Q. At what age does Pseudoexfoliative Glaucoma (PXFG) typically onset?
A) Before 20 years
B) Between 20 and 30 years
C) Older than 50 years
D) Between 30 and 40 years
Answer: C) Older than 50 years
Explanation: Pseudoexfoliative Glaucoma (PXFG) typically has its onset in individuals older than 50 years. The age of onset can vary significantly between populations.
👁️ Pseudoexfoliation Syndrome (PXF) and Pseudoexfoliative Glaucoma (PXG)
Aetiology | Epidemiology | Incidence | Predisposing Factors
🧬 AETIOLOGY
🔹 Pseudoexfoliation Syndrome (PXF)
PXF is a systemic, age-related disorder of the extracellular matrix, characterized by abnormal production and progressive accumulation of fibrillar material in ocular and systemic tissues.
Key Pathogenic Features:
- PXF material is an amyloid-like, elastic microfibrillopathy composed of:
- Elastin
- Fibrillin-1
- Fibulin
- Laminin
- Cross-linked glycoproteins
- Originates primarily from:
- Non-pigmented ciliary epithelium
- Trabecular meshwork endothelial cells
- Iris pigment epithelium
- Lens epithelium
- Accumulates on:
- Anterior lens capsule
- Iris
- Corneal endothelium
- Zonules
- Trabecular meshwork
Etiological Processes:
- Defective elastogenesis
- Dysregulation of extracellular matrix metabolism
- Oxidative stress
- Imbalance in matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs)
- Abnormal LOXL1 gene expression (see below)
🔹 Genetic Component
- LOXL1 gene (Lysyl Oxidase-Like 1) on chromosome 15q24:
- Encodes enzyme critical for elastin and collagen cross-linking
- SNPs (e.g., rs3825942, rs1048661) strongly associated with PXF and PXG
- Present in 90%+ of PXF patients but also found in unaffected individuals, suggesting gene-environment interaction
🌍 EPIDEMIOLOGY
Global Prevalence of PXF:
- Highly variable by geography and ethnicity
- Higher prevalence in:
- Scandinavian countries (up to 30% in those >60 years)
- Mediterranean regions (e.g., Greece, Turkey)
- Russia, India, Iceland, South Africa
- Lower prevalence in:
- African Americans
- Native Chinese and Japanese
- Arctic Inuit populations
- North American Caucasians (~1–2%)
Global Prevalence of PXG:
- Among patients with PXF, 15–30% develop PXG
- PXG accounts for up to 25% of secondary glaucomas worldwide
- PXF is unilateral initially, but up to 80% become bilateral over 10 years
- PXG is more common in females and elderly populations (peak incidence >70 years)
📊 INCIDENCE
| Region | PXF Prevalence | PXG Incidence (if PXF present) |
|---|---|---|
| Iceland | 26% (age ≥60) | 20–30% |
| Sweden | 23% | ~20% |
| India | 6–18% | 15–25% |
| United States | 1–2% | 10–15% |
| Japan | <1% | <5% |
- Annual conversion rate from PXF to PXG: ~1–2% per year (depending on risk factors)
⚠️ PREDISPOSING AND RISK FACTORS
✅ Ocular Risk Factors
| Risk Factor | Mechanism |
|---|---|
| Accumulation of PXF material | Deposits on trabecular meshwork impair aqueous outflow |
| Pigment dispersion | From iris rubbing → added TM blockage |
| Zonular instability | Lens support compromised → surgical risk |
| Sampaolesi’s line | Indicates pigment overload in angle |
| Poor pupillary dilation | Atrophic, rigid iris; complicates exams/surgery |
✅ Systemic and Genetic Risk Factors
| Risk Factor | Mechanism |
|---|---|
| Advanced age | Elastotic degeneration increases with age; PXF rare <50 years |
| Female sex | Slightly more common; hormonal factors hypothesized |
| Family history of PXF/PXG | Polygenic inheritance (LOXL1, CLU, CNTNAP2, APOE) |
| Scandinavian or Mediterranean ancestry | Higher LOXL1 SNP prevalence |
| Vascular dysregulation | Vasospasm or ischemia may reduce TM perfusion |
| Oxidative stress | Higher levels of reactive oxygen species in aqueous humor |
| Exposure to UV or cold climates | Associated with higher PXF expression in LOXL1 carriers |
✅ Environmental/Behavioral Factors
| Risk Factor | Mechanism |
|---|---|
| Geographic latitude | Increased UV exposure in northern latitudes may stimulate elastogenesis |
| Solar radiation | Linked to LOXL1 overexpression in exposed ocular tissues |
| Sleep apnea | May increase optic nerve susceptibility |
| Smoking | May contribute to oxidative damage |
| Systemic hypertension | Common comorbidity, though direct link is unclear |
📌 Summary Table: PXF → PXG
| Category | PXF | PXG |
|---|---|---|
| Definition | Accumulation of abnormal fibrillar material in anterior segment | Secondary open-angle glaucoma due to PXF obstruction |
| Incidence | Common in elderly; variable by geography | Occurs in 15–30% of PXF patients |
| Onset | Typically unilateral at first | Often progresses to bilateral |
| IOP | Normal in early PXF | Often elevated and fluctuating |
| Risk Factors | Age, LOXL1, UV exposure, oxidative stress | Pigment load, angle pigmentation, poor TM function |
| Clinical Findings | PXF on lens, iris, Sampaolesi’s line | Glaucomatous cupping + VF loss |
| Prognosis | Variable | Faster progression than POAG |
Key Clinical Pearls
- PXF is the most common identifiable cause of secondary open-angle glaucoma.
- Patients with PXF require lifelong monitoring, even with normal IOP, due to risk of later conversion to PXG.
- LOXL1 variants are necessary but not sufficient for disease development—environmental triggers are key.
- PXF and PXG are asymmetrical diseases—one eye may appear normal for years.
- PXG is more resistant to medical therapy and has faster optic nerve progression than POAG.