Introduction

Since the emergence of acquired immunodeficiency syndrome (AIDS) reported in 1981, several drugs have been developed to combat effectively the human immunodeficiency virus (HIV). Currently we have three classes of antiretroviral specific: reverse transcriptase inhibitors (nucleoside) reverse transcriptase inhibitors (non-nucleoside) and protease inhibitors, which can be used alone or combined. The association of two reverse transcriptase inhibitors with a protease inhibitor, popularly known as the cocktail is called HAART (Highly Active Antiretroviral Therapy).

Didanosine or ddI is a purine analogue with antiretroviral activity against HIV-1 and HIV-2, including strains resistant to zidovudine (AZT). Intracellularly is converted by the enzyme 5-nucleotidase IMP-dd (dideoxytinosina 5 monophosphate) which ultimately is metabolized to its active form d-ATP (2-3 Dideoxyadenosine triphosphate), which acts as a competitive substrate dATP the viral enzyme reverse transcriptase ( competitive inhibitor). Peripheral neuropathy and pancreatitis are considered the main side effects of didanosine dose dependent, usually occurring in the first 3 to 6 months of use. Cases of retinal toxicity in HIV-positive children are reported with the use of high doses of ddI, but few cases are reported in adults. The aim of this study is to describe an unusual case of retinal toxicity due to the use of didanosine in HIV-positive adults. CASE CS, 32, female, Caucasian, born in Rio de Janeiro, HIV positive for 6 years, asymptomatic, attended the service of Ophthalmology for routine eye examination. She had CD4 + 140 cells/mm3 and undetectable viral load, classified as stage A2 by the CDC (Centers for Disease Control 1992).

The patient was taking zidovudine (AZT) and didanosine (DDI) for three years. On examination she had visual acuity equal to 1.0 and intraocular pressure of 13mmHg in both eyes. Slit-lamp examination did not detect changes in the anterior segment. Fundus lesions observed nummular yellowish-shaped belt 360 ° in the equatorial region of both eyes. We performed fluorescein angiography showed that the presence of nummular pigment changes with multiple areas of atrophy of the retinal pigment epithelium by circumscribed areas of hypopigmentation located in the equatorial region. There was also a slight reduction of peripheral vascularization.

The patient had normal blood count, chest X-ray unchanged, VDRL negative, negative serology for toxoplasmosis and CMV IgG positive. We believe the injuries sustained by the patient as being secondary to the use of didanosine.

Discussion

There are several opportunistic diseases that affect the eyes in the acquired immunodeficiency syndrome (AIDS), these related mainly to CD4 + counts below 200 cells/mm3. The main ocular infection in AIDS is retinitis, cytomegalovirus (CMV). Opportunistic diseases have, in most cases, the typical clinical picture that enables the diagnosis only by an ophthalmologist. In the case described the patient did not show any changes characteristic of opportunistic disease, and all exams were negative.

Some drugs used in treatment of AIDS or related diseases can cause eye disease. Cidofovir and rifabutin, drugs for the treatment of CMV and atypical mycobacteria are respectively associated with anterior uveitis. Our patient had no inflammation in the anterior segment and neither did these drugs. So far, two drugs used in treatment of AIDS or related diseases are related to retinal involvement. Clofazimine is a drug used to treat Hansen's disease and in cases of atypical mycobacteria.

Cunningham et al. described a case of maculopathy type bull's eye which they saw as secondary to the use of clofazimine. Despite the suspension of the drug there was no improvement in the eye. Whitcup et al. described a case of HIV positive children who presented with peripheral nummular in both eyes. The authors explained the appearance of lesions to the use of high doses of DDI. Later a larger study was conducted where three children were found with the same peripheral lesions secondary to high doses of DDI. Despite these well-documented lesions secondary to the use of didanosine are quite rare. Classically these changes related to the IDD affected only children who received high doses of the drug. Cobo et al. described the first cases of retinopathy associated with IDD in adults. In all cases described in the literature patients had peripheral nummular lesions in both eyes, as described in our patient.

Lalonde et al. described a single case of anterior uveitis and cystoid macular edema associated with zidovudine (AZT). Our patient never had macular disorder or anterior uveitis. The combination of AZT with macular edema was reported only once, although AZT is the drug of first choice in the treatment of HIV infection. Whitcup et al. performed pathological study which showed that the lesions occur primarily in the retinal pigment epithelium and subsequently affect the choriocapillaris. The mechanism by which the retinal pigment epithelium is damaged due to the DDI is still unknown, but appears to be related to the drug's effect on the mitochondrial DNA. This report demonstrates the importance of routine eye examination in HIV patients, even when patients do not present a risk of opportunistic disease eye.