Acute unilateral vision loss, redness, blurred vision, floaters, ocular pain, and photophobia. Affected patients are usually immunocompetent.

(See Figures 12.13.1 and 12.13.2.)

Figure 12.13.1: The triad of retinitis, vasculitis, and vitritis in a patient with acute retinal necrosis.

Figure 12.13.2: Retinal detachment in a patient with acute retinal necrosis.

Critical

The American Uveitis Society criteria include one or more foci of retinal necrosis with discrete borders in the peripheral retina, rapid progression of disease in the absence of antiviral therapy, circumferential spread, evidence of occlusive vasculopathy with involvement of  arterioles, and prominent inflammatory reaction in the AC and/or vitreous. If untreated, the circumferential progression of necrosis may become confluent and spread posteriorly. The macula is typically spared early in the disease course.

Other

AC reaction; KP; conjunctival injection; episcleritis or scleritis; increased IOP; sheathed retinal arterioles and sometimes venules, especially in the periphery; retinal hemorrhages (minor finding); optic disc edema; delayed RRD occurs in approximately 70% of patients secondary to large irregular posterior breaks. Usually begins unilaterally but may involve the second eye in one-third of cases within weeks to months. An optic neuropathy with disc edema or pallor sometimes develops.

See 12.3, Posterior Uveitis.

• CMV retinitis: See 12.12, Cytomegalovirus Retinitis.

• PORN: Rapidly progressive retinitis characterized by clear vitreous and sheet-like opacification deep to normal-looking retinal vessels, and occasional spontaneous vitreous hemorrhage. PORN is usually found in immunocompromised individuals and frequently leads to rapid bilateral blindness due either to the infection itself or to secondary retinal detachment, making prompt diagnosis and treatment essential. Unlike ARN, pain and vitritis are minimal and macular involvement occurs early.

• Syphilis: Pleomorphic uveitis. Can present as a focal necrotizing retinitis. See 12.10, Syphilis.

• Toxoplasma retinochoroiditis: Primary toxoplasmosis can appear as a focal or fulminant retinitis (in an immunocompromised patient) without the classic adjacent pigmented chorioretinal scar. See 12.9, Toxoplasmosis.

• Behçet disease: Most common posterior manifestation is a vasculitis which may be occlusive and can have an associated focal necrotizing retinitis. See 12.5, Retinal Vasculitis.

• Sarcoidosis: Pleomorphic uveitis. Can present as a focal infiltrative retinitis.

• Fungal or bacterial endophthalmitis: See 12.17, Endogenous Bacterial Endophthalmitis and 12.18, Endogenous Fungal Endophthalmitis.

• Vitreoretinal lymphoma: Consider in patients >50 years of age with refractory unilateral vitritis, yellow-white subretinal infiltrates, absence of pain, or other signs of intraocular inflammation (quiet IVFA).

ARN is a clinical syndrome caused by the herpes virus family: most commonly VZV (older patients), less commonly HSV (younger patients), or rarely, CMV or Epstein–Barr virus (EBV).

See 12.3, Posterior Uveitis, for a nonspecific uveitis workup.

1. History: Risk factors for AIDS or other immunocompromised states (iatrogenic, autoimmune, malignancy, or genetic)? If yes, the differential diagnosis includes CMV retinitis and PORN. Ask about history of shingles (especially herpes zoster ophthalmicus) or herpes simplex infections. Head trauma (including neurosurgery) and ocular surgery may precipitate ARN. Rarely, ARN can follow localized immunosuppression with periocular or intravitreal corticosteroid injections. Most patients have no identifiable precipitating factors.

2. Complete ocular examination: Evaluate the AC and vitreous for cells, measure IOP, and perform a dilated fundus examination using indirect ophthalmoscopy; gentle scleral depression as necrotic retina has an increased risk of retinal detachment.

3. 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, CMV, and toxoplasmosis 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. Negative testing helps to rule out the disease.

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

   • Consider HIV testing.

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

5. Consider IVFA to identify retinal vasculitis and areas of ischemia.

6. Ultrawide field imaging may be useful in documenting and following up peripheral lesions.

7. Consider MRI of the brain and orbits with and without contrast and lumbar puncture if large cell lymphoma, tertiary syphilis, encephalitis, or optic nerve dysfunction is suspected.

NOTE All patients with ARN should be referred to a retina specialist.

1. Prompt inpatient or outpatient treatment. The goal is to halt and regress the retinitis in the involved eye and decrease the incidence of disease in the fellow eye. Treatment does not reduce the rate of retinal detachment in the first eye.

2. Oral antivirals (valacyclovir 1 to 2 g t.i.d. or famciclovir 500 mg t.i.d. preferred; acyclovir 800 mg five times per day second-line option as it achieves lower intravitreal levels) with supplemental intravitreal injections with foscarnet (2.4 mg/0.1 mL) or ganciclovir (2 mg/0.1 mL) given one to two times per week. Alternative therapy includes intravenous acyclovir 10 mg/kg t.i.d. for 5 to 14 days (requires dose adjustment for renal insufficiency) with supplemental intravitreal injections as noted above, followed by oral valacyclovir 1 g t.i.d. or acyclovir 400 to 800 mg five times per day. Either of these regimens is maintained for up to 14 weeks from the onset of infection. Involvement of the second eye typically starts within 6 weeks of initial infection. Published literature suggests that primary treatment with oral antivirals in conjunction with the above intravitreal injections has similar efficacy as intravenous therapy. Stabilization and early regression of retinitis are usually seen within 4 days. The lesions may progress during the first 48 hours of treatment. The ideal duration of oral antiviral therapy remains unproven, but since replicating virus in the AC can be found up to 2 months after the onset of disease, a minimum of 2 months of therapy is recommended, and some experts recommend lifetime therapy to reduce the risk of second-eye involvement (especially if the first eye becomes nonfunctional).

3. Topical cycloplegic (e.g., atropine 1% t.i.d.) and topical steroid (e.g., prednisolone acetate 1% q2–6h) in the presence of anterior segment inflammation.

4. The benefits of antiplatelet therapy (e.g., aspirin 81 to 650 mg daily) to minimize vascular thrombosis and help prevent further retinal ischemia remain unproven.

5. Systemic steroids may be considered, particularly when the optic nerve is thought to be involved. Steroids are usually delayed at least 24 to 48 hours after the initiation of antiviral therapy, or until regression of retinal necrosis is evident. A typical oral corticosteroid regimen is prednisone 60 to 80 mg/d for 1 to 2 weeks followed by a taper over 2 to 6 weeks.

6. See 9.7, Uveitic Glaucoma, for increased IOP.

7. Consider prophylactic barrier laser photocoagulation posterior to active retinitis to wall off or prevent subsequent RRD (efficacy remains unclear). 

8. Pars plana vitrectomy, with long-acting gas or silicone oil, is the best way to repair the associated complex RRD. Proliferative vitreoretinopathy is common.

1. Patients are seen daily initially and are examined every few weeks to months for the following year; examination of both eyes is essential.

2. A careful fundus evaluation is performed at each visit to rule out retinal holes that may lead to a detachment. If barrier laser demarcation has been done and the retinitis subsequently crosses the posterior margin, consider applying additional laser therapy.

3. Pupillary evaluation should be performed, and optic neuropathy should be considered if the retinopathy does not explain the amount of visual loss.