Interesting Retinal Cases

Wyburn Mason syndrome also known as Bonnet-Bechaume-Blanc syndrome, Vascular Malformation Syndrome or Racemose Angiomatosis is a rare, non-hereditary congenital neurocutaneous disorder leading to arteriovenous malformations (AVMs).

The exact etiology is currently unknown however it is hypothesized that it is caused by a sporadic abnormality in the development of blood vessels during embryonic or fetal growth.²

The incidence and prevalence rates of this syndrome are currently unknown¹ and the disease does not have any racial or gender predilection, females and males are equally affected.²

General Pathology

Wyburn-Mason Syndrome presents with multiple blood vessels malformation of the brain, orbit, retina, and skin. It can affect the entire retina (29.8%) or be focal in one or more quadrants of the retina (70.2%).³ AVMs can occur in 61.5%.³ These lesions are direct artery-to-vein communications without a capillary system in between to mitigate the high-flow arterial blood. The resulting turbulence in the vessel can cause vessel wall damage, which may result in thrombosis and occlusion and proliferative complications such as rubeosis iridis, retinal neovascularization etc. This can also occur from areas of non perfusion (see peripheral non-perfusion on attached FA image) 

Retinal AVMs tend to grow slowly, but pregnancy, onset of menstruation and trauma can accelerate growth.⁴ Retinal hemorrhage and retinal vein occlusions are two of the most frequently occurring ocular complications of this syndrome.⁶ Macular edema is also a potential complication and is thought to occur secondary to elevated venous pressure and lack of capillaries which in turn causes the venous system to leak and cause retinal edema. Intra vitreal Anti-VEGF is sometimes used to treat macular edema as it decreases vascular permeability by increasing tight junctions thereby reducing leakiness of vessels. 

AVMs in the brain cortex can have visual manifestations. If present in the occipital lobe, visual symptoms and headaches may occur. The visual symptoms are typically brief and transient. Hemispheric AVMs can cause homonymous visual field defects. Diminished blood flow to cerebral visual territories can present as transient vision loss.^4,5

Diagnosis

The diagnosis of Wyburn-Mason syndrome is made by clinical examination. Dilated funduscopic exam can reveal the typical appearance of arteriovenous malformations of the retina. Brain MRI can determine the presence and extent of intracranial AVMs. The diagnosis of the syndrome is usually delayed until late childhood because of the rarity of cutaneous manifestations. 

Physical examination

Orbital AVMs are common and can present as unilateral proptosis. Orbital ultrasound should be considered for those with suspicion of orbital AVM. Ocular motility abnormalities including nystagmus or strabismus may also be a sign for orbital involvement. 

Complications of AVMs including retinal hemorrhages, vitreous hemorrhage and macular edema. Optic atrophy may also be present. Even though Wyburn-Mason is classified as one of the phakomatoses, skin manifestations are not as commonly seen.

Small AVMs may be asymptomatic whereas larger AVMs may cause significant vision loss due to retinal ischemia. If AVMs are diagnosed at an early age, there is a higher risk of systemic involvement. 

Oculal signs and symptoms include Proptosis, Blepharoptosis, Abnormally dilated vessels of the conjunctiva, Nerve palsies, Nystagmus, Strabismus, Decreased visual acuity or total blindness (retinal ischemia, intraocular lesions), Vitreous Hemorrhage, Vein occlusions, Retinal Detachment, Secondary Glaucoma (Neovascular Glaucoma), Rubeosis Iridis, Optic Disc Edema, Optic Atrophy.

Neurological symptoms include Severe Headaches, Vomiting, Seizures, Paralysis (from Cranial nerves), Nuchal Rigidity, Epistaxis, Hemorrhaging, Hydrocephalus, Hemiparesis, Hemiplegia or Death.

Diagnostic procedures and associated findings: 

Dilated Funduscopic Exam: reveal unilateral tortuous dilated retinal vessels

Fluorescein angiography: demonstrates rapid filling of vascular anomalies without significant leakage 

Magnetic Resonance Imaging: indicates the location, size, mass effect, edema of intracranial arteriovenous malformations 

Cerebral angiography: displays the characteristics of feeding arteries and draining veins, indicates the exact architecture of the anomaly 

Optical Coherence Tomography: enlarged thickened retinal vessels and retinal edema, when present, can be visualized²

Differential diagnosis

• Sturge-Weber Syndrome
• Von Hippel- Lindau Disease
• Rendu-Osler-Weber Disease (Hereditary hemorrhagic telangiectasis)
• Capillary Retinal Hemangiomas
• Familial Retinal Arteriolar Tortuosity

Medical Management

Wyburn-Mason Syndrome patients should be followed by a cohort of physicians including ophthalmology, primary care, radiology, neurology and/or neurosurgery, and hematology. The majority of retinal AVM cases are stable.¹ Treatment is reserved for patients who are visually compromised or symptomatic. Management of Wyburn-Mason syndrome is conservative although surgical options are available. Patients with retinal AVMs are recommended to have brain imaging to rule out intracranial AVMs. Regular ophthalmologic evaluations are required to monitor AVMs and their potential complications. 

Surgical Management

Certain brain AVMs, depending on location, can be surgically resected. For AVMs that are not amenable to surgery, alternative measures, such as embolization and radiation therapy, may be considered.⁷

Complications

Retinal AVMs can be complicated by retinal hemorrhages (28.1%), retinal vein occlusions (17.5%), vitreous hemorrhage (10%), and secondary glaucoma (secondary to neovascularization or elevated episcleral venous pressure).³ Retinal ischemia resulting in neovascular glaucoma is associated with a poor prognosis. Mechanical compression of the optic nerve can occur and lead to gradual or complete blindness. Retinal edema and detachments have also been reported.

Prognosis

Patients with Wyburn Mason syndrome may remain asymptomatic; however, some patients have significantly decreased vision or total blindness due to late ocular complications, particularly ischemic complications.⁶ Long-term results indicate that the recurrence rate for extracranial AVMs after surgical resection is 81% and 98% with embolization.⁸ Of note, this condition is associated with high morbidity and mortality due to the high risk of spontaneous cerebral AVM hemorrhage.² The AVMs in the retina can remain stable over several years. Spontaneous resolution has been reported, but it is rare. Because of ocular complications of AVMs, including ischemic vascular occlusions, patients will need to be regularly monitored.³

References

1. Kaplan, Henry J. “Wyburn Mason Syndrome.” Retina Image Bank, 2013, imagebank.asrs.org/file/6211/wyburn-mason-syndrome.
2. So JM, Holman RE. Wyburn-Mason Syndrome. [Updated 2020 Feb 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
3. Schmidt D, Pache M, Schumacher M. The congenital unilateral retinocephalic vascular malformation syndrome (Bonnet-Dechaume-Blanc syndrome or Wyburn-Mason syndrome): review of the literature. Surv Ophthalmol. 2008;53:227-49.
4.  Miller, Neil R., et al. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. Williams & Wilkins, 1998.
5. Medina, Flávio Maccord, et al. “Rhegmatogenous Retinal Detachment in Wyburn-Mason Syndrome: Case Report.” Arquivos Brasileiros De Oftalmologia, vol. 73, no. 1, 2010, pp. 88–91., doi:10.1590/s0004-27492010000100017.
6.  Qin XJ, Huang C, Lai K. Retinal vein occlusion in retinal racemose hemangioma: a case report and literature review of ocular complications in this rare retinal vascular disorder. BMC Ophthalmol. 2014;14:101. Published 2014 Aug 21. doi:10.1186/1471-2415-14-101
7. Warrier S, Prabhakaran VC, Valenzuela A, Sullivan TJ, Davis G, Selva D. Orbital Arteriovenous Malformations. Arch Ophthalmol. 2008;126(12):1669–1675. doi:10.1001/archophthalmol.2008.501
8. Link T, Kam Y, Ajlan R. Ocular infarction following ethanol sclerotherapy of an arteriovenous malformation. Am J Ophthalmol Case Rep. 2019;15:100457. Published 2019 Apr 25. doi:10.1016/j.ajoc.2019.100457