2. IntroductionâŠ
âȘ Pseudoexfoliation syndrome (PXF) or exfoliation syndrome is the most
common identifiable cause of open angle glaucoma
âȘ When eye with PXF develops secondary open-angle glaucoma
ï pseudoexfoliation glaucoma (PXG)
âȘ Systemic disorder with important eye manifestations- open and closed-
angle glaucoma, cataract with zonular instability.
âȘ Also associated with increased systemic risk of cardiovascular disorders
3. Epidemiology and GeneticsâŠ
âȘ More common in older age groups- late 60âs and early 70âs
âȘ U/L or B/L- mostU/L cases become B/L over 20 years
âȘ 40% of patients with PXF develop PXG
âȘ More common in women, but men at higher risk for glaucoma
âȘ Geographically- Scandinavian countries, Europe, UK, Middle East and
South EastAsia
âȘ High risk conferred by mutations in the LOXL1 gene at locus 15q22,
coding for elastic fibre components of the ECM
4. Etiology and PathogenesisâŠ
âȘ Grey-white fibrillary extracellular material composed of a protein
core surrounded by GAGâs is produced by abnormal BM of ageing
epithelial cells in the trabeculum, equatorial lens capsule, iris and
ciliary body
âȘ Deposited on the anterior lens capsule, zonules, ciliary body, iris,
trabeculum, anterior vitreous face and conjunctiva
5. âȘ Inherited microfibrillopathyï ultrastructural
appearance of random 10 to 12 nm fibrils,
arranged in a fibrillogranular matrix or coiled
as spirals
âȘ The material behaves like a sticky
âChristmas treeâ type of protein,
aggregating a large number of elastic tissue
and basement membrane proteins
âȘ Polymorphisms in the coding of LOXL1 gene
âȘ LOXL1 enzyme- essential for formation of
elastin fibres
7. Ocular and Systemic Sources
âȘ Many cell types- lens capsule epithelium, iris epithelium, vascular
endothelium, corneal endothelium, and Schlemm's canal
endothelium, conjunctiva
âȘ Other extrabulbar sites- extraocular muscles, orbital septa, posterior
ciliary arteries, vortex veins, and central retinal vessels
âȘ PEX material demonstrated in lung, heart, liver, gallbladder, skin,
kidney, and cerebral meninges
âȘ Associated with a number of vascular disorders, hearing loss and
Alzheimer disease.
8. Clinical and Pathological changesâŠ
âȘ Corneal changes (pseudoexfoliation
endotheliopathy)
ï Flakes of pseudoexfoliation
material and pigment accumulation
on the corneal endothelium (diffuse or
as a vertical spindle similar to the
Krukenberg spindle)
ï Specular microscopy of the corneal
endothelium -significantly lower than
normal cell density and changes in cell
size and shape.
9. âȘ Ultrastructural studies have revealed clumps of pseudoexfoliation
material adhering to the corneal endothelium and incorporated into
the posterior Descemet's membrane.
10. âȘ Iris changes (pseudoexfoliation
iridopathy)
ï Pseudoexfoliation material seen as
white flecks on the pupillary margin of the
iris, with loss of pigment at the pupillary
ruff
11. ï Iris transillumination typically reveals a
moth-eaten pattern near the pupillary
sphincter or diffuse mid-peripheral
transillumination defects.
12. ï Light and scanning electron microscopy demonstrate
pseudoexfoliation material on the posterior surface of the iris
ï Fluorescein angiographic studies of the iris have revealed
hypoperfusion, peripupillary leakage, and neovascularization
ï Vascular abnormalities or abnormal extracellular matrix production
causes iris hypoxia ï atrophy of the iris pigment epithelium, stroma,
and muscle cells
ï Blood aqueous barrier defect, pseudo-uveitis
13. âȘ Lens, zonule and ciliary body changes
ï 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
ï Cataracts occur frequently
a
b
c
14. ï A precapsular film has been noted on the anterior lens capsule of
older individuals, which has a ground-glass appearance
ï It has been suggested that the precapsular layer may be a precursor
of the PXS
15. ï Pseudoexfoliation material may be
detected earliest on the ciliary processes
and zonules
ï Involvement of the zonules can lead to lens
subluxation and phacodonesis .
ï PEX aggregates at the origin and anchorage
of the zonules and invades the zonular
lamellae, creating areas of weakness
ï Proteolytic enzymes facilitate zonular
disintegration.
16. GonioscopyâŠ
âȘ Trabecular hyperpigmentation-most
marked inferiorly, patchy distribution
âȘ Scalloped band of pigment running on to
or anterior toSchwalbe line
ï Sampaolesi line
âȘ PXF deposits in the trabeculum can give
rise to a âdandruff-likeâ appearance.
âȘ Narrow angles present in some casesï
increased risk of angle closure, probably
due to zonular laxity.
17. Ultrasound biomicroscopic findingsâŠ
âȘ 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 GlaucomaâŠ
âȘ Risk of PXGï 5% at 5 years, 15% at 10 years
âȘ Majority of patients have a c/c open angle glaucoma, mostly
unilateral
âȘ Open angle glaucoma
ï Mechanisms of rise in IOP - local production of pseudoexfoliation
material
ï endothelial cell damage of the trabecular meshwork
ï passive deposition of PEX material and pigment originating from
elsewhere in the anterior segment.
19. ï Active PEX production within
the trabecular meshwork,
Schlemm's canal, and collector
channels, as well as passive
deposition of PEX material within
intertrabecular spaces
ï swelling of the juxtacanalicular
meshwork and gradual narrowing
ofSchlemm's canal
20. ï IOP runs higher, fluctuates, more difficult to control than POAG
ï Higher prevalence of glaucomatous optic neuropathy, NRR damage
more diffuse
ï 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. âȘ Acute increases in IOP
ï PXS with open angles may present with acute glaucoma mimicking
angle-closure glaucoma
âȘ AngleClosureGlaucoma- rare
ï zonular weakness, causing anterior movement of the lens
ï lens thickening from cataract formation
ï increased adhesiveness of the iris to the lens due to PEX material,
sphincter muscle degeneration
ï iris rigidity from hypoxia
23. ManagementâŠ
âȘ Challenging to manage due to IOP fluctuation- set lower target
pressure
âȘ Medical treatment
ï Same as for POAG
ï Excellent response to prostaglandin analogues
ï high incidence of late failure
âȘ Laser trabeculoplasty
ï particularly effective, possibly because of trabecular
hyperpigmentation.
ï argon laser trabeculoplasty
24. âȘ Trabeculectomy
ï Same success rate as in POAG.
âȘ Trabecular aspiration
ï With light tissue contact confers short-term benefit
ï Can be performed with cataract surgery or trabeculectomy.
âȘ CataractSurgery
25. PrognosisâŠ
âȘ Worse than in POAG
âȘ the IOP is significantly elevated and exhibits greater fluctuation.
âȘ Patients with PXF to be reviewed every 6 months
ï Patient with unilateral PXG and PXF in the fellow eye - high risk (50%
in 5 years) of developing PXG in fellow eye.
ï Patient with unilateral PXG with normal fellow eye has low risk
26. Management of CataractâŠ
âȘ Frequently indicated
âȘ Higher than average risk of zonular and capsular breaks
âȘ Poor pupillary dilatation, synechiae b/w iris epithelium and peripheral
anterior lens capsule
âȘ Preoperativelyï look for phacodonesis, asymmetric AC depth,
endothelial compromise,UBM may be helpful
âȘ Intraoperativelyï minimize zonular stress during nucleus
manipulation and cortex removal
27. âȘ Large capsulorrhexisï minimizes zonular stress, prevents capsular
phimosis
âȘ During hydrodissectionï tap center of nucleus to decompress fluid
pressure on weak posterior capsule
âȘ Small pupilï iris hooks, minisphincterotomies, sector iridectomy
âȘ CapsularTension Ringï to stabilize the capular bag
âȘ Early postoperative periodï fibrinoid iritis may be present; can be
reduced by using heparin surface modified IOLs
28. ReferencesâŠ
ï Becker-Shaffer's Diagnosis and Therapy of the
Glaucomas, 8th Edition
ï Shields' Textbook of Glaucoma 6th Edition
ï Kanski's Clinical Ophthalmology: A Systematic
Approach, 8th Edition
ï American Academy of Ophthalmology-Glaucoma