Sturge-Weber Syndrome Glaucoma

Sturge-Weber syndrome (SWS) is a congenital neurocutaneous syndrome characterized by facial port-wine hemangioma, ipsilateral leptomeningeal hemangioma, and ocular hemangioma, caused by somatic mosaic mutations in the GNAQ gene.
Glaucoma is the most important ocular complication in SWS, occurring in 30–70% of cases when the hemangioma involves the eyelid.
Approximately 60% are early-onset type (from birth to 4 years, mainly due to angle dysgenesis), and about 40% are late-onset type (after infancy, mainly due to elevated episcleral venous pressure), requiring different treatment strategies.
For early-onset type, trabeculotomy or goniotomy is selected; for late-onset type, medical treatment with aqueous suppressants is first-line therapy ¹⁾.
Choroidal hemangioma is frequently associated, and the risk of choroidal hemorrhage and retinal detachment during surgery is high, making surgical technique selection and preoperative preparation extremely important ¹⁾.
Although more refractory than developmental glaucoma, early good intraocular pressure control can preserve visual acuity.

1. Glaucoma Associated with Sturge-Weber Syndrome

Sturge-Weber syndrome (SWS), also called encephalotrigeminal angiomatosis, is a congenital neurocutaneous syndrome (phakomatosis). Its three main features are facial port-wine hemangioma (nevus flammeus) in the trigeminal nerve distribution, ipsilateral leptomeningeal hemangioma, and ocular hemangioma. In 1879, Sturge reported a case of facial hemangioma with buphthalmos, hemiplegia, and epilepsy, and in 1929, Weber established it as a syndrome.

The cause is a somatic mosaic mutation (post-zygotic mutation) of the GNAQ gene, which is not hereditary and mostly occurs sporadically ⁴⁾⁸⁾. It is thought to be due to abnormal vascular development caused by sympathetic nerve dysfunction during the fetal period. The incidence is rare, occurring in 1 in 50,000 births, with no racial or gender predilection ⁵⁾⁷⁾.

Roach Classification

SWS is classified into the following three types based on clinical features.

Classification (Roach)	Features
Type I (Classic)	PWS + neurological symptoms + glaucoma
Type II	PWS + glaucoma (no neurological involvement)
Type III (Rarest)	Meningeal angioma only

Epidemiology

Glaucoma is the most important ocular complication in SWS, and it has the highest incidence of glaucoma among phakomatoses ²⁾. When the eyelid is involved with hemangioma, glaucoma develops at a high frequency of 30–70%. Choroidal hemangioma occurs in about 40% of patients.

Based on the timing of onset, glaucoma is broadly divided into early-onset and late-onset types. About 60% are early-onset, occurring from immediately after birth to 4 years of age, with abnormal angle development as the main cause. The remaining 40% are late-onset, occurring after infancy, and are associated with elevated episcleral venous pressure and choroidal hemangioma. Onset is often before 10 years of age.

Q What is Sturge-Weber syndrome?

Sturge-Weber syndrome is a congenital neurocutaneous disorder characterized by the triad of facial port-wine stain in the trigeminal nerve distribution, ipsilateral leptomeningeal angioma, and ocular angioma. It is caused by a somatic mosaic mutation in the GNAQ gene, is not hereditary, and most cases are sporadic ⁴⁾⁸⁾. Neurological symptoms such as epilepsy (75–90% develop by age 3), intellectual disability, and hemiparesis, along with glaucoma (30–70%), are major complications. There are also type II (glaucoma only) and type III (meningeal angioma only) without the full triad. See the “Causes and Risk Factors” section for details.

2. Main Symptoms and Clinical Findings

Fundus photograph of Sturge-Weber syndrome

Zhang X, et al. Isolated diffuse choroidal hemangioma without systemic symptoms: a case report. BMC Ophthalmol. 2023. Figure 2. PMCID: PMC10324158. License: CC BY.

The right eye shows a diffuse darker red color compared to the fellow eye, with scattered yellowish-white lesions in the posterior pole. This corresponds to choroidal hemangioma discussed in the section “2. Main Symptoms and Clinical Findings.”

Subjective Symptoms

In early-onset type, lacrimation, photophobia, and blepharospasm are initial symptoms. Visual impairment occurs with increased corneal diameter and corneal opacity (buphthalmos). Haab striae, which are breaks in Descemet’s membrane, may be observed.

Late-onset type resembles primary open-angle glaucoma clinically, with few subjective symptoms in the early stage. As it progresses, visual field loss and decreased visual acuity occur.

Clinical Findings (Findings Confirmed by Physician Examination)

Ocular Findings

Glaucoma: The most important ocular complication, occurring at a high frequency of 30–70% when the eyelid is involved with hemangioma ¹⁾
Choroidal hemangioma: Occurs in about 40% of patients. The fundus appears diffusely red (tomato ketchup fundus). May cause exudative retinal detachment.
Fluorescein angiography findings: Early phase shows large choroidal vessel pattern, late phase shows hyperfluorescence of the entire tumor area.
Dilation and tortuosity of episcleral and conjunctival vessels: Observed as a sign of elevated episcleral venous pressure.
Angle findings (early-onset type): Angle dysgenesis with high insertion of the iris root.
Angle findings (late-onset type): Minimal angle abnormalities, but blood is often observed in the angle, suggesting elevated episcleral venous pressure.

Systemic Findings

Port-wine stain (nevus flammeus): Present at birth in the distribution of the first (V1) and second (V2) branches of the trigeminal nerve. Usually unilateral but can be bilateral⁷⁾. Becomes darker and thicker with age.
Epileptic seizures: Occur in about 80% of patients. 75–90% develop seizures by age 3. Seizures are seen in 95% of patients with bilateral leptomeningeal involvement.
Neurological symptoms: May include intellectual disability (about 50%), contralateral hemiparesis, and homonymous hemianopia. Cerebral cortical atrophy and calcification progress due to leptomeningeal angiomatosis.
Adult-onset cases: Cases with first seizure at age 55 have been reported⁵⁾. Atypical cases with port-wine stain outside the face may have delayed diagnosis.

3. Causes and Risk Factors

GNAQ Gene Mutation

SWS is caused by a somatic mosaic mutation in the GNAQ gene (chromosome 9q21.2, c.548G→A, p.Arg183Gln)⁸⁾. This mutation leads to constitutive activation of the Gαq signaling pathway, resulting in uncontrolled proliferation of endothelial cells and vascular malformations⁴⁾. Since it is a somatic mosaic mutation rather than a germline mutation, it is not hereditary. Molecular diagnosis requires biopsy of affected tissue (usually skin)⁴⁾.

Detection of GNAQ mutations is influenced by the affected tissue sample and analysis method, so molecular diagnosis should be interpreted in conjunction with clinical findings.

Risk Factors for Glaucoma

Port-Wine Stain Distribution and Risk

V1 area only: Glaucoma risk 6.7%

V2 area only: Glaucoma risk almost none

V1 + V2 areas: Glaucoma risk significantly increased to 31.8%

V1 + V2 + V3 areas: Neurological symptom risk increases 4-fold

Differences in Onset Timing and Etiology

Early-onset type (approximately 60%): Mainly due to abnormal development of the angle. Presents with buphthalmos and increased corneal diameter ¹⁾

Late-onset type (approximately 40%): Mainly due to increased episcleral venous pressure and involvement of choroidal hemangioma ¹⁾

Eyelid involvement: When the hemangioma extends to the eyelid, the incidence of glaucoma significantly increases

Bilateral PWS: More likely to be associated with SWS compared to unilateral PWS ⁷⁾

4. Diagnosis and Examination Methods

Diagnosis of glaucoma associated with SWS requires precise intraocular pressure measurement and examination of the anterior segment, angle, and fundus. In children, examination under general anesthesia is often necessary.

Ophthalmic Examination

Intraocular pressure measurement: In children, Goldmann applanation tonometry is often difficult; rebound tonometry (e.g., iCare) is useful. Care is needed in interpreting measurements due to corneal edema or thinning.
Anterior segment examination: Check for increased corneal diameter (normal newborn: approximately 10.5 mm), corneal opacity, and Haab’s striae (tears in Descemet’s membrane).
Gonioscopy: Essential for classifying the type of glaucoma and selecting treatment. In early-onset type, angle dysgenesis (high insertion of the iris root) is seen. In late-onset type, blood may be observed in the angle, suggesting elevated episcleral venous pressure.
Fundus examination: Evaluate optic disc cupping (enlarged cupping). If choroidal hemangioma is present, the fundus may appear diffusely red.

Diagnosis of Choroidal Hemangioma

Fluorescein angiography is useful. Early phase shows large choroidal vascular patterns, and late phase shows hyperfluorescence of the entire tumor area. Diffuse choroidal hemangioma may be difficult to identify on routine fundus examination.

Systemic examination

Head CT detects calcifications in the cerebral cortex. Even in neonates without calcifications, gadolinium-enhanced MRI can detect leptomeningeal angioma. SPECT for cerebral blood flow evaluation is also used as an adjunct.

Differential diagnosis

SWS is one of the phakomatoses and a representative disease causing choroidal hemangioma. Differentiation from other phakomatoses is important.

Disease	Characteristic ocular findings	Location of hemangioma/tumor
SWS	Choroidal hemangioma, glaucoma	Face + leptomeninges
von Hippel-Lindau disease	Retinal hemangioma (temporal periphery)	Retina, cerebellum, kidney
Neurofibromatosis type 1	Iris Lisch nodules	Cutaneous neurofibroma
Tuberous sclerosis	Retinal hamartoma	Brain, skin, kidney, heart

Klippel-Trenaunay-Weber syndrome also presents with cutaneous hemangiomas similar to SWS, but is distinguished by venous malformations of the limbs and hypertrophy of bone and soft tissue.

Q How is glaucoma in SWS diagnosed?

In patients with facial port-wine stains, regular ophthalmic examinations including intraocular pressure measurement are essential. In children, intraocular pressure measurement using a rebound tonometer, anterior segment examination (corneal diameter, corneal opacity, presence of Haab striae), gonioscopy (assessment of angle abnormalities), and fundus examination (evaluation of optic disc cupping, detection of choroidal hemangioma) are performed. Examination under general anesthesia is often necessary in children. In late-onset cases, the presence of blood in the angle or dilation of episcleral vessels is useful for differential diagnosis. Fluorescein angiography is essential for evaluating choroidal hemangioma, and head CT and contrast-enhanced MRI are performed for systemic evaluation.

5. Standard Treatment

Treatment of glaucoma associated with SWS requires different strategies depending on the age of onset and pathogenic mechanism.

Treatment of Early-Onset Type (Congenital/Infantile Onset)

Surgical treatment is necessary for congenital or infantile-onset glaucoma ¹⁾. Trabeculotomy or goniotomy is the first-line treatment ¹⁾. However, the success rate is lower compared to primary congenital glaucoma, and additional surgery is often required.

Trabeculectomy carries a risk of severe suprachoroidal hemorrhage or expulsive hemorrhage due to bleeding from the hemangioma. In general, the response to glaucoma surgery is poor, and trabeculectomy or tube shunt surgery is often required.

Treatment of Late-Onset Type (Onset after Infancy)

In older patients, because episcleral venous pressure is elevated, medical treatment is the first choice ¹⁾. Aqueous humor suppressants (beta-blockers, carbonic anhydrase inhibitors) are considered most effective. The intraocular pressure-lowering effect of prostaglandin analogs has been reported to be inconsistent.

Surgical Treatment (When Medications Fail)

When drug therapy or outflow reconstruction surgery is ineffective, trabeculectomy or tube shunt surgery may be considered¹⁾.

Filtration Surgery / Tube Shunt

Trabeculectomy: Outcomes may improve with the use of antimetabolites (mitomycin C). However, in SWS eyes, the risk of choroidal effusion and expulsive hemorrhage is very high¹⁾.

Ahmed device: Reported cumulative success rates of 79% at 24 months and 30% at 60 months.

Two-stage Baerveldt device: A report showed that all eyes achieved intraocular pressure below 21 mmHg at a mean follow-up of 35 months.

Pediatric GDD meta-analysis: Analysis of 1,221 eyes showed success rates of 87% (95% CI: 83-91%) at 12 months and 77% (95% CI: 71-83%) at 24 months⁹⁾.

Management of Intraoperative and Postoperative Complications

Choroidal hemorrhage/effusion: In cases with choroidal hemangioma, rapid intraocular pressure reduction carries a high risk of choroidal detachment and hemorrhage¹⁾.

Preventive measures: Preoperative intraocular pressure reduction with hyperosmotic agents, posterior sclerotomy, pre-placed scleral flap sutures, and additional tight sutures.

Device selection: Use of valved (Ahmed) or two-stage (Baerveldt) GDD reduces the risk of hypotony.

Cyclophotocoagulation: For refractory cases, cyclophotocoagulation (CPC) may be considered. A report showed that 10 of 16 eyes (62.5%) maintained intraocular pressure between 6 and 22 mmHg without complications (mean follow-up 8.87 years).

Advantages of the Two-Stage Technique

In the two-stage technique, a capsule is formed around the plate several weeks before the tube is inserted into the anterior chamber. This prevents excessive intraocular pressure reduction immediately after surgery and minimizes the risk of choroidal effusion and hemorrhage. This method is particularly useful in cases with choroidal hemangioma, such as SWS.

Netarsudil (Rho Kinase Inhibitor)

There are reports that netarsudil effectively lowers intraocular pressure in glaucoma associated with SWS even when added as a fourth- or fifth-line agent. It has a mechanism that promotes aqueous humor outflow from the trabecular meshwork.

Treatment of Choroidal Hemangioma

Diffuse choroidal hemangioma associated with SWS may require management in parallel with glaucoma treatment.

Asymptomatic cases: Observation
Visual impairment due to serous retinal detachment: Retinal photocoagulation, transpupillary thermotherapy (TTT), or photodynamic therapy (PDT) may be selected. However, PDT is not covered by insurance.
Diffuse choroidal hemangioma: Consider PDT or low-dose radiation therapy (approximately 20 Gy).
Exudative retinal detachment: Cryocoagulation is indicated. If the effect is insufficient, radiation therapy is performed.
Oral beta-blocker propranolol: There are reports of possible tumor shrinkage, but it is not covered by insurance.

Prognosis

Although more refractory than developmental glaucoma, if good intraocular pressure control is achieved early, vision can be preserved. However, if the choroidal hemangioma enlarges and causes exudative retinal detachment, cryocoagulation may not be sufficiently effective, leading to severe visual impairment.

Because the lesions involve the cornea, lens, retina, and nerve, achieving good vision is often difficult. The life expectancy of SWS patients is shorter than that of the general population, and bilateral leptomeningeal involvement leads to more severe neurological symptoms and a poorer prognosis.

Q What are the special considerations in glaucoma treatment for SWS?

The most important consideration is surgical complications related to choroidal hemangioma. In SWS, choroidal hemangioma is present in about 40% of cases, and rapid intraocular pressure reduction during glaucoma surgery carries a risk of choroidal effusion, hemorrhage, and retinal detachment ¹⁾. Preventive measures include preoperative administration of hyperosmotic agents, performing posterior sclerotomy, tight suturing of the scleral flap, and use of valved or two-stage drainage devices. Also note that alpha-2 receptor agonists (brimonidine) are contraindicated in children under 2 years of age ¹⁾. For details, refer to the “Standard Treatment” section.

6. Pathophysiology and Detailed Pathogenesis

GNAQ Mutation and Vascular Malformations

The underlying cause of SWS is a somatic mosaic mutation in the GNAQ gene (c.548G→A, p.Arg183Gln)⁸⁾. This mutation constitutively activates the Gαq signaling pathway, leading to uncontrolled proliferation of endothelial cells and vascular malformations⁴⁾. Because the mutation occurs in somatic cells early after fertilization, the distribution of mutant cells determines the diversity of clinical phenotypes (types I–III).

Mechanisms of Intraocular Pressure Elevation

The Glaucoma Clinical Practice Guidelines (5th edition) list the following five mechanisms for intraocular pressure elevation in SWS¹⁾.

Primary angle dysgenesis: Congenital developmental abnormality of the aqueous outflow pathway, a major cause of early-onset type
Schlemm’s canal atrophy: Structural abnormality of the aqueous outflow pathway contributing to intraocular pressure elevation¹⁾
Elevated episcleral venous pressure: Venous return is impaired by hemangiomas on the ocular surface and within the orbit, increasing resistance to aqueous outflow. This is the main cause of late-onset type¹⁾
Peripheral anterior synechia (PAS) formation: Neovascularization of the iris and angle can lead to secondary angle-closure glaucoma²⁾³⁾
Increased permeability of thinned vessel walls associated with choroidal hemangioma: Exudation from the choroid contributes to intraocular pressure elevation¹⁾

Histological Findings in Early-Onset Type (Angle Dysgenesis)

Histological examination of enucleated eyes has revealed the following findings, which are similar to those seen in primary congenital glaucoma.

Wide uveal trabecular meshwork
Ciliary muscle directly attached to the trabecular meshwork
Underdeveloped scleral spur
Anteriorly inserted iris root

In cases that develop in infancy, developmental abnormalities of the angle are considered the most important factor.

Mechanism of late-onset type (elevated episcleral venous pressure)

In cases that develop in late adolescence to adulthood, elevated episcleral venous pressure due to hemangioma is the main cause ¹⁾. Gonioscopy shows minimal angle abnormalities, but blood is often observed in the angle, correlating with elevated episcleral venous pressure. In this condition, aqueous humor suppressants are considered most effective, and medical therapy is the first-line treatment.

Other mechanisms

Premature aging of the trabecular meshwork: Proposed as a mechanism causing chronic open-angle glaucoma in young adults.
Pathology of choroidal hemangioma: Abnormal proliferation of blood vessels in the choroid produces a red to reddish-orange elevated lesion in the fundus. Those associated with SWS are often diffuse with indistinct borders, presenting a different clinical picture from solitary choroidal hemangioma.
Brain pathology: Leptomeningeal hemangioma causes venous stasis; initially, blood perfusion increases compensatorily, but subsequently cerebral blood flow and glucose metabolism decrease, leading to neuronal degeneration and atrophy.

Q Why do treatment methods differ between early-onset and late-onset types?

This is because the mechanisms of glaucoma development are fundamentally different between the two. In the early-onset type, congenital angle dysgenesis is the main cause, and there is a problem with the trabecular meshwork or angle structure itself, so angle surgery (trabeculotomy or goniotomy) that physically opens the outflow pathway is effective ¹⁾. In contrast, in the late-onset type, elevated episcleral venous pressure is the main cause, and the angle structure itself is relatively normal. When episcleral venous pressure is high, aqueous humor suppressants are most effective, and medical therapy is the first-line treatment ¹⁾. If medical therapy is ineffective, filtering surgery or tube shunt surgery that can bypass the episcleral venous system is considered. For details, see the section on “Standard treatment”.

7. Latest research and future prospects

In the management of glaucoma associated with SWS, future progress is expected in the following areas.

Molecular diagnosis of GNAQ somatic mosaic mutation: The GNAQ mutation identified by Shirley et al. in 2013 clarified the molecular basis of SWS and port-wine hemangioma ⁸⁾. In the future, early diagnosis and personalized treatment based on genetic testing are expected.
Two-stage glaucoma drainage device: The usefulness of the two-stage Baerveldt device has been reported as a method to reduce the risk of choroidal complications associated with conventional filtration surgery.
Netarsudil (Rho kinase inhibitor): As a drug that promotes aqueous humor outflow from the trabecular meshwork, its efficacy for glaucoma associated with SWS has been reported.
Importance of multidisciplinary collaboration: Long-term management of SWS requires collaboration among pediatrics, neurology, ophthalmology, dermatology, and psychiatry ⁶⁾. It has been reported that psychiatric complications affect surgical outcomes, and the importance of comprehensive care including psychological support is recognized.
Pulsed dye laser treatment for port-wine stains: Early initiation is recommended, but complete disappearance of skin discoloration is rare. The treatment outcome is better for the central forehead than for the central face.

8. References

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European Glaucoma Society. Terminology and Guidelines for Glaucoma, 5th Edition. PubliComm, Savona. 2020.
European Glaucoma Society. Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025.
Yeom S, Comi AM. Updates on Sturge-Weber Syndrome. Handb Clin Neurol. 2015;132:157-168. doi:10.1016/B978-0-444-62702-5.00011-1.
Yadav PS, Adhikari P, Mehta B, et al. Unmasking Sturge-Weber Syndrome in Adulthood: A Case with Extrafacial Port-Wine Stain and Delayed Neurological Symptoms. Ann Med Surg. 2024;86:3679-3682.
Ainuz BY, Wolfe EM, Wolfe SA. Surgical Management of Facial Port-Wine Stain in Sturge Weber Syndrome. Cureus. 2021;13(1):e12637.
Pathak BD, Sharma S, Adhikari A, et al. Sturge-Weber Syndrome with Bilateral Port-Wine Stain. Case Rep Pediatr. 2022;2022:2191465.
Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971-1979.
Stallworth JY, O’Brien KS, Han Y, Oatts JT. Efficacy of Ahmed and Baerveldt glaucoma drainage device implantation in the pediatric population: A systematic review and meta-analysis. Surv Ophthalmol. 2023;68(4):616-629.

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