HAART may help AIDS patients ‘cure’ CMV retinitis

Issue: September 1, 1999

ByRochelle Nataloni

---Candida corneal ulcer with a hypopyon in an HIV-positive patient who is also an active drug user.

SAN FRANCISCO — The major categories of immunosuppression that can put people at risk for unusual or opportunistic ocular infections are AIDS; long-term use of immunosuppressive drugs used for organ transplantation, bone marrow transplantation, or rheumatic conditions, such as lupus or rheumatoid arthritis; and cancers, such as leukemia or lymphoma.

Less frequently, a congenital defect results in an inherited immunodeficiency state. “Today, AIDS is far and away the most common,” said Emmett Cunningham Jr., MD, PhD, MPH. “Before it was probably seen most often in patients who were on long-term immunosuppressive agents, either because they had an organ or bone marrow transplant or because they had an underlying autoimmune disease that required immunosuppression. Other causes like malignancy or inherited immune deficiencies, while recognized, are pretty rare and not seen very often.”

Dr. Cunningham is director of the Ocular Immunology Laboratory at the Francis I. Proctor Foundation, University of California San Francisco Medical Center.

New CMV presentations

Left fundus of a patient showing whitening and scattered hemorrhages typical of CMV retinitis. Satellite lesions at the edge of the lesion are characteristic of CMV infection (left). Three months following treatment with intravitreous followed by intravenous ganciclovir, the retinitis is inactive and the vision remains 20/20 (right).
COURTESY OF EMMETT T. CUNNINGHAM, JR., MD, PHD, MPH.

Regardless of cause, the most common opportunistic eye infection seen in patients who are immunosuppressed is cytomegalovirus (CMV) retinitis, Dr. Cunningham said. “CMV is a ubiquitous organism. Many people are infected with it at some point during their life, but in the setting of a normal immune system, they handle it well and it doesn’t lead to any long-lasting clinical disease,” Dr. Cunningham told Ocular Surgery News. “Some people develop a flu-like illness during the primary infection and then develop an immune reaction to it that keeps the virus suppressed or latent for the patient’s entire life. But when the immune system is suppressed, the CMV comes out,” he said.

It has been recognized now for 15 years that patients who are HIV-positive can develop CMV retinitis at some point during their illness, and it is almost always when their T cells are very low, at a very advanced stage of the disease.

“The patients’ CD 4-positive T lymphocytes are almost always under 100 cells per cubic milliliter, and more often than not, under 50 cells per cubic milliliter,” Dr. Cunningham said. The advent of HAART (highly active anti-retroviral therapy), which fights HIV and thereby strengthens the immune system, has produced reversal in the declining T-cells. Consequently, T-cells increase, and people regain their ability to fight CMV.

“Today we’re seeing different presentations for CMV retinitis in HIV-positive patients than we were used to seeing over the past 15 years,” he said. For example, some patients who develop CMV retinitis just after or just prior to starting HAART have spontaneous and sustained resolution of the retinitis without any specific CMV medications. “They cure the CMV retinitis by themselves as their immune system strengthens,” Dr. Cunningham said. “It happens infrequently, however, because it’s a matter of timing. The patient has to be developing the CMV right at the point when he or she is getting the combination drug therapy, and the CMV has to be as yet unrecognized,” he explained.

Patients who have an area of inactive retinitis because they previously had CMV that is currently inactive can develop an immune reaction to the virus.

“It’s either there latently, or pieces of the virus are left from the infection,” Dr. Cunningham said. “They can develop an immune reaction to that as their immune system gets stronger, resulting in a moderate to severe vitreous inflammation. They can develop cystoid macular edema (CME), or they can develop an epiretinal membrane, and all three of those can decrease vision. To treat the vitreous inflammation, we usually use steroids, either given orally or as a periocular injection. To treat the epiretinal membrane, when it’s severe enough, we use surgery,” he said.

As many as 10% to 15% of organ transplant patients will have some evidence at eye exam of having had a recent CMV infection. Recently, it has been recognized that like the patients who are immunosuppressed by HIV but have a strengthened immune system, many patients who have undergone an organ or bone marrow transplant have a somewhat weakened, but not terribly weakened, immune system. “They can develop CMV that will either heal spontaneously or be associated with a more prominent vitreous inflammation,” Dr. Cunningham said.

In an article published last year in the American Journal of Ophthalmology, Janet Davis, MD, of the Anne Bates Leach Eye Hospital at the Bascom Palmer Eye Institute at the University of Miami School of Medicine, reported that a multicenter review of cardiac transplantation yielded a 13% incidence of systemic CMV infection by pathologic or clinical diagnosis with laboratory confirmation.

“Occult CMV retinitis in transplant patients appears to be more common than recognized,” she wrote. “Seven of 14 patients were asymptomatic in the series by Egbert and associates. In our series, four of six patients were asymptomatic despite CMV lesions.” Dr. Davis recommends screening patients 3 to 4 months after cardiac transplantation for CMV or its sequelae.

Left fundus of a patient with inactive, juxtafoveal (zone 1) CMV retinitis complicated by epiretinal membrane formation (left, asterisk) and cystoid macular edema (right). Such complications were observed infrequently prior to combination antiretroviral therapy, but occur commonly in patients on HAART who experience immune reconstitution with elevated CD4+ T-lymphocyte counts.
COURTESY OF EMMETT T. CUNNINGHAM, JR., MD, PHD, MPH.

AIDS-related corneal infections

Ramzi Hemady, MD, of the University of Maryland Department of Ophthalmology, reported a connection between AIDS patients and fungus infections at the American Academy of Ophthalmology meeting in New Orleans. From earlier studies concerning non-herpetic corneal infections in AIDS patients, Dr. Hemady began to notice a trend.

“It seemed fungi outnumbered bacteria as the cause of corneal ulcers in these patients, so I decided to look more specifically at the fungal causes of corneal infections in patients with AIDS,” Dr. Hemady told Ocular Surgery News.

A retrospective study carried out at four sites across the country was designed to report the characteristics and outcomes of fungal keratitis occurring in individuals infected with HIV. There were 13 episodes of fungal keratitis in 12 HIV-infected individuals; 10 patients were females and two were males. All were drug abusers and all denied recent ocular trauma, ocular surgery or contact lens wear. Their mean CD4 count on presentation was 143 cells [per milliliter]. Candida albicans was cultured from all of the eyes. No other fungi were cultured, although six episodes involved multiple organisms.

“The interesting thing was that every single one was caused by the same kind of fungus,” Dr. Hemady said. “Some patients responded to treatment, while others didn’t. There didn’t seem to be anything that pointed to why some responded and some didn’t.”

Dr. Hemady suggested that drug abuse might have been a contributing factor in the development of keratitis. “Usually, Candida will affect eyes or corneas that are compromised immunologically — so that’s a major association with AIDS,” Dr. Hemady said. “Interestingly, the development of these corneal fungal infections didn’t seem to correlate with the patients’ CD4 counts, so that’s why I think the association should be made that not only were they infected with the HIV virus, but that they were all drug abusers.”

Dr. Hemady says that when a patient who has AIDS presents with a corneal infection, he or she should be cultured for fungi.

“Treatment should be tailored toward Candida if you suspect a fungus,” he said. “When you see someone with a corneal infection, you don’t immediately think of fungus because it’s so rare in the Northern Hemisphere. But AIDS patients who come in with a corneal infection — especially those who are drug abusers — should be cultured for fungi.”

For Your Information:

Emmett Cunningham Jr., MD, PhD, MPH, can be reached at the Francis I. Proctor Foundation, University of California San Francisco Medical Center; (415) 502-2669; fax: (415) 476-0527; e-mail: emmett@itsa.ucsf.edu. Dr. Cunningham has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Ramzi Hemady, MD, can be reached at the Maryland Center for Eye Care, Department of Ophthalmology, University of Maryland, 22 S. Greene St., 6th Floor, Baltimore, MD 21201; (410) 328-5933; fax: (410) 328-6346. Dr. Hemady has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Janet Davis, MD, can be reached at Bascom Palmer Eye Institute, Anne Bates Leach Eye Hospital, 900 N.W. 17th St., P.O. Box 016880, Miami, FL 33101; (305) 326-6377; fax: (305) 326-6417. Dr. Davis has no direct financial interest in any of the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

Reference:

Fishburne BC, Mitrani AA, Davis JL. Cytomegalovirus retinitis following cardiac transplantation. Am J Ophthalmol. 1998;125:104-106.