case 6 - pseudoexfoliation · case 6 - pseudoexfoliation case history: ... the combination of these...
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Case 6 - Pseudoexfoliation
Case History:
A 65-year-old Caucasian woman presented to her optometrist for a check-up. She had never had an
eye examination, but felt like her left eye might be weaker than her right. She was otherwise
asymptomatic.
She reported no family history of ocular disease. Her medical history included high cholesterol
controlled with a statin.
Examination:
Right eye Left eye
Habitual vision 6/7.5 6/9.5
Pinhole VA 6/6 6/6
Pupils Left RAPD Goldmann IOP 17mmHg 23mmHg
Slit lamp examination
Anterior segment
Unremarkable White fluffy deposits on the anterior lens capsule and pupillary margin
Optic Nerve
See disc photos See disc photos
Retina Clear and flat Clear and flat
Gonioscopy Open angle Open angle. Patchy pigmentation of trabecular meshwork and anterior to trabecular meshwork
Corneal pachymetry 570 m 572 m
Question 1: What other information might have been useful at this point?
Answer 1:
• Did the patient have a history of eye trauma?
• How well did the pupil dilate after the instillation of mydriatics?
• Was there evidence of white material or pigment deposition elsewhere?
o What was the pattern of deposition on the anterior lens surface?
o Was pigment seen on the corneal endothelium?
• Was there peripupillary iris tranillumination? What was the shape of the pupil?
• At what time of day was the IOP measured?
• What were the patient’s colour vision testing results?
• What was the patient’s refractive error?
The patient did not have a history of any eye trauma. The IOP was measured prior to dilation, at
around 9:00 am. The patient had a low hyperopic refractive error. There was peripupillary iris
transillumination and pupillary ruff atrophy, and some light scattered pigment on the corneal
endothelium. On Ishihara testing, the patient could identify all plates correctly with each eye. There
was no red desaturation between eyes on red cap testing. The pupil appeared to be regular in shape,
but did not dilate well with 1% tropicamide. With moderate pupil dilation, it was possible to visualise
the deposition of material on the anterior lens surface as a bullseye pattern.
Question 2:
Describe the disc appearance in the photos below.
(a)
(b)
Figure 1: Disc photo at presentation. Right (a), Left (b).
Answer 2:
The right optic disc is of average size with a temporal crescent of pigmented peripapillary atrophy.
The CDR is approximately 0.3. and there is no thinning or focal notching of the neuroretinal rim.
There is no RNFL haemorrhage. The left optic disc is average in size, with a temporal crescent of
pigmented peripapillary atrophy. It has a number of glaucomatous features and there is
considerable inter-eye asymmetry. There is increased cupping, with a CDR of approximately 0.75.
There is focal thinning of the inferior neuroretinal rim, with notching at the 5 o’clock position and
bayoneting of blood vessels. There is no RNFL haemorrhage. Each nerve has distinct margins and the
neuroretinal rim appears well-perfused.
Question 3: Based on the case history and initial examination findings, discuss the differential
diagnoses and appropriate investigations.
Answer 3:
There are no overt signs of any intraocular disease in the right eye. However, in the left eye there is
elevated IOP, an RAPD, and pathological cupping of the disc suggesting a glaucomatous optic
neuropathy. Slit lamp examination revealed the presence of white fluffy material deposited on the
anterior lens capsule and pupillary margin. Pigment was noted in the trabecular meshwork on
gonioscopy. The combination of these findings suggests left pseudoexfoliative glaucoma (PXG). Most
patients with PXF glaucoma are asymptomatic. However, because disease progression is often more
rapid than primary open angle glaucoma (POAG), these patients need to be watched closely, and
treated aggressively.
Differential diagnoses include:
• Pigment dispersion syndrome (PDS): pigment cells slough off from the posterior iris and can
accumulate in the angle. This occurs more commonly in younger, male, myopic patients and
is more often a bilateral condition whereas it is common for PXF to present with unilateral
findings (although it can also be bilateral). Iris transillumination defects in PDS are usually
found in the mid-peripheral iris and are radial in orientation, whereas, in PXF, the
transillumination defects are near the pupillary margin. PDS often presents with a vertical
line of pigment on the corneal endothelium (Krukenberg spindle), which is not usually a
feature of PXF.
• Trauma/previous ocular surgery can also lead to heavy trabecular pigmentation. Our patient
has no history of ocular trauma.
• True exfoliation of the lens occurs when there is dehiscence and schisis of the anterior lens
capsule, appearing as a wrinkling of the capsule, or a free-floating flap. This delamination
generally occurs in patients with a history of exposure to high levels of infrared radiation (eg.
glassblowers or welders).
• Ocular amyloidosis: amyloidosis is a group of diseases with build-up of amyloid fibrils
(abnormal proteins) in tissues (including, in some cases, the eye). The practitioner may find
white deposits present in the eyes of patients with amyloidosis but this is very uncommon in
the eye and systemic manifestations are often present, including involvement of the skin,
kidneys and heart. A number of ocular structures can be affected, including the lids, cornea,
iris, trabecular meshwork, lens, retina and vitreous.
The diagnosis of PXF glaucoma is primarily clinical and can be done at the slit lamp. Additional
structural (ocular imaging) and functional (visual field) testing is essential, in order to be able to
determine the glaucoma severity, and to monitor disease progression. These will be discussed
further below.
Question 4:
Describe the patient’s visual field and OCT results (below).
Figure 2a: OCT RNFL
Figure 2b: OCT macular scan
Figure 3a: Visual field right eye
Figure 3b: Visual field left eye
Answer 4:
The RNFL OCT scan of the right eye shows excellent signal strength (9/10) and the reference circle is
well-centred. The RNFL thickness map shows thickness values within ‘age-normal’ limits.
Neuroretinal rim thickness is also within normal limits, and the scan does not reveal any focal
thinning. The left RNFL OCT scan shows acceptable signal strength (6/10). The reference circle is
well-centred. The RNFL thickness graphs shows a reduction in RNFL thickness in all quadrants except
nasally, with the most pronounced thinning in the inferior quadrant. There is also corresponding loss
of the neuroretinal rim thickness. The RNFL Deviation map in the left eye shows thinning superiorly
and inferiorly in the typical arcuate pattern seen in glaucoma. This is not seen in the right eye.
Macular OCT of the ganglion cell complex (GCC) in the right eye shows good signal strength (8/10),
with appropriate retinal layer segmentation. The thickness values are within age-normal limits and
there is no localised loss of GCC thickness. The left eye GCC scan shows is of adequate signal
strength (6/10). Due to the slightly lower signal strength, the retinal layers are less clearly
demarcated on the false colour image, however, the layer segmentation appears to be accurate.
There is generalised loss (lowest 1% of ‘normal values) in all six GCC sectors in the left eye.
Visual fields testing (Humphrey SITA standard 24-2) for both eyes was moderately unreliable with
4/14 (28.6%) and 4/17 (23.5%) fixation losses in the right and left eyes respectively, exceeding the
20% cut-off for test reliability (Yaqub, 2012). The mean deviation (MD) was +0.51 dB in the right eye
and -5.86 dB in the left eye. The usual MD threshold for a visual field to be ‘within normal limits’ is -2
dB (Yaqub, 2012). The pattern standard deviation (PSD) is a measure of focal loss within the field. A
localised defect will give rise to a high PSD while a generalised defect will give rise to a low PSD. The
PSD of the right eye is ‘within normal limits’, whereas the left eye has a PSD of 7.21 dB (p < 0.5%).
Having a high PSD is consistent with glaucomatous visual field loss, except in the case of advanced
glaucoma when there is loss of sensitivity in both the superior and inferior visual fields causing lower
pattern standard deviation as the visual field loss is no longer localised. The left eye Total Deviation
probability map matches the Pattern Deviation probability map well, with approximately 1dB
adjustment for general depression.
The glaucoma hemifield test (GHT) uses five zones in each hemifield and tests them for symmetry.
The GHT is “Outside normal limits” when sensitivities in at least one zone in one hemifield are
significantly different from the sensitivities in the corresponding zone in the other hemifield
(p<0.01). The GHT is “Borderline” when the difference is less significant (p-value between 0.01 and
0.03). Our patient has a GHT result of ‘within normal limits’ in the right eye and ‘outside normal
limits in the left visual field, indicating statistically significant differences between the superior and
inferior visual fields. The pattern of visual field loss (superior arcuate defect and inferior nasal step)
in the patient’s left eye matches the pattern of RNFL thinning on OCT as discussed above.
Question 5: Describe the pathophysiology of pseudoexfoliation syndrome (PXF) and
pseudoexfoliative glaucoma (PXG).
Answer 5: PXF is an age-related systemic microfibrillopathy, caused by progressive accumulation and
gradual deposition of extracellular grey and white material over various tissues. The deposits are
composed of elastic fibres (fibrillin and alpha-elastin) and non-collagenous basement membrane
materials (laminin) which form fibrils. This is thought to arise from abnormalities of the extracellular
matrix and the basement membrane. In PXF, there is deposition of extracellular fibrillar material on
the trabecular meshwork, pupillary margin, lens zonules, the face of the ciliary body and the corneal
endothelium. The origin of this material is unknown, although there have been suggestions it is from
cells in the structures listed above and also in cells outside the eye such as fibrocytes, blood vessel
and muscle cells (Zenkel 2014). When a patient with PXF develops glaucoma it is referred to as
pseudoexfoliative glaucoma (PXG).
Ocular abnormalities associated with PXF include:
• Pigmentation pathology, with peripupillary iris depigmentation, which can manifest as
“moth-eaten” transillumination and trabecular meshwork hyperpigmentation. Pigment
deposition can also occur on the corneal endothelium (Nazarali, Damji, & Damji, 2018).
• Lens and zonular pathology including cataract and lens subluxation. Pseudoexoliative
material is often found on the anterior lens capsule in a central disc and peripheral band
pattern with a clear mid zone in between. The intermediate zone is thought to be due to
rubbing of the iris/pupil over the lens. The exact pathophysiology of cataract formation in
PXF is not clear, but PXF is a well-established risk factor for development or progression of
cataract. A 12 year study of 1045 patients showed a 3-4 times greater risk in requiring
cataract surgery during that period of time if they had PXF at baseline vs those without
(Arnarsson, Sasaki, & Jonasson, 2013). Additionally, the deposition of PXF material leads to
weakening of the zonules, resulting in increased risk of zonular dialysis and spontaneous
subluxation or dislocation of the lens. This makes cataract surgery more complex and
difficult to perform as the pupil often dilates poorly and there are other complications such
as increased risk of capsular tear, post-operative pressure spikes, corneal oedema and
increased incidence of capsular opacification.
• Corneal changes, including corneal endothelial compromise and decompensation. There is
thought to be a corneal endotheliopathy associated with PXF. Suggested mechanisms
include hypoxic changes in the anterior chamber, accumulation of extracellular matrix,
fibroblastic changes in the endothelium and increased concentration of TGF beta leading to
reduced density of the corneal endothelium and changes to endothelial cell morphology,
potentially leading to corneal oedema and decompensation. (Tekin, Inanc, & Elgin, 2019).
• Optic nerve, most commonly secondary open angle, although a smaller number of patients
are susceptible to secondary angle closure glaucoma. Secondary open angle glaucoma is
thought to arise from increased IOP due to an increase in trabecular outflow resistance. It is
thought that contact and friction between the lens and iris causes the ‘shedding’ of pigment
from the abnormal epithelium into the anterior chamber and this deposits in the trabecular
spaces and near the endothelium of Schlemm’s canal. There is also suggestion that the
abnormal endothelial cells of the trabecular meshwork and Schlemm’s canal themselves
contribute to the deposition/accumulation of material.
• Central retinal vein occlusion, due to alteration of vascular structure in PXF. The mechanism
of CRVO in PXF is not fully understood, but suggested mechanisms include the accumulation
of PXF material disrupting the structure of the basement membrane and leading to
endothelial dysfunction, increased serum oxidative stress or increased homocysteine levels
causing degradation of elastic structures in the arterial wall. (Tekin et al., 2019)
Question 6: What are the risk factors for PXF, including genetic risk factors?
Answer 6: Evidence from multiple meta-analyses has shown an association of variants in the LOXL1
gene with PXF. LOXL1 is part of a family of enzymes that are involved in the linking of collagen and
elastin in the extracellular matrix. Three single-nucleotide polymorphisms have been identified and
mutations in the gene coding for these enzymes lead to disruption of extracellular matrix
metabolism, resulting in accumulation of elastic fibre components.
In a 2007 study, LOXL1 gene variants were found in 99% of Scandinavian subjects with PXG, the
population in which the disease was first discovered (Thorleifsson et al., 2007). Interestingly, a large
number of controls who had the gene variants were unaffected.
Other loci, such as POMP (affecting ubiquitin-conjugating enzymes), TMEM136 (affecting vascular
endothelia) and AGPAT1 (affecting omega-6 polyunsaturated fatty acid levels), have been found to
be associated with increased susceptibility to PXF and may suggest biological pathways for
pathogenesis (Aung et al., 2017).
PXF is associated with increasing age, with significant increases in prevalence after the age of 70
years. Worldwide, studies have yielded a large range in PXF prevalence values, ranging from 0.3 –
30% for those over the age of 60 years (Nazarali et al., 2018). PXF is more common in certain
geographic locations and among certain ethnic groups. It is well-established that PXF is more
prevalent in Scandinavian/Nordic populations. In Iceland, the prevalence is 17.7% in 70-79 year olds
and 40.6% in those over 80 year of age (Nazarali et al., 2018).
High prevalence rates have also been found in Black African populations in Ethiopia (25% of open
angle glaucoma is due to PXF). In South Africa prevalence is higher in Black individuals compared
with White South Africans (20% vs 1.4% respectively) (Nazarali et al., 2018). Within Asia there is
significant variation, with East Asian countries having prevalence values of 0.11% (South Korea),
2.38% (China), 3.4% (Japan) and Middle Eastern countries generally having higher prevalence (5% in
Turkey and 9.3% in Saudi Arabia (Nazarali et al., 2018).
Some environmental factors have been suggested. Stein et al described a latitude effect, where
those who resided at higher latitudes had greater prevalence of PXF (Stein et al., 2011). This was also
noted amongst the population in the USA, where those in the northern parts of the country had
greater rates than those in the middle and the south. Ultraviolet radiation has also been shown to
upregulate the expression of LOXL1 as well as the deposition materials found in PXF (Jiwani &
Pasquale, 2015).
Question 7: What systemic findings are related to PXF?
Answer 7: There have been reports of pseudoexfoliative material being found in visceral organs
(heart, lungs, liver, pancreas, intestines), skin, myocardium, meninges and vessel walls. Diseases that
have been suggested to have associations with PXF include cerebrovascular disease, aortic
aneurysm, coronary artery disease, peripheral vascular disease, hypertension, neurosensory hearing
loss, renal artery stenosis and Alzheimer’s-like dementia (Bettis, Allingham, & Wirostko, 2014).
Most of the listed diseases are related to the vascular changes. Although the exact mechanism has
not been fully elucidated, we know that PXF affects the elastic microfibrillar system which plays a
significant role in the extracellular matrix of blood vessels, particularly arteries and arterioles similar
to CRVO as discussed in question 5 (Tekin et al., 2019). .
Question 8: What is the prognosis of pseudoexfoliative glaucoma (PXG)?
Answer 8: PXG is more aggressive and has a poorer prognosis compared with POAG. Patients with
PXG tend to have larger fluctuations in IOP, making it difficult to capture the full range of IOP during
clinic hours. IOP tends to be higher at glaucoma diagnosis in PXG patients. Patients with PXG have
been shown to have greater visual field loss, progressive disc damage due to increased IOP
fluctuation, reduced response to medications, faster progression of the disease and increased need
for surgical treatment.
PXG is a mostly asymmetric but bilateral disease, where the disease may only be clinically detectable
in one eye at the slit lamp, as was the case with our patient. However, laboratory analysis of
conjunctival biopsy would likely show the presence of pseudoexfoliative material bilaterally. It has
been reported that those with clinically evident bilateral PXF tend to be older and have greater
incidence of glaucoma compared to those with unilateral disease (Plateroti, Plateroti,
Abdolrahimzadeh, & Scuderi, 2015).
Question 9: What are the non-surgical treatment options for PXG?
Answer 9: Topical ocular anti-hypertensive medical therapy is usually the first-line treatment and
may yield a good response initially, although control may not be able to be maintained over time.
Generally, a topical prostaglandin analogue, beta blocker, alpha agonist or carbonic anhydrase
inhibitor, or a combination of these agents, is used as the agent of choice (Tekin et al., 2019). A
prostaglandin analogue may be favoured as this class of medications has a longer duration of action
(once daily dosing), and results in reduced diurnal IOP fluctuation.
Laser trabeculoplasty, in the form of argon laser trabeculoplasty (ALT) and selective laser
trabeculoplasty (SLT), is often utilised after medical therapy treatment (or as a first line treatment
for some patients) and usually before surgical procedures are undertaken. In studies of SLT in PXF,
there was a 31.5% mean reduction in IOP at 12 months, and 31.4% at 18 months (Leahy & White,
2015)
Our patient was initially started on topical treatment and eventually reached triple therapy of
bimatoprost 0.03% at night and dortim (dorzolamide 2% and timolol 0.5%) twice a day. In addition,
she had three SLT treatments over a period of seven years, with diminishing efficacy. Her glaucoma
continued to progress despite maximal medical and laser treatment. She later had cataract surgery
together with a hydrus stent after the SLT treatments. She is currently awaiting a Xen implant. If this
procedure is unsuccessful, the patient will likely require a trabeculectomy.
Since complications with cataract surgery occur more often with advanced PXG cases, there may be
a preference to perform cataract surgery in the earlier stages of PXG due to the increased late-stage
zonular fragility and harder nuclei, as well as removing one of the primary locations of
pseudoexfoliative material, the lens. (Tekin et al., 2019).
Question 10: What are the surgical treatments options for PXG?
Answer 10:
As PXF glaucoma can progress aggressively and there is a lack of therapy to address the underlying
cause, patients may be more likely to require surgical treatment (as is the case for our patient).
Trabeculectomy remains the gold-standard surgical procedure in the management of PXF glaucoma.
Antifibrotic agents, such as mitomycin C or 5-fluorouracil are often used in order to prevent bleb
failure due to scarring. However, there are a number of surgical challenges that can make
trabeculectomy difficult for patients with PXF glaucoma (Hollo, Katsanos, & Konstas, 2015):
• Vitreous loss due to zonular damage
• A tendency for more pronounced inflammatory reaction
• Hyphema from microneovascularization of the iris
• Synechiae formation due to inflammatory reaction involving the iris
• Choroidal haemorrhage/choroidal detachment due to very low pressure or a precipitous
drop in pressure
Glaucoma-drainage devices or shunts may also be utilised in the management of PXF glaucoma.
These lower IOP by draining aqueous humour to the external subconjunctival space. These devices
are useful in patients who have either had previously failed trabeculectomy or have more complex
glaucoma (Tseng 2017).
Question 11: What are MIGS devices?
Answer 11:
Minimally invasive glaucoma surgeries (MIGS) are newer surgical techniques and devices designed to
treat glaucoma and are considered to be safer and less invasive than conventional glaucoma surgery
(eg. trabeculectomy, or tube-shunt surgery). Meta-analysis of 9 randomised controlled trials and 21
case series show some effectiveness in lowering IOP and glaucoma drug use along with a good safety
profile (Lavia, Dallorto, Maule, Ceccarelli, & Fea, 2017).
To drain aqueous humour from the anterior chamber, MIGS devices target 3 anatomical spaces
(Fingeret & Dickerson, 2018)
1) Schlemm’s canal. This is achieved by bypassing the trabecular meshwork. This accesses the
natural outflow pathway and, as it is buffered by episcleral venous pressure, removes the
risk of hypotony. Devices include iStent (Glaukos) and Hydrus microstent (Ivantis).
The iStent is an L-shaped stent around 1.0mm long and made of heparin-coated titanium.
The long leg of the L is aimed to be placed inside Schlemm’s canal with the short leg
protruding into the anterior chamber.
The Hydrus is an 8mm long crescent tube with multiple windows along its length made of
nickel-titanium alloy. The device is placed into Schlemm’s canal leaving one to two
millimetres of the inlet segment in the anterior chamber. Schlemm’s canal is effectively
dilated and stented to allow greater aqueous outflow.
A trabectome is another MIGS procedure that is used for an ab interno trabeculotomy. It is
an angle-based procedure where a handpiece is inserted into the anterior chamber via a
small clear-corneal incision and positioned into Schlemm’s Canal. The bent tip fits into the
canal and can be advanced parallel to the angle and the device delivers energy causing
ablation of the trabecular meshwork without damaging nearby structures. These procedures
also preserve the conjunctiva so penetrating surgery or aqueous shunt-device implantation
can be performed further down the track. A study analysing the 5 year results of trabectome
combined with phacoemulsification performed in 93 glaucoma patients showed that PXG
patients had higher success rate compared with other glaucomas (Esfandiari et al., 2019).
This is thought to be because the surgery removes the diseased tissue with ablation of the
trabecular meshwork as well as the phacoemulsification removing the lens, which is a source
of pseudoexfoliative material.
2) Suprachoroidal space/supraciliary space. The supraciliary space is the virtual space between
the ciliary body and the sclera and is continuous with the suprachoroidal space. Stents are
placed in the anterior chamber angle with the device and applicator which makes a blunt
dissection between the scleral spur and the iris/ciliary body. These are non-physiological
targets for drainage and thus tissue resistance is relied upon to limit aqueous outflow (as
there is a risk of hypotony). There is also a risk of scarring at the surgery area leading to
failure of the device. An example of such a device is CyPass micro-stent (Novartis).
The Cypass device was voluntarily withdrawn by Alcon Research LTD in August 2018 based
on data from the COMPASS-XT long-term safety study. The study demonstrated a clinically
and statistically significant increase in corneal endothelial cell loss reported in the CyPass
micro-stent group compared with the cataract surgery-only control group (18.4% vs 7.5%
loss respectively at 48 months (p = 0.0001), and 20.4% vs 10.1% loss at 60 months (p =
0.0032) (Lane, 2018). The results provided by Alcon suggest a relationship between the
depth of the implant and endothelial cell loss, where greater anterior chamber exposure
may result in more endothelial cell loss at five years. Since then the FDA has issued a Class I
recall, the most serious type of recall.
3) Subconjunctival space. An example of this type of device is the XEN Gel Stent (Allergan). The
stent is a 6mm tube placed in a scleral tunnel created by a bevelled needle applicator,
terminating just under the conjunctiva. Aqueous humour flows from the anterior chamber
through the stent and forms a filtering bleb under the conjunctiva. Outflow resistance is
determined by the length of the tube and width of the bore which can be adjusted to
prevent hypotony. Similar to devices targeting the suprachoroidal space, it is a non-
physiological target for drainage. Sometimes antifibrotics are used together with these
devices to reduce bleb scarring similar to trabeculectomy.
Recommended reading:
Nazarali, S., Damji, F., & Damji, K. F. (2018). What have we learned about exfoliation syndrome since its discovery by John Lindberg 100 years ago? Br J Ophthalmol, 102(10), 1342-1350. doi:10.1136/bjophthalmol-2017-311321 Lane, S. (2018). Overview of the results from the 5 year follow up study of the CyPass Microstent. Retrieved from ESCRS Scientific Presentation: Fingeret, M., & Dickerson, J. E., Jr. (2018). The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma. Optom Vis Sci, 95(2), 155-162. doi:10.1097/opx.0000000000001173
References:
Arnarsson, A., Sasaki, H., & Jonasson, F. (2013). Twelve-year Incidence of Exfoliation Syndrome in the Reykjavik Eye Study. Acta Ophthalmol, 91(2), 157-162. doi:10.1111/j.1755-3768.2011.02334.x Aung, T., Ozaki, M., Lee, M. C., Schlotzer-Schrehardt, U., Thorleifsson, G., Mizoguchi, T., . . . Khor, C. C. (2017). Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat Genet, 49(7), 993-1004. doi:10.1038/ng.3875 Bettis, D. I., Allingham, R. R., & Wirostko, B. M. (2014). Systemic diseases associated with exfoliation syndrome. Int Ophthalmol Clin, 54(4), 15-28. doi:10.1097/iio.0000000000000044 Esfandiari, H., Shah, P., Torkian, P., Conner, I. P., Schuman, J. S., Hassanpour, K., & Loewen, N. A. (2019). Five-year clinical outcomes of combined phacoemulsification and trabectome surgery at a single glaucoma center. Graefes Arch Clin Exp Ophthalmol, 257(2), 357-362. doi:10.1007/s00417-018-4146-y Fingeret, M., & Dickerson, J. E., Jr. (2018). The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma. Optom Vis Sci, 95(2), 155-162. doi:10.1097/opx.0000000000001173 Hollo, G., Katsanos, A., & Konstas, A. G. (2015). Management of exfoliative glaucoma: challenges and solutions. Clin Ophthalmol, 9, 907-919. doi:10.2147/opth.S77570 Jiwani, A. Z., & Pasquale, L. R. (2015). Exfoliation Syndrome and Solar Exposure: New Epidemiological Insights Into the Pathophysiology of the Disease. Int Ophthalmol Clin, 55(4), 13-22. doi:10.1097/iio.0000000000000092 Lane, S. (2018). Overview of the results from the 5 year follow up study of the CyPass Microstent. Retrieved from ESCRS Scientific Presentation: Lavia, C., Dallorto, L., Maule, M., Ceccarelli, M., & Fea, A. M. (2017). Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis. PLoS One, 12(8), e0183142. doi:10.1371/journal.pone.0183142 Leahy, K. E., & White, A. J. (2015). Selective laser trabeculoplasty: current perspectives. Clin Ophthalmol, 9, 833-841. doi:10.2147/opth.S53490 Nazarali, S., Damji, F., & Damji, K. F. (2018). What have we learned about exfoliation syndrome since its discovery by John Lindberg 100 years ago? Br J Ophthalmol, 102(10), 1342-1350. doi:10.1136/bjophthalmol-2017-311321 Plateroti, P., Plateroti, A. M., Abdolrahimzadeh, S., & Scuderi, G. (2015). Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma: A Review of the Literature with Updates on Surgical Management. J Ophthalmol, 2015, 370371. doi:10.1155/2015/370371 Stein, J. D., Pasquale, L. R., Talwar, N., Kim, D. S., Reed, D. M., Nan, B., . . . Richards, J. E. (2011). Geographic and climatic factors associated with exfoliation syndrome. Arch Ophthalmol, 129(8), 1053-1060. doi:10.1001/archophthalmol.2011.191 Tekin, K., Inanc, M., & Elgin, U. (2019). Monitoring and management of the patient with pseudoexfoliation syndrome: current perspectives. Clin Ophthalmol, 13, 453-464. doi:10.2147/opth.S181444
Thorleifsson, G., Magnusson, K. P., Sulem, P., Walters, G. B., Gudbjartsson, D. F., Stefansson, H., . . . Stefansson, K. (2007). Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science, 317(5843), 1397-1400. doi:10.1126/science.1146554 Yaqub, M. (2012). Visual fields interpretation in glaucoma: a focus on static automated perimetry. Community Eye Health, 25(79-80), 1-8. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678209/pdf/jceh_25_79-80_001.pdf
Case 6 Exam:
Question 1: How many people globally are estimated to have pseudoexfoliation syndrome (Nazarali
2018)?
Answer A: 500,000-1,000,000
Answer B: 5 – 10 million
Answer C: 20 – 30 million
Answer D: 60 – 70 million
Answer E: 100 – 120 million
Question 2: On which of the following ocular structures would you not expect to find
pseudoexfoliative material deposition?
Answer A: Lens capsule
Answer B: Trabecular meshwork
Answer C: Pupillary margin
Answer D: Lens zonules
Answer E: Corneal epithelium
Question 3: Which of the following is not a known risk factor for pseudoexfoliation syndrome?
Answer A: Older age
Answer B: Male gender
Answer C: Living at a more northern latitude
Answer D: Increased UV exposure
Answer E: LOXL1 gene mutation
Question 4: Which of the following is not a systemic disease associated with pseudoexfoliation
syndrome?
Answer A: Alzheimer’s-like dementia
Answer B: Cardiovascular disease
Answer C: Renal artery stenosis
Answer D: Hypertension
Answer E: Obstructive sleep apnoea
Question 5: Cataract surgery for patients with exfoliation syndrome is typically no more difficult than
routine cataract surgery. True or false?
Question 6: Which of the following is not considered a MIGS procedure?
Answer A: ExPRESS shunt
Answer B: Trabectome
Answer C: iStent
Answer D: Hydrus micro-stent
Answer E: Xen gel stent
Question 7: Which of the following treatments does not increase aqueous humour outflow?
Answer A: Brimonidine
Answer B: Latanoprost
Answer C: Dorzolamide
Answer D: Pilocarpine
Answer E: Selective laser trabeculoplasty
Question 8: Which of the following pattern of visual field loss is least typical of glaucoma
Answer A: Nasal step
Answer B: Arcuate scotoma
Answer C: Generalized depression
Answer D: Unilateral hemianopia
Answer E: Paracentral scotoma
Question 9: What was the adverse event that lead to Alcon recalling its CyPass device?
Answer A: Endothelial cell loss
Answer B: Cataract progression
Answer C: Hypotony
Answer D: Choroidal detachment
Answer E: Endophthalmitis
Question 10: SLT produces an average decrease in IOP of approximately 30%. True or false?
Question 11: Which of the following MIGS procedures does not match with its intended target
drainage area?
Answer A: iStent = Schelmm’s canal
Answer B: CyPass Micro-stent = Suprachoroidal space
Answer C: XEN Gel Stent = Subconjunctival space
Answer D: Hydrus microstent = Subconjunctival space
Answer E: None of the above
Question 12: What is the primary purpose of mitomycin C in trabeculectomy surgery
Answer A: To reduce post-operative intraocular inflammation
Answer B: To prevent failure of the filter bleb due to scarring
Answer C: To reduce the amount of blood loss from the scleral incision
Answer D: To reduce the likelihood of post-operative hypotony
Answer E: None of the above
Question 13: With regard to the glaucoma hemifield test, which of the following is false.
Answer A: ‘Outside Normal Limits’ indicates statistically significant inferior-superior asymmetry
Answer B: It compares corresponding and mirrored areas in the temporal and nasal visual fields
Answer C: It cannot be used to diagnose glaucoma
Answer D: It is a measure of localised visual field loss
Answer E: It is available in both the Humphrey SITA 30-2 and 24-2 protocols
Question 14: In the Esfandiari study (2019), which analysed results from combined
phacoemulsification and trabectome surgery, which type of glaucoma was associated with a higher
success rate?
Answer A: POAG
Answer B: Chronic angle closure glaucoma
Answer C: Pigmentary glaucoma
Answer D: Pseudoexfoliative glaucoma
Answer E: Mixed mechanism
Question 15: Krukenberg spindle is the name given to any pigment deposition found on the
posterior surface of the cornea in patients with pseudoexfoliation syndrome. True or false?
Question 16: Which gene is most associated with PXF?
Answer A: CACNA1A
Answer B: POMP
Answer C: LOXL1
Answer D: AGPAT1
Answer E: RBMS3
Question 17: Which population group has the greatest prevalence of PXF (Nazarali 2018)?
Answer A: Scandinavian
Answer B: White South African
Answer C: Eastern Asian
Answer D: South East Asian
Answer E: Middle Eastern
Question 18: What is the length of an iStent?
Answer A: 2 mm
Answer B: 0.5 mm
Answer C: 0.02 mm
Answer D: 0.1 mm
Answer E: 1 mm
Question 19: Which of the underlined word(s) is untrue in the following statement about optical
coherence tomography? ‘Optical coherence tomography is an imaging technique that uses high-
coherence, near-infrared light of relatively long wavelength, to capture micrometre-resolution of
2D/3D images from within optical scattering media, which in our clinical setting is biological tissue.
Answer A: High
Answer B: Infrared
Answer C: Long
Answer D: Micrometre
Answer E: Biological
Question 20: There are better outcomes in performing cataract surgery in the early stages of PXG
than the later stages. True or false?
Question 21:In a patient with no angle closure or pupil block, which of the following treatments is
least likely to be used in PXF glaucoma?
Answer A: Topical ocular antihypertensives Answer B: Oral acetazolamide
Answer C: Laser trabeculoplasty
Answer D: Tube shunt surgery
Answer E: Trabeculectomy
Question 22: What percentage of prescriptions are not filled, or filled and not taken, in the United
States? (Fingeret 2018)
Answer A: 5%
Answer B: 12%
Answer C: 27%
Answer D: 41%
Answer E: 60%
Question 23: Which of the following is least likely to be a risk factor for POAG?
Answer A: Strong family history
Answer B: Age > 40
Answer C: Corneas thinner than 555 m
Answer D: European heritage
Answer E: Diabetes and hypertension
Question 24: Which artefact from automated perimetry is correctly matched with its cause?
Answer A: Lens rim - The patient’s corrective lens is decentered or set too far from the eye, the lens
rim may project on the visual field
Answer B: Cloverleaf visual field – If the patient stops paying attention and ceases to respond part-
way through the test or they are malingering
Answer C: High false positive rate - When a patient repeatedly responds when no test stimulus is
presented
Answer D: High false negative rate – When, on several occasions, a patient fails to respond to a
stimulus presented in a location when a dimmer stimulus was previously seen
Answer E: All of the above
Question 25: A diagnosis of pseudoexfoliation glaucoma cannot be made clinically and requires
further investigation including brain imaging and blood tests. True or false?