|POST GRADUATE SECTION
|Year : 2013 | Volume
| Issue : 3 | Page : 183-186
Pseudoexfoliative syndrome: Revisited
Purvi R Bhagat, Granthali A Pawar
Glaucoma Services, M & J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, Gujarat, India
|Date of Submission||13-Apr-2013|
|Date of Acceptance||17-Jun-2013|
|Date of Web Publication||23-Aug-2013|
Purvi R Bhagat
Glaucoma Services, M & J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
Pseudo exfoliation syndrome is the most common cause of secondary open angle glaucoma wherein due to poorly understood reasons, an unknown substance, a pseudoexfoliative material, is deposited on the anterior lens capsule and other structures of the anterior segment, especially the cornea, iris, pupillary margins, angles and zonules. Fifty percent of these patients ultimately develop glaucoma. The glaucoma when developed is more aggressive, exhibits more pressure fluctuations and is more resistant to standard lines of care and management. Therefore, these cases require close follow-ups and lifelong monitoring. Cataract surgery in these cases also requires special pre-operative planning and intraoperative management because of the attendant problems like poorly dilating pupils and zonular weakness. A major concern with this condition is that the deposition of the material continues throughout the life of the patient leading to unexpected complications at any time, which warrants intensive counseling patient. After extensive internet surfing and literature search, we herein attempt to present the important features of this common, but yet under recognized and less understood disease.
Keywords: Glaucoma, pseudoexfoliation, secondary open angle glaucoma, subluxation
|How to cite this article:|
Bhagat PR, Pawar GA. Pseudoexfoliative syndrome: Revisited. J Clin Ophthalmol Res 2013;1:183-6
Pseudo exfoliation syndrome (PXS) (synonyms: senile exfoliation of the lens capsule, senile uveal exfoliation, fibrillinopathy epithelio capsularis, basement membrane exfoliation syndrome) is the most common cause of secondary open angle glaucoma.  It is not a true exfoliation of the lens capsule. An unknown substance is deposited on the anterior lens capsule and other structures of the anterior segment. Glaucoma is not a frequent accompaniment of this condition; however, when it occurs it is called pseudoexfoliation glaucoma, glaucoma capsulare or capsular glaucoma.
| Epidemiology|| |
PXS is more common in older age groups, with most cases occurring in the late 6 th or 7 th decade, the incidence doubling with every decade after it.  The condition may be unilateral or bilateral. Some unilateral cases may become bilateral with time.  Females are more affected than males, but incidence equals in both sexes in case of pseudo-exfoliation (PEX) glaucoma. 
Strong genetic association is seen with LOX1 gene and mitochondrial or autosomal inheritance pattern has been noted with genomic imprinting.  Higher incidence of disease is seen in cold climates especially in Norway, Finland. 
Prevalence of PXS in open angle glaucoma is 3-47%. 
| Etiology and Pathogenesis|| |
The exact cause is unknown. It has been found that there is deposition of homogenous eosinophilic periodic acid Schiff positive substance (PEX material) of unknown origin, rich in polysaccharides mainly comprising of gylcoaminoglycans, at various ocular sites. It reacts variably with stains like congo red, thioflavin-T and thioflavin-S suggestive of amyloid material. 
Most of the patients are asymptomatic while few may notice diminution of vision (due to senile cataractous changes or due to the glaucomatous optic neuropathy).
The hallmark of PXS is the deposition of whitish dandruff-like material on the anterior lens capsule. In classical cases, three zones of PEX material deposition maybe seen on the anterior capsule - a central disc-shaped zone and a peripheral scalloped zone with a clear intermediate zone. The intermediate clear zone results from the movement of the iris over the lens capsule, which clears away the material and can be difficult to identify until the pupil has been adequately dilated  [Figure 1] and [Figure 2].
|Figure 2: The three characteristic zones: Peripheral scalloped, intermediate clear and central disc|
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Histologically, there are five regions on the lens as compared to the three clinical regions, the additional two regions being the anterior and posterior equatorial area.  There may be the presence of a nuclear cataract, whereas pseudophakic patients may show PEX material deposited on the intra-ocular lens.
Endothelium may be the site of production of the PEX material. Aqueous currents may also lead to deposition of the material on endothelium. Corneal decompensation may occur due to decreased endothelial count, pleomorphism and thickening of Descemet's membrane.  Deposition of PEX material and pigment on the corneal endothelium arranged similar to Krukenberg spindles in pigmentary glaucoma may also be seen. PXS endotheliopathy differs from Fuch's disease in that in PXS, the guttate are more or less diffuse. 
Fleck like PEX material at the pupillary margin with the loss of pigments in pupillary ruff is a frequent finding. Iris transillumination reveals a moth-eaten pattern near the pupillary sphincter with poorly dilating pupils  [Figure 3], [Figure 4] and [Figure 5].
The trabecular meshwork shows moderate to excessive pigmentation. This pigmentation is uneven as opposed to that in pigmentary glaucoma. PEX material may be seen in angle structures and Sampaolesi's line (pigmented line anterior to Schwalbe's line) may be present. The angles are usually open, but sometimes maybe narrow, necessitating an iridotomy  [Figure 6].
Ciliary body and zonules
Deposition of PEX material on ciliary processes, lens zonules and ciliary body is seen [Figure 7] and [Figure 8]. Involvement of lens zonules leads to weakening of zonules and increased incidence of zonular dialysis and subluxation/dislocation of lens.  These findings can be very well visualized with the help of the ultrasound biomicroscope (UBM).
Lamina cribrosa may show increased elastosis. 
PEX material may also been seen deposited on conjunctiva, iris, orbit, orbital vessels, retinal vessels, skin of eye lids, retroauricular and gluteal area, connective tissue of lungs, liver, gall bladder, kidneys and cerebral meninges. 
Intraocular pressure (IOP) may be normal, though 20% of newly diagnosed patients have glaucoma or raised IOP at the time of diagnosis. Fifty percent of these patients ultimately develop glaucoma. Close follow-up of these patients is required as they are prone to IOP spikes and are resistant to medical management.
The diagnosis is mainly clinical.
UBM may reveal the presence of zonular dialysis, degree of lens subluxation and also quantify the angle width and lens thickness. This may aid the surgeon to plan the management accordingly.
Visual fields may show glaucomatous defects.
Optical coherence tomography and scanning laser ophthalmoscopy may reveal glaucomatous disc damage and retinal nerve fiber layer losses; though, these may often be inconclusive because of the presence of lens changes.
Intraocular complications of PXS is described in [Table 1].
| Pseudo-exfoliative Glaucoma|| |
Pseudoexfoliative glaucoma is a type of secondary glaucoma with a more aggressive course. No steroid responders are seen as opposed to patients with primary open angle glaucoma.
- Deposition of PEX material in angle structures.
- Disorganization of the juxtacanalicular region with reduced size of Schlemm's canal in an advanced stage.
- Pigment deposition is considered to be a significant factor as there is a direct correlation between the amount of trabecular pigmentation and incidence of glaucoma.
- Elastotic degeneration of the optic nerve.
Differential diagnosis of PXS
- Pigment dispersion syndrome
[Table 2] describes the differentiating features.
- Capsular delamination (true exfoliation): It is a rare condition, usually occurring in those exposed to infrared radiation, as in glass blowers. It is seen as a clear membrane with free edge floating in aqueous.
- Primary amyloidosis: It is a less common disorder having multiple systemic manifestations.
- Pigment dispersion due to iritis: It will be accompanied by the presence of peripheral anterior synechia, posterior synechia, other features of inflammation and absence of PEX material on lens.
|Table 2: Differences between pseudoexfoliation and pigment dispersion syndrome|
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| Systemic Associations|| |
Retrospective studies show increased incidence of developing acute cerebrovascular disease, chronic cerebral conditions like Alzheimer's disease, increased levels of plasma homocysteine contributing to higher risk for cardiovascular disease. 
| Management|| |
Baseline annual optic nerve head drawings, frequent IOP measurements, perimetry and optic nerve and nerve fiber layer imaging should be performed followed by frequent follow-ups.
A lower target pressure should be set as these patients are more prone to higher diurnal variations and pressure spikes. These cases are also more resistant to standard lines of management. Drugs that enhance outflow facility like prostaglandin analogues are preferred to those that decrease aqueous production as they cause sledging of PEX material in aqueous and increased deposition on the trabecular meshwork.
Glaucoma diagnosed →
Start pressure lowering topical agents and follow-up →
Not controlled →
Laser trabeculoplasty/iridotomy (according to angle status) →
Argon laser trabeculoplasty and selective laser trabeculoplasty give good pressure control initially but later on pressure may rise again requiring a repeat treatment →
Not controlled →
Recently, bimanual trabecular aspiration has been tried for resistant cases. Trabecular debris and pigments are cleared using 100-200 mm Hg suction cannula attached to aspiration probe. The aspiration cannula is 400 μ in diameter and has 450 horizontal angulation. The anterior chamber is irrigated with a separate irrigation probe. The procedure can be combined with cataract extraction. Though it is safe and effective in controlling IOP, regression of effect is seen over a time due to continued uncontrolled liberation of the PEX material and pigments. 
Cataract extraction with posterior chamber intraocular lens (IOL) implantation can be done for patients with significant cataract with due consideration given to zonular dialysis that may co-exist. Capsular tension ring should be kept handy while dealing with cataract in such patients. Special care has to be taken to protect the corneal endothelium as it is quite often compromised. Poorly dilating pupils may pose an extra challenge during surgery and may also mask the diagnosis of lens subluxation pre-operatively. Since, the process of deposition of PEX material continues, the possibility of a delayed IOL displacement has to be kept in mind and also explained to patient. UBM done before surgery will help in better diagnosis and management of these cases.
| Recent Advances|| |
Genetic studies have demonstrated an autosomal dominant inheritance. One pedigree has also suggested mitochondrial inheritance, similar to Leber's hereditary optic neuropathy, Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia.
Dietary supplementation of vitamin B12 and folic acid has been found to reduce hyperhomocysteinemia. Confirmatory results are still awaited. 
| References|| |
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|2.||Stamper RL, Lieberman MF. Secondary open angle glaucoma. Becker Shaffer's Diagnosis and Therapy of the Glaucomas. 8 th ed., chapter 18. US: Mosby Elsevier; 2009. p. 266-93. |
|3.||Thorleifsson G, Magnusson KP, Sulem P, Walters GB, Gudbjartsson DF, Stefansson H, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science 2007;317:1397-400. |
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|5.||Morrison JC, Green WR. Light microscopy of the exfoliation syndrome. Acta Ophthalmol Suppl 1988;184:5-27. |
|6.||Shield BM, Arlingham RR. Pseudo-exfoliation syndrome. Shield's Text Book of Glaucoma. 5 th ed. Philadelphia: Lippincott Willliams & Wilkins; 2005. |
|7.||Riedel PJ, Samuelson TW. Pseudo-exfoliative glaucoma. Yanoff and Duker's Ophthalmology. 3 rd ed. American Academy of Ophthalmology, Inc. Published by Elsevier Inc.; 1998. p. 1172-3. |
|8.||Jacobi PC, Dietlein TS, Krieglstein GK. Bimanual trabecular aspiration in pseudoexfoliation glaucoma: An alternative in nonfiltering glaucoma surgery. Ophthalmology 1998;105:886-94. |
|9.||Vessani RM, Ritch R, Liebmann JM, Jofe M. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol 2003;136:41-6. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2]