10. Arteritic AION

What is anterior ischemic optic neuropathy (AION), and in whom is it most common?

AION is an acute ischemic optic neuropathy caused by impaired blood supply to the anterior optic nerve. It is the most common cause of acute optic neuropathy in elderly patients.

What are the two major types of AION, and what conditions are they associated with?

• Non-arteritic AION: associated with vascular risk factors

  • Diabetes

  • Hypertension

  • Hypercholesterolemia

  • Sleep apnea

• Arteritic AION: associated with giant cell arteritis, also called temporal arteritis

What is the pathogenesis of arteritic ischemic optic neuropathy?

Arteritic ION results from inflammatory vascular occlusion of the optic nerve blood supply, especially near the lamina cribrosa.
Key mechanisms include:

• Occlusion or infarction of optic nerve blood supply

• Immune-mediated inflammation

• Luminal obstruction causing ischemia

Why does giant cell arteritis cause arteritic AION?

Giant cell arteritis is an inflammatory vasculitis that affects medium and large arteries.
It causes vessel wall inflammation, narrowing, and occlusion, which can reduce blood flow to the optic nerve and cause arteritic AION.

Why is arteritic AION considered an ocular and medical emergency?

Arteritic AION is an emergency because it is commonly caused by giant cell arteritis, which can rapidly cause severe, irreversible vision loss and may threaten the fellow eye if untreated.

What systemic disease is strongly associated with giant cell arteritis?

Polymyalgia rheumatica, or PMR. About 50% of patients with giant cell arteritis have symptoms of PMR.

Besides giant cell arteritis, what systemic diseases can be associated with arteritic ischemic optic neuropathy?

Arteritic ION can be associated with rheumatologic and inflammatory disorders, including:

• Systemic lupus erythematosus

• Polyarteritis nodosa

• Rheumatoid arthritis

• Behçet’s disease

What is the typical epidemiology of giant cell arteritis?

Giant cell arteritis is the most common vasculitis in the elderly.

• Usually age >60 years

• Incidence about 18 per 100,000 per year

• More common in females than males, about 3:2 or 3:1

• More common in Caucasians

• Unusual in Black and Asian populations

What are the major demographic and genetic risk factors for giant cell arteritis?

• Age >50, especially elderly

• Female sex

• Northern European ancestry

• Family history

• Genetic susceptibility, including HLA polymorphisms

What clinical and lifestyle factors increase risk for giant cell arteritis?

Risk factors include:

• History of polymyalgia rheumatica

• History of vascular disease

• Smoking

• Low body mass index

• Estrogen deficiency

What is the basic pathophysiology of giant cell arteritis, and what size vessels does it affect?

Giant cell arteritis is believed to be an autoimmune inflammatory response against arterial elastic tissue.

It primarily affects medium and large arteries, causing vessel wall inflammation → luminal narrowing/occlusion → ischemia.

Which arteries are typically involved in giant cell arteritis?

GCA commonly affects branches supplying the head and eye, especially:

• Temporal arteries

• Posterior ciliary arteries

• Ophthalmic artery

• Central retinal artery

Besides cranial arteries, what major systemic arteries can be affected in giant cell arteritis?

GCA may also involve large systemic arteries, including:

• Aorta

• Coronary

• Subclavian

• Femoral

• Radial

• Cerebral

• Hepatic

• Renal

• Mesenteric

• Iliac arteries

What are the classic systemic symptoms of giant cell arteritis?

• New-onset headache, often described as throbbing or pressure-like

• Jaw claudication

• Scalp tenderness

• Neck or shoulder muscle ache/stiffness

• Weight loss

• Low-grade fever

• Fatigue

What is jaw claudication in giant cell arteritis?

Jaw claudication is pain, fatigue, or discomfort while chewing, especially with chewing tougher foods or using the gums/jaw repeatedly.

When can systemic symptoms of giant cell arteritis occur relative to ocular symptoms?

Systemic symptoms can occur weeks to months before ocular symptoms.
Some patients may have occult GCA, where systemic symptoms are minimal or absent despite ocular involvement.

What inflammatory lab findings support a diagnosis of giant cell arteritis?

GCA commonly causes elevated inflammatory markers:

• Elevated ESR: often >40 mm/hr

• Elevated CRP: normal is <2.45 mg/dL

• CRP is more sensitive than ESR

• Anemia may also be present

How do you estimate the upper limit of a “normal” ESR by age and sex?

• Males: normal ESR ≈ age / 2

• Females: normal ESR ≈ (age + 10) / 2

Which inflammatory marker is more sensitive for giant cell arteritis: ESR or CRP?

CRP is more sensitive than ESR for GCA.

• CRP sensitivity ≈ 100%

• ESR sensitivity ≈ 92% when ESR is >47 mm/hr

What temporal artery findings are suggestive of giant cell arteritis?

The temporal artery may be:

• Tortuous

• Nodular

• Swollen

• Red

• Tender

• Lacking a palpable pulse

Why are systemic signs important in suspected GCA-related vision loss?

• ↑ ESR / ↑ CRP

• Anemia

• Tender or abnormal temporal artery

• New headache, jaw claudication, scalp tenderness

What additional imaging tests can be used in suspected giant cell arteritis, and what are their limitations?

Imaging may help support GCA diagnosis, but temporal artery biopsy is more definitive.

• MRI angiography

  • Can assess vascular involvement

  • Limitations: invasive/contrast dye risks, false negatives

• PET scan

  • Not ideal for cranial GCA

  • Useful for detecting large-vessel vasculitis

• Ultrasonography

  • Can show the halo sign

  • About 80% sensitivity/specificity

What is the “halo sign” on ultrasound in giant cell arteritis?

The halo sign is a dark, hypoechoic ring around the temporal artery caused by arterial wall edema/inflammation.

What is the diagnostic importance of temporal artery biopsy in giant cell arteritis?

Temporal artery biopsy is highly useful because a positive biopsy supports GCA in about 90-95% of cases.

What histologic findings are seen on temporal artery biopsy in GCA?

Classic biopsy findings include:

• Fragmentation/disruption of the internal elastic lamina

• Swollen endothelium

• Patchy degeneration of smooth muscle cells

• Granulomatous inflammation with macrophages, lymphocytes, and/or giant cells

• Fibrosis, hyaline thickening, and thrombosis

What are the major systemic complications of untreated giant cell arteritis?

Untreated GCA causes increased morbidity and mortality due to vascular occlusion.

Major complications include:

• Blindness

• Stroke

• Aortic aneurysm

How does treatment affect mortality in giant cell arteritis?

If GCA is treated, there is no increased mortality.
If untreated, morbidity and mortality increase due to vascular occlusion complications such as blindness, stroke, and aortic aneurysm.

What is the typical disease course of giant cell arteritis?

GCA can be self-limiting within 1-2 years, but untreated disease can still cause serious vascular complications before resolution.

What ocular symptoms can occur in giant cell arteritis before permanent vision loss?

Early ocular symptoms may include:

• Blurred vision

• Transient visual disturbance

• Amaurosis fugax

• Diplopia

What is amaurosis fugax in GCA, and why is it clinically important?

Amaurosis fugax is transient monocular vision loss due to temporary ocular ischemia.

In GCA, it occurs in about 10% of patients and may appear days to months before AION.

How common is diplopia in giant cell arteritis, and what does it suggest?

Diplopia can be a presenting symptom in GCA.

Frequency:

• Reported range: 2-43%

• Average: about 12%

What are the major ocular signs of giant cell arteritis?

Major ocular signs include:

• Arteritic AION

• Ophthalmoparesis, especially 6th nerve palsy

• Central retinal artery occlusion

• Ptosis, unilateral or bilateral

How can giant cell arteritis cause diplopia or ocular motility problems?

GCA can cause ophthalmoparesis due to ischemia affecting ocular motor nerves or extraocular muscle blood supply.

Common findings include:

• 6th nerve palsy → impaired abduction → horizontal diplopia

• Ptosis → can be unilateral or bilateral

What are unusual ocular signs that may occur in giant cell arteritis?

Unusual signs include:

• Anterior segment ischemia

  • White eye

  • Hypotony

  • Corneal edema

  • Anterior chamber reaction

• Marginal corneal ulceration

• Scintillating scotoma

• Visual hallucinations

• Conjunctivitis

• Bilateral uveitic glaucoma

How common is visual loss in giant cell arteritis, and what is the most common cause?

Visual loss occurs in about 12–50% of GCA cases.

Most common cause:

• Infarct of the prelaminar optic nerve → arteritic AION, about 90%

Other causes:

• Central retinal artery occlusion: 1–3%

• Ischemic retinopathy: 7%

Why is untreated GCA considered a vision-threatening emergency?

Untreated GCA can rapidly involve the fellow eye.
About 65% of untreated patients with vision loss develop binocular vision loss.

Timing of second-eye involvement:

• 1/3 within 24 hours

• 1/3 within 1 week

• 1/3 within 4 weeks

When does the risk of additional vision loss decrease in GCA?

The risk of further vision loss becomes low after 6 months, especially with treatment.

What is the typical visual presentation of arteritic AION?

Arteritic AION typically presents with sudden, painless vision loss.

What are the key clinical signs of arteritic AION?

Arteritic AION typically shows:

• Decreased visual acuity

• Afferent pupillary defect (APD)

• Pale, swollen optic nerve head

• Possible sectoral peripapillary hemorrhages

• May be associated with cilioretinal artery occlusion

How severe is visual acuity loss in arteritic AION?

Visual loss is often severe:

• 20/40 or better: 18%

• 20/40–20/200: 24%

• 20/200 or worse: 58%

How does visual acuity loss compare between arteritic and non-arteritic AION?

Arteritic AION causes more severe vision loss than non-arteritic AION.

Comparison pattern:

• NA-AION: more likely to have better acuity, including >20/40

• A-AION: more likely to have severe acuity loss, especially <20/200

What optic disc finding helps distinguish arteritic AION from non-arteritic AION?

Arteritic AION classically causes a pale, swollen optic nerve head due to severe ischemia.

What vascular retinal findings may accompany arteritic AION?

Arteritic AION may be associated with:

• Sectoral peripapillary hemorrhages

• Cilioretinal artery occlusion

How do arteritic AION and non-arteritic AION differ in patient risk factors and systemic associations?

Non-arteritic AION:

• Males ≈ females

• Associated with vascular risk factors: diabetes, HTN, hypercholesterolemia, sleep apnea

• Typically no systemic symptoms

• ESR/CRP usually normal

Arteritic AION:

• Females > males

• Associated with GCA/temporal arteritis and polymyalgia rheumatica

• Systemic symptoms: headache, jaw claudication, weight loss, scalp tenderness, malaise

• ESR/CRP typically elevated

What optic disc findings help distinguish non-arteritic AION from arteritic AION?

Non-arteritic AION:

• Hyperemic disc edema

• More flame-shaped hemorrhages

• Small crowded disc at risk

• Segmental optic nerve head edema

Arteritic AION:

• Pale, chalky-white swollen disc

• Retinal ischemia and cotton wool spots may be present

• Normal-to-large cup

• Diffuse optic nerve head edema

How do treatment and prognosis differ between arteritic and non-arteritic AION?

Non-arteritic AION:

• No proven effective treatment

• Up to 3-line improvement in ~43%

• Fellow eye involvement <30%

Arteritic AION:

• Requires high-dose steroids urgently

• Poor prognosis for visual recovery

• Fellow eye may be involved in up to 95% if untreated

What retinal and visual function signs can occur in arteritic ischemic optic neuropathy?

Arteritic ION may show:

• Constricted retinal arterioles in ~50%

• Decreased color vision / red desaturation

• Nerve fiber bundle field defects

Common field defects:

• Altitudinal defects, often inferior: 70–80%

• Central scotoma: ~30%

What visual field defect is most characteristic of arteritic ION?

The most common visual field defect is an altitudinal defect, often inferior, occurring in about 70-80% of cases.

What is the risk to the fellow eye in untreated arteritic ION?

Untreated arteritic ION has a high risk of fellow-eye involvement.
About 65% may develop an attack in the other eye within hours to days.

Is vision loss from arteritic ION reversible?

Vision loss is generally irreversible, because it results from ischemic infarction of the optic nerve.

However, if pulse steroids are given within 36 hours of acute vision loss, vision may significantly improve in some cases.

What conditions should be considered in the differential diagnosis of arteritic AION?

Differential diagnoses include:

• Non-arteritic AION

• Central retinal vein occlusion

• Compressive optic neuropathy

• Papilledema

• Buried optic disc drusen

• Other optic neuritis causes, such as:

  • Sarcoidosis

  • Syphilis

How can central retinal vein occlusion mimic arteritic AION, and what fundus findings suggest CRVO instead?

CRVO can cause vision loss with optic disc edema, but it typically has prominent retinal vascular findings:

• Diffuse retinal hemorrhages

• Cotton wool spots

• Macular edema

• Optic disc edema

What immediate workup should be done when arteritic AION from GCA is suspected?

Initial management should include:

• Ask about GCA symptoms

  • Headache

  • Jaw claudication

  • Scalp tenderness

  • Weight loss, malaise, fever

  • PMR symptoms

• Order CBC, ESR, and CRP stat

• Arrange temporal artery biopsy within 1 week

What is the main treatment for arteritic AION due to suspected GCA?

Treat immediately with high-dose systemic corticosteroids, typically around 40–60 mg/day prednisone.

Effects:

• Relieves systemic symptoms

• Usually gives little improvement in visual acuity

• Decreases risk of vision loss in the other eye

• Often required long-term

Why is urgent steroid treatment critical in arteritic AION?

Without treatment, there is a much higher risk of bilateral visual loss.
The slide notes a 3× greater chance of bilateral vision loss without treatment.

What medication may be used as low-dose therapy to reduce vascular complications in GCA?

Low-dose aspirin, commonly 75 mg, may be used to help reduce thrombotic/ischemic complications such as stroke.

What is the general long-term steroid taper strategy for arteritic AION/GCA?

After initial treatment for 2-4 weeks, taper gradually:

• Decrease by 10 mg every 2 weeks until 20 mg

• Then decrease by 2.5 mg every 2-4 weeks until 10 mg

• Then decrease by 1 mg every 1-2 months

How long should symptoms and ESR remain controlled during treatment for GCA?

Symptoms and ESR should remain normalized for 6-12 months or longer.

What are important complications of long-term corticosteroid therapy?

Long-term steroids can cause Cushing-like complications, including:

• Weight gain

• Muscle wasting

• Increased blood pressure

• Increased infections

• Delayed wound healing

• Stomach irritation

• Cataracts

• Osteoporosis

What are steroid-sparing therapies used in long-term management of GCA?

Steroid-sparing therapies may include:

• Methotrexate

• Abatacept

What is the role of tocilizumab in giant cell arteritis treatment?

Tocilizumab (Actemra) is an FDA-approved steroid-sparing agent for GCA.

Mechanism/main effect:

• IL-6 receptor antagonist → reduces inflammatory signaling

Clinical use:

• Given as a subcutaneous injection

• Used with steroids to help achieve remission and reduce steroid exposure

What is the role of upadacitinib in giant cell arteritis treatment?

Upadacitinib (RINVOQ) is a steroid-sparing agent used in GCA.

Mechanism/main effect:

• Janus kinase (JAK) inhibitor → decreases inflammatory cytokine signaling

Clinical details:

• Oral medication

• Dose on slide: 15 mg PO daily

What is the treatment goal in a treat-to-target approach for GCA?

The treatment target is remission, defined as:

• Absence of clinical symptoms

• Absence of systemic inflammation

Main goals:

• Maintain remission

• Prevent tissue ischemia

• Prevent vascular damage

How should treatment selection and monitoring be individualized in GCA?

Treatment choice should be based on:

• Disease severity and activity

• Comorbidities

• Predictors of outcome

• Response during follow-up

Monitoring:

• Assess disease activity as frequently as every 1–4 weeks until remission

• Once stable on therapy, monitor every 3–6 months

• After remission, maintain with the minimal effective dose

• Drug-free remission may be possible in some patients

What is the absolute requirement before applying the 2022 ACR/EULAR classification criteria for giant cell arteritis?

The patient must be ≥50 years old at the time of diagnosis.

Also, these criteria should be applied only after:

• A diagnosis of medium- or large-vessel vasculitis is being considered

• Alternate diagnoses mimicking vasculitis have been excluded

What score is needed to classify a patient as having giant cell arteritis using the 2022 ACR/EULAR criteria?

A total score of ≥6 points is needed to classify the patient as having GCA.

In an older patient with blurry vision, what findings in this case suggest optic neuropathy rather than refractive blur?

Clinical criteria include:

• Morning stiffness in shoulders/neck: +2

• Sudden visual loss: +3

• Jaw or tongue claudication: +2

• New temporal headache: +2

• Scalp tenderness: +2

• Abnormal temporal artery exam: +2

What systemic symptoms should raise suspicion for giant cell arteritis?

Classic systemic symptoms of GCA include:

• New-onset headache: common, about 67–85%

• Jaw claudication

• Scalp tenderness

• Neck or shoulder muscle ache/stiffness

• Weight loss

• Low-grade fever

• Fatigue

When can systemic symptoms of GCA occur relative to ocular symptoms?

Systemic symptoms may occur weeks to months before ocular symptoms.

However, some patients may have occult GCA, meaning they have little or no systemic symptoms despite significant ocular disease.

Why is GCA considered both an ocular and medical emergency?

GCA is an emergency because it can cause severe ischemic complications, including:

• Permanent vision loss

• Fellow-eye involvement

• Myocardial infarction

• Aortic dissection

• Stroke or large-vessel ischemia

What is the key rule for sudden vision loss in patients over age 50?

In any patient >50 years old with sudden vision loss, GCA must be ruled out urgently.

Workup/treatment should include:

• Ask about systemic GCA symptoms

• Order CBC, ESR, CRP stat

• Refer urgently to neuro-ophthalmology or the ER

• Start systemic steroids ASAP if suspected

Should steroid treatment wait until temporal artery biopsy confirms GCA?

No. If GCA is suspected, treat with systemic steroids immediately, even before temporal artery biopsy.

Why: Delaying treatment increases risk of irreversible vision loss and fellow-eye involvement.