Ocular Involvement in Sturge-Weber Syndrome

Maryam Mushtaq

Introduction

An 11-year old boy presented to his optometrist with a 2-week history of intermittent flashing lights and blurred vision in his right eye. His medical background included amblyopia secondary to strabismus and a port-wine stain (naevus flammeus) above his right eye, both of which were corrected in early childhood with patching and laser treatment, respectively. Whilst at the optometrist, fundoscopy was performed which highlighted an ambiguous lesion in his right eye temporal to the optic disc that could not be characterised. He was referred urgently to the acute eye clinic, where a B-scan and fundus fluorescein angiography (FFA) were performed. These investigations, along with slit lamp examination, were highly suggestive of a choroidal haemangioma. Given his history of a port-wine stain, he was referred to a specialist centre to explore the possibility of a diagnosis of Sturge-Weber syndrome. This article aims to shed light on this rare neurocutaneous disorder, and the ocular manifestations associated with these affected individuals.

Background

Sturge-Weber syndrome (SWS) is the third most common congenital neurocutaneous syndrome (also generally known as the phakomatoses) after neurofibromatosis and tuberous sclerosis, and typically presents in early childhood or adolescence (1). It is unique to the other phakomatoses in that it is not hereditary which was echoed in this case by the lack of any family history. The condition is specifically attributed to somatic, gain-of-function mutations in the GNAQ gene. However recently, GNA11 variants have also been linked to the syndrome, with these patients typically presenting with subtle phenotypic particularities (2). These genetic variants lead to the dysregulation of multiple signalling pathways, ultimately resulting in either proliferative capillary overgrowth, or the development of endothelial cells with impaired differentiation, which are accompanied by a progressive dilation of vasculature resembling immature venules (3). The characteristic triad of symptoms comprises of a port wine stain (or naevus flammeus) which is a facial capillary malformation, an ipsilateral vascular anomaly in the brain referred to as leptomeningeal haemangioma, and the presence of ocular haemangiomas (4). While it is common for the skin, eyes, and central nervous systems (CNS) to be affected simultaneously (trisymptomatic), patients may also exhibit involvement of only two systems (bisymptomatic) or the sole involvement of either the skin or CNS (monosymptomatic). Research indicates that port-wine stains encompassing the entire V1 segment often correlate with underlying ophthalmic and neurologic involvement. This observation could serve as an initial indicator of the condition and should prompt further assessment (5).

Choroidal Haemangioma

As in this patient case, ocular manifestations of SWS typically involve choroidal haemangiomas, which can be found in as many as 71% of patients; however conjunctival and episcleral haemangiomas can also be seen (6). Choroidal haemangiomas are benign vascular tumours which can present as far-sightedness (hyperopia), blurred or distorted vision (metamorphopsia), or flashing lights, due to elevation of the overlying retina. They can also be asymptomatic and detected only during routine eye examinations. These haemangiomas occur in two distinct clinical forms: a circumscribed form that is almost always isolated and non-syndromic, and a diffuse form that is strongly associated with SWS and generally identified ipsilaterally to any port-wine stain that may be present (4). Diffuse forms can lead to thickening of the choroid around the optic disc, potentially causing notable disc cupping that mimics the appearance of glaucomatous optic neuropathy (7). Another complication is raised intraocular pressure, which is generally caused by elevated episcleral and orbital venous pressure, angle malformation, or a combination of the two. Eventually, serous retinal detachment may occur. The objective of treatment is to mitigate or reverse visual loss linked to secondary retinal detachment, glaucoma, or other complications. The preferred treatment for circumscribed small-medium sized choroidal haemangiomas is photodynamic therapy (PDT), which may be used in conjunction with intravitreal anti-vascular endothelial growth factor (anti-VEGF) drug therapy in eyes with a substantial amount of subretinal fluid, a subfoveal tumour location, or both (8).

Glaucoma

Glaucoma represents a prevalent and intricate manifestation of SWS, affecting approximately 30-70% of individuals with the condition (4). The age of onset displays a bimodal peak, with an early-onset (congenital) form affecting roughly 60% of patients, and commonly associated with malformation of the anterior chamber angle. The later-onset form emerges during childhood and adolescence, impacting 40% of cases, and is usually attributed to an increased episcleral venous pressure (9). The presence of blood in the angle on gonioscopy would support a later-onset picture. While the most common type of glaucoma in individuals with SWS is open-angle glaucoma characterised by progressive visual field loss, instances of acute glaucoma attacks stemming from chamber angle closure have also been documented (10). The management of glaucoma in individuals with SWS is complicated due to its early onset and resistance to conventional therapy. When angle abnormalities are present, surgical intervention is typically necessary, with goniotomy or trabeculotomy as the common options (9). In contrast, with late-onset glaucoma, the initial approach involves medical therapy; with aqueous suppressants and miotics often proving to be the most effective. If surgical treatment is eventually needed, due to trabeculectomy circumventing the episcleral venous system, it remains the preferred procedure for these cases.

Conclusion

In essence, while Sturge-Weber syndrome remains a rare disorder (occurring at an estimated frequency of between 1:20,000 and 1:50,000 live births), its associated ocular involvement and equal likelihood of affecting individuals across various demographic backgrounds (11), necessitates careful consideration; especially when encountering young patients exhibiting these specific symptoms. A comprehensive understanding of the genetic underpinnings, diverse ocular manifestations, and available treatment modalities is essential for delivering optimal care, ensuring timely referrals to the appropriate specialists, and ultimately enhancing the quality of life for individuals affected by this complex neurocutaneous syndrome.

References

  1. Klar N, Cohen B, Lin D. Neurocutaneous syndromes. Handb Clin Neurol. 2016;135:565-589.
  2. Thorpe J, Frelin LP, McCann M, et al. Identification of a mosaic activating mutation in GNA11 in atypical Sturge-Weber syndrome. J Invest Dermatol. 2021;141:685–688.
  3. Huang L, Bichsel C, Norris AL, et al. Endothelial GNAQ p. R183Q increases ANGPT2 (Angiopoietin-2) and drives formation of enlarged blood vessels. Arterioscler Thromb Vasc Biol. 2022;42(1):e27–e43.
  4. Pascual-Castroviejo I, Díaz-Gonzalez C, García-Melian RM, et al. Sturge-Weber syndrome: study of 40 patients. Pediatr Neurol 1993;9:283-8.
  5. Zallmann M, Leventer RJ, Mackay MT, Ditchfield M, Bekhor PS, Su JC. Screening for Sturge-Weber syndrome: a state-of-The-art review. Pediatr Dermatol. 2018;35(1):30–42.
  6. Sullivan TJ, Clarke MP, Morin JD. The ocular manifestations of the Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 1992;29:349-56.
  7. Arora KS, Quigley HA, Comi AM, et al. Increased choroidal thickness in patients with Sturge-Weber syndrome. JAMA Ophthalmol. 2013;131:1216–1219.
  8. Patrianakos TD, Nagao K, Walton DS. Surgical management of glaucoma with the Sturge-Weber syndrome. Int Ophthalmol Clin. 2008;48:63–78.
  9. Iwach AG, Hoskins HD, Hetherington J, et al. Analysis of surgical and medical management of glaucoma in Sturge-Weber syndrome. Ophthalmology 1990;97:904-9.
  10. Maruyama I, Ohguro H, Nakazawa M. A case of acute angle-closure glaucoma secondary to posterior scleritis in patient with Sturge-Weber syndrome. Jpn J Ophthalmol. 2002;46:74–77.
  11. Thomas-Sohl KA, Vaslow DF, Maria BL. Sturge-Weber syndrome: a review. Pediatr Neurol 2004;30:303-10.

Leave a Reply