CYTOMEGALOVIRUS RETINITIS

Cytomegalovirus (CMV) retinochoroiditis occurs primarily in the unborn infant and the immunocompromised adult. This once uncommon disease became common with the advent of acquired immunodeficiency syndrome (AIDS). In the early years of the US AIDS epidemic, 30% of human immunodeficiency virus (HIV)-positive patients developed CMV retinitis. Since the introduction of antiretroviral therapy in 1996, the prevalence of this disease has decreased dramatically.

Symptoms

Symptoms of CMV are present in up to 75% of infected eyes. Peripheral CMV retinitis typically produces floaters and visual field cuts. Posterior pole disease is more frequently accompanied by blurred vision or blind spots. Isolated macular disease or CMV optic neuritis is uncommon but can cause profound and sudden loss of vision.

Clinical Features

Cytomegalovirus retinitis has two clinical presentations: fulminant and indolent. Fulminant CMV retinitis is classically described as a “pizza” fundus; it causes a necrotizing retinitis that produces confluent retinal whitening associated with retinal hemorrhages and vascular sheathing. Vitreous and anterior chamber cells are invariably present. Indolent or granular CMV retinitis has less edema and a faint, gray opacification with little hemorrhage or vascular sheathing. In both types, the leading edge of infection will display an advancing, irregular, granular border often with small, isolated satellite lesions. Healed, old infection is characterized by fibroglial retinal scarring and mottling of the underlying retinal pigment epithelium.

Frosted branch angiitis is a rare association. Immune recovery uveitis may be seen in patients following successful anti-HIV therapy.

Ancillary Testing

Fluorescein angiography is not necessary for the diagnosis or management of CMV retinitis. Serial fundus photography is integral to the management of this disease.

Pathology/Pathogenesis

Cytomegalovirus is a DNA virus and a member of the herpesvirus family. It has been identified in all layers of the retina. Infection spreads by cell-to-cell transmission of the virus. Histopathologically, CMV retinitis destroys retinal architecture; many enlarged cells containing Cowdry type A intranuclear eosinophilic inclusions with surrounding clear zones give the cells an “owl’s eye” appearance.

Treatment/Prognosis

Immune reconstitution in transplant patients or AIDS patients can induce resolution of CMV retinitis. The first three drugs approved for treatment of CMV retinitis are ganciclovir, foscarnet, and cidofovir. Although the choice of agent and route of therapy is complex, in general, patients are started on induction therapy followed by maintenance therapy. Approximately 85% of treated patients will respond, but reactivation is the rule, prompting reinduction or switching to a new agent. Intravitreal gancyclovir implants are an alternative to systemic antiviral therapy. Retinal detachment is a particularly severe complication that may occur in 15% to 40% of eyes.

Systemic Evaluation

All patients suspected of having CMV retinitis should undergo HIV testing. If positive, CD4 and viral load counts should be performed. Cytomegalovirus retinitis is most commonly observed in patients with CD4 counts less than 50 µL. Most HIV-positive patients are CMV seropositive, so attempts to isolate virus from nonocular body fluids are non-diagnostic. Polymerase chain reaction (PCR)-based analysis of vitreous fluid offers highly diagnostic sensitivity and specificity and can be used in atypical or unresponsive cases.

Cytomegalovirus retinitis is characterized by fullthickness retinitis associated with retinal hemorrhage. It commonly affects the posterior fundus in a perivascular distribution.

Cytomegalovirus retinitis may demonstrate a leading edge of active retinitis and a wake of atrophy of the retina and retinal pigment epithelium reminiscent of a brush fire.

Peripheral cytomegalovirus retinitis often has a granular pattern with less intraretinal hemorrhage. Small satellite lesions extending from the main area of retinitis are common.

Untreated cytomegalovirus retinitis may result in a diffuse retinitis associated with intraretinal hemorrhage resembling a “pizza” fundus.

Old cytomegalovirus infection is characterized by fibroglial retinal scarring and mottling of the underlying retinal pigment epithelium.

A late complication of cytomegalovirus retinitis is retinal detachment, as seen inferiorly below the active retinitis in this figure. Retinal detachment results from multiple holes in the thin, atrophic retina in areas of previous infection.

Diffuse unilateral subacute neuroretinitis (DUSN) is an infectious disease caused by a nematode that may be found in the vitreous or subretinal space. It may cause profound loss of vision in one eye, usually in children or young adults. There is one case report of bilateral DUSN.

Symptoms

Patients can present with acute visual loss ranging from 20/30 to 20/200. Floaters and ocular discomfort are less common symptoms. In approximately 50% of patients, particularly children, visual loss is insidious, and the patient comes to medical attention only late in the course of disease. By that time severe visual loss is permanent.

Clinical Features

Findings in early DUSN include mild vitritis, mild optic disc edema, and recurrent crops of multifocal, graywhite outer retinal lesions. The round, white nematode may be found adjacent to these active lesions. Findings in late DUSN include optic atrophy, narrowed retinal arterioles, and striking degenerative changes in the retinal pigment epithelium (RPE) and retina (“unilateral wipe-out syndrome”). A relative afferent pupillary defect is usually present.

Ancillary Testing

Fluorescein angiography in early DUSN shows that the gray-white areas of retinitis are hypofluorescent early but stain late. There is optic nerve hyperfluorescence. Angiography is not helpful in locating the nematode. Fluorescein angiography in late DUSN shows widespread hyperfluorescence caused by window defects resulting from the damaged RPE. The electroretinographic findings range from subnormal to extinguished in the affected eye (and normal in the fellow eye).

Pathology/Pathogenesis

Diffuse unilateral subacute neuroretinitis is caused by at least two different nematodes, neither of which has been definitively identified. The smaller of the two measures 400 µm to 1000 µm in length and is thought to possibly be Ancylosytoma caninum. The larger measures 1500 µm to 2000 µm in length and is thought to possibly be

Baylisascaris procyonis. The pathogenesis of DUSN appears to be mediated by worm waste products acting as toxins damaging both the inner and outer retina. Thus, visual loss is thought to be caused by physiologic retinal damage by worm end products rather than by anatomic retinal damage by the migrating worm itself.

Treatment/Prognosis

Photocoagulation of the nematode is the treatment of choice. It effectively kills the worm, causes little or no inflammation, and inactivates the disease process. Visual prognosis is good only if the worm is killed shortly after the onset of visual loss. In eyes in which the nematode cannot be located and destroyed, oral thiabendazole or ivermectin have been tried to arrest the disease.

Systemic Evaluation

Patients with DUSN do not manifest systemic disease. Stool samples do not show ova or parasites. Eosinophilia is rare. Serologic studies are prone to error in interpretation. Thus, a systemic evaluation is of little help in making the diagnosis of DUSN.

Diffuse unilateral subacute neuroretinitis is considered one of the inflammatory white dot syndromes. Clusters of small white dots are visible in the vicinity of the nematode.

End-stage diffuse unilateral subacute neuroretinitis is characterized by optic disc pallor, retinal vascular narrowing, and diffuse mottling of the retinal pigment epithelium.

Diffuse unilateral subacute neuroretinitis is caused by a mobile, small, white nematode located in the potential space between the neurosensory retina and the retinal pigment epithelium. (Photograph courtesy Ditte Hess, CRA, and Rick Stratton.)

This fluorescein angiogram reveals a “salt and pepper” pattern of hyperfluorescence as a result of the retinal pigment mottling.

Fundus photograph in a patient with diffuse unilateral subacute neuroretinitis reveals a small nematode located nasal to the optic disc.

Fundus photograph of the same patient following laser photocoagulation of the nematode. Laser photocoagulation is effective when the nematode

is detected early in the disease course.