Human Immunodeficiency Virus (HIV) is a retrovirus which causes a multisystemic disease called Acquired Immune Deficiency Syndrome (AIDS). The first reported case of HIV was in Los Angeles in 1981. Ocular manifestations commonly are seen in HIV patients, and the first description of the same was made by Maclean more than 20 years ago. Ocular involvement in HIV could be caused by opportunistic infections, vascular abnormalities, neoplasms, neuro-ophthalmic conditions, and adverse effects of medications.
HIV is a retrovirus which replicates in CD4 T lymphocytes. Transmission occurs by exposure to blood and other body fluids. The natural history of an untreated HIV-infected person can be divided into three stages, namely, stages of primary infection, clinical latency, and, finally, opportunistic infections called AIDS. The Centers for Disease Control and Prevention (CDC) defines AIDS as being present when there is an AIDS-defining disease or a CD4 T-cell count less than 200 microliters. Some studies suggest that an HIV test should be requested if there is atypical, bilateral, treatment-unresponsive ocular toxoplasmosis or suspicion of cytomegalovirus (CMV) retinitis.
The World Health Organization (WHO) estimates that since the early 1980s, more than 50 million people worldwide have been infected with HIV, and the global prevalence rate is thought to be 0.8%. It is possible that 15,000 to 20.000 new infections occur every day. More than 1 million children are infected with HIV. About three-quarters of HIV patients are assumed to develop the ocular disease. Most of the HIV patients are from developing countries. Studies suggest that between 5 to 25% of all HIV patients in developing countries may become blind in their lifetime. Diseases of the retina and choroid are the most common in HIV patients, and they may cause visual loss. Retinal micro vasculopathy and CMV retinitis are seen in almost 30% to 40% of HIV patients. CMV retinitis is less common in developing countries compared to developed countries, and the HIV infected in the developing countries are more prone to infections by Toxoplasma, tuberculosis, Herpes zoster ophthalmic, and papillomavirus-associated squamous cell tumors. This difference reflects more exposure to these causative agents and higher death rates early in the course of the disease.
Ocular involvement in HIV infection occurs most commonly due to opportunistic infections and neoplasms. Opportunistic infections like CMV retinitis occur with a significantly reduced CD4 T-cell count and are one of the common causes of blindness in HIV patients. Unlike other diseases, ocular infection in these immunosuppressed patients is associated with minimal inflammatory signs. HIV has been isolated from tears, cornea, vitreous, and chorioretinal tissue in affected persons. The ocular structures affected by HIV include the adnexa, anterior segment, posterior segment, and orbit. Neuroophthalmological manifestations also may be seen. The institution of highly active antiretroviral therapy (HAART) has caused a dramatic improvement in the immune status of HIV-infected individuals and a change in the clinical presentation and course of opportunistic infections. However, improvement in immunity may be associated with an inflammatory response called immune recovery uveitis. Drug toxicity of newer therapeutic agents also has been reported.
Adnexal involvement in HIV-infected persons may include herpes zoster ophthalmicus (HZO), Kaposi sarcoma, molluscum contagiosum, and conjunctival microvasculopathy. HZO is a vesiculobullous dermatitis in the course of the ophthalmic division of the trigeminal nerve caused by the Varicella zoster virus (VZV). It is seen in 5% to 15% of HIV patients and may be associated with a simultaneous occurrence of keratitis, scleritis, uveitis, retinitis, or encephalitis. Kaposi sarcoma is a highly-vascularized, mesenchymal tumor and may present as painless, violaceous lesions on the eyelid skin or conjunctiva. Molluscum contagiosum is a dermatitis caused by a poxvirus and characterized by multiple, small, painless umbilicated lesions on the eyelid skin. Seventy percent to 80% of HIV patients may present with conjunctival microvasculopathy, characterized by segmental dilatation and narrowing of blood vessels, comma-shaped vascular segments, and sludging of blood column. The cause is thought to be either immune complex deposition, increased plasma viscosity or invasion of vascular endothelium by HIV and is found to correlate with retinal microangiopathy.
Anterior segment involvement in HIV includes keratoconjunctivitis sicca, keratitis, and iridocyclitis. Keratoconjunctivitis sicca, or dry eyes, are seen in approximately 20% of HIV patients and are thought to be an HIV-mediated inflammatory destruction of lacrimal glands. Keratitis in HIV is rare, seen in less than 5% of cases, but can lead to loss of vision. Herpes simplex virus and varicella-zoster virus are the most common causes. They may be recurrent and resistant to treatment. Microsporidia are protozoa which can cause a punctuate epithelial keratopathy. Bacterial and fungal keratitis also may be seen. Iridocyclitis is fairly common in HIV; mild iridocyclitis may be seen in association with VZV or CMV retinitis and severe iridocyclitis in association with toxoplasmosis, syphilis, tuberculosis, and bacterial or fungal retinitis. Medications, like Rifabutin and Cidofovir, prescribed for HIV patients also may cause iridocyclitis. Clinical examination in cases of iridocyclitis may reveal KPs, cells in AC, patches of iris necrosis, posterior synechiae, and hypopyon.
Posterior segment involvement in HIV is quite common and can cause visual loss. They include Retinal microangiopathy, CMV retinitis, VZV retinitis, toxoplasma retinchoroiditis, and bacterial and fungal retinitis. Patients may complain of floaters, flashes of light, decreased visual acuity or visual field defects. Retinal microangiopathy is the most common ophthalmic manifestation of HIV and is associated with low CD4 T-cell counts. It is characterized by the presence of cotton wool spots, retinal hemorrhages, and microaneurysms. The pathogenesis is thought to be similar to that of conjunctival microvasculopathy. CMV retinitis affects nearly 30% to 40% of HIV-infected individuals and is usually seen with CD4 counts less than 100/microliters. Fundus examination reveals full thickness intraretinal opacification associated with retinal hemorrhages. There is minimal AC reaction, and the vitreous is generally clear. Loss of vision can occur due to the direct involvement of macula or optic nerve, retinal detachment, and immune recovery uveitis. Widespread use of HAART has caused a change in the natural history of CMV retinitis, leading to marked reduction in the incidence of this condition and clinical findings not seen in classical CMV retinitis like AC and vitreous inflammation. Retinal whitening and hemorrhages characterize VZV retinitis, but the lesions are usually multifocal, progress rapidly, and may be associated with skin lesions. Toxoplasma retinochoroiditis in patients with HIV is usually bilateral and multifocal and may be associated with central nervous system (CNS) involvement. Ocular syphilis is seen in 2% of patients and may present as anterior segment inflammation or diffuse intraocular involvement. Infectious choroiditis also may be seen which may be caused by Pneumocystis, Cryptococcus or TB.
Neurophthalmic manifestations are seen in 10% to 15 % of patients with HIV and include papilloedema, cranial nerve palsies, ocular motility disorders, and visual field defects. Cryptococcal meningitis, CNS lymphoma, neurosyphilis, and toxoplasmosis may cause these symptoms.
Orbital involvement is rare in HIV and includes orbital lymphoma and orbital cellulitis, usually caused by Aspergillus.
Ocular toxicities may develop in patients receiving medications for HIV or opportunistic infections. These include uveitis with Cidofovir and Rifabutin, retinal pigment epithelial abnormalities with high dose Didanosine, corneal epithelial inclusions with intravenous Cidofovir or Acyclovir, and corneal subepithelial deposits with Atovaquone. Patients with CMV retinitis on HAART may suffer from a condition called immune recovery uveitis which causes diminution of vision and is characterized by cataract, vitritis, macular edema, optic disc edema, and epiretinal membrane.
Ocular manifestations of HIV are different from that of adults. Children have a lower incidence of CMV retinitis, but they have a higher incidence of Keratitis sicca and ocular toxoplasmosis and also are at a risk of neurodevelopmental delay. A fetal AIDS-associated embryopathy also has been characterized by the downward obliquity of eyes, hypertelorism, prominent palpebral fissures, and blue sclera.
Because of the wide range of clinical manifestations of HIV in the eye, a detailed history and evaluation are of utmost importance. A thorough history, disease progression by monitoring CD4 counts, slit lamp examination, and dilated fundoscopy are useful. The CD4 T-cell count and, more recently, viral load can be taken as a predictor of ocular involvement in patients with HIV. Visual acuity, visual field testing, testing of ocular movements, pupillary examination, and fundus examination are important in detecting the various infections and other conditions associated with HIV.
Keratoconjunctivitis sicca requires dry eye evaluation using tests like Schirmer test and Rose Bengal staining. Gram-staining and cultures may be done in cases of keratitis when the cause is not obvious. Dilated fundus examination can diagnose posterior segment involvement with a direct or indirect ophthalmoscope, and investigations may be done like venereal disease research laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test, and tests for TB. Orbital involvement requires CT scan, MRI, biopsy, and culture in most cases. Evaluation of a patient with HIV presenting with neuro-ophthalmological manifestations requires MRI and lumbar puncture for cytology, culture, and antigen-antibody testing.
Treatment of the ocular manifestation depends upon the presenting ocular pathology. Treatment of Herpes zoster ophthalmicus includes systemic acyclovir, famciclovir, valacyclovir and, in resistant cases, intravenous foscarnet. Kaposi sarcoma is managed by radiation therapy and institution of HAART therapy. Molluscum contagiosum can be treated by cryotherapy, curettage, and surgical excision. Treatment of Keratoconjunctivitis sicca includes artificial tears and long-acting lubricants. Keratitis is treated depending on the cause: viral keratitis by oral acyclovir or famciclovir; microsporidial keratitis by oral itraconazole, topical fumagillin, and oral albendazole; bacterial and fungal keratitis with appropriate antimicrobial therapy. Iridocyclitis is treated with topical corticosteroids started only after instituting appropriate antimicrobial therapy if an infection is suspected. CMV retinitis is treated with drugs such as oral valganciclovir, oral or intravenous ganciclovir, foscarnet, and cidofovir. Treatment of toxoplasma retinochoroiditis is with pyrimethamine and sulfonamides; steroids are not indicated.
With the widespread implementation of HAART and advent of better medications, the lifespan of patients with HIV is increasing. They are also more prone to develop the ocular manifestations and have an increased risk of visual loss. HIV is a disorder that affects many organs and thus it best managed by an interprofessional team. It is highly recommended that HIV patients be referred to an ophthalmologist when they present with any visual complaint. Comprehensive eye examination in HIV-infected individuals should be conducted. Health education regarding the ocular manifestations and complications will increase awareness and reduce morbidity.
|||Prevalence of ocular manifestations of HIV/AIDS in the highly active antiretroviral therapy (HAART) era: a different spectrum in Central South China., Luo J,Jing D,Kozak I,Huiming Z,Siying C,Yezhen Y,Xin Q,Luosheng T,Adelman RA,Forster SH,, Ophthalmic epidemiology, 2013 Jun [PubMed PMID: 23713918]|
|||Ocular manifestations of HIV/AIDS., Moraes HV Jr,, Current opinion in ophthalmology, 2002 Dec [PubMed PMID: 12441844]|
|||Ocular manifestations of HIV infection., Cunningham ET Jr,Margolis TP,, The New England journal of medicine, 1998 Jul 23 [PubMed PMID: 9673303]|
|||Ocular manifestations of HIV infection., Robinson MR,Ross ML,Whitcup SM,, Current opinion in ophthalmology, 1999 Dec [PubMed PMID: 10662248]|
|||Posterior segment ocular manifestations of HIV/AIDS patients., Chiotan C,Radu L,Serban R,Cornăcel C,Cioboată M,Anghelie A,, Journal of medicine and life, 2014 Sep 15 [PubMed PMID: 25408764]|