Introduction

In this chapter, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings (Tables 1 and 2).

Table 1 Disorders associated with retinal vasculitis
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Table 2 Differential diagnosis of retinal vasculitis based on ophthalmoscopic findings
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Fundus Fluorescein Angiography

Intravenous fluorescein angiography is an essential component of the evaluation and management of retinal vasculitis. Characteristic features seen with fluorescein angiography in active vasculitis include leakage of dye due to breakdown of the inner blood-retinal barrier and staining of the blood vessel wall with fluorescein. Such leakage may be focal as seen in sarcoidosis or multiple sclerosis or more diffuse as seen in Behçet’s disease and retinal vasculitis associated with tuberculoprotein hypersensitivity. Diffuse capillary leakage is also a common finding in many conditions such as Behçet’s disease and birdshot chorioretinopathy.

Identification of the Involved Retinal Vessels

Retinal vasculitis affecting predominantly the veins (phlebitis) has been described in association with Behçet’s disease, tuberculosis, sarcoidosis, multiple sclerosis, pars planitis, retinal vasculitis associated with tuberculoprotein hypersensitivity, and human immunodeficiency virus infection. Retinal arteritis is more commonly seen in acute retinal necrosis; idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN); and systemic vasculitides such as systemic lupus erythematosus (SLE), polyarteritis nodosa, and granulomatosis with polyangiitis (GPA); Churg-Strauss syndrome; and cryoglobulinemia.

Cotton-Wool Spots

Cotton-wool spots representing microinfarcts of the retina due to precapillary retinal arteriolar occlusion are most often found in association with systemic vasculitides such as SLE, polyarteritis nodosa, granulomatosis with polyangiitis (GPA), Churg-Strauss syndrome, and cryoglobulinemia. Susac syndrome is a rare disease of unknown pathogenesis. It is also caused by microangiopathy affecting the arterioles of the brain, retina, and cochlea, giving the classic triad of encephalopathy, branch retinal arterial occlusions, and sensorineural hearing loss. The underlying process is believed to be a small vessel vasculitis causing microinfarcts of the retina, brain, and cochlea.

Intraretinal Infiltrates

Intraretinal infiltrates are characteristic of infectious processes, but in the absence of these, they are pathognomonic of Behçet’s disease. These transient white patches of retinitis often with small adjacent hemorrhages are almost always seen in patients with active posterior Behçet’s uveitis. Typically, they are silent on fundus fluorescein angiography.

Necrotizing Retinitis

Retinal vasculitis may be associated with necrotizing retinitis due to ocular toxoplasmosis, acute retinal necrosis, cytomegalovirus (CMV) retinitis, and rarely human T cell lymphoma virus type 1 (HTLV-1) associated uveitis.

Aneurysmal Dilatations of the Retinal and Optic Nerve Head Arterioles

IRVAN is a rare clinical entity characterized by bilateral retinal arteritis, numerous aneurysmal dilatations of the retinal and optic nerve head arterioles, peripheral retinal vascular occlusion, neuroretinitis, and uveitis. Visual loss is due to exudative maculopathy and neovascular sequelae of retinal ischemia. Arterial macroaneurysms, occurring in elderly female patients with sarcoidosis associated with peripheral multifocal chorioretinitis, have been described. These patients had severe cardiovascular disease.

Frosted Branch Angiitis

The retinal findings include swelling of the retina and severe sheathing of the retinal venules, creating the appearance of frosted tree branches. Additional findings include intraretinal hemorrhages, hard exudates, and serous exudative detachments of the macula and periphery. Fluorescein angiography demonstrates leakage of dye from the vessels, but no evidence of decreased blood flow or occlusion. Patients who have the appearance of frosted branch angiitis are classified into three subgroups. First are patients with lymphoma or leukemia whose disease is due to infiltration with malignant cells (frosted branch-like appearance). Second is the group of patients who have associated viral infections or autoimmune disease. Frosted branch angiitis was reported in patients with systemic lupus erythematosus, Crohn’s disease, toxoplasmic retinochoroiditis, human T cell lymphoma virus type 1 infection, AIDS associated with small patches of retinitis, HIV without CMV retinitis, herpes simplex virus infection, and Epstein-Barr virus infection. In these patients, frosted branch angiitis is a clinical sign, possibly of immune complex deposition (secondary frosted branch angiitis). Finally, there is the group of otherwise healthy young patients (acute idiopathic angiitis).

Retinal Ischemia

Ischemic retinal vasculitis is frequently seen secondary to tuberculosis and retinal vasculitis associated with tuberculoprotein hypersensitivity. Ischemic retinal vasculitis may also be secondary to Behçet’s disease and multiple sclerosis. Retinal periphlebitis associated with sarcoidosis is usually nonocclusive, sometimes subclinical, and only visible on fluorescein angiography, associated with typical segmental cuffing or more extensive sheathing and perivenous exudates, which are usually indicated as “candle wax drippings.” Development of capillary nonperfusion and subsequent neovascularization as well as branch and central retinal vein occlusions have been described.

Diagnostic Evaluation

The search for a cause in patients with retinal vasculitis often involves a multidisciplinary approach and laboratory investigation (Table 3). Discrimination between infectious or noninfectious etiology of retinal vasculitis is important because treatment is different. In cases of diagnostic doubt, malignancy must be ruled out and should certainly be considered if, after an initial improvement with therapy, the patient’s disease rapidly becomes refractory to treatment.

Table 3 Diagnostic studies performed on patients with retinal vasculitis
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The laboratory workup of a patient with retinal vasculitis should be based on differential diagnosis derived from a detailed history, review of systems, and physical examination. If the patient’s medical history, review of systems, or ocular examination suggests an underlying systemic disease, then the diagnostic workup should be tailored for that disease.

Key Points

  • Differential diagnosis of retinal vasculitis is based on ophthalmoscopic and fluorescein angiographic findings.

  • Multidisciplinary team approach is essential in evaluation and treatment.

  • Thorough history, review of systems, and physical examination are essential.

  • The diagnostic workup should be tailored according to the patient’s medical history, review of systems, and physical examination.