Steven T. Bailey

BASICS

DESCRIPTION

• Cytomegalovirus (CMV) retinitis is a full thickness retinal necrosis resulting in progressive vision loss.

• CMV is an ubiquitous herpes virus.

• Retinitis occurs in immunosuppressed hosts, typically those infected with human immunodeficiency virus (HIV) and a CD4+ count <50 cells/mL.

• Leading cause of acquired immunodeficiency syndrome (AIDS) related blindness

• Treated with immune reconstitution with highly active anti-retroviral therapy (HAART) and anti-CMV medications

EPIDEMIOLOGY

Incidence

• AIDS patients pre-HAART era: 30% lifetime probability

• HAART era: Reduced incidence by 75–80%

• Much less common in non-HIV immunosuppressed individuals

RISK FACTORS

• HIV+ with CD4 <50 cells/mL

• HIV-associated microvasculopathy

• Organ transplant recipients

• Steroid treatment

• Systemic chemotherapy

• Malignancies, that is, leukemia, lymphoma

GENERAL PREVENTION

• Safe sex practice

• Avoid contact with bodily fluids

• Ophthalmic examination with dilated fundus examination for high risk individuals

PATHOPHYSIOLOGY

• CMV transmission: Transplacental, contact with bodily fluids, blood transfusion, organ transplant

• Immunosuppressed host susceptible to primary infection or reactivation of latent infection

• CMV reaches eye through the bloodstream

• All layers of retina infected resulting in full thickness retinal necrosis

• Untreated retinitis slowly progressively enlarges over weeks to months

• Rhegmatogenous retinal detachment may develop in 15–40% of eyes

ETIOLOGY

Cytomegalovirus beta-herpes virus.

COMMONLY ASSOCIATED CONDITIONS

• CMV pneumonitis

• CMV colitis and esophagitis

• CMV transverse myelitis and meningoencephalitis

• Congenital CMV infection

DIAGNOSIS

HISTORY

• May be asymptomatic

• Decreased central or peripheral vision

• New onset of floaters

• AIDS with CD4+ count <50 cell/mL

• Leukemia, lymphoma, and aplastic anemia

• Organ transplant recipient

• Systemic immunosuppression chemotherapy

PHYSICAL EXAM

• Visual acuity: Decreased or normal

• Confrontation to visual fields: Decreased or normal

• Afferent papillary defect may be present

• Typically minimal anterior and/or vitreous inflammation

• Fulminant retinitis with retinal edema, retinal hemorrhage, and vasculitis

• Indolent/granular retinitis with faint grainy retinal opacification

• Zone I: Within 3000 microns from fovea

• Zone II: Peripheral to zone 1 to vortex veins

• Zone III: Peripheral to zone 2 to ora serrata

DIAGNOSTIC TESTS & INTERPRETATION

Lab

• HIV Serology (if unknown)

• CD4+ T-lymphocyte count

• HIV ribonucleic acid (RNA) blood level

Imaging

Initial approach

Fundus photography

Follow-up & special considerations

Serial fundus photographs are useful to evaluate for disease progression.

Diagnostic Procedures/Other

If clinical diagnosis unclear, polymerase chain reaction (PCR) of vitreous or aqueous humor samples can detect CMV.

DIFFERENTIAL DIAGNOSIS

• Acute retinal necrosis (HSV or VZV)

• Progressive out retinal necrosis (VZV)

• HIV-associated retinopathy

• Syphilis

• Toxoplasmosis

• Endophthalmitis

• Tuberculosis

TREATMENT

MEDICATION

First Line

• HAART naïve with Zone I disease: Intravitreal ganciclovir implant 4.5 mg with oral valganciclovir (1) (see dose below)

• Heart naïve with Zone II/III disease: Valganciclovir oral 900 mg b.i.d for 3 weeks followed by maintenance dose of 900 mg per day (2)

• HAART experienced with Zone 1 disease: Ganciclovir implant with oral Valganciclovir

• HAART experienced with Zone II/III disease: Oral Valganciclovir +/− ganciclovir implant

• Zone I disease: May also consider intravitreal ganciclovir injection 2 mg/0.1 mL twice weekly or foscarnet 2.4 mg/0.1 mL twice weekly until ganciclovir implant available

• Valganciclovir toxicities: Renal toxicity, neutropenia, anemia, thrombocytopenia

• Initiate HAART or alter HAART if ineffective

• If HAART naïve, consider treatment of CMV retinitis prior to HAART to limit immune recovery uveitis

Second Line

• Ganciclovir: Induction dose 5 mg/kg IV b.i.d for 14–21 days. Oral maintenance dose: 1000 mg PO t.i.d. Intravenous (IV) maintenance dose: 5 mg/kg IV daily or 6 mg/kg IV 5 days/week

• Ganciclovir toxicities: Renal toxicity, neutropenia, anemia, thrombocytopenia

• Foscarnet: Induction dose: 90 mg/kg IV b.i.d for 14–21 days. Maintenance dose: 90 mg/kg IV daily.

• Foscarnet toxicities: Renal impairment, neutropenia, anemia, electrolyte imbalances

• Cidofovir: Induction dose: 5 mg/kg IV weekly for 2 weeks. Maintenance dose: 5 mg/kg IV every 2 weeks

• Cidofovir toxicities: Nephrotoxicity, ocular hypotony, and iritis

ADDITIONAL TREATMENT

Issues for Referral

• Retina specialist for evaluation and treatment of suspected CMV retinitis

• Infectious disease specialist to evaluate for other end-organ CMV related disease and/or other opportunistic infections

• General internist, oncologist, or hematologist for non-HIV related CMV retinitis

Additional Therapies

Low vision evaluation for those with substantial vision loss.

SURGERY/OTHER PROCEDURES

• Surgical insertion of ganciclovir sustained release implant – lasts 6–10 months

• Surgical repair of retinal detachment may include vitrectomy, scleral buckle, and silicone oil or gas endotamponade.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• Those on HAART with CD4+ counts >100–150 cells/mL for 3–6 months may discontinue the anti-CMV drugs (3)

• Reactivation of CMV retinitis may present with appearance of a new lesion or expansion of previously inactive border.

• Reactivation is treated with re-induction with anti-CMV medications and possible adjustment in HAART to establish immune recovery.

• Evaluate for ganciclovir resistance if treatment response is inadequate.

Patient Monitoring

Frequent dilated fundus examinations dependent on extend of CMV retinitis and degree of immune recovery.

PATIENT EDUCATION

• Symptoms of CMV retinitis: Floaters, photophobia, central or peripheral vision loss

• Appropriate medication use and side effect profile

PROGNOSIS

Dependent on ability of immune recovery – much less likely to lose significant vision in HAART era.

COMPLICATIONS

• Vision loss

• Retinal detachment

• Immune recovery uveitis may result in: Macular edema, epiretinal membrane, neovascularization of the retina, and cataract

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