CLINICAL

  POSTERIOR

‘WHAT’S UP WITH MY LEFT EYE?’

IS THIS PATIENT’S VISION LOSS DUE TO HIS HIV DIAGNOSIS?

SHERROL A. REYNOLDS, O.D., F.A.A.O.

A 35 YEAR-OLD very thin African-American male presented complaining of difficulty seeing out of his left eye for a duration of roughly one week. He said four days preceding his vision loss, he saw floaters that he, “tried to swat out of the way.”

His medical history was positive for HIV, with which he said he had been diagnosed one-year prior. In addition, the patient confessed to non-compliance with his prescribed, highly active antiretroviral therapy. Further, his last CD4 T-lymphocyte count was 40 cells/mm3, and he said he didn’t know what his viral load was.

The patient’s BCVA was 20/20 OD and CF @ 1’ OS. Ocular motilities were unremarkable OU, but a marked afferent pupillary defect and constriction on confrontation VFs were observed OS. In OD, an isolated cotton wool spot (CWS) was detected. Examination of OS revealed mild anterior uveitis and vitritis and extensive hemorrhagic retinitis with exudates surrounding the optic nerve. Hemorrhagic patches of retinitis were also observed in the temporal retina OS.

Could this patient’s ocular issues stem from HIV-caused cytomegalovirus (CMV)? Also, did his CD4 T-lymphocyte counts of 40 cells/mm3 put him at higher risk?

Here, I discuss HIV, related opportunistic infections, its ocular symptoms, clinical signs and diagnosis/management to help you decide.

Note the isolated cotton wool spots.
Courtesy Drs. Greg Black and Alexandra Schuette

HIV

A widespread misconception exists among the American public that HIV is no longer a serious problem, which, unfortunately, is not true. Despite a decrease in the number of HIV-infections since the height of the epidemic in the mid-1980s, rates of new diagnoses remain a concern.

About 36.7 million people worldwide are living with HIV, according to the World Health Organization, while in the United States the CDC estimates that currently 1.2 million people have HIV, with nearly one in eight not aware of it.

The incurable condition affects all ages, sexes and races, however, most new infections occur among gay or bisexual men, followed by African-American heterosexual women, according to the CDC. Compared with other races and ethnicities, African Americans are the most heavily affected population with 44% of new HIV diagnoses, followed by Latinos, also according to the CDC.

HIV is transmitted through blood and genital fluids, shared intravenous drug paraphernalia and maternal infection. It attacks and destroys the body’s immune system; specifically the CD4 lymphocytes (T cells). Untreated, HIV leads to opportunistic infections or cancers, signaling AIDS, the advance stage of the disease.

The spectrum of ocular manifestations of HIV range from adnexal to posterior segment disorders, including the optic nerve and the optic tract, and are the most common clinical findings of HIV, occurring in roughly 70% to 80% of HIV-infected patients during the course of the illness, according to the Journal of Clinical and Diagnostic Research. The most common ocular complication, HIV retinal microvasculopathy, typically seen clinically as CWS, may be the first and consistent sign of the infection in many cases. While some ocular disorders may be asymptomatic, opportunistic infections, such as CMV, can be rapidly destructive to the eye.

CMV, a herpes virus, is the most common cause of intraocular infection in HIV-infected patients. CMV retinitis, the leading cause of vision loss in these patients, typically occurs in one eye before becoming bilateral.

Without proper treatment, CMV retinitis can cause blindness in less than 6 months, according to the Journal of AIDS & Clinical Research. Also, although the prevalence of CMV has decreased, due to advances in antiretroviral therapy, between 10% and 20% of HIV-infected patients worldwide can be expected to lose vision in one or both eyes as a result of ocular cytomegalovirus, states the International Journal of Clinical Medicine.

Note the hemorrhagic retinitis.

OCULAR SYMPTOMS

The ocular symptoms of HIV-infected patients may include decreased VA, dry eyes, double vision (cranial nerve palsies), flashes, floaters, peripheral vision loss, redness (especially with anterior segment complications, such as herpes keratitis or iridocyclitis) and proptosis, ptosis and eyelid edema from orbital involvement.

The ocular symptoms of CMV retinitis include the four “Fs”:

• Failing vision

• Floaters

• Flashes

• Field deficits

OCULAR CLINICAL SIGNS

A myriad of ocular changes can be seen in HIV-infected patients. They are grouped as:

• Adnexal/Anterior segment. These include mulluscum contagiosum, Kaposi sarcoma, dry eyes, conjunctival microvasculopathy, corneal infection (herpetic, bacterial or fungal keratitis), iridocyclitis, microsporidiosis and conjunctival squamous-cell carcinoma.

• Posterior segment. Non-infectious HIV retinal microvasculopathy, retinopathy (CWS, roth-spot hemorrhages, intraretinal hemorrhages and microvascular changes — microaneurysms and telangiectasia); opportunistic infections, such as CMV retinitis, acute retinal necrosis, progressive outer retinal necrosis, also known as PORN, toxoplasmosis retinochoroiditis, syphilitic chorioretinitis, tuberculous choroiditis/choroidal granuloma and candida retinitis comprise the posterior segment.

The clinical signs of CMV retinitis are:

• Anterior uveitis

• Vitritis

• Perivascular lesions (thick white infiltrate with retinal hemorrhage, described as “pizza pie” or “cottage cheese with ketchup” in appearance)

• Exudates and vascular sheathing

• Satellite lesions (granular lesion with less hemorrhage)

• Necrotic retina (mottled pigmentation from hyperplasia of the retinal pigment epithelium (RPE).

DIAGNOSIS/MANAGEMENT

The following should be used to aid in the proper diagnosis of HIV-related ocular complications, including CMV retinitis.

• Ocular photography. Both anterior and retinal photography are important in capturing, monitoring and documenting therapeutic response as well as educating patients on both anterior and retinal HIV-complications. Serial photography is essential in determining the progression or recurrence of CMV retinitis, which involves documentation of border changes or the development of new lesions. This becomes particularly important in determining treatment response.

• Fundus autofluorescence (FAF). This is useful in differentiating active and inactive CMV retinitis. Specifically, it demonstrates hyperFAF at the border of CMV retinitis.

• SD-OCT. This enables the view of structural changes, such as changes at the vitreoretinal interface (traction) and inflammatory precipitates, hyperreflective CWS lesion in the nerve fiber layer, macular edema, foveal thickening or infarct, destruction of inner and outer retinal tissues from retinitis, such as CMV, and RPE elevation or thinning, indicating choroidal involvement.

• Fluorescein and indocyanine green angiography. This shows areas of capillary non-perfusion and leakage, signaling retinitis and choroiditis.

In terms of management, any suspected HIV-eye disease infection requires a thorough case history, including preexisting conditions, medication use, health behaviors, seeking treatment for a sexually transmitted disease, such as syphilis, and recent exposures (sex or drug activity). If not already performed, a prompt medical workup is required as well. This includes HIV testing by the patient’s primary care physician. Additionally, any patient younger than age 50 who presents with isolated CWS, herpes infection or any of the previously mentioned opportunistic infections is an HIV infection suspect and requires a medical work-up. Once a diagnosis is made, the patient is prescribed highly active antiretroviral therapy, also known as HAART, which has dramatically improved prognosis with firm adherence.

Duration of disease and disease progression, as indicated by three-month CD4 T-lymphocyte cell counts and viral load (a blood test that detects the virus in your blood), should be assessed and documented. Low CD4 (less than 200/micro liter) and a high viral load (> 100,000) are risks for the development of HIV-related eye disease. Also, the single most important risk factor for the development of CMV retinitis in HIV patients remains a CD4+ T cell count <50 cells/μL states the American Journal of Ophthalmology.

HIV-infected patients should have a yearly comprehensive eye exam. CWS and retinal hemorrhage, a common HIV retinal microvasculopathy finding, typically resolves in six to 12 weeks, thus requiring follow-ups in three-month intervals. Additionally, HIV retinopathy may resemble diabetic and hypertensive retinopathy, so those conditions should be ruled-out during the medical assessment.

Treatment of anterior segment complications depends on the type and severity of the condition. For example, patients who have active keratitis or iridocyclitis may require constant (daily/weekly) follow-up until resolution. Those who have retinal disease, such as CMV retinitis, require prompt care and comanagement with a retinal specialist and the patient’s treating physician. CMV retinitis, in particular requires close monitoring for recurrence, as it may be subtle and, therefore, go undetected. Treatment includes an intravitreal injection or implant of anti-viral therapy and, if needed, retinal detachment surgery.

THE ANSWER

If you diagnosed this patient as having CMV retinitis, you are correct! The patient was immediately referred to a retinal specialist and received a sustained-release intraocular anti-viral implant. He was counseled about his condition and also put on systemic antivirals in attempt to protect the contralateral eye. Unfortunately, the patient never returned for follow-up.

HIV infection remains a significant clinical problem. Early recognition of HIV-related eye diseases, such as CMV, and appropriate management are imperative in order to improve these patients’ visual outcome and potentially save their lives. OM

DR. REYNOLDS is an associate professor at the Nova Southeastern University College of Optometry and clinical preceptor/attending in the college’s diabetes and macular clinic. She is a fellow of the Optometric Retina Society and chairperson for the Florida Optometric Association Healthy Eyes Healthy People Committee. Comment at tinyurl.com/OMcomment.