Image: Anthony P Khawaja CMT/CC BY
Hayley J McDonald
Graeme Jenkins Optometrists, Aldinga SA
Pseudoexfoliation glaucoma (PXG) is an aggressive and sight-threatening condition that may be more difficult to manage than primary open angle glaucoma.
Clinical signs of pseudoexfoliation (PXF) that aid diagnosis include pseudoexfoliative deposits on the lens and iris, transillumination defects and iris pigment granule dispersion. These changes lead to accumulation of material in the trabecular meshwork, inhibiting aqueous outflow and causing the IOP to rise.1
The ocular health of a now 77-year-old Caucasian man (SG) had been examined over a 15-year period. No family history of glaucoma was present and there were no other systemic risk factors present with the exception of systemic steroid treatment.
The fluctuation in IOP control can be seen in Figure 1, noting that only the left eye has PXG with no pathology or clinical signs present in the right eye.
Figure 1. IOP response over time
PXF material was first noted in the left eye in 2003, with IOP of OD 17 and OS 21 mmHg and cup/disc ratios 0.7 OU at the time. Perimetry testing showed no abnormalities.
The patient’s IOP continued to rise steadily until 2007 when IOP reached OD 15 and OS 25 mmHg. The visual field remained unaffected but PXG was diagnosed at this time and OS latanoprost 0.005% nocte was initiated.
In 2009 he was diagnosed with polymyalgia rheumatica, a chronic inflammatory disorder that causes pain and stiffness in the hip, shoulder and other large joints.2 Systemic steroids are the mainstay of treatment and are used to manage the symptoms of the disease, with a slowly tapering dose.
The steroid treatment in this case caused a profound rise in IOP (peak of 30 mmHg). To maintain control, brinzolamide 1% bid was prescribed in addition to the current prostaglandin analogue. The patient remains on low dose oral steroids to manage the symptoms of this systemic condition.
Further fluctuations in IOP can be observed in 2010 and 2015, when 180-degree SLT, and bilateral phacoemulsification and IOL insertion were performed respectively.
PXF is a systemic disorder, with deposits found around the blood vessels of connective tissue. Organs affected include the lung, liver, kidney and meninges; however, no causation of cerebrovascular and cardiovascular diseases or increase in mortality has been shown.3
The diagnosis of PXF is based on its characteristic clinical appearance: two annular zones of white deposits on the anterior lens capsule, separated by a clear zone where the iris contacts and rubs against the capsule.4 Flaky white material and loose pigment cells can also be deposited throughout the anterior segment. Dilation is critical to diagnosis, with up to 79 per cent of PXF missed when examining undilated patients.5 These characteristic signs of PXF are linked with reduced aqueous outflow via the trabecular meshwork.1
Other less visible changes to ocular structures are frequently linked with damage caused by matrix metalloproteinases mediated clearance of PXF material. These include poor response to mydriatic or miotics due to fibrotic and disorganised iris muscles, low endothelial cell density, and weakened zonules prone to subluxation or dislocation.6
In eyes with PXF, the risk of developing glaucomatous damage is 5.3 per cent and 15.4 per cent in five and 10 years, respectively.6-8 In addition to a higher risk of developing glaucoma, eyes with PXF tend to have worse visual fields at the time of glaucoma diagnosis, require a greater number of treatment steps, have a more severe clinical course, and are more likely to require laser or surgical interventions.9
The prevalence of PXF within populations varies greatly, with the highest rates reported in Scandinavian countries.10 PXF is present in 5.9 per cent of Indigenous Australians but there is a very low association with glaucoma.11 The Blue Mountains Eye Study found a rate of 2.3 per cent among Caucasian Australians.12
Several genetic variants have been found that predispose a person to developing PXF. Most notable is the LOXL1 gene, involved in the crosslinking of collagen and elastin fibres in the extra-cellular matrix.13 Carriers of the gene are 100 times more like to develop PXG.14
As with other glaucoma conditions, the primary method of treatment is the reduction of IOP. The treatment approach for PXG is largely the same as that for POAG. A target pressure of 30 per cent reduction is generally considered appropriate, although somewhat harder to reach with a lower hypotensive response to topical medications.4,15 The efficacy of a treatment regime over time and the target pressure must be constantly reevaluated due to the resistant and aggressive nature of PXG disease.
Topical hypotensive medication is the first line of therapy for PXG, just as it is for POAG. Monotherapy is recommended initially but a low threshold for changing or combining drops is required to ensure that the pressure is adequately controlled.
Statistically significant results, with a clinically significant 30 per cent IOP reduction, have been shown for latanoprost 0.005% and travoprost 0.004% monotherapy in addition to dorzolamide 2% + timolol 0.05% combination therapy.16,17
Dorzolamide 2% and timolol 0.5% monotherapies have been shown to be slightly less efficacious but still achieve a 20 per cent IOP reduction in PXG patients.17
Laser trabeculoplasty and glaucoma surgeries
Argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) increase aqueous outflow through the trabecular meshwork. Both demonstrate a 20 to 30 per cent reduction in IOP, with no statistically significant difference between the two treatments in PXG.18,19
SLT has been shown to have equivalent IOP-lowering results in both PXG and POAG when used as either a first-line or secondary therapy.18,20 Additionally, PXF does not appear to increase the risk of complications.18-20
The majority of literature on surgical interventions for PXG investigate trabeculectomy. When compared to POAG, PXG patients undergoing trabeculectomy had statistically lower IOP levels initially but were more likely to require additional medication, have treatment failure overall and progress to blindness.9,21 Despite this, there is no apparent difference in complication rates following surgery.9
The indications for laser and surgical procedures are similar in PXG to those of POAG with broadly equivalent results.15,21
The presence of PXF greatly increases both the risk of cataract formation and the risk of surgical complications. However, phacoemulsification procedures have been shown to reduce IOP in eyes with PXF by 20 per cent (compared to a 3.6 per cent change in control eyes) in the year following, and maintain a lowered IOP for up to seven years.8,22
The mechanism that causes the reduction in IOP is unknown but has been hypothesised to be linked with aspiration of pseudoexfoliative material or wash-out effect on the trabecular meshwork.
Despite the more severe prognosis for PXG compared to POAG, it is a condition that is readily able to be managed by optometric clinicians. Thorough screening, timely diagnosis and continued monitoring are critical to ongoing patient care.
Table 1. Differential diagnosis of pseudoexfoliation glaucoma3-5
Table 2. Pseudoexfoliation glaucoma key points
1. Ekström C. Risk factors for incident open-angle glaucoma: a population-based 20-year follow-up study. Acta Ophthalmol 2012; 90: 4: 316-321.
2. Saad ER et al. Polymyalgia rheumatica: background, pathophysiology, etiology [Internet]. 2015 [cited 14 January 2016]. Available from: emedicine.medscape.com/article/330815.
3. Shrum K. Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation. Am J Ophthalmol 2000; 129: 1: 83-86.
4. Ritch R, Schlötzer-Schrehardt U. Exfoliation syndrome. Surv Ophthalmol 2001; 45: 4: 265-315.
5. Layden WE, Shaffer RN. Exfoliation Syndrome. Trans Am Ophthalmol Soc 1973; 71: 128-148.
6. Ritch R. Exfoliation syndrome and occludable angles. Trans Am Ophthalmol Soc 1994; 92: 845–944.
7 Jeng S, Karger R, Hodge D, Burke J et al. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma 2007; 16: 1: 117-121.
8 Åström S. Long-term follow-up of pseudoexfoliation, intraocular pressure and glaucoma. Umeå, Sweden: Umeå University Medical Dissertations, 2013.
9. Konstas AG, Jay JL, Marshall GE, Lee WR. Prevalence, diagnostic features, and response to trabeculectomy in exfoliation glaucoma. Ophthalmology 1993; 100: 5: 619-627.
10. Aasved H. Prevalence of fibrillopathia epitheliocapsularis (pseudoexfoliation) and capsular glaucoma. Trans Ophthalmol Soc U K 1979; 99: 2: 293-295.
11. Landers J, Henderson T, Craig J. Prevalence of pseudoexfoliation syndrome in indigenous Australians within central Australia: The Central Australian Ocular Health Study. Clin Exp Ophthalmol 2012; 40: 5: 454-457.
12. Mitchell P, Wang JJ, Hourihan F. The relationship between glaucoma and pseudoexfoliation: the Blue Mountains Eye Study. Arch Ophthalmol 1999; 117: 10: 1319-1324.
13. Elhawy E, Kamthan G, Dong C, Danias J. Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations. Hum Genomics 2012; 6: 1: 22.
14. Thorleifsson G, Magnusson KP, Sulem P, Walters GB et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science 2007; 317: 5843: 1397-1400.
15. NHMRC. Guidelines For the Screening, Prognosis, Diagnosis, Management and Prevention of Glaucoma. Canberra: National Health and Medical Research Council; 2010. Available at: https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cp113_glaucoma_120404.pdf. [Accessed 15 January 2015].
16. Parmaksiz S, Yüksel N, Karabas VL, Ozkan B et al. A comparison of travoprost, latanoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma. Eur J Ophthalmol 2006; 16: 1: 73-80.
17. Heijl A, Strahlman E, Sverrisson T, Brinchman-Hansen O et al. A comparison of dorzolamide and timolol in patients with pseudoexfoliation and glaucoma or ocular hypertension. Ophthalmology 1997; 104: 1: 137-142.
18. Shazly TA, Smith J, Latina MA. Long-term safety and efficacy of selective laser trabeculoplasty as primary therapy for the treatment of pseudoexfoliation glaucoma compared with primary open-angle glaucoma. Clin Ophthalmol 2010; 5: 5-10.
19. Kent SS, Hutnik CM, Birt CM, Damji KF et al. A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation. J Glaucoma 2015; 24: 5: 344-347.
20. Ayala M, Chen E. Comparison of selective laser trabeculoplasty (SLT) in primary open angle glaucoma and pseudoexfoliation glaucoma. Clin Ophthalmol 2011; 5: 1469-1473.
21. Landers J, Martin K, Sarkies N, Bourne R, Watson P. A twenty-year follow-up study of trabeculectomy: risk factors and outcomes. Ophthalmology 2012; 119: 4: 694-702.
22. Cimetta DJ, Cimetta AC. Intraocular pressure changes after clear corneal phacoemulsification in nonglaucomatous pseudoexfoliation syndrome. Eur J Ophthalmol 2008; 18: 1: 77-81.
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