HIV-Associated Infections of the Retina and Optic Nerve

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Image Credit: Bruce Blausen

The posterior segment of the eye functions by maintaining the shape of the eyeball, holding the lens in place, and triggering nerve impulses to the brain from photoreceptor cells on the back of the eyes.

The retina, choroid (the vascular layer of the eye), and optic nerve comprise much of the posterior segment, with a number of HIV-associated disorders presenting within these ocular layers, more often in later-stage HIV disease.

Disorders of the posterior segment—primarily presenting with vascular changes to the retina—are seen in as many as 50% to70% of patients with HIV, and may sometime result in persistent or acute damage to the retina (called retinopathy).

Other HIV-associated infections of the posterior segment include:

Cytomegalovirus

Cytomegalovirus (CMV) is a herpesvirus that infects more than half of the adult population, rarely presenting with disease in those with competent immune systems (other than, occasionally, with mononucleosis-like symptoms). While it is often passed perinatally from mother to child, it can also be transmitted in adulthood through sexual contact. As such, CMV prevalence among men who have sex with men is approximately 90%, as it is with people with advanced HIV disease.

CMV can present in the eyes in a number of ways, although it most often does so with a sometimes debilitating inflammation of the retina, known simply as retinitis. The disease most often occurs in patients whose CD4 count has dropped below 50 cells/mL and manifests symptoms ranging from the perception of floaters to visual loss and even blindness.

Once CMV lesions are identified on the retina, they can progress quite rapidly, often within weeks. Without medical intervention, the lesions can progress centrifugally (expanding outward from the center), diminishing visual acuity and sometimes leading to the complete loss of vision. While CMV retinitis often presents bilaterally (in both eyes), it can also present unilaterally (in one eye).

Valganciclovir is considered the drug of choice for the treatment of CMV retinitis, prescribed orally as a twice-daily dose during the induction period, followed by a once-daily  dose for the maintenance period. Ganciclovir may also be prescribed but is delivered intravenously, rather than orally, for a period of around 21 days.

Alternately, intravitreal ganciclovir implants—literally, minute injectable rods delivered directly to the site of infection—are sometimes inserted into the eye. Often used in more profound cases of CMV retinitis, it allows for prolonged, sustained drug concentrations in the vitreous humor (the clear gel that fills the space between the lens and retina).

Toxoplasma

Toxoplasma is the most common cause of retinochoroiditis (infection of the retina and/or choroid) in the general population, and the second most common in people with HIV. 

Caused by the protozoan parasite, Toxoplasma gondii, the disease affects over 200,000 people in the U.S. annually, and is spread either perinatally or by ingestion of tainted meat. Most often associated with cats (although it is present in many warm-blooded creatures), contact with cat feces is also seen to be significant cause of T. gondii transmission.

When toxoplasmosis presents in the eye, it manifests with a yellow-white to light-gray lesion accompanied by inflammation of the vitreous humor. Identification can usually be made with an eye exam, with antibody-based blood tests providing serological confirmation.

Topical steroids are sometimes used to treat milder cases of toxoplasma retinochoroiditis, while more severe cases are often prescribed a combination of pyrimethamine, folinic acid and sulfadiazine.  For people with advanced HIV disease, on-going chronic treatment may be required, oftentimes with the use of trimethoprim-sulfamethoxazole, the combination of which is generally well tolerated.

Cryptococcosis

Cryptococcosis is an infection caused by inhaling airborne,​ Cryptococcal neoformans spores, which can often manifest with meningitis (the sometimes life-threatening inflammation of the protective membranes that surround the brain and spinal cord). Most ocular involvement develops as a secondary presentation during severe bouts of cryptococcal meningitis, particularly when accompanied by septicemia.

Ocular infections can be routed either through the central nervous system (CNS) via the optic nerve or through the bloodstream when the disease is disseminated (i.e., spread beyond the source infection).

On examination, multiple yellowish lesions can be identified on the choroid and/or retina. If left untreated, the spread of infection to the tissues of the optic nerve can sometimes result in visual loss.

Systemic treatment of cryptococcal meningitis is generally delivered by means of intravenous amphotericin B and flucytosine, considered the treatment of choice. Antifungal medications are also often prescribed when ocular involvement is suspected.

Tuberculosis

Tuberculosis (TB) tends to be less common than other HIV-associated eye diseases but is sometimes seen in HIV patients with active pulmonary TB. It tends to present as a nodule-like granuloma on the choroid and can manifest at higher CD4 counts (greater than 150 cells/mL) than other HIV-associated infections of the posterior segment. Systemic treatment with anti-TB drugs is typically prescribed as the recommended course of action.

Sources

Rocha Lima, B. "Ophthalmic Manifestations in HIV Infection." Digital Journal of Ophthalmology. October 29, 2004; 10(3): online version.

Sudhakar, P.; Kedar, S.; and Berger, J. "The neuro-ophthalmalogy of HIV/AIDS review of Neurobehavioral HIV Medicine." Neurobehavioral HIV Medicine. September 17, 2012; 2012(4):99-111.

Jackson, J.; Erice, A.; Englund, J.; et al. "Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1." Transfusion. March-April, 1988; 28(2):187-189.

Stewart, M. "Optimal management of cytomegalovirus retinitis in patients with AIDS." Clinical Ophthalmology. April 6, 2010; 4:285-299.

Zhang, M.; Zhang, J.; and Liu, Y. "Clinical presentations and therapeutic effects of presumed choroid tuberculosis." Retina. April 2012; 32(4):805-813.

Harrell, M. and Carvounis, P. "Current Treatment of Toxoplasma Retinochoroiditis: An Evidence-Based Review." Journal of Ophthalmology. August  13, 2014; DOI http://dx.doi.org/10.1155/2014/273506.

Perfect, J.; Dismukes, W.; Dromer, F.; et al. "Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Updates by the Infectious Diseases Society of America." Clinical Infectious Diseases.  January 4, 2010; DOI: 10.1086/649858.

Espino Barros Palau, A.; Morgan, L.; Foroozan, R.; et al. "Neuro-ophthalmic presentations and treatment of Cryptococcal meningitis-related increased intercranial pressure." Canadian Journal of Ophthalmology. October 2014; 49(5):473-477.

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