REVIEW ARTICLE

Encephalotrigeminal Angiomatosis (Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome): A Review

Syril Dorairaj, MD* and Robert Ritch, MD*
Abstract: Sturge-Weber syndrome (SWS) (encephalotrigeminal
angiomatosis) is a phakomatosis associated with port-wine stains of the face, seizures, mental retardation, and usually ipsilateral meningeal vascular malformations. The classic form affects leptomeninges, eyes, and face. Although the precise etiology and pathogenesis are unclear, the postulated defect is primary venous dysplasia with failure of the primordial embryonic venous plexus to regress. A spontaneous somatic mutation in broblast bronectin gene expression in the vascular malformation may occur during embryonic development. Ocular involvement is characterized by conjunctival, episcleral, retinal, and choroidal vascular abnormalities. The vascular lesions have been inconsistently described as angiomas, hemangiomas, and vascular malformations. Based on the endothelial cellular activity, they can be considered vascular malformations (or port-wine stains), which never regress spontaneously. Congenital, developmental, and adult-onset glaucoma are often seen when the malformations involve the distribution of the rst branch of the trigeminal nerve. Both mechanical and vascular causes have been proposed to account for the development of glaucoma. The mechanical theory is based on obstruction of aqueous outow secondary to developmental anterior chamber angle abnormalities, and the vascular theory is based primarily on elevated episcleral venous pressure. Management of glaucoma in patients with SWS is often challenging and is aimed at controlling intraocular pressure and preventing progressive visual loss and blindness. It also carries an increased risk for surgical complications. This review summarizes the literature regarding the genetics, clinical features, and management of ocular complications of SWS with special focus on glaucoma. Key Words: Sturge-Weber syndrome, encephalotrigeminal angiomatosis, phakomatosis, glaucoma, anterior chamber angle (Asia-Pac J Ophthalmol 2012;1: 226Y234)

literature regarding the clinical features and management of ocular complications of these syndromes (Table 1) with special focus on glaucoma. In 1860, Schirmer3 described a patient with a facial vascular malformation and glaucoma. William Allen Sturge4 later reported a 6-year-old hemiparetic, epileptic girl with a facial vascular malformation and ipsilateral congenital glaucoma and hypothesized that a cerebral angioma resulted in the neurologic defect. Kalischer5 conrmed the association between facial and intracranial vascular malformations at autopsy. In 1922, Weber6 was the rst to demonstrate the associated intracranial calcications in this syndrome radiographically. The postulated pathogenesis of SWS is a primary venous dysplasia, with failure of regression of a primordial embryonic venous plexus that is normally present at 5 to 8 weeks of gestation. It has been suggested that a spontaneous somatic mutation occurs during this period of embryonic development.7 Sturge-Weber syndrome can be classied into 3 types according to extent of involvement. Type I is most common, with a classic manifestation of port-wine stain and intracranial leptomeningeal vascular malformation, with or without ocular abnormalities, such as glaucoma. Type II involves a port-wine stain and possible glaucoma, but no brain abnormalities. Type III is characterized by leptomeningeal angiomatosis without cutaneous lesions or ocular abnormalities. This form is usually diagnosed during imaging for epilepsy. Various combinations of involved structures may occur. However, there is no description of a form involving the leptomeninges and eyes while sparing the face.8

GENETIC FACTORS
There is no sex predominance, and unlike other neurocutaneous disorders, such as neurobromatosis or tuberous sclerosis, SWS occurs sporadically, although a few familial clusters have been reported. Somatic mutations with complex interactions between the extracellular matrix, vascular innervation, and endothelium contribute to the abnormal development and function of blood vessels in SWS.9 The sporadic nature suggests a somatic mutation, as do cultured broblast chromosome and mRNA data.7,10,22 Familial capillary malformations (port-wine stain) and arteriovenous malformations have been linked to mutations of the RASA1 gene.11 Speculation regarding minor chromosomal aberrations has not been conrmed. Fibronectin gene expression in port-wine stainYderived broblasts is increased and may reect a somatic mutation.12 More recently, Tanwar et al13 recommended that patients with SWS with congenital glaucoma and gyral calcication should undergo CYP1B1 (cytochrome P450) mutation analysis. Increased expression of endothelin 1 has been noted in the abnormal blood vessels of patients with SWS.99

turge-Weber syndrome (SWS) is a congenital syndrome dened by the association of a facial capillary malformation (port-wine stain), with a vascular malformation of the eye and/or brain (leptomeningeal vascular malformations).1,2 It occurs sporadically, with an estimated incidence of 1 in 20,000 to 50,000 live births. Klippel-Trenaunay-Weber syndrome consists of cutaneous limb hemangioma, vascular hyperplasia, and osseous hypertrophy and can be associated with SWS (Fig. 1). Some have considered them variations on a common theme. This review summarizes

From the *Einhorn Clinical Research Center, New York Eye and Ear Infirmary, New York, NY; Hamilton Glaucoma Center, Shiley Eye Center and Department of Ophthalmology, University of California, San Diego, CA; and Department of Ophthalmology, New York Medical College, Valhalla, NY. Received for publication March 28, 2012; accepted May 21, 2012. Supported by the HRH Prince Khalid bin Abdullah Al-Saud Research Fund of the New York Glaucoma Research Institute, New York, NY. The authors have no funding or conicts of interest to declare. Reprints: Robert Ritch, MD, The New York Eye and Ear Infirmary, 310 E 14th St, New York, NY 10003. E-mail: ritchmd@earthlink.net. Copyright * 2012 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0b013e31826080a9

SYSTEMIC INVOLVEMENT Facial Vascular Malformation

The hallmark of SWS is a facial cutaneous vascular malformation (nevus ammeus, port-wine stain). A port-wine

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FIGURE 1. Klippel-Trenaunay-Weber syndrome consists of cutaneous limb hemangioma, vascular hyperplasia, and osseous hypertrophy. Note diffuse melanocytosis typically seen in oculodermal melanocytosis (PPV).

stain consists of loosely arranged, dilated, thin-walled capillaries in the dermis and subcutaneous tissue. It is present at birth, is usually unilateral, and involves the region of distribution of the rst and second divisions of the trigeminal nerve14 (Fig. 2). Port-wine stains15 occur laterally, unlike salmon patch lesions, which are in the midline. They are variably sized and generally at and blanch under pressure; in very rare cases, they may assume a tuberous aspect. The color may vary under the inuence of factors such as thermal changes, strains, respiratory activity, and fever. Bilaterality occurs in 10%16 to 30%17 of cases. The supraorbital region is almost always affected, although exceptions have been reported.18 Facial hypertrophy in the region associated with the angioma is common (Fig. 3). The extent of the facial nevus is not proportional to the presence and severity of the neurological symptoms, nor is its location a reliable indicator of the presence of the cerebral lesion. Vascular malformations of the oral and nasal cavities occur concomitantly. In the oral cavity, the upper palate is commonly affected but frequently underdiagnosed, because most of the patients are not routinely examined for the presence of oral lesions.19,78
TABLE 1. Glaucoma in the Phakomatoses A. Commonly associated with glaucoma 1. Encephalotrigeminal angiomatosis (Sturge-Weber) 2. Klippel-Trenaunay-Weber (combined form) 3. Oculodermal melanocytosis (nevus of Ota) B. Occasionally associated with glaucoma 1. Neurofibromatosis (von Recklinghausen) 2. Angiomatosis retinae (von Hippel-Lindau) C. Rarely associated with glaucoma 1. Basal cell nevus syndrome 2. Tuberous sclerosis (Bourneville) 3. Klippel-Trenaunay-Weber (in pure form) 4. Diffuse congenital hemangiomatosis 5. Racemose angioma of the retina (Wyburn-Mason) D. Unassociated with glaucoma 1. Ataxia-telangiectasia (Louis-Bar)
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FIGURE 2. Port-wi Port-wine stain in a case with SWS. A, V1 distribution. B, Unilateral V1 and V2 involvement and bilateral V3 involvement. Note the involvement also of the lower lip. C, Bilateral SWS and unilateral oculodermal melanocytosis (PPV).

Leptomeningeal Vascular Malformation

Leptomeningeal vascular malformations are present in nearly 98% of cases with SWS. A meningeal racemose vascular malformation usually occurs ipsilateral to the facial vascular malformations and is usually located to the pia mater over the parieto-occipital region. Progressive calcication (tram-line) frequently occurs in the subintimal layer of the meningeal arteries, possibly due to vascular stasis and may obliterate the vascular lumen (Fig. 4A). These abnormalities can also be diagnosed by other imaging modalities, such as magnetic resonance imaging (MRI) (Fig. 4B) or computed tomography (CT) scan

FIGURE 3. Facial hypertrophy in the region associated with the angioma associated with V1 and V2 involvement. Note involvement of the upper lip. www.apjo.org

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FIGURE 4. A, X-ray of the skull in a case with SWS showing tram track calcication. B, Magnetic resonance imagingYaxial T1-weighted MRI showing left cerebral atrophy with leptomeningeal angiomatosis. C, Cranial CT scan showing prominent subcortical white matter calcication.

(Fig. 4C). Magnetic resonance imaging feature of the diffused choroidal hemangiomas was thickening of the posterior wall of the globe on unenhanced T1-weighted images. Upon injection of contrast material, there is crescentic enhancement, thickest at the posterior pole, extending to the anterior portion of the globe. And there has been evidence showing the superiority of MRI in detecting bilateral lesion to CT images. Calcication and atrophy of the external layers of the cerebral cortex may result in mental retardation. Approximately 60% of patients have intellectual decits, and 85% have seizures.20 Partial seizures, which may occur in 70% to 90% of those with the disorder by 3 years of age, typically occur contralateral to the vascular malformation and worsen with age. Infantile spasms and generalized seizures are also observed. Other neurological complications secondary to leptomeningeal vascular malformations include vascular headache, stroke-like episodes, contralateral hemiparesis, hemiatrophy, and hemianopia. The fundamental abnormality in the central nervous system is venous stasis due to the lack of normal cortical venous development that leads to a hypoperfused state in the affected brain parenchyma, with progressive inability to meet metabolic demands. Skeletal malformations, such as hemihypertrophy of the face and body, have also been reported. Localized or diffuse visceral angiomas may occur in the kidneys, spleen, intestine, pancreas, lungs, and thyroid. Oral manifestations include unilateral vascular hyperplasia of the oral mucosa and/or gingival changes ranging from slight vascular hyperplasia to large masses, which may interfere with mouth closure.

that when the vascular malformations involve the upper lid, there is ipsilateral intraocular involvement. Exceptions may occur.22 Rarely, orbital involvement results in exophthalmos. Iris hyperchromia occurs in 7% to 8% of cases,23 and iris neovascularization has been reported.24 Tortuous retinal vessels and scleral melanosis may also occur. Scleral melanosis can occur in phakomatosis pigmentovascularis (PPV), a combined SWS/Klippel-Trenaunay-Weber and oculodermal melanocytosis, which is invariably associated with glaucoma. The clinical manifestations of PPV have a common embryological origin. The primary defect affects tissues originating in the prosencephalic and mesencephalic neural crest. These give rise to vascular and other tissue malformations or melanocytosis in the meninges, eye and dermis. Phakomatosis pigmentovascularis is classied as a disorder of neural crest migration and

OCULAR INVOLVEMENT
Ocular complications arise primarily from vascular abnormalities of the conjunctiva, episclera, retina, and choroid. When the facial vascular malformation involves the eyelid, ocular circulatory abnormalities may occur (Fig. 5). Andersons21 rule states
FIGURE 5. Prominent episcleral vessels visible on slit lamp examination. A, Mild. B, Severe. C, Dilated episcleral veins. * 2012 Asia Pacific Academy of Ophthalmology

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FIGURE 6. Findus photograph showing an isolated choroidal hemangioma (A); corresponding uorescein angiogram of choroidal hemangioma (B.)

differentiation. Because the trabecular meshwork cells also derive from the embryonic neural crest, developmental anomalies of the angle may occur in these syndromes, accounting for congenital glaucoma.25,26 Choroidal vessels also exhibit angiomatous changes; the vascular malformation has a honeycomb pattern and is generally not pigmented, varying in color from gray to yellow, thus appearing lighter than the surroundings when transilluminated. Choroidal hemangiomas, which occur in 40% of cases,16 are the most common abnormality, except perhaps for conjunctival involvement. Of all the cases of choroidal hemangiomas noted on examination of enucleated specimens, 50% occur in encephalotrigeminal vascular malformations.27 Choroidal hemangiomas are usually of the diffuse type and are evident at birth. The diffuse hemangioma leads to choroidal thickening and generally involves more than half of its area. It is composed of large, thin-walled vascular channels with a at single layer of endothelial cells (Fig. 6A) and is usually composed of both capillary and cavernous hemangiomas. Decreased visual acuity can result from progressive hyperopia, destruction of underlying choriocapillaris and degeneration of overlying retinal pigment epithelium, retinal detachment, and sector visual eld defects from degeneration of the nerve ber layer. In some cases, diffuse uveal involvement occurs, which has been termed tomato catsup fundus, which means diffused bright red fundus.28 The hemangioma may be so large as to involve nearly the entire choroid, predisposing to expulsive choroidal hemorrhage. It is imperative to recognize any diffuse choroidal hemangioma preoperatively by thorough fundoscopy to avoid expulsive choroidal hemorrhage. Recognition of a choroidal hemangioma can often be difcult because of slow growth. It may be easily overlooked in younger patients. It is always important to compare the fundus of one eye with that of the fellow eye for evidence of change in color, retinal vascular tortuosity, or serous retinal detachment. It appears as an orange-yellow, slightly elevated mass. There may or may not be any leakage on uorescein angiography. If there is leakage on uorescein angiography, it will demonstrate early hyperuorescence with late leakage and dye stain (Fig. 6B). On A-scan ultrasound, the tumors show high reectivity and increased choroidal thickening (Fig. 7).

involving the lid, tarsus, and conjunctiva. When the cutaneous vascular malformation is unilateral, the glaucoma is nearly always unilateral and ipsilateral to it. Contralateral35,36 and bilateral29 glaucoma with unilateral cutaneous vascular malformation has also been reported. Bilateral angiomas may be accompanied by either unilateral or bilateral glaucoma, although the former is more typical.37 Presentation of glaucoma is bimodal; 60% develop glaucoma in infancy when the eye is susceptible to increased intraocular pressure (IOP); 40% develop glaucoma in childhood or early adulthood. Early-onset glaucoma causes infants to develop enlarged corneal diameters and myopia. In a large series of 174 patients with increased IOP, 84 had buphthalmos.38 Alexander and Norman31 reported that two thirds of their patients had buphthalmos ipsilateral to the nevus, and the remaining one third had

GLAUCOMA ASSOCIATED WITH ENCEPHALOTRIGEMINAL ANGIOMATOSIS

Elschnig29 and Nakamura30 were the rst to realize an etiologic relationship between encephalotrigeminal angiomatosis and glaucoma. Glaucoma occurs in 30% to 70% of patients with SWS.31Y34 Usually, the glaucoma is associated with an angioma
* 2012 Asia Pacific Academy of Ophthalmology FIGURE 7. Ultrasound image showing dome-shaped hemangioma that blends with diffusely thickened choroid. Note that the A scan shows high internal reectivity. www.apjo.org

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glaucoma without buphthalmos. Buphthalmos without increased IOP has also been reported.39 Eighty-eight percent of patients with choroidal hemangiomas develop glaucoma,40 which may be congenital, adult onset, or secondary to inammation, usually following retinal detachment. Diffuse choroidal hemangioma increases the risk of developing glaucoma.

MECHANISM OF GLAUCOMA
A few mechanisms for development of glaucoma in SWS have been proposed. The mechanical theory is based on abnormalities of the outow pathway, leading to blockage of aqueous humor outow, increased IOP, and glaucoma. Patients with congenital and infantile glaucoma in SWS (0Y2 years of age) demonstrate gonioscopic abnormalities similar to children with primary congenital glaucoma, with a high insertion of the iris and increased opacication of tissues over the angle. Numerous authors have believed that glaucoma is secondary to developmental anomalies that result in chamber angle malformations. Histology reveals a poorly developed scleral spur, thickened uveal meshwork, and iris root inserted anteriorly on the base of the trabecular meshwork.21,41Y47 In some cases, supercial iris stroma appears to cover the meshwork and extend to an insertion on or near Schwalbe line. This is similar to the description sometimes reported in neurobromatosis.48 Posterior displacement and incomplete development of Schlemm canal has been described.43,94 Persistent embryonic mesodermal tissue may also be found in the angle.49 Hemorrhage from the choroidal hemangioma may result in subretinal hemorrhage and retinal detachment with forward displacement of the iris and angle closure, either on a mechanical basis or due to neovascularization.16,44,50Y53,94 In contrast, patients with late-onset glaucoma usually have normal anterior chamber angles or only mild abnormalities. These patients, however, have signs of elevated episcleral venous pressure (EVP), a key factor in the development of glaucoma: elevated IOP caused by arteriovenous shunts within the episcleral vascular malformations. Patients who develop glaucoma during adolescence usually have a scleral vascular malformation with increased EVP. Various theories in the older literature related elevated IOP to the presence of vascular malformations that might increase aqueous humor production, decrease aqueous outow, change the components of aqueous uid, or interfere with extrascleral drainage. Some authors invoked vascular hypertrophy as the cause for glaucoma.29,54,100 Increased number and/or size of choroidal vessels was postulated to cause choroidal congestion with increased transudation and/or decreased outow of aqueous humor.55,94 Miller56,101 found glaucomatous eyes in SWS to have a normal outow coefcient and concluded that elevated IOP was the result of increased aqueous production. Furthermore, ultrasound biomicroscopy has shown dilated intrascleral vessels and supraciliary uid, supporting the hypothesis of elevated EVP as the cause of open-angle glaucoma.57 Weiss47 found vascular hamartias of the anterior episclera and conjunctiva in all patients examined. Although in the earlier literature, patients without episcleral vascular malformations were reported, these vascular malformations may be subtle and occasionally evident only at surgery. Weiss hypothesized that the increased pulse pressure present on tonography indicated an arteriovenous stula and that a combination of elevated EVP (indirectly deduced by the presence of engorged vessels) and congenital angle malformation contributed in variable proportions to elevated IOP.

Phelps58 examined 19 patients with encephalotrigeminal angiomatosis and glaucoma. All had episcleral hemangiomas, the extent of which correlated roughly with the severity of the glaucoma. Elevated EVP was present in 11 of 12 eyes in which this was measured. Two patients without glaucoma had small episcleral hemangiomas. Angle deformities of a congenital nature were seen in only 2 patients. Phelps concluded that an elevated EVP caused by arteriovenous shunts was etiologically responsible for the glaucoma. Cibis et al32 found that trabeculectomy specimens from patients with SWS demonstrated changes in the trabecular meshwork and Schlemm canal similar to ndings in advanced age and chronic open-angle glaucoma. They suggested that the primary cause of juvenile glaucoma might be premature aging of the outow pathway. The most likely cause for elevated IOP seems to be a combination of developmental angle anomalies and elevated EVP,59,60 which may result in alterations of the meshwork similar to those found with aging. The relative contribution of each is dependent on the individual case. In a recent retrospective review of cases with port-wine stain, it was reported that glaucoma was more common if the lesion was bilateral and present on both upper and lower lids.61 The study also found a signicant association of glaucoma in cases with episcleral vascular malformations, iris heterochromia, and choroidal hemangioma.

MANAGEMENT OF GLAUCOMA
Management of SWS must be individualized for each patient. Glaucoma that manifests early in life may be treated with goniotomy or trabeculotomy as a reasonable rst step. Glaucoma that occurs later in life is suspected to be due to elevated EVP, and a drainage procedure, such as trabeculectomy or drainage implant, may be considered.59 Medical treatment is warranted if buphthalmos is not present and if the pressure can be adequately controlled. In a preliminary report, oral isosorbide dinitrate reduced IOP in glaucomatous eyes of patients with SWS43,62 but subsequently did not prove to be of value. All of the modern ocular hypotensive medications can be used in management of glaucoma but with a much lower efcacy. Latanoprost has been the most widely studied. The proposed mechanism of action of latanoprost to increase aqueous humor outow through the uveal-scleral pathway may circumvent the abnormal trabecular outow channels and elevated EVP. The results reported with use of latanoprost are not very encouraging in patients with SWS.63,64 It was also proposed by Altuna et al63 that prostaglandin use may lead to increased episcleral vascular engorgement and a greater risk if ltration surgery is required.

Laser and Cryotherapy

If medical treatment fails, as frequently happens, or if the glaucoma is congenital, surgical intervention is necessary. Argon laser trabeculoplasty may reduce IOP.65 Argon laser photocoagulation applied to the conjunctival vascular malformation for cosmetic reasons does not lower IOP.66 Q-switched Nd:YAG laser goniotomy failed to control the glaucoma in an 8-year-old child who was previously unsuccessfully treated with goniotomy and trabeculotomy.67 van Emelen et al68 demonstrated that primary cryotherapy of the ciliary body as a primary procedure with adjunctive medications was effective and safe in decreasing IOP below 22 mm Hg in 6 of the 7 eyes for a mean of 4.5 years. However, if the pressure-lowering effect is insufcient, the patient may require conventional surgery. If external ltration fails, cyclocryotherapy can also be attempted as a last resort.69 Cyclodiathermy has also been reported.70
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General and Preoperative Anesthetic Considerations

Because there is a need for repeated examination under anesthesia, careful preoperative evaluation and a proper anesthetic management plan are of utmost signicance. It is challenging because of difcult examination in view of young age, possible mental retardation, systemic involvement, and parental compliance. Patients with seizures should be treated with antiepileptic drugs to achieve control of convulsive disorders in the perioperative period. This can be accomplished by coordination of care across multiple disciplines, including neurologists and pediatricians.71 The anesthesiologist should be aware that the patient has SWS, as the presence of a spinal cord or brain vascular malformations may increase the risk of an intracerebral bleed or disseminated intravascular coagulation with anesthesia.72 Patients with vascular malformations of the spinal cord should avoid peridural or spinal anesthesia to prevent hemorrhage and cord compression. In addition, it is critical to prevent hypertension, which could result in hemorrhage.

The second serious complication is sudden onset of choroidal effusion after opening the globe, caused by rapid transudation of uid from the intravascular to the extravascular space in the face of elevated episcleral (and choroidal) venous pressure when the IOP is suddenly lowered.82Y84 Adverse consequences of this may be minimized by performing a posterior sclerotomy before opening the eye.74,82 Ali et al85 reported trabeculectomy in 7 eyes with complications that included shallowing of the anterior chamber, choroidal effusion, prolapse of the ciliary processes, vitreous loss, prolonged hyphema, and expulsive choroidal hemorrhage. However, these complications did not adversely affect nal postoperative visual acuity or IOP. The authors concluded that the risk of expulsive hemorrhage was reduced by the prompt control of IOP by tight suturing of the scleral ap either with releasable sutures or with sutures that could be lysed postoperatively.

Glaucoma Implants
Glaucoma drainage implants have been used with some success in management of glaucoma in SWS. Most of the devices implanted have been on late-onset disease. Budenz et al86 reported 10 eyes that underwent a 2-stage Baerveldt implant procedure with 100% success (IOP G21 mm Hg) after an average follow-up of 35 months. The Krupin-Denver valve87 has also been used, but long-term follow-up results are not available. Similar to trabeculectomy, drainage device implantation is associated with intraoperative and postoperative complications, including choroidal hemorrhage, tube-cornea touch, transcorneal/conjunctival tube erosion, tube retraction, iritis, hypotony, cataract, and retinal detachment. Celebi et al88 used an anterior chamber maintainer to stabilize IOP and minimize the risk of intraocular hemorrhage owing to sudden pressure changes when an Ahmed valve was implanted. They showed favorable outcomes in IOP control in all patients with no intraocular hemorrhage or choroidal effusion intraoperatively. They concluded that this method might reduce the risk of intraoperative suprachoroidal effusion and expulsive hemorrhage by stabilizing IOP within normal limits during the surgery.

Goniotomy, Trabeculotomy, and Trabeculectomy

Goniotomy in congenital glaucoma offers the advantage of preserving the conjunctiva in case future ltration is required. Nevertheless, this procedure, even when repeated, is frequently unsuccessful.73,74 In a retrospective study by Olsen et al,75 16 eyes of SWS patients younger than 4 years with documented angle appearances similar to congenital glaucoma received either goniotomy or trabeculotomy. Intraocular pressure was controlled in 66.7% after 1 or more procedures for a median follow-up of 5.4 years. Of the initial goniotomy eyes, two thirds required a second surgical procedure, and of the initial trabeculotomy eyes, half required a second procedure.75 Trabeculectomy may be the best choice if the angle appears clinically normal. Trabeculectomy76,77 bypasses any component of the glaucoma caused by elevated EVP, whereas goniotomy does not. Trabeculotomy may reduce the risk of expulsive hemorrhage that occurs with open surgical procedures.32 Combined trabeculotomy-trabeculectomy73,78 probably does not improve success signicantly over trabeculectomy, but it is reasonable to try if an initial goniotomy or trabeculotomy fails. Of the 30 patients with SWS with either early or late onset of glaucoma, Iwach et al79 reported that 24% of those undergoing trabeculectomy had intraoperative choroidal effusion, whereas none undergoing trabeculotomy or goniotomy did. The average stable interval of IOP control after goniotomy was 8 months, which increased to 9 years with additional goniotomies and medical therapy. Goniotomy produced a shorter duration of IOP control in patients older than 4 years. However, because trabeculectomy did not improve these results and has a higher risk of choroidal expansion, the authors concluded that goniotomy might still be the preferred initial surgical procedure in older children and young adults. Christensen and Records43 also recommended goniotomy if medical therapy was unsuccessful in juvenile or adult-onset glaucoma accompanied by a mild angle anomaly. Two serious complications may result from ltering procedures in this disease. Expulsive choroidal hemorrhage may occur as soon as the globe is entered or immediately thereafter, because of the presence of a choroidal hemangioma.43,80 Precautionary measures should be taken before surgery to reduce IOP as much as possible, and hyperosmotic agents are strongly recommended. Radiotherapy of the choroidal hemangioma might protect against expulsive hemorrhage.81 Vitreous loss and bleeding from episcleral vessels are also more common.
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Management of Choroidal Vascular Malformations

Treatment of choroidal hemangioma aims at involution of the lesion, with reduction of subretinal and intraretinal uid with minimal disruption of neurosensory retina. The treatment typically faces numerous challenges, and the decision to treat is based primarily on visual acuity potential and of retinal detachment. Therapeutic options may be limited because of the diffuse nature of the choroidal hemangioma in SWS. The surgery involves a high risk of hemorrhage secondary to abnormal vasculature. At this time, the therapeutic options include external beam radiation therapy, proton beam therapy, brachytherapy, photodynamic therapy, and antiYvascular endothelial growth factor treatment.89Y92

CONCLUSIONS
Glaucoma is the most common ocular complication of SWS, affecting 30% to 70% of patients. However, several important controversies complicate our ability to care for these patients that include the questions of managing multiple medical and anesthetic problems associated with SWS. For the ophthalmologist, accurate diagnosis and management of patients with SWS need liaison with pediatricians, neurologist, radiologist, and anesthetists. The management of glaucoma in patients with SWS is a major challenge, and the treatment of choice remains controversial. After failure of medical treatment, surgical
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management in the form of goniotomy or trabeculotomy has been recommended, but the success rate of these procedures in the long-term control of IOP has been relatively low. Glaucoma drainage devices are an option in management of lateonset glaucoma. It is hoped that, with further delineation of the mechanisms responsible for the glaucoma and genetic counseling, we may develop more successful modalities of managing patients with SWS.
REFERENCES
1. Cersoli M, Campanile S, Campanile A, et al. Unusual findings in SWS. Am J Neuroradiol. 1989;10: S85. 2. Lo W, Marchuk DA, Ball KL, et al. Brain Vascular Malformations Consortium National Sturge-Weber Syndrome Workgroup. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012;54:214Y223. 3. Schirmer R. Ein fall von telangiektasie. Graefes Arch Ophthalmol. 1860;7:119Y120. 4. Sturge WA. A case of partial epilepsy due to a lesion of one of the vasomotor centers of the brain. Trans Clin Soc London. 1879;12:162Y167. 5. Kalischer S. Demonstration des Gehirns eines Kindes mit Telangiectasie der linksseitigen Gesichtskopfhaut und Hirnoberflache. Ber Klin Wochenschr. 1887;34:1059. 6. Weber FP. On the association of extensive hemangiomatosis nevus of the skin with cerebral (meningeal) hemangioma. Proc R Soc Med. 1928;22:431Y432. 7. Comi AM, Hunt P, Vawter MP, et al. Increased fibronectin expression in Sturge-Weber syndrome fibroblasts and brain tissue. Pediatr Res. 2003;53:762Y769. 8. Puttgen KB, Lin DD. Neurocutaneous vascular syndromes. Childs Nerv Syst. 2010;26:1407Y1415. 9. Jentarra G, Snyder SL, Narayanan V . Genetic aspects of neurocutaneous disorders. Semin Pediatr Neurol. 2006;13:43Y47. 10. Huq AH, Chugani DC, Hukku B, et al. Evidence of somatic mosaicism in Sturge-Weber syndrome. Neurology. 2002;59:780Y782. 11. Eerola I, Boon LM, Mulliken JB, et al. Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet. 2003;73:1240Y1249. 12. Zhou Q, Zheng JW, Yang XJ, et al. Fibronectin: characterization of a somatic mutation in Sturge-Weber syndrome (SWS). Med Hypotheses. 2009;73:199Y200. 13. Tanwar M, Sihota R, Dada T, et al. Sturge-Weber syndrome with congenital glaucoma and cytochrome P450 (CYP1B1) gene mutations. J Glaucoma. 2010;19:398Y404. 14. Yamanaka R. Naevus Flammeus mit gleichseitigem Glaukom. Klin Mbl Augenheilkd. 1927;78:372Y375. 15. Mulliken MD, Glowacki J. Hemangiomas and vascular malformations in infants and children; a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69:412Y420. 16. Duke-Elder S. Diseases of the lens and vitreous; glaucoma and hypotony. In: System of Ophthalmology. St Louis, MO: CV Mosby Co; 1969. 17. Shaffer RN, Weiss DI. Congenital and Pediatric Glaucomas. St Louis, MO: CV Mosby Co; 1970. 18. Vannas M. Naevus flammeus pa hogra armen och handen och glaucoma pa hogra ogat. Finska Lak-Sallsk Handl. 1934;76:399Y401. 19. Teekhasaenee C, Ritch R, Rutnin U, et al. Ocular findings in oculodermal melanocytosis, Arch Ophthalmol. 1990;108:1114Y1120.

20. Beck RW, Hanno R. The phakomatoses. Int Ophthalmol Clin. 1985;25:97Y116. 21. Anderson JR. Hydrophthalmia or Congenital Glaucoma. London: Cambridge University Press; 1939. 22. Walsh FB, Hoyt WF. Clinical Neuroophthalmology. 3rd ed. Baltimore, MD: Williams & Wilkins Co, 1969. 23. Alexander GL. The Sturge-Weber syndrome. The phakomatoses. In: Vinken PJ, Bruyn GW, ed. Handbook of Clinical Neurology. Amsterdam: North Holland Pub Co; 1972:223Y240. 24. Verma L, Kumar A, Garg SP, et al. Iris neovascularization in Sturge Weber syndrome. Indian J Ophthalmol. 1991;39:82Y83. 25. Teekhasaenee C, Ritch R. Glaucoma in phacomatosis pigmentovascularis. Ophthalmology. 1997;104:150Y157. 26. Tripathi BJ, Tripathi RC. Neural crest origin of human trabecular meshwork and its implications for the pathogenesis of glaucoma. Am J Ophthalmol. 1989;107:583Y590. 27. Duke-Elder S. Diseases of the uveal tract. In: System of Ophthalmology. St Louis, MO: CV Mosby Co; 1966. 28. Susac JO, Smith JL, Scelfo RJ. The tomato-catsup fundus in Sturge-Weber syndrome. Arch Ophthalmol. 1974;92:69Y70. 29. Elschnig A. Naevus vasculosis mit gleichseitigem hydrophthalmus. Z Augenheilkd. 1918;39:189Y190. 30. Nakamura B. Angeborener halbseitiger naevus flammeus mit hydrophthalmus und knochenverdickung derselben Seite. Klin Mbl Augenheilkd. 1922;69:312Y313. 31. Alexander GL, Norman RM. The Sturge-Weber syndrome. Bristol: John Wright & Sons, Ltd; 1960. 32. Cibis GW, Tripathi RC, Tripathi BJ. Glaucoma in Sturge-Weber syndrome. Ophthalmology. 1984;91:1061Y1071. 33. Sujansky E, Conradi S. Outcome of Sturge-Weber syndrome in 52 adults. Am J Med Genet. 1995;57:35Y45. 34. Sullivan TJ, Clarke MP, Morin JD. The ocular manifestations of the Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus. 1992;29:349Y356. 35. Duhamel E, Goetz G. A propos de langiomatose ence phalotrigemine e. Bull Soc Ophthalmol Fr. 1954;6:541Y544. tiologie der Sturge-Weberschen 36. Sto ermer J. Krankheitsbild und A Erkrankung. Medizinische. 1956;6:221Y227. 37. Pollard ZF, Sessums SO, Maddox F. Bilateral congenital glaucoma in Sturge-Weber syndrome. Glaucoma. 1991;13:21Y23. 38. Danis P. Aspects ophthalmologiques des angiomatoses du syste ` me ne rveux. Acta Neurol Psychiatr Belg. 1950;50:615Y679. 39. King G, Schwartz GA. Sturge-Weber syndrome. Arch Int Med. 1954;94:743. 40. Fitzpatrick TB, Kitamura H, Kukita A, et al. Ocular and dermal melanocytosis. Arch Ophthalmol. 1956;56:830Y832. 41. Barkan O. Goniotomy for glaucoma associated with nevus flammeus. Am J Ophthalmol. 1957;43:545Y549. 42. Berkow TW. Retinitis pigmentosa associated with Sturge-Weber syndrome. Arch Ophthalmol. 1966;75:72Y76. 43. Christensen GR, Records RE. Glaucoma and expulsive hemorrhage mechanisms in the Sturge-Weber syndrome. Ophthalmology. 1979;86:1360Y1366. 44. Font RL, Ferry AP. The phakomatoses. Int Ophthalmol Clin. 1972;12:1Y50. 45. Gass JDM. The phakomatoses. In: Smith JL, ed. Neuro-ophthalmology. St Louis, MO: CV Mosby Co; 1965. 46. Kwitko ML. Glaucoma in Infants and Children. New York: Appleton-Century-Crofts; 1973.

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47. Weiss DI. Dual origin of glaucoma in encephalotrigeminal angiomatosis. Trans Ophthalmol Soc UK. 1973;93:477. 48. Grant WM, Walton DS. Distinctive gonioscopic findings in glaucoma due to neurofibromatosis. Arch Ophthalmol. 1968;79:127Y134. 49. Sedlacek J, Vrabec F. Angioma of the choroid and Sturge-Weber-Krabbes syndrome. Cesk Oftal. 1961;17:232Y237. 50. Hermans EH, Grosfeld JCM, Valk LE. Naevus epitheliomatides multiplex, een vijfde facomatose. Ned Tijdschr Geneeskd. 1959;103:1795Y1801. 51. Hogan M, Zimmerman L. Ophthalmic Pathology, An Atlas and Textbook. Philadelphia, PA: WB Saunders Co; 1962. 52. Lawford JB. Naevus of left side of face: naevus of choroid, subretinal hemorrhage and detached retina in left eye. Trans Ophthalmol Soc UK. 1885;5:136. 53. Paton L, Collins ET. Angioma of the choroid. Trans Ophthalmol Soc UK. 1919;39:157Y162. 54. Ba r C. Ein bemerkenswerter Fall von Feuermal und Glaukom. Z Augenheilkd. 1925;57:628Y630. 55. Stoll KL. Nevus flammeus and glaucoma. Trans Am Acad Ophthalmol Otol. 1936;41:534Y539. 56. Miller SJH. Symposium: the Sturge-Weber syndrome. Proc R Soc Med. 1963;56:419Y421. 57. Kranemann CF, Pavlin CJ, Trope GE. Ultrasound biomicroscopy in Sturge-WeberYassociated glaucoma. Am J Ophthalmol. 1998;125:119Y121. 58. Phelps CD. The pathogenesis of glaucoma in Sturge-Weber syndrome. Ophthalmology. 1978;85:276Y286. 59. Jorgenson JS, Guthoff R. Sturge-Weber syndrome: glaucoma with elevated episcleral venous pressure. Klin Mbl Augenheilkd. 1987;191:275Y278. 60. Shiau T, Armogan N, Yan DB, et al. The role of episcleral venous pressure in glaucoma associated with Sturge-Weber syndrome. J AAPOS. 2012;16:61Y64. 61. Khaier A, Nischal KK, Espinosa M, et al. Periocular port wine stain: the Great Ormond Street Hospital experience. Ophthalmology. 2011;118:2274Y2278. 62. Kandarakis A, Johnson TD, Ziegler LP, et al. The effect of nitrates on intraocular pressure in Sturge-Weber syndrome. Glaucoma. 1985;7:120Y126. 63. Altuna JC, Greenfield DS, Wand M, et al. Latanoprost in glaucoma associated with Sturge-Weber syndrome: benefits and side-effects. J Glaucoma. 1999;8:199Y203. 64. Yang CB, Freedman SF, Myers JS, et al. Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber syndrome. Am J Ophthalmol. 1998;126:600Y602. 65. Robin AL, Pollack IP. Argon laser trabeculoplasty in secondary forms of open angle glaucoma. Arch Ophthalmol. 1983;101:382Y384. 66. Mosier MA, Smythe BA. Conjunctival photocoagulation in Sturge-Weber syndrome. Arch Ophthalmol. 1992;110:1530Y1531. 67. Yumita A, Shirato S, Yamamoto T, et al. Goniotomy with Q-switched Nd:YAG laser in juvenile developmental glaucoma: a preliminary report. Jpn J Ophthalmol. 1984;2:349Y355. 68. van Emelen C, Goethals M, Dralands L, et al. Treatment of glaucoma in children with Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus. 2000;37:29Y34. 69. Wagner RS, Caputo AR, Del Negro RG, et al. Trabeculectomy with cyclocryotherapy for infantile glaucoma in the Sturge Weber syndrome. Ann Ophthalmol. 1988;20:289Y291. 70. Waked N, Hamard H, Godde-Jolly D, et al. Cyclodiathermy: is it effective in the treatment of glaucoma? J Franc dOphthal. 1990;13:159Y164.

71. Batra RK, Gulaya V, Madan R, et al. Anaesthesia and the Sturge-Weber syndrome. Can J Anaesth. 1994:41:133Y136. 72. DeLeon-Casasola OA, Lema MJ. Anesthesia for patients with Sturge-Weber disease and Klippel-Trenaunay syndrome. J Clin Anaesth. 1991;3:409Y413. 73. Board RJ, Shields MB. Combined trabeculotomy-trabeculectomy for the management of glaucoma associated with Sturge-Weber syndrome. Ophthalmic Surg. 1981;12:813Y817. 74. Walton DS. Hemangioma of the lid with glaucoma. In: Chandler PA, Grant WM, eds. Glaucoma. Philadelphia, PA: Lea & Febiger; 1979. 75. Olsen KE, Huang AS, Wright MM. The efficacy of goniotomy/ trabeculotomy in early-onset glaucoma associated with the Sturge-Weber syndrome. J AAPOS. 1998;2:365Y368. 76. Keverline PO, Hines DA. Trabeculectomy for adolescent onset glaucoma in the Sturge-Weber syndrome. J Pediatr Ophthalmol. 1976;13:144Y148. 77. Rosenbaum LJ. Glaucoma in Sturge Weber syndrome. Birth Defects Orig Art Ser. 1982;18:645Y649. 78. Agarwal HC, Agarwal HC, Sandramouli S, et al. Sturge-Weber syndrome: management of glaucoma with combined trabeculotomy-trabeculectomy. Ophthalmic Surg. 1993;24:399Y402. 79. Iwach AG, Hoskins HD Jr, Hetherington J Jr, et al. Analysis of surgical and medical management of glaucoma in Sturge-Weber syndrome. Ophthalmology. 1990;97:904Y909. 80. Theodossiadis G, Damanakis A, Koutsandrea C. Aderhauteffusion wa hrend einer antiglaukomatosen operation bei einem Kind mit Sturge-Weber syndrom. Klin Mbl Augenheilkd. 1985;186: 300Y302. 81. Alberti W, Greber H, John V, et al. Radiotherapy of hemangioma of the choroid. Strahlentherapie. 1983;159:160Y167. 82. Bellows AR, Chylack LT Jr, Epstein DL, et al. Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels. Arch Ophthalmol. 1979;97:493Y497. 83. Ritch R, Simmons RJ, Krupin T, et al. Cases in controversy: serous retinal detachment after glaucoma filtration surgery in Sturge-Weber Syndrome. J Glaucoma. 1992;1:58. 84. Turut P, Madelain T, Milazzo S. Uveal effusion following trabeculectomy in a case of Sturge-Weber-Krabbe syndrome. Bull Soc Ophthalmol Fr. 1985;85:33Y34. 85. Ali MA, Fahmy IA, Spaeth GL. Trabeculectomy for glaucoma associated with Sturge Weber syndrome. Ophthalmic Surg. 1990;21:352Y355. 86. Budenz DL, Sakamoto D, Eliezer R, et al. Two-staged Baerveldt glaucoma implant for childhood glaucoma associated with Sturge-Weber syndrome. Ophthalmology. 2000;107:2105Y2110. 87. Miani P, Brusini P. Krupin-Denver filtering valve implant for glaucoma in Sturge-Weber syndrome. Glaucoma. 1984;6:194Y195. 88. Celebi S, Alago z G, Aykan U. Ocular findings in Sturge-Weber syndrome. Eur J Ophthalmol. 2000;10:239Y243. 89. Chan RV , Yonekawa Y, Lane AM, et al. Proton beam irradiation using a light-field technique for the treatment of choroidal hemangiomas. Ophthalmologica. 2010;224:209Y216. 90. Hannouche D, Frau E, Desjardins L, et al. Efficacy of proton therapy in circumscribed choroidal hemangiomas associated with serious retinal detachment. Ophthalmology. 1997;104:1780Y1784. 91. Shields CL, Honavar SG, Shields JA, et al. Circumscribed choroidal hemangioma: clinical manifestations and factors predictive of visual outcome in 200 consecutive cases. Ophthalmology. 2001;108:2237Y2248. 92. Tsipursky MS, Golchet PR, Jampol LM. Photodynamic therapy of choroidal hemangioma in Sturge-Weber syndrome, with a

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review of treatments for diffuse and circumscribed choroidal hemangiomas. Surv Ophthalmol. 2011;56:68Y85. 93. Comi AM. Pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509Y516. 94. Dunphy EB. Glaucoma accompanying nevus flammeus. Trans Am Ophthalmol Soc. 1934;32:143Y152. 95. Onesti MG, Fioramonti P, Carella S, et al. Surgical and laser treatment of Sturge-Weber syndrome. Aesthetic Plast Surg. 2009;33:666Y668. 96. Patrianakos TD, Nagao K, Walton DS. Surgical management of glaucoma with the Sturge Weber syndrome. Int Ophthalmol Clin. 2008;48:63Y78.

97. Teekhasaenee C, Ritch R, Rutnin U, et al. Glaucoma in oculodermal melanocytosis, Ophthalmology. 1990;97;562Y570. 98. Weber FP. Angioma-formation in connection with hypertrophy of limbs and hemihypertrophy. Br J Dermatol. 1907;190:231Y233. 99. Zhou Q, Zheng JW, Yang XJ, et al. Detection of RASA1 mutations in patients with sporadic Sturge-Weber syndrome. Childs Nerv Syst. 2011;27:603Y607. 100. Zaun W. Ueber die Beziehungen zwischen Naevus flammeus and angeborenem Glaukom. Klin Monatsbl Augenheilkd. 1924;72:57. 101. Beltman J. Ueber angeborene Telangiektasien des Auges als Ursache von Glaucoma simplex. Graefes Arch Clin Exp Ophthalmol. 1904;59:502.

One of the penalties for refusing to participate in politics is that you end up being governed by your inferiors. Plato, 424/423 BC - 348/347 BC, Greek philosopher and mathematician.

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