February 14, 2019
6 min read
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Woman presents with unilateral blurry vision

Fundoscopic exam of the right eye showed a yellow area of retinitis in the superotemporal and temporal periphery.

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A 72-year-old woman was referred to the New England Eye Center for evaluation of 1 to 2 months of progressive blurry vision in the right eye. The patient was referred by the internal medicine team at Tufts Medical Center where she was admitted for progressive dysphagia, shortness of breath, weight loss, dizziness and lightheadedness. Her ocular history was notable for hyperopia, presbyopia and astigmatism. Her medical history included coronary artery disease, HIV, gastroesophageal reflux and hearing impairment. Her surgical history included coronary artery stent placement, bilateral tubal ligation and left humeral fracture repair. Before her admission, she was not on any medications. She had no known drug allergies. She had never smoked or used any illicit drugs and did not drink alcohol. Family history did not include any history of eye disease. Her review of systems was unremarkable aside from the above.

Examination

The patient’s corrected visual acuity in the right eye was 20/200 and did not improve with pinhole; in the left eye, visual acuity was 20/30. Pupils were equal, round and reactive to light bilaterally, with a trace afferent pupillary defect on the right. IOP was 18 mm Hg in both eyes. Motility was full. Visual fields were diffusely constricted to confrontation on the right and full on the left. External exam showed normal lids and adnexa bilaterally. Anterior segment exam was notable only for mild nuclear sclerosis bilaterally.

Fundus of the right eye
Figure 1. Fundus of the right eye showed a yellow area of retinitis in the superotemporal and temporal periphery. Periphery of the left eye was unremarkable.

Source: Malgorzata Dymerska, MD, and Shilpa J. Desai, MD

OCT of the macula
Figure 2. OCT of the right macula revealed CME. OCT of the left macula showed vitreomacular adhesion and normal retinal foveal contour without fluid.

Fundoscopic examination of the right eye revealed 1+ vitritis. The optic nerve appeared pink and healthy. The foveal reflex was blunted, and there were small intraretinal hemorrhages in the temporal macula (Figure 1). Telangiectatic shunt vessels were also present in the temporal macula from the superotemporal to inferotemporal arcades. In the superotemporal peripheral, there was an area of yellow granular pigmentation, compatible with retinitis. In the areas of pigmentation, the normal retinal vasculature appeared obliterated. Left eye fundoscopic examination revealed clear vitreous, a healthy optic nerve, a normal macula and a small area of flat choroidal pigmentation in temporal macula.

OCT of the right macula revealed cystoid macular edema (CME) (Figure 2). OCT of the left macula showed vitreomacular adhesion and normal retinal foveal contour without fluid.

What is your diagnosis?

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Retinitis

The differential diagnosis for retinitis in an immunocompromised patient includes a number of infectious as well as vascular etiologies. Cytomegalovirus (CMV) retinitis may present in an indolent manner with a granular area of retinitis. While previously common among patients with HIV, CMV retinitis is less uncommon in this population with the efficacy of modern antiretroviral therapy. Syphilis can present in a myriad of ways, including with ground-glass or placoid areas of retinitis and vitritis. Toxoplasma classically presents with a discrete fluffy, white retinal lesion that is fairly well demarcated. These tend to appear adjacent to old pigmented retinal scars. However, they can be multifocal and have an atypical appearance in immunocompromised individuals. Necrotizing herpetic retinopathies, such as acute retinal necrosis and progressive outer retinal necrosis, are possibilities. Acute retinal necrosis classically starts as multifocal white lesions that coalesce and spread circumferentially. In immunocompromised individuals, retinal necrosis may spread rapidly and with minimal associated inflammation, as is the case in progressive outer retinal necrosis. The unilateral intraretinal hemorrhages and telangiectatic shunt vessels seen in the macula, associated with CME, are most likely secondary to a branch retinal vein occlusion, which may have occurred before the onset of retinitis or afterward, possibly as a result of it.

Area of retinitis
Figure 3. Area of retinitis in the right eye remained stable at 2 months after presentation.

Diagnosis

The patient had a history of HIV diagnosed 6 years before presentation and had been off of all antiretroviral therapy for more than 3 years. CD4 count at the time of initial evaluation was 11 cells/mm3 (normal: 500 to 1,000 cells/mm3). HIV viral load was 142,511 copies/mL. CMV viral load was 1,541,883 copies/mL. QuantiFERON-TB Gold, treponemal antibody and toxoplasma IgG antibody were all negative. She underwent an esophagogastroduodenoscopy, which revealed findings consistent with CMV esophagitis. With a CD4 count less than 200 cells/mm3 and CMV esophagitis, she was given a new diagnosis of AIDS. She did not undergo aqueous or vitreous sampling, given her CD4 count, CMV viral load and examination. She was clinically diagnosed with CMV retinitis.

Discussion

CMV is the largest herpes virus. It is a highly prevalent virus, with more than 80% of people older than age 80 years exhibit seropositivity. Healthy individuals at the time of their initial exposure are typically asymptomatic or have flu-like symptoms. CMV then becomes latent but can be reactivated by any local or systemic immunodeficiency.

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In patients with AIDS, CMV retinitis is the most common etiology of vision loss. It is most likely to occur with CD4 counts less than 50 cells/mm3. In the beginning of the AIDS epidemic, it was estimated that 25% to 42% of AIDS patients developed CMV retinitis. After the introduction of highly active antiretroviral therapy (HAART), it is estimated that the incidence of CMV retinitis dropped by about 80%.

The fundoscopic appearance of CMV retinitis typically follows one of three clinical patterns. The fulminant presentation is characterized by hemorrhagic necrosis on the background of yellow or white retinal lesions that may be centered around the vessels. This is the classic “blood and thunder” appearance. Granular presentation, which our patient had, typically has little or no necrosis or hemorrhage and is found in the periphery. Perivascular presentation has the frosted branch angiitis appearance, with lesions closely surrounding retinal vasculature.

Treatment of CMV retinitis depends on the location and extent of the lesions. If lesions are immediately sight-threatening, based on their proximity to the optic nerve and the macula, it is generally recommended that treatment start with local intravitreal therapy (intravitreal ganciclovir or foscarnet) along with systemic therapy. Otherwise, systemic therapy alone is generally sufficient. Systemic therapy can include oral valganciclovir, IV ganciclovir, IV foscarnet or IV cidofovir. Choice of the specific agent depends on location and extent of ocular and systemic manifestations, patient preference of oral or IV therapy, patient comorbidities given the side effect profiles of the drugs, and historical response to past treatments. The systemic agent is given in high doses for an induction period of 2 to 3 weeks, followed by lower doses as maintenance therapy.

Most significant complications of CMV retinitis in AIDS patients are retinal detachment and immune reconstitution uveitis. Retinal detachment occurs in up to 24% of patients with CMV retinitis and can happen long after lesions become inactive. Similarly, immune reconstitution uveitis can occur weeks to years after initiation of HAART, even once retinitis is completely inactive. Due to the risk for retinal detachment and immune reconstitution uveitis, patients with a history of CMV retinitis require close lifelong follow-up.

Clinical course continued

Our patient was started on IV ganciclovir immediately upon her diagnosis of CMV retinitis and esophagitis. She continued to receive it twice daily for the first 2 weeks, after which time she was transitioned to oral valganciclovir 900 mg twice daily. During the first week after her diagnosis, she also received three intravitreal injections of foscarnet into the right eye, one every 2 to 3 days. Her vision in the right eye improved to 20/50 after the first week. She was started on HAART 2 weeks after initial diagnosis; the delay was intentional in order to lower the risk for immune reconstitution uveitis. Her most recent CD4 count, 2 months after initial presentation, is 27 cells/mm3. Her HIV viral load is now undetectable, and her CMV viral load is 128 copies/mL. The area of retinitis has been stable (Figure 3). There are still areas of intraretinal hemorrhage in the temporal macula, and CME persists. Further treatment of the CME has been not been pursued so far due to the patient’s persistent severely compromised immune system and the risk for precipitating retinal detachment with anti-VEGF injections.

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