Etiologies of proptosis: a review

Nicole J. Topilow, Ann Q. Tran, Eubee B. Koo, Chirsfouad R. Alabiad


Proptosis, the protrusion of the eyeball from the orbit, results from a wide variety of pathologies that can be vision- or life-threatening. Clinical history, associated physical exam findings, and imaging features are all crucial in establishing the underlying etiology. The differential diagnosis is broad, and includes infectious, inflammatory, vascular, and neoplastic entities that range from benign and indolent, to malignant and aggressive. While treatment varies significantly based on the disease process, all are aimed at preserving vision, salvaging the globe, preventing disfigurement, and reducing mortality. Both internists and general ophthalmologists should be familiar with the causes of proptosis in order to initiate the work-up for, and appropriately triage, affected patients.


proptosis, orbital tumors, orbital inflammation, orbital infection, orbital vascular anomalies

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Rootman J. Diseases of the Orbit: A Multidisciplinary Approach. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2003.

Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. 2nd ed. Philadelphia: Elsevier Saunders; 2011.

Aviv RI, Casselman J. Orbital imaging: Part 1. Normal anatomy. Clin Radiol. 2005 Mar;60(3):279-87.

Conneely MF, Hacein-Bey L, Jay WM. Magnetic resonance imaging of the orbit. Semin Ophthalmol. 2008 May-Jun;23(3):179-89.

Hallinan JT, Pillay P, Koh LH, Goh KY, Yu WY. Eye Globe Abnormalities on MR and CT in adults: An Anatomical Approach. Korean J Radiol. 2016 Sep-Oct; 17(5): 664–673.

Aviv RI1, Miszkiel K. Orbital imaging: Part 2. Intraorbital pathology. Clin Radiol. 2005 Mar;60(3):288-307.

Rootman J1, Heran MK, Graeb DA. Vascular malformations of the orbit: classification and the role of imaging in diagnosis and treatment strategies. Ophthalmic Plast Reconstr Surg. 2014 Mar-Apr;30(2):91-104.

Fledelius HC. Ultrasound in ophthalmology. Ultrasound Med Biol. 1997;23(3):365-75.

Yan L, He G, Zhou X, Zheng Y, Zhu Y, Yang J, Zhang M, Zhou Y. Clin Radiol. 2017 Sep;72(9):798. Contrast-enhanced ultrasound in the diagnosis of orbital space-occupying lesions.

Ekhlassi T, Becker N. Preseptal and orbital cellulitis. Dis Mon. 2017 Feb;63(2):30-32.

Tsirouki T, Dastiridou AI, Ibánez Flores N, Cerpa JC, Moschos MM, Brazitikos P, Androudi S. Orbital cellulitis. Surv Ophthalmol. 2018 Jul - Aug;63(4):534-553.

Danishyar A, Sergent SR. Orbital Cellulitis. StatPearls Publishing. 2019.

Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 1994 Jul-Aug;39(1):3-22.

Spellberg B1, Walsh TJ, Kontoyiannis DP, Edwards J Jr, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009 Jun 15;48(12):1743-51.

Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, Herbrecht R, Langston A, Marr KA, Schiller G, Schuster M, Wingard JR, Gonzalez CE, Revankar SG, Corcoran G, Kryscio RJ, Hare R. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006 Jan;50(1):126-33.

Nithyanandam S, Jacob MS, Battu RR, Thomas RK, Correa MA, D'Souza O. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol. 2003 Sep;51(3):231-6.

Hirabayashi KE, Kalin-Hajdu E, Brodie FL, Kersten RC, Russell MS, Vagefi MR. Retrobulbar Injection of Amphotericin B for Orbital Mucormycosis. Ophthalmic Plast Reconstr Surg. 2017 Jul/Aug;33(4):e94-e97.

Har-El G. Endoscopic management of 108 sinus mucoceles. Laryngoscope. 2001 Dec;111(12):2131-4.

Capra GG, Carbone PN, Mullin DP. Paranasal Sinus Mucocele. Head Neck Pathol. 2012 Sep; 6(3): 369–372.

Devars du Mayne M, Moya-Plana A, Malinvaud D, Laccourreye O, Bonfils P. Sinus mucocele: natural history and long-term recurrence rate. Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Jun;129(3):125-30.

Zukin LM, Hink EM, Liao S, Getz AE, Kingdom TT, Ramakrishnan V. Endoscopic Management of Paranasal Sinus Mucoceles: Meta-analysis of Visual Outcomes. Otolaryngol Head Neck Surg. 2017 Nov;157(5):760-766.

Lloyd G, Lund VJ, Savy L, Howard D. Optimum imaging for mucoceles. J Laryngol Otol. 2000 Mar;114(3):233-6.

Capra, GG, Carbone, PN, Mullin, DP. Head and Neck Pathol. 2012 Sep; 6(3): 369.

Loo JL, Looi AL, Seah LL. Visual outcomes in patients with paranasal mucoceles. Ophthalmic Plast Reconstr Surg. 2009 Mar-Apr;25(2):126-9.

Kim YS, Kim K, Lee JG, Yoon JH, Kim CH. Paranasal sinus mucoceles with ophthalmologic manifestations: a 17-year review of 96 cases. Am J Rhinol Allergy. 2011 Jul-Aug;25(4):272-5

Obeso S, Llorente JL, Rodrigo JP, Sanchez R, Mancebo G, Suarez C. Paranasal sinuses mucoceles. Our experience in 72 patients. Acta Otorrinolaringol Esp. 2009;60(5):332–9.

Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477-588.

Kamminga N, Jansonius NM, Pott JR, Links TP. Unilateral proptosis: the role of medical history. Br J Ophthalmol. 2003 Mar; 87(3): 370–371.

Weiler DL. Thyroid eye disease: a review. Clin Exp Optom. 2017 Jan;100(1):20-25.

Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves' ophthalmopathy. ypoer

Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, Gorman CA. Clinical features of Graves' ophthalmopathy in an incidence cohort. Am J Ophthalmol. 1996 Mar;121(3):284-90.

Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. J Clin Endocrinol Metab. 2013 Apr;98(4):1443-9.

Khong JJ, Finch S, De Silva C, Rylander S, Craig JE, Selva D, Ebeling PR. Risk Factors for Graves' Orbitopathy; the Australian Thyroid-Associated Orbitopathy Research (ATOR) Study. J Clin Endocrinol Metab. 2016 Jul;101(7):2711-20.

Kung AW, Yau CC, Cheng A. The incidence of ophthalmopathy after radioiodine therapy for Graves' disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab. 1994 Aug;79(2):542-6.

Li Z, Cestari DM, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018 Nov;29(6):528-534.

Mouritis M, et al. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clinical Endocrinology1997. 47; 9-14

Bahn RS. Graves' ophthalmopathy. N Engl J Med. 2010 Feb 25;362(8):726-38.

Trokel SL, Hilal SK. Recognition and differential diagnosis of enlarged extraocular muscles in computed tomography. Am J Ophthalmol. 1979 Apr;87(4):503-12.

Bailey CC, Kabala J, Laitt R, Goddard P, Hoh HB, Potts MJ, Harrad RA. Magnetic resonance imaging in thyroid eye disease. Eye (Lond). 1996;10(5):617-9.

Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016 Mar;5(1):9-26.

Zang S, Ponto KA, Kahaly GJ. Clinical review: intravenous glucocorticoids for graves' orbitopathy: efficacy and morbidity. Journal of Clinical Endocrinology and Metabolism. 2011;96(2):320–332.

Smith TJ, Kahaly GJ, Ezra DG. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017; 4;376(18):1748-1761.

Sy A, Eliasieh K, Silkiss RZ. Clinical Response to Tocilizumab in Severe Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg. 2017 May/Jun;33(3):e55-e57.

Strianese D. Update on Graves disease: advances in treatment of mild, moderate and severe thyroid eye disease. Curr Opin Ophthalmol. 2017 Sep;28(5):505-513.

Gillespie EF, Smith TJ, Douglas RS. Thyroid eye disease: towards an evidence base for treatment in the 21st century. Curr Neurol Neurosci Rep. 2012 Jun;12(3):318-24.

Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS.

Lutalo PM, D'Cruz DP. Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis). J Autoimmun. 2014 Feb-Mar;48-49:94-8.

Cotch MF, Hoffman GS, Yerg DE, Kaufman GI, Targonski P, Kaslow RA. The epidemiology of Wegener's granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheum. 1996 Jan;39(1):87-92.

Muller K, Lin JH. Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and pathologic findings. Arch Pathol Lab Med. 2014 Aug;138(8):1110-4.

Sfiniadaki E, Tsiara I, Theodossiadis P, Chatziralli I. Ocular Manifestations of Granulomatosis with Polyangiitis: A Review of the Literature. Ophthalmol Ther. 2019 Jun;8(2):227-234.

Evans M, Sharma O, LaBree L, Smith RE, Rao NA. Differences in clinical findings between Caucasians and African Americans with biopsy-proven sarcoidosis. Ophthalmology. 2007 Feb;114(2):325-33.

Pasadhika S, Rosenbaum JT. Ocular sarcoidosis. Clin Chest Med. 2015 Dec;36(4):669-83.

Demirci H, Christianson MD. Orbital and adnexal involvement in sarcoidosis: analysis of clinical features and systemic disease in 30 cases. Am J Ophthalmol. 2011 Jun;151(6):1074-1080.e1.

Beegle SH, Barba K, Gobunsuy R, Judson MA. Current and emerging pharmacological treatments for sarcoidosis: a review. Drug Des Devel Ther. 2013 Apr 12;7:325-38.

Mukherjee B, Ambreen A, Alam MS. Sarcoidosis of the ocular adnexa. Ann Allergy Asthma Immunol. 2017 Apr;118(4):512-513.

Yeşiltaş YS, Gündüz AK. Idiopathic Orbital Inflammation: Review of Literature and New Advances. Middle East Afr J Ophthalmol. 2018 Apr-Jun;25(2):71-80.

Ding ZX, Lip G, Chong V. Idiopathic orbital pseudotumour. Clin Radiol. 2011 Sep;66(9):886-92.

Mombaerts I, Goldschmeding R, Schlingemann RO, Koornneef L. What is orbital pseudotumor? Surv Ophthalmol. 1996 Jul-Aug;41(1):66-78.

Carruthers MN, TopazianMD, Khosroshahi A, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis 2015; 74:1171–1177.

Wallace Z, Mattoo H, Mahajan V, et al. Predictors of relapse in IgG4-related disease following rituximab. Rheumatology 2016; 55:1000–1008.

Derzko-Dzulynsky L. IgG4-related disease in the eye and ocular adnexa. Curr Opin Ophthalmol. 2017 Nov;28(6):617-622.

Christie B, Block L, Ma Y, Wick A, Afifi A. Retrobulbar hematoma: A systematic review of factors related to outcomes. J Plast Reconstr Aesthet Surg. 2018 Feb;71(2):155-161.

Fattahi T, Brewer K, Retana A, Ogledzki M. Incidence of retrobulbar hemorrhage in the emergency department. J Oral Maxillofac Surg. 2014 Dec;72(12):2500-2.

Kohli GS, Patel BC. Carotid Cavernous Fistula. StatPearls Publishing 2018 Dec.

Ellis JA, Goldstein H, Connolly ES Jr, Meyers PM. Carotid-cavernous fistulas. Neurosurg Focus. 2012 May;32(5):E9.

Smoker WR, Gentry LR, Yee NK, Reede DL, Nerad JA. Vascular lesions of the orbit: more than meets the eye. Radiographics. 2008 Jan-Feb;28(1):185-204.

Kumar RR, Singh A, Singh A; Abhishek. Embolization of a deep orbital varix through endovascular route. Indian J Ophthalmol. 2015 Mar;63(3):270-2.

Vadlamudi V1, Gemmete JJ2, Chaudhary N2, Pandey AS2, Kahana A. Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin. J Neurointerv Surg. 2016 Aug;8(8):e30.

Arat YO, Mawad ME, Boniuk M. Orbital venous malformations: current multidisciplinary treatment approach. Arch Ophthalmol. 2004 Aug;122(8):1151-8.

Hamedani M, Pournaras JA, Goldblum D. Diagnosis and management of enophthalmos. Surv Ophthalmol. 2007 Sep-Oct;52(5):457-73.

Nassiri N, Rootman J, Rootman DB, Goldberg RA. Orbital lymphaticovenous malformations: Current and future treatments. Surv Ophthalmol. 2015 Sep-Oct;60(5):383-405.

Saha K, Leatherbarrow B. Orbital lymphangiomas: a review of management strategies. Curr Opin Ophthalmol. 2012 Sep;23(5):433-8.

Haik BG, Karcioglu ZA, Gordon RA, Pechous BP. Capillary hemangioma (infantile periocular hemangioma). Surv Ophthalmol. 1994 Mar-Apr;38(5):399-426.

Jockin YM, Friedlander SF. Periocular infantile hemangioma. Int Ophthalmol Clin. 2010 Fall;50(4):15-25.

Sullivan TJ. Vascular Anomalies of the Orbit--A Reappraisal. Asia Pac J Ophthalmol (Phila). 2018 Sep-Oct;7(5):356-363.

Calandriello L, Grimaldi G, Petrone G, Rigante M, Petroni S, Riso M, Savino G. Cavernous venous malformation (cavernous hemangioma) of the orbit: Current concepts and a review of the literature. Surv Ophthalmol. 2017 Jul - Aug;62(4):393-403.

Pontes FS, de Oliveira JI, de Souza LL, de Almeida OP, Fregnani ER, Vilela RS, Silva WM, Fonseca FP, Pontes HA. Clinicopathological analysis of head and neck rhabdomyosarcoma: A series of 10 cases and literature review. Med Oral Patol Oral Cir Bucal. 2018 Mar 1;23(2):e188-e197.

Turner JH, Richmon JD. Head and neck rhabdomyosarcoma: a critical analysis of population-based incidence and survival data. Otolaryngol Head Neck Surg. 2011 Dec;145(6):967-73.

Amer KM, Thomson JE, Congiusta D1, Dobitsch A, Chaudhry A, Li M, Chaudhry A, Bozzo A, Siracuse B, Aytekin MN, Ghert M, Beebe KS. Epidemiology, Incidence, and Survival of Rhabdomyosarcoma Subtypes: SEER and ICES Database Analysis. J Orthop Res. 2019 Oct;37(10):2226-2230.

Karcioglu ZA, Hadjistilianou D, Rozans M, DeFrancesco S. Orbital Rhabdomyosarcoma. Cancer Control. 2004 Sep-Oct;11(5):328-33.

Sohaib SA, Moseley I, Wright JE. Orbital rhabdomyosarcoma — the radiological characteristics. Clinical Radiology. 1998 May;53(5):357-362.

Shields JA, Shields CL. Rhabdomyosarcoma: Review for the Ophthalmologist. Survey of Ophthalmology. 2003 Jan-Feb;48(1):39-57.

Olsen TG. Heegaard S. Orbital Lymphoma. Surv Ophthalmol. 2019 Jan - Feb;64(1):45-66.

Olsen TG, Holm F, Mikkelsen LH, Rasmussen PK, Coupland SE, Esmaeli B, Finger PT, Graue GF, Grossniklaus HE, Honavar SG, Khong JJ, McKelvie PA, Mulay K, Sjö LD, Vemuganti GK, Thuro BA, Heegaard S. Orbital Lymphoma- An International Multicenter Retrospective Study. Am J Ophthalmol. 2019 Mar;199:44-57.

Decaudin D, de Cremoux P, Vincent-Salomon A, Dendale R, Rouic LL. Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options. Blood. 2006 Sep 1;108(5):1451-60.

Gerbino G, Boffano P, Benech R, Baietto F, Gallesio C, Arcuri F, Benech A. Orbital lymphomas: clinical and radiological features. J Craniomaxillofac Surg. 2014 Jul;42(5):508-12.

von Holstein SL, Therkildsen MH, Prause JU, Stenman G, Siersma VD, Heegaard S. Lacrimal gland lesions in Denmark between 1974 and 2007. Acta Ophthalmol. 2013 Jun;91(4):349-54.

Andreasen S, Esmaeli B, Holstein SL, Mikkelsen LH, Rasmussen PK, Heegaard S. An Update on Tumors of the Lacrimal Gland. Asia Pac J Ophthalmol (Phila). 2017 Mar-Apr;6(2):159-172.

Tse DT, Kossler AL, Feuer WJ, et al. Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma. Ophthalmology. 2013 Jul;120(7):1313-23.

Farazdaghi MK, Katowitz WR, Avery RA. Current treatment of optic nerve gliomas. Curr Opin Ophthalmol. 2019 Sep;30(5):356-363.

Avery RA1, Fisher MJ, Liu GT. Optic pathway gliomas. J Neuroophthalmol. 2011 Sep;31(3):269-78.

Dutton JJ. Optic nerve sheath meningiomas. Surv Ophthalmol. 1992 Nov-Dec;37(3):167-83.

Parker RT, Ovens CA, Fraser CL, Samarawickrama C. Optic nerve sheath meningiomas: prevalence, impact, and management strategies. Eye Brain. 2018 Oct 24;10:85-99.

Eddleman CS, Liu JK. Optic nerve sheath meningioma: current diagnosis and treatment. Neurosurg Focus. 2007;23(5):E4.

Ahmad SM, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr Opin Ophthalmol. 2007 Sep;18(5):405-13.

Goldberg RA, Rootman J, Cline RA. Tumors metastatic to the orbit: a changing picture. Surv Ophthalmol. 1990 Jul-Aug;35(1):1-24.



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