Review Article

Ocular Manifestations of the Sturge–Weber Syndrome

Kiana Hassanpour1,2, MD, MPH; Ramin Nourinia1, MD; Ebrahim Gerami1, MD; Ghavam Mahmoudi1, MD
Hamed Esfandiari3, MD

1Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical
Sciences, Tehran, Iran

2Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

ORCID:
Kiana Hassanpour: http://orcid.org/0000-0002-1788-7352
Ramin Nourinia: http://orcid.org/0000-0002-2630-1069

Abstract
Sturge–Weber syndrome (SWS) or encephalotrigeminal angiomatosis is a non-inherited
congenital disorder characterized by neurologic, skin, and ocular abnormalities. A somatic
activating mutation (R183Q) in the GNAQ gene during early embryogenesis has been
recently recognized as the etiology of vascular abnormalities in SWS. Approximately, half
of the patients with SWS manifest ocular involvement including glaucoma as the most
common ocular abnormality followed by choroidal hemangioma (CH). The underlying
pathophysiology of glaucoma in SWS has not been completely understood yet. Early onset
glaucoma comprising 60% of SWS glaucoma have lower success rates after medical and
surgical treatments compared with primary congenital glaucoma. Primary angle surgery
is associated with modest success in the early onset SWS glaucoma while the success
rate significantly decreases in late onset glaucoma. Filtration surgery is associated with
a higher risk of intraoperative and postoperative choroidal effusion and suprachoroidal
hemorrhage. CH is reported in 40–50% of SWS patients. The goal of treatment in patients
with CH is to induce involution of the hemangioma, with reduction of subretinal and
intraretinal fluid and minimal damage to the neurosensory retina. The decision for treating
diffuse CHs highly depends on the patient’s visual acuity, the need for glaucoma surgery,
the presence of subretinal fluid (SRF), its chronicity, and the potential for visual recovery.

Keywords: Choroidal Hemangioma; Glaucoma; Ocular Manifestations; Sturge-weber Syndrome

J Ophthalmic Vis Res 2021; 16 (3): 415–431

INTRODUCTION

Sturge–Weber Syndrome (SWS) or
encephalotrigeminal angiomatosis is a rare

Correspondence to:

Ramin Nourinia, MD. Labbafinejad Medical Center,
Department of Ophthalmology, Paidarfard St., Boostan
9 St., Pasdaran, Tehran 16666, Iran.
Email: ramin.retin@gmail.com
Received: 05-07-2020 Accepted: 08-04-2021

Access this article online

Website: https://knepublishing.com/index.php/JOVR

DOI: 10.18502/jovr.v16i3.9438

congenital disorder that mainly affects the brain,
skin, and eyes. The complete spectrum of SWS
is characterized by leptomeningeal hemangioma,
facial angiomatosis or port-wine stain (PWS), and
ocular abnormalities.[1]

Roach et al classified SWS into three types: Type
1 (the most common) includes leptomeningeal and

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How to cite this article: Hassanpour K, Nourinia R, Gerami E, Mahmoudi
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Sturge-Weber Syndrome; Hassanpour et al

facial angioma with or without glaucoma; Type 2
presents with facial angioma as the most prominent
manifestation with or without glaucoma, but no
brain involvement; Leptomeningeal angioma is the
only manifestation of Type 3, the rarest type, that is
frequently diagnosed by brain scans.[2]

SWS occurs sporadically with an incidence
ranging from 1 in 20,000 to 50,000 live births. No
race or gender predilection has been identified.
Despite a few familial clusters, SWS is considered
non-hereditary.[3]

Children with SWS usually present with PWS
or nevous flammeus as a congenital birthmark.
PWS occurs in 3 per 1,000 births as a red or
pink macula on the forehead, frequently unilateral.
However, only 5–15% of children with PWS show
other features of SWS.[4, 5] V1 or V2 distribution
of PWS, the original description of PWS, has
been recently challenged by Waelchli et al.[6]
They proposed that facial involvement follows
embryological vasculature rather than trigeminal
nerve distribution.[6]

Neurologic signs and symptoms including
seizure, headache, stroke-like episodes,
hemiparesis, visual field deficits, and cognitive
impairment variably present throughout life.
Seizure is often the initial neurologic presentation
in 80% of SWS patients, starting in the first year
of life.[7] Mental retardation is also a common
neurologic feature.[8, 9]

The eye is found to be affected in approximately
half of the patients with SWS. In the present review,
we aim to further discuss the ocular manifestations
of SWS with emphasis on glaucoma and diffuse
choroidal hemangioma (CH) as the two most
common ocular complications.

METHODS

We searched Medline using PubMed and
Google Scholar, reviewing articles published
between 1970 and 2020. Our keywords
included multiple combinations of “Sturge-Weber
Syndrome”, “glaucoma”, “pathophysiology”, and
“pathogenesis”. The following medical subject
headings (MeSH) were also used.

• Sturge-Weber Syndrome/complications*
• Sturge-Weber Syndrome/physiopathology*
• Sturge-Weber Syndrome/surgery*
• Sturge-Weber Syndrome/therapy*

• Disease Management*
• Glaucoma*/diagnosis
• Glaucoma*/etiology
• Glaucoma*/therapy
• Humans
• Intraocular Pressure/physiology*
• Sturge Weber Syndrome
• Syndrome, Sturge-Weber
The articles were reviewed and only articles

published in English language with available full-
texts were included in the present study.

Pathophysiology of SWS

Most SWS manifestations result from vascular
abnormalities. There are mainly two hypotheses
proposed primarily to explain vascular
malformations in SWS. The first hypothesis
assumes a genetic mutation affecting vascular
regulation during early embryogenesis, while
the second hypothesis emphasizes on the role
of a focal vascular dysplasia in the brain and
subsequent involvement of the overlying eye and
skin.

Shirly et al[10] found a somatic activating mutation
(R183Q) in the GNAQ gene which produces
a protein (G alpha subunit q) regulating the
signaling process that results in cell proliferation
and inhibition of apoptosis. The mutation is also
reported in the PWS blood vessels, either in
isolation or associated with SWS.[11–13] The sporadic
inheritance of the disease supports the occurrence
of a somatic mutation that does not affect the
germline. The primitive vascular plexus enters
the brain, skin, and eye in the first trimester.[14]
Therefore, somatic mutation within this interval
correlates well with the clinical signs of SWS.
Parsa et al proposed a local primary venous
dysplasia in the brain as the primary insult.
Consequently, collateral venous vessels transmit
venous hypertension to the overlying eye and
skin causing choroidal vascular anomalies and
PWS, respectively.[15] Parsa’s hypothesis does not
contradict the occurrence of a somatic mutation
like GNAQ, however, it is unable to completely
explain the bilateral PWS and absence of brain
involvement in some patients with SWS.[14]

Ocular manifestations

A significant portion of the patients with SWS
present with ocular involvement, especially

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Sturge-Weber Syndrome; Hassanpour et al

Figure 1. Left image shows conjunctival and episcleral abnormal tortuous vessels in a patient with Sturge-Weber syndrome.
Presence of blood in the Schlemm’s canal in gonioscopy of the same patient.

Figure 2. Left image shows diffuse choroidal hemangioma as diffuse dark and saturated red areas making “tomato-ketchup
appearance” in the fundus of a patient with Sturge-Weber syndrome. Severe exudative retinal detachment is evident in optical
coherence tomography images of the same patient.

glaucoma. Table 1 summarizes the ocular
manifestations of SWS [Table 1].[16]

Glaucoma

Glaucoma remains the most common ocular
complication of SWS, which occurs in 30–70%
of the patients. Glaucoma in SWS has a bimodal
presentation: early onset glaucoma in 60% of
the cases and late onset glaucoma in 40% of
patients. The mechanism of early onset glaucoma
is not determined yet but is attributed to abnormal
angle development. While the appearance of the
angle shares common abnormalities with primary
congenital glaucoma including the anterior iris
insertion to the trabecular meshwork (TM), direct
attachment of the ciliary muscles to the TM rather
than to the scleral spur, and increased opacification
of tissues of the angle,[17] the exact site of pathology
is not identified. Some distinct characteristics of
angle in SWS include flat iris insertion in some parts
of the angle,[18] prominent vascular loops at the
iris root, and the presence of blood in Schlemm’s

canal [Figure 1].[17, 19] In a histopathologic study,
Rosenbaum et al did not find any TM abnormality
with light and electron microscopic examination but
abnormal vessels were present in all of their four
cases.[20] The link between early onset glaucoma
and SWS could be explained with the fact that
SWS is primarily a vascular abnormality and there
is a strong body of evidence that suggests SC and
collector channels are developed from a venous
plexus in early weeks of gestation.[21] Therefore, it
is plausible to think that the resistance to outflow in
early onset glaucoma is located in the distal outflow
pathway. The less than favorable response to angle
surgery in these cases also supports more distal
pathology rather than TM. There is not enough
evidence regarding the role of elevated episcleral
venous pressure (EVP) in early onset glaucoma;
engorged vessels that are seen in adult onset
glaucoma have not been reported in early onset
glaucoma.

Since the collagen fibers are more elastic in
early years of life, these children often develop
secondary structural changes such as globe

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Sturge-Weber Syndrome; Hassanpour et al

Table 1. Summary of ocular findings in Sturge-Weber syndrome[16]

Orbital
General

Proptosis
Lids
Ptosis
Port-wine birthmarks of eyelid

Extraocular
Sclera

Nevoid marks or vascular dilation of the episclera
Large, anomalous vessels in the episclera
Dilation and tortuosity of episcleral vessels
Episcleral hemangiomas

Conjunctiva
Conjunctival telangiectasia
Conjunctival hemangiomas
Dilation and tortuosity of conjunctival vessels
Large, anomalous vessels in the conjunctiva

Intraocular
Anterior Segment

Increased corneal diameter
Iris discoloration
Telangiectasia of the iris with heterochromia
Dilation and tortuosity of the iris vessels
Sluggish pupils
Anisocoria or other disturbances in pupil reactions
Deep anterior chamber angle
Glaucoma
Ectopia lentis

Choroid
Choroidal hemangioma
Angioid streaks

Retina
Dilation and tortuosity of retinal vessels
Retinal arteriovenous aneurysm
Varicosity of retinal veins
Glioma
Retinal detachment
Central retinal vein occlusion

Optic Nerve
Arteriovenous angioma
Papilledema
Optic atrophy
Optic nerve cupping
Optic nerve drusen

Other
Strabismus
Nystagmus
Loss of vision
Cortical blindness
Abnormal visual field due to the lesions in visual pathway
Anisometropia

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Sturge-Weber Syndrome; Hassanpour et al

Table 2. Summary of important studies investigating different surgeries in the treatment of glaucoma associated with Sturge-
Weber syndrome

Author, year Surgery No. of eyes No. of
patients

Age at
surgery

(Mean ±±± SD,
and/or
range)

Outcome Length of
follow-up

(Mean ±±± SD,
and/or
range)

Wagner et al[40] 1988 Trabeculotomy
combined with
cyclotherapy

6 5 Three weeks
to nine years

All achieved
controlled IOP
Two patients

needed additional
surgery

Average 4.5
years From
three to eight

years

Iwach et al[38] Goniotomy[49]
Trabeculotomy[9]
Trabeculectomy[21]

20 eyes Early
onset 16 eyes
late onset

30 patients Not
separately
reported

Median stable
time for

goniotomy and
medical therapy
101 months. For
trabeculotomy 21

months For
trabeculectomy

23 months

Mean 10
years Range:
2–21 years

Olsen et al[39] 1998 Goniotomy
Trabeculotomy

12 4 14 Mean 10 ± 4
months Zero
days to four

years

IOP ≤ 22 mm Hg
in 66.7% of the
eyes after one or
more goniotomy
or trabeculotomy

5.4 years
Range: 1.4–15

years

Wu et al[44] 2017 Trabeculotomy ab
externo

34 32 Median (IQR)
= 3 months
(1.25, 6.75)

Cumulative
proportion of

overall success:
94.1%, 90.5%,

86.6%, 86.6%, and
86.6% at three
months, six

months, one year,
two years, and
three years,
respectively

Median (IQR)
= 15.5 months
(9.50, 25.50)

Irkec et al[37] 1999 Trabeculotomy
and guarded

filtration surgery

6 5 Between 23
days and 9

years

Lowered IOP in
five eyes; two
eyes needed

additional medical
therapy

6.3 Range:
2–11 years

Sood et al[46] 2017 Combined
trabeculotomy

and
trabeculectomy

22 20 Mean 18.64 ±
29.74 months

0.7–96
months

41.7% (10/24) of
eyes qualified and
modified qualified

success No
complete success

Mean SD
134.73 ±

67.77 months
61–288
months

Board and Shields[48] (1981) Combined
trabeculotomy

and
trabeculectomy

5 5 Two months
to fifteen
years

Despite
postoperative IOP

control, it
increased in three
patients who had
longer follow-ups
No additional
surgeries were

needed

Median 11
months 6–36

months

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Sturge-Weber Syndrome; Hassanpour et al

Table 2. Continued.

Author, year Surgery No. of eyes No. of
patients

Age at
surgery

(Mean ±±± SD,
and/or
range)

Outcome Length of
follow-up

(Mean ±±± SD,
and/or
range)

Agarwal et al[47] 1993 Combined
trabeculotomy

and
trabeculectomy

18 16 Mean 17.8
months
Range:

Birth–7 years

(≤22 mm Hg) in 11
eyes (61.1%)

42 months
Range: 1–8

years

Mandal et al[45] 1999 Combined
trabeculotomy

and
trabeculectomy

10 9 1.5 ± 3.0
years Range:
1 month–9

years

All eyes
maintained a

postoperative IOP
< 16 mmHg
without

medication

27.6 ± 16.4
months

Range: 12–64
months

Ali et al[49] 1990 Trabeculectomy 7 6 Mean 22.42
years Range:
7–38 years

Two eyes w/o
meds Four eyes
with meds One
eye needed

repeat
trabeculectomy

Nine months
to Nine years

Mohamed et al[54] 2018 Trabeculectomy
with MMC With

Ologen

10 10 8 8 3–5 years Complete and
qualified success
in 80% and 20%
in MMC, 70% and
20% in Ologen

12 months

Hamush et al[56] 1999 Ahmed glaucoma
valve implantation

10 9 10 days–25.5
years Only
three >10
years

Cumulative
probability of

success of 79%,
59%, and 30% at
24, 42, and 60

months,
respectively

Mean 910.5
days (SD 6
574.1 days)

Kaushik et al[57] 2019 Ahmed glaucoma
valve implantation

24 18 7.91 ± 5.02
Range: 1–15

Cumulative
probability of

success rate was
75%

2.12 ± 0.87
years

Budenz et al[58] 2000 Baerveldt
glaucoma

implantation

10 9 Six weeks
and thirteen

years

All eyes had
adequate IOP
control (≤21

mmHg) without
the need for
additional

glaucoma surgery

35 months
Range:
10–50

Amini et al[59] 2007 Molteno drainage
device

9 7 9.6 +/– 3.7
years Range:
5–17 years

The cumulative
probability of
success was
97.2% at 12

months, 78.02% at
24 months, and

43.34% at the final
follow-up

32 +/– 4.7
months
Range:
20–36
months

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Sturge-Weber Syndrome; Hassanpour et al

Table 2. Continued.

Author, year Surgery No. of eyes No. of
patients

Age at
surgery

(Mean ±±± SD,
and/or
range)

Outcome Length of
follow-up

(Mean ±±± SD,
and/or
range)

Audren et al[55] 2006 Non-penetrating
deep sclerectomy

9 9 Eleven
days to

twenty-four
years

Success rates
(including no
need for

anti-glaucoma
medications) were
56%, 28%, and 0%
at 6, 13, and 26
months post
surgery

26.3
months

Range: 6–48
months

Table 3. Summary of important studies investigating different treatment strategies in diffuse choroidal hemangioma associated
with SWS. Only studies with more than three cases were included

Author, year Treatment modality No. of eyes Age at surgery (Mean
±±± SD, and/or range)

Outcome

Randon et al[76] 2018 External beam
radiotherapy (20 Gy in

10 fractions)

26 eyes of 25 patients Five years (4–41) years Reduced tumor
thickness (4.5 mm, 2.7
mm at the last visit)
Resolved retinal
detachment in all

except two
Schilling et al[77] 1999 External beam

radiotherapy (20 Gy)
15 eyes of 12 patients

with diffuse CH
18.3 years Exudative RD

resolution Shrinkage
of the tumor was seen

in five eyes
Arepalli et al[82] 2013 Plaque brachytherapy

(Iodine-125 plaque)
5 eyes 13 years Median 11

Range: 11–27 years
Complete regression
of SRF in all cases

Zografos et al[81] 1998 Proton beam
radiotherapy

6 eyes with diffuse CH Not reported Resolution of
exudative RD tumor

regression

enlargement, tears in Descemet’s membrane, and
corneal edema.

Elevated EVP secondary to episcleral and
choroidal vascular abnormalities contribute to late-
onset glaucoma. EVP normally ranges between
8 and 10 mmHg. The exact relationship between
chronic EVP rise and IOP is yet to be determined;
however, chronically untreated elevated EVP
can increase the IOP and remains the primary
mechanism of glaucoma in etiologies like carotid-
cavernous fistula, thyroid ophthalmopathy, and
late-onset glaucoma in SWS. In support of this
pathophysiology, Phelps et al[18] investigated EVP
in 12 patients with SWS. The mean EVP (±SD) was
18.1 ± 6.4 mm that was significantly higher than an
average of 9.1 ± 1.6 mm Hg in the normal fellow
eyes. Subsequently, Shiau et al[22] confirmed their

findings in 22 eyes with SWS. The possible role
of SC and collector channels dysfunction which
could potentially exacerbate the effect of high EVP
in adult glaucoma has not been evaluated.

Accelerated aging of the angle structures has
been reported in pathological investigations of
late-onset glaucoma. First proposed by Cibis
et al, a similar mechanism like primary open-angle
glaucoma is also considered as the underlying
mechanism.[17] It is not clear if these changes are
primary or develop in response to long-term high
IOP.

Angle closure glaucoma has also been reported
in SWS, although significantly less common
than open-angle mechanism. Murayama et al[23]
reported a 14-year-old boy with unilateral acute
angle closure glaucoma secondary to posterior

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Sturge-Weber Syndrome; Hassanpour et al

scleritis in SWS. They postulated swelling of the
ciliary body, choroidal effusion, anterior rotation
of the ciliary processes, and swelling of the lens
to be the underlying mechanism of angle closure.
Ectopia lentis[24] and angle neovascularization
secondary to retinal pathologies[25] have been
reported to contribute to angle-closure glaucoma
in SWS.

Diagnosis

All infants born with PWS should undergo thorough
and frequent ophthalmic examinations. Repeat
ophthalmic examinations every few months during
the first years of life are recommended. IOP
measurement in all sessions is mandatory even
if the angle structure appears normal. If no sign
of glaucoma is detected, an annual ophthalmic
checkup is recommended.[26]

The risk of glaucoma is associated with the
pattern of PWS and is estimated to be 25% with
a large unilateral PWS and 35% with bilateral
involvement.[27, 28] It is notable that nearly 40% of
SWS patients have bilateral PWS.[29]

Glaucoma treatment

Glaucoma management in SWS is challenging
and depends on the onset of the disease and
the underlying pathophysiology. While medical
therapy is usually tried as first-line therapy for early
onset glaucoma, surgery is ultimately needed for
the majority of the patients. Medical management
remains the first choice in the late-onset glaucoma
in SWS.

Medical treatment

Aqueous suppressants (beta-blockers and
carbonic anhydrase inhibitors) and the outflow
facilitators such as prostaglandin analogs have
been successfully used. Agents lowering EVP are
the potential future drugs that are not currently
available.[22] Awad et al[30] reviewed 22 eyes
with mostly early onset glaucoma (20 eyes) and
found that antiglaucoma medications successfully
controlled the IOP in only seven eyes of five
patients within 62 months of follow-up. Van Emelen
et al[31] retrospectively reviewed the records of 19
SWS patients with the mean age of 8.2 years.
Eight patients developed glaucoma (eight eyes

with early onset glaucoma vs one eye with late-
onset glaucoma). Seven out of eight patients
(87.5%) treated by beta-blockers and carbonic
anhydrase inhibitors needed glaucoma surgery to
lower the IOP. Latanoprost is the most frequently
investigated hypotensive agent.[32–34] Yang et al[34]
used latanoprost in six SWS glaucoma with the age
ranging from 4 to 19 years. Only two eyes that had
juvenile onset glaucoma responded to latanoprost
with a mean IOP reduction of 8.8 mm Hg. Similarly,
Altuna et al[32] investigated latanoprost in 18 SWS
patients with the mean age of 19.7 ± 12.4 years and
reported a success rate of 16.7% (3 of 18 patients) at
the six-months follow-up. The causes for failure in
this study were glaucoma surgery (seven patients),
additional medical therapy (three patients), and
intolerable conjunctival hyperemia (one patient).

In another study by Ong et al, 17 eyes with
SWS glaucoma who started on latanoprost were
retrospectively evaluated. The mean age of the
patients at the onset of glaucoma diagnosis and
the latanoprost start was 2.59 and 6.8 years,
respectively. Fifty percent of the patients achieved
successful outcomes after one year. However,
treatment failure was reported as early as one
month after the start of latanoprost in five (29.4%)
patients.[33]

Wagnanski et al[35] investigated the effect of
oral propranolol (2 mg/kg) on IOP in four SWS
infants with age ranging from 8 to 44 weeks.
Despite IOP reduction at one week after the
initiation of the treatment, IOP increased to an
average of 20.7 (range 14–30) mmHg after one
month. Subsequently, Kaushik et al[36] used oral
propranolol (2 mg/kg divided into two doses) one
week before glaucoma surgery in SWS patients.
These studies indicate that while oral propranolol
temporarily lowers the IOP and can potentially be
useful perioperatively, it is not suitable for long term
in SWS glaucoma.

Surgical treatment

In glaucoma unresponsive to medical treatment,
the choice of surgery needs to be decided on
a case by case basis. Some surgeons prefer
angle surgery as the primary operation in early
onset glaucoma.[39, 40] While the exact pathology
of early onset glaucoma in SWS is not determined,
several studies reported favorable outcomes with
goniotomy or trabeculotomy.[37–40] Angle surgery

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Sturge-Weber Syndrome; Hassanpour et al

removes the resistance at the level of TM and
enhances the outflow through the physiologic
pathways.

Studies investigating goniotomy or
trabeculotomy as the initial surgical procedure
report modest efficacy. Iwach et al[38] reviewed
angle surgery in 20 eyes with early onset and 16
eyes with late-onset SWS glaucoma. They reported
the median stable time after a single goniotomy to
be eight months in early onset glaucoma. However,
it increased to nearly nine years after multiple
goniotomies and adjunctive medical therapy.
They found significantly shorter stable period in
patients older than four years after goniotomy.
Furthermore, trabeculectomy was performed in
21 eyes and achieved a stable duration interval
with a median of 26 months. Additionally, 40% in
the early onset and 17% in the late-onset group
experienced choroidal effusion. Considering the
higher rates of complications after trabeculectomy,
the authors recommended goniotomy as the initial
surgical choice in early onset SWS glaucoma. In
another study by Olsen et al,[39] 16 eyes of 14
patients with SWS glaucoma were studied. All
patients were under four years of age. Twelve
eyes underwent goniotomy while four eyes
received trabeculotomy. Two-third of patients in
the goniotomy group and half of the patients in the
trabeculotomy group required a second procedure.
One or more angle procedures resulted in IOP
control in 66.7% of the patients after a median
follow-up of 5.4 years. Wu et al[41] retrospectively
reviewed the clinical outcomes of trabeculutomy
ab externo in 34 eyes with SWS glaucoma. The
median age of patients at the time of surgery
was three months. Complete (without any need
for further glaucoma medications) and qualified
(with the use of topical medications) success was
achieved in 86.6% and 66%, respectively, with
a median follow-up of 15.5 months. The authors
concluded early diagnosis of glaucoma in SWS
patients might lead to higher surgical success
after trabeculotomy ab externo. Nevertheless,
angle surgeries in SWS glaucoma achieve lower
success rates compared with primary congenital
glaucoma.[42] Most individuals will need further
surgeries or adjunctive medications to achieve the
target IOP.[43] Lower success rate of angle surgery
in SWS indicates resistance in more distal outflow
pathway. Wu et al[44] showed that individuals
with multiple episcleral vascular abnormal
networks responded poorly to trabeculotomy

compared to individuals with a simple episcleral
vascular abnormal network. Their study supports
a role for vessel-related factors in early onset
glaucoma. Gonioscopy before any angle surgery
is recommended in SWS to look for the landmarks
of the angle as well as the presence of blood in
the SC. The risk of intraoperative or postoperative
hyphema varies between 25% and 88.2% after
trabeculotomy in different studies.[37–39, 41]

Combined trabeculotomy/trabeculectomy as
the initial operation has been suggested in
early onset glaucoma to address more distal
resistance.[45–48] Recently, Sood et al[46] reported
combined trabeculotomy/trabeculectomy in 24
eyes of 20 patients with SWS glaucoma with the
overall success rate of 41.7% within 134.7 ± 67.7
months follow-up. Board and Shields investigated
combined trabeculotomy/trabeculectomy in five
SWS patients with the age ranging from 2 months
to 15 years. Median length of follow-up was 11
months. Three patients with a longer duration of
follow-up experienced IOP increase, however,
none of the patients underwent additional
surgeries. In another study, the records of
combined trabeculotomy/trabeculectomy was
reviewed in 10 eyes of which 9 had early
onset SWS glaucoma with the mean age of
1.5 ± 3 years. Postoperative IOP remained
<16 mmHg in all patients within the mean
follow-up period of 27.6 ± 16.4 months.[45]
Similarly, Agarwal et al[47] investigated combined
trabeculotomy/trabeculectomy in 18 eyes with
SWS glaucoma. Eleven eyes (61.1%) had IOP ≤22
mm Hg after a mean follow-up of 42 months. Three
patients underwent repeat surgeries.

Trabeculectomy remains an important surgical
option in late-onset glaucoma associated with
SWS. Ali et al[49] reported favorable outcomes
with trabeculectomy in six patients with late-onset
glaucoma (mean age of 22.4 years) in nine months
to nine years of follow-up. Nevertheless, four
patients needed additional medical treatment and
one patient underwent repeat trabeculectomy.
In SWS patients, there is a serious risk of
choroidal effusion or expulsive hemorrhages
after trabeculectomy. Iwach et al[38] reported
intraoperative choroidal effusions in 24% of cases
undergoing trabeculectomy including 40% of five
cases in the early onset group and 17% of 12 cases
of the late-onset group. Direct communication
between the arteriolar system and choroidal
vasculature, without any intervening vascular

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Sturge-Weber Syndrome; Hassanpour et al

bed, results in a high choroidal vascular pressure.
This high pressure is opposed by an increased
IOP associated with increased EVP. When the
IOP is reduced during the filtration surgery, the
unopposed high choroidal vascular pressure
causes choroidal effusion.[38]

The mechanism underlying choroidal effusion
is similar to effusion formation observed with
significant IOP reduction after glaucoma surgery,
which results in rapid transudation of fluid from
the intravascular spaces into the extravascular
space.[50] However, faster formation, more massive
effusions, and higher prevalence are observed
after filtration surgeries in patients with SWS.[48, 51]
Accordingly, the presence of CH poses the
eyes at a greater risk of both intraoperative or
postoperative choroidal effusions. Pandey et al[52]
reported that 83.3% of the eyes that developed
choroidal effusion had CH. Regardless of CH,
higher choroidal vascular pressure and also
vascular abnormalities such as abnormal vascular
innervation[7] and significant fragility[51] make these
patients more susceptible to choroidal effusion or
hemorrhage.

To reduce the risk of choroidal effusion or
expulsive hemorrhage, various modifications
during surgery have been reported. Prophylactic
posterior sclerotomy has been traditionally used
by many surgeons.[43] However, Eibschitz-
Timoshi et al questioned the need for
sclerotomy after investigating 17 eyes undergoing
trabeculectomy.[53] The authors reported
no significant suprachoroidal hemorrhage
and effusion in surgeries with modern
techniques. Measurements such as generous
use of viscoelastic devices for AC formation,
maximum preoperative IOP control, prophylactic
radiotherapy or laser photocoagulation of the CH
are recommended to prevent the suprachoroidal
hemorrhage.[43]

In a randomized clinical trial, Mohamed et al
compared the outcomes of Mitomycin-C (MMC)
augmented trabeculectomy and collagen matrix
implant (Ologen) in the management of glaucoma
in SWS.[54] Twenty eyes of 16 SWS glaucoma
patients with the age ranging from three to five
years were divided into two groups. Complete
and qualified success accounted for 80% and
20%, respectively, of patients in the MMC
group after one year, while the corresponding
values in the Ologen group were 70% and 20%,
respectively. Complications in the MMC group

included polycystic bleb in six patients, blebitis in
one patient, and shallow anterior chamber in two
eyes. Despite failure in 10%, the complication rate
was minimal in the Ologen group. While physical
spacers could improve the long-term outcomes of
bleb function, these biodegradable implants could
simultaneously act as physical resistance against
overfiltration in the early postoperative days
which is beneficial in offsetting suprachoroidal
hemorrhage in SWS patients.

Non-penetrating surgeries like deep
sclerectomy serve as alternatives to
trabeculectomy. These modalities hypothetically
lower the risk of choroidal effusion because of
lower fluctuation of IOP during the procedures.
Audren et al[55] investigated non-penetrating deep
sclerectomy in a series of nine eyes. The success
rates without additional need for medical treatment
were 56%, 28%, and 0% at 6, 13, and 26 months
after surgery, respectively. However, two eyes
developed choroidal effusion after NPDS.

Glaucoma drainage devices have been
effectively used in SWS glaucoma. Hamush et al
implanted Ahmad glaucoma valve (AGV) in 11 SWS
glaucoma patients.[56] The cumulative probability
of success was 79%, 59%, and 30% at 24, 42, and
60 months, respectively. Similarly, Kaushik et al
reported the results of AGV implantation in 24
eyes of 20 patients.[57] The cumulative probability
of success was 75% with a mean follow-up of 2.12
± 0.87 years. Reported complications included
intraoperative hyphema in four (16.67%) eyes,
hypotony in three (12.5 %) eyes, and choroidal
detachment in three eyes. Budenz et al studied
two-staged Baerveldt glaucoma implantation in 10
eyes of nine patients and reported adequate IOP
control in all operated eyes (≤21 mmHg) without
the need for additional glaucoma surgery.[58]

Amini et al investigated Molteno implantation
in nine eyes of seven patients.[59] The cumulative
probability of relative success was 97.2% at 12
months, 78.02% at 24 months, and 43.34% at the
final follow-up. Postoperatively, massive choroidal
effusion occurred in three patients which needed
surgical drainage. Two eyes experienced bleb
encapsulation and underwent needling bleb
revision with 5-fluorouracil. Visually significant
cataract and corneal endothelial touch prompting
tube repositioning occurred in two patients,
respectively.

Cyclodestructive procedures are usually limited
to the eyes with low visual potential or eyes at

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Sturge-Weber Syndrome; Hassanpour et al

higher risk of intraoperative complications.[40]
However, Van Emelen et al used it as the
primary surgical option in seven eyes with
SWS glaucoma.[31] The authors found that
cyclodestructive procedures reduced the IOP
to <22 mm Hg in six of the seven eyes with a mean
duration of 4.5 years. The presence of episcleral
hemangioma over the ciliary body makes the
procedure more challenging.[42]

Table 2 summarizes various surgical treatments
in the glaucoma associated with SWS.

Regardless of surgery types, patients need
frequent and close follow-up examinations.
Complications such as choroidal effusion and
hypotony should be treated accordingly because
chronically untreated choroidal effusions often
lead to bleb failure or reduced visual acuity.

Laser treatment of facial PWS raised the concern
of increasing IOP through the reduction of vascular
channels serving to balance the venous pressure
gradient.[15] Sharan et al retrospectively compared
28 cases that underwent facial laser treatment and
patients without laser treatment and did not find
any difference between groups in terms of newly
developed or exacerbating glaucoma.[60]

Choroidal Hemangioma (CH)

CH, arising from choroidal vasculature, is a
benign vascular tumor classified into two
types of circumscribed and diffuse. Diffuse
CH invariably correlates with SWS; patients with
SWS often develop a diffuse type of CH. However,
circumscribed CH has been occasionally reported
in SWS.[61, 62] The prevalence of diffuse CH is
40–50% and is usually ipsilateral to the PWS.[63]

Diffuse CH is often detected during funduscopy
as dark and saturated red area with the “tomato
ketchup” appearance. Symptomatic patients
present with reduced visual acuity, scotoma or
flashing, refractive error, serous or exudative
retinal detachment, macular edema, and retinal
pigment epithelium (RPE) alterations with macular
involvement.

Histopathologic investigations of diffuse CHs
show some differences with circumscribed CHs
and reveal containing considerable numbers of
the enlarged pre-existing vessel and vascular
channels lined with endothelium and complete
lack of cellular proliferation of vessel walls. Areas
of clustered vascular abnormalities mimicking

circumscribed types have also been reported in
diffuse hemangiomas.[64]

Diagnosis

Indirect ophthalmoscopy reveals the characteristic
pattern of the fundus, so-called tomato ketchup
appearance [Figure 2].[65] Ultrasound, both B-scan
and A-scan mode, is routinely used to confirm the
hemangioma diagnosis in SWS patients. Diffuse
thickening of the choroid in B-scan combined
with high internal reflectivity of A-scan spikes
confirms diffuse CH diagnosis.[66] Fluorescein
angiography, though difficult in children, shows
rapid and speckled hyperfluorescent areas in the
early phases due to the choroidal and vascular
nature of the tumor. Similar to the circumscribed
hemangiomas, though more widespread, staining
with or without late leakage appears in the late
phases.[67] However, FA is more helpful in adults
and patients with circumscribed CH. Indocyanine
green (ICG) angiography shows the extension,
vascularity, and arteriovenous shunts of choroidal
changes; but this is an invasive diagnostic modality
and may not be used in all cases especially in
children.[68]

Recently, enhanced depth optical coherence
tomography (EDI-OCT) has been employed in the
diagnosis of CHs and following their response to
treatment as well.[69] Diffuse choroidal thickening
in the involved eye and the fellow eye as well are
observed by EDI-OCT.[70] Surve et al investigated
the role of swept-source optical coherence
tomography (SS-OCT) in a large series of 34 eyes
of 17 SWS patients.[71] SS-OCT findings included
loss of choroidal vascular pattern, increased
choroidal thickness, and invisible sclerochoroidal
interface. The authors reported a detection
rate of 86.36% for SS-OCT compared with 50%
clinically, 52.94% with FA, and 82.35% with ICG
angiography. In addition, it has been shown that
the outer retinal layers may be thinner in SWS
patients with CH.[72] A recent study reported small
white dot-shaped “micro-drusen-like” changes of
the retina in patients with diffuse CH.[73]

Furthermore, Griffith et al showed ocular
enhancement in magnetic resonance imaging of
SWS patients consistent with diffuse CHs.[74] It has
been shown that the CH on MRI images looks like
sickle-shaped enhanced regions, thickest over the
posterior portion of the globe and thinner toward
the ciliary body.

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Sturge-Weber Syndrome; Hassanpour et al

The authors proposed MRI may play a
substantial role in the diagnosis of diffuse CH.
The advantage of MRI is that the children with
SWS require neuroimaging irrespective of ocular
findings that can be combined with ophthalmic
sequences.[75]

Management

The goal of treatment in patients with CHs is
to induce involution of the hemangioma, with
reduction of subretinal and intraretinal fluid
and minimal damage of neurosensory retina.
The decision for treating diffuse CHs highly
depends on the patients’ visual acuity, the
need for glaucoma surgeries, the presence of
SRF and its chronicity and the visual recovery
potential. Treatment of CHs may be difficult and
therapeutic modalities may be limited because
both juxtapapillary and foveal regions are often
involved. The main risk of surgery in these cases
is the increased risk of hemorrhage secondary
to abnormal dilated episcleral and choroidal
vasculature.

Various treatment modalities have been
investigated including laser photocoagulation,
plaque brachytherapy, external beam,
proton beam, and stereotactic radiotherapy,
photodynamic therapy (PDT), and anti-VEGF
injections. The primary goal of treatment remains
the resolution of SRF, however, treatment can also
lead to the shrinkage of the CH mass.

Radiation-based modalities including external
beam, plaque brachytherapy, proton beam, and
stereotactic are rapidly expanding techniques.
Randon et al investigated external beam
radiotherapy (20 Gy in 10 fractions) in a large
series (26 eyes of 25 patients) with diffuse CH.[76]
The treatment resulted in tumor regression; the
mean thickness reached from 4.5 mm at baseline
to 2.8 mm in the first year, and 2.7 mm at the
last visit. The retinal detachment was resolved
in all except two patients. Similarly, Schilling
et al reported the result of low-dose radiation
therapy in CH.[77] Their study included 15 eyes
of 12 patients with diffuse CH associated with
SWS. The resolution of retinal detachment (in all
patients) besides the shrinkage of the tumor (in
five patients) was observed. Many other small
case series reported the promising result of
EBRT.[78–80]

Other techniques of radiation have been
investigated in diffuse CH treatments. Proton
beam radiation delivers an exact dose of radiation
to a specific tissue. Zografos et al used the
proton beam to treat six eyes with diffuse CH.
They reported full resolution of the SRF in all of
the treated eyes.[81] Arepalli et al investigated
plaque brachytherapy in five cases with diffuse CH
associated with SWS.[82] Complete regression of
SRF was observed in all patients.

The main drawback of these technologies
remains the high cost and unavailability in many
hospitals. Furthermore, SRF generally resorbs
slower after radiation (over several months)
compared with PDT. Normal ocular tissues are
also exposed to radiation doses with subsequent
radiation-induced cataract, retinopathy, and optic
neuropathy. However, the latter disadvantage
occurs generally after EBRT and is reduced with
other radiation-based treatments.

PDT allows for selective occlusion of vascular
structures by photochemical destruction of
vascular endothelial cells. PDT with verteporfin
showed promising results for circumscribed
CH. Correspondingly, multispot treatment has
been applied in diffuse CH which causes
the atrophy of the hemangioma vessels and
reduces the leakage. Various isolated case
reports used PDT and consistently reported
complete resolution of SRF besides tumor
involution.[83–87] The main advantage of PDT
includes the selective nature of the treatment
preserving the overlying retinal vasculature and
RPE. Currently, no significant complication has
been reported with PDT. However, the studies
investigating PDT in diffuse CH are usually
small case series (to date <15 cases) that make
concluding difficult.

Some studies showed reduction of SRF after
intravitreal injection of anti-VEGF agents.[88]
However, the continuous production of VEGF
leads to unsuccessful long-term results with
anti-VEGF therapy.[89]

Oral propranolol therapy was investigated in
a few reports and revealed moderate effects in
the resolution of exudative retinal detachment.[90]
The mechanisms which have been proposed
for propranolol as a treatment modality for
hemangioma can be classified into short-, mid-
, and long-term effects. The most probable
cause of the short-term effect is vasoconstriction.

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Sturge-Weber Syndrome; Hassanpour et al

Blocking the release of proangiogenic factors
such as VEGF, bFGF, MMP-2, and MMP-9 may
lead to mid-term effects. The long-term effects
may be related to the induction of apoptosis
in endothelial cells and subsequent tumor
regression.[91, 92] Serious side effects such as
bradycardia and hypotension have been reported
in cases using high-dose systemic propranolol.
It has been shown that the intravitreal injection
of propranolol leads to higher concentration
of propranolol at the retinal level and lack of
systemic side effects in comparison to the
systemic usage of propranolol.[93, 94] The safe
dose of intravitreal propranolol was determined in
animal models and an experimental study showed
that the intravitreal injection of propranolol was
safe.[95] Intravitreal propranolol has also been
reported to be effective for the treatment of
retinal angiomatosis.[96] In addition, Nourinia
et al successfully treated two cases of SWS with
exudative retinal detachment secondary to diffuse
CH with an intravitreal injection of propranolol
(unpublished data).

Other Ocular Abnormalities

PWS presents in the face of most patients with
SWS. Vascular lesions on the eyelid, abnormal
vascular lesions of the conjunctiva, episcleral
hemangiomas, and dilated vessels of the retina
are variably present in SWS patients and all are
often ipsilateral to the PWS. Abnormal conjunctival
vessels may be diffuse or localized. The diffuse
type usually makes a pink or red hue in the affected
eye. Iris heterochromia may also be present and
is interestingly associated with a higher risk (45%)
of ipsilateral glaucoma development.[16, 97] Ocular
melanocytosis and iris mammillations have also
been reported in SWS.[61, 98] Combined cilioretinal
artery occlusion and hemiretinal vein occlusion was
reported in a nine-year old boy diagnosed with
SWS.[99]

Visual acuity results of 25 studies and visual
field results of 12 studies were systematically
reviewed to analyze the visual outcome of patients
with SWS. The authors reported that VA was
significantly reduced in 28% of eyes with glaucoma
and 67% of eyes with diffuse CH. However, 70%
of total SWS patients have normal visual acuity.
Homonymous hemianopia was the most commonly
reported visual field defect and was present in
approximately 40% of the patients.[100]

SUMMARY

As the SWS mainly affects the brain, skin, and
the eyes, a multidisciplinary approach including
the neurologic, ophthalmic, and dermatologic
evaluations are essential in the management
of the disease. All involved specialists may
face challenges in diagnosis, treatment, and
determining the prognosis in patients with SWS.
Considering the rare nature of the disease, most
studies focusing on SWS are small case series.

Currently, most patients with glaucoma
associated with SWS need surgical management.
Since the lower success rates are achieved in
these patients, the adjunctive medical therapy
and the need for repeat surgeries should also
be considered. The elucidation of the exact
mechanism of glaucoma as the most common
ocular complication can help better control of the
disease.

Elevated EVP as a possible mechanism in
the early onset glaucoma needs more clinical
and experimental investigations. If the role of
elevated EVP is further recognized, combined
trabeculotomy and trabeculectomy can serve
as the initial surgical procedure in the early
onset glaucoma. Moreover, medical interventions
targeting the EVP may have promising results.

The effect of SWS on the quality of life has
been investigated with emphasis on neurological
signs and symptoms[101] but the possible effect of
ocular complications on the quality of life of these
patients has not been evaluated. Furthermore, the
discovery of genetic mutations can be helpful
in diagnosis and management of SWS.[102]
Further recognition of mutations, the possible
molecular and cellular interactions and their
downstream proteins can be targeted as promising
treatments.[103] Biomarker development to detect
the association between clinical symptoms and
disease prognosis is another area of research.
Ocular involvement mostly diagnosed by optical
coherence tomography will be a part of the future
biomarkers.[104]

Financial Support and Sponsorship

Nil.

Conflicts of Interest

The authors do not have any conflicts of interest.

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Sturge-Weber Syndrome; Hassanpour et al

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