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
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
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
▪ Preoperativelylook 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
Notas do Editor
Conjunctiva- another independent source of the material .
-suggesting a systemic process involving generalized abnormal elastin metabolism.
These findings have also been observed in the unaffected eye of unilateral cases, leading the researchers to suggest that these corneal endothelial changes might serve as an early sign of the disorder
which the investigators believe indicate that the pseudoexfoliation material was formed by degenerative endothelial cells
These findings are more pronounced with increasing age of the patient, longer duration of the disease, and the presence of glaucoma, and they may represent secondary features of the disease.
Atrophy of the pigment epithelium may be associated with anterior chamber melanin dispersion, which may be seen as a whorl-like pattern of pigment particles on the iris sphincter and pigment deposition on the peripheral iris, whereas atrophy of the muscle cells may account for the poor mydriasis, which is also a typical finding in the PXS
a fibrillar layer similar to pseudoexfoliation material
It may antedate the appearance of PXF by several years. The pigment lies on the surface of the trabeculum.
Studies indicate that there is active exfoliation production in the trabecular meshwork, Schlemm canal and collector channels as well as passive deposition withi intertrabecular spaces swelling of juxtacanalicular meshwork and gradual narrowing and disorganization of canal architecture
(i.e., a red eye, corneal edema, and IOP often higher than 50 mm Hg)
Other problems include a postoperative pressure spike, corneal oedema, increased incidence of capsular opacification and contraction, and IOL subluxation.