Human Immunodeficiency Virus (HIV) Associated Retinopathy
The most common retinal manifestation of human immunodeficiency virus (HIV) is a retinal microvasculopathy, also known as noninfectious acquired immunodeficiency syndrome (AIDS) retinopathy. This microvasculopathy is characterized by diabetic retinopathy-like findings including cotton-wool spots and retinal hemorrhages or microaneurysms in the posterior pole and/or periphery. Opportunistic infections such as cytomegalovirus (CMV) retinitis, acute retinal necrosis (ARN), and progressive outer retinal necrosis (PORN) are more visually devastating viral retinal infections associated with HIV and require emergent systemic and/or local antiviral therapy. Very rarely HIV can cause a primary retinal infection.
Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection in AIDS and may also occur in other immunocompromised patients, especially in those with CD4 counts under 50/mm 3 . In the era of highly active antiretroviral therapy, the immune status of AIDS patients has dramatically improved and opportunistic retina infections such as CMV retinitis are more rarely encountered. Symptoms will vary, as peripheral disease (zone 3) may go unnoticed by patients. Visual changes will be perceived by patients if the infection involves the posterior pole (zone 1). Mild intraocular inflammation in the anterior chamber and vitreous may be present. The classic retinal findings of CMV retinitis include a hemorrhagic retinitis with a sectoral or perivascular distribution.
A “frosted branch angiitis” in areas with and without retinitis may be appreciated. Retinal venous occlusive disease and optic disc neovascularization may complicate the course. Patients should be closely monitored for the eventual development of rhegmatogenous retinal detachment requiring surgical intervention to prevent severe vision loss and blindness.
Acute Retinal Necrosis Syndrome
Acute retinal necrosis (ARN) syndrome can affect immunocompromised or immunocompetent patients and most typically occurs in otherwise healthy individuals. Clinical characteristics include (1) concentric areas of peripheral retinal necrosis with discrete borders; (2) relentless posterior progression of disease or development of new foci in the absence of antiviral therapy; (3) eventual macular involvement in the absence of antiviral therapy; (4) presence of an occlusive obliterative angiopathy; and (5) marked anterior and vitreal inflammation. Optic atrophy and rhegmatogenous retinal detachment due to multiple ragged round retinal tears at the border of resolved disease may complicate the course in a significant number of patients. The etiology of ARN is due to the herpes group of viruses that affect all layers of the retina. Herpes simplex virus type 1 and 2 (HSV-1, HSV-2) and varicella zoster virus (VZV) are the most common causative agents. Patients with HIV or AIDS are at risk for developing ARN following herpes zoster ophthalmicus, even after the skin lesions resolve.
Acute Retinal Necrosis Syndrome: Herpes Simplex Type 1
Acute Retinal Necrosis Syndrome: Herpes Simplex Type 2
Progressive Outer Retinal Necrosis
Progressive outer retinal necrosis (PORN) is a severe variant of a necrotizing herpetic retinopathy in profoundly immunocompromised patients with CD4 counts less than 5/mm 3 . It is believed to be the second most frequent opportunistic retinal infection after CMV retinitis in patients with AIDS. Clinical laboratory evidence suggests that the varicella zoster virus is the causal agent. Early clinical manifestations include patchy deep retinal lesions in the posterior pole and peripheral fundus, unlike ARN, which is typically peripheral in the early stages of disease. These discrete areas of retinal opacification are usually multiple and can range in size from 50 to several thousand microns in diameter. The retinitis is characterized by primary involvement of the outer retina with sparing of the inner retina until later stages of the disease process. The acute lesions progress rapidly, resulting in confluent patches of full-thickness necrosis with minimal or no aqueous or vitreal inflammation. A retinal vasculopathy is not characteristic of PORN. A perivascular lucency thought to represent early removal of necrotic debris or edema can result in a pattern of scarring that has a “cracked-mud” appearance. Optic nerve involvement, including swelling and atrophy, may occur. End-stage PORN leads to retinal detachment and blindness.
Epstein–Barr Virus Retinitis
The Epstein–Barr virus (EBV) may very rarely cause a retinitis that produces whitening of the retina with patterns that have indistinct margins and very minimal hemorrhage and inflammation.
Rubeola virus may very rarely cause a chronic progressive encephalitis and retinitis that affects primarily children and young adults. It is the result of a persistent infection of immune-resistant measles virus (rubeola). A variety of central nervous system (CNS) abnormalities are associated with this infection, and there may be ocular manifestations that can lead to blindness.
Congenital Rubella Syndrome
The congenital rubella syndrome, caused by the rubella virus, may be associated with microphthalmos, congenital cataracts, iris abnormalities, and coloboma formation of various ocular structures. Children born to mothers who contracted rubella in the first trimester of pregnancy are at high risk of deafness and pigmentary retinopathy that consists of patchy RPE atrophy and pigment epithelial mottling and hyperplasia referred to as “salt and pepper” retinopathy. Active ocular inflammation and/or retinitis are not appreciated with this syndrome. In later life, such patients are subject to choroidal neovascularization and disciform scarring of the macula.
Acute Retinal Pigment Epitheliitis
Coxsackievirus may be the etiology of infectious diseases of the retina and pigment epithelium with predilection for the central macula. A multifocal perifoveal reaction associated with pigment epithelial changes and macular edema, as well as a papillitis, is a very rare clinical presentation associated with this virus. A more typical association is the acute idiopathic maculopathy (AIM) syndrome, wherein there is increasing evidence of coxsackievirus as an etiological agent.
Acute Idiopathic Maculopathy
Acute idiopathic maculopathy (AIM) is a rare disorder that affects healthy young adults. Patients present with sudden central vision loss, usually in one eye. Symptoms often follow a viral prodrome, presumed to be coxsackievirus that is the etiology of hand-foot-mouth disease. During the acute phase, a neurosensory detachment overlying a grayish plaque at the level of the RPE is seen, often eccentric to the fovea, which may simulate the appearance of choroidal neovascularization. Associated intraretinal hemorrhages, few vitreous cells, and a mild papillophlebitis may be present and the FA shows rapid and severe subretinal leakage. Most cases resolve spontaneously over several weeks with near-complete recovery of vision. A lasting “bull’s-eye” pigment epithelial maculopathy is typically seen following resolution of the acute lesion.
Rift Valley Virus
Rift Valley fever is a viral zoonosis that primarily affects animals but also has the capacity to infect humans. The virus is a member of the Phlebovirus genus, and it was first identified in the Rift Valley of Kenya. It is transmitted to humans from direct or indirect contact with the blood of an infected animal or the bite of an insect, most commonly the Aedes mosquito. Systemic disease, including hemorrhagic fever and meningoencephalitis, may occur. When it affects the eye, there is usually retinal vascular involvement, which may include hemorrhage, vasculitis, and occlusive disease.
West Nile Virus
West Nile virus, a member of the flavivirus family, is transmitted by a mosquito and may result in severe systemic, CNS, and ocular manifestations. In the fundus, a vitritis with scattered creamy-yellow circular or round chorioretinal lesions may develop that resembles multifocal choroiditis. As they heal, they leave atrophic areas. Linear scars are characteristic. Retinal hemorrhages and exudates may also be noted.
Dengue Virus Maculopathy
The dengue virus is an RNA virus (of the flavivirus family) with four distinct serotypes that is widespread in tropical climate locales. It causes the clinical disease dengue fever, which is marked by high fevers, joint and bone pain, headache, and rash. In its most severe form victims suffer from dengue hemorrhagic fever, which is characterized by the aforementioned symptoms in addition to thrombocytopenia and often multiorgan failure. Dengue virus can cause a maculopathy associated with blurred vision and/or a scotoma. Fundus findings include macular and/or optic disc edema, retinal hemorrhages, venous sheathing, and yellow subretinal dots. More recently, multimodal imaging findings typical of acute macular neuroretinopathy have been described in these patients. Oral and intravenous steroids are the mainstay of treatment as the pathogenesis is postulated to be immune-mediated.
Toxoplasmosis infection is caused by the obligate intracellular protozoan, Toxoplasma gondii . There are two stages of the life cycle of the protozoan found in humans. The tachyzoites, measuring about 6 µm in length, comprise the first stage and the bradyzoites, thousands of which may be contained in cysts measuring up to 200 µm in diameter, comprise the second stage. Toxoplasmosis retinitis is the most common retinal infection and is typically only active in one eye at a time.
In immunocompromised patients, the CNS is the preferred site of infection, with cerebral toxoplasmosis reported in as many as 40% of autopsy eyes. Ocular toxoplasmosis is much less common than cerebral toxoplasmosis, accounting for less than 1% of AIDS-related retinal infections in the USA. Systemic infection with T. gondii is most commonly asymptomatic and approximately 500 million people worldwide have antibodies to the organism.
Most toxoplasmosis infections are in otherwise healthy hosts and symptoms are due to reactivation of organisms. Pre-existing chorioretinal scars indicate prior infection. Primarily acquired toxoplasmosis infection of the retina with an absence of pre-existing chorioretinal scars is more typical in AIDS patients. Acute toxoplasmic lesions (primary or reactivated) are focal yellow–white areas of necrotizing retinitis associated with a severe vitritis (“headlight in the fog”). The lesions have fluffy borders with few scattered hemorrhages. Vascular sheathing may be prominent (Kyrieleis plaques).
Congenital Toxoplasmosis Scars
Acute Toxoplasmic Lesions
Toxoplasmosis with Kyrieleis Plaques
Toxoplasmosis and Choroidal Neovascularization
Patients with toxoplasmosis retinitis may experience a significant decline in vision from recurrent infection or from secondary choroidal neovascularization.
Giardia is a protozoan organism that can cause ocular complications such as pigment epithelial changes in a “salt and pepper” pattern. Giardiasis may also be associated with mild non-specific intraocular inflammation.
Leprosy or Hansen disease is caused by Mycobacterium leprae . Systemic manifestations are the result of nerve damage leading to structural deformities of the hands and feet. Cutaneous scarring, which includes a remarkable leonine appearance of the face, is characteristic of this disease. Ocular manifestations include sclerokeratitis and cataract formation. Retinal manifestations are very rare as the organism prefers infestation of tissues associated with cooler environments.
Tuberculosis remains a major cause of morbidity and mortality worldwide. The HIV-infected population accounts for most of the increase in the prevalence of this infection. Choroidal tubercles and tuberculomas are the most common manifestation of ocular tuberculosis. Uveitis, optic neuritis, and retinal vasculitis in the posterior pole and peripheral fundus may also be encountered.