Blurred vision, floaters, flashes, visual field loss.

Critical

Disruption of the blood–retinal barrier. Manifests as retinal sheathing around vessels and/or retinal vascular leakage on IVFA. May have associated retina, choroidal, AC, or vitreous inflammation. Cotton-wool spots due to microinfarcts of the retinal nerve fiber layer. May be occlusive with signs of peripheral ischemia or neovascularization. Complications include CME, retinal neovascularization, branch retinal vein and branch retinal artery occlusions.

Diagnostic Categories

• Determining whether the inflammation primarily affects the retinal venules (phlebitis), arterioles (arteritis), or both (mixed vasculitis) can help create an effective differential diagnosis list.

• See Table 12.5.1.

  TABLE 12.5.1: Differential Diagnosis for Retinal Vasculitis

  Primary Arteritis	Primary Phlebitis	Mixed Vasculitis	Occlusive Vasculitis
  HSV/VZV	CMV	Behçet disease	ANCA-associated
  ANCA-associated	HIV	IBD-associated	Behçet disease
  IRVAN	MS	Syphilis	GCA
  PAN	Sarcoidosis		HSV/VZV/CMV
  SLE	TB		Sarcoidosis
  			SLE
  			Susac syndrome
  			Syphilis
  			Tuberculosis

  HSV, herpes simplex virus; VZV, varicella-zoster virus; ANCA, antineutrophil cytoplasmic antibody; IRVAN, idiopathic retinal vasculitis, aneurysms, neuroretinitis; PAN, polyarteritis nodosa; SLE, systemic lupus erythematosus; CMV, cytomegalovirus; HIV, human immunodeficiency virus; MS, multiple sclerosis; IBD, inflammatory bowel disease; GCA, giant cell arteritis; TB, tuberculosis.

• HSV/VZV: Associated retinal vasculitis is most commonly seen in association with ARN syndrome (retinitis, vasculitis, and vitritis), but can occur in isolation. Most frequently is an occlusive vasculitis. See 12.13, Acute Retinal Necrosis.

• Antineutrophil cytoplasmic antibody (ANCA) associated:

  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg–Strauss disease): ANCA-associated vasculitis featuring obstructive airway disease (asthma), nasal polyps, elevated eosinophils, and mononeuritis multiplex (e.g., foot or wrist drops).

  • Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis): ANCA-associated vasculitis featuring nephritis,  orbital inflammation, sinusitis, and pulmonary inflammation.

• Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN): Three major criteria (retinal vasculitis, aneurysmal dilations at arterial bifurcations, and neuroretinitis) and three minor criteria (peripheral capillary nonperfusion, retinal neovascularization, and macular exudation). The etiology is unknown. Typically seen in young or middle-aged patients.

• Polyarteritis nodosa (PAN): Multisystem medium vessel vasculitis that often presents with hypertension, renal failure, neuropathy, and rash. More common in males ages 40 to 60 years. Can be associated with hepatitis B.

• Systemic lupus erythematosus (SLE): Typically presents with cotton-wools spots, retinal hemorrhage, and vascular occlusions. May be caused by either immune complex deposition in retinal vessels or by antiphospholipid syndrome. Multisystem disease with the most frequent manifestations including arthritis, myalgia, butterfly rash, and renal dysfunction.

• CMV: Associated retinal vasculitis is most commonly seen in the setting of severe immunosuppression and CMV retinitis. See 12.12, Cytomegalovirus Retinitis.

• HIV retinopathy: Presents with cotton-wool spots, retinal hemorrhages, and microaneurysms. See 12.11, HIV Retinopathy.

• MS: Most commonly presents as intermediate uveitis, but can also have a segmental phlebitis.

• Sarcoidosis: Pleomorphic uveitis. When affecting the retinal vessels it is classically a phlebitis with yellow exudates or “candlewax drippings.” Can be occlusive.

• TB: Pleomorphic uveitis. When causing a retinal vasculitis it preferentially affects the venules. Can be occlusive.

• Behçet disease: Typical demographic is aged 20 to 40 years, especially in patients of Japanese, Turkish, or Middle Eastern descent. Other than vasculitis, ocular manifestations include bilateral “shifting” hypopyon (due to lack of fibrin in the AC reaction), vitritis, waxy optic nerve pallor, focal necrotizing retinitis, and scleritis. Systemic features necessary for diagnosis include painful oral aphthous ulcers (well-defined borders with a white-yellow necrotic center, often with surrounding erythema, found in 98% to 100% of patients) at least three times per year and two of the following: genital ulcers, skin lesions, positive Behçetine (pathergy) test (formation of a local pustule that appears 48 hours after skin puncture with a needle), and eye lesions. Other systemic features include arthritis, hemoptysis from pulmonary artery involvement, renal involvement, gastrointestinal disease with bowel ulceration, epididymitis, neuro-Behçet (e.g., vasculitis, encephalitis, cerebral venous thrombosis, neuropsychiatric symptoms), and skin findings (erythema nodosum, pseudofolliculitis, palpable purpura, superficial thrombophlebitis, or dermographism) (see Figure 12.5.1).

  Figure 12.5.1: Occlusive hemorrhagic vasculitis in a patient with Behçet disease.

  

• IBD-associated: More commonly associated with Crohn disease. Causes a mild–moderate intermediate uveitis with peripheral vasculitis.

• Syphilis: Pleomorphic uveitis which can affect retinal arterioles and venules. See 12.10, Syphilis.

• Giant cell arteritis (GCA): Occlusive vasculitis of medium and large blood vessels that can rapidly result in severe ischemic vision loss in both eyes. See 10.17, Arteritic Ischemic Optic Neuropathy (Giant Cell Arteritis).

• Susac syndrome: Triad of retinal arteriolar occlusions (not at branch points), encephalopathy (lesions are classically located in the corpus callosum), and sensorineural hearing loss.

1. Obtain a thorough history and review of systems. In particular, ask about a history of sexually transmitted diseases, high-risk sexual activity, intravenous drug use, joint pains, neurologic deficits, headaches, bloody or loose bowel movements, jaw pain, weight loss, fever, night sweats, international travel, hearing loss difficulty breathing, rash, and ulcers (oral or genital). 

2. Complete ocular examination, including an IOP check, gonioscopy, and a dilated fundus examination.

3. Consider OCT to detect associated CME.

4. Perform an IVFA to detect subtle vasculitis, peripheral nonperfusion, peripheral neovascularization, or to monitor response to therapy.

5. Consider ICGA to detect subtle choroidal lesions and choroidal malperfusion.

6. Focused serologic testing based on history and examination:

   • Treponemal test (syphilis EIA, FTA-ABS, TP-PA), followed by confirmatory nontreponemal test (RPR, VDRL). See 12.10, Syphilis.

   • Interferon gamma releasing assay (IGRA, QuantiFERON Gold) and/or PPD. Consider chest imaging (CXR or CT chest) to assess for signs of active or prior pulmonary disease.

     • In those at risk for TB (e.g., immigrants from high-risk areas such as India, HIV-positive patients), homeless patients, or prisoners.

     • If considering immunosuppressive therapy (especially biologics).

   • Serologic testing for antibodies against HSV, VZV, and CMV can be useful in ruling out a disease as the causative etiology (IgG and/or IgM negative). The presence of positive IgG titer is not necessarily indicative of active disease, but rather prior exposure. Very elevated IgG titers may make you more suspicious for active disease, and a positive IgM indicates recent infection, but again are not fully diagnostic.

   • ACE, lysozyme, and chest imaging (CXR or CT chest).

   • ANCA testing: c-ANCA is more associated with GPA, and p-ANCA is more associated with EGPA, although neither are mutually exclusive.

   • HLA-B51 testing is neither sensitive, nor specific and has minimal clinical utility. Behçet disease is a clinical diagnosis.

7. Consider an AC paracentesis to detect DNA for CMV, HSV, VZV, or toxoplasmosis-associated disease. See Appendix 13, Anterior Chamber Paracentesis.

1. Consider topical prednisolone acetate 1% or difluprednate 0.05% q1–2h while awaiting workup results.

2. Treat infectious etiologies with appropriate antimicrobials prior to using local long-acting steroids or systemic steroids.

   • Oral acyclovir 400 mg five times per day or valacyclovir 500 mg t.i.d. for HSV-associated disease. Oral acyclovir 800 mg five times per day or valacyclovir 1000 mg t.i.d. for VZV-associated disease.

   • Oral valganciclovir 900 mg b.i.d. for CMV-associated disease.

   • For syphilis treatment, see 12.10, Syphilis.

   • For TB treatment, refer the patient to an internist, infectious disease specialist, or public health officer for consideration of systemic treatment. Patients with ocular TB frequently have no pulmonary disease but still require systemic four-drug antituberculous therapy. Concomitant oral steroids or steroid-sparing immunosuppression may be necessary.

3. Consider a trial of oral steroids after appropriate negative infectious workup.

4. Consider local steroid injection, particularly if the disease is unilateral, the eye is pseudophakic, and there is no history of steroid response ocular hypertension.

5. If the disease becomes persistent consider long-acting local steroids (0.19 mg or 0.59 mg fluocinolone acetonide implants) versus systemic steroid-sparing immunosuppression (e.g., antimetabolites, calcineurin inhibitors, and anti-TNF agents).

6. IVFA-guided panretinal photocoagulation should be considered in those with severe peripheral nonperfusion, active peripheral neovascularization, or complication from active peripheral neovascularization (e.g., vitreous hemorrhage).

1. In the acute phase, patients are reevaluated every 1 to 14 days, depending on the severity of the condition.

2. In the chronic phase, well-controlled phase, reexamination is performed every 3 to 6 months.