Ophthalmology – Giant Cell Arteritis

Basics

Description

Giant cell arteritis (GCA), also called temporal arteritis, is a systemic inflammatory vasculitis involving predominantly medium- and large-sized arteries. Inflammation within the arterial wall causes intimal proliferation, progressive narrowing of the vascular lumen, and ultimately tissue ischemia.

GCA is one of the most important ophthalmic emergencies because it can produce sudden, severe, and usually irreversible visual loss. Once one eye is affected, the fellow eye is at substantial risk if treatment is not started immediately. Systemic glucocorticoid therapy therefore should not be delayed while awaiting confirmatory testing when clinical suspicion is high. 

The most common ocular cause of visual loss is arteritic anterior ischemic optic neuropathy (AAION). Other ocular ischemic manifestations include central or branch retinal artery occlusion, cilioretinal artery occlusion, posterior ischemic optic neuropathy, and ocular ischemic syndrome.

Epidemiology

GCA occurs almost exclusively in adults older than 50 years and becomes increasingly common with advancing age. Women are affected more frequently than men, and the disease is particularly common in individuals of Northern European or Scandinavian ancestry. 

Genetic susceptibility appears to contribute to disease risk. Associations with particular HLA class II alleles, especially HLA-DRB1 variants, have been described, although GCA is not a simple Mendelian genetic disorder.

Prevention

There is no established method for preventing the development of GCA.

The major preventable complication is permanent visual loss, and prevention depends on recognizing the disease promptly and initiating adequate glucocorticoid therapy before irreversible ischemic injury occurs.

Pathophysiology

Both the innate and adaptive immune systems contribute to GCA.

Activation of dendritic cells within susceptible arterial walls promotes recruitment and activation of CD4-positive T lymphocytes and macrophages. These cells release inflammatory cytokines and organize into a granulomatous inflammatory response.

Macrophages and multinucleated giant cells may accumulate near the internal elastic lamina and contribute to destruction of the arterial wall.

Cytokines such as interleukin-6 contribute to the systemic acute-phase response, producing elevated inflammatory markers and constitutional symptoms.

Progressive inflammation produces intimal hyperplasia, luminal stenosis, thrombosis, and vascular occlusion, resulting in ischemia of structures supplied by the affected arteries.

Etiology

The precise cause of GCA remains unknown.

It is thought to develop in genetically susceptible older individuals after inappropriate activation of the immune system. Infectious triggers have been proposed, but no single infectious organism has been established as the cause.

Commonly Associated Conditions

GCA is strongly associated with polymyalgia rheumatica (PMR).

PMR typically causes bilateral aching and morning stiffness involving the shoulder girdle, neck, hips, and pelvic girdle. The two conditions can occur independently or together.

Diagnosis

History

Patients older than 50 years with possible GCA should be specifically questioned about systemic, cranial, and visual symptoms.

Constitutional manifestations may include fatigue, malaise, fever, decreased appetite, night sweats, and unintentional weight loss.

A new-onset or substantially changed headache is a common presenting symptom. The headache may be temporal but can occur elsewhere.

Patients may describe scalp tenderness, such as discomfort when brushing their hair or resting the head on a pillow.

Jaw claudication is particularly suggestive of GCA. Patients describe aching or fatigue of the jaw muscles when chewing that improves with rest. Tongue claudication and facial pain occur less frequently.

Symptoms of associated polymyalgia rheumatica include proximal muscle aching and marked morning stiffness.

Visual Symptoms

Visual manifestations require urgent attention.

Patients may experience transient monocular visual loss, episodes of dimming or graying of vision, diplopia, or sudden permanent visual loss.

Importantly, some patients with ocular GCA have few or no constitutional symptoms. Therefore, the absence of headache, jaw claudication, fever, or polymyalgia symptoms does not exclude the diagnosis.

Physical Examination

Temporal Arteries

The temporal arteries should be examined for tenderness, thickening, nodularity, reduced pulsation, or absence of pulse.

A normal temporal artery examination does not exclude GCA.

Arteritic Anterior Ischemic Optic Neuropathy

The classic ophthalmic manifestation is AAION.

The optic disc is typically markedly swollen and often has a characteristic pale or chalky-white appearance, in contrast to the more frequently hyperemic disc swelling seen in nonarteritic anterior ischemic optic neuropathy.

Visual acuity may be profoundly reduced. A relative afferent pupillary defect, dyschromatopsia, and severe visual-field loss are common when involvement is unilateral or asymmetric.

Later, the optic disc becomes pale and atrophic.

Retinal Arterial Occlusion

GCA can cause central, branch, or cilioretinal artery occlusion.

When an older patient develops retinal arterial occlusion without an obvious embolic source, especially in association with systemic symptoms or elevated inflammatory markers, GCA must be considered urgently.

Diplopia

Transient or persistent diplopia may result from ischemia affecting the third, fourth, or sixth cranial nerve or their vascular supply.

Diagnostic Tests and Interpretation

Inflammatory Markers

There is no single laboratory test that definitively confirms or excludes GCA.

The initial laboratory evaluation typically includes erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete blood count, and platelet count.

Most patients have elevated ESR and CRP, but normal inflammatory markers can occasionally occur. Consequently, a normal ESR alone must never be used to exclude GCA when the clinical presentation is strongly suggestive.

CRP is often particularly useful because it responds rapidly to systemic inflammation and is less strongly influenced by factors such as age and anemia.

Thrombocytosis and a normocytic anemia may provide additional supportive evidence.

Vascular Ultrasound

Modern practice increasingly uses vascular ultrasonography in the initial evaluation of suspected GCA when appropriate expertise is available.

The updated EULAR imaging recommendations identify ultrasound of the temporal and axillary arteries as the first-line imaging test in suspected GCA, with characteristic findings including arterial wall thickening and the hypoechoic “halo” sign. 

Ultrasound is operator dependent and should ideally be performed rapidly because glucocorticoid therapy can reduce inflammatory imaging findings.

Temporal Artery Biopsy

Temporal artery biopsy (TAB) remains an important method of confirming cranial GCA, particularly where vascular ultrasound expertise is limited or when imaging is inconclusive.

Biopsy should not delay treatment in a patient with threatened or established visual loss.

The ACR/Vasculitis Foundation guideline favors obtaining an adequate biopsy specimen and recommends biopsy relatively soon after glucocorticoid initiation when used diagnostically. 

Because GCA can produce skip lesions, a negative biopsy does not completely exclude the disease.

If the biopsy is negative but clinical suspicion remains high, additional vascular imaging or evaluation of the contralateral temporal artery may be appropriate.

Large-Vessel Imaging

GCA can involve the aorta and its major branches in addition to the cranial arteries.

Depending on the clinical presentation, CT angiography, MR angiography, PET imaging, or vascular ultrasound may be used to identify extracranial large-vessel involvement. Current guidelines recognize vascular imaging as an important component of diagnosis and assessment. 

Fluorescein Angiography

In patients with suspected ocular ischemia, fluorescein angiography may show delayed or patchy choroidal filling, prolonged retinal arterial filling, and areas of choroidal nonperfusion.

These findings can support the diagnosis of arteritic ischemic optic neuropathy but do not replace systemic evaluation for GCA.

Pathological Findings

Temporal artery biopsy classically demonstrates granulomatous inflammation involving the arterial wall, often with lymphocytes, macrophages, and multinucleated giant cells.

Giant cells are characteristic but not required for the diagnosis.

Disruption of the internal elastic lamina, intimal thickening, and luminal narrowing may be present.

Inflammation may occur in discontinuous segments, producing the characteristic skip lesions.

Differential Diagnosis

The major ophthalmic differential diagnosis is nonarteritic anterior ischemic optic neuropathy (NAION).

Compared with NAION, AAION generally occurs in an older patient, produces more profound visual loss, and is more likely to show markedly pale or chalky optic disc swelling.

Other conditions that may mimic portions of the clinical syndrome include other vasculitides, infectious diseases, compressive optic neuropathy, retinal vascular occlusion from embolic disease, and inflammatory optic neuropathies.

Treatment

GCA is a medical and ophthalmic emergency when visual symptoms are present.

The primary goal is to prevent additional ischemic injury, particularly blindness in the fellow eye, stroke, and other vascular complications.

Glucocorticoid Treatment

High-dose systemic glucocorticoids remain the foundation of initial therapy. Treatment should begin immediately when GCA is strongly suspected and should not wait for biopsy or imaging confirmation. 

For patients without visual ischemia, current guidelines recommend high-dose oral glucocorticoid therapy, with the precise regimen individualized to clinical circumstances. 

For patients with threatened or established visual loss or other cranial ischemic complications, pulse intravenous glucocorticoids such as methylprednisolone are commonly used initially, followed by high-dose oral glucocorticoid therapy. The ACR/Vasculitis Foundation guideline conditionally favors IV pulse glucocorticoids in patients with threatened vision loss. 

Tocilizumab and Steroid-Sparing Therapy

Modern treatment increasingly incorporates tocilizumab, an interleukin-6 receptor inhibitor, to reduce relapse and cumulative glucocorticoid exposure.

The ACR/Vasculitis Foundation guideline conditionally recommends tocilizumab plus glucocorticoids over glucocorticoids alone for many patients with newly diagnosed GCA. 

Methotrexate may be considered as an alternative steroid-sparing agent in selected patients, particularly when tocilizumab is unsuitable.

Treatment decisions should generally involve rheumatology or another physician experienced in systemic vasculitis.

Glucocorticoid Taper

Once disease control has been achieved, glucocorticoids are gradually tapered.

The taper must be individualized according to symptoms, inflammatory markers, recurrence risk, treatment-related toxicity, and use of steroid-sparing therapy.

EULAR guidance recommends reducing glucocorticoids progressively after remission rather than maintaining prolonged high doses; many patients still require treatment for an extended period. 

Rapid tapering can precipitate relapse.

Management of Glucocorticoid Complications

Because affected patients are usually older and may require prolonged treatment, complications of glucocorticoids are clinically important.

Patients require assessment and prevention of osteoporosis, hyperglycemia or diabetes, hypertension, infection, gastrointestinal complications, weight gain, mood disturbance, sleep disruption, cataract, and glaucoma.

Calcium and vitamin D supplementation, osteoporosis risk assessment, and additional bone-protective therapy may be appropriate depending on individual risk.

Referral

Patients with suspected ocular GCA require immediate ophthalmologic evaluation and urgent systemic treatment.

Rheumatology or internal medicine involvement is important for confirmation of the diagnosis, glucocorticoid tapering, steroid-sparing therapy, and monitoring of systemic vascular disease.

Patients with substantial visual impairment may benefit from low-vision rehabilitation.

Ongoing Care and Follow-Up

Follow-up should assess both disease activity and treatment toxicity.

Patients should be questioned repeatedly about recurrence of headache, scalp tenderness, jaw claudication, polymyalgia symptoms, constitutional symptoms, transient visual disturbances, or new visual loss.

ESR and CRP can be useful in monitoring many patients, but clinical assessment remains essential. This is particularly important in patients receiving tocilizumab because IL-6 blockade can suppress CRP and ESR even when clinical disease assessment remains necessary.

Large-vessel disease may require periodic vascular imaging depending on the initial pattern of arterial involvement and subsequent clinical course.

Patient Education

Patients should understand that recurrent symptoms can indicate disease relapse even while taking treatment.

They should seek immediate medical attention for any new transient or permanent visual disturbance, including dimming, graying, a curtain over the vision, or diplopia.

They should also report recurrent headache, scalp tenderness, jaw pain with chewing, or symptoms of polymyalgia rheumatica.

The adverse effects of long-term glucocorticoid therapy and the importance of medication adherence and laboratory monitoring should be carefully explained.

Prognosis

The prognosis for recovery of vision after established arteritic ischemic optic neuropathy is poor. Treatment is primarily intended to prevent further deterioration and protect the fellow eye rather than restore already infarcted optic nerve tissue.

Visual deterioration can occasionally continue during the first days after treatment is started, emphasizing the importance of rapid recognition and therapy.

Without treatment, the risk of sequential involvement of the fellow eye is very high. Prompt systemic glucocorticoids dramatically reduce this risk.

The systemic prognosis is generally favorable with appropriate treatment, although relapses are common and patients require long-term monitoring.

Complications

The principal ophthalmic complications are permanent severe visual loss from AAION, retinal arterial occlusion, posterior ischemic optic neuropathy, and bilateral blindness.

Systemic vascular complications include ischemic stroke, aortic aneurysm or dissection, myocardial ischemia, and less commonly mesenteric ischemia.

Treatment itself can cause substantial morbidity through long-term glucocorticoid exposure, making careful steroid tapering and the use of appropriate steroid-sparing therapies important components of modern management.