Group 1
Abnormal capillary network: Present between major arteries and veins.
Clinical significance: Lesions are small and usually asymptomatic. Intracranial involvement is rare.
Ocular symptoms of Wyburn-Mason syndrome
Key Points at a Glance
Section titled “Key Points at a Glance”1. What is Wyburn-Mason syndrome?
Section titled “1. What is Wyburn-Mason syndrome?”Wyburn-Mason syndrome (WMS) is an extremely rare non-hereditary congenital neurocutaneous disease characterized by arteriovenous malformations (AVM). It is also known as Bonnet-Dechaume-Blanc syndrome or racemose angiomatosis. It is classified as one of the phakomatoses.
The combination of retinal and cerebral AVMs with facial vascular changes was first described in 1932. In 1937, Bonnet, Dechaume, and Blanc reported two cases with similar findings. In 1943, R. Wyburn-Mason reported nine clinical cases, and the name has since become established.
Unilateral retinal-cerebral vascular malformation consisting of an intracranial AVM (especially near the thalamus and midbrain), ipsilateral retinal AVM, and ipsilateral facial skin vascular malformation. The inheritance pattern is unclear. Approximately 105 cases have been reported to date 2). Incidence and prevalence are unknown, with no racial or gender predilection.
In a narrative review of 34 case reports, the mean age at diagnosis was 15.6 years 1). The sex ratio was nearly equal (53% male, 47% female), with a mean age at diagnosis of 13.6 years for females and 17.4 years for males 1).
In the Cerebrofacial Arteriovenous Metameric Syndrome (CAMS) classification, WMS is classified as CAMS-2 2). CAMS-2 involves the maxilla, cheek, cerebral cortex, diencephalon, optic nerve, and retina.
Q
Is Wyburn-Mason syndrome an inherited disease?
A
This syndrome is a non-hereditary congenital disorder. No specific gene or inheritance pattern has been identified. It is presumed to be caused by sporadic abnormalities in vascular development during the embryonic period.
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”Subjective Symptoms
Section titled “Subjective Symptoms”The clinical presentation of WMS varies depending on the number, location, and type of AVMs. Although present from birth, symptoms may first appear in the 20s or 30s in some cases.
The breakdown of chief complaints in a review of 34 cases is as follows1).
- Decreased vision: Most common, accounting for 59% of all cases. It was the sole complaint in 50%.
- Headache: 14%. Some cases are accompanied by seizures or hemiparesis.
- Asymptomatic: 12%. Discovered incidentally.
- Strabismus: 6%.
- Proptosis: Presents as unilateral protrusion due to orbital AVM.
Other reported findings include abnormally dilated conjunctival vessels, ptosis, nystagmus, nerve palsy, and color vision abnormalities.
Clinical Findings
Section titled “Clinical Findings”Retinal AVMs are classified into three groups by Archer et al.1)
Group 2
Absence of capillary bed: No capillary network between arteries and veins.
Clinical significance: Risk of retinal edema, hemorrhage, and vision loss. Low risk of intracranial involvement.
Group 3
Extensive and complex AVM: Consists of dilated, tortuous large vessels with indistinguishable arteries and veins.
Clinical significance: High risk of visual impairment. Highest likelihood of intracranial AVM association, and is a requirement for formal diagnosis of WMS.
Retinal AVM may involve the entire retina (29.8%) or be localized to one or more quadrants (70.2%). Orbital AVM is present in 61.5% of cases.
Major ocular complications associated with retinal AVM include:
- Retinal hemorrhage: Occurs in 28.1% of cases.
- Retinal vein occlusion: Found in 17.5% of cases.
- Vitreous hemorrhage: Occurs in 10% of cases.
- Secondary glaucoma: Caused by neovascularization or elevated episcleral venous pressure.
- Optic atrophy: Results from mechanical compression of the optic nerve.
- Macular edema: May appear as intraretinal edema without vascular occlusion.
- Retinal detachment: Rhegmatogenous retinal detachment has been rarely reported.
Ocular findings include optic atrophy, neovascular glaucoma, macular edema, vitreous hemorrhage, retinal detachment, as well as proptosis, conjunctival telangiectasia, color vision impairment, exotropia, and limited eyelid opening.
Q
What kind of visual impairment occurs?
A
Small AVMs are often asymptomatic. Large AVMs can cause significant vision loss due to retinal ischemia. Causes of visual impairment include obstruction of the visual field by the AVM, choroidal infarction, vascular occlusion, optic disc edema, and optic atrophy. Risk is particularly high in group 3 of the Archer classification.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”The exact cause of WMS is unknown. It is presumed to result from sporadic vascular developmental abnormalities occurring before the 7th week of gestation in the primitive vascular mesenchyme, developing optic cup, and anterior neural tube1)2). Therefore, retinal AVMs and intracranial AVMs tend to occur on the same side1).
This syndrome has the following characteristics:
- No specific genes or inheritance patterns have been identified.
- There is no predilection for any race or sex.
- No known risk factors have been reported.
- No recommended preventive measures exist.
Retinal AVMs tend to grow slowly, but growth may accelerate during pregnancy, menarche, or after trauma.
4. Diagnosis and Testing Methods
Section titled “4. Diagnosis and Testing Methods”Diagnosis of WMS is based on thorough clinical examination. The coexistence of group 3 AVM and intracranial AVM is a diagnostic requirement for WMS. Because skin symptoms are less common than in other phakomatoses, diagnosis is often delayed until late childhood.
The main examination methods are shown below.
| Examination method | Main role | Usage rate |
|---|---|---|
| Dilated fundus examination | Detection of retinal AVM | 94%1) |
| MRI | Intracranial AVM evaluation | 62%1) |
| OCT | Long-term follow-up | 41%1) |
- Dilated fundus examination: Confirms unilateral tortuous and dilated retinal vessels. This is the most basic test, performed in 94% of patients in a narrative review 1).
- Fluorescein angiography: Shows rapid filling of vascular abnormalities without significant leakage. Used in 35% of patients 1). Also useful for detecting smaller lesions.
- Optical coherence tomography (OCT): Visualizes inner retinal and photoreceptor layers, recommended for long-term follow-up 1). Also useful for detecting macular edema and serous retinal detachment.
- Brain MRI: Evaluates the location, size, mass effect, and edema of intracranial AVMs. If retinal AVM is detected, exclusion of intracranial AVM is mandatory.
- Cerebral angiography: The gold standard for demonstrating the feeding arteries and draining veins of intracranial AVMs 1). Due to invasiveness, usually limited to preoperative planning in symptomatic patients.
- Ultrawide field imaging: Can be captured with non-contact fundus camera and is advantageous for pediatric patients as it does not require sedation 1).
Retinal racemose hemangioma is a high-flow dilated arteriovenous anastomosis with no fluorescent leakage from the abnormal vessels. When associated with Wyburn-Mason syndrome, a non-hereditary malformation, brain and orbital contrast MRI is necessary to confirm cerebral and brainstem AVM.
Differential Diagnosis
Section titled “Differential Diagnosis”- Sturge-Weber syndrome
- Von Hippel-Lindau disease
- Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia)
- Retinal capillary hemangioma
- Familial retinal arteriolar tortuosity
5. Standard Treatment
Section titled “5. Standard Treatment”Management of WMS is generally conservative. Most retinal AVMs are stable, and observation is the mainstay of treatment.
In a narrative review, 50% of 22 cases with documented management strategies were managed conservatively 1). Cases with no changes in retinal and cerebral AVMs over 27 years of follow-up have also been reported 1).
Retinal racemose hemangioma is not a true tumor but a congenital retinal arteriovenous anastomosis. It is usually not an indication for photocoagulation.
When Treatment Intervention Is Needed
Section titled “When Treatment Intervention Is Needed”Indications for active treatment include visual impairment or an annual rupture rate of the AVM exceeding 2.2%1)2).
- Catheter embolization: Minimally invasive with few complications, and is most recommended for treatment of orbital AVF and intracranial AVM2). It occludes the feeding artery using a liquid embolic agent (ethylene vinyl alcohol copolymer)2).
- Surgical resection: Performed for certain intracranial AVMs. It is considered optimal for AVMs smaller than 3 cm1).
- Radiation therapy: Options include linear accelerator, Gamma Knife, and CyberKnife. However, there is a risk of endocrine dysfunction affecting the hypothalamic-pituitary axis, making it undesirable for children1).
Management of Retinal AVM Complications
Section titled “Management of Retinal AVM Complications”- Retinal neovascularization and neovascular glaucoma: Treated with panretinal photocoagulation (PRP).
- Macular edema: Intravitreal injection of anti-VEGF agents (bevacizumab, ranibizumab) has been reported to be effective1). There is also a report that posterior sub-Tenon triamcinolone injection reduced cystoid macular edema1).
- Vitreous hemorrhage: If it does not resolve within a few weeks, consider vitrectomy.
- Tractional retinal detachment: This is an indication for vitrectomy.
Q
Why is observation without treatment sometimes chosen?
A
Most retinal AVMs are stable and have a low risk of bleeding 1). On the other hand, treatment interventions themselves carry risks of bleeding and complications, so observation is chosen if there are no symptoms. For intracranial AVMs, regular monitoring is recommended if the annual rupture rate is 2.2% or less 1).
6. Pathophysiology and Detailed Mechanisms
Section titled “6. Pathophysiology and Detailed Mechanisms”AVMs in WMS are direct connections between arteries and veins without an intervening capillary bed. High-flow arterial blood enters the veins without passing through normal capillary beds, causing turbulent flow within the vessels.
This turbulence causes the following conditions.
- Vascular wall damage: The elasticity of the blood vessel wall decreases, and vascular sclerosis progresses. The tendency for aneurysm formation increases.
- Thrombosis and vascular occlusion: Ischemia occurs downstream of the occluded vessel.
- Steal phenomenon: Blood shunting to the AVM reduces blood flow to surrounding arteries and tissues.
Histological findings of AVM include irregularly thickened muscle layers in the arterial and venous walls. Interstitial hemorrhage may also be present.
Pathology in the Retina
Section titled “Pathology in the Retina”Retinal AVMs cause secondary changes due to hemodynamic alterations, leading to reduced blood flow to the peripheral capillary bed.
Venous occlusion results in progressive ischemia, leading to the following complications:
- Rubeosis iridis
- Retinal neovascularization
- Neovascular glaucoma
The mechanism of macular edema is debated. It is thought that high intraluminal pressure not mediated by capillaries causes back pressure in the capillaries surrounding the malformation, leading to leakage. Additionally, retinal ischemia due to steal phenomenon may upregulate VEGF.
Intracranial Pathology
Section titled “Intracranial Pathology”Intracranial AVMs are most commonly located in the midbrain, followed by the thalamus, hypothalamus, optic chiasm, and suprasellar region 1). AVMs in the occipital lobe may cause visual symptoms and headaches. Cerebral hemisphere AVMs can lead to homonymous hemianopia.
7. Latest Research and Future Prospects (Investigational Stages)
Section titled “7. Latest Research and Future Prospects (Investigational Stages)”Intravitreal injection of anti-VEGF drugs
Section titled “Intravitreal injection of anti-VEGF drugs”In a narrative review by Shameem et al. (2024), three cases (two with bevacizumab, one with ranibizumab) who received intravitreal anti-VEGF injections were reported 1). Bevacizumab contributed to improvement of intraretinal fluid and neurosensory retinal detachment, leading to visual acuity improvement. Ranibizumab was used for exudation from a retinal arterial macroaneurysm and was effective.
The exact mechanism by which anti-VEGF drugs reduce macular edema is unknown, but it is presumed to involve decreased vascular permeability and increased tight junction proteins.
CyberKnife treatment
Section titled “CyberKnife treatment”Liu et al. (2012) used CyberKnife (30 Gy) for an orbital AVM (distal right ophthalmic artery), but the treatment was unsuccessful and vision deteriorated significantly 1). This report suggests that surgical resection is optimal for AVMs smaller than 3 cm, and that complication rates increase for those larger than 6 cm.
Advances in wide-field fundus imaging
Section titled “Advances in wide-field fundus imaging”Non-contrast ultrawide field colour imaging does not require sedation and has been reported for use in children as young as 3 years old1). It is attracting attention as a new modality useful for screening and long-term follow-up of pediatric patients.
8. References
Section titled “8. References”- Shameem Y, Irshad S, Mirza N, Hassan N. Wyburn-Mason Syndrome: A Narrative Review. Cureus. 2024;16(8):e68070.
- Vaithialingam B, Gopal S, Sohrab M. Catheter Embolization of an Orbital Arteriovenous Fistula in a Patient With Wyburn-Mason Syndrome. Cureus. 2023;15(3):e36949.
- Arredondo-Cardona SD, Contreras-Duque N, Martínez-Blanco AM, Bonilla-Escobar FJ. RETINAL RACEMOSE HEMANGIOMA ASSOCIATED WITH INTRACRANIAL VASCULAR MALFORMATION (WYBURN-MASON SYNDROME). Retin Cases Brief Rep. 2026;20(1):70-73. PMID: 39666838.