Exophthalmos: Causes and Diagnosis of Eye Protrusion

Exophthalmos (synonym: proptosis) is a forward protrusion of the eyeball due to an increase in the volume of the orbital contents within a rigid bony "box." It is not a diagnosis, but an umbrella symptom, encompassing conditions ranging from thyroid ophthalmopathy to tumors, vascular malformations, infection, and trauma. The terms "exophthalmos" and "proptosis" are used interchangeably in clinical practice; the distinction is primarily historical and lexical. [1]

The protrusion is measured with an exophthalmometer (usually a Hertel one): approximately 12-21 mm is considered normal, while asymmetry of >2 mm warrants further diagnostic evaluation. Race, age, and facial skeletal structure are taken into account in the interpretation (upper limits are higher in African Americans, while in children, the value increases with age). Radiological exophthalmometry using CT is helpful when bony landmarks are displaced following injury or surgery. [2]

Clinical management depends on the rate of progression, pain, diplopia, decreased vision, noise/pulsation, fever, and medical history (trauma, thyroid disease, sinusitis, oncology). A number of conditions require immediate action: orbital compartment syndrome with retrobulbar hemorrhage, purulent orbititis, carotid-cavernous fistula, and vision-threatening thyroid neuropathy. [3]

In this article, I'll break it down: from codes and epidemiology to causes, step-by-step diagnostics, differential diagnosis, and modern treatment (including targeted therapy for thyroid eye disease, endovascular techniques for fistulas, oncologic approaches for lymphoma/metastases, etc.). If needed, I'll supplement it with adapted tips for physicians/patients.

ICD-10 and ICD-11 codes

In ICD-10-CM, the category "exophthalmos" is represented by block H05.2 "Exophthalmic conditions." A separate block is H05.20 "Unspecified exophthalmos," as well as subcategories for lateral displacement, orbital edema, hemorrhage, and others. In practice, the cause (e.g., thyrotoxicosis with diffuse goiter) and orbital manifestations are coded simultaneously. [4]

In ICD-11, symptoms of displacement of the eyeball are classified in block 9A20 "Displacement of eyeball"; 9A20.00 "Outward displacement of eyeball" corresponds to exophthalmos/proptosis. For clinical precision, ICD-11 uses post-coordination: an etiologic code (e.g., 5A02.0 for Graves' disease/diffuse toxic goiter) and clarifications (side, course of the disease, etc.) are added to 9A20.00. [5]

Table 1. Frequently used codes

System	Code	Name / Note
ICD-10-CM	H05.2	Exophthalmic conditions (exophthalmic conditions). [6]
ICD-10-CM	H05.20	Unspecified exophthalmos (unspecified exophthalmos). [7]
ICD-11 MMS	9A20.00	Outward displacement of the eyeball (exophthalmos/proptosis). [8]
ICD-11 MMS	5A02.0	Thyrotoxicosis with diffuse goitre (Graves' disease; cited as a cause of exophthalmos). [9]

Epidemiology

Exophthalmos is most commonly associated with thyroid ophthalmopathy (TO), which occurs in approximately 25-50% of patients with Graves' disease; the population incidence of TO is approximately 1.6-9.6 per 100,000 person-years (higher in women). In TO, exophthalmos may be asymmetrical and associated with eyelid retraction and restrictive diplopia.[10]

Other major causes include orbital tumors (adults: venous cavernous malformation/"cavernous hemangioma," lymphomas, metastases; children: rhabdomyosarcoma), infections (orbital cellulitis), and vascular pathologies (carotid-cavernous fistulas, orbital varices). It is clinically significant that in children and young adults, inflammatory and infectious causes are more common, while in adults, thyroid, tumor, and vascular causes are more common. [11]

The incidence of pulsating exophthalmos is low and almost always indicates a carotid-cavernous fistula (CCF) or other arteriovenous shunts; at the present stage, the primary tactic is endovascular occlusion (transvenous/transarterial), with high efficiency. [12]

Exophthalmometry standards vary by race and age; the accepted clinical "red line" is asymmetry >2 mm, while absolute values >21-22 mm require evaluation in conjunction with the patient's anthropometry. For children, values increase with growth. [13]

Reasons

Exophthalmos occurs due to an increase in the volume of orbital contents: muscles, fatty tissue, vascular structures, tumors, or inflammatory infiltrate/pus/blood.

1. Endocrine-autoimmune: thyroid ophthalmopathy (Graves orbitopathy). Immune activation of fibroblasts via TSHR/IGF-1R → edema, glycosaminoglycans, then fibrosis, enlargement of the extraocular muscle bellies and fat volume. [14]
2. Tumors: venous cavernous malformation (previously "cavernous hemangioma"), lymphomas, meningiomas, metastases (mammary gland, etc.). Typically slow growth, painlessness, one-sidedness. [15]
3. Vascular: carotid-cavernous fistulas (pulsating proptosis, chemosis, noise), orbital varices (intermittent exophthalmos during straining). [16]
4. Infectious: orbital cellulitis (pain with movement, fever, ophthalmoplegia, chemosis), abscesses. [17]
5. Trauma/hemorrhage: retrobulbar hemorrhage (acute, painful; risk of compartment syndrome), post-traumatic vascular fistulas. [18]
6. Granulomatosis/immune: sarcoidosis, IgG4-related orbital disease, granulomatosis with polyangiitis. [19]

Table 2. Etiological baskets and clinical clues

Group	"Hints" at the reception	What confirms
Thyroid	Eyelid retraction, dryness, diplopia, positive TRAb	MRI/CT: thickening of the muscle bellies, tendon sparing; thyroid profile
Tumors	Slow increase, no pain, one-sided	MRI/CT: lesion/capsule; in case of lymphoma - preference for radiation
Vascular	Pulsation/noise, chemosis, ↑IOP, intermittent nature	Angiography/CT-A/MR-B: fistula/varix
Infections	Pain with movement, fever, ophthalmoplegia	CT scan of the orbits and sinuses, leukocytosis, cultures
Injury	Fresh blow/surgery; rapid swelling/pain	CT: hematoma/fracture; orbital pressure

Risk factors

Smoking, unstable thyroid status, and high TRAb titers increase the risk of severe EOP and pronounced exophthalmos; radioiodine without steroid prophylaxis in at-risk patients is an additional trigger. Lipid/glycemic control and smoking cessation reduce the likelihood of vision-threatening forms. [20]

Vascular causes: skull base trauma and aneurysm are the key to CCS; in young individuals without trauma, "indirect" fistulas are possible due to arterial hypertension/connective tissue features. Orbital varices cause position-dependent proptosis (cough, tilt). [21]

Tumor and lymphoproliferative processes most often manifest as slow unilateral proptosis; in patients over 50 years of age and/or with a history of cancer, the threshold for MRI/biopsy is low. Lymphomas respond specifically to low-dose radiotherapy. [22]

Orbital infections most often follow sinusitis (ethmoiditis/frontal sinusitis), odontogenic lesions, or trauma; diabetes and immunosuppression increase the risk of severe course. [23]

Table 3. Risks and how to influence them

Risk	What to do now
Smoking + Graves	Urgent smoking cessation; control of euthyroidism
Radioiodine in a patient at risk	Oral steroid prophylaxis according to EUGOGO
Basal skull trauma	Early angiography/CT-A in "pulsating" proptosis
Sinusitis/odontogenic lesions	Sanation, low threshold CT of orbits and sinuses

Pathogenesis

In thyroid ophthalmopathy, antibodies to TSHR/IGF-1R activate orbital fibroblasts: hyaluronan synthesis increases, along with an influx of water and inflammatory cells, leading to fibrosis. The extraocular muscle bellies and fat increase in volume, causing the orbital apex to become overcrowded, leading to proptosis, restriction, and risk of optic nerve compression. [24]

Vascular fistulas create arteriovenous shunting in the cavernous sinus: venous hypertension, congestion, chemosis, increased intraocular pressure, "pulsation." Orbital varices are thin-walled dilated veins with "dynamic volume," hence intermittent proptosis. [25]

Tumors increase volume by mass effect; lymphomas infiltrate soft tissues, and venous cavernous malformations slowly grow within the muscular cone. Orbital cellulitis causes edema and infiltration, increasing venous resistance and intraocular pressure. [26]

Symptoms

The key symptom is protrusion (unilateral/bilateral), often with eyelid retraction, chemosis, limited movement, and/or diplopia. Pain with movement is typical of orbititis, pulsation/noise is typical of KKS, and slow, painless growth is typical of a tumor. [27]

Decreased color vision/visual acuity, RAPD, and "fog" are signs of optic nerve compression (orbital apex with EOP, tumors, and hematomas). Increased IOP associated with chemosis and episcleral congestion is a marker of a vascular cause. [28]

Table 4. “Portraits” of common causes of exophthalmos

Cause	Pain	Speed	Peculiarities
Thyroid	No/minimal	Weeks-months	Eyelid retraction, diplopia, dryness
Orbitite	Yes (increases with movement)	Days	Fever, ophthalmoplegia, chemosis
KKS	Throbbing discomfort	Weeks	Noise/pulsation, chemosis, ↑IOP
Tumor	Usually no	Weeks-months	Unilateral slow growth
Hematoma	Sharp pain	Minutes-hours	Trauma, decreased vision, emergency

Classification, forms and stages

1. By etiology: endocrine (EOP), tumor, vascular, infectious, traumatic, granulomatous/immune. [29]
2. By tempo: acute (hours-days; hemorrhage, orbititis), subacute (weeks), chronic (months; tumors, EOP).
3. By nature: axial (along the optic nerve; tumor inside the cone), non-axial (lateral/medial “shift”), pulsating (KKS), intermittent (varices). [30]
4. By degree (exophthalmometry): mild, moderate, severe (guidelines are set by clinical and anthropometric data; asymmetry >2 mm is pathological). [31]

Complications and consequences

Risks include: compression optic neuropathy (especially with EOP and tumors), exposure keratopathy with ulceration, persistent diplopia, intraocular hypertension and secondary glaucoma (with venous congestion), and intracranial complications of infections. Delayed treatment for orbititis/hematoma/CCS can lead to irreversible vision loss. [32]

When to see a doctor

Urgent (same day): sudden proptosis after trauma, pain with visual impairment, fever + pain with eye movements, pulsation/tinnitus, rapidly growing chemosis, new diplopia, "threatening" corneal surface symptoms. These are scenarios of compartment syndrome, orbititis, or corneal edema – hospitalization is required. [33]

Fast (in the next few days): slowly increasing unilateral proptosis without pain (suspected tumor/lymphoma), progressive diplopia, symptoms of EOP with signs of neuropathy (dyschromatopsia, RAPD). [34]

Table 5. "Red Flags"

Flag	What could be behind this?
Sharp pain + injury + decreased vision	Retrobulbar hematoma (decompression!)
Pain when moving + fever	Orbital cellulitis/abscess
Pulsating proptosis + noise	Carotid-cavernous fistula
RAPD/colour vision deficiency	Optic nerve compression

Diagnostics

Step 1. Examination and measurements. Visual acuity/color, pupils (RAPD), exophthalmometry (Hertel/Naugle), IOP, eye movements, slit lamp (chemosis/keratopathy), orbital auscultation (noise). Record a photo "frontal/profile". Asymmetry >2 mm is pathological. [35]

Step 2. Basic laboratory. Complete blood count, C-reactive protein/ESR (infection/inflammation), thyroid profile + TRAb if EOP is suspected, basic coagulation tests in vascular scenarios. [36]

Step 3. Visualization.
- CT of the orbits/sinuses in case of trauma/infection/suspected abscess; provides bone and rapid assessment of soft tissues.
- MRI of the orbits/brain with contrast in case of tumor/EOP/suspected orbital apex.
- CT-A/MRI-B/angiography in case of pulsation/noise (diagnosis of CCS; further endovascular tactics). [37]

Step 4. Targeted tests. OCT RNFL/GCL and perimetry if nerve compression is suspected; cultures and blood cultures if orbititis; biopsy if tumor/lymphoma (needle/incisional biopsy is often sufficient). [38]

Table 6. What and why to prescribe

Situation	First visualization	Additionally
Trauma/acute edema	CT scan of the orbits	In case of vision loss - decompression according to the clinic
Fever/pain	CT scan of the orbits and sinuses	Blood cultures; if complications arise, MRI
Pulsation/noise	CT-A/MR-B/DSA	Transition to endovascular treatment
Slow increase	MRI of the orbits	Biopsy for suspected tumor/lymphoma

Differential diagnosis

Proptosis vs. "pseudoproptosis." The latter is caused by high myopia, bupphthalmos, orbital asymmetry, and, less commonly, contralateral enophthalmos. Exophthalmometry and CT scans dot the i's and cross the t's. [39]

EOP vs. orbititis. Orbititis presents with pain during movement, fever, and ophthalmoplegia; EOP is usually painless, with eyelid retraction and tendon-sparing thickening of the muscle bellies on MRI. [40]

Vascular vs. tumor. Pulsation/chemosis/increased intraocular pressure and rapidly changing edema suggest a fistula/varix; slow, painless axial proptosis suggests a tumor (venous cavernous malformation/lymphoma). Angiography/MRI resolves the dispute. [41]

Table 7. Quick "forks"

Sign	More for…
Pain/fever/ocular pain	Orbitite
Pulsation/noise/chemosis	KKS
Slow axial growth	Tumor/lymphoma
Eyelid retraction + diplopia	EOP

Treatment

General principles. Treat the underlying cause, not the "bulge." If vision/surface is threatened, simultaneously protect the cornea (gels/ointments/protection), control intraocular pressure, and provide pain relief. Emergency situations (orbital hematoma, orbititis with abscess, corneal congestion with progressive edema/increased intraocular pressure, vision-threatening EOP) require immediate escalation and teamwork (ophthalmologist, ENT/neurosurgeon/infectious disease specialist/interventional radiologist). [42]

Thyroid ophthalmopathy (active moderate-to-severe). First-line therapy according to EUGOGO is intravenous methylprednisolone at a total of 4.5 g/12 weeks ± sodium mycophenolate; this is more effective and safer than oral regimens. In cases of resistant/dominant proptosis, treprotumumab (an IGF-1R inhibitor) is used, which significantly reduces exophthalmos and diplopia; sensorineural hearing impairment and hyperglycemia have been described in some patients; monitoring is required. In visually threatening ophthalmopathy (DON), a GCS pulse and urgent decompression are necessary if a rapid response is not achieved. [43]

Orbital cellulitis. Hospitalization, IV broad-spectrum antibiotics covering strepto-, staphylococcal-, and anaerobic bacteria; CT to rule out subperiosteal/orbital abscess; drainage if no improvement within 24-48 hours or if vision deteriorates. Monitor vision, pupils, and movements daily; steroids only as an adjuvant after starting antibiotics and ruling out abscess/fungus. [44]

Carotid-cavernous fistula. The basic tactic is endovascular occlusion (transvenous/transarterial; coils/glue/flow-diverter as indicated). Modern series demonstrate high efficacy and safety; the choice of approach is individualized (fistula type, anatomy, center experience). If an endovascular solution is impossible, open options are rare. [45]

Orbital varices (venous malformations). In stable, asymptomatic cases, observation is recommended; in cases of pain/bleeding/pronounced proptosis, interventional (sclerotherapy) or surgical approaches are recommended in experienced hands; the decision is strictly individualized based on angio-MRI/CT. [46]

Venous cavernous malformation (formerly "cavernous hemangioma"). The most common benign orbital tumor in adults; if symptoms occur (diplopia, decreased vision), removal (anterior/lateral orbitotomy, endoscopic approaches) is recommended. For small, asymptomatic lesions, surveillance is possible. [47]

Orbital lymphomas. Often present with painless proptosis; the main method is radiation therapy (including low-dose/ultra-low-dose regimens for indolent B-cell forms) with high local control rates; systemic therapy is based on histotype/stage (managed by a hematologist). [48]

Metastases/malignant tumors. Multidisciplinary tactics: systemic antitumor therapy according to the profile + local control (radiation/surgery for decompression, correction of proptosis/pain). Rarely - combined orbital decompression for nerve compression. [49]

Retrobulbar hematoma/orbital compartment syndrome. Clinical findings are more important than imaging: if vision is threatened, immediate lateral canthotomy/cantholysis and decompression are recommended, followed by a CT scan. Early response is crucial for preserving vision. (Classic "field" ophthalmic management.)

Rehabilitation and surface protection. For exposure: gels/ointments, silicone occluders/moisture chambers, short-term dressing treatments; for persistent exposure: tarsorrhaphy. For diplopia: prisms, exercises; for persistent restriction (EOP): muscle surgery in the inactive phase after decompression (if necessary). [50]

Table 8. “Who gets what”: treatment summary by group

Group	Base	Escalation
EOP	IV MP 4.5 g/12 weeks ± mycophenolate	Treprotumumab; in DON - decompression
Orbitite	IV AB + CT	Abscess drainage
KKS	Endovascular occlusion	Alternative accesses/devices
Variks	Observation	Sclerotherapy/surgery as indicated
"Cavernous hemangioma"	Observation or removal if symptoms occur	Modern minimally invasive approaches
Lymphoma	Radiation (low doses for indolent)	Systemic therapy according to a hematologist

Prevention

Smoking cessation and rapid euthyroidism reduce the risk of severe EOP and pronounced proptosis; steroid prophylaxis is recommended in patients at risk for radioiodine use. Prevention of sinusitis/odontogenic lesions reduces the likelihood of orbititis. Facial protection during sports/work and a proper post-trauma protocol reduce the risk of hematomas and CCS. [51]

Forecast

It depends entirely on the cause and the speed of treatment initiation. With EOP, modern regimens and targeted therapy improve appearance and function; with lymphomas, there are high rates of local control with radiation therapy. Endovascular treatment of fistulas results in high closure rates with minimal invasion. Late infections, hematomas, and nerve compression are the main sources of irreversible loss if time is wasted. [52]

Table 9. Exophthalmometry: norms and interpretation

Parameter	Meaning/rule
Norm (adults, reference)	12-21 mm
Asymmetry	>2 mm - pathological
Upper limits	Higher in African Americans; lower in children
Children's meanings	Grow with age (≈13.2 mm <4 years → ≈16.2 mm by 13-17 years)
When to do CT exophthalmometry	Trauma/displacement of bony landmarks, preoperative planning

Table 10. Visualization tools for exophthalmos

Method	What does it give?	To whom
CT scan of the orbits/sinuses	Bone, hematomas, abscesses, soft tissue volume	Trauma, infection, acute scenarios
MRI of the orbits/brain	Soft tissue, orbital apex, nerve	EOP, tumors, neuropathy
CT-A/MR-B/DSA	Shunts, venous congestion, sinus anatomy	Suspected of KKS
OCT RNFL/GCL	Optic nerve compression	EOP/tumor monitoring
Perimetry	Visual field defects	Neuropathy/monitoring

FAQ

Is exophthalmos always a thyroid disorder?
No. Thyroid ophthalmopathy is a common cause, but not the only one: there are tumors, infections, vascular, and traumatic cases. Diagnosis is based on clinical examination and imaging. [53]

Normal "protrusions" - how many mm?
Approximately 12-21 mm; asymmetry >2 mm is a reason for examination. Norms vary among different races and in childhood. [54]

What's that pulsating and noisy sound? It's
a classic sign of a carotid-cavernous fistula. These days, it's usually treated endovascularly. [55]

Is it possible to treat exophthalmos with pills due to thyroid disease?
In the active stage of exophthalmos, intravenous steroids (± mycophenolate) are used; with severe proptosis, treprotumumab is used. If vision is threatened, decompression is recommended. The choice is strictly individual. [56]

When to sound the alarm?
Immediately: sharp pain/loss of vision, pulsation/noise, fever + pain with eye movements, rapid chemosis - these are scenarios where delay is dangerous. [57]