Key words
pseudotumor cerebri - idiopathic intracranial hypertension - headache
Introduction
In 1904 the German neurologist Max Nonne introduced the term pseudotumor cerebri (PTC)
to describe the clinical syndrome of chronically elevated intracranial pressure of
unknown etiology. As diagnostic options grew broader and more effective over time,
however, numerous pathological conditions that can cause chronically high intracranial
pressure were identified, which occasioned its classification into a primary and secondary
form.
For years the term pseudotumor cerebri has been used as an umbrella term for chronic
intracranial hypertension without further specifying its underlying cause. Pseudotumor
cerebri has a primary form, idiopathic intracranial hypertension (IIH), and various
secondary forms that can co-occur with other diseases, such as cerebral venous sinus
thrombosis or hormonal changes[1]
[2]. The following review is limited to the primary form of PTC.
The prevalence of IIH is 8.6 cases per 100 000 in the general population [3]
[4], although the number is probably much higher considering that existing epidemiological
studies are several decades old and apply different diagnostic criteria. Moreover,
because the clinical presentation of IIH can be so similar to other primary headache
disorders such as migraine or tension-type headache, especially their chronic forms,
the disease may be underdiagnosed [5]
[6]. Furthermore, most persons suffering from IIH are overweight [7]
[8]; against the backdrop of increasing worldwide obesity, the prevalence of IIH is
also assumed to be growing [9]. In approximately 90% of adult cases, IIH affects women of reproductive age [10], although the relationship to gender is largely unclear. No such gender-specific
differences have been observed in children suffering from IIH, especially young, prepubertal
children [11]
[12]
[13].
Pathophysiology
The production and absorption of cerebrospinal fluid (CSF) is finely balanced. IIH
was initially thought to be caused by an overproduction of CSF, a belief now largely
refuted, which is why current research is focused on the absorption of CSF and venous
drainage.
In IIH, patients are usually very obese, intracranial pressure is clearly correlated
with BMI, and weight loss is the most effective treatment option. These facts suggest
that obesity-related high intra-abdominal and intrathoracic pressure increases cerebral
venous pressure and reduces the absorption of CSF, ultimately causing intracranial
pressure to rise. Even as plausible as this hypothesis may seem, several questions
remain to be answered. It does not explain female preponderance, especially because
women, unlike men, tend to accumulate fat around the hips rather than the abdomen.
Moreover, the majority of obese women do not suffer from IIH, and unlike adults, children
with IIH are usually not at all overweight. Obesity alone can therefore not sufficiently
explain the underlying pathomechanism of IIH [13].
This has led to speculation over the last several years that various hormonal factors
may be the link between obesity and IIH. Therefore, the role of hormonal processes
that occur in adipose tissue receive increasing attention [14]
[15]. In IIH patients, for example, the serum leptin concentration is significantly higher
than in obese control subjects, pointing the discussion to central leptin resistance
[16]
[17]. Interestingly, leptin concentration in the affected patients is higher in women
than in men, and hence this mechanism might explain why women are particularly affected
by IIH. It is also known that sex hormones, especially androgen, are markedly altered
in IIH patients. Because its availability is regulated by 11ß-hydroxysteroid dehydrogenase
type 1 (11ß-HSD1), the potential role of glucocorticoids, especially cortisol, is
also discussed. 11ß-HSD is especially active in adipose tissue and increased activity
boosts cortisol production. Cortisol’s effect on glucocorticoid and mineralocorticoid
receptors could increase the production of CSF [15]. This mechanism could not only explain the development of intracranial hypertension
but also the female preponderance. However, current data does not suffice to draw
specific pathophysiological conclusions.
Another hypothesis posits that one or more transverse sinus stenoses (TSS) impede
venous drainage, and like the previously described mechanism, cause intracranial pressure
to rise. In support of this hypothesis, TSS was identified in approximately 90% of
adult IIH patients, and in cases of bilateral TSS, endovascular treatment of the stenoses
may alleviate or eliminate IIH [18]
[19]
[20]. In contrast, hemodynamic models show that only bilateral TSS are able to block
drainage enough to significantly impair CSF absorption [21]. Neither can this mechanism explain why predominantly women are affected by IIH.
It is also far from clear whether TSS are primary or secondary, i. e., from external
compression due to elevated intracranial pressure, because TSS in IIH are usually
very prolonged and in some cases remit after pressure is relieved. If the genesis
is secondary, TSS may still induce a vicious circle: high intracranial pressure could
cause TSS, which could trigger or worsen a drainage block, thus impairing CSF absorption
even further and thereby increasing intracranial pressure. Ultimately this would lead
to a further secondary increase in TSS and could further aggravate the clinical picture.
Because endovascular treatment could break this vicious circle, its efficacy cannot
help to differentiate between primary and secondary TSS.
Clinical Presentation and Diagnostics
Clinical Presentation and Diagnostics
Due to increasing diagnostic options, especially imaging procedures, diagnostic criteria
for IIH have been modified several times over the past decades. The current diagnostic
criteria from Friedman et al. are based on a modified version of the Dandy criteria
[1]. According to these criteria the presence papilledema; an unremarkable neurological
examination except for cranial nerve disorders (especially paresis of the abducens);
a cMRT without structural lesions, signs of hydrocephalus or meningeal enhancement;
physiological CSF composition; and opening pressure of ≥25 cm CSF in adults and ≥
8 cm CSF in children (in non-sedated children of normal weight ≥25 cm) are required
for the diagnosis of IIH [1]. A novelty in the current version of the diagnostic criteria is the possibility
to diagnose IIH even in the absence of papilledema if uni- or bilateral abducens paresis
is present. If both, papilledema and abducens paresis are absent, a definitive diagnosis
is not possible, however a probable diagnosis can still be made if cMRT reveals an
empty sella, a flattened posterior aspect of the optic globe, a distended perioptic
subarachnoid space (with or without a tortuous optic nerve) and a transverse sinus
stenosis [1].
Nevertheless, leaving the diagnostic criteria aside, the clinical presentation is
characterized primarily by headache, impaired vision and a number of other symptoms
including cranial nerve palsies, olfactory disturbances, cognitive deficits, and tinnitus.
Headache
Up to 90% of IIH patients suffer from headache, which is the most commonly reported
symptom and the main impetus for the initial medical consultation [7]
[22]. IIH-associated headache is defined in the diagnostic criteria of the International
Headache Society (ICHD 3 beta) [23]. A definitive diagnosis requires an elevated opening pressure of >25 cm CSF concurrent
with headache that meets two of the three following criteria: Headache has developed
in temporal relation to IIH or led to its discovery, headache is relieved by reducing
intracranial hypertension, and headache is aggravated in temporal relation to increase
in intracranial pressure. In contrast to the 2004 headache criteria (ICHD-2), the
current criteria no longer require headache relief after a reduction in intracranial
pressure [23]. This change was absolutely essential in light of the fact that many patients can
continue to suffer from chronic headache for a long time after pressure has been reduced
and intracranial pressure normalized [24].
The clinical presentation of IIH-associated headache is extremely variable, which
is why the clinical characteristics of headache were removed from the diagnostic criteria
and mentioned only briefly in the comments [23]. The headache is typically described as a bilateral frontal or retro-orbital pressure
and occurs almost daily [23]
[24]. Patients often report worsening with coughing, straining, sneezing or physical
exertion [24]. The headache can also be unilateral, have a throbbing character and may even be
accompanied by nausea as well as photo- and phonophobia, making it very difficult
to differentiate it from other primary headache disorders such as chronic migraines
[7]
[24]
[25].
Visual disorders
IIH patients frequently suffer from visual disorders. These are primarily caused by
pressure-induced papilledema, which can be identified in the overwhelming majority
of patients and may be localized uni- or bilaterally [7]
[26]
[27]
[28]. Given that IIH can occur without concomitant papilledema, it has been removed as
a mandatory diagnostic criteria in the new IIH diagnostic criterion [1] and in those for IIH-associated headache (ICHD C beta) [23].
Papilledema induced by chronic intracranial pressure is usually progressive and causes
numerous visual disorders. The most frequently reported visual disorders include obscurations,
an enlarged blind spot, an inferior arcuate visual field defect, photopsias, and a
loss of visual acuity [7]
[27]. As the accompanying papilledema, which is their main underlying cause, visual disturbances
are progressive and can cause irreversible deficits that may lead to complete blindness
if effective pressure-reducing treatment is not initiated as soon as possible. Pathophysiologically,
the chronic increase in pressure in the CSF space leads to an elevated pressure in
the optic nerve sheaths resulting in an abnormally high pressure on the optic nerve
tissue. This increased pressure reduces the pressure gradient between the intraocular
and CSF pressure, which physiologically proceeds centripetally from the eye [29]
[30]. This decreases axoplasmic transport, which in turn causes axonal swelling in the
intrabulbar segment of the optic nerve [30]. The retrobulbar segment, where the nerve fibers are myelinated, is not affected.
A prelaminar compression of the small, especially venous, capillaries develops secondarily
to this axonal swelling. These alterations can also lead to other phenomena such as
small hemorrhages in the area of the papilla. Ultimately the changes described cause
atrophy in the papilla and irreversible loss of optic nerve function [30]. Imaging techniques can reliably identify both the macroscopic and the microstructural
changes resulting from the increased pressure in the area of the optic nerve sheaths
[31]
[32]
[33].
No correlation has been observed between the degree of papilledema and the headache
[34]. This may be due to the physiological narrowness of the connection between the intracranial
subarachnoid space and the optic nerve sheaths, which is also deemed responsible for
the occasional several-day latency between acute increases in intracranial pressure
and the development of papilledema [30]. Moreover, intracranial pressure is subject to physiological changes over the course
of a day, which cannot have short-term effects on the optic nerves owing to the aforementioned
narrowness. Even if this would be the case, it would take a longer amount of time
to influence axonal transport and cause visual consequences. Nonetheless there are
signficant correlations with longer-term parameters. For example, the severity of
the papilledema and loss of visual acuity correlate with the incidence of therapy
failure [35]. The same is true for evidence of hemorrhages in the area of the papilla, which
can already be present with mild visual impairment [36].
In light of the frequency and potential irreversibililty of the visual deficits and
their serious long-term impact on quality of life, the diagnostic work-up for a suspected
IIH should always include a comprehensive ophthalmological assessment with funduscopy
and perimetry. There has been increasing discussion over recent years as to the value
of optical coherence tomography (OCT) in diagnosing IIH. OCT is a non-invasive procedure
that enables, among other things, objective, high-resolution measurement of the thickness
of the retinal nerve fiber layer (RFNL). The application of OCT in IIH appears very
attractive at first, especially to monitor progress, which can prove useful in individual
cases [37]
[38]. An OCT measurement, however, says nothing about the condition of the tissue. For
example, in papilledema an initially measured thickening of the RFNL can normalize
over the course of the disease, yet it remains unclear whether this normalization
is due to a decrease in axonal swelling or the development of papillar atrophy [39]. OCT can therefore augment an ophthalmological examination with funduscopy and perimetry,
but certainly not replace it.
In addition to the diagnostic procedures cited, transorbital sonographic measurement
of the diameter of the optic nerve sheaths is becoming more important in the diagnosis
of intracranial hypertension, because this procedure offers another non-invasive and
rapid method for identifying distended optic nerve sheaths and thus supports diagnosis
[40]
[41]
[42]
[43]. To obtain reliable results, however, the examiner must have extensive experience
with this procedure. Due to the relatively low specificity of the procedure, a transorbital
sonographic examination is no substitute for a funduscopic examination and even less
for the other diagnostic tests (imaging, CSF pressure measurement).
Cranial nerve palsies
Cranial nerve palsies are observed relatively frequently with IIH. In most cases the
abducens nerve is affected, yet palsies may also occur in the oculomotor [44], trochlear [45], trigeminal [46] or facial [47] nerves, or even simultaneously in multiple cranial nerves [48]. The cranial nerve palsies usually abate after effective treatment of the elevated
CSF pressure [47]
[49], so the overall prognosis for these attendant symptoms is commonly good.
Abducens palsy is always accompanied by horizontal double vision and can occur uni-
or bilaterally, as is the case in the other cranial nerve palsies. Abducens palsy
occurs in nearly 10–20% of adult cases of IIH [50], yet its incidence in children could be significantly higher [51]. IIH patients with an attendant abducens palsy more frequently tend to have a higher
BMI and a higher CSF pressure compared to patients without cranial nerve palsy [51]. It is not exactly clear why abducens nerve palsy develops in IIH, but it is speculated
that the brainstem suffers a discrete downward displacement due to the chronic increase
in intracranial pressure, which puts traction on Dorello’s canal near the abducens
bridge, damaging the nerves [51]. This pathomechanism could also adequately explain why abducens paresis frequently
occurs bilaterally in IIH. Similar mechanisms are assumed to underlie the other IIH-associated
cranial nerve alterations.
Olfactory dysfunction
Olfactory dysfunction in IIH has been known for several years [52]
[53]. Approximately 80% of IIH patients suffer from hyposmia, although it is usually
mild or moderate, which is probably why it was overlooked for so long. In a clinical
study with 17 IIH patients and 17 age- and sex-matched healthy controls, Kunte et
al. systematically investigated the occurrence of olfactory impairment in IIH using
so-called “sniffin sticks”. This test measures odor threshold, discrimination, and
identification and can be used to assess them individually and to calculate a TDI
score. The study was able to demonstrate that odor discrimination and identification
were significantly impaired in the majority of patients. The authors also demonstrated
that the patients most affected were those diagnosed within the prior three months
and who experienced significant clinical deterioration in those three months. This
subgroup also evidenced a reduced odor threshold [53].
The underlying mechanisms have yet to be elucidated. Nonetheless, structural changes
in the olfactory nerve are known to occur [54]. In this regard, it was shown that IIH patients, especially those in an early stage
of the disease, had reduced olfactory bulb volume [54]. This is most probably the structural correlate for the frequently verifiable functional
deficit [55]
[56]
[57]. It remains unclear whether the reduced olfactory bulb volume is simply the direct
result of the increased intracranial pressure. The fact that relieving pressure through
a lumbar puncture considerably improves olfactory function in a short time suggests
that this may be the case [58].
Tinnitus
IIH patients frequently report uni- or bilateral pulsatile tinnitus [7]. The underlying cause of this alteration remains unclear. The most popular hypothesis
assumes that pulsatile tinnitus could arise from one or more TSS. It is postulated
that audible turbulences in the blood flow occur due to the vascular narrowing. This
hypothesis is supported by the fact that invasive elimination of the stenosis using
an intravascular stent frequently resolves the tinnitus. In a prospective study of
29 IIH patients with TSS and pulsatile tinnitus who were treated with a stent placed
in the transverse sinus, Boddu et al. demonstrated that in all treated patients the
tinnitus remitted on the day of the intervention. During the two-year follow-up phase,
10% of patients were restenosed when the tinnitus reappeared. Even though these data
offer strong support for a causal relationship, other studies must be conducted to
validate this pathophysiological connection especially because the number of IIH patients
with stenosis who experience pulsatile tinnitus is unknown as is the number of IIH
patients with tinnitus who have a TSS.
Cognitive deficits
Indications of cognitive deficits in IIH have been increasing for several years. The
assumption was first based on case reports and small clinical studies in which individual
cognitive domains were examined [59]
[60]
[61]. In a prospective study, Yri et al. showed that patients with IIH frequently suffer
from a global cognitive dysfunction. The most severe deficits were found in processing
speed and reaction time [62]. The exact mechanism that causes the identified deficits remains unclear. The deficits
could conceivably be the direct result of the increased intracranial pressure, however
even after intracranial pressure is normalized through adequate treatment, the cognitive
deficits commonly persist at least at the three-month follow-up [62]. Therefore, some evidence points to cognitive deficits having more complex and long-lasting
causes than simple mechanical compression from increasing intracranial pressure. Because
patients with IIH often experience a depressed mood during their illness, which in
itself can impair cognitive function, it cannot be ruled out that this kind of connection
also underlies the described association. In spite of the currently available data,
however, further prospective studies with longer follow-up phases are urgently needed,
because the cognitive deficits significantly reduce the quality of life and are an
essential burden for social participation and occupational reintegration. For these
reasons, and especially because it remains unclear if the deficits are reversible,
a diagnostic evaluation of IIH should also include neuropsychological testing for
early detection of cognitive dysfunction.
CSF diagnostics
The clinical work-up for IIH requires a lumbar puncture to measure the opening CSF
pressure. Not only should the opening pressure be measured, but the CSF composition
should be analyzed to rule out any secondary causes. To prevent any influence on the
measurements, pressure is measured with the patient in supine position and in an unsedated
state. According to the current diagnostic criteria, an opening pressure of ≥25 cm
CSF in adults ≥28 cm CSF in children is considered pathological [1]. CSF pressure can vary widely, even during the course of a day. If there is a justifiable
suspicion of a PTC, a second lumbar puncture should be considered under certain circumstances
depending on clinical symptoms [63]. Temporary continuous pressure measurement may be necessary in rare and justified
cases [64]
[65]. The CSF composition should be unremarkable [1].
Magnetic resonance imaging (MRI)
MRI has gained increasing importance in diagnosing IIH over the last several years
and should be an essential component of the diagnostic evaluation. First it is required
to rule out diseases that can cause a secondary increase in intracranial pressure
as well as to identify IIH-specific changes. The most significant IIH-associated changes
in a cerebral MRI include an empty sella, a flattened posterior aspect of the optic
globe, a distended perioptic subarachnoid space with or without a tortuous optic nerve,
and the presence of uni- or bilaterally localized TSS [1]
[33]
[66]
[67]
[68]. Based on the fact that TSS are verifiable in up to 90% of IIH patients and may
play a causative role, an MR venography (MRV) should also be conducted in addition
to a structural MRI [19]. The MRV not only allows to identify a TSS but more importantly it can also rule
out sinus or cranial vein thromboses. This is particularly signficant because thromboses
can also occur as clinically inapparent microthromboses that could still impede venous
drainage and thus increase intracranial pressure and, in some circumstances, lead
to further secondary TSS from the external pressure [20]. It is not yet clear whether TSS is the cause or the consequence of intracranial
hypertension.
To sum up, however, it should be noted that changes identified in the MRI can substantially
support the diagnosis of an IIH but due to their sensitivity and specificity current
MR techniques can by no means replace lumbar puncture and measurement of the CSF opening
pressure.
Treatment
The principal aims of IIH treatment are the preservation of visual acuity and the
relief of headache. Treatment should always follow a multimodal approach consisting
primarily of effective weight loss augmented by pharmacological treatment with carboanhydrase
inhibitors. Invasive therapeutic procedures such as fenestration of the optic nerve
sheaths, endovascular procedures and shunt systems should be used only in treatment-resistant
cases, especially if the risk of visual loss is significant.
Weight loss
Considering the highly significant correlation between obesity and chronic intracranial
hypertension, weight loss should always be the main component of treatment. Numerous
studies have now shown that weight loss significantly reduces intracranial pressure,
papilledema, the associated visual disturbances and headache [69]. Even small changes can have a major influence on the course of the disease. Interestingly,
this is also true for patients whose weight is initially normal [8]. Successful weight loss must always be carefully monitored to ensure it is maintained,
because regaining of weight is associated with an increased recurrence of IIH [70]. If weight loss cannot be maintained in the severely obese, surgical intervention
through bariatric surgery should be considered, although the invasivity of this procedure
warrants restricting it to treatment-resistant cases [71].
Lumbar puncture
The lumbar puncture is the essential component of the diagnostic workup of IIH. Due
to its invasiveness, however, its importance in the treatment of IIH is only secondary.
It can still be considered as a bridging measure prior to an endovascular or surgical
intervention in treatment-resistant situations where vision loss is imminent.
The sudden drop in intracranial pressure induced by the lumbar puncture usually temporarily
relieves the headache, although strictly speaking this observation has not yet been
proven in any prospective clinical study. The same is true for the effect of the acute
drop in pressure on other IIH-associated symptoms. Interestingly, the lessening of
headache intensity in some IIH patients lasts for several weeks, although the amount
of fluid drained is replaced after a few hours [72]. Even a puncture-induced leak persisting several days cannot sufficiently explain
this observation. It is feasible, however, that relieving the pressure reestablishes
a stable equilibrium between CSF production and absorption, thus reducing secondary
pressure-induced TSS and thereby improving venous drainage and CSF absorption [73]
[74]
[75]
[76]. Further studies are needed to confirm this hypothesis.
Pharmaceutical treatment
Carboanhydrase inhibitors form the first-line pharmaceutical treatment of IIH. Carboanhydrase
is localized in the choroid plexus and regulates the production of hydrogen carbonate
(HCO3
−) and hence CSF secretion [77]. Inhibiting this enzyme reduces CSF production [78] and therefore reduces CSF pressure [79].
Acetazolamide is the most frequently used carboanhydrase inhibitor in the treatment
of IIH, and the typical dose range is between 500–2 000 mg. Although administered
for many years to treat IIH, until recently the use acetazolamide had been based on
the results of open or uncontrolled studies without a placebo group [80]
[81]. The first randomized placebo-controlled study on the efficacy of acetazolamide
in treating IIH was conducted just a few years ago. The study showed that acetazolamide,
at the study dose of up to 4 g daily, improved papilledema, visual deficits, and headache
[82]. In spite of the relatively frequent gastrointestinal side effects, the treatment
significantly improved quality of life [83]. This clinical improvement in all the aspects cited continued throughout a follow-up
period of 12 months [84]. Acetazolamide brought about significant weight loss in the study, which probably
contributed substantially to its efficacy [82]
[85].
In cases where acetazolamide is not effective, tolerated, or contraindicated, topiramate
can be given as an alternative at a dose between 50–200 mg. To date, however, there
have been no randomized, placebo-controlled studies to verify its efficacy. Only a
few open studies without a placebo group suggest its efficacy in IIH [80]
[86]. Paresthesias, mood swings, and cognitive deficits are among the most frequent side
effects [87]. The essential mode of action is thought to be the inhibition of the carboanhydrase.
Topiramate frequently also leads to significant weight loss, however, thus likely
substantially contributing to its efficacy.
Furosemide is yet another pharmaceutical option. Furosemide also inhibits carboanhydrase,
thereby reducing CSF production and hence CSF pressure [88]. The dosage range for the treatment of IIH is usually between 30 and 80 mg a day.
There have been no randomized, placebo-controlled studies on its efficacy in the treatment
of IIH to date.
Besides the carboanhydrase inhibitors described, octreotide is showing promise for
use in IIH. This drug is a long-acting, synthetic somatostatin analog that also inhibits
the effect of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Existing
data suggest that octreotide could considerably improve papilledema and the associated
visual deficits as well as the headache [89]
[90]
[91]
[92]. Its efficacy thereby extends far beyond its known analgesic effect [93]. Its precise mode of action in IIH is unknown. The idea to use octreotide originated
from the observation that treatment with GH or IGF-1 could trigger a secondary PTC
[90]
[94]. However, the patients treated in the three cited studies suffered from IIH, i. e.,
there were no pathological hormonal changes present. All studies were open studies
or case reports, however, so further studies to test its efficacy are essential.
Endovascular treatment
An endovascular stent can be an effective treatment option in the case of one or more
verified stenoses in the transverse sinus [18]
[20]. The specific mode of action remains unclear, but it is assumed that eliminating
the TSS improves venous drainage, which in turn increases CSF absorption, ultimately
reducing CSF pressure [95]
[96]. In spite of the relatively good data on its efficacy, endovascular treatment should
be considered only in treatment-resistant cases. For one thing, the long-term data
on efficacy and safety is limited. Furthermore, complications such as stent displacement,
in-stent thrombosis, or sinus perforation with consecutive subdural hematoma are not
uncommon [97].
Fenestration of the optical nerve sheaths
This invasive procedure consists of an incision in the meninges surrounding the optical
nerve. The mode of action has not yet been elucidated. It is assumed that the incision
reduces the CSF pressure around the optic nerve, but it is not clear why this effect
persists even though the meningeal lesion heals after a short time, thereby eliminating
the CSF leak. Numerous studies have already proven the efficacy of fenestration in
reducing papilledema and its associated visual deficits, however data on its long-term
efficacy and safety are insufficient [98]
[99]. This intervention should therefore be considered only in particular treatment-resistant
cases where the risk of irreversible vision loss is high [6].
CSF diversion procedures
A shunt system aims to reduce pressure by circumventing the physiological CSF drainage
pathway. Either a ventriculoperitoneal or a lumboperitoneal shunt can be used, whereby
the former is preferable because it is associated with a lesser risk of side effects
and necessary shunt revisions [100]. Nonetheless, potentially dangerous side effects such as shunt infection or dysfunction
can occur with the procedure. Furthermore, data on long-term efficacy and safety are
sparse [101]. This data does suggest that in most cases placement of a shunt system positively
affects the visual deficits but not the headache. Furthermore, for a variety of reasons
more than half of the patients require a shunt revision [101]
[102]. Against this backdrop, this intervention should be considered only in treatment-resistant
patients with a significant risk of irreversible vision loss.
