Therapy Insight: The Recognition and Treatment of Retinal Manifestations of Systemic Vasculitis

Petros Aristodemou; Miles Stanford


Nat Clin Pract Rheumatol. 2006;2(8):443-451. 

In This Article

Pathogenesis and Clinical Signs of Retinal Involvement

Occlusions of the Central Retinal Artery Circulation

Cotton-wool spots are focal accumulations of axoplasmic components of the nerve fiber layer (Figure 2). Cotton-wool spots are thought to be caused by focal, inner-retinal ischemia due to terminal arteriolar occlusion, although it has been suggested that they are sentinel lesions of wider areas of retinal ischemia or of other, nonischemic pathology.[2] Proximal blockage of blood flow can take the form of occlusion of a branch of the retinal artery (Figure 3) or of a branch of the central retinal artery. As these are end arteries, occlusion leads to necrosis of the inner retina in the affected area. Acute occlusion is characterized by inner-retinal cellular edema, which is responsible for the pale, swollen and opaque appearance of areas affected by retinal arterial occlusions (cloudy swelling). In central retinal artery occlusion, the foveola is visible as a cherry-red spot, as it is solely supplied by the choroid, whose color shows through.[3] Retinal vein occlusions (branch or central) can be ischemic or nonischemic. These occlusions cause a retinopathy that is characterized by flame-shaped and punctate hemorrhages and, occasionally, cotton-wool spots.[2] Retinal venous disease is a rare feature of systemic vasculitis, and usually occurs in the context of long-standing systemic hypertension or abnormal coagulability, such as is present in antiphospholipid syndrome.[4]

Figure 2.

Systemic lupus erythematosus retinopathy. A color fundus photograph that shows systemic lupus erythematosus retinopathy, manifest as cotton-wool spots in a pigmented fundus.

Figure 3.

Giant cell arteritis. A color fundus photograph that shows a pale, swollen, optic disk with accompanying cilio-retinal artery occlusion. Note the cloudy retinal swelling (blue arrow) and break-up of the blood column in the artery (green arrow), indicating lack of flow.

Occlusions of the Posterior Ciliary Artery Circulation

Each terminal choroidal arteriole supplies an independent lobule (segment) of the lamina choriocapillaris. Occlusion of these terminal arterioles produces a corresponding perfusion defect, and its extent depends on the shape of the affected lobule. In the posterior pole, the lobules are small and polygonal, whereas the anterior lobules are large and radially elongated.[5] Choroidal infarction is clinically manifest as pigment clumping and atrophy of the overlying retinal pigment epithelium of the area supplied by the affected choroidal arteriole (spots, streaks or wedge-shaped infarcts). These changes are chronic. Since the retinal pigment epithelium lies anteriorly to the choroid, direct observation of ischemia or inflammation of the choroidal vessels is rarely possible in the acute stage.

Anterior ischemic optic neuropathy (AION) occurs following hemodynamic changes in the posterior ciliary artery circulation, which supplies the optic nerve head. The pathophysiology of AION is not well understood, although both ischemic and reperfusion injury are thought to cause neuronal damage. In the acute phase, the optic disk is ischemic, with resulting blockage of retrograde axoplasmic flow from retinal ganglionic axons. This ischemia produces a swollen and pale optic nerve head, which is evident in the majority of patients with AION[6] (Figure 3). Optic-disk atrophy ensues over the following weeks. The most common cause of arteritic AION is giant cell arteritis. Table 1 distinguishes the features of arteritic from nonarteritic AION. Fluorescein angiography is of particular diagnostic value in equivocal cases—in this technique, fluorescein dye is injected into a peripheral vein and its transit through the choroidal and retinal circulations is recorded with serial photographs of the fundus. A substantially delayed choroidal filling time is observed in patients with AION caused by giant cell arteritis, compared with those who have nonarteritic AION (Figure 4).[7]

Figure 4.

Fluorescein angiograms showing normal choroidal perfusion, and delayed choroidal perfusion in giant cell arteritis. (A) Normal choroidal perfusion in the early venous phase of the fluorescein angiogram. (B) Delayed perfusion in a patient with giant cell arteritis, which leads to a watershed (white arrows) that runs vertically through the optic disk.

Ophthalmic or Carotid Artery Compromise

Rarely, chronic ocular hypoperfusion can result from pathology of the carotid or ophthalmic artery and can cause ocular ischemic syndrome. This syndrome is characterized by punctate retinal hemorrhages, vascular tortuosity, cotton-wool spots, arteriovenous shunts, macular edema and neovascularization of the optic disk and/or retina. Characteristically, retinal arterial pulsation at the optic disk can be elicited by exerting gentle pressure on the eye.

Scleral or Orbital Inflammation

In posterior scleritis, thickening of the sclera can restrict the opening through which the optic nerve passes, resulting in nerve compression. Optic nerve compression can also occur in the presence of orbital inflammation, owing to the effects of increased mass in the confined orbital space. In compressive optic neuropathy, the optic disk is swollen, with flame hemorrhages, but lacks the characteristic pallor seen in AION.[8]

Similarly, mass effects caused by posterior scleritis or orbital inflammation can also produce forward displacement of the posterior wall of the globe. This displacement can cause choroidal folds (linear folds that occur at the posterior part of the eye caused by external compression) as shown in Figure 5, and a hypermetropic shift in refraction (compression of the back of the eye causes a flattening distortion of the globe, and blurring of vision that can be corrected by the addition of a convex lens). The inflammation associated with posterior scleritis can cause retinal detachment due to the accumulation of exudate under the neural retina. Box 1 describes the principles of patient management for the retinal signs related to systemic vasculitis.

Figure 5.

Posterior scleritis. A color fundus photograph that shows choroidal folds over the macula (encircled in green).


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