Myriad infectious diseases may result in neuro-ophthalmic manifestations. This text covers the most common infections that produce neuro-ophthalmic symptoms and occur in the United States.
Human Immunodeficiency Virus Infection
Neuro-ophthalmic disorders associated with human immunodeficiency virus (HIV) infection may result either from direct infection or from indirect causes such as secondary opportunistic infections, malignancy, microvasculopathy, or uveitis. The eye, afferent visual pathways, and ocular motor system can all be affected. BCSC Section 9, Uveitis and Ocular Inflammation, discusses the following conditions in detail.
Human immunodeficiency virus
HIV infection causes acute and chronic CNS manifestations. Acute aseptic meningitis and meningoencephalitis affect 5%–10% of patients, soon after initial HIV infection. Headache, fever, and meningeal signs may accompany a mononucleosis-like syndrome. Occasionally, altered mental status, seizures, optic neuropathy, and cranial neuropathies occur, most commonly CN VII paresis.
HIV encephalopathy, also known as the AIDS dementia complex or HIV-associated neurocognitive disorder, begins with impaired memory and concentration, behavior changes, and mental slowness. Abnormal pursuit, saccadic eye movements, and saccadic intrusions (square-wave jerks) may be present. Late manifestations include profound dementia, behavior changes, psychosis, psychomotor impairment, weakness, visual neglect, visual hallucinations, seizures, and tremor. An optic neuropathy may develop. MRI demonstrates cerebral atrophy and areas of white matter hyperintensity on T2-weighted images that correspond to areas of demyelination produced by the virus.
Ocular signs of HIV infection include cotton-wool spots, perivasculitis, and retinal hemorrhages. Subtle structural and functional retinal and optic nerve abnormalities, termed HIV-associated neuroretinal disorder (HIV-NRD), have been reported in HIV-infected patients without infectious retinitis or any apparent funduscopic abnormalities. Risk factors for this disorder include low CD4+ T cell counts, detectable HIV RNA in the blood, and hepatitis C infection. Patients with HIV-NRD may demonstrate thinner retinal nerve fiber layer, subtle loss of color vision and/or contrast sensitivity, visual field deficits, and subnormal electrophysiologic responses. Studies found that HIV-NRD is associated with increased mortality and increased risk of bilateral visual impairment. Antiretroviral therapy decreases but does not eliminate the risk of HIV-NRD.
Jabs DA, Drye L, Van Natta ML, Thorne JE, Holland GN; Studies of the Ocular Complications of AIDS Research Group. Incidence and long-term outcomes of the human immunodeficiency virus neuroretinal disorder in patients with AIDS. Ophthalmology. 2015;122(4):760–768.
Central nervous system lymphoma
After Kaposi sarcoma, which is the most common AIDS-associated neoplasia of the eyelid or conjunctiva, high-grade B-cell non-Hodgkin lymphoma is the second most common malignancy in patients with AIDS and the most common neoplasm to affect the CNS. CNS lymphoma can cause diplopia from CN III, IV, or VI involvement. Lymphomatous infiltration of the orbit and optic nerve may lead to ONH swelling and vision loss. The diagnosis is made by confirming the presence of neoplastic lymphomatous cells in the CSF or through results of stereotactic brain or meningeal biopsy. Changes shown on MRI scan may resemble those of toxoplasmosis, but they are typically periventricular with subependymal spread. Treatment consists of a combination of radiotherapy and chemotherapy.
Cytomegalovirus (CMV) infection is a common opportunistic infection and a major cause of vision loss in HIV-infected patients. CMV retinitis is often the presenting manifestation of untreated advanced HIV infection and primarily occurs in patients with extremely low CD4+ T-lymphocyte cell counts. Within the CNS, CMV infection causes optic neuritis and brainstem encephalitis. Anterior optic nerve infection produces acute loss of vision with ONH swelling; this condition usually occurs in patients with severe CMV retinitis. Other patients exhibit anterior optic neuropathy with minimal retinitis (Fig 14-19). Posterior optic neuropathy, which is rare, is characterized by slowly progressive loss of vision without ONH edema. Brainstem involvement may cause ptosis, internuclear ophthalmoplegia, ocular motor CN palsies, horizontal and vertical gaze paresis, and nystagmus.
The diagnosis of CMV infection is made clinically, based on the characteristic ocular findings. Results of serologic tests and cultures may indicate elevations or be inconclusive. Polymerase chain reaction diagnostic testing of CSF may be an important molecular tool. See BCSC Section 9, Uveitis and Ocular Inflammation, for a complete discussion of CMV diagnosis and treatment.
Figure 14-19 Cytomegalovirus (CMV) optic neuritis. A, Fundus photograph shows optic nerve head (ONH) appearance of a 42-year-old woman who presented 3 weeks after noticing inferior shadows in the right eye. Visual acuity was 20/20, but visual field testing (B) demonstrated an inferior arcuate visual field defect. The patient’s medical history was remarkable for transfusion 18 months prior, with evidence of subsequent Pneumocystis jiroveci pneumonia. She was found to be HIV-seropositive, and a diagnosis of CMV optic neuritis was made.
(Courtesy of Steven A. Newman, MD.)
Butler NJ, Thorne JE. Current status of HIV infection and ocular disease. Curr Opin Ophthalmol. 2012;23(6):517–522.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.