Pseudoexfoliation syndrome
- 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 ▪ 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
Editor's Notes
- #8: Conjunctiva- another independent source of the material . -suggesting a systemic process involving generalized abnormal elastin metabolism.
- #9: 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
- #10: which the investigators believe indicate that the pseudoexfoliation material was formed by degenerative endothelial cells
- #13: 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
- #15: a fibrillar layer similar to pseudoexfoliation material
- #17: 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
- #22: (i.e., a red eye, corneal edema, and IOP often higher than 50 mm Hg)
- #28: Other problems include a postoperative pressure spike, corneal oedema, increased incidence of capsular opacification and contraction, and IOL subluxation.