Sturge-Weber Syndrome and Secondary Glaucoma
Sturge-Weber Syndrome (SWS), also known as encephalotrigeminal angiomatosis, is a congenital neuro-oculocutaneous syndrome that presents at birth. SWS was first reported by Dr. Schirmer in 1860 with later descriptions by Dr. Sturge in 1897 and Dr. Weber in 1922. It is characterized as a part of the neuroectodermal dysplasias, also known as phakomatoses. Unlike other phakomatoses, SWS is not hereditary. The incidence has been reported to be 1 per 50,000 live births and, no racial or sex predilection has been found.
SWS can be classified as trisymptomatic when the skin, eye, and central nervous system (CNS) are affected; bisymptomatic when the skin and CNS or the skin and eye are affected; and monosymptomatic when the skin or the CNS is affected. The typical triad consists of facial capillary malformation (port wine stain or nevus flammeus), an ipsilateral vascular anomaly in the brain (leptomeningeal hemangioma), and ocular hemangioma.
Cutaneous Manifestations and Treatment
The most common type of vascular malformation is port wine stain (PWS), with an overall incidence of 0.3% in live births. The incidence of SWS in patients with a PWS has been reported to be between  and 5%. A PWS is a well delineated red macule that is present at birth and gets darker and thicker with age. In addition, many small and large dark nodules can grow on the surface, resembling pyogenic granulomas.
The PWS is typically present in the V1 and V2 distributions of the trigeminal nerve. Leptomeningeal and ocular hemangiomas are usually accompanied by PWS in the eyelids, with the upper eyelid being more frequently affected than the lower. If the PWS is present bilaterally, the likelihood of having SWS is higher than when the PWS is present unilaterally. In some cases, the ipsilateral nasal and buccal mucosa may also be involved on the side of PWS.
The distribution of PWS along various branches of the trigmenial nerve determines the severity of associated neurological deficits and associated glaucoma. Hennedige et al. reported that patients with PWS only in the V1 dermatome had a 6.7% risk of glaucoma and 26.7% risk of neurologic manifestations. They reported no risk of glaucoma and a lower risk of neurologic manifestations, 3.1%, when only the V2 distribution was involved. When both the V1 and V2 dermatomes were involved, the risk of both glaucoma (31.8%) and neurologic manifestations (54.5%) was much higher. They also observed that, if all three dermatomes (V1, V2, V3) were involved, the risk of neurologic manifestations quadrupled.
The PWS has been reported to improve with pulsed dye laser photocoagulation. This laser uses thermolysis and results in irreversible damage to blood vessels but spares other components of the skin. Often, multiple treatments are required with minimal to no side effects. However, the patients rarely get a 100% clearance of their skin discoloration. Central forehead stains have a better outcome than do central facial stains. The patients with V2 involvement tend to have the worst outcome after laser treatment. By the fifth decade of life, approximately 65% of patients will have hypertrophy and nodules within the lesions. Therefore, many psychological benefits have been reported after the laser treatment of PWS.
Neurologic Manifestations and Treatment
The most common neurological manifestation in SWS is seizures, with partial seizures being the most common type. Seizures are present in approximately 80% of patients and usually develop during the first year of life. The seizures will manifest before the first year of age in 75% of the patients, although some patients may experience seizures for the first time as adults. Seizures will be present in 95% of patients with bilateral leptomeningeal lesions and 75% of patients with unilateral lesions. Bilateral lesions present in 7% to 26% of cases and are usually accompanied by more severe neurological symptoms compared to unilateral lesions. There is also an association between earlier onset of seizures and the development of other neurological manifestations such as contralateral hemiparesis, hemianopsia, hemiplegia, mental retardation, developmental delay, or behavioral problems. Developmental delay, mental retardation, and headaches occur in approximately 50% of patients with SWS. In addition, approximately 30% of patients will be severely mentally handicapped. However, patients with no seizures before 2 years of age will have normal intelligence and development.
The leptomeningeal lesions are present at birth and usually located in the occipital and parietal lobes of the meninges.8 These can be detected by magnetic resonance imaging or computed tomography. Even though computed tomography is very effective in detecting intracranial calcifications, these are usually not present in neonates. Therefore, the best method to diagnose the leptomeningeal lesions is magnetic resonance imaging with gadolinium contrast.
The most important aspect in the treatment of SWS is seizure control. Management of seizures with anticonvulsant therapy has been reported to have favorable results in approximately half of the patients with SWS. Nevertheless, the majority of patients will require more than one medication for treatment. In cases where seizures cannot be managed with medical therapy, surgical therapy may be beneficial. When seizures are poorly controlled and are present in only one hemisphere, hemispherectomy has been reported to have favorable results, with approximately 80% of the patients being seizure free after the procedure.
Ocular Manifestations and Treatment
Ocular manifestations of SWS include conjunctival, episcleral, and choroidal hemangiomas. Choroidal hemangiomas may be present in up to 71% of patients with SWS and may be circumscribed or diffuse. SWS is usually associated with the diffuse variant that often presents in patients with late-onset glaucoma. The treatment of patients with glaucoma and diffuse choroidal hemangiomas is extremely challenging and may be associated with devastating complications, such as choroidal effusions, retinal detachments, or severe hemorrhages. Since these patients are usually refractory to medical therapy, other treatment options have been used. These include radiotherapy, stereotactic radiotherapy, plaque radiotherapy, proton beam, anti-vascular endothelial growth factors, and photodynamic therapy. Glaucoma is one of the most challenging ocular manifestations of SWS.
Glaucoma presents in 30-70% of patients with SWS. Of the systemic hamartosis, SWS has the highest incidence of glaucoma. Approximately 60% of patients present with glaucoma at birth and 40% manifest glaucoma later in life. The incidence of glaucoma increases when the PWS involves the eyelid. It presents most often ipsilateral to the PWS but can also manifest bilaterally.
The two main mechanisms of glaucoma in SWS are malformation of the anterior chamber angle and an elevated episcleral venous pressure. An abnormal anterior chamber angle has been demonstrated in enucleated eyes with SWS. The abnormalities of the anterior chamber angle in patients with SWS resemble those seen in eyes with primary congenital glaucoma. These findings include a wider uveal meshwork, a ciliary muscle that is directly attached to the trabecular meshwork, an under-developed scleral spur, and an iris root that is inserted anteriorly.
When glaucoma is present at birth, it is due to a malformation of the anterior chamber angle, and patients manifest typical signs of congenital glaucoma, including buphthalmos, anisometropia, and amblyopia. When it presents later, it is usually secondary to elevated episcleral venous pressure.4,49 When gonioscopy is performed in older children and adults with SWS and glaucoma, either minimal or no angle abnormality may be present. In addition, when gonioscopy is performed in older patients, blood is usually seen in the angle, correlating with an increase in episcleral venous pressure. Another mechanism of glaucoma is thought to be premature aging of the trabecular meshwork that causes an early onset chronic open angle glaucoma, presenting in early adulthood. When neovascularization is present in the iris or angle, peripheral anterior synechiae may develop and result in secondary angle closure glaucoma.
Managing glaucoma in patients with SWS is complex because of early onset and resistance to conventional therapy. For early onset glaucoma with associated angle abnormalities, surgical intervention is usually required, with either goniotomy or trabeculotomy. However, the outcomes are generally worse than those observed with primary congenital glaucoma, and these cases often require additional surgery with trabeculectomy or a glaucoma drainage device. Olsen et al. assessed the efficacy of goniotomy and trabeculotomy in 15 eyes. They found that the intraocular pressure (IOP) was controlled in 66.7% (10/15 eyes) after one or more goniotomy or trabeculotomy procedures, with a median follow-up of 5.4 years. The range of the patients’ age was from birth to 4 years, with a mean of 11.8 months. Iwach and colleagues reported the median stable interval of IOP control after a single goniotomy or trabeculotomy to be 8 and 21 months, respectively, in patients younger than 4 years. In a study of 6 patients who underwent trabeculectomy and were followed from 9 months to 9 years, IOP was controlled in two eyes without medical therapy and in four eyes with medical therapy. Only one patient had a repeat trabeculectomy with adjunctive medical therapy to maintain adequate IOP. A combined trabeculotomy with trabeculectomy was assessed in 10 eyes with glaucoma associated with SWS. All eyes maintained IOP of less than 16 mm Hg without medication during a mean postoperative follow up of 27.8 months.
For late onset glaucoma, medical therapy is initiated first; aqueous suppressants and miotics tend to be the most successful. Prostaglandin analogues have been reported to have inconsistent response rates. Laser trabeculoplasty appears to be of limited use. If medical therapy is ineffective, trabeculectomy remains the procedure of choice for late onset cases, because it bypasses the episcleral venous system. Outcomes of trabeculectomy may be improved with the use of antimetabolites. Of note, trabeculectomy is associated with a much higher risk of choroidal effusions or suprachoroidal hemorrhages in eyes with SWS.
Glaucoma drainage devices have also been shown to be effective for glaucoma secondary to SWS. Hamush et al. treated 11 eyes with the Ahmed glaucoma drainage device. The cumulative probability of success was 79% at 24 months, 59% at 42 months, and 30% at 60 months. Success was defined as an IOP < 21 mmHg on the last two measurements with no additional surgery or complications like hemorrhage or retinal detachments. A two-staged Baerveldt glaucoma drainage device was used in another study for the treatment of 10 eyes with SWS and glaucoma. Patients were, on average, 7 years old, and surgical success, defined as IOP<21 mm Hg after an average of 35 months of follow up, was 100%. The two-stage technique allows encapsulation to occur around the plate for a few weeks prior to insertion of the tube into the anterior chamber, minimizing the risk of hypotomy and subsequent choroidal effusion or hemorrhage.
Another treatment option is cyclophotocoagulation (CPC) which can be performed in patients with refractory glaucoma or in patients who are likely to have much higher risk of intraoperative or postoperative complications (choroidal expulsive hemorrhage or choroidal detachment) after glaucoma filtration surgery. In a study of 16 children (16 eyes) with a mean follow-up of 8.87 years in which CPC was performed, 10 eyes (62.5%) maintained an IOP between 6-22 mm Hg without any complications associated with the treatment.
Klippel-Trenaunay-Weber Syndrome (KTS)
This syndrome, a rare cause of secondary glaucoma that should be distinguished from SWS, is characterized by a localized or diffuse capillary malformation that overlies a venous malformation and/or lymphatic malformation with associated soft tissue and bone hypertrophy. In addition to the extensive cutaneous hemangiomas affecting the face, similar to SWS, the trunk and limbs are involved. Dysplastic veins and hypertrophy of bone and soft tissues are often present in the affected extremity, a lower limb in 90% of the patients. Malformations of deep veins increase the risk of deep vein thrombosis and pulmonary embolism. Visceral organ involvement is associated with greater morbidity secondary to internal hemorrhage. Cerebral hemangiomas may also occur, causing epilepsy and mental retardation.
Patients with SWS have a lower life expectancy than does the general population. When the leptomeningeal lesions are bilateral, patients usually have more severe neurological manifestations and a worse prognosis.
SWS is a rare, sporadic disorder with glaucoma being the most common ocular manifestation. Treatment of glaucoma requires an understanding of underlying pathology and mechanisms to guide appropriate surgical intervention. In general, lower surgical success and increased intraoperative and postoperative complications are observed in these patients when compared to other types of glaucomas. Several precautionary steps can be taken to minimize these complications, including preoperative reduction of IOP with hyperosmotic agents, placement of posterior sclerotomies prior to entering the eye, preplacement of flap sutures or additional and tight sutures during trabeculectomy, use of valved or two-stage glaucoma drainage devices, or radiotherapy of choroidal hemangiomas prior to intraocular surgery. Because multiple organs are involved in SWS, a multidisciplinary approach is recommended to deliver comprehensive care and optimize overall outcomes.
- Comi AM. Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Neurologist 2011;17:179-84.
- Schirmer. Ein Fall von Teleangiektasie: Archives of ophthalmology, 1860:119-121.
- Thomas-Sohl KA, Vaslow DF, Maria BL. Sturge-Weber syndrome: a review. Pediatr Neurol 2004;30:303-10.
- Sullivan TJ, Clarke MP, Morin JD. The ocular manifestations of the Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 1992;29:349-56.
- Awad AH, Mullaney PB, Al-Mesfer S, et al. Glaucoma in Sturge-Weber syndrome. J AAPOS 1999;3:40-5.
- Pascual-Castroviejo I, Díaz-Gonzalez C, García-Melian RM, et al. Sturge-Weber syndrome: study of 40 patients. Pediatr Neurol 1993;9:283-8.
- Jacobs AH, Walton RG. The incidence of birthmarks in the neonate. Pediatrics 1976;58:218-22.
- Hennedige AA, Quaba AA, Al-Nakib K. Sturge-Weber syndrome and dermatomal facial port-wine stains: incidence, association with glaucoma, and pulsed tunable dye laser treatment effectiveness. Plast Reconstr Surg 2008;121:1173-80.
- Lee JB, Kim M, Lee SC, et al. Granuloma pyogenicum arising in an arteriovenous haemangioma associated with a port-wine stain. Br J Dermatol 2000;143:669-71.
- Kim TH, Choi EH, Ahn SK, et al. Vascular tumors arising in port-wine stains: two cases of pyogenic granuloma and a case of acquired tufted angioma. J Dermatol 1999;26:813-6.
- Carrasco L, Pastor A, Fariña C, et al. Acral arteriovenous tumor developed within a nevus flammeus in a patient with Sturge-Weber syndrome. Am J Dermatopathol 2003;25:341-5.
- Castanedo-Cazares JP, Lepe V, Moncada B. Pyogenic granuloma within port-wine stains. Eur J Dermatol 2002;12:616.
- Valeyrie L, Lebrun-Vignes B, Descamps V, et al. Pyogenic granuloma within port-wine stains: an alarming clinical presentation. Eur J Dermatol 2002;12:373-5.
- Tallman B, Tan OT, Morelli JG, et al. Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Pediatrics 1991;87:323-7.
- Rosen S, Smoller B. Pathogenesis of port wine stains. A new hypothesis. Med Hypotheses 1987;22:365-8.
- Smoller BR, Rosen S. Port-wine stains. A disease of altered neural modulation of blood vessels? Arch Dermatol 1986;122:177-9.
- Scherer K, Lorenz S, Wimmershoff M, et al. Both the flashlamp-pumped dye laser and the long-pulsed tunable dye laser can improve results in port-wine stain therapy. Br J Dermatol 2001;145:79-84.
- Léauté-Labréze C, Boralevi F, Pedespan JM, et al. Pulsed dye laser for Sturge-Weber syndrome. Arch Dis Child 2002;87:434-5.
- Fitzpatrick RE, Lowe NJ, Goldman MP, et al. Flashlamp-pumped pulsed dye laser treatment of port-wine stains. J Dermatol Surg Oncol 1994;20:743-8.
- Morelli JG, Weston WL, Huff JC, et al. Initial lesion size as a predictive factor in determining the response of port-wine stains in children treated with the pulsed dye laser. Arch Pediatr Adolesc Med 1995;149:1142-4.
- Nguyen CM, Yohn JJ, Huff C, et al. Facial port wine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser. Br J Dermatol 1998;138:821-5.
- Renfro L, Geronemus RG. Anatomical differences of port-wine stains in response to treatment with the pulsed dye laser. Arch Dermatol 1993;129:182-8.
- Batta K. Management of large birthmarks. Semin Neonatol 2000;5:325-32.
- Geronemus RG, Ashinoff R. The medical necessity of evaluation and treatment of port-wine stains. J Dermatol Surg Oncol 1991;17:76-9.
- Sujansky E, Conradi S. Outcome of Sturge-Weber syndrome in 52 adults. Am J Med Genet 1995;57:35-45.
- Oakes WJ. The natural history of patients with the Sturge-Weber syndrome. Pediatr Neurosurg 1992;18:287-90.
- Griffiths PD, Boodram MB, Blaser S, et al. Abnormal ocular enhancement in Sturge-Weber syndrome: correlation of ocular MR and CT findings with clinical and intracranial imaging findings. AJNR Am J Neuroradiol 1996;17:749-54.
- Kramer U, Kahana E, Shorer Z, Ben-Zeev B. Outcome of infants with unilateral Sturge-Weber syndrome and early onset seizures. Dev Med Child Neurol 2000;42:756-9.
- JB B. Sturge-Weber Syndrome. In: Vascular Birthmarks of the Head and Neck, Hochman M (Ed), Facial Plastic Surgery Clinics of North America, 2001:569.
- Sujansky E, Conradi S. Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children. J Child Neurol 1995;10:49-58.
- Klapper J. Headache in Sturge-Weber syndrome. Headache 1994;34:521-2.
- Martí-Bonmatí L, Menor F, Poyatos C, et al. Diagnosis of Sturge-Weber syndrome: comparison of the efficacy of CT and MR imaging in 14 cases. AJR Am J Roentgenol 1992;158:867-71.
- Truhan AP, Filipek PA. Magnetic resonance imaging. Its role in the neuroradiologic evaluation of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. Arch Dermatol 1993;129:219-26.
- Arzimanoglou A, Aicardi J. The epilepsy of Sturge-Weber syndrome: clinical features and treatment in 23 patients. Acta Neurol Scand Suppl 1992;140:18-22.
- Arzimanoglou AA, Andermann F, Aicardi J, et al. Sturge-Weber syndrome: indications and results of surgery in 20 patients. Neurology 2000;55:1472-9.
- Kossoff EH, Buck C, Freeman JM. Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide. Neurology 2002;59:1735-8.
- Bourgeois M, Crimmins DW, de Oliveira RS, et al. Surgical treatment of epilepsy in Sturge-Weber syndrome in children. J Neurosurg 2007;106:20-8.
- Ito M, Sato K, Ohnuki A, Uto A. Sturge-Weber disease: operative indications and surgical results. Brain Dev 1990;12:473-7.
- Tuxhorn IE, Pannek HW. Epilepsy surgery in bilateral Sturge-Weber syndrome. Pediatr Neurol 2002;26:394-7.
- Celebi S, Alagöz G, Aykan U. Ocular findings in Sturge-Weber syndrome. Eur J Ophthalmol 2000;10:239-43.
- Zografos L, Bercher L, Egger E, et al. [Treatment of eye tumors by accelerated proton beams. 7 years experience]. Klin Monbl Augenheilkd 1992;200:431-5.
- Zografos L, Bercher L, Chamot L, et al. Cobalt-60 treatment of choroidal hemangiomas. Am J Ophthalmol 1996;121:190-9.
- Sagong M, Lee J, Chang W. Application of intravitreal bevacizumab for circumscribed choroidal hemangioma. Korean J Ophthalmol 2009;23:127-31.
- Anand R. Photodynamic therapy for diffuse choroidal hemangioma associated with Sturge Weber syndrome. Am J Ophthalmol 2003;136:758-60.
- Bains HS, Cirino AC, Ticho BH, et al. Photodynamic therapy using verteporfin for a diffuse choroidal hemangioma in Sturge-Weber syndrome. Retina 2004;24:152-5.
- 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.
- van Emelen C, Goethals M, Dralands L, et al. Treatment of glaucoma in children with Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 2000;37:29-34.
- Amirikia A, Scott IU, Murray TG. Bilateral diffuse choroidal hemangiomas with unilateral facial nevus flammeus in Sturge-Weber syndrome. Am J Ophthalmol 2000;130:362-4.
- Weiss DI. Dual origin of glaucoma in encephalotrigeminal haemangiomatosis. Trans Ophthalmol Soc U K 1973;93:477-93.
- Cibis GW, Tripathi RC, Tripathi BJ. Glaucoma in Sturge-Weber syndrome. Ophthalmology 1984;91:1061-71.
- Phelps CD. The pathogenesis of glaucoma in Sturge-Weber syndrome. Ophthalmology 1978;85:276-86.
- Nelson LB CJ, Harley RD. Pediatric ophthalmology 3rd ed. Philadelphia: WB Saunders, 1991:p. 437-40.
- Karl E. Olsen ASH, and Martha M. Wright. The Efficacy of Goniotomy/Trabeculotomy in Early-Onset Glaucoma Associated With the Sturge- Weber Syndrome: AAPOS, 1999.
- Ali MA, Fahmy IA, Spaeth GL. Trabeculectomy for glaucoma associated with Sturge-Weber syndrome. Ophthalmic Surg 1990;21:352-5.
- Mandal AK. Primary combined trabeculotomy-trabeculectomy for early-onset glaucoma in Sturge-Weber syndrome. Ophthalmology 1999;106:1621-7.
- Hamush NG, Coleman AL, Wilson MR. Ahmed glaucoma valve implant for management of glaucoma in Sturge-Weber syndrome. Am J Ophthalmol 1999;128:758-60.
- Budenz DL, Sakamoto D, Eliezer R, et al. Two-staged Baerveldt glaucoma implant for childhood glaucoma associated with Sturge-Weber syndrome. Ophthalmology 2000;107:2105-10.
- Agarwal HC, Sandramouli S, Sihota R, et al. Sturge-Weber syndrome: management of glaucoma with combined trabeculotomy-trabeculectomy. Ophthalmic Surg 1993;24:399-402.
- Kocyła-Karczmarewicz B, Klimczak-Slaczka D, Grałek M, et al. [Childhood glaucoma associated with Sturge-Weber syndrome --the efficacy of cyclofotocoagulation and other therapeutic methods]. Klin Oczna 2006;108:180-3.
- Purkait R, Samanta T, Sinhamahapatra T, et al. Overlap of sturge-weber syndrome and klippel-trenaunay syndrome. Indian J Dermatol 2011;56:755-7.
- Rahman M, Rahman S, Akhter S, et al. Overlapping of Sturge Weber syndrome and Klippel Trenaunay Weber syndrome. Mymensingh Med J 2008;17:78-81.