CMV Retinitis

Cytomegalovirus (CMV) retinitis is a necrotising retinitis caused by reactivation of latent CMV in immunosuppressed patients, and the commonest ocular opportunistic infection in advanced HIV disease.

• Occurs at CD4 counts under 50 cells/microlitre (rarely up to 100); incidence has fallen over 80 percent with effective antiretroviral therapy, but remains common where HIV is diagnosed late.
• Other settings: organ and haematopoietic stem cell transplant recipients, patients on high dose immunosuppression or biologics, congenital CMV, and rarely immunocompetent patients with anterior uveitis and raised pressure.
• Spreads from retinal cell to cell, progressing about 250 micrometres per week at the border, if untreated causes full thickness necrosis, atrophy and retinal detachment (risk about 20 to 30 percent per eye year in untreated patients).

• Painless blurred vision, floaters, flashes, field defects (peripheral or central), usually unilateral at first and bilateral in about 30 to 40 percent over time; minimal anterior chamber inflammation and vitritis (low inflammation in AIDS).
• Fulminant (oedematous) form: dense white retinal opacification with haemorrhages along the vessels ("pizza pie", "cheese and ketchup" appearance), typically near the arcades.
• Indolent (granular) form: peripheral granular, less haemorrhagic lesion, with a slowly advancing border and central atrophy.
• Frosted branch angiitis: perivascular sheathing.
• Immune recovery uveitis after antiretroviral therapy: vitritis, macular oedema, epiretinal membrane, in patients with CD4 above 100 and controlled retinitis.
• Zone of involvement: zone 1 (within 1500 micrometres of the optic disc or 3000 micrometres of fovea) is sight threatening.

• Clinical diagnosis from characteristic fundus lesions in an at risk patient, with dilated fundus examination and wide field photography to document lesion size and for monitoring.
• Aqueous or vitreous polymerase chain reaction for CMV DNA (high sensitivity) when atypical, and to exclude varicella zoster, herpes simplex, toxoplasmosis, syphilis.
• HIV testing, CD4 count and viral load; CMV viral load in blood; full blood count and renal function before therapy.
• Optical coherence tomography for macular involvement.

• Systemic anti-CMV therapy (induction 2 to 3 weeks, then maintenance):
  • Valganciclovir 900 mg orally twice daily for 21 days, then 900 mg once daily for maintenance (needs normal renal function; adjust to creatinine clearance).
  • Intravenous ganciclovir 5 mg/kg every 12 hours for 14 to 21 days, then 5 mg/kg daily. Adverse effects: neutropenia, thrombocytopenia (give granulocyte colony stimulating factor if neutrophils fall below 0.5 x 10^9/L).
  • Foscarnet 90 mg/kg intravenously every 12 hours (or 60 mg/kg every 8 hours) for 14 to 21 days, then 90 to 120 mg/kg daily, with saline hydration; nephrotoxicity and electrolyte disturbances (calcium, magnesium, potassium) require monitoring. Used for ganciclovir resistance (UL97 mutations) or marrow suppression.
  • Cidofovir 5 mg/kg weekly for 2 weeks then every 2 weeks, with probenecid 2 g orally 3 hours before and 1 g at 2 and 8 hours after, and saline hydration; nephrotoxicity, anterior uveitis and hypotony limit use.
• Intravitreal therapy for sight threatening zone 1 disease or intolerance of systemic therapy: ganciclovir 2 mg in 0.05 mL (or foscarnet 2.4 mg in 0.1 mL) twice weekly for 3 to 4 injections, then weekly.
• Antiretroviral therapy: start or optimise immediately in HIV (within 2 weeks of anti-CMV therapy), the most important determinant of long term control; maintenance anti-CMV therapy can be stopped when CD4 count is above 100 cells/microlitre for 3 to 6 months and retinitis is inactive.
• Retinal detachment (about 15 to 30 percent): pars plana vitrectomy with silicone oil tamponade.
• Immune recovery uveitis: topical, periocular (sub-Tenon triamcinolone 40 mg) or short oral steroid while continuing antivirals.
• Monitor every 2 to 4 weeks initially with fundus photographs; relapse is signalled by lesion border advance or new lesions.