Ocular Manifestations of HIV Infection

Updated: Jun 14, 2022
  • Author: Luca Rosignoli, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Ocular manifestations of human immunodeficiency virus (HIV) infection historically have been common. [1] Although approximately 70-80% of HIV-infected patients have been treated for an HIV-associated eye disorder during their illness, these numbers have appeared to decrease with the development of increasingly efficacious HIV antiviral therapy.

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. [1] 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:

·       Retinal or conjunctival microvasculopathy

·       Cytomegalovirus (CMV) retinitis

·       Progressive outer retinal necrosis

·       Mycobacterium avium complex infection

·       Cryptococcosis

·       Microsporidiosis

·       HIV encephalopathy

·       Progressive multifocal leukoencephalopathy

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 remains 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. [1]

For other discussions of HIV infection, see HIV DiseasePediatric 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.


Adnexal Manifestations

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 [1] :

·       Herpes zoster ophthalmicus (HZO)

·       Kaposi sarcoma

·       Molluscum contagiosum

·       Conjunctival microvasculopathy

Herpes zoster ophthalmicus

Herpes zoster is a painful vesiculobullous dermatitis that results from the localized reactivation of varicella-zoster virus (VZV) infection. [2] Over 90% of the general population develops serologic evidence of a VZV infection by adolescence and the prevalence of VZV infection is ~100% by 60 years old. [3]  VZV reactivation manifests as a painful rash following a dermatomal distribution. [2]

Herpes zoster ophthalmicus affects the first division of the trigeminal nerve. [2] Adnexal manifestations include vesicular involvement of eyelid margin and follicular conjunctivitis. Predisposing factors for herpes zoster include aging, immunosuppression, trauma, irradiation, surgery, or debilitating systemic disease. [2] 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 in HIV-positive patients is greater than in the non-infected population, and apparently it has 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 for a herpes zoster event. [4]

Kaposi sarcoma

Kaposi sarcoma is a painless mesenchymal-derived vascular tumor that most often affects the skin and mucous membranes. It is caused by human herpesvirus type 8. Kaposi sarcoma occurs in about 25% of patients who are HIV positive. In about 20% of these patients, the eyelids or conjunctiva are affected. [1, 5]

Molluscum contagiosum

Molluscum contagiosum is the most common ocular adnexal manifestation in patients who are HIV positive. It is a highly contagious dermatitis caused by DNA poxviruses, and it may affect mucous membranes as well as skin. [6] Molluscum contagiosum lesions may resemble small keratoacanthoma, cryptococcosis, or basal cell carcinomatoses and can be distinguished by the presence of a central white material consisting of infected cells.

The DNA poxvirus spreads by direct contact with infected persons or by fomites. [6] Viral particles from lid lesions can be shed in tears, causing a toxic keratoconjunctivitis or chronic follicular conjunctivitis.

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.

Conjunctival microvasculopathy

Several conjunctival microvascular changes occur in as many as 70-80% of patients who are HIV positive. 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 contributory. Direct infection of the conjunctival vascular endothelium by HIV has been suggested as a possible cause. [1]


Anterior Segment Manifestations

The anterior segment comprises the cornea, episclera, sclera, anterior chamber, angle, and iris. More than 50% of HIV-positive patients manifest anterior segment complications, including dry eyes (keratoconjunctivitis sicca), corneal infection (keratitis), andiridocyclitis. Common symptoms include irritation, pain, photophobia, and decreased vision. [7]

Keratoconjunctivitis sicca

Dry eyes (keratoconjunctivitis sicca) are seen in about 10-20% of patients who are HIV positive, usually during later stages of the disease. Importantly, HIV-mediated inflammation is believed to result in aqueous tear deficiency via damage to lacrimal and accessory lacrimal glands. [8]

Infectious keratitis (non-herpetic)

Bacterial and fungal keratitides are not more frequent in HIV patients, but these infections tend to be more severe in the immunocompromised host. The most common etiology of fungal keratitis is Candida, 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 filamentous fungi (eg, Fusarium or Aspergillus species) also can be  inoculated following trauma with organic 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. [9]

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. Microsporidia are very difficult to culture, but can be seen readily within corneal or conjunctival epithelial cells with the use of Masson trichrome or Giemsa stain.

The organism can infect the cornea and conjunctiva. [10]  In immunocompetent patients, microsporidiosis may result in a necrotizing stromal keratitis, whereas HIV-positive patients tend to develop epithelial keratitis. [3]

Herpetic keratitis

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 commonly is responsible for oral and ocular infections, whereas HSV-2 is responsible for genital infections. However, cases of HSV-2 causing ocular infections and HSV-1 causing genital infections have been reported. 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. Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are the most common causes of infectious keratitis in HIV-positive patients, and the incidence of herpetic keratitis is higher in HIV-positive patients than in the general US population. Keratitis due to VZV usually is associated with herpes zoster ophthalmicus, with or without the presence of dermatitis. VZV keratitis occurs in fewer than 5% of patients who are HIV positive, but it may cause permanent visual loss. 


Iridocyclitis in patients who are HIV positive can be 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 endophthalmitis. Iridocyclitis also can result from medications used to treat opportunistic infections related to HIV (eg, rifabutin, cidofovir). Iridocyclitis also can manifest as part of autoimmune disease.


Posterior Segment Manifestations

Disorders of the retina, choroid, or optic nerve are seen in more than 50% of patients who are HIV positive and are less likely in patients who are on HAART. [3]

Common presenting complaints include floaters, flashing lights, scotomas or other visual field defects, and decreased visual acuity. Presence of an afferent pupillary defect strongly suggests optic nerve involvement. Diagnoses often are based on clinical evidence seen on funduscopic examinations.

HIV retinopathy

HIV retinal microvasculopathy once occurred in as many as 50-70% of HIV-infected patients. However, it is likely that the increased use of highly active antiretroviral therapy (HAART) has lowered the prevalence of the retinal microvasculopathy. [11]

The exact etiology of HIV-associated microvasculopathy is unclear. Increased erythrocyte aggregation (possibly related to increased fibrinogen levels in HIV-positive patients compared with HIV-negative controls), increased plasma viscosity, immune complex deposition, and decreased erythrocyte deformability may be contributory. [12, 13]

Arteriolar occlusion in HIV retinal microvasculopathy leads to interruption of the axoplasmic flow and the subsequent accumulation of axoplasmic debris, which manifests as cotton-wool spots.

Chorioretinitis secondary to opportunistic infections

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 AIDS. [14]

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 jirovecii.

Cytomegalovirus retinitis

CMV is the most common opportunistic ocular infection in patients with AIDS and is caused by 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, whereas in adolescence and adulthood, it mostly is transmitted through sexual contact or blood transfusion. The seropositive prevalence of CMV is about 50% in adults and 95-100% in homosexuals and patients with AIDS.

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 those with AIDS  and 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 and spreads centrifugally from that focus. 

Acute retinal necrosis

ARN is a fulminant vaso-occlusive necrotizing retinitis secondary to VZV (most commonly), 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 severity of ARN depends on the degree of the patient's immunocompromise, although this disease also can affect immunocompetent patients

The incidence of VZV-associated retinitis after herpes zoster ophthalmicus in patients who are HIV positive is 4-17%; the frequency of retinitis associated with HSV or CMV infection is 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.

Progressive outer retinal necrosis

PORN is a rapidly progressive, necrotizing retinitis that has been reported in patients with advanced AIDS (CD4+< 50/ µL). The most common cause is VZV reactivation, although cases secondary to HSV have been described. The incidence of PORN is much lower than that of ARN.

Although the exact pathophysiologic mechanism for PORN has not been completely elucidated, 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. Some 71% of cases eventually develop bilateral involvement with 67% of affected eyes ultimately developing a visual acuity of no-light-perception. [14]

Non-necrotizing herpetic retinitis

Retinitis associated with herpetic infection, but not following the pattern of retinal necrosis characteristic of ARN and PORN, is categorized as non-necrotizing retinitis. This disease first was described in immunocompetent patients with atypical cases of posterior uveitis resistant to immunosuppression following positive VZV/HSV PCR of aqueous humor samples. [15]  Clinical signs are nonspecific and can include multifocal retinal vasculitis, papillitis and vitritis. To our awareness, no cases have been described in HIV-positive patients. It currently is unknown whether immunocompromise affects the incidence of non-necrotizing retinitis.


Ocular 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.


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. Ocular TB most commonly affects the choroid. Although primary TB infection of the conjunctiva or cornea can occur, intraocular and orbital TB generally are secondary to disseminated infection. [3]

Pneumocystis jirovecii choroidopathy

Infectious choroiditis represents fewer than 1% of ocular disorders in HIV-positive patients, with Pneumocystis jirovecii being the most common identified organism. P jirovecii choroidopathy tends to occur in HIV-positive patients with disseminated infection and presents with scattered placoid lesions with only mild vitritis. This infection is associated with long-term use of aerosolized pentamidine. [16]

Toxoplasma chorioretinitis

Toxoplasmosis is the most common cause of chorioretinitis, 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.

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 chorioretinitis. In HIV-positive cases of toxoplasma chorioretinitis, brain imaging should be considered to rule out concurrent central nervous system involvement.

Histoplasma chorioretinitis

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 patients with AIDS. This disease tends to have a fulminant course, usually complicated by disseminated intravascular coagulation.

Cryptococcal chorioretinitis

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.

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 hematogenously. Most intraocular cryptococcal infections have been seen in association with cryptococcal septicemia with severe meningeal infection in the setting of immunocompromise.

Neuro-ophthalmologic manifestations

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). [17]


Orbital Manifestations

Orbital complications are uncommon in HIV-positive patients. The most common complications include orbital lymphoma and orbital cellulitis due to opportunistic organisms. Cases of orbital cellulitis secondary to Candida albicans, Mycobacterium tuberculosis and Aspergillus have been described. [18]  HIV-associated aspergillosis typically occurs in patients with CD4+ cell counts below 100/µL. Additionally, both HSV and VZV have been reported to affect extraocular muscles and their associated cranial nerves resulting in oculomotor palsy.


Ocular Manifestations in Children

Ocular Manifestations in Children

Children with HIV infection are less likely to have ocular manifestations, including cytomegalovirus (CMV) retinitis. 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.

Children with HIV infection are less likely to have ocular manifestations, including cytomegalovirus (CMV) retinitis. [19]  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 often is associated with neuro-ophthalmic complications.


Ocular Manifestations in Developing Countries

Most HIV-infected individuals are in developing countries, particularly, sub-Saharan Africa and Southeast Asia. [20, 21, 22] The prevalence of CMV retinitis among 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. This increased prevalence may be secondary to increased exposure to causative agents and lack of access to antiretroviral therapy in these countries.


Ocular Toxicity of Antiretroviral Drugs

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. Although mild uveitis may be treatable with topical corticosteroids, severe uveitis and hypotony can cause permanent visual loss. [23]

High-dose didanosine has been associated with retinal pigment epithelial abnormalities. Intravenous ganciclovir and acyclovir have been associated with corneal epithelial inclusions, whereas atovaquone is associated with corneal subepithelial deposits. With the exception of pigment epithelial changes, these adverse effects can resolve following discontinuation of the drug.


Complications of Ocular Manifestations

Adnexal complications

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. [1]

Anterior segment complications

The concurrent presence of encephalopathy in patients with keratoconjunctivitis sicca may cause lagophthalmos and decreased blink rate, increasing the risk for development of neurotrophic keratitis.

Chronic follicular conjunctivitis frequently presents with associated punctate epithelial erosions and/or superficial vascular pannus on the cornea. 

Complications of varicella-zoster virus (VZV) ocular infection include pseudodendritic keratitis (and increased risk for superimposed infectious keratitis), stromal keratitis with subsequent scarring, disciform keratitis, iritis, and trabeculitis with associated intraocular hypertension.

Blepharoconjunctivitis may occur in patients with recurrent ocular HSV infection. Stromal keratitis and uveitis occur in fewer than 10% of patients with primary herpes simplex virus (HSV) infection. 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. In severe cases, retinal detachment may develop.

Posterior segment complications

Complications of CMV retinitis include papillitis, seen in about 5% of these patients, and retinitis. Cystoid macular edema, retinal vascular occlusion, and rhegmatogenous retinal detachment (RRD) may result from CMV retinitis. [24]  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 thought to be secondary to a response to CMV antigens. IRU is generally 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 developing IRU, induction of CMV therapy before initiation of HAART should be considered.

Acute retinal necrosis (ARN) frequently presents with 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. After the resolution of the retinitis, however, traction between the posterior hyaloid  and the resulting gliotic scar of the necrotic retina may occur, leading to retinal tears at the interface between the normal and necrotic retina with subsequent RRD. In as many as 75% of cases, ARN may be complicated by RRD 2-3 months after onset. [25]

Complications of progressive outer retinal necrosis (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.

Posterior segment complications of syphilitic infection may include posterior placoid chorioretinitis, neuroretinitis, vitritis, pigmentary chorioretinopathy, choroiditis, papillitis, choroidal neovascular membranes, and retinal vasculitis. Posterior segment complications of tuberculosis include scleritis, disseminated chorioretinitis, panophthalmitis, and papillitis. These ocular manifestations tend to occur in patients with other extrapulmonary disease.

Pneumocystis jirovecii choroidopathy usually results in minimal vitritis. The major cause of morbidity and/or mortality in patients with P jirovecii infection results from the debilitating pneumonia.

Chorioretinal scarring secondary to posterior segment pathology can result in the formation of choroidal neovascular membranes. Intraocular inflammation can lead to the development of epiretinal membranes. Cases of choroidal neovascularization after Toxoplasma chorioretinitis have been described. [26]  

Disseminated histoplasmosis has a high mortality rate in patients with AIDS. 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 may develop.

The most frequent intraocular sequela of cryptococcal infection is chorioretinitis. With inadequate treatment, endophthalmitis may result. Other reported ocular complications of cryptococcal infection include disc edema, optic atrophy, and ophthalmoplegia.


Clinical Presentation

Herpes zoster ophthalmicus/varicella-zoster virus

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. [27]

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 (resulting in Hutchinson’s sign) increases the likelihood of ocular involvement.

Acute tissue changes may include the following:

·       Eyelids: ptosis, edema, hemorrhagic necrosis

·       Cornea: pseudodendritic keratitis, stromal keratitis, disciform keratitis, neurotrophic keratitis

·       Iris/trabecular meshwork: iritis, iris atrophy, trabeculitis

·       Episclera/sclera: episcleritis/scleritis

·       Retina/choroid: necrotizing or non-necrotizing retinitis, vascular occlusion, choroiditis

Neurologic complications of HZO may include optic neuritis, vasculitis, encephalitis, external ocular muscle palsies, acute neuralgia, and postherpetic neuralgia.

Herpes simplex virus

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 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 epithelial defect 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:

·       Incomplete dermatomal distribution

·       Larger dendrites with central ulceration and terminal bulbs

·       Rare skin scarring

·       Rare postherpetic neuralgia

·       Patchy iris atrophy

·       Rare bilateral involvement

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.

Stromal keratitis occurs as a result of immunologic reaction to viral antigens. It can be subdivided into non-necrotizing (disciform or interstitial keratitis) or necrotizing. Both HSV and VZV can result in stromal keratitis.

Disciform keratitis primarily affects the corneal endothelium and presents with a deep annular lesion with overlying stromal edema. Keratic precipitates and a mild iritis also can occur. Interstitial keratitis presents with single or multiple stromal opacities without significant edema (since the corneal endothelium usually is not affected). Scarring and neovascularization can complicate both disorders.

Necrotizing herpetic keratitis presents and behaves similarly to bacterial or fungal keratitis with painful, progressive suppurative stromal infiltration and overlying epithelial defect. Progressive thinning can occur, with the potential for corneal perforation. Both HSV and VZV can result in this presentation.

Kaposi sarcoma

Kaposi sarcoma usually presents on the eyelid as a painless, violet-brown papule. It may involve the conjunctiva and orbit. Kaposi sarcoma of the conjunctiva usually appears as reddish-blue, vascularized, subconjunctival lesions most frequently seen in the inferior fornix as nodular or diffuse lesions.

Molluscum contagiosum

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 patients who are HIV positive than in patients who are HIV negative. 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.

Fungal keratitis

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.

Microsporidia keratoconjunctivitis

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:

·       Foreign-body sensation, eye pain, or both

·       Light sensitivity

·       Ocular redness

·       Excessive tearing

·       Blurred or decreased vision

HIV-associated retinal microvasculopathy

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:

·       Cotton-wool spots

·       Intraretinal hemorrhages

·       Roth spots

·       Retinal microaneurysms

Cytomegalovirus retinitis

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 lesions tend to be single or multiple 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.

Acute retinal necrosis

Patients with ARN usually present with eye pain associated with decreased visual acuity, floaters, and history of recent HSV or VZV 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 also is involved. Associated anterior uveitis, retinal vasculitis, episcleritis, scleritis, or retinal detachment may be present.

Progressive outer retinal necrosis

Patients with progressive outer retinal necrosis (PORN) usually present with minimal anterior chamber inflammation and minimal vitritis. In general, the lesions in PORN tend to be multifocal, deep in 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:

·       Optic neuritis

·       Active chorioretinitis

·       Retinal vasculitis

·       Conjunctivitis

·       Episcleritis/scleritis

·       Dacryoadenitis

·       Dacryocystitis

·       Interstitial keratitis

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:

·       Iris roseata - reddish spots or engorged vascular tufts that resolve with treatment

·       Iris papulosa - the roseata spots increase in size to resemble a papule

·       Iris nodosa - the area of iris lesion forms a large yellow-red nodule

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 usually is 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 choroidopathy

Pneumocystis jirovecii 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.

Toxoplasma chorioretinitis

Transplacental infection resulting in toxoplasma chorioretinitis occurs 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 chorioretinitis, encephalitis with associated intracerebral calcification, hydrocephalus, and mental retardation.

Ocular manifestation often consists of bilateral chorioretinitis 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. Optic disc swelling, neuroretinitis, mild granulomatous iritis, localized vasculitis, and retinal artery or vein occlusion in the area of the inflammation may be present. In immunosuppressed patients, the inflammatory reaction in the choroid, retina and vitreous tends to be milder than in immunocompetent patients.

Vitreous precipitates on the posterior surface of the detached vitreous may be present. Occasionally, a chorioretinal scar may be seen in the uninvolved eye.

Histoplasma chorioretinitis

The typical triad of ocular histoplasmosis syndrome comprises the following:

·       Yellowish-white, punched-out circular lesions (“histo spots”) scattered in the fundus

·       A macular choroidal neovascular membrane (CNVM), seen as a grayish-green patch underneath the retina

·       One or more areas of atrophy or scarring adjacent to the optic disc

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 gastrointestinal 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 is most commonly 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. Immunodeficient patients may have a negative histoplasmin skin test. The vitreous aspirates obtained during pars plana vitrectomy may be used to isolate the organisms.

Cryptococcal chorioretinitis

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.



Herpes zoster ophthalmicus

The diagnosis of HZO primarily is by history and examination. However, baseline complete blood count, electrolytes, glucose, blood urea nitrogen, and creatinine may be necessary prior to starting antiviral drugs.

Herpetic keratitis

The diagnosis of HSV keratitis primarily is 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. In cases of interstitial keratitis, other etiologies such as syphilis, tuberculosis, and Lyme disease should be ruled out. When managing nectrotizing keratitis, bacterial, fungal, and protozoal etiology should be ruled out. The presence of the typical dermatomal rash and the clinical differentiation of pseudodendrites from dendrites can aid in the differentiation of VZV keratitis from HSV keratitis. However, the two etiologies often are difficult to distinguish when corneal involvement extends beyong the epithelium. Aqueous humor PCR can aid in differentiation of etiology in cases with concurrent iridocyclitis.

Fungal keratitis

History should include contact lenses use, lens-care regimen, previous corneal disease, and topical or systemic steroid use. Deep corneal scrapings or even corneal biopsy for Giemsa, periodic acid-Schiff, or Gomori methenamine-silver staining with culture and sensitivity may be indicated, particularly in cases with persistent ulceration resistant to conventional antimicrobial therapy.


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.

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. [28]

Viral retinitis (acute retinal necrosis, progressive outer retinal necrosis, CMV retinitis)

CD4 count can help in distinguishing the etiology of retinitis: ARN can occur in immunocompetent patients, whereas CMV retinitis and PORN usually are associated with immunosuppression. However, the ultimate diagnosis relies on PCR-based analysis of aqueous or vitreous humor, which offers high diagnostic specificity and sensitivity in the diagnosis of VZV, HSV, or CMV retinitis. Vitreous sampling usually is 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 cases of CMV retinitis, the patient should have a workup for systemic CMV infection that includes testing of urine and serum CMV titers.


Diagnosis of ocular syphilis in patients with HIV follows the same algorithm used for HIV-negative patients and should include 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. [29]  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.


Other causes of granulomatous disease, such as sarcoidosis, syphilis, leprosy, and brucellosis should be ruled out. Quantiferon Gold or purified protein derivative (PPD) skin test can help in identifying previous exposure to tuberculosis. With concurrent HIV, induration of more than 5 mm on PPD testing is considered positive. Positive culture for Mycobacterium tuberculosis is needed to confirm the diagnosis of active tuberculosis and direct treatment.

Pneumocystic jirovecii

Diagnosis of systemic P jirovecii infection relies on induced sputum or bronchioalveolar lavage. Use of aerosolized pentamidine should be noted. Diagnosis of P jirovecii choroiditis relies on the identification of multiple choroidal lesions in the setting of positive sputum studies. Fluorescein angiography can be used to better characterize the choroidal lesions, which show early hypofluorescence and late hyperfluorescence.

Toxoplasma chorioretinitis

In the workup, syphilis, tuberculosis, herpetic retinitis, and toxocariasis should be considered as differential diagnoses. Positive serology for toxoplasma IgG and IgM, as well as aqueous humor PCR can be used to diagnose this condition.

Although the presence of a characteristic chorioretinal scar can aid in diagnosis, pre-existing scars may be absent. Fluorescein angiogram or OCT-angiogram may be helpful when a choroidal neovascular membrane is suspected. Head imaging is essential to rule out CNS involvement in the immunocompromised patient.

Histoplasma chorioretinitis

In the workup, consider toxoplasmosis and multifocal choroiditis with panuveitis as differential diagnoses. Inquiring about possible time spent in the Ohio-Mississippi River Valley area is important. The Amsler grid should be used to assess the central visual field for each eye. Fluorescein angiography or OCT-A may be used to detect a choroidal neovascular membrane.

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

Neuro-ophthalmologic disease

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.


Treatment & Management

Herpes zoster ophthalmicus

Recommended treatment for herpes zoster ophthalmicus (HZO) in the setting of systemic immunocompromise is intravenous acyclovir 10 mg/kg 3 times per day for 7 days, followed by oral acyclovir [1] 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 the onset of the vesicular lesions.

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 can be considered as alternative therapeutic options. However, use of valacyclovir has been associated with increased risk for thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome in the setting of concurrent HIV infection. If HZO is unresponsive to acyclovir, famciclovir, or valacyclovir, intravenous foscarnet should be considered. 

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.

Topical capsaicin, oral amitriptyline or gabapentin may be useful in reducing the symptoms of postherpetic neuralgia.

Herpetic keratitis

Treatment of HSV/VZV keratitis in the setting of concurrent HIV has not been established. Treatment strategies depend on the extent of ocular involvement and follow the conclusions of the Herpetic Eye Disease Studies, which investigated the management of herpetic eye involvement in the immunocompetent host.  

Kaposi sarcoma

Radiation therapy is effective for eyelid and conjunctival Kaposi sarcoma. [1]  Adverse effects of radiation therapy include loss of lashes, skin irritation, and conjunctivitis. Local cryotherapy of eyelid and conjunctival lesions may be performed. [30]

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. [31]

Molluscum contagiosum

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. As cell mediated immunity is restored with HAART, therapy initiation can worsen the ocular surface inflammatory response to viral particles shed from molluscum lesions affecting the eyelids. Lesion removal therefore should be considered before or during HAART initiation. [3]

Fungal keratitis

Initially, corneal infiltrates and ulcers usually are treated as bacterial infections until the results of cultures and/or staining are obtained. If cultures indicate fungal keratitis, then treatment with topical natamycin 5% (50 mg/mL) and cycloplegic agent should be initiated

For deep stromal infection, combination medication should be considered; options include topical amphotericin B, topical fumagillin, miconazole or clotrimazole and/or oral fluconazoleitraconazole, 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.

Cytomegalovirus retinitis

Specific agents and modalities for the treatment of CMV retinitis include the following:

·       Oral valganciclovir

·       Oral, intravenous, and intravitreal ganciclovir

·       Intravenous and intravitreal foscarnet or combined intravenous ganciclovir and foscarnet

·       Intravenous and intravitreal cidofovir

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.

Ganciclovir induction dosage is 5 mg/kg IV every 12 hours for 14 days. This usually is followed by a maintenance IV dose of 5 mg/kg/day for 7 days. Dosage should be adjusted for renal impairment. The significant adverse effect of ganciclovir therapy is myelosuppression. CBC with differential should be monitored 2-3 times a week during the 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, ganciclovir treatment should be discontinued

To prevent immunosuppression, he zidovudine dosage may need to be reduced during treatment of CMV retinitis with ganciclovir, unless hematopoietic growth factors (eg, regramostim, filgrastim) are used concurrently.

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.

Foscarnet induction dosage is 60 mg/kg IV every 8 hours for 14 days, followed by a maintenance IV dose of 90-120 mg/kg/day. Foscarnet can result in renal toxicity. 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.

Cidofovir induction dosage is 5 mg/kg IV over 1 hour once weekly for 2 weeks, followed by maintenance dose of 5 mg/kg over 1 hour once every other week. This drug also is nephrotoxic. Concurrent use of probenecid with cidofovir reduces the risk for renal toxicity. Other adverse effects of cidofovir include iritis and ocular hypotony. It also is a major risk factor for immune recovery uveitis (IRU) among patients with CMV retinitis who are receiving HAART. [32]

Immune recovery uveitis

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 typically is 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. [32, 33, 34]  

Acute retinal necrosis and progressive outer retinal necrosis

Severe manifestations of herpetic disease require hospitalization for IV antiviral therapy. Acyclovir 5-10 mg/kg/day IV is given in 3 divided doses for 1 week, followed by oral acyclovir 800 mg 5 times daily for the following 1-2 months. Kidney function should be monitored while on antiviral therapy, with appropriate dose adjustment. Supplementary intravitreal foscarnet or ganciclovir once to twice weekly should be considered.

Systemic steroids may be considered following initiation of appropriate antiviral therapy and regression of retinitis. Prednisone, 60-80 mg orally daily for 1-2 weeks followed by a taper over 2-6 weeks has been used. However, the therapeutic role of systemic steroid therapy in the immunocompromised host has not been well-established and may place the patient at further risk for HIV-related complications. Prior to steroid initiation, tuberculosis and syphilis should be ruled out.

Topical steroids and cycloplegic agents can be used in case of severe anterior chamber reaction.

Use of retinal laser photocoagulation to surround the necrotic lesion is controversial. For retinal detachment, vitrectomy, membranectomy, endolaser, and silicone oil infusion usually are required.


All HIV-positive patients with syphilitic eye findings are considered to have neurosyphilis and are treated accordingly. Treatment of syphilis is with intravenous penicillin G (24 million U/day for 7-10 days). Relapse may occur despite 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), although penicillin desensitization should be considered.

Cycloplegia and topical steroid therapy are 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,  INH and rifampin should be continued for an additional 7 months. Drug resistance is most common with streptomycin and INH; however, this may be minimized using multiple bactericidal antituberculous drugs. For patients with pulmonary cavitary lesions, respiratory culture can help detect resistant strains.

Pyridoxine 25 mg orally daily usually is added to the regimen to prevent peripheral neuritis.

Toxoplasma chorioretinitis

Although small, peripheral chorioretinal lesions can be monitored in the immunocompetent patient, immunocompromised hosts with active lesions should be treated regardless of disease extent.

For active chorioretinitis within 2-3 mm of the disc or fovea, which threatens vision, or peripheral lesion associated with severe vitritis, therapy  is continued for 3-6 weeks. First-line regimen is 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 alone (if the patient is allergic to sulfa drugs) or in combination with sulfadiazine as alternative treatment. Patients on clindamycin should be monitored for the possible adverse effect of pseudomembranous colitis. Other alternative therapeutic regimens include 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, 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.

Histoplasma chorioretinitis

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.

Cryptococcal chorioretinitis

Early diagnosis and treatment of cryptococcal chorioretinitis are 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.

Other disorders

Topical fumagillin has been used successfully to treat keratoconjunctivitis secondary to microsporidiosis. [35, 36]

Pneumocystis jirovecii 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).


Questions & Answers


What is the prevalence of ocular manifestations of HIV infection?

What is the role of CD4+ T-cell counts in predicting ocular complications of HIV infection?

What are the common ocular adnexal lesions of HIV infection?

What is herpes zoster ophthalmicus (HZO) in HIV infection?

What is the role of Kaposi sarcoma in the ocular manifestations of HIV infection?

What is the role of molluscum contagiosum in the ocular manifestations of HIV infection?

What is the role of conjunctival microvasculopathy in HIV infection?

What is the prevalence of anterior segment ocular complications of HIV infection?

What is the prevalence of keratoconjunctivitis sicca in HIV infection?

What is the role of infectious keratitis in the ocular manifestations of HIV infection?

What is the role of herpes simplex virus keratitis in the ocular manifestations of HIV infection?

What is the role of fungal keratitis in the ocular manifestations of HIV infection?

What is the role of microsporidiosis in the ocular manifestations of HIV infection?

What is the role of iridocyclitis in the ocular manifestations of HIV infection?

What is the prevalence of posterior segment ocular complications of HIV infection?

What are the signs and symptoms of posterior segment ocular manifestations in HIV infection?

What is HIV retinopathy?

What is HIV-related retinochoroiditis?

What is the role of cytomegalovirus (CMV) in the ocular manifestations of HIV infection?

What is the role of acute retinal necrosis in the ocular manifestations of HIV infection?

What is the role of progressive outer retinal necrosis in the ocular manifestations of HIV infection?

What is ophthalmic syphilis in HIV infection?

What is the role of tuberculosis in the ocular manifestations of HIV infection?

What is the role of pneumocystis jiroveci choroidopathy in the ocular manifestations of HIV infection?

What is the role of toxoplasma retinochoroiditis in the ocular manifestations of HIV infection?

What is the role of histoplasma chorioretinitis in the ocular manifestations of HIV infection?

What is the role of cryptococcal infection in the ocular manifestations of HIV infection?

What causes the neuro-ophthalmologic complications of HIV infection?

What are most common orbital complications in HIV infection?

What is the prevalence of ocular complications in children with HIV infection?

Which ocular manifestations of HIV infection are most prevalent in developing countries?

What is the role of antiviral drug toxicity in the etiology of ocular complications of HIV infection?

What are the processes of ocular manifestations in HIV infection?

Which ocular manifestations of HIV infection cause inflammation?

Which ocular manifestations of HIV infection cause nerve damage?

Which ocular manifestations of HIV infection cause scarring?

What are the anterior segment ocular manifestations of HIV infection?

What are the posterior segment ocular manifestations in HIV infection?

Which clinical history findings are characteristic of herpes zoster ophthalmicus in HIV infection?

What are the signs and symptoms of herpes zoster ophthalmicus in HIV infection?

What are the possible neurologic complications of herpes zoster ophthalmicus in HIV infection?

Which clinical history findings are characteristic of ocular Kaposi sarcoma in HIV infection?

Which clinical history findings are characteristic of molluscum contagiosum in HIV infection?

Which clinical history findings are characteristic of varicella-zoster virus keratitis in HIV infection?

What are the signs and symptoms of varicella-zoster virus (VZV) infection in HIV infection?

Which clinical history findings are characteristic of herpes simplex virus (HSV) keratitis in HIV infection?

What are the signs and symptoms of herpes simplex virus (HSV) infection in HIV infection?

What is the basis for a diagnosis of herpes simplex virus (HSV) in HIV infection?

Which clinical history findings are characteristic of fungal keratitis in HIV infection?

Which clinical history findings are characteristic of microsporidia keratoconjunctivitis in HIV infection?

Which clinical history findings are characteristic of HIV-associated retinal microvasculopathy?

Which clinical history findings are characteristic of cytomegalovirus retinitis in HIV infection?

Which clinical history findings are characteristic of acute retinal necrosis in HIV infection?

Which clinical history findings are characteristic of progressive outer retinal necrosis in HIV infection?

Which clinical history findings are characteristic of ophthalmic syphilis in HIV infection?

What are the signs and symptoms of ophthalmic syphilis in HIV infection?

Which clinical history findings are characteristic of ocular tuberculosis in HIV infection?

Which clinical history findings are characteristic of pneumocystis choroidopathy in HIV infection?

Which clinical history findings are characteristic of toxoplasma retinochoroiditis in HIV infection?

Which clinical history findings are characteristic of ocular histoplasma chorioretinitis in HIV infection?

Which clinical history findings are characteristic of cryptococcal chorioretinitis in HIV infection?

How is herpes simplex keratitis in HIV infection diagnosed?

How is herpes zoster ophthalmicus (HZO) in HIV infection diagnosed?

How is fungal keratitis in HIV infection diagnosed?

How is microsporidiosis in HIV infection diagnosed?

How is HIV retinopathy diagnosed?

How is cytomegalovirus (CMV) retinitis in HIV infection diagnosed?

How is acute retinal necrosis and progressive outer retinal necrosis in HIV infection diagnosed?

How is ophthalmic syphilis in HIV infection diagnosed?

How is ocular tuberculosis in HIV infection diagnosed?

How is pneumocystic jiroveci in HIV infection diagnosed?

How is toxoplasma retinochoroiditis in HIV infection diagnosed?

How is histoplasma chorioretinitis in HIV infection diagnosed?

How is cryptococcal chorioretinitis in HIV infection diagnosed?

How is neuro-ophthalmologic disease in HIV infection diagnosed?

How is herpes zoster ophthalmicus (HZO) in HIV infection treated?

How is ocular Kaposi sarcoma in HIV infection treated?

How is molluscum contagiosum in HIV infection treated?

How is varicella-zoster virus (VZV) keratitis in HIV infection treated?

How is fungal keratitis in HIV infection treated?

How is iridocyclitis in HIV infection treated?

How is cytomegalovirus (CMV) retinitis in HIV infection treated?

How is immune recovery uveitis in HIV infection treated?

How is acute retinal necrosis and progressive outer retinal necrosis in HIV infection treated?

How is ophthalmic syphilis in HIV infection treated?

How is ocular tuberculosis in HIV infection treated?

How is toxoplasma retinochoroiditis in HIV infection treated?

How is histoplasma chorioretinitis in HIV infection treated?

How is cryptococcal chorioretinitis in HIV infection treated?

How is keratoconjunctivitis in HIV infection treated?

How is Pneumocystis jiroveci ocular infection in HIV infection treated?

How are HIV retinopathy and conjunctival microvasculopathy in HIV infection treated?

How is keratoconjunctivitis sicca in HIV infection treated?

How are the neuro-ophthalmologic manifestations of HIV infection treated?

How is progressive multifocal leukoencephalopathy (PML) in HIV infection treated?