ophthalmology, glaucoma

1. Pseudoexfoliation
Syndrome
Presenter: Dr. Gloria George Moderator: Dr. Ajay R. Kamath

2. Introduction…
▪ Pseudoexfoliation syndrome (PXF) or exfoliation syndrome is the most
common identifiable cause of open angle glaucoma
▪ When eye with PXF develops secondary open-angle glaucoma
pseudoexfoliation glaucoma (PXG)
▪ Systemic disorder with important eye manifestations- open and closed-
angle glaucoma, cataract with zonular instability.
▪ Also associated with increased systemic risk of cardiovascular disorders

3. Epidemiology and Genetics…
▪ More common in older age groups- late 60’s and early 70’s
▪ U/L or B/L- most U/L cases become B/L over 20 years
▪ 40% of patients with PXF develop PXG
▪ More common in women, but men at higher risk for glaucoma
▪ Geographically- Scandinavian countries, Europe, UK, Middle East and
South East Asia
▪ High risk conferred by mutations in the LOXL1 gene at locus 15q22,
coding for elastic fibre components of the ECM

4. Etiology and Pathogenesis…
▪ Grey-white fibrillary extracellular material composed of a protein
core surrounded by GAG’s is produced by abnormal BM of ageing
epithelial cells in the trabeculum, equatorial lens capsule, iris and
ciliary body
▪ Deposited on the anterior lens capsule, zonules, ciliary body, iris,
trabeculum, anterior vitreous face and conjunctiva

5. ▪ Inherited microfibrillopathy ultrastructural
appearance of random 10 to 12 nm fibrils,
arranged in a fibrillogranular matrix or coiled
as spirals
▪ The material behaves like a sticky
“Christmas tree” type of protein,
aggregating a large number of elastic tissue
and basement membrane proteins
▪ Polymorphisms in the coding of LOXL1 gene
▪ LOXL1 enzyme- essential for formation of
elastin fibres

6. Current concept in the pathogenesis of PXS

7. Ocular and Systemic Sources
▪ Many cell types- lens capsule epithelium, iris epithelium, vascular
endothelium, corneal endothelium, and Schlemm's canal
endothelium, conjunctiva
▪ Other extrabulbar sites- extraocular muscles, orbital septa, posterior
ciliary arteries, vortex veins, and central retinal vessels
▪ PEX material demonstrated in lung, heart, liver, gallbladder, skin,
kidney, and cerebral meninges
▪ Associated with a number of vascular disorders, hearing loss and
Alzheimer disease.

8. Clinical and Pathological changes…
▪ Corneal changes (pseudoexfoliation
endotheliopathy)
Flakes of pseudoexfoliation
material and pigment accumulation
on the corneal endothelium (diffuse or
as a vertical spindle similar to the
Krukenberg spindle)
Specular microscopy of the corneal
endothelium -significantly lower than
normal cell density and changes in cell
size and shape.

9. ▪ Ultrastructural studies have revealed clumps of pseudoexfoliation
material adhering to the corneal endothelium and incorporated into
the posterior Descemet's membrane.

10. ▪ Iris changes (pseudoexfoliation
iridopathy)
Pseudoexfoliation material seen as
white flecks on the pupillary margin of the
iris, with loss of pigment at the pupillary
ruff

11. Iris transillumination typically reveals a
moth-eaten pattern near the pupillary
sphincter or diffuse mid-peripheral
transillumination defects.

12. Light and scanning electron microscopy demonstrate
pseudoexfoliation material on the posterior surface of the iris
Fluorescein angiographic studies of the iris have revealed
hypoperfusion, peripupillary leakage, and neovascularization
Vascular abnormalities or abnormal extracellular matrix production
causes iris hypoxia  atrophy of the iris pigment epithelium, stroma,
and muscle cells
Blood aqueous barrier defect, pseudo-uveitis

13. ▪ Lens, zonule and ciliary body changes
The characteristic appearance of PEX
material on the anterior lens capsule has
three distinct zones:
a) a translucent, central disc with occasional
curled edges;
b) a clear zone;
c) a peripheral granular zone, which may
have radial striations
Cataracts occur frequently
a
b
c

14. A precapsular film has been noted on the anterior lens capsule of
older individuals, which has a ground-glass appearance
It has been suggested that the precapsular layer may be a precursor
of the PXS

15. Pseudoexfoliation material may be
detected earliest on the ciliary processes
and zonules
Involvement of the zonules can lead to lens
subluxation and phacodonesis .
PEX aggregates at the origin and anchorage
of the zonules and invades the zonular
lamellae, creating areas of weakness
Proteolytic enzymes facilitate zonular
disintegration.

16. Gonioscopy…
▪ Trabecular hyperpigmentation-most
marked inferiorly, patchy distribution
▪ Scalloped band of pigment running on to
or anterior to Schwalbe line
Sampaolesi line
▪ PXF deposits in the trabeculum can give
rise to a ‘dandruff-like’ appearance.
▪ Narrow angles present in some cases
increased risk of angle closure, probably
due to zonular laxity.

17. Ultrasound biomicroscopic findings…
▪ Useful tool to look for presence of exfoliative material on zonules or
peripheral lens capsule, zonular weakness and breakage esp. when pupil
cannot be easily dilated

18. Course of Glaucoma…
▪ Risk of PXG 5% at 5 years, 15% at 10 years
▪ Majority of patients have a c/c open angle glaucoma, mostly
unilateral
▪ Open angle glaucoma
Mechanisms of rise in IOP - local production of pseudoexfoliation
material
endothelial cell damage of the trabecular meshwork
passive deposition of PEX material and pigment originating from
elsewhere in the anterior segment.

19. Active PEX production within
the trabecular meshwork,
Schlemm's canal, and collector
channels, as well as passive
deposition of PEX material within
intertrabecular spaces
swelling of the juxtacanalicular
meshwork and gradual narrowing
of Schlemm's canal

20. IOP runs higher, fluctuates, more difficult to control than POAG
Higher prevalence of glaucomatous optic neuropathy, NRR damage
more diffuse
Immunoelectron microscopic studies of the lamina cribrosa have
shown elastosis - abnormal regulation of elastin synthesis or
degradation, in the optic nerve head of patients with PXS

21. ▪ Acute increases in IOP
PXS with open angles may present with acute glaucoma mimicking
angle-closure glaucoma
▪ Angle Closure Glaucoma- rare
zonular weakness, causing anterior movement of the lens
lens thickening from cataract formation
increased adhesiveness of the iris to the lens due to PEX material,
sphincter muscle degeneration
iris rigidity from hypoxia

22. Differential Diagnosis
Capsular Delamination or true exfoliation
Primary Amyloidosis
Pigment Dispersion Syndrome

23. Management…
▪ Challenging to manage due to IOP fluctuation- set lower target
pressure
▪ Medical treatment
Same as for POAG
Excellent response to prostaglandin analogues
high incidence of late failure
▪ Laser trabeculoplasty
particularly effective, possibly because of trabecular
hyperpigmentation.
argon laser trabeculoplasty

24. ▪ Trabeculectomy
Same success rate as in POAG.
▪ Trabecular aspiration
With light tissue contact confers short-term benefit
Can be performed with cataract surgery or trabeculectomy.
▪ Cataract Surgery

25. Prognosis…
▪ Worse than in POAG
▪ the IOP is significantly elevated and exhibits greater fluctuation.
▪ Patients with PXF to be reviewed every 6 months
Patient with unilateral PXG and PXF in the fellow eye - high risk (50%
in 5 years) of developing PXG in fellow eye.
Patient with unilateral PXG with normal fellow eye has low risk

26. Management of Cataract…
▪ Frequently indicated
▪ Higher than average risk of zonular and capsular breaks
▪ Poor pupillary dilatation, synechiae b/w iris epithelium and peripheral
anterior lens capsule
▪ Preoperativelylook for phacodonesis, asymmetric AC depth,
endothelial compromise, UBM may be helpful
▪ Intraoperatively minimize zonular stress during nucleus
manipulation and cortex removal

27. ▪ Large capsulorrhexis minimizes zonular stress, prevents capsular
phimosis
▪ During hydrodissection tap center of nucleus to decompress fluid
pressure on weak posterior capsule
▪ Small pupil iris hooks, minisphincterotomies, sector iridectomy
▪ CapsularTension Ring to stabilize the capular bag
▪ Early postoperative period fibrinoid iritis may be present; can be
reduced by using heparin surface modified IOLs

28. References…
Becker-Shaffer's Diagnosis and Therapy of the
Glaucomas, 8th Edition
Shields' Textbook of Glaucoma 6th Edition
Kanski's Clinical Ophthalmology: A Systematic
Approach, 8th Edition
American Academy of Ophthalmology-Glaucoma