CMV Retinitis

Updated: Oct 20, 2016
  • Author: Michael Altaweel, MD, FRCSC; Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

Background

Cytomegalovirus (CMV) is a ubiquitous DNA virus that infects the majority of the adult population. In the immunocompetent host, infection is generally asymptomatic or limited to a mononucleosis-like syndrome. Like many other herpesviruses, CMV remains latent in the host and may reactivate if host immunity is compromised.

In immunocompromised individuals, primary infection or reactivation of latent virus can lead to opportunistic infection of multiple organ systems. In the eye, CMV most commonly presents as a viral necrotizing retinitis with a characteristic ophthalmoscopic appearance (see image below). [1] Untreated CMV retinitis inexorably progresses to visual loss and blindness. [2]

Retinitis typically starts in the midperiphery and Retinitis typically starts in the midperiphery and can progress in a "brush fire" pattern.

Although postnatally acquired CMV retinitis is seen most commonly in patients with acquired immunodeficiency syndrome (AIDS), transplant patients [3, 4] or other patients receiving immunosuppressive medications are also at risk. [5] High viral load and severe deficit in immune function combine to increase the potential for developing CMV retinitis.

Multiple antiviral agents, delivered locally, systemically, or in combination, are currently in use to delay or arrest the progress of the disease. [6] In addition, highly active antiretroviral therapy (HAART) for HIV infection has revolutionized the treatment of CMV retinitis by allowing immune reconstitution in many individuals. [7, 8, 9]

Over a period of 5 years, the incidence of opportunistic infections has reduced, and newly diagnosed cases of CMV retinitis have decreased by up to 83%.

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Pathophysiology

Transmission of CMV occurs through placental transfer, breast milk, saliva, sexually transmitted fluids, blood transfusions, and organ or bone marrow transplants. In the immunocompetent pediatric or adult host, infection is generally asymptomatic or limited to a mononucleosis-like syndrome with signs and symptoms including fever, myalgia, cervical lymphadenopathy, and mild hepatitis.

CMV generally dwells as a latent intracellular virus in immunocompetent children and adults. CMV may reactivate if host immunity is compromised. In immunocompromised individuals, primary infection or reactivation of latent virus can lead to opportunistic infection of multiple organ systems, including the skin (eg, rashes, ulcers, pustules), lungs (eg, interstitial pneumonitis), gastrointestinal tract (eg, colitis, esophagitis), peripheral nerves (eg, radiculopathy, myelopathy), brain (eg, meningoencephalitis), and eye (eg, retinitis, optic neuritis). [10]

In the eye, CMV commonly presents as a viral necrotizing retinitis with vitreitis and may result in retinal detachment. Untreated CMV retinitis inexorably progresses to visual loss and blindness.

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Epidemiology

Frequency

United States

CMV is ubiquitous, infecting 50-80% of the adult population. Clinically evident disease is found almost exclusively in immunosuppressed individuals. Prior to HAART, CMV occurred in 25-40% of all AIDS patients and was the most common opportunistic infection in AIDS patients with a CD4 count below 50 cells/μL. While HAART has decreased the incidence of CMV retinitis by 55-83%, the decline in AIDS-related mortality has led to an increase in the number of patients with CMV disease.

In a prospective cohort study, Sugar et al estimated the incidence of CMV retinitis in the post-HAART era among 1600 AIDS patients without CMV retinitis at enrollment. They found an incident rate of 0.36/100 person-years, with the highest rate observed among patients with CD4 counts below 50 cells/μL [11] .

Patients with AIDS and CMV are also at risk of cataract, which is likely to be an increasingly important cause of visual morbidity in this population. A study of 489 AIDS patients diagnosed with CMV retinitis found a high prevalence of cataract. Potentially modifiable risk factors identified included large retinal lesion size and use of silicone oil in retinal detachment repair. [12]

CMV retinitis remains a leading cause of visual loss in patients with AIDS and is increasing in organ transplant recipients as the number of those procedures performed each year increases. In a series of 304 recipients of allogeneic hematopoietic stem cell transplantation, CMV retinitis developed in 13 (4%). This represented 23% (13 of 56) of those with significant CMV viremia. [4]

International

The frequency of CMV retinitis in other developed countries is equivalent to that of the United States. The prevalence of CMV retinitis in HIV-infected individuals in developing countries is generally lower than in North America and Western Europe. The lower reported prevalence of CMV retinitis in developing countries, particularly those on the African continent, may be attributed the fact that many HIV-infected individuals die before their immune function deteriorates to the level at which CMV retinitis typically occurs. [13] In general, the incidence of CMV in developing countries reflects the spread of the HIV virus and the availability of antiretroviral medications. [14, 15]

When identified, CMV retinitis has often progressed to the debilitating stage, and intervention is less likely to achieve visual recovery. Improved screening programs and availability of oral valganciclovir are required to improve management of CMV retinitis in this setting. [16]

Mortality/Morbidity

CMV retinitis frequently results in considerable loss of visual acuity, and, without treatment, it almost universally leads to blindness. [17, 18] Severe visual loss primarily occurs from the direct spread of retinitis into the posterior pole, affecting central vision, or from retinal detachment (RD) secondary to multiple retinal breaks in the peripheral, necrotic retina. [19, 20]

Early and aggressive treatment with antiviral medication for both CMV and HIV, combined with improved surgical techniques for RD repair, has helped to improve the visual outcomes in these patients.

Untreated CMV leads to progressive visual loss and eventual blindness.

Retinal detachment occurs in up to 29%. [21]

CMV retinitis causes full thickness necrosis of the retina.

Retinitis permanently destroys the retina; lesions change appearance with treatment but do not become smaller. Areas of retina affected by retinitis can develop erosive holes despite resolution of the retinitis.

If the CD4 count is less than 100 cells/μL, CMV retinitis will develop in 20-30% of patients over a year, although retinitis typically develops if the CD4 count is reduced below 50 cells/μL. Of these patients, 5-10% develop other systemic infections (eg, pneumonitis, colitis, esophagitis).

With the advent of HAART and immune reconstitution, some patients suffer from a relatively new condition known as immune recovery uveitis (IRU). [22, 23, 24] IRU occurs when the poor immune response of an immunocompromised individual is suddenly increased as the patients restored immune system recognizes and reacts to viral antigens in the retina. This reaction can lead to several complications, including uveitis, leading to hypotony, cataract, and glaucoma; epiretinal membrane (ERM); and cystoid macular edema (CME). [25, 26]

CMV immune recovery retinitis denotes patients who develop active CMV retinitis within 6 months after starting antiretroviral therapy. This may occur despite a CD4 count greater than 50 cells/μL, indicating the need to conduct careful surveillance after initiation of systemic therapy. [27]

Despite improvements in systemic treatment for AIDS, the 5-year mortality for those diagnosed with CMV retinitis is 3 deaths per 100 person-years for those with previously diagnosed retinitis and 26.1 deaths per 100 person-years for those with newly diagnosed CMV retinitis. [28]

Patients with newly diagnosed CMV retinitis have a 5-year rate of vision loss to less than 20/40 in 11.8 of 100 eye-years and to 20/200 or worse in 5.1 of 100 eye-years. [28]

Sex

Although the incidence of CMV retinitis is the same among men and women, the prevalence is higher in men than in women because of the higher prevalence of AIDS in men. The prevalence of CMV retinitis in the heterosexual community has been steadily increasing.

Age

The age of most individuals developing CMV retinitis is 20-50 years.

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