Title: Exophthalmos

{{short description|Bulging of the eye anteriorly out of the orbit}}
{{redirect-distinguish|Proptosis|Ptosis (eyelid)}}
{{distinguish|text=[[Exophthalmus]] weevils}}
{{more citations needed|date=May 2010}}
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{{Infobox medical condition
| name          = Exophthalmos
| image         = Girl aged 17 years with marked proptosis Wellcome L0062481.jpg
| caption       = Bilateral exophthalmos in a 17-year-old girl with facial symptoms of [[Pfeiffer syndrome]]
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'''Exophthalmos''' (also called '''exophthalmus''', '''exophthalmia''', '''proptosis''', or '''exorbitism''') is a bulging of the [[eye]] anteriorly out of the [[orbit (anatomy)|orbit]].  Exophthalmos can be either bilateral (as is often seen in [[Graves' disease]]) or unilateral (as is often seen in an orbital tumor). Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma.

Exophthalmos has endocrine causes. In the case of Graves' disease, the displacement of the eye results from abnormal connective tissue deposition in the orbit and [[extraocular muscles]], which can be visualized by [[Computed axial tomography|CT]] or [[MRI]].&lt;ref name=Epstein&gt;{{cite book|author1=Owen Epstein |author2=David Perkin |author3=John Cookson |author4=David P de Bono |title=Clinical examination |edition=3rd|publisher=Mosby|location=St. Louis|date=April 2003|isbn=0-7234-3229-5}}&lt;/ref&gt;

If left untreated, exophthalmos can cause the eyelids to fail to close during sleep, leading to [[cornea]]l dryness and damage. Another possible complication is a form of redness or irritation called [[superior limbic keratoconjunctivitis]], in which the area above the cornea becomes inflamed as a result of increased friction when blinking. The process that is causing the displacement of the eye may also compress the [[optic nerve]] or [[ophthalmic artery]], and lead to [[blindness]].

==Causes==
Many patients with exophthalmos have a history of endocrine abnormalities, including thyroid related disease or &quot;thyrotoxic activity&quot;. Other endocrine related causes of exophthalmos include infection and &quot;IgG4-related disease&quot;. The most common cause of exophthalmos in adults is eye disease associated with a dysfunctioning thyroid gland. Exophthalmos in children is possible and most likely caused by tumors or cancers like leukemia.&lt;ref name=&quot;Butt_2023&quot;&gt;{{cite book | vauthors = Butt S, Patel BC | chapter = Exophthalmos | date = June 2023 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 32644749 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK559323/ }}&lt;/ref&gt; In rare cases, exophthalmos can occur in patients with normal thyroid function or underactive thyroid function.&lt;ref&gt;&quot;Exophthalmos (bulging eyes) | nidirect&quot;. ''www.nidirect.gov.uk''. 2018-12-18. Retrieved 2025-02-10.&lt;/ref&gt;

The thyroid gland is stimulated by thyroid-stimulating hormone (TSH). The majority of patients with Grave's disease have antibodies called thyroid-stimulating antibodies, which are immune to the thyroid stimulating hormone. The thyroid stimulating hormone has some receptors in the fat cells around the eyeballs.&lt;ref name=&quot;Havard_1979&quot;&gt;{{cite journal | vauthors = Havard CW | title = Progress in endocrine exophthalmos | journal = British Medical Journal | volume = 1 | issue = 6169 | pages = 1001–4 | date = April 1979 | pmid = 582020 | pmc = 1598686 | doi = 10.1136/bmj.1.6169.1001 | url = }}&lt;/ref&gt; The immune system attacks the fatty tissues, as well as other tissues around the eyes, causing them to stick out from the sockets.&lt;ref name=&quot;www.medicalnewstoday.com_2017&quot;&gt;{{cite web | title = Exophthalmos: Causes, symptoms, and treatment. | work = www.medicalnewstoday.com | date = 2017-05-22 | access-date = 2025-02-10 | url = https://www.medicalnewstoday.com/articles/experimental-stem-cell-therapy-could-heal-injured-corneas-restore-vision }}&lt;/ref&gt; There is something called exophthalmos-producing substance, which competes with thyroid stimulating hormone receptors. The affinity of the exophthalmos-producing substance is strengthened if there is also &quot;ophthalmologic immunoglobulins&quot;.&lt;ref name=&quot;Havard_1979&quot; /&gt;

Exophthalmos can also happen from something that pushes the eye toward the front of the socket. Some examples include blood clots, tumors, infection, or trauma..&lt;ref name=&quot;www.medicalnewstoday.com_2017&quot; /&gt;

According to the [[NCBI]], the following conditions feature exophthalmos:&lt;ref&gt;{{Cite web |title=Proptosis | id = Concept Id: C0015300  | work = MedGen | publisher = U.S. National Library of Medicine |url=https://www.ncbi.nlm.nih.gov/medgen/41917 |access-date=2024-03-24 |language=en}}&lt;/ref&gt;
* [[Wolf-Hirschhorn syndrome|4p partial monosomy syndrome]]
[[File:Casazza 1.jpg|thumb|Exophthalmos in Acrocephalosyndactyly type 1]]
* [[Apert syndrome|Acrocephalosyndactyly type I]]
* [[Acrofrontofacionasal dysostosis]] type 2
* [[Loeys-Dietz syndrome|Aneurysm-osteoarthritis syndrome]]
* [[Antley-Bixler syndrome]]
* [[Atelosteogenesis type I]]
* [[Autism spectrum disorder]] due to [[AUTS2]] deficiency
* [[Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome]]
* [[Autosomal dominant]] [[Robinow syndrome]] 1–3
* [[Autosomal recessive]] [[congenital ichthyosis]] 4B
* [[infantile malignant osteopetrosis|Autosomal recessive osteopetrosis]] 5, 7
* Autosomal recessive Robinow syndrome
* [[Axenfeld-Rieger anomaly]] with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities
* [[Axenfeld-Rieger syndrome]] type 3
* [[Beare-Stevenson cutis gyrata syndrome]]
* [[Beckwith-Wiedemann syndrome]]
* [[Bohring-Opitz syndrome]]
* [[Cardio-facio-cutaneous syndrome]]
* [[Catel-Manzke syndrome]]
* Childhood [[hypophosphatasia]]
* [[Chondrodysplasia]] with [[joint dislocations]], gPAPP type
[[File:Davis Oxycephalus 1.jpg|thumb|Exophthalmos in cloverleaf skull]]
* [[Kleeblattschaedel|Cloverleaf skull syndrome]]
* [[COG1]] [[congenital disorder of glycosylation]]
* [[Cole-Carpenter syndrome]] 1, 2
* [[Congenital myopathy]] 22A, classic
* Congenital myopathy 22B, severe fetal
* [[Cornelia de Lange syndrome]] 1
* [[Craniosynostosis]] 4
* [[Craniosynostosis and dental anomalies]]
[[File:Crouzon Syndrome 5.jpg|thumb|Exophthalmos in Crouzon syndrome]]
* [[Crouzon syndrome]]
* [[Crouzon syndrome with acanthosis nigricans|Crouzon syndrome-acanthosis nigricans syndrome]]
* [[Cutis laxa]], autosomal recessive, types 1B and 2E
* Developmental and [[epileptic]] [[encephalopathy]], 48, 75, and 80
* [[Donnai-Barrow syndrome]]
* [[Ehlers-Danlos syndrome]], spondylodysplastic type, 1 and 2
* Familial [[hyperthyroidism]] due to mutations in [[TSH receptor]]
* [[Fibrochondrogenesis]] 1
* [[Fibrous dysplasia]] of jaw
* [[Filippi syndrome]]
* Fontaine [[progeroid syndrome]]
* [[Frank-Ter Haar syndrome]]
* [[Graves disease]], susceptibility to, 1
* [[H syndrome]]
* [[Holoprosencephaly]] 2, 3, and 11
* [[X-linked intellectual disability|Intellectual disability, X-linked]], syndromic 33
* [[Jackson-Weiss syndrome]]
* [[Keppen-Lubinsky syndrome]]
* [[Kniest dysplasia]]
* [[Larsen syndrome|Larsen]]-like syndrome, [[B3GAT3]] type
* [[Donohue syndrome|Leprechaunism syndrome]]
* [[Liver disease]], severe congenital
* [[Loeys-Dietz syndrome]] 1, 2
* [[Mandibuloacral dysplasia]] progeroid syndrome
* Mandibuloacral dysplasia with type A [[lipodystrophy]]
* Mandibuloacral dysplasia with type B lipodystrophy
* Marbach-Rustad progeroid syndrome
* [[Marshall-Smith syndrome]]
* [[Melnick-Needles syndrome]]
* [[Microcephalic osteodysplastic primordial dwarfism]], type 3
[[File:Turricephalus (microcephalic type).jpg|thumb|Exophthalmos in microcephaly (with [[turricephaly]])]]
* [[Microcephaly]] 3, primary, autosomal recessive
* Microcephaly 5, primary, autosomal recessive
* [[Muenke syndrome]]
* [[NDE1]]-related [[microhydranencephaly]]
* Neonatal pseudo-hydrocephalic progeroid syndrome
* Nestor-Guillermo progeria syndrome
* [[Neu-Laxova syndrome]] 1, 2
* [[Ogden syndrome]]
* [[Osteogenesis imperfecta]] types 7, 8
* [[Pallister-Killian syndrome]]
* [[Periventricular nodular heterotopia]] 7
* [[Pontocerebellar hypoplasia]] types 3, 10
* [[marfanoid-progeroid-lipodystrophy syndrome|Progeroid and marfanoid aspect-lipodystrophy syndrome]]
* [[Prolidase deficiency]]
* [[Restrictive dermopathy]] 2
* [[Loeys-Dietz syndrome|Rienhoff syndrome]]
* [[Ritscher-Schinzel syndrome]] 4
* [[Roberts syndrome|Roberts-SC phocomelia syndrome]]
* Robinow syndrome, autosomal recessive 2
* [[Rubinstein-Taybi syndrome]] due to [[CREBBP]] mutations
* [[Sclerosteosis]] 1
* [[Shprintzen-Goldberg syndrome]]
* [[Spondyloepimetaphyseal dysplasia]] with joint laxity, type 1, with or without fractures
* [[Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome]]
* Spondylometaphyseal dysplasia with [[corneal dystrophy]]
* [[Tetralogy of Fallot]]
* [[Thyroid hormone resistance]], generalized, autosomal recessive
* [[Yunis-Varon syndrome]]

==Anatomy==
{{see also|Anatomical terms of location}}
Proptosis is the anterior displacement of the eye from the orbit.  Since the orbit is closed off posteriorly, medially and laterally, any enlargement of structures located within will cause the anterior displacement of the eye.&lt;ref name=Robbins&gt;{{cite book| vauthors = Mitchell RN |title=Pocket companion to Robbins and Cotran pathologic basis of disease|publisher=Elsevier Saunders|location=Philadelphia, PA|isbn=978-1-4160-5454-2|chapter=Eye|date=2011|edition=8th}}&lt;/ref&gt;  Swelling or enlargement of the lacrimal gland causes inferior medial and anterior dislocation of the eye.  This is because the lacrimal glands are located superiorly and laterally in the orbit.&lt;ref name=Robbins /&gt;

==Diagnosis and treatment==
=== Measurement ===
Measurement of the degree of exophthalmos is performed using an [[exophthalmometer]].

Most sources define exophthalmos/proptosis as a protrusion of the globe greater than 18&amp;nbsp;mm.&lt;ref name=Epstein /&gt;

The term exophthalmos is often used when describing proptosis associated with [[Graves' disease]].&lt;ref&gt;{{EMedicine|article|1218575|Exophthalmos (Proptosis)}}&lt;/ref&gt;

=== Treatment ===
Exophthalmos is a progressive disease, so early detection and treatment is ideal. Diagnosing this condition may include imaging scans such as CT or MRI as well as blood tests to determine if the thyroid gland is functioning properly. Often, eye protrusion is measured to see how the disease progresses. Treatment for this disease includes radiation, surgery, and quitting smoking.&lt;ref name=&quot;www.medicalnewstoday.com_2017&quot; /&gt; Many times exophthalmos symptoms improve when hyperthyroidism is controlled, possibly using corticosteroid hormone replacement therapy.&lt;ref name=&quot;Butt_2023&quot; /&gt;&lt;ref name=&quot;Havard_1979&quot; /&gt;

==Animals==
[[Image:Exophthalmos in pug.JPG|thumb|Exophthalmos in a Pug]]
Exophthalmos is commonly found in [[dog]]s.  It is seen in [[cephalic index|brachycephalic]] (short-nosed) dog breeds because of the shallow [[orbit (anatomy)|orbit]].  It can lead to [[keratitis]] secondary to exposure of the [[cornea]].  Exophthalmos is commonly seen in the [[pug]], [[Boston terrier]], [[Pekingese]], and [[shih tzu]]. It is a common result of [[head trauma]] and pressure exerted on the front of the neck too hard in dogs. In cats, eye proptosis is uncommon and is often accompanied by facial fractures.&lt;ref&gt;{{cite web | title = Prolapse of the Eye | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/30119.htm | access-date = 2007-03-23 }}&lt;/ref&gt;

About 40% of proptosed eyes retain vision after being replaced in the [[orbit (anatomy)|orbit]], but in cats very few retain vision.&lt;ref&gt;{{cite conference | vauthors = Gelatt KN | title = Treatment of Orbital Diseases in Small Animals | conference = Proceedings of the 27th World Congress of the World Small Animal Veterinary Association | year = 2002 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2002&amp;PID=2641 | access-date = 2007-03-23 }}&lt;/ref&gt;   Replacement of the eye requires general [[anesthesia]].  The eyelids are pulled outward, and the eye is gently pushed back into place.  The eyelids are sewn together in a procedure known as [[tarsorrhaphy]] for about five days to keep the eye in place.&lt;ref name=Gelatt_1999&gt;{{cite book | veditors = Gelatt KN |title=Veterinary Ophthalmology |date=1999 |publisher=Lippincott Williams &amp; Wilkins |isbn=978-0-683-30076-5 }}{{page needed|date=February 2023}}&lt;/ref&gt;  Replaced eyes have a higher rate of [[keratoconjunctivitis sicca]] and [[keratitis]] and often require lifelong treatment.  If the damage is severe, the eye is removed in a relatively simple [[surgery]] known as [[enucleation of the eye]].

The [[prognosis]] for a replaced eye is determined by the extent of damage to the [[cornea]] and [[sclera]], the presence or absence of a [[pupillary light reflex]], and the presence of ruptured [[muscles of orbit|rectus muscle]]s.  The rectus muscles normally help hold the eye in place and direct eye movement.  Rupture of more than two rectus muscles usually requires the eye to be removed, because significant blood vessel and nerve damage also usually occurs.&lt;ref name=Gelatt_1999/&gt;  Compared to brachycephalic breeds, dochilocephalic (long-nosed) breeds usually have more trauma to the eye and its surrounding structures, so the prognosis is worse.&lt;ref&gt;{{cite conference | vauthors = Bjerk E | title = Ocular Injuries in General Practice | conference = Proceedings of the 29th World Congress of the World Small Animal Veterinary Association | year = 2004 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&amp;PID=8722&amp;O=Generic | access-date = 2007-03-23 }}&lt;/ref&gt;

==See also==
* [[Boston's sign]]
* [[Carotid-cavernous fistula]]
* [[Enophthalmos]]
* [[Von Graefe's sign]]

==References==
{{reflist}}

{{Medical resources
|   ICD10          = {{ICD10|H|05|2|h|00}}
|   ICD9           = {{ICD9|376.2}}-{{ICD9|376.3}}
|   ICDO           =
|   OMIM           =
|   MedlinePlus    = 003033
|   eMedicineSubj  = oph
|   eMedicineTopic = 616
|   DiseasesDB     = 18612
|   MeshID         = D005094
}}
{{Eye pathology}}
{{Authority control}}

[[Category:Disorders of eyelid, lacrimal system and orbit]]
[[Category:Dog diseases]]