Research Article: Cytomegalovirus Retinitis: The Neglected Disease of the AIDS Pandemic

Date Published: December 1, 2007

Publisher: Public Library of Science

Author(s): David Heiden, Nathan Ford, David Wilson, William R Rodriguez, Todd Margolis, Bart Janssens, Martha Bedelu, Nini Tun, Eric Goemaere, Peter Saranchuk, Kalpana Sabapathy, Frank Smithuis, Emmanuel Luyirika, W. Lawrence Drew

Abstract: The authors describe CMV retinitis in resource-poor settings and suggest possibilities for management.

Partial Text: Cytomegalovirus (CMV), a member of the herpesvirus family, was a familiar cause of blindness and death in patients with advanced AIDS in Western countries prior to the introduction of highly active antiretroviral therapy (HAART). CMV retinitis then occurred in roughly one-third of patients with AIDS, and accounted for over 90% of cases of HIV-related blindness [1]. Extraocular CMV disease was a major cause of AIDS-related morbidity and mortality [2]. CMV retinitis is now clinically infrequent in patients with AIDS in developed countries, thanks to the widespread availability of HAART, although the problem has not disappeared [3,4]. Successful fundamentals of management are screening eye examinations in patients with low CD4 counts, and effective anti-CMV treatment with ganciclovir and related compounds, combined with HAART.

In developing countries CMV infection is usually acquired in childhood, and nearly 100% of adults are seropositive [8,9,10]. Like other herpesvirus infections, CMV may remain latent for life. Overt clinical disease occurs with waning immunity.

The “gold standard” for diagnosis of CMV retinitis is examination of the retina through a dilated pupil by a skilled clinician using an indirect ophthalmoscope. Dilation of the pupil is critical, because CMV retinitis can occur anywhere in the retina and without a dilated pupil only a fraction of the retina can be examined. Retinal examination is highly sensitive and specific, and can be performed by any clinician after about one month’s training. Diagnosis of CMV retinitis does not require laboratory tests or eye tests [18]. Patients are typically easy to examine because the ocular media is clear and the pupil dilates well. With a skilled examiner and a cooperative patient with dilated pupils, the exam can be performed in less than two minutes.

CMV retinitis does not cause pain or redness in the involved eye. Characteristic symptoms are floaters, scotoma, photopsia, and blurred vision, [12,25] and although some reports suggest symptoms are common [25], they are frequently discounted or ignored. Clinical experience shows that limiting retinal examination only to patients with symptoms is not reliable, and that systematic retinal screening examination of vulnerable patients with or without symptoms is essential [26]. The efficacy of screening asymptomatic patients has been demonstrated [27], and meets generally accepted criteria for appropriate screening interventions: the disease is common, treatable, and easy to diagnose at an early stage, and the consequence of blindness is severe. Determination of visual acuity with an eye chart, the most commonly used eye screening test, measures only foveal function, representing less than 1% of the retinal surface, and is a poor test for CMV retinitis.

Successful treatment of CMV in patients with AIDS requires both specific medication against CMV and recovery of immune function through the use of antiretroviral therapy. Antiretrovirals are continued indefinitely, while specific treatment for CMV retinitis is continued at least until the retinitis resolves. Once there is some restitution of immune function and the CD4 count is increased to above 100 cells/μl (and commonly after at least three months), reactivation of CMV retinitis is unlikely [29,30]. Thus specific treatment of CMV retinitis is usually required for only a limited vulnerable window of time.

We have unequivocally observed that CMV retinitis is causing blindness in a young population in developing countries (Table 2), even though the full scope of the problem remains to be defined.

Treatment of opportunistic infections is an integral part of HIV management at the primary care level, and treatment of CMV retinitis should be included. Patients with CMV retinitis are often too sick or lack adequate financial or social support to reach specialists [52]. In most places in the developing world there are too few ophthalmologists to manage the CMV problem, and like other specialists, they are concentrated in major cities, relatively inaccessible to rural locations and to the poor [53]. Ophthalmologists are often not highly motivated to care for patients with AIDS, and have other priorities, including a growing backlog of 45 million patients waiting for sight-restoring cataract surgery globally [54].

The realistic place for managing CMV infection, like other opportunistic infections, is in the AIDS clinic by the AIDS doctors. Diagnosis and management of CMV infection should become part of routine care. Screening for CMV retinitis should be part of the initial evaluation of high-risk patients (at minimum all patients with CD4 counts below 50 cells/μl, and possibly other groups) when they first enter HIV care. The screening technique should be the same as in Western countries: study of the entire retina through a fully dilated pupil using an indirect ophthalmoscope.



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