Ocular Manifestations of the Sturge–Weber Syndrome
Sturge–Weber syndrome (SWS) or encephalotrigeminal angiomatosis is a non-inherited congenital disorder characterized by neurologic, skin, and ocular abnormalities. A somatic activating mutation (R183Q) in the GNAQ gene during early embryogenesis has been recently recognized as the etiology of vascular abnormalities in SWS. Approximately, half of the patients with SWS manifest ocular involvement including glaucoma as the most common ocular abnormality followed by choroidal hemangioma (CH). The underlying pathophysiology of glaucoma in SWS has not been completely understood yet. Early onset glaucoma comprising 60% of SWS glaucoma have lower success rates after medical and surgical treatments compared with primary congenital glaucoma. Primary angle surgery is associated with modest success in the early onset SWS glaucoma while the success rate significantly decreases in late onset glaucoma. Filtration surgery is associated with a higher risk of intraoperative and postoperative choroidal effusion and suprachoroidal hemorrhage. CH is reported in 40–50% of SWS patients. The goal of treatment in patients with CH is to induce involution of the hemangioma, with reduction of subretinal and intraretinal fluid and minimal damage to the neurosensory retina. The decision for treating diffuse CHs highly depends on the patient’s visual acuity, the need for glaucoma surgery, the presence of subretinal fluid (SRF), its chronicity, and the potential for visual recovery.
Choroidal Hemangioma, Glaucoma, Ocular Manifestations, Sturge-weber Syndrome
1. Thomas-Sohl KA, Vaslow DF, Maria BL. Sturge-Weber syndrome: a review. Pediatr Neurol 2004;30:303–310.
2. Comi AM, Roach ES, Bodensteiner J. Sturge-weber 5 syndrome. 2015. Handbook of Clinical Neurology, Elsevier; Volume 132; Pages 157-168.
3. Behrman RE, Vaughan VC. Nelson textbook of pediatrics. J Dev Behav Pediatr 1988;9:239–243.
4. Ch’ng S, Tan ST. Facial port-wine stains – clinical stratification and risks of neuro-ocular involvement. J Plast Reconstr Aesthet Surg 2008;61:889–893.
5. Nguyen C, Yohn J, Huff C, Weston W, Morelli J. 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;138:821–825.
6. Waelchli R, Aylett SE, Robinson K, Chong WK, Martinez AE, Kinsler VA. New vascular classification of port-wine stains: improving prediction of Sturge-Weber risk. Br J Dermatol 2014;171:861–867.
7. Comi AM. Topical review: pathophysiology of Sturge- Weber syndrome. J Child Neurol 2003;18:509–516.
8. Pascual-Castroviejo I, Díaz-Gonzalez C, García-Melian RM, Gonzalez-Casado I, Muñoz-Hiraldo E. Sturge- Weber syndrome: study of 40 patients. Pediatr Neurol 1993;9:283–288.
9. Pascual-Castroviejo I, Pascual-Pascual S-I, Velazquez- Fragua R, Viaño J. Sturge-Weber syndrome. Study of 55 patients. Can J Neurol Sci 2008;35:301–307.
10. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge–Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013;368:1971–1979.
11. Nakashima M, Miyajima M, Sugano H, Iimura Y, Kato M, Tsurusaki Y, et al. The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge-Weber syndrome. J Hum Genet 2014;59:691–693.
12. Tan W, Nadora DM, Gao L, Wang G, Mihm Jr MC, Nelson JS. The somatic GNAQ mutation (R183Q) is located within the blood vessels of port wine stains. J Am Acad Dermatol 2016;74:380.
13. Uchiyama Y, Nakashima M, Watanabe S, Miyajima M, Taguri M, Miyatake S, et al. Ultra–sensitive droplet digital PCR for detecting a low–prevalence somatic GNAQ mutation in Sturge–Weber syndrome. Sci Rep 2016;6:22985.
14. Comi AM. Sturge–Weber syndrome. In: Islam MP, Roach ES, editors. Handbook of clinical neurology. Volume 132. Elsevier; 2015. p. 157–168.
15. Parsa CF. Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge–Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc 2013;111:180–215.
16. Levin AV, Enzenauer RW. The eye in pediatric systemic disease. Springer; 2017.
17. Cibis GW, Tripathi RC, Tripathi BJ. Glaucoma in Sturge- Weber syndrome. Ophthalmology 1984;91:1061–1071.
18. Phelps CD. The pathogenesis of glaucoma in Sturge- Weber syndrome. Ophthalmology 1978;85:276–286.
19. Mwinula JH, Sagawa T, Tawara A, Inomata H. Anterior chamber angle vascularization in Sturge-Weber syndrome. Report of a case. Graefes Arch Clin Exp Ophthalmol 1994;232:387–391.
20. Rosenbaum LJ. Glaucoma in Sturge-Weber syndrome. Birth Defects Orig Artic Ser 1982;18:645–649.
21. Ramírez JM, Ramírez AI, Salazar JJ, Rojas B, De Hoz R, Triviño A. Schlemm’s canal and the collector channels at different developmental stages in the human eye. Cells Tissues Organs 2004;178:180–185.
22. Shiau T, Armogan N, Yan DB, Thomson HG, Levin AV. The role of episcleral venous pressure in glaucoma associated with Sturge–Weber syndrome. J AAPOS 2012;16:61–64.
23. 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.
24. Su WW. Acute primary angle-closure in Sturge-Weber syndrome. Am J Ophthalmol Case Rep 2018;10:101–104.
25. Lee DH, Shin J, Seo JH, Byon IS, Jung JH, Lee JE. Mobile lens-induced angle closure glaucoma and rubeosis iridis in Sturge Weber syndrome. Int J Ophthalmol 2015;8:1080– 1082.
26. Comi AM. An overview of current and future treatment options for Sturge–Weber syndrome. Expert Opin Orphan Drugs 2014;2:1015–1025.
27. 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;121:1173–1180.
28. Piram M, Lorette G, Sirinelli D, Herbreteau D, Giraudeau B, Maruani A. Sturge–Weber syndrome in patients with Facial Port-Wine stain. Pediatr Dermatol 2012;29:32–37.
29. Uram M, Zubillaga C. The cutaneous manifestations of Sturge-Weber syndrome. J Clin Neuroophthalmol 1982;2:245–248.
30. Awad AH, Mullaney PB, Al-Mesfer S, Zwaan JT. Glaucoma in Sturge-Weber syndrome. J AAPOS 1999;3:40–45.
31. Van Emelen C, Goethals M, Dralands L, Casteels I. Treatment of glaucoma in children with Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 2000;37:29–34.
32. Altuna JC, Greenfield DS, Wand M, Liebmann JM, Taglia DP, Kaufman PL, et al. Latanoprost in glaucoma associated with Sturge-Weber syndrome: benefits and side-effects. J Glaucoma 1999;8:199–203.
33. Ong T, Chia A, Nischal K. Latanoprost in port wine stain related paediatric glaucoma. Br J Ophthalmol 2003;87:1091–1093.
34. Yang CB, Freedman SF, Myers JS, Buckley EG, Herndon LW, Allingham RR. Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber syndrome. Am J Ophthalmol 1998;126:600–602.
35. Wygnanski-Jaffe T, Spierer A, Melamed S, Ben-Zion I. The effect of oral propranolol on intraocular pressure in infants with Sturge–Weber syndrome glaucoma. Eur J Ophthalmol 2015;25:134–136.
36. Kaushik S, Kataria P, Joshi G, Singh R, Handa S, Pandav SS, et al. Perioperative propranolol: a useful adjunct for glaucoma surgery in Sturge-Weber syndrome. Ophthalmol Glaucoma 2019;2:267–274.
37. Irkeç M, Kiratli H, Bilgiç S. Results of trabeculotomy and guarded filtration procedure for glaucoma associated with Sturge-Weber syndrome. Eur J Ophthalmol 1999;9:99–102.
38. Iwach AG, Hoskins Jr HD, Hetherington Jr J, Shaffer RN. Analysis of surgical and medical management of glaucoma in Sturge-Weber syndrome. Ophthalmology 1990;97:904– 909.
39. Olsen KE, Huang AS, Wright MM. The efficacy of goniotomy/trabeculotomy in early-onset glaucoma associated with the Sturge-Weber syndrome. J AAPOS 1998;2:365–368.
40. Wagner R, Caputo A, Del RN, Neigel J. Trabeculectomy with cyclocryotherapy for infantile glaucoma in the Sturge- Weber syndrome. Ann Ophthalmol 1988;20:289–291, 295.
41. Wu Y, Yu R, Chen D, Xu L, Zhu L, Li M, et al. Early trabeculotomy ab externo in treatment of Sturge-Weber syndrome. Am J Ophthalmol 2017;182:141–146.
42. Patrianakos TD, Nagao K, Walton DS. Surgical management of glaucoma with the Sturge Weber syndrome. Int Ophthalmol Clin 2008;48:63–78.
43. Javaid U, Ali MH, Jamal S, Butt NH. Pathophysiology, diagnosis, and management of glaucoma associated with Sturge-Weber syndrome. Int Ophthalmol 2018;38:409–416.
44. Wu Y, Peng C, Ding X, Zeng C, Cui C, Xu L, et al. Episcleral hemangioma distribution patterns could be an indicator of trabeculotomy prognosis in young SWS patients. Acta Ophthalmol 2020;98:e685–e690.
45. Mandal AK. Primary combined trabeculotomytrabeculectomy for the management of glaucoma associated with Sturge–Weber syndrome. Ophthalmology 1999;106:1621–1627.
46. Sood D, Rathore A, Sood I, Kumar D, Sood NN. Longterm intraocular pressure after combined trabeculotomytrabeculectomy in glaucoma associated with Sturge- Weber syndrome. Eur J Ophthalmol 2018;28:210–215.
47. Agarwal H, Sandramouli S, Sood N. Sturge-Weber syndrome: management of glaucoma with combined trabeculotomy-trabeculectomy. Ophthalmic Surg Lasers Imaging Retina 1993;24:399.
48. Board RJ, Shields MB. Combined trabeculotomytrabeculectomy for the management of glaucoma associated with Sturge-Weber syndrome. Ophthalmic Surg Lasers Imaging Retina 1981;12:813–817.
49. Ali MA, Fahmy IA, Spaeth GL. Trabeculectomy for glaucoma associated with Sturge-Weber syndrome. Ophthalmic Surg Lasers Imaging Retina 1990;21:352–355.
50. Bellows AR, Chylack Jr LT, Hutchinson BT. Choroidal detachment: clinical manifestation, therapy and mechanism of formation. Ophthalmology 1981;88:1107–1115.
51. Bellows AR, Chylack LT, Epstein DL, Hutchinson BT. Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels. Arch Ophthalmol 1979;97:493–497.
52. Pandey A, Balekudaru S, George R, Lingam V, Panday M. Surgical management of glaucoma in Sturge–Weber syndrome. Glauc Open Access 2015;1:1.
53. Eibschitz-Tsimhoni M, Lichter PR, Del Monte MA, Archer SM, Musch DC, Schertzer RM, et al. Assessing the need for posterior sclerotomy at the time of filtering surgery in patients with Sturge-Weber syndrome. Ophthalmology 2003;110:1361–1363.
54. Mohamed TH, Salman AG, Elshinawy RF. Trabeculectomy with Ologen implant versus mitomycin C in congenital glaucoma secondary to Sturge Weber Syndrome. Int J Ophthalmol 2018;11:251.
55. Audren F, Abitbol O, Dureau P, Hakiki S, Orssaud C, Bourgeois M, et al. Non-penetrating deep sclerectomy for glaucoma associated with Sturge–Weber syndrome. Acta Ophthalmol Scand 2006;84:656–660.
56. Hamush NG, Coleman AL, Wilson MR. Ahmed glaucoma valve implant for management of glaucoma in Sturge- Weber syndrome. Am J Ophthalmol 1999;128:758–760.
57. Kaushik J, Parihar JKS, Jain VK, Mathur V. Ahmed valve implantation in childhood glaucoma associated with Sturge–Weber syndrome: our experience. Eye 2019;33:464–468.
58. Budenz DL, Sakamoto D, Eliezer R, Varma R, Heuer DK. Two-staged Baerveldt glaucoma implant for childhood glaucoma associated with Sturge-Weber syndrome. Ophthalmology 2000;107:2105–2110.
59. Amini H, Razeghinejad MR, Esfandiarpour B. Primary single-plate Molteno tube implantation for management of glaucoma I children with Sturge–Weber syndrome. Int Ophthalmol 2007;27:345–350.
60. Sharan S, Swamy B, Taranath DA. Port-wine vascular malformations and glaucoma risk in Sturge–Weber syndrome. J AAPOS 2009;13:374–378.
61. Abdolrahimzadeh S, Scavella V, Felli L, Cruciani F, Contestabile MT, Recupero SM. Ophthalmic alterations in the Sturge–Weber syndrome, Klippel-Trenaunay syndrome, and the Phakomatosis Pigmentovascularis: an independent group of conditions. Bio Med Res Int 2015;2015:786519.
62. Formisano M, Abdolrahimzadeh B, Mollo R, Bruni P, Malagola R, Abdolrahimzadeh S. Bilateral diffuse choroidal hemangioma in Sturge Weber syndrome: a case report highlighting the role of multimodal imaging and a brief review of the literature. J Curr Ophthalmol 2019;31:242–249.
63. Ferry A, Combs J. Other phakomatoses. Retina 2001;1:596–600.
64. Witschel H, Font RL. Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature. Surv Ophthalmol 1976;20:415–431. 65. Shanmugam PM, Ramanjulu R. Vascular tumors of the choroid and retina. Indian J Ophthalmol 2015;63:133.
66. Scott IU, Alexandrakis G, Cordahi GJ, Murray TG. Diffuse and circumscribed choroidal hemangiomas in a patient with Sturge-Weber syndrome. Arch Ophthalmol 1999;117:406–407.
67. Horgan N, O’Keefe M, McLoone E, Lanigan B. Fundus fluorescein angiographic characterization of diffuse choroidal hemangiomas. J Pediatr Ophthalmol Strabismus 2008;45:26–30.
68. Giovannini A, Scassellati-Sforzolini B, D’Altobrando E, Mariotti C, Rutili T, Tittarelli R. Choroidal findings in the course of idiopathic serous pigment epithelium detachment detected by indocyanine green videoangiography. Retina 1997;17:286–293.
69. Shields CL, Manalac J, Das C, Saktanasate J, Shields JA. Review of spectral domain enhanced depth imaging optical coherence tomography of tumors of the choroid. Indian J Ophthalmol 2015;63:117.
70. Arora KS, Quigley HA, Comi AM, Miller RB, Jampel HD. Increased choroidal thickness in patients with Sturge- Weber syndrome. JAMA Ophthalmol 2013;131:1216–1219.
71. Surve A, Azad S, Venkatesh P, Kumar V, Chawla R, Gupta V, et al. Choroidal vascular pattern in cases of Sturge-Weber syndrome. Ophthalmol Retina 2019;3:1091–1097.
72. Abdolrahimzadeh S, Felli L, Plateroti AM, Perdicchi A, Contestabile MT, Recupero SM. Spectral domain optical coherence tomography evidence of retinal nerve fiber layer and ganglion cell loss in adult patients with neurofibromatosis type 1. Retina 2016;36:75–81.
73. Abdolrahimzadeh S, Parisi F, Mantelli F, Perdicchi A, Scuderi G. Retinal pigment epithelium–photoreceptor layer alterations in a patient with Sturge–Weber syndrome with diffuse choroidal hemangioma. Ophthalmic Genet 2017;38:567–569.
74. Griffiths PD, Boodram MB, Blaser S, Altomare F, Buncic JR, Levin AV, et al. Abnormal ocular enhancement in Sturge-Weber syndrome: correlation of ocular MR and CT findings with clinical and intracranial imaging findings. Am J Neuroradiol 1996;17:749–754.
75. Griffiths P. Sturge-Weber syndrome revisited: the role of neuroradiology. Neuropediatrics 1996;27:284–294.
76. Randon M, Lévy-Gabriel C, Abbas R, Dendale R, Lumbroso L, Desjardins L, et al. Results of external beam radiotherapy for diffuse choroidal hemangiomas in Sturge–Weber syndrome. Eye 2018;32:1067–1073.
77. Schilling H, Sauerwein W, Lommatzsch A, Friedrichs W, Brylak S, Bornfeld N, et al. Long term results after low dose ocular irradiation for choroidal haemangiomas. Br J Ophthalmol 1997;81:267–273.
78. Ritland J, Eide N, Tausjø J. External beam irradiation therapy for choroidal haemangiomas. Visual and anatomical results after a dose of 20 to 25 Gy. Acta Ophthalmol Scand 2001;79:184–186.
79. Grant LW, Anderson C, Macklis RM, Singh AD. Low dose irradiation for diffuse choroidal hemangioma. Ophthalmic Genet 2008;29:186–188.
80. Gottlieb JL, Murray TG, Gass JDM. Low-dose external beam irradiation for bilateral diffuse choroidal hemangioma. Arch Ophthalmol 1998;116:815–817.
81. Zografos L, Egger E, Bercher L, Chamot L, Munkel G. Proton beam irradiation of choroidal hemangiomas. Am J Ophthalmol 1998;126:261–268.
82. Arepalli S, Shields CL, Kaliki S, Emrich J, Komarnicky L, Shields JA. Diffuse choroidal hemangioma management with plaque radiotherapy in 5 cases. Ophthalmology 2013;120:2358–2359.e2.
83. Anand R. Photodynamic therapy for diffuse choroidal hemangioma associated with Sturge Weber syndrome. Am J Ophthalmol 2003;136:758–760.
84. Bains HS, Cirino AC, Ticho BH, Jampol LM. Photodynamic therapy using verteporfin for a diffuse choroidal hemangioma in Sturge–Weber syndrome. Retina 2004;24:152–155.
85. Hussain RN, Jmor F, Damato B, Heimann H. Verteporfin photodynamic therapy for the treatment of choroidal haemangioma associated with Sturge-Weber syndrome. Photodiagnosis Photodyn Ther 2016;15:143–146.
86. Singh A, Rundle P, Vardy S, Rennie I. Photodynamic therapy of choroidal haemangioma associated with Sturge–Weber syndrome. Eye 2005;19:365–367.
87. Tsipursky MS, Golchet PR, Jampol LM. Photodynamic therapy of choroidal hemangioma in Sturge-Weber syndrome, with a review of treatments for diffuse and circumscribed choroidal hemangiomas. Surv Ophthalmol 2011;56:68–85.
88. Shoeibi N, Ahmadieh H, Abrishami M, Poorzand H. Rapid and sustained resolution of serous retinal detachment in Sturge-Weber syndrome after single injection of intravitreal bevacizumab. Ocul Immunol Inflamm 2011;19:358–360.
89. Wong WT, Liang KJ, Hammel K, Coleman HR, Chew EY. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease. Ophthalmology 2008;115:1957–1964.e3.
90. Thapa R, Shields CL. Oral propranolol therapy for management of exudative retinal detachment from diffuse choroidal hemangioma in Sturge-Weber syndrome. Eur J Ophthalmol 2013;23:917–919.
91. Lamy S, Lachambre M-P, Lord-Dufour S, Béliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vasc Pharmacol 2010;53:200–208.
92. Ristori C, Filippi L, Dal Monte M, Martini D, Cammalleri M, Fortunato P, et al. Role of the adrenergic system in a mouse model of oxygen-induced retinopathy: antiangiogenic effects of β-adrenoreceptor blockade. Invest Ophthalmol Vis Sci 2011;52:155–170.
93. Martini D, Monte MD, Ristori C, Cupisti E, Mei S, Fiorini P, et al. Antiangiogenic effects of β2−adrenergic receptor blockade in a mouse model of oxygen−induced retinopathy. J Neurochem 2011;119:1317–1329.
94. Mains J, Tan LE, Wilson C, Urquhart A. A pharmacokinetic study of a combination of beta adrenoreceptor antagonists–In the isolated perfused ovine eye. Eur J Pharma Biopharma 2012;80:393–401.
95. Nourinia R, Kanavi MR, Kaharkaboudi A, Taghavi SI, Aldavood SJ, Darjatmoko SR, et al. Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization. Invest Ophthalmol Vis Sci 2015;56:8228–8235.
96. Karimi S, Nikkhah H, Ahmadieh H, Safi S. Intravitreal injection of propranolol for the treatment of retinal capillary hemangioma in a case of Von Hippel-Lindau. Retin Cases Brief Rep 2020;14:305–309.
97. Aggarwal NK, Gandham SB, Weinstein R, Saltzmann R, Walton DS. Heterochromia iridis and pertinent clinical findings in patients with glaucoma associated with Sturge– Weber syndrome. J Pediatr Ophthalmol Strabismus 2010;47:361–365.
98. Plateroti AM, Plateroti R, Mollo R, Librando A, Contestabile MT, Fenicia V. Sturge-Weber syndrome associated with monolateral ocular melanocytosis, iris mammillations, and diffuse choroidal haemangioma. Case Rep Opthalmol 2017;8:375–384.
99. Bakri SS, Jomar D, Alsulaiman SM, Abouammoh MA. Combined cilioretinal artery and hemi-retinal vein occlusion in Sturge Weber syndrome: expanding the clinical spectrum. Saudi J Ophthalmol 2018;32:234–237.
100. Koenraads Y, van Egmond−Ebbeling MB, de Boer JH, Imhof SM, Braun KP, Porro GL, et al. Visual outcome in Sturge–Weber syndrome: a systematic review and Dutch multicentre cohort. Acta Ophthalmol 2016;94:638–645.
101. Lo W, Marchuk DA, Ball KL, Juhász C, Jordan LC, Ewen JB, et al. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge–Weber syndrome brain involvement. Dev Med Child Neurol 2012;54:214– 223.
102. Alejandro J, Luat AF, Juhász C, Ho ML, Argersinger DP, Cavuoto KM, et al. A multidisciplinary consensus for clinical care and research needs for Sturge-Weber syndrome. Pediatr Neurol 2018;84:11–20.
103. Nguyen V, Hochman M, Mihm MC, Nelson JS, Tan W. The pathogenesis of port wine stain and Sturge Weber syndrome: complex interactions between genetic alterations and aberrant MAPK and PI3K activation. Int J Mol Sci 2019;20:2243.
104. Comi AM, Sahin M, Hammill A, Kaplan EH, Juhász C, North P, et al. Leveraging a Sturge-Weber gene discovery: an agenda for future research. Pediatr Neurol 2016;58:12–24.