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?