Ocular manifestations of human immunodeficiency virus (HIV) infection have historically been common. While approximately 70-80% of HIV-infected patients have been treated for an HIV-associated eye disorder during the course of their illness, recently these numbers have appeared to decrease with the development of increasingly efficacious HIV antiviral cocktails.
In general, the CD4+ T-lymphocyte count has been used to predict the onset of certain general conditions and ocular infections in patients who are HIV positive. A CD4+ T-cell count below 500/µL is associated with Kaposi sarcoma, lymphoma, and tuberculosis. A CD4+ T-cell count below 250/µL is associated with pneumocystosis and toxoplasmosis. A CD4+ T-cell count less than 100/µL is associated with the following:
The predictive value of the CD4+ T-cell count for ocular complications in HIV infection has been called into question by reports of CMV retinitis in patients with CD4+ cell counts higher than 200 cells/µL. These patients reportedly were taking highly active antiretroviral therapy (HAART). While such findings may argue against the protective effect of an increased CD4+ cell count, the possibility that the CMV retinitis preceded the recovery of CD4+ cell count was not ruled out. Thus, whether a reconstituted T-cell count will serve as a better predictor of specific ocular infection is under active evaluation.
Despite these uncertainties, the CD4+ cell count has remained the predicting parameter for the occurrence of specific ocular infection in patients who are HIV positive, at least until antigen-specific tests of T-lymphocyte function become widely available.
For other discussions of HIV infection, see HIV Disease, Pediatric HIV Infection, and Antiretroviral Therapy for HIV Infection.
For patient education information, see the Immune System Center and Sexually Transmitted Diseases Center, as well as HIV/AIDS.
The ocular adnexa consist of the eyelids, the conjunctiva, and the lacrimal drainage system. Common ocular adnexal lesions in HIV-infected patients include the following:
Herpes zoster is a painful vesiculobullous dermatitis that results from the localized reactivation of varicella-zoster virus (VZV) infection. The virus travels down the involved nerve, causing pain followed by a vesicular rash in the dermatome.
Herpes zoster can involve any dermatome, but particularly T3 to L3 and cranial nerve V (most commonly the ophthalmic division, V1). Herpes zoster of the ophthalmic division of the trigeminal nerve, with or without ocular involvement, is referred to as HZO.
Predisposing factors for herpes zoster include aging, immunosuppression, trauma, irradiation, surgery, or debilitating systemic disease. In the general population, the most common predisposing factor for herpes zoster is age over 60 years; by age 80 years, as many as 50% of adults who are seropositive with VZV will develop zoster, of which HZO represents a small fraction. HZO affects about 5-15% of patients who are infected with HIV.
The incidence of herpes zoster, unlike that of many of the other opportunistic infections seen in HIV disease, has apparently not decreased with the advent of highly active antiretroviral therapy (HAART). In one study, patients on HAART and those with CD4+ cell counts between 50 and 200/µL seemed to be at the highest risk of a herpes zoster event.[1]
Kaposi sarcoma is a painless mesenchymal-derived vascularized tumor that most often affects the skin and mucous membranes. It is caused by human herpesvirus type 8. Kaposi sarcoma is seen commonly in patients who are infected with HIV, where 3 histologic types of tumors have been described based on appearance of the vascular endothelium and the number of spindle cells.
Kaposi sarcoma occurs in about 25% of patients who are HIV positive. In about 20% of these patients, the eyelids or conjunctiva are affected.[2]
Molluscum contagiosum is the most common ocular adnexal manifestation in patients who are HIV positive. It is a highly contagious dermatitis caused by DNA poxvirus, and it may affect mucous membranes as well as skin.
The DNA poxvirus spreads by direct contact with infected persons or by fomites. The small, painless, umbilicated lesions contain poxvirus particles that are released into tears with associated toxic keratoconjunctivitis.
Molluscum contagiosum is more frequent and severe in patients who are HIV positive than in patients who are HIV negative. The eyelid is involved in 5% of HIV-positive patients.
Several conjunctival microvascular changes commonly are seen in HIV-positive patients during the course of the disease. These changes include segmental vascular dilation and narrowing, microaneurysm formation, and appearance of comma-shaped vascular fragments.
The specific etiology of the microvascular changes is not known; however, increased plasma viscosity and immune-complex deposition are believed to be involved. Direct infection of the conjunctival vascular endothelium by HIV has been suggested as a possible cause.
These microvascular changes occur in as many as 70-80% of patients who are HIV positive.
The anterior segment comprises the cornea, the anterior chamber, and the iris. More than 50% of HIV-positive patients manifest anterior segment complications, including dry eyes (keratoconjunctivitis sicca), corneal infection (keratitis), and anterior chamber inflammation (iridocyclitis). Common symptoms include irritation, pain, photophobia, and decreased vision.[3, 4]
Dry eyes (keratoconjunctivitis sicca) are seen in about 10-20% of patients who are HIV positive, usually during later stages of the disease. The etiology is related to HIV-mediated inflammation and damage of the accessory and major lacrimal glands.[5]
Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are the most common causes of infectious keratitis in HIV-positive patients. Keratitis due to VZV usually is associated with herpes zoster ophthalmicus, with or without the presence of dermatitis. In HIV-infected patients, compared with the general population, VZV and HSV keratitis tend to reoccur more often, and they may be resistant to treatment.[6, 7]
Bacterial and fungal keratitis are not more frequent in HIV patients, but these infections tend to be more severe. The most common organism is Candida, especially in intravenous drug users. Microsporida organisms have also has been implicated. In general, Gram stain and cultures are used to guide treatment. Microsporidia are very difficult to culture, but it is seen readily within corneal or conjunctival epithelial cells with the use of Masson trichrome or Giemsa stain.
VZV is morphologically identical to HSV. Like HSV, VZV can establish latency after primary infection with subsequent reactivation of the disease when the host's immune system is compromised. Primary VZV infection (ie, chickenpox) is spread by airborne respiratory droplets that contain the virus or by direct contact with cutaneous lesions. It is extremely contagious to susceptible individuals. VZV primary infection usually develops during childhood, and the disease tends to be mild and self-limited.
VZV keratitis occurs in fewer than 5% of patients who are HIV positive, but it may cause permanent visual loss. The prevalence of VZV keratitis is higher in HIV-infected patients than in the general US population.
HSV is a DNA virus that often infects humans. Two strains of HSV exist: HSV-1 and HSV-2.
In the United States, approximately 50-90% of adults have serum antibodies to HSV-1. HSV infection is spread by direct contact with infectious secretions from infected carriers. HSV-1 is commonly responsible for oral and ocular infections, while HSV-2 is responsible for genital infections. However, some cases of HSV-2 causing oral or ocular infections and of HSV-1 causing genital infections have been reported.
Like VZV, HSV can establish latency after primary infection with subsequent reactivation of the disease when the host individual's immune system is compromised. Following primary infection, HSV may spread from the epithelial site of infection to sensory nerve endings in the infected tissue; from there, the virus is transported up the nerve axon to the cell body.
In the cell body, the viral genome enters the nucleus, where it persists in a latent nonpathogenic state until reactivation in a pathogenic or immunocompromised state. Following reactivation, HSV is transported down the nerve axon to the epithelial cells on the ocular surface or cornea.
About 0.15% of the population has a history of external ocular HSV infection, and approximately 67% of patients with HSV infections develop epithelial keratitis. The prevalence of HSV keratitis is higher in HIV-infected patients than in the general US population.
Candidal species are the most common fungal organisms causing keratitis in HIV-positive patients, especially in intravenous drug users. Other fungal organisms known to cause keratitis include Fusarium and Aspergillus species.
Immunosuppression predisposes HIV-positive patients to fungal infections. The nonfilamentous fungi (eg, Candida species) are very common in compromised eyes, particularly with immunosuppression. The filamentous fungi (eg, Fusarium or Aspergillus species) are seen in association with trauma with vegetable matter.
In some developing countries, fungal keratitis may be an indicator of HIV infection. In a study from Africa, 26 of 32 (81.2%) patients with fungal keratitis were found to be HIV positive; 60 of 180 (33%) of those with nonfungal keratitis were HIV positive. Fusarium solani was the most common organism, accounting for 75% of cases with fungal keratitis.[8]
Microsporidia are intracellular protozoa that have emerged as important opportunistic parasitic organisms in HIV-positive patients. Five species have been identified in patients who are HIV positive.
Immunosuppression predisposes patients who are HIV positive to infection by microsporidia. In general, ocular involvement of microsporidia is very rare, although the organism is capable of causing corneal and conjunctival infection.[9]
Iridocyclitis in patients who are HIV positive tends to be mild and often is associated with retinitis due to CMV, HSV, or VZV. When iridocyclitis is severe, it usually is seen in association with ocular toxoplasmosis, tuberculosis, syphilis, or bacterial or, rarely, fungal retinitis. Other causes of iridocyclitis in HIV-positive patients include medications (eg, rifabutin, cidofovir).
The etiology of iridocyclitis in HIV-positive patients includes sequelae of retinitis, retinochoroiditis, and drug toxicity. Iridocyclitis may manifest as part of generalized autoimmune and endogenous uveitis (eg, Reiter syndrome).
Posterior segment structures involved in HIV-positive patients include the retina, choroid, and optic nerve head. Disorders of at least one of these structures are seen in more than 50% of patients who are HIV positive.
Common presenting complaints include floaters, flashing lights, scotomas or other visual field defect, and decreased visual acuity. Presence of an afferent pupillary defect strongly suggests significant optic nerve involvement. Diagnoses often are based on clinical evidence seen on funduscopic examinations.
HIV retinal microvasculopathy once occurred in as many as 50-70% of HIV-infected patients.[10] However, it is likely that the increased use of highly active antiretroviral therapy (HAART) has lowered the prevalence of the retinal microvasculopathy.
Arteriolar occlusion in HIV retinal microvasculopathy leads to interruption of the axoplasmic flow and the subsequent accumulations of axoplasmic debris, which manifests as cotton-wool spots.
The specific etiology of the microvascular changes has not been elucidated completely. The cause of retinal microvasculopathy in patients who are infected with HIV is similar to that suggested for conjunctival vascular changes, namely increased plasma viscosity, immune-complex deposition, and a direct cytopathic effect of the virus on the retinal vascular endothelium.
Viruses are the most common cause of infectious retinitis and/or choroiditis. Viruses are obligate intracellular parasites that can damage the retina and/or choroid, either by direct invasion or by their ability to alter the host immune system.
Cytomegalovirus (CMV) is the most common cause of necrotizing retinitis in patients who are HIV positive. Varicella-zoster virus (VZV) and, less commonly, HSV may cause acute retinal necrosis (ARN). This necrotizing retinitis may be unilateral or bilateral. Another form of necrotizing retinitis, progressive outer retinal necrosis (PORN), may occur in advanced HIV disease.[11] To date, VZV is the only organism associated with PORN.
Common bacterial causes of retinitis in patients who are HIV positive include Treponema pallidum (syphilis) and Mycobacterium tuberculosis. Fungal causes of retinitis and/or choroiditis include Pseudallescheria boydii, Cryptococcus neoformans, and Histoplasma capsulatum, as well as Candida, Sporothrix, and Aspergillus species. Parasitic causes include Toxoplasma gondii and Pneumocystis jiroveci.
CMV is the most common cause of intraocular infection in patients with AIDS. This disease, which may result in blindness or death, represents a reactivation of latent CMV infection.
Primary infection by CMV usually is asymptomatic and is predominantly transmitted perinatally. In childhood, the major mode of transmission is by close contact, while in adolescence and adulthood, it is mostly transmitted through sexual contact or blood transfusion. The seropositive prevalence of CMV is about 50% in adults and 95-100% in homosexual and AIDS patients.
Reactivation of latent CMV infection commonly is seen in the setting of immunocompromise, such as in patients on long-term immunosuppressive therapy. Before the advent of highly active antiretroviral therapy (HAART), CMV was the most common opportunistic infection in AIDS patients with a CD4+ cell count below 50/µL. In the HAART era, the incidence of CMV retinitis has declined, and the survival after diagnosis has increased to well over 1 year.
CMV retinitis starts as a single lesion in most cases. Infection spreads centrifugally from that focus; new lesions are relatively uncommon, even persistent viremia. The spread of infection has been shown to be relentless in the setting of continued immunodeficiency, with advancement of lesion borders toward the fovea at a median rate of 24 µm/day.
ARN is a fulminant retinal vaso-occlusive necrotizing retinitis that may complicate VZV, HSV, or, rarely, CMV infections. HIV-positive patients with ARN tend to have a CD4+ cell count greater than 60/µL and usually have an associated history of VZV or HSV dermatitis.
The underlying pathophysiologic mechanisms for ARN rests on the virulence of these viruses following their reactivation, especially in the immunocompromised host. The severity of ARN depends on the degree of the patient's immunocompromise.
The incidence of VZV-associated retinitis after herpes zoster ophthalmicus in patients who are HIV positive is 4-17%; the frequencies of retinitis associated with HSV or CMV infections are much lower. ARN has been associated with either HSV-1 or HSV-2, with a similar course and severity of the infection as seen in VZV-induced ARN. A 2:1 male-to-female predilection to the occurrence of ARN exists.
PORN is a rapidly progressive, necrotizing retinitis that has been reported in patients with advanced AIDS. It is associated with a history of VZV infection in patients with AIDS. The incidence of PORN is much lower than that of ARN.
While the exact pathophysiologic mechanism for PORN has not been elucidated completely, the general consensus is that severe immunocompromise, along with a previous infection with at least VZV, are necessary. PORN also has been described in patients with severe immunocompromise secondary to chemotherapy.
Ophthalmic syphilis is believed to result from the proliferation and subsequent infiltration of Treponema pallidum spirochetes into ocular structures. Histologic evaluation demonstrates mononuclear and polymorphonuclear cell infiltration of the involved ocular tissue, particularly the cornea, iris, retina, and choroid. A modification of the host response to syphilis in HIV-infected patients may occur, which is partly responsible for the rapid course of CNS involvement in these patients.
The increase in the HIV-infected population has, in part, contributed to the resurgence of reactivation of latent tubercle bacilli in previously infected individuals. Tuberculosis represents a significant cause of granulomatous uveitis in patients who are HIV positive.
Reactivation of quiescent tubercle bacilli as a result of immunocompromise has been demonstrated to account for close to 90% of new cases of ocular tuberculosis. The caseating tubercle contains the inactive organism until reactivation. Inflammation of tuberculosis usually manifests as areas of necrosis surrounded by mononuclear and giant cells.
Infectious choroiditis represents fewer than 1% of ocular disorders in HIV-positive patients, with Pneumocystis jiroveci being the most common identified organism. P jiroveci choroidopathy tends to occur in HIV patients with disseminated infection. An increased association with long-term use of aerosolized pentamidine prophylaxis has been seen.[12]
Toxoplasmosis is the most common cause of retinochoroiditis, accounting for about 30-50% of all posterior uveitis cases. Ocular manifestation usually follows systemic disease.
Infection with T gondii may be congenital, but most cases are acquired later in life. T gondii is an intestinal parasite in cats. The organism usually forms cysts that contain many organisms. The cysts may exist in 1 of 3 forms: (1) oocysts, in cat feces; (2) tachyzoites, proliferative form; and (3) bradyzoites, encysted form. Infection in humans may occur either by inhalation or by consuming poorly cooked meat or unpasteurized milk that has been infested with the organism.
In general, toxoplasma infection is well tolerated in most tissues of the body, except the eyes. T gondii may remain as bradyzoites within an inactive chorioretinal scar until reactivated as a result of immunosuppression. The exact mechanism of reactivation has not been elucidated completely. However, it is the transformation of the bradyzoites into tachyzoites that allows for new infection of the retina and choroid, leading to recurrent retinochoroiditis.
H capsulatum is a small, gram-positive, mycelial dimorphic fungus, approximately 3-5 mm in diameter. The organism is endemic in the central and eastern United States, particularly the Mississippi-Ohio River Valley, as well as Central America, Asia, Turkey, Israel, and Australia. The organism enters the body via the respiratory tract by inhalation of spores.
Acute histoplasmosis tends to be benign and self-limiting, mostly affecting the pulmonary system. The infection may be subclinical.
In disseminated histoplasmosis, the organism spreads hematogenously, producing lesions throughout the body, especially in the reticuloendothelial system of the liver, spleen, lymph nodes, and bone marrow. Risk factors contributing to the dissemination of infection include a defective immune system, such as that seen in AIDS or malignancies; an immature immune system in infants; or iatrogenic immunosuppression. Disseminated histoplasmosis is uncommon in immunocompetent adults.
Disseminated histoplasmosis has a high mortality in AIDS patients. This disease tends to have a fulminant course, usually complicated by disseminated intravascular coagulation.
Cryptococcus neoformans is a budding, spore-forming, yeastlike fungus, with a diameter of 5-10 µm. A clear mucinous capsule usually surrounds this organism. This capsule can be detected easily by India ink and mucicarmine preparations. The distribution of the organism is worldwide. Infection from C neoformans most frequently is acquired from pigeon or other bird droppings. This organism has been isolated from soil, fruit, and milk.
Cryptococcal infection occurs by inhalation of airborne spores. Organisms initially remain in the lungs, then spread hematogenously to other parts of the body. This organism has predilection for the brain and meninges. Intraocular infection may occur either via direct extension from the CNS or through the bloodstream from a localized or disseminated cryptococcal infection.
Most intraocular cryptococcal infections have been seen in association with cryptococcal septicemia with severe meningeal infection. This often occurs in immunocompromised individuals or debilitated patients (eg, HIV-positive patients or patients with malignant lymphoma, Hodgkin lymphoma, or systemic lupus erythematosus).
Neuro-ophthalmologic complications are seen in approximately 10-15% of patients who are infected with HIV. The common causes of neuro-ophthalmologic complications include cryptococcal meningitis, meningeal and parenchymal lymphoma, neurosyphilis, and toxoplasmosis. More diffuse encephalopathy may be due to either direct effects of the virus (HIV retinopathy) or to superimposed infection from Polyomavirus causing progressive multifocal leukoencephalopathy (PML).[13]
Orbital complications are uncommon in HIV-positive patients. The most common complications include orbital lymphoma and orbital cellulitis due to Aspergillus infection. HIV-associated aspergillosis typically occurs in patients with CD4+ cell counts below 100/µL.
Lymphomas are treated with radiation and chemotherapy, whereas orbital cellulitis is amenable to systemic antibiotics.
Children with HIV infection are less likely to have ocular manifestations, including cytomegalovirus (CMV) retinitis.[14] The reason for this difference is uncertain, but it may be related to an altered immune response to HIV or lower prevalence of CMV seropositivity in children. However, HIV-infected children are at increased risk for neurodevelopmental delay, which is often associated with neuro-ophthalmic complications.
Most HIV-infected individuals are in developing countries, particularly, sub-Saharan Africa and Southeast Asia.[15, 16, 17, 18] The prevalence of CMV retinitis among these HIV-infected persons in these developing countries is lower than in developed countries.
However, ocular complications of toxoplasmosis and tuberculosis, herpes zoster ophthalmicus, and papillomavirus-associated conjunctival squamous cell tumor are more prevalent in HIV-infected persons in developing countries. The reason for this difference is believed to be related to the frequencies of the causative agents and the poor control of HIV infection in these countries.
As many as 33% of HIV-infected patients on high-dose rifabutin experience intraocular inflammation, especially when an antifungal azole is used concurrently. Cidofovir causes uveitis in about 25-30% of patients and may lower intraocular pressure in as many as 10% of patients. While mild uveitis may be treatable with topical corticosteroids, severe uveitis and hypotony can cause permanent visual loss[19] ; therefore, medication should be discontinued.
High-dose didanosine has been associated with retinal pigment epithelial abnormalities. Intravenous ganciclovir and acyclovir have been associated with corneal epithelial inclusions, while atovaquone is associated with corneal subepithelial deposits. These adverse effects are dose related and resolve following discontinuation of the drug, with the exception of abnormal retinal pigment epithelial changes.
The consequences of ocular manifestations of HIV infection can result from any of the following 3 processes:
Inflammatory changes can affect almost all adnexal, ocular, and orbital tissues. The infectious/noninfectious inflammatory process may manifest as a keratitis or vasculitis, iritis, ischemic papillitis or retrobulbar optic neuritis, and orbital vasculitis. Other complications may include retinitis or encephalitis.
Nerve damage may be associated with neurotrophic keratitis. Cranial nerve palsies have been reported in as many as 33% of cases of herpes zoster ophthalmicus, with the third cranial nerve being the most frequently affected. The cranial nerve involvement may take place within the orbit or the cavernous sinus.
Tissue scarring may result in eyelid deformities, including marginal notching, loss of cilia, trichiasis, and cicatricial entropion. Scarring and occlusion of the lacrimal puncta or canaliculi may occur.
Some of the complications of ocular Kaposi sarcoma include trichiasis and entropion formation. Untreated ocular Kaposi sarcoma may lead to obstructive disruption of the visual axis.
Chronic follicular conjunctivitis frequently is present with occasional associated punctate epithelial erosions and/or superficial vascular pannus on the cornea. Severe keratitis due to molluscum contagiosum tends to mimic chlamydial keratoconjunctivitis. It is uncommon to find conjunctivitis and superficial keratitis in HIV-positive patients.
With conjunctival microvasculopathy, there is no reported morbidity or mortality.
The concurrent presence of encephalopathy in patients with keratoconjunctivitis sicca may cause incomplete eyelid closure and decreased blink rate, leading to worsened dry eyes.
Complications of varicella-zoster virus (VZV) ocular infection include subepithelial infiltrates, stromal keratitis, disciform keratitis, uveitis, and increased intraocular pressure. Varicella keratitis is a self-limited disease. Corneal scarring may occur, but it is rare.
Stromal keratitis and uveitis occur in fewer than 10% of patients with primary herpes simplex virus (HSV) infection. Blepharoconjunctivitis may occur in patients with recurrent ocular HSV infection. It may or may not be associated with epithelial keratitis. Other complications of HSV infection include dendritic and geographic epithelial keratitis, nonnecrotizing stromal keratitis, and iridocyclitis.
Fungal keratitis may be complicated by uveitis, endophthalmitis, and/or retinitis. These complications may cause vitreous abscesses or retinal hemorrhages with or without Roth spots. In severe cases, retinal detachment may develop.
In HIV-positive patients infected with microsporidia, superficial keratoconjunctivitis is the most common complication seen.
Complications of CMV retinitis include papillitis, seen in about 5% of these patients, and it can lead to significant visual loss. If left untreated or if inadequately treated, CMV retinitis progresses (usually less rapidly than HSV or HZV retinitis) to involve a larger area of the retina including the macular and/or foveal. Cystoid macular edema, retinal vein or artery occlusion, rhegmatogenous retinal detachment (RRD), or blindness may result from inadequately treated CMV retinitis in these patients.[20]
The incidence of RRDs tends to increase with time in patients with CMV retinitis, with a cumulative probability of 26-61% in different studies.
Immune recovery uveitis (IRU) is a HAART-dependent inflammatory response that may occur in up to 63% of patients with regressed CMV retinitis and elevated CD4+ counts. IRU is caused by a response to CMV antigens, which is made possible by immune recovery. IRU generally is recognized in its most severe form by an increase in intraocular inflammatory reactions within weeks after starting HAART, or it may manifest later by the presence of inflammation and may be associated with vision loss from epiretinal membrane, cataract, neovascularization of the retina or optic disc, and cystoid macular edema.
Patients with large areas of CMV retinitis and a history of cidofovir use have an increased risk for IRU. To reduce the risk of IRU, delay HAART use until induction of CMV therapy.
Acute retinal necrosis (ARN) frequently is complicated by anterior uveitis, retinal and choroidal vasculitis, vitritis, and papillitis. Episcleritis, scleritis, or optic neuropathy also may be present. During the initial phase of the infection, the severity of the retinitis can lead to exudative retinal detachment. Following the resolution of the retinitis, however, traction between the vitreous and the resulting gliotic scar of the necrotic retina may occur and can cause retinal breaks at the interface between the normal and necrotic retina. Subsequently, this may result in RRD. In as many as 75% of cases, ARN may be complicated by RRD 2-3 months after onset.[21]
Complications of herpes zoster ophthalmicus (progressive outer retinal necrosis, or PORN) may include macular retinitis, optic nerve disease, acute vitreous hemorrhage, and/or retinal detachment. Up to 66% of patients diagnosed with PORN become blind within 6 weeks of diagnosis despite aggressive treatment.
Syphilitic anterior uveitis may be complicated by cataract and glaucoma formation. Posterior segment complications may include posterior placoid chorioretinitis, neuroretinitis, vitritis, pigmentary chorioretinopathy, choroiditis, papillitis, choroidal neovascular membranes, and retinal vasculitis.
Complications of tuberculosis include the following:
These ocular manifestations tend to occur in patients with other extrapulmonary disease.
With Pneumocystis jiroveci choroidopathy, usually minimal vitreous inflammation occurs. The major cause of morbidity and/or mortality in patients with P jiroveci infection results from the debilitating pneumonia.
Ocular complications of Toxoplasma gondii infection depend on the mode of infection. Infection with T gondii may be congenital or acquired. In general, ocular complications include infantile retinochoroiditis, leukocoria, and anterior and posterior uveitis.
Disseminated histoplasmosis has a high mortality rate in AIDS patients. This disease tends to have a fulminant course, usually complicated by disseminated intravascular coagulation. Ocular complications of disseminated histoplasmosis include retinitis, choroiditis, optic neuritis, or uveitis. Secondary choroidal neovascularization also may develop.
The most frequent intraocular sequela of cryptococcal infection is chorioretinitis. In the absence of treatment, or because of poor management, endophthalmitis may result. Other reported ocular complications of cryptococcal infection include papilledema, optic atrophy, and ophthalmoplegia.
For neuro-ophthalmologic manifestations, the most common complications include papilledema due to increased intracranial pressure, cranial nerve palsies, ocular motility disorders, and visual field defects.
Clinical manifestation of herpes zoster ophthalmicus (HZO) may be acute, chronic, or relapsing. The acute lesions usually develop within 3 weeks of the rash. These lesions may resolve rapidly and completely, or they may pursue a chronic course for months to years. Recurrence is a characteristic feature of the disease, and relapse may occur as late as 10 years after the primary infection.[22]
Vesicular rash in the distribution of all or one of the divisions of the trigeminal nerve is one of the early clinical manifestations. Fever, malaise, and headache also may be part of the presenting complaint. Crusts usually develop after the sixth day. Involvement of the nasociliary nerve often is associated with ocular involvement, although severe ocular complications can occur with vesicular rash anywhere on the forehead.
Acute tissue changes may include the following:
Neurologic complications of HZO may include the following:
Kaposi sarcoma usually presents on the eyelid as a painless, violet-brown papule. It may involve the orbit with associated eyelid and conjunctival edema. Kaposi sarcoma of the conjunctiva usually appears as reddish-blue, vascularized, subconjunctival lesions most frequently seen in the inferior fornix as nodular or diffuse lesion. Eyelid and conjunctival Kaposi sarcoma tend to mimic chalazion and localized subconjunctival hemorrhage, respectively.
Molluscum contagiosum is characterized by multiple, small, painless, umbilicated lesions. The lesions of molluscum contagiosum tend to be larger, more numerous, and faster growing in HIV-positive patients than in HIV-negative patients. Compared with keratoacanthoma, molluscum contagiosum is smaller and associated with less inflammation. It may give rise to elevated, pearly, umbilicated nodules on the eyelids. The lesions are seen easily on the eyelids, but they sometimes may be missed with casual examination.
Diagnosis is based on clinical findings of the characteristic skin lesions. Molluscum contagiosum is a self-limiting disease with spontaneous resolution taking months to years.
VZV infection usually manifests with fever, malaise, and cutaneous rash, which typically lasts 7-10 days. The cutaneous manifestations usually start as macules and progress to papules, vesicles, and, ultimately, pustules, which dry and crust. The vesicles may be on the eyelid margins or bulbar conjunctiva. Associated papillary conjunctivitis with membrane formation may be present. Other signs include decreased corneal sensation and increased intraocular pressure.
Clinical features of VZV infection that distinguish it from herpes simplex virus (HSV) infection include the following:
Primary ocular HSV infection often presents as unilateral blepharoconjunctivitis. The conjunctival inflammatory response is frequently follicular, with associated preauricular lymphadenopathy. Cutaneous vesicles on the eyelid skin or margin appear in most of the cases.
Follicular conjunctivitis caused by HSV sometimes may be difficult to distinguish from that caused by adenovirus. Helpful distinguishing features include the characteristic dendritic morphology of HSV keratitis, presence of cutaneous vesicles, absence of an associated epidemic, and the predominant unilaterality (approximately 10% of HSV keratitis cases are bilateral, whereas most of the adenovirus keratoconjunctivitis cases are bilateral).
Patients with dendritic epithelial keratitis may have no obvious symptoms, or they may complain of mild foreign-body sensation, photophobia, redness, and blurred vision.
Recurrent HSV epithelial keratitis usually manifests as characteristic dendritic branching. The lesions may start as distinct punctate epithelial keratitis, which then coalesce into dendritic-shaped lesions composed of swollen opaque epithelial cells within days.
The dendritic terminals have a peculiar bulblike morphology. A narrow ulcer often develops in the center of the dendrite within days of onset, usually as a result of lysis of virus-infected cells. The opaque cells around the central ulcer stain well with rose bengal and fairly well with fluorescein. The predisposing factors for developing geographic ulcers include the HSV strain, topical or systemic immunosuppressive therapy, and HIV infection.
Clinical features of HSV infection that distinguish it from VZV infection include the following:
Other conditions that may produce dendritic epithelial lesions include VZV, healing epithelial defects, and soft contact lens wear.
Diagnosis of HSV predominantly is based on clinical features and staining pattern with rose bengal and/or fluorescein. In the absence of such classic clinical features, tissue culture, and/or antigen detection techniques may be helpful.
Patients with fungal keratitis usually present with eye pain, photophobia, discharge, foreign-body sensation, or a history of ocular trauma with vegetable material. Slit-lamp examination usually reveals corneal stromal infiltrate with a feathery border. Associated small focal lesions around the primary corneal infiltrate often are present, along with conjunctival injection, anterior chamber reaction, and hypopyon.
Superficial keratoconjunctivitis is more common in HIV-positive patients with microsporidia infection, while focal stromal keratitis tends to occur more commonly in healthy individuals infected with microsporidia.
Patients may present with the following:
HIV-associated retinal microvasculopathy often is asymptomatic and transient, but it may contribute to the optic nerve atrophy seen in many of the patients. Common findings may include the following:
Patients with CMV retinitis typically complain of floaters, photopsias, or visual loss, without associated eye pain or injection. Patients tend to have good vision at diagnosis of CMV retinitis.
Often, minimal anterior chamber reaction is present. The characteristic lesion tends to be a single lesion or multiple white lesions with a granular irregular feathery border associated with retinal edema and necrosis. Associated intraretinal hemorrhage may or may not be present initially. Over time, the lesions of CMV retinitis may coalesce with a full-thickness retinal whitening often associated with intraretinal hemorrhage.
Patients with ARN usually present with eye pain associated with decreased visual acuity, floaters, and history of recent HSV or HZV infection. In early disease, funduscopic examination often reveals small, necrotic yellowish lesions in the periphery, which rapidly spread into a larger confluent white area, most often involving the entire peripheral retina, and then progress toward the posterior pole.
In about 36% of cases, the contralateral eye is also involved. Associated anterior uveitis, retinal vasculitis, episcleritis, scleritis, or retinal detachment may be present.
Patients with progressive outer retinal necrosis (PORN) usually present with minimal anterior chamber inflammation, with no vitritis or retinal vasculitis. In general, the lesions in PORN tend to be multifocal, deep to the retina, opaque, and patchy. Typically, the lesions start from the posterior pole and spread with extreme rapidity to involve the entire retina.
Ocular manifestations of syphilis can mimic any ocular inflammatory disorder. The initial presentation of ocular syphilis is unilateral with subsequent contralateral eye involvement in 50% of cases.
Ocular manifestations of syphilis vary with the stage of the disease. In the primary stage, eyelid or conjunctival chancre is present. In the secondary or tertiary stage, iridocyclitis or more diffuse intraocular inflammation is present.
Other manifestations of secondary and/or tertiary syphilis include the following:
Dissemination of the disease in secondary syphilis may be accompanied by arthralgia, headache, low-grade fever, and maculopapular rash.
Three distinct patterns of iris findings may be seen before or during the active stage of the disease, as follows:
Inadequately treated syphilis or untreated disease sets the stage for tertiary syphilis, which includes the development of an obliterative endarteritis in about one third of cases. Optic atrophy, old chorioretinitis, chronic iritis, and Argyll-Robertson pupils also are seen in this stage.
Ocular tuberculosis is usually accompanied by constitutional symptoms, such as malaise, night sweats, and other pulmonary complaints, including shortness of breath and dyspnea.
Ocular tuberculosis can take a variety of forms. The most common ocular manifestation is anterior uveitis and disseminated choroiditis. The anterior segment inflammation may be granulomatous or nongranulomatous, with varied severity. Usually, granulomatous keratitic precipitates and posterior synechiae are present.
It is possible to have anterior uveitis without clinically active tuberculosis. Untreated chronic uveitis from tuberculosis can gradually result in panophthalmitis. Choroidal tubercle invasion in miliary tuberculosis may cause unifocal or multifocal yellowish, grayish, or whitish choroiditis, mostly in the posterior pole.
These lesions tend to show delayed hyperfluorescence that increase in size on fluorescein angiography. With time, these lesions heal with residual scars that may or may not have pigmentation. Sequela of subretinal neovascularization arising from the area of scars may be present.
Pneumocystis jiroveci choroidopathy can cause mild visual loss, but most patients are asymptomatic. Funduscopic examination usually reveals multifocal, round, creamy, yellow, deep choroidal lesions mostly in the posterior pole. These choroidal lesions may measure 0.5-2 disc diameters in size. Usually, minimal vitritis with no retinal vascular changes is present. Fluorescein angiography shows early hypofluorescence with late staining of the choroidal lesions.
Transplacental infection of toxoplasma retinochoroiditis to the fetus has been shown to occur in 20% of pregnancies with active maternal infection. The severity of the fetal infection depends on the stage of pregnancy. In the first trimester, toxoplasmosis can result in abortion or in an infant with retinochoroiditis, encephalitis with associated intracerebral calcification, hydrocephalus, and mental retardation.
Ocular manifestation often consists of bilateral retinochoroiditis in the posterior pole, particularly in the macula region. Ocular manifestation may become evident during or shortly after a systemic infection, or months to years later.
The usual ocular lesion of toxoplasmosis is a focal necrotizing retinitis, with white infiltration and surrounding retinal edema. Anterior segment uveitis, with keratic precipitates and anterior chamber cells and flare, is common. The areas of retinitis may be single or multiple, small or large, and frequently are adjacent to inactive chorioretinal scars. Vitreous cellular reactions over the areas of retinitis often are present.
Vitreous precipitates on the posterior surface of the detached vitreous may be present. In addition, vitreous debris, optic disc swelling, neuroretinitis, mild granulomatous iritis, localized vasculitis, and retinal artery or vein occlusion in the area of the inflammation may be present. Occasionally, a chorioretinal scar may be seen in the uninvolved eye.
The typical triad of ocular histoplasmosis syndrome comprises the following:
A pigmented rim separating the disc from the area of atrophy or scarring may be present. The formed macular CNVM may be associated with retinal neurosensory detachment, subretinal blood or exudate, or a pigmented ring evolving into a disciform scar.
In children, histoplasmosis often manifests as disseminated disease, with fever, hepatosplenomegaly, nausea, vomiting, diarrhea, and weight loss. Interstitial pneumonia is expected to develop within a few weeks and may be fatal if not treated aggressively.
Adults with disseminated histoplasmosis often present with fever and acute pneumonia. The central nervous system, kidneys, and GI tract often are involved secondarily.
Ocular involvement in disseminated histoplasmosis may include retinitis, choroiditis, optic neuritis, or uveitis. The retinitis often appears as discrete multiple, yellowish-white intraretinal and subretinal infiltrates, approximately one-fourth to one-sixth disc diameter. The granulomatous choroiditis of histoplasmosis may appear as small white drusenoid bodies.
The disease rarely is diagnosed acutely but most commonly is recognized by the clinical appearance of the lesion. Patients often are diagnosed with ocular histoplasmosis following the development of choroidal neovascularization leading to significant loss of central vision.
During acute illness from disseminated histoplasmosis, diagnosis can be made from positive blood cultures and cultures of urine, mouth ulcers, and/or tissue biopsies. Liver biopsies have been reported to be positive for Histoplasma capsulatum in as many as 80% of patients. A high fixation titer for histoplasmin complement substantiates the diagnosis. Immunodefective patients may have a negative histoplasmin skin test. The vitreous aspirates obtained during pars plana vitrectomy may be used to isolate the organisms.
The most common intraocular manifestation of cryptococcal infection is chorioretinitis. This usually starts as multiple, yellowish-white, minimally elevated chorioretinal lesions. The size of these lesions ranges from one-fifth to one disc diameter. Usually, minimal or no associated vitritis is present. In the absence of proper treatment, these lesions may progress to endophthalmitis. This usually results in the development of vitritis with haze, debris, and vitreous exudates, which may extend throughout the entire vitreous.
The diagnosis of HSV keratitis is primarily clinical, and the use of fluorescein and rose bengal dyes will highlight the characteristic corneal dendrites with terminal bulbs. Laboratory studies, including virus culture, direct fluorescent antibody tests for HSV antigens, and polymerase chain reaction (PCR) testing for HSV DNA, can help to confirm the diagnosis.
The diagnosis of HZO is primarily by history and examination. However, baseline complete blood count, electrolytes, glucose, blood urea nitrogen, and creatine may be necessary prior to starting antiviral drugs.
When a clear diagnosis cannot be made, a noncontrast CT scan should be considered to evaluate for other causes of new-onset headache.
The workup for fungal keratitis includes a detailed history and complete ophthalmologic examination. The history should include contact lenses use, lens-care regimen, previous corneal disease, and topical or systemic steroid use.
A thorough slit lamp examination is important. Deep corneal scrapings or even corneal biopsy for Giemsa, periodic acid-Schiff, or Gomori methenamine-silver staining with culture and sensitivity to define treatment, particularly with persistent ulcer may be indicated.
A history and detailed ophthalmic examination should be performed to diagnose microsporidiosis. Spores, sporoblasts, meronts, and sporonts can be identified in conjunctival or corneal scrapings from affected patients. The spores are Gram positive and acid-fast by staining.
Microsporidia are very difficult to culture, but they are seen readily within corneal or conjunctival epithelial cells with the use of Masson trichrome or Giemsa staining. The diagnosis may be aided by the use of electron microscopy and confocal microscopy in vivo.
A history and complete ophthalmologic examination with dilated funduscopic examination should be performed for diagnosis of HIV retinopathy. Significant retinal nerve fiber layer loss occurs in HIV patients without CMV retinitis but with low CD4+ counts. Third-generation optical coherence tomography (OCT) may be useful in establishing a diagnosis of early subclinical HIV-associated visual functional loss.[23]
A history and complete ophthalmologic examination with dilated funduscopic examination should be performed for diagnosis of CMV retinitis. Conjunctival swabs in combination with PCR can be used to confirm the diagnosis. PCR-based analysis of vitreous humor offers high diagnostic specificity and sensitivity. Vitreous sampling is usually reserved for patients with atypical lesions, for individuals in whom disease is not responsive to treatment, or for patients for whom a vitreous biopsy would carry little added risk.
In addition, the patient should have a workup for systemic CMV infection that includes testing of urine and serum CMV titers.
For diagnosis of acute retinal necrosis (ARN), perform a detailed history and a complete ophthalmologic examination with dilated funduscopic examination. Check for HSV-1, HSV-2, and CMV IgG and IgM titers.
The workup of progressive outer retinal necrosis (PORN) is similar to that for ARN, except that the serology focuses on varicella-zoster virus (ZVZ) IgG and IgM titers.
Diagnoses of ocular syphilis should include obtaining a specific treponemal-antibody assay (fluorescent treponemal antibody absorption [FTA-ABS] or microhemagglutination Treponema pallidum [MHA-TP]) and a nonspecific treponemal-antibody assay (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] test).
The VDRL test becomes positive 1-3 weeks after the appearance of the chancre. The VDRL and RPR tests may show a false-negative result in early primary, latent, or late syphilis. FTA-ABS and MHA-TP are highly sensitive and specific in all stages of syphilis.
Lumbar puncture may be performed if the patient has a positive FTA-ABS test combined with neurologic or neuro-ophthalmologic signs, papillitis, active chorioretinitis, or uveitis.
VDRL or RPR results correlate with disease activity, so these tests are useful in monitoring response to treatment. FTA-ABS and MHA-TP results do not reverse to normal, so they are not helpful in assessing the patient’s response to treatment.
Perform a detailed history and physical examination, attempting to rule out other causes of granulomatous disease, such as sarcoidosis, syphilis, leprosy, and brucellosis. Order a chest radiograph.
Perform a purified protein derivative (PPD) skin test. A reaction induration of more than 5 mm is considered positive in patients with the following:
A PPD reaction induration of more than 10 mm is considered positive for persons with the following:
A PPD reaction induration of more than 15 mm is considered positive in individuals with no risk factors for tuberculosis. The QuantiFERON-TB Gold in-Tube test and T-Spot TB test are used to measure the immune system’s reaction to tuberculosis bacteria.
Culture for positive growth of Mycobacterium tuberculosis is needed to confirm the diagnosis of tuberculosis.
Perform a detailed history for P jiroveci pneumonia and use of aerosolized pentamidine. Obtain induced sputum or bronchoalveolar lavage (BAL) for histopathologic evaluation. Complete an ophthalmologic examination. Request a medical consultation.
In the workup, consider syphilis, tuberculosis, and toxocariasis as differential diagnoses. Perform a detailed history and ophthalmologic examination. Serologic detection of antibodies to T gondii is important. Current available testing assays include the indirect hemagglutination assay (IHA) and the immunofluorescent antibody (IFA) test. This test measures both the IgG and IgM antibodies to T gondii. Request that the laboratory perform a 1:1 dilution, as only a positive result is required.
Some less commonly used tests include the Sabin-Feldman dye and the enzyme-linked immunosorbent assay (ELISA) tests. PCR and cytologic demonstration of the organism in vitreous samples could be useful in some cases. Diagnosis of ocular toxoplasmosis requires the demonstration of a characteristic retinochoroiditic lesion and a positive serology at any titer. Fluorescein angiogram may be helpful when a choroidal neovascular membrane is suspected.
In the workup, consider toxoplasmosis and multifocal choroiditis with panuveitis as differential diagnoses. Perform a detailed history and complete ophthalmologic examination, including dilated funduscopic examination. Inquiring about possible time spent in the Ohio-Mississippi River Valley area is important. Also ask about possible exposure to fowl. The Amsler grid should be used to assess the central visual field for each eye. Fluorescein angiography may be used to detect a choroidal neovascular membrane.
Perform a detailed history and ophthalmologic examination for diagnosis of cryptococcal chorioretinitis. Diagnosis of cryptococcal chorioretinitis mostly is based on the clinical findings. A diagnostic vitreous tap may be performed, and the samples are examined by direct smear using India ink and cultured on Sabouraud agar at 37°C. Organism growth often takes place within 24-48 hours, producing mucoid, cream, or pink colonies.
Evaluation of neuro-ophthalmologic manifestations in HIV typically includes a magnetic resonance imaging (MRI) brain scan followed by a lumbar puncture to obtain cerebrospinal fluid for cell count, cytologic studies, culture, and antibody and antigen testing. Computed tomography of the head may be useful for patients with toxoplasmosis and cryptococcus.
Recommended treatment for herpes zoster ophthalmicus (HZO) is intravenous acyclovir 10 mg/kg 3 times per day for 7 days, followed by oral acyclovir 800 mg to 1 g 3-5 times per day for an additional 7 days. This regimen is most effective when started within 72 hours of onset of the vesicular lesions. This treatment reduces the frequency of recurrences.
Oral acyclovir has been demonstrated in a randomized clinical trial to reduce the shedding of the virus from the vesicles, decrease systemic spreading of the virus, and reduce the severity and duration of HZO complications (eg, dendritic keratitis, stromal keratitis, uveitis). However, oral acyclovir does not affect the incidence, severity, or duration of postherpetic neuralgia.
Famciclovir 500 mg 3 times per day for 7 days and valacyclovir 1000 mg 3 times per day for 7 days has an advantage of causing fewer adverse effects. If HZO is unresponsive to acyclovir, famciclovir, or valacyclovir, intravenous foscarnet should be tried.
Topical antiviral agents have not been shown to be effective for the management of HZO.
If intraocular inflammation is present, a topical cycloplegic agent (ie, scopolamine 0.25% tid) and a topical steroid (ie, prednisolone acetate 1% q1-2h) should be started.
Generally, it is recommended that oral steroids be avoided because of the risk of further immunosuppression of the patient and exacerbation of the infection. However, oral steroids have been used by dermatologists for the treatment of HZO to reduce the incidence of postherpetic neuralgia in patients older than 60 years.
Alternatively, topical capsaicin 0.25% ointment applied to the involved skin twice daily, or amitriptyline 25 mg by mouth 3 times daily may be useful in reducing the symptoms of postherpetic neuralgia.
In case of persistent punctate keratopathy, treatment with copious, nonpreserved ocular lubricant ointments, bandage contact lenses, or tarsorrhaphy may be needed.
Radiation therapy is effective for eyelid and conjunctival Kaposi sarcoma. Adverse effects of radiation therapy include loss of lashes, skin irritation, and conjunctivitis. Local cryotherapy of eyelid and conjunctival lesions may be performed.[24]
Intralesional chemotherapy with vinblastine, alpha interferon, and liposomal daunorubicin may be administered. Surgical excision of the tumor may be performed in some patients with severe symptoms.[25]
Molluscum contagiosum lesions of the skin can be treated with incision (with or without curettage), cryotherapy, or various topical agents, including phenol and trichloroacetic acid. Surgical treatment, although useful for individual lesions, may be inappropriate for patients with multiple lesions of the eyelids. Reconstitution of immune function with HAART can result in resolution of molluscum contagiosum without therapy directed toward the virus, but clearing of cutaneous lesions can take 5-6 months after the initiation of therapy.
Recommended treatment is oral acyclovir 800 mg 5 times per day or famciclovir 125-500 mg by mouth 3-5 times per day. Chronic treatment may be required for VZV keratitis. This usually minimizes symptoms and shortens the duration of viral shedding.
Severe disciform stromal keratitis that causes significant reduction in visual acuity may be treated with topical corticosteroids.
Most cases of HSV epithelial keratitis resolve spontaneously within several weeks. The rationale for treatment is to decrease corneal damage due to lytic viral infection and virus-incited immunologic response. Debridement of HSV epithelial keratitis with a dry cotton-tipped applicator or a cellulose sponge can hasten resolution and decrease the load of infectious virus and viral antigens.
Medical treatment includes the use of vidarabine ophthalmic 3% ointment 5 times daily for 14 days and/or trifluridine ophthalmic 1% solution every 3 hours for 14 days; ganciclovir 0.15% ophthalmic gel 5 times daily until the ulcer heals and then 3 times a day for 7 days; or acyclovir topical 3% ointment 5 times daily for 14 days or oral dosage form 400 mg 5 times daily for 7 days; or famciclovir 500 mg by mouth 3 times daily for 7 days.
HSV neurotrophic keratopathy is a condition that should be managed with nonpreserved lubricants, eyelid patching, bandage contact lenses, and sometimes autologous serum and nerve growth factor.
Initially, corneal infiltrates and ulcers are usually treated as bacterial infections until the results of cultures and/or staining are obtained. If cultures indicate fungal keratitis, then the following action is recommended:
For deep stromal infection, combination medication is recommended: topical amphotericin B, topical fumagillin, miconazole or clotrimazole and/or oral fluconazole, itraconazole, or albendazole.
Topical corticosteroid drops are used frequently but with extreme caution and with proper antimicrobial coverage when infection is suspected. If toxicity from the medication is suspected, the dose should be tapered or the causative agent should be discontinued.
Specific agents and modalities for the treatment of CMV retinitis include the following:
These agents act by inhibiting CMV DNA polymerase.
Valganciclovir is the drug of choice for the treatment of CMV retinitis because of its convenience, lower cost, and lack of complications associated with IV administration. Valganciclovir is the valine ester of ganciclovir. The addition of the valine moiety increases the absorption of ganciclovir tenfold.
Valganciclovir is available as a 450-mg tablet. The recommended dose for induction is 900 mg twice a day and then 900 mg once a day for maintenance. Adverse effects are similar to those of intravenous ganciclovir and require periodic monitoring of complete blood count and renal function. Given the need for lifelong therapy for CMV retinitis in some HIV-positive patients, valganciclovir is a welcome alternative to long-term administration of intravenous antivirals.
When using ganciclovir, start induction with 5 mg/kg IV every 12 hours for 14 days, then change to a maintenance IV dose of 5 mg/kg/day for 7 days. Adjust the dose accordingly for patients with renal insufficiency. The significant adverse effect with ganciclovir is myelosuppression. Monitor CBC with differential 2-3 times a week during induction phase and weekly thereafter. If the absolute neutrophil count drops below 500/mL (see the Absolute Neutrophil Count calculator) or the platelet count drops below 10,000/mL, discontinue ganciclovir treatment.
During the treatment of CMV retinitis with ganciclovir, the dose of zidovudine may need to be reduced, unless hematopoietic growth factors (eg, regramostim, filgrastim) are used concurrently. This prevents exacerbation of myelosuppression.
Alternatively, intravitreal ganciclovir may be implanted to ensure adequate and prolonged intravitreal concentration of the drug. However, this does not preclude the use of oral ganciclovir to control the systemic infection.
When using foscarnet, start induction with 60 mg/kg IV every 8 hours for 14 days, then change to a maintenance IV dose of 90-120 mg/kg/day. Hydration with 1000 mL of isotonic sodium chloride solution is recommended because of renal toxicity associated with foscarnet. Therefore, it is recommended that electrolyte status, particularly calcium and magnesium, serum creatine, and hemoglobin, be monitored 2-3 times per week for 2 weeks and weekly thereafter.
Dosage adjustment is recommended if renal insufficiency is present, and the drug should be discontinued if serum creatine is greater than 2.8 mg/dL.
When using cidofovir, start induction with 5 mg/kg IV over 1 hour once weekly for 2 weeks, then change to a maintenance dose of 5 mg/kg over 1 hour once every other week. This drug is nephrotoxic. Concurrent use of probenecid with cidofovir and hydration with 1-2 L of normal saline reduces the risk of renal toxicity. Other adverse effects of cidofovir include iritis and ocular hypotony. It is also a major risk factor for immune recovery uveitis (IRU) among patients with CMV retinitis who are receiving HAART.[26]
Inflammation in the anterior chamber is treated with topical corticosteroids in a frequency typical of treating other forms of anterior uveitis. Immune recovery uveitis (IRU) with more severe vitreous inflammation and/or cystoid macular edema is typically treated with periocular corticosteroids (triamcinolone acetonide 40 mg) or short courses of oral corticosteroids, without recurrence of the CMV retinitis. The main advantage of periocular corticosteroids is the production of therapeutic local drug levels to avoid the potential problems of systemic corticosteroids in these immunosuppressed patients.[26, 27, 28]
Start acyclovir 5-10 mg/kg/day IV in 3 divided doses for 1 week, then change to oral acyclovir 800 mg 5 times daily for the following 1-2 months. Monitor blood urea nitrogen and creatine levels because of the nephrotoxic effect of acyclovir.
Start a slow tapering dosage of prednisone, 60-100 mg orally daily 24 hours after starting acyclovir, and continue for about 1-2 months. Be sure to obtain a chest radiograph and PPD before starting the oral steroid. Add ranitidine 150 mg orally twice daily for steroid-induced gastritis.
Use a topical steroid, such as prednisolone acetate 1%, instilled every 2-6 hours, and a cycloplegic agent, such as homatropine 5% instilled 2-3 times daily.
In fulminant cases, IV ganciclovir and/or cidofovir, with intravitreal ganciclovir and/or foscarnet, may be considered. Ganciclovir, foscarnet, and cidofovir are given in the same dosages as for CMV retinitis (see above).
Use of retinal laser photocoagulation to surround the necrotic lesion is controversial.
For retinal detachment, vitrectomy, membranectomy, endolaser, and silicone oil infusion usually is required.
All HIV-positive patients with syphilitic eye findings are considered to have tertiary syphilis and are treated accordingly. Treatment of syphilis is with intravenous penicillin G (24 million U/day for 7-10 days). Relapse may occur in spite of adequate treatment. For penicillin-allergic patients, alternatives include tetracycline 500 mg 4 times per day or doxycycline 200 mg twice a day by mouth for 30 days or a third-generation cephalosporin (eg, ceftriaxone).
Cycloplegia with either cyclopentolate 2% or homatropine 5% 3 times daily and prednisolone acetate 1% 4 times daily is recommended if anterior segment inflammation is present.
Patients should be given isoniazid (INH) 300 mg orally daily, rifampin 600 mg orally daily, and pyrazinamide 25-35 mg/kg orally daily for 2 months; then, continue with INH and rifampin for an additional 7 months. Drug resistance is most common with streptomycin and INH; however, this may be minimized by the use of multiple bactericidal antituberculous drugs.
Pyridoxine 25 mg orally daily usually is added to the regimen to prevent peripheral neuritis.
For small peripheral retinochoroiditis (not affecting or threatening the macula), treat anterior chamber inflammation with a topical cycloplegic with or without a topical steroid (eg, prednisolone acetate 1% qid). The topical steroid should be tapered gradually as the anterior chamber inflammation resolves.
For active retinochoroiditis within 2-3 mm of the disc or fovea, which threatens vision, or peripheral lesion associated with severe vitritis, start first-line therapy for 3-6 weeks, as follows: (1) pyrimethamine 75 mg PO load, 25 mg PO twice daily, plus, (2) folinic acid 3-5 mg PO twice weekly (to reduce the adverse effect of bone marrow toxicity of pyrimethamine), and (3) sulfadiazine 2 g PO load, then 1 g PO 4 times daily.
Clindamycin 300 mg PO 4 times daily may be used with sulfadiazine as alternative treatment. Patients on clindamycin should be monitored for the possible adverse effect of pseudomembranous colitis. Other alternative therapeutic regimens include the following: trimethoprim/sulfamethoxazole (160 mg/800 mg) 1 tablet PO twice daily, with or without clindamycin.
Platelet count and CBC should be monitored once to twice weekly for patients on pyrimethamine. If the platelet count falls below 100,000, then a reduction in the dose along with an increase in the dose of folinic acid, should be initiated. It is important that patients on pyrimethamine avoid taking vitamins containing folic acid.
Retinal laser photocoagulation, cryotherapy, and vitrectomy have been used as adjunct therapy in the treatment of ocular toxoplasmosis.
For disseminated histoplasmosis, amphotericin or ketoconazole is the recommended pharmacologic treatment of choice. Patients with AIDS usually receive a higher dose of amphotericin B (1-2.5 g), followed by daily ketoconazole (lifelong), or weekly-maintenance amphotericin B treatment.
Laser retinal photocoagulation may be used to treat choroidal neovascular membrane (CNVM) in the macula. Treatment is recommended within 72 hours of the diagnosis of CNVM with positive fluorescein angiography.
Amsler grid use daily is recommended to assess central vision, and patients are advised to report any sudden change in vision as soon as possible.
Early diagnosis and treatment of cryptococcal chorioretinitis is important. Combination treatment with flucytosine and intravenous amphotericin B is considered the treatment of choice for disseminated or meningeal cryptococcal infection. However, there have been cases of cryptococcal chorioretinitis successfully treated with intravenous amphotericin B alone.
Fluconazole and itraconazole have been reported to be effective in the treatment of cryptococcal chorioretinitis.
Early vitrectomy is recommended with persistent vitritis despite treatment.
Topical fumagillin has been used successfully to treat keratoconjunctivitis secondary to microsporidiosis.[29, 30]
Pneumocystis jiroveci ocular infection is treated with intravenous trimethoprim/sulfamethoxazole or intravenous pentamidine.
No treatment is indicated for HIV retinopathy or conjunctival microvasculopathy. These patients require observation only.
In patients with keratoconjunctivitis sicca, artificial tears and long-acting lubricating ointments used in association with punctal plugs provide symptomatic relief.
Options for neuro-ophthalmologic manifestations in HIV include radiation for lymphoma and specific antibiotics for infectious causes.
No treatment is available for progressive multifocal leukoencephalopathy (PML).