Human Immunodeficiency Virus (HIV) is a retrovirus which causes a multisystemic disease called Acquired Immune Deficiency Syndrome (AIDS). Ocular manifestations are commonly seen in HIV patients, and the first description of the same was by Maclean more than 20 years ago. HIV retinopathy is fairly common in HIV positive patients and is the most common cause of loss of vision in these patients.
HIV is a retrovirus which replicates in CD 4 T lymphocytes transmitted 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 the stage of opportunistic infections, called AIDS. CDC defines AIDS as being present when there is an AIDS-defining disease or a CD4 T cell count less than 200/microliters. Retinopathy in HIV/AIDS may be due to microvasculopathy or opportunistic infections or malignancies. HIV microvasculopathy is considered to be the commonest posterior segment HIV manifestation and is seen in 40% to 60% of HIV-positive patients. Image result for cytomegalovirus (CMV) retinitis is thought to be one of the commonest vision-threatening posterior segment manifestation of HIV, but its incidence is declining in the highly-active antiretroviral therapy (HAART) era.
As of December 2006, the WHO estimates that, globally, there are about 39.5 million people infected with HIV. 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 extremely common in HIV patients and may cause visual loss. It is suggested that greater lifespans of patients with HIV result in increasing numbers of patients with opportunistic infections of the retina. There is also a difference in the infection patterns seen in developed and developing countries. 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 (TB), and herpes zoster virus (HZV). This difference reflects more exposure to these causative agents, differences in HIV subtypes and higher death rates early in the course of the disease in the developing world.
Ocular involvement in HIV occurs most commonly due to opportunistic infections and neoplasms. Opportunistic infections like CMV retinitis occur with a significantly reduced CD4 T-cell count. Unlike other diseases, ocular infection in these immunosuppressed patients is associated with minimal inflammatory signs. HIV microvasculopathy, which is also sometimes called HIV retinopathy, is thought to be due to either immune complex deposition, increased plasma viscosity or invasion of vascular endothelium by HIV. Its prevalence is inversely proportional to the CD4 count.
Opportunistic infections in the posterior segment are manifestations of disseminated disease in AIDS and can manifest as retinitis or choroiditis. Retinitis is more commonly seen compared to choroiditis. Retinitis in quiet eyes occurs with lower CD4 counts and is most commonly due to CMV or progressive outer retinal necrosis (PORN) whereas retinitis in an inflamed eye is associated with higher CD4 counts and may be due to acute retinal necrosis (ARN), toxoplasmosis, syphilis, or late stages of cryptococcosis.
Unusual malignancies have also been reported in the posterior segment of patients suffering from HIV.
The institution of 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.
Microvasculopathy, the most common ocular manifestation of HIV, is seen in 40% to 60% of HIV positive patients and is associated with low CD4 counts. Most patients are asymptomatic. Clinical findings include cotton wool spots at the posterior pole. It may be associated with intraretinal hemorrhages and microvascular changes like microaneurysms and telangiectasia. It can be differentiated from CMV retinitis by the presence of fewer hemorrhages and the absence of subtle iritis or vitritis.
Large vessel occlusions like central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and branch retinal artery occlusion (BRAO) are infrequently seen and may be associated with a viral retinitis.
CMV retinitis is the commonest ocular opportunistic infection in AIDS patients. Before the introduction of HAART, it was a very common cause of blindness in HIV/AIDS and remains so in developing countries. There are three clinical forms of CMV retinitis. The classical form also called the pizza or cottage cheese with ketchup retinopathy is characterized by confluent areas of retinal necrosis with hemorrhages seen in the posterior pole. These lesions enlarge and may coalesce and ultimately lead to full thickness retinal necrosis, gliosis, and pigment epithelial atrophy. Patients may present with loss of visual field or acuity. The second form, the indolent variety, is characterized by granular peripheral retinal lesions with little or no hemorrhages. The third form is called frosted branch angiitis, which is characterized by marked vascular sheathing. Loss of vision in CMV retinitis can occur due to the direct involvement of macula or optic nerve, RD and also due to immune recovery uveitis. Widespread use 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 necrotizing viral retinitis, but the lesions are usually multifocal, progress rapidly and may be associated with skin lesions. There are two clinical forms: ARN and PORN. ARN is characterized by peripheral retinal necrosis, associated with marked anterior uveitis and vitritis. Pain is usually seen, associated with blurred vision and floaters. Multifocal, deep retinal infiltrates, with minimal vitritis characterize PORN.
Toxoplasma retinochoroiditis in HIV patients is usually bilateral and multifocal and may be associated with central nervous system (CNS) involvement. The retinal lesions may resemble CMV retinitis, but have fewer hemorrhages and marked intraocular inflammation.
Ocular syphilis is seen in 2% of patients and may present as anterior segment inflammation or diffuse intraocular involvement. Pneumocystis carinii choroiditis is another opportunistic infection, characterized by bilateral, multifocal, yellowish, choroidal lesions, associated with a clear vitreous. Cryptococcal choriditis may also be seen. Mycobacterium tuberculosis may cause the development of multifocal choroidal tubercles, mainly at the posterior pole.
Patients with CMV retinitis on HAART may suffer from a condition called immune recovery uveitis which causes dimunition of vision and is characterized by cataract, vitritis, macular edema, optic disc edema, epiretinal membrane and proliferative vitreoretinopathy. It is the leading cause of new visual loss in persons with AIDS and is seen in about 16% to 63% of HAART responders. The severity of inflammation is dependant on the immunity, severity of CMV retinitis, CMV antigen load and previous treatment.
A thorough history, disease progression by monitoring CD 4 counts, slit lamp examination and dilated fundoscopy is useful. The CD4 T-cell count and now more recently viral load can be taken as a predictor of ocular involvement in HIV patients. 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. Posterior segment involvement in HIV patients can be diagnosed by dilated fundus examination with a direct or indirect ophthalmoscope, and investigations may be done, for example, VDRL test, FTA-ABS test, and tests for TB.
CMV retinitis is treated with drugs such as valganciclovir, oral or intravenous ganciclovir, ganciclovir implant, fomivirsen, foscarnet, and cidofovir.
Necrotising herpetic retinitis requires aggressive treatment with antivirals. ARN is managed with systemic acyclovir, followed by barrage laser photocoagulation after resolution of retinitis to prevent retinal detachment.
Treat retinal choroiditis with pyrimethamine and sulfonamides; steroids are not indicated.
Pneumocystis choroiditis can be treated with systemic pentamidine, trimethoprim, and sulfamethoxazole or dapsone.
Fluconazole maintenance therapy is recommended for prophylaxis against cryptococcosis for all HIV patients.
Anti-TB drugs are used for ocular tuberculosis and penicillin for ocular syphilis.
With the widespread implementation of HAART and advent of better medications, the lifespan of HIV patients is increasing. They are also more prone to develop the ocular manifestations and at risk for visual loss. Comprehensive eye examination in HIV infected individuals should be conducted. Health education regarding the ocular manifestations and complications will increase awareness and reduce morbidity.
HIv patients are best managed by a multidisciplinary team because of multiple organ involvement. When the eye is involved, the ophthalmologist should be consulted immediately. The infectious disease consultant, internist and the primary care provider should educate the patient on the importance of HAART. It is important for the primary care givers and nurse practitioner to know that visual loss in an HIV cannot only be from medications but from opportunistic infections like herpes, treponema, toxoplasma and herpes.
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