Arteritic optic neuropathy and GCA

Vascular Anatomy of the Anterior Optic Nerve Head

Understanding the pathophysiology of ischaemic optic neuropathies requires precise knowledge of the microvascular supply to the optic nerve head (ONH). Unlike the superficial retinal nerve fibre layer (which receives perfusion from the central retinal artery), the deeper prelaminar, laminar, and retrolaminar regions of the optic disc are supplied exclusively by the posterior ciliary artery (PCA) circulation, derived from the ophthalmic artery:

1. Short Posterior Ciliary Arteries (SPCAs): Typically 2 to 3 main SPCAs pierce the posterior sclera medial and lateral to the optic nerve, branching into 10 to 20 terminal arterioles that coalesce within the scleral ring to form the anastomotic Circle of Zinn-Haller.
2. Watershed Zones: The SPCAs establish distinct sectoral vascular territories (superior vs. inferior, medial vs. lateral). The boundary between these terminal arteriolar territories forms a physiological "watershed zone" across the optic disc. This watershed arrangement explains why ischaemic insults to the ONH characteristically manifest as sectoral or altitudinal visual field defects respecting the horizontal meridian.

Anterior Ischaemic Optic Neuropathy (AION) denotes acute ischaemic infarction of the ONH supplied by the SPCAs. It is classified into two fundamentally distinct entities:

• Arteritic AION (AAION): Infarction secondary to systemic vasculitic occlusion of the SPCAs, caused by Giant Cell Arteritis (GCA).
• Non-Arteritic AION (NAION): Infarction secondary to localized, non-vasculitic microvascular hypoperfusion of the SPCAs.

Arteritic Anterior Ischaemic Optic Neuropathy (AAION) & Giant Cell Arteritis

Giant Cell Arteritis (GCA), historically termed temporal arteritis or Horton disease, is a systemic, granulomatous necrotising vasculitis that selectively affects medium- and large-sized arteries possessing a well-developed internal elastic lamina. Its predilection for cranial branches of the external carotid artery (superficial temporal, facial, maxillary, occipital) and ophthalmic artery branches (SPCAs) renders it the single most devastating ophthalmic emergency in elderly patients.

Epidemiology & Pathogenesis

• Age: Exclusively affects individuals aged $\ge 50$ years, with incidence rising exponentially with each decade (peak incidence 70 to 80 years, mean age ~75 years). GCA is virtually unknown below age 50.
• Sex & Ethnicity: Female-to-male ratio of 2:1 to 3:1. Overwhelmingly common in populations of Northern European ancestry.
• Immunopathogenesis: Activated dendritic cells in the arterial adventitia recruit CD4+ T-helper cells (Th1 and Th17 lineages) via chemokine signaling. Interferon-gamma (IFN-$\gamma$) secreted by Th1 cells triggers macrophage recruitment, fusion into foreign-body or Langhans-type multinucleated giant cells, and the production of matrix metalloproteinases (MMPs) that degrade the internal elastic lamina. Concurrently, systemic overproduction of interleukin-6 (IL-6) drives the intense acute-phase systemic inflammatory response, while platelet-derived growth factor (PDGF) stimulates myofibroblast migration, producing concentric intimal hyperplasia and luminal thrombosis.

Ocular Manifestations of GCA

• Arteritic AION (AAION, ~85% of ocular GCA): Sudden, profound, catastrophic, painless visual acuity loss in one eye. The vast majority present with visual acuity of count fingers, hand motions, or no light perception (NLP), accompanied by a striking relative afferent pupillary defect (RAPD).
• Fundus Appearance: The characteristic ophthalmoscopic sign is chalky-white, pallid optic disc oedema ("pallid disc swelling"). Unlike the hyperaemic swelling of NAION, the severe transmural ischaemia of AAION starves prelaminar capillaries of blood, yielding an intensely pale, milky, swollen disc. Peripapillary flame haemorrhages and cotton-wool spots are common.
• Cilioretinal Artery Occlusion: Because the cilioretinal artery (present in 20-30% of eyes) arises directly from the SPCA circulation rather than the central retinal artery, the combination of anterior ischaemic optic neuropathy and a cilioretinal artery occlusion is virtually characteristic of GCA.
• Choroidal Hypoperfusion: Fluorescein angiography (FFA) reveals patchy, markedly delayed choroidal filling ($>15$ seconds; normally $<5$ seconds), reflecting diffuse posterior ciliary artery occlusion.
• Ocular Warning Signs: Amaurosis fugax (transient monocular visual obscurations occurring days or weeks prior to infarction) and transient binocular diplopia (due to ischaemic cranial nerve III or VI paresis or ischaemia of the extraocular muscles).

Systemic Features & High-Yield Diagnostic Signs

• New-Onset Headache (60-80%): Severe, persistent, throbbing headache, typically temporal or occipital, frequently worse at night.
• Scalp Tenderness: Pain elicited when brushing hair or resting the head on a pillow; palpation of the superficial temporal artery reveals a tender, nodular, thickened, pulseless, cord-like vessel.
• Jaw Claudication (characteristic): Ischaemic cramping pain in the masseter and temporalis muscles elicited after 1 to 2 minutes of chewing or talking, resolving with rest. Jaw claudication carries the highest positive likelihood ratio (LR+ 4.2) for a positive temporal artery biopsy.
• Tongue Claudication & Infarction: Severe pain or ischaemic necrosis of the tongue due to lingual artery vasculitis.
• Polymyalgia Rheumatica (PMR, 50%): Proximal, bilateral aching and morning stiffness in the neck, shoulder girdle, and hip girdle, lasting $>45$ minutes.
• Constitutional Symptoms: Unexplained low-grade fever of unknown origin (FUO), profound fatigue, anorexia, and dramatic unintentional weight loss.

Diagnostic Evaluation and Urgent Treatment for GCA

Suspect GCA in an older patient with new headache, scalp tenderness, jaw claudication, constitutional symptoms, polymyalgia or ischaemic visual symptoms. Some patients lack systemic symptoms or have normal inflammatory markers. Pallid disc swelling and severe loss raise concern, but no isolated sign is sufficient.

Obtain ESR, CRP and blood count/platelets promptly without delaying treatment when suspicion is high. CRP units matter: 2.45 mg/dL equals 24.5 mg/L, not 10 mg/L. Do not apply an invented fixed triad sensitivity to rule disease out.

EULAR 2023 recommends ultrasound as first-line imaging when expertise and timely access are available, including temporal and axillary arteries. Alternative imaging or temporal-artery biopsy depends on availability, probability and concordance. Biopsy samples should be adequately long because of segmental skip lesions; an exact compulsory 1.5–2.5 cm interval is not shared by all guidance. A negative biopsy does not exclude disease when the clinical evidence is convincing.

Visual-threat GCA requires immediate high-dose systemic corticosteroids. IV methylprednisolone pulses are often used for acute ischaemic visual loss; if IV delivery would delay care, start appropriate oral treatment immediately. Investigations must not postpone protection of the other eye. Coordinate rheumatology for confirmation, taper and steroid-sparing treatment such as tocilizumab when indicated, with bone/metabolic/infection protection. Under IL-6 inhibition, normal CRP may not reliably indicate absence of relapse. Isolated PMR without GCA needs its own evaluation and treatment rather than automatically the same high-dose regimen.