medical therapy
- Drops if the patient has glaucoma
- Possible use of antioxidants
- Lower Homocysteine if the level is high in plasma or tear film
Medical follow up
Routine annual eye screening exam with dilation
Complications
- Glaucoma or optic nerve cupping
- Cataract surgery complications:
- Drop nucleus or lens fragment
- Zonular dialysis
- Diffuse zonular weakness with or without phacodonesis
- Lens subluxation, either the natural lens or intraocular lens (acutely or delayed presentation)
- Anterior chamber fibrinoid syndrome after cataract extraction
- Anterior capsular contraction syndrome: Anterior capsule fibrosis and phimosis
- Other systemic problems
Additional Resources
- Diagnose This: Pseudoexfoliation syndrome. https://www.aao.org/diagnose-this-player/diagnose-this-pseudoexfoliation-syndrome San Francisco: American Academy of Ophthalmology, 2016. Accessed January 06, 2023.
- Porter D, Vemulakonda GA. Blood Pressure. American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/anatomy/blood-pressure-list. Accessed January 06, 2023.
