Corneal and External Ocular Infections in Acquired Immunodeficiency Syndrome


Key Concepts

  • Human immunodeficiency virus has been identified in tears, cornea, and conjunctiva, but to date there have been no reports of human immunodeficiency virus (HIV) transmission in the practice of ophthalmology.

  • There is a broad spectrum of corneal and external ocular disorders that occur in HIV-infected individuals, and they may present with atypical features and have a prolonged or more severe course.

  • Herpes zoster ophthalmicus occurs with a greater prevalence in HIV-infected individuals, and aggressive, early treatment with antivirals should be initiated to minimize anterior segment complications.

  • Given the potential for increased risk of recurrence, long-term systemic antiviral therapy should be considered for HIV-infected individuals presenting with herpes simplex virus keratitis.

  • Molluscum contagiosum infection of the eyelids and face in individuals with depressed cell-mediated immunity secondary to HIV can follow a more aggressive course and may be difficult to eradicate.

  • Ocular surface squamous neoplasia occurs more frequently in patients with HIV, affects younger patients, and has a more aggressive course than in noninfected individuals.

  • Kaposi sarcoma of the adnexa and conjunctiva is associated with human herpes virus-8 and can be an acquired immunodeficiency syndrome (AIDS)-defining illness.

  • The clinical presentation of bacterial keratitis in individuals with HIV infection may be more aggressive, recalcitrant to treatment, and characterized by a fulminant course with a lack of typical inflammatory signs.

  • Microsporidial infection can present as a chronic epithelial keratopathy and conjunctivitis in individuals with AIDS.

The eye is a target organ for many of the secondary disorders that occur in individuals infected with human immunodeficiency virus (HIV). Attention has been focused primarily on retinal pathology, but with the introduction of highly active antiretroviral therapy (HAART), patients are less likely to fall victim to blinding posterior segment infections. In these individuals, care can be focused on numerous HIV-related disorders involving the cornea, ocular surface, and adnexa of the eye, which occurs more frequently than posterior segment manifestations. In the anterior segment, both infectious and noninfectious disorders can occur in a spectrum of severity that ranges from asymptomatic problems to painful and vision-threatening disease.

Viral Infections

Human Immunodeficiency Virus

Human immunodeficiency virus has been identified in tears, cornea, and conjunctiva, and as such, there is concern regarding the transmissibility of the virus from these sites. Proper precautions regarding possible contamination of contact lenses, tonometers, and other instruments by tears or surface-infected cells have become the concern of all ophthalmologists and ophthalmic personnel. , However, to date, there have been no reports of HIV transmission in the practice of ophthalmology. Contact lenses appear to be disinfected adequately by heat and hydrogen peroxide disinfection systems. Tonometer tips are effectively disinfected by swabbing with 70% isopropyl alcohol followed by air drying. Contaminated instruments should be cleaned mechanically to remove blood, mucus, and other particulate organic matter. Disinfection may be achieved by heat or by 10-minute soaks in 3% hydrogen peroxide, 70% ethanol, 70% isopropyl alcohol, or a 1:10 solution of household bleach. ,

Before corneal tissue is offered for transplantation, it is screened by reviewing donor history for evidence of acquired immunodeficiency syndrome (AIDS) or high-risk factors for HIV infection, and cadaveric blood is tested for HIV antibodies and HIV nucleic acid. No documented cases of HIV transmission after keratoplasty have been reported, despite the fact that corneal grafts inadvertently taken from HIV-seropositive individuals have been transplanted before the status of the donor was discovered. The lack of seroconversion may reflect the avascular nature of the cornea and/or an extremely low inoculum.

More recently, HIV-induced anterior uveitis has been described in a small number of patients. , In six patients, anterior segment inflammation and keratic precipitates were present, while conjunctival hyperemia and retinal lesions were not. All patients had a high intraocular:plasma HIV-1 RNA ratio and were not receiving HAART at the time of diagnosis. There was no response to topical corticosteroids, but after the administration of HAART, signs and symptoms resolved in all patients, and the intraocular and plasma HIV loads decreased.

With the introduction of HAART, and the subsequent improvement in length and quality of life in patients with HIV, the landscape of ocular disorders has changed, with noninfectious conditions of the anterior segment becoming more common. , Ocular surface disease, including keratoconjunctivitis sicca and blepharitis, has been reported to occur in 10% to more than 50% of HIV-positive patients in recent studies. , Although the mechanism remains unclear, a recent prospective study demonstrated that ocular inflammatory complications in HIV infected individuals may be driven by a novel cytokine profile. For the clinician, attention should be paid to signs and symptoms of ocular surface disease in patients with HIV, so that treatment can be initiated to improve their long-term quality of life.

Cytomegalovirus

Although cytomegalovirus (CMV) is not associated with clinical findings consistent with conjunctivitis, immunohistochemical (IHC) studies of conjunctival tissue in patients with HIV have demonstrated positive staining for CMV antigen, and electron microscopy showed intranuclear and intracytoplasmic viral particles consistent with a herpes group virus and intracytoplasmic membrane-bound homogeneous dense bodies characteristic of CMV. CMV DNA has also been detected by polymerase chain reaction (PCR) in the conjunctiva of AIDS patients diagnosed clinically with CMV retinitis, , as well as HIV-positive patients without evidence of CMV retinitis.

In the cornea, CMV has been reported as a cause of corneal epithelial keratitis. These lesions are characterized by a slightly elevated, opaque, branching, nonulcerative epitheliopathy that recurs after corneal scrapings and persists despite oral and topical antiviral therapy. Stromal keratouveitis can also subsequently develop. Other investigators have described an isolated stromal keratitis that was presumed to be secondary to CMV infection.

Corneal endothelial deposits are routinely seen with CMV retinitis, , although they have also been reported in HIV-positive and CMV-positive patients without concomitant ocular disease. These fairly distinct deposits, which have been described as being diffuse, fine, refractile, and stellate, are best seen with retroillumination. They have also been described as microscopic, opaque, linear flecks arranged in a reticular-like fashion with no direct effect on vision. Histologically, these corneal deposits have been found to be composed of macrophages and fibrin material without lymphocytes, and without evidence of endothelial cell CMV infection. It has been suggested that they are the result of mild ocular inflammation associated with CMV infection of the retina. Recent evidence has also suggested that CMV may be an etiologic factor in corneal endotheliitis and chronic anterior uveitis in patients without evidence of HIV or systemic immunodeficiency. , Based on this finding, it could be speculated that some cases of chronic anterior uveitis of undetermined cause in patients with AIDS might be related to CMV, in view of its ubiquitous nature in this population.

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