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HIV patient presents with flashes, blurred vision
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Ocular oncology is a challenging field in which primary eye pathology must be carefully distinguished from secondary systemic spread. As such, ophthalmologists may be the first to discover either an underlying malignancy or metastasis of a pre-existing cancer. In those cases where no primary tumor has been identified, the eye may often be the most amenable site for biopsy, thereby providing a medical team with a tissue diagnosis.
The case
A 40-year-old black male with HIV/AIDs presented with 2 days of flashes and blurry vision in the left eye, which he described “like looking in a fun house mirror.” He had no prior ocular history and denied recent trauma.
At the time of his evaluation, the patient was immunosuppressed with a CD4 count of 32 cells/mm3 but had an undetectable viral load on highly active antiretroviral therapy. He was taking Bactrim (sulfamethoxazole, trimethoprim; AR Scientific) prophylaxis for Pneumocystis jiroveci pneumonia but no other pertinent medications. Of note, he was undergoing further work-up for numerous chest and liver masses identified by a computed tomography scan of the chest and abdomen that had been obtained to evaluate recent shortness of breath.
Sunil Srivastava
Priyanka Kumar
Upon examination, his vision was 20/20 in both eyes. IOP was normal at 18 and 19 in the right and left eye, respectively. Pupils were equally round and reactive, without any afferent pupillary defect noted. Anterior segment slit lamp exam was unremarkable except for conjunctival melanosis. Extraocular movements were intact in both eyes. Monocular visual fields were full to gross confrontation. Funduscopic exam of the right eye was unremarkable.
Fundus examination of the left eye revealed clear vitreous, a normal optic nerve with trace glial tissue overlying the nasal aspect of the disc, normal vessels and two light orange choroidal masses in both the superior and inferior quadrants of the nasal retina. The macula was flat. B-scan ultrasonography of the lesions demonstrated two, possibly confluent, masses in the choroidal space adjacent to the nerve without vitreous involvement (Figure 1).
Figures 1a-1c. Funduscopic exam of the left eye is notable for two light orange choroidal masses in the superior and inferior quadrants of the nasal retina, confirmed on B-scan ultrasonography.
Images: Srivastava S, Kumar P
At this time, an MRI of the brain and orbits was obtained, which not only confirmed the two choroidal lesions, jointly measured as 8 mm × 5 mm × 13 mm, but also identified one 17 mm × 10 mm × 20 mm lesion in the superior aspect of the left posterior parietal lobe of the brain. Although the primary tumor was thought to be of lung origin, the patient’s respiratory status prevented him from safely undergoing bronchoscopy with biopsy. As such, the patient underwent liver biopsy, although his ocular lesions would have also been amenable to fine needle aspiration.
Subsequent laboratory evaluations and pathology were consistent with a primary neuroendocrine tumor. The patient was started on chemotherapy but returned 4 weeks later with worsened vision in the left eye.
Once again, examination of the right eye was unremarkable. Exam of the left eye was notable for hand motion vision, a normal IOP of 14, presence of an afferent pupillary defect and a normal anterior segment exam. Funduscopic exam revealed significant growth of the two masses, retinal hemorrhage, a new lesion in the macula and an exudative retinal detachment. Repeat B-scan ultrasonography revealed one large, lobulated, avascular mass (12.5 mm × 22 mm × 20 mm) of medium to high reflectivity at 9 o’clock posterior to the equator, as well as a second lesion of similar reflectance (4 mm × 9.5 mm × 10.5 mm) at 2 o’clock, with an associated inferior retinal detachment (Figure 2).
Figures 2a-2c. Funduscopic exam of the left eye revealed one large, lobulated, avascular mass at 9 o’clock with a new lesion in the macula, retinal hemorrhage, and an associated exudative retinal detachment, confirmed on B-scan ultrasonography.
The diagnosis
Neuroendocrine or carcinoid tumors are typically low-grade malignancies, usually arising from the gastrointestinal tract or pulmonary system. They consist of cells containing neurosecretory granules that release hormones, including serotonin, insulin and adrenocorticotropin hormone. Despite the variety of neuroendocrine malignancies, most can be initially identified with simple blood work for elevated levels of proteins such as synaptophysin and chromogranin, as well as urine tests for the metabolite of serotonin, 5-hydroxyindoleacetic acid.
The overall incidence of neuroendocrine tumors is 2.5 to 5 per 100,000, with only 33% of these being malignant. Common sites of metastasis are the lymph nodes, liver and bone. Ocular metastases, however, are extremely rare. A well-cited study published by Harbour and colleagues reported that only 2.2% of uveal metastases are of neuroendocrine origin. Traditionally, neuroendocrine tumor metastases to the choroid originate from the lung, whereas orbital metastases are gastrointestinal in origin.
Patients with HIV are especially susceptible to developing malignancies, and they often present at an earlier age of onset with atypical pathology and more aggressive clinical behavior. Importantly, the spectrum of neoplasia in HIV-infected patients has changed dramatically in the era of antiretroviral therapy. The incidence of AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkins’ lymphoma, has decreased, whereas the incidence of those tumors, collectively classified as non-AIDS-defining cancers, has significantly increased. These non-AIDS-defining cancers are now a major factor contributing to mortality in patients with HIV. The occurrence of neuroendocrine tumors, however, has not been well-characterized in the setting of concurrent HIV infection.
Ultimately, identifying metastases in patients with carcinoid tumors, regardless of HIV status, is important prognostically, as their presence is associated with a much poorer 5-year survival rate. Studied treatment regimens for choroidal lesions include brachytherapy, chemotherapy, external beam radiation, or any combination of those modalities, as well as photodynamic therapy for smaller lesions. Upcoming therapeutics call for the use of radio-labeled hormones targeted to the tumor cells, with subsequent radiation delivered only to the tissue of interest.
Our patient’s tumor proved to be extremely aggressive, and despite external beam radiation to the eye and systemic chemotherapy, his metastatic burden continued to grow and he elected to go on hospice care.