retina case study
What O.D.s Need to Know About HIV
A routine eye evaluation leads to a diagnosis of HIV

A recent case at the Miami Veterans Affairs Medical Center illustrates the ocular manifestations of HIV/AIDS. Furthermore, it helped me appreciate the sensitive nature of this diagnosis and the proper way to educate the patient and request an HIV test.

Case Report

A 49-year-old African-American male presented to the Miami VA Medical Center for a routine ocular evaluation. His only ocular complaint was decreased near vision. The patient denied ocular or systemic diseases. Visual acuity was 20/20 OU at distance without correction. Confrontation visual fields were full to finger counting in each eye. Extra- ocular motilities revealed no restrictions. Pupils were equally round and reactive and there was no relative afferent pupil defect (RAPD).

Goldmann applanation showed that his IOP was 11mmHg OD and 12mmHg OS. Slit lamp examination of the anterior segment was unremarkable, slit lamp examination of the posterior segment revealed a pink, healthy and intact neuroretinal rim OU. The maculas were flat and clear OU. I noted scattered cotton wool spots in the right eye between the optic nerve head and the macula. Similar lesions were absent in the left eye and there were no other signs of vascular abnormality in either eye. Binocular indirect ophthalmoscopy revealed the retinal periphery was clear, flat and intact 360 degrees OU.

The differential diagnosis of cotton wool spots includes diabetes, hypertension, systemic lupus erythematosus, HIV retinopathy and alpha interferon retinopathy. The patient did not have a known history of the above systemic conditions. Recent lab work revealed a normal fasting blood glucose level and normal HbA1c. I checked his blood pressure, which was 110/70mmHg, right arm sitting. The patient did not have hepatitis C and had therefore not been treated with alpha interferon. A review of the patient's medical record showed not one single episode of elevated blood glucose or elevated blood pressure in the past eight years.

At this point the likely diagnosis became HIV retinopathy. The patient had never been tested for HIV and he denied any behavior that would put him at risk. However, further review of his medical record revealed two prior episodes of gonorrhea and one prior episode of syphilis. Furthermore, the patient had a history of many infections in the past three years, including bronchitis, otitis and upper respiratory tract infections. Review of his most recent blood work revealed a low white blood cell count and history showed a similar finding one year prior.

Up against denial

I told the patient that I suspected HIV retinopathy and that he should be tested. I offered to order the test through the laboratory at the Miami VA Medical Center, but the patient refused, stating that he could not emotionally deal with a positive test result. I educated him on the advances in treatment of HIV and on the services that would be available to him through the VA. He still would not consent to the lab test. So I referred him to the psychology department and special immunology and set-up a follow-up appointment for one month later. He was a no show for all of the appointments.

Taking the first step

Figure 1: Posterior pole of the right eye, illustrates several cotton wool spots surrounding the optic nerve head.

The patient returned to the emergency room two months after I had initially seen him, due to acute respiratory distress. He was diagnosed with an upper respiratory tract infection and was again educated on the need for an HIV test and treatment with the special immunology department. This time he agreed to the testing. Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot tests showed that he was positive for HIV.

At this time his CD4+ T lymphocyte count was 5 cells/μL and his viral load was equal to 295,000 cells/mL. A biopsy of a lump on the right side of his neck revealed HIV-related non-Hodgkin's Bell cell lymphoma. The special immunology department initiated highly active anti-retroviral therapy and the patient experienced immune recovery. This has continued — his CD4 count is still good and his viral load is undetectable.

AIDS review

Figure 2: Posterior pole of the left eye, illustrating the unremarkable appearance of this fundus.

Acquired immunodeficiency syndrome (AIDS) was first reported in the United States in 1981. It is caused by the human immunodeficiency virus (HIV), which attacks CD4+ T-lymphocyte cells, known as helper T cells. CD4+ T-lymphocyte cells are part of the body's natural line of defense; when these cells are attacked, the body becomes susceptible to infections and certain cancers. AIDS is diagnosed by the presence of an opportunistic infection, or AIDS-defining illness, or when the number of CD4+ T-lymphocyte cells drops below 200. Healthy people have between 500 and 1,500 CD4+ T-lymphocyte cells in one milliliter of blood.

The Centers for Disease Control and Prevention (CDC) estimate that at the end of 2004, 415,193 persons in the United States had AIDS. In 2004, 70% of reported cases of HIV infection were in males.

 Testing tips

When you suspect HIV/AIDS, it's important to know that patients must give informed consent for the test. HIV tests do not test for the virus itself but instead detect the presence of antibodies the body produces to fight HIV infection. The ELISA test is the most common screening test for the disease. It is highly sensitive but not very specific. HIV antibodies may not be detectable in blood for up to six months after initial infection. But after this six-month period the ELISA very rarely has a false negative result. On the other hand, false positives are very common, so a positive ELISA must be confirmed.

The Western Blot is the most common confirmatory test and it's very specific, so false positives are very rare. In both the ELISA and the Western Blot, the patient's blood is added to an antigen preparation; if HIV anti- bodies are present in the blood sample, they'll react with the HIV antigens in the preparation. Together the ELISA and Western Blot are more than 99% accurate.

On the matter of privacy

HIV tests are either confidential or anonymous. In confidential testing, the person's name is recorded with the test results. Medical personnel and state health departments may have access to the information. In anonymous testing, the person's name is not recorded. Instead the individual is given a code that he or she uses to retrieve the result of the test.

Forty-five U.S. states and territories offer anonymous testing, while all states offer confidential testing; eleven offer only confidential tests.

Choosing treatment

HIV and AIDS are monitored through the CD4+ T-lymphocyte count and the viral load. The CD4 count serves as the major clinical indicator of immunocompetence in patients with HIV infection. It's usually the most important consideration in a doctor's decision to initiate antiretroviral therapy. The CD4 count determines which type of opportunistic infection prophylaxis a patient should receive.

The viral load measures the amount of HIV-RNA virus present in 1mL of blood. When the viral load is low, a patient's CD4+ T-lymphocyte count rises. U.S. treatment guidelines suggest that anyone with a viral load of >30,000/mL should be treated with antiviral drugs. At times a viral load test result will come back as "undetectable" — this means that the level of HIV virus in the blood sample is below the threshold for detection. Some tests are more sensitive than others. An "undetectable" result does not mean that the patient is cured or no longer infectious.

Knowledge of the HAART

As of October 2003, there were 20 approved antiretroviral agents for the treatment of HIV/AIDS. HAART refers to a combination of drug regimens that synergistically control HIV infection and preserve immune function. The combination therapy is capable of suppressing viral replication and keeping it at very low levels. HAART usually combines two nucleoside reverse transcriptase inhibitors and at least one protease inhibitor or non-nucleoside reverse transcriptase inhibitor to HIV.

HIV and the eye

Before the introduction of highly active antiretroviral therapy (HAART) in 1996, ocular manifestations of HIV and AIDS were very common. AIDS reti-nopathy or noninfectious reti-nopathy, which consists of cotton-wool spots with or without intraretinal hemorrhages, was the most common presentation. Low CD4+ T-lymphocyte counts, especially those less than 50, and higher viral loads are strongly associated with cotton-wool spots. They're observed in association with other systemic vascular conditions including diabetes, hypertension and lupus erythematosus. They represent the common pathologic expression of focal ischemia at the level of the nerve fiber layer.

The mechanisms underlying the ischemia in AIDS are poorly understood. Some theories propose the HIV virus has a direct toxic effect on the vascular endothelium. Others suggest the cause is immune complexes depositing within the vascular endothelium, or an increase in fibrogen levels promoting focal clotting.

Although the clinical picture of ocular involvement in HIV infection has changed dramatically since the advent of potent antiretroviral therapy, microangiopathy is still the most common retinal manifestation (post-HAART).

►Other posterior segment manifestations of HIV and AIDS include: cytomegalovirus retinitis (CMV), necrotizing herpetic retinopathy, toxoplasmosis, and syphilis. CMV is the most common AIDS-related ocular opportunistic infection. Prior to HAART, it was seen in 30% of all AIDS patients.

CMV retinitis occurs almost exclusively in patients whose CD4 counts are <50 cells/mL. Diagnosis is based on the clinical appearance of a confluent retinal necrosis with extensive hemorrhage.

Immune recovery uveitis (IRU) can still occur in patients with a history of CMV retinitis who have experienced immune recovery through HAART, which may have allowed them to discontinue anti-CMV therapy.

Necrotizing herpetic retinopathy is a posterior segment inflammation induced by herpes viruses. The two clinical patterns of necrotizing herpetic retinopathy are acute retinal necrosis and progressive outer retinal necrosis.

Ocular toxoplasmosis in AIDS patients is often bilateral in contrast to the unilateral disease seen in immunocompetent patients. It is thought that in AIDS patients, ocular toxoplasmosis is a primary infection rather than a reactivation.

Syphilis and HIV infection are associated with each other at a high rate. Patients with ocular syphilis should be tested for HIV, and HIV-positive patients should be routinely screened for syphilis. Ocular syphilis in AIDS may present as iritis, vitritis, papillitis, neuroretinitis, or retinal vasculitis.

►Anterior segment manifestations of HIV and AIDS include the following: dry eye, herpes simplex, herpes zoster ophthalmicus, molloscum contagiosum and kaposi's sarcoma of the conjunctiva. Herpes infections and molloscum contagiosum run a longer course and are more severe in HIV/AIDS patients.

Take-away lessons

This case illustrates several important points regarding the management of HIV/AIDS:

►Patients must give informed written consent prior to an HIV test. In a situation such as this, it is necessary to educate the patient on the possibility of HIV/AIDS. Explain that a positive diagnosis can help the patient gain access to highly effective antiretroviral treatment. Due to the sensitive nature of the test, you should know where anonymous testing is provided in your neighborhood of practice.

►Although the advent of HAART has greatly reduced the ocular complications of HIV and AIDS, you need to know what they are. Some patients cannot tolerate highly-active antiretroviral therapy, putting them at risk for ocular manifestations of HIV/AIDS.

►Finally, many people with HIV are diagnosed late in their illness — 38% of those diagnosed in 2002 received an AIDS diagnosis within one year of receiving positive HIV test results. Our patient was diagnosed with AIDS at the same time he tested positive for HIV. It's not surprising that he had HIV microangiopathy with a CD4+ T-lymphocyte count of 5. OM

References available upon request.

Dr. Hunter joined the Miami VA Medical Center in August of 2003. She is also a clinical instructor at the Nova Southeastern University College of Optometry. Contact her at Megan.Hunter@va.gov.