1. Ocular manifestation of HIV
Getachew. K
December, 201917/12/2019 1

2. Introduction
• Human Immunodeficiency Virus (HIV) is a retrovirus which causes a
multisystemic disease called Acquired Immune Deficiency Syndrome
(AIDS).
• The first reported case of HIV was in Los Angeles in 1981. Ocular
manifestations commonly are seen in HIV patients, and the first
description of the same was made by Maclean more than 20 years ago.
• Ocular involvement in HIV could be caused by opportunistic
infections, vascular abnormalities, neoplasms, neuro-ophthalmic
conditions, and adverse effects of medications.
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3. History
• The identification in 1981 of a cluster of gay men with unusual clinical manifestations later ascribed to
infection with human immunodeficiency virus-I (HIV-I) was followed within a year by publication of
typical ocular manifestations: cotton wool spots, cytomegalovirus, periphlebitis, and conjunctival
Kaposi sarcoma.
• The acquired cellular immunodeficiency syndrome, rapidly became the world-wide focus of numerous
surveys of eye disease, randomized clinical trials, and case series detailing optimal management of the
ocular complications of AIDS.
• After 1996 ocular manifestations were modified by the improved immune status achieved by many
patients who were treated with highly active anti-retroviral therapy (HAART)
• The earliest retrospectively described case of AIDS is believed to have been in Norway beginning in
1966.
• In the beginning, the CDC did not have an official name for the disease, often referring to it by way of
the diseases that were associated with it, for example, lymphadenopathy, the disease after which the
discoverers of HIV originally named the virus.
• They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had
been set up in 1981.
• In the general press, the term GRID, which stood for gay-related immune deficiency, had been
coined. The CDC, in search of a name, and looking at the infected communities coined "the 4H
disease", as it seemed to single out homosexuals, heroin users, hemophiliacs, and Haitians. However,
after determining that AIDS was not isolated to the gay community, it was realized that the term GRID
was misleading and AIDS was introduced at a meeting in July 1982.By September 1982 the CDC
started using the name AIDS.(Wikipedia)
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4. Etiology
• HIV is a retrovirus which replicates in CD4 T lymphocytes.
Transmission occurs by exposure to blood and other body fluids.
• The natural history of an untreated HIV-infected person can be divided
into three stages, namely, stages of primary infection, clinical latency,
and, finally, opportunistic infections called AIDS.
• The Centers for Disease Control and Prevention (CDC) defines AIDS
as being present when there is an AIDS-defining disease or a CD4 T-
cell count less than 200 microliters.
• Some studies suggest that an HIV test should be requested if there is
atypical, bilateral, treatment-unresponsive ocular toxoplasmosis or
suspicion of cytomegalovirus (CMV) retinitis.
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5. Pathophysiology
• Ocular involvement in HIV infection occurs most commonly due to
opportunistic infections and neoplasms. But also can be due to drug related
and direct infections.
• Opportunistic infections like CMV retinitis occur with a significantly
reduced CD4 T-cell count and are one of the common causes of blindness in
HIV patients.
• Unlike other diseases, ocular infection in these immunosuppressed patients
is associated with minimal inflammatory signs.
• HIV has been isolated from tears, cornea, vitreous, and chorioretinal tissue
in affected persons.
• The ocular structures affected by HIV include the adnexa, anterior segment,
posterior segment, and orbit.
• Neuro ophthalmological manifestations also may be seen.
• The institution of highly active antiretroviral therapy (HAART) has caused
a dramatic improvement in the immune status of HIV-infected individuals
and a change in the clinical presentation and course of opportunistic
infections.17/12/2019 5

6. Ocular manifestation of HIV
• Adnexal involvement in HIV-infected persons may include herpes
zoster ophthalmicus (HZO), Kaposi sarcoma, molluscum
contagiosum, and conjunctival microvasculopathy.
• Anterior segment involvement in HIV includes keratoconjunctivitis
sicca, keratitis, and iridocyclitis.
• Posterior segment involvement in HIV is quite common and can cause
visual loss. They include Retinal microangiopathy, CMV retinitis,
VZV retinitis, toxoplasma retinchoroiditis, and bacterial and fungal
retinitis.
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7. Manifestations of HIV Infection in the Ocular
Adnexa include:
• Herpes zoster ophthalmicus
• Kaposi's sarcoma
• Molluscum contagiosum
• Squamous cell carcinoma/intraepithelial neoplasia of
conjunctiva
• Cutaneous lymphoma
• Trichomegaly/Hypertrichosis
• Conjunctival microvasculopathy
• Preseptal cellulitis
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8. HZO
• Also Called varicella Zoster or shingles.
• Caused by human herpes virus 3 the same virus that causes varicella
(chicken pox) in children.
• It is seen in 5% to 15% of HIV patients and may be associated with a
simultaneous occurrence of keratitis, scleritis, uveitis, retinitis, or
encephalitis.
• Reactivation of latent infection in the sensory trigeminal ganglia causes
vesiculo-bullous dermatitis involving the ophthalmic distribution of the
trigeminal nerve.
• Ophthalmic divisions of trigeminal nerve is affected >20x more than other
divisions of the 5th CN.
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9. Cont… HZO
• OHZ in someone younger than 50 years of age is uncommon, and
should raise the suspicion of systemic immunosuppression due to
malignancy, pharmacologic immunosuppression, or HIV infection.
• OHZ typically occurs at CD4+ T-lymphocyte counts of less than 200
cells/μL, and is considered disseminated if it involves multiple
dermatomes or unrelated organ systems.
• It manifests with a maculo-papulo-vesicular rash which often is
preceded by pain.
• Usually involves a single dermatome and does not cross the midline
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10. HZO
• Involvement of the lateral nasal wall skin up to the tip of the nose in the
HZO dermatitis indicates that the nasociliary branch of ophthalmic
division of trigeminal nerve is affected.
• Papules/Vesicles seen at the tip of the nose in OHZ involving
nasociliary nerve is called “Hutchinson's” sign
• This nerve gives sensory innervation to the intraocular structures
(cornea, iris.) Because of this, OHZ involving nasociliary branch can
have associated intraocular inflammation and vision loss.
• In these patients keratitis, scleritis, uveitis, retinitis, or central nervous
system involvement may develop.
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11. Treatment
• Acyclovir 800mg po 5x/day for 7-10 days.
• If Acyclovir is given with in 72 hours of the onset of dermatitis, it can
reduce pain and prevent the onset of severe ocular complications.
• Alternative drug is Famicyclovir 500mg po 5x/day for 7-10 days
• Topical steroids are useful in the management of sclerokeratitis,
keratouveitis, interstitial keratitis, anterior corneal stromal infiltrates,
and disciform keratitis.
• Topical cycloplegic drugs (Atropine or cyclopentolate) prevent ciliary
spasm associated with OHZ inflammation.
• Herpes zoster retinitis, optic neuritis, chorioreti-nitis…are best treated
with a combination of systemic steroids and acyclovir i.v.
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12. Kaposi sarcoma
• highly-vascularized, mesenchymal tumor and may present as painless,
violaceous lesions on the eyelid skin or conjunctivamicroangiopathy.
• Occurs in up to 25% of HIV-infected patients, and it is often the
presenting sign of disease.
• A member of the herpes virus family, human herpes virus-8 (HHV-8),
is associated in the pathogenesis of Kaposi's sarcoma.
• Kaposi's sarcoma involving the ocular adnexa will develop in
approximately 5% of patients infected with HIV.
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13. Kaposi's sarcoma
• Both the eyelids and the conjunctiva may be involved.
• Conjunctival lesions are most commonly found in the inferior fornix, but
may occur on any aspect of the palpebral or bulbar conjunctiva.
• Conjunctival Kaposi's sarcoma is often mistaken for benign
subconjunctival hemorrhage.
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14. Treatment of Kaposi's sarcoma
• Radiation therapy is effective in treating eyelid and conjunctival
Kaposi's sarcoma, but it can be associated with loss of lashes, skin
irritation, and a mild conjunctivitis.
• Alternatively, lesions of the eyelid may be treated by cryotherapy or
intralesional chemotherapy.
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15. Molluscum contagiosum
• A highly contagious papulonodular dermatitis caused by a poxvirus.
• Both the skin and mucous membranes may be affected, typically with multiple,
small, umbilicated lesions.
• characterized by multiple, small (1-3 mm in size ) with a central depression,
painless umbilicated lesions on the eyelid skin.. The lesions are more likely to be
numerous and bilateral in HIV infection but patients may be asymptomatic unless
the eyelid margin is involved.
• Crusted, painful vesicles suggest herpetic infection.
• Seventy percent to 80% of HIV patients may present with conjunctival
microvasculopathy, characterized by segmental dilatation and narrowing of blood
vessels, comma-shaped vascular segments, and sludging of blood column.
• The cause is thought to be either immune complex deposition, increased plasma
viscosity or invasion of vascular endothelium by HIV and is found to correlate
with retinal.
• Treatment options include cryotherapy, incision and curettage or excision.
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16. Trichomegally
• Acquired trichomegaly, or hypertrichosis of the eyelashes, typically
occurs in the late stages of HIV infection.
• The cause is unknown, although elevated viral titers, drug toxicity, and
poor nutrition have been implicated as contributing factors.
• Excessively long lashes may be trimmed, as needed, if they interfere
with the use of eyeglasses or if the patient finds them cosmetically
unacceptable.
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17. CONJUNCTIVAL MICROVASCULOPATHY
• Most HIV-infected patients will eventually develop conjunctival
microvascular changes which includes:
• Segmental vascular dilatation and narrowing,
• Microaneurysm formation,
• The appearance of comma-shaped vascular fragments, and a visible
granularity to the flowing blood-column, termed “sludging.”
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18. CONJUNCTIVAL MICROVASCULOPATHY
• These changes are usually most evident near the limbus inferiorly, and
are highly correlated with the occurrence of retinal microvasculopathy.
• The reason is unknown but suggested theories included:
• HIV-induced increase in plasma viscosity,
• HIV-related immune complex deposition,
• And direct infection of the conjunctival vascular endothelium by HIV.
• No treatment is indicated.
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19. Manifestations of HIV Infection in the Anterior
Segment of the eye include:
• Keratoconjunctivitis sicca
• Infectious keratitis
• Viral keratitis—herpes zoster virus, herpes simplex virus
• Bacterial and fungal keratitis
• Microsporidial keratitis
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20. • Keratoconjunctivitis sicca, or dry eyes, are seen in approximately 20% of HIV patients
and are thought to be an HIV-mediated inflammatory destruction of lacrimal glands.
• Keratitis in HIV is rare, seen in less than 5% of cases, but can lead to loss of vision.
• Herpes simplex virus and varicella-zoster virus are the most common causes. They
may be recurrent and resistant to treatment.
• Microsporidia are protozoa which can cause a punctuate epithelial keratopathy.
Bacterial and fungal keratitis also may be seen.
• Iridocyclitis is fairly common in HIV; mild iridocyclitis may be seen in association with
VZV or CMV retinitis and severe iridocyclitis in association with toxoplasmosis,
syphilis, tuberculosis, and bacterial or fungal retinitis.
• Medications, like Rifabutin and Cidofovir, prescribed for HIV patients also may cause
iridocyclitis.
• Clinical examination in cases of iridocyclitis may reveal KPs, cells in AC, patches of
iris necrosis, posterior synechiae, and hypopyon.
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21. KERATOCONJUNCTIVITIS SICCA
• Keratoconjunctivitis sicca, or dry eye, occurs in 10% to 20% of HIV-infected
patients, typically at late stages of their illness.
• Patients complain of irritation and burning uncomfortable red eyes
• Abnormal Schirmer's testing and interpalpebral rose bengal staining are
invariably present.
• It is most probably related to combined effects of HIV-mediated inflammation
and destruction of the lacrimal and salivary glands and direct HIV infection of
the conjunctiva.
• Concurrent exposure due to lagophthalmos and decreased blink rate can worsen
the keratopathy.
• Treatment consists of artificial tear supplement and long-acting lubricating
ointments, which are applied at bedtime.
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22. VIRAL KERATITIS
• Herpes zoster ophthalmicus is often associated with either a dendritic
epithelial or disciform stromal keratitis in HIV-infected patients.
• However, also occur with transient or no skin lesions, a condition
termed herpes zoster sine herpete and reported to occur rarely in HIV-
positive persons.
• Decreased corneal sensation and elevated intraocular pressure are
clues to the diagnosis. Treatment is similar to that for herpes zoster
ophthalmicus, as discussed earlier.
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23. BACTERIAL AND FUNGAL KERATITIS
• Bacterial keratitis and fungal keratitis do not appear to be more
common in HIV-positive persons, but when they do occur, they tend to
be more severe and have a higher tendency toward perforation.
• Various reported organisms have included α-hemolytic streptococci,
Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas
aeruginosa,
• Treatment should be aggressive, with intensive use of fortified topical
antibiotics.
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24. Fungal and bacterial keratitis respectively
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25. MICROSPORIDIAL KERATITIS
• Microsporidia are obligate intracellular parasites known to cause
gastroenteritis, sinusitis, pneumonitis, and urogenital infections in
HIV-infected patients.
• In these patients, ocular infection with microsporidia is uncommon,
but when present typically produces a punctate epithelial keratopathy
with a mild papillary conjunctivitis.
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26. MICROSPORIDIAL KERATITIS
• Microsporidia are extremely difficult to culture, but can be readily
seen within Geimsa-stained corneal or conjunctival epithelial cells.
• Treatment options include oral itraconazole, topical propamidine,
topical fumagillin, and oral albendazole.
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27. Posterior segment manifestations of HIV Infection
• Retinal microvasculopathy
• HIV retinopathy
• Cytomegalovirus retinitis
• Varicella-zoster virus retinitis
• Toxoplasmosis retinochoroiditis
• Bacterial and fungal retinitis
• Other Infectious Retino-choroiditis (syphilis, TBC…)
• Intraocular lymphoma
• Patients may complain of floaters, flashes of light, decreased visual acuity or visual
field defects.
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28. RETINAL MICROVASCULOPATHY
• Retinal microvasculopathy occurs in Retinal microangiopathy is the most
common ophthalmic manifestation of HIV (more than 50% of HIV-infected
patients.)
• Associated with low CD4 T-cell counts. It is characterized by the presence
of cotton wool spots, retinal hemorrhages, and microaneurysms.
• The pathogenesis is thought to be similar to that of conjunctival
microvasculopathy.
• All forms of retinal microvasculopathy increase in frequency in more
advanced stages of HIV infection.
• They can be distinguished from infectious retinitis by a size less than 500
microns, a feathered edge, and transience, with fading over 6 to 8 weeks
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29. HIV retinopathy
• 50-70 % of HIV patients.
• Arteriolar occlusion in HIV retinal micro vascularity leads to interruption
of the axoplasmic flow and the subsequent accumulation of axoplasmic
debris, which manifests as cotton wool spots
• Increased plasma viscosity, immune –complex deposition, and a direct
cytopathic effect of the virus on the retinal vascular endothelium are
believed to be involved.
• Asymptomatic and transient but it may contribute to the optic nerve
atrophy seen in many of patients.
• common findings include cotton wool spots, intraretinal haemorrhages ,
roth spots(white centred haemorrhages ,retinal micro aneurysms
• No treatment is indicated, but only observation.
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30. CMV retinitis
• Affects nearly 30% to 40% of HIV-infected individuals and is usually seen
with CD4 counts less than 100/microliters.
• Fundus examination reveals full thickness intraretinal opacification
associated with retinal hemorrhages.
• There is minimal AC reaction, and the vitreous is generally clear.
• Loss of vision can occur due to the direct involvement of macula or optic
nerve, retinal detachment, and immune recovery uveitis.
• Widespread use of HAART has caused a change in the natural history of
CMV retinitis, leading to marked reduction in the incidence of this
condition and clinical findings not seen in classical CMV retinitis like AC
and vitreous inflammation.
• Before the era of HAAR, CMV retinitis affected up to 40% of HIV-infected
patients.
• CMV retinitis typically occurs at CD4+ T-lymphocyte counts of less than 50
cells/mm3, and almost always at counts less than 100 cells/mm3.
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31. Toxoplasmosis Retinochoroiditis
• Ocular toxoplasmosis affects less than 1% of HIV-infected patients.
• Toxoplasmosis retinochoroiditis in HIV-positive patients is usually
distinguished by
• The occurrence of a moderate to severe anterior chamber and vitreous
inflammation,
• A relative lack of retinal hemorrhage, and
• The presence of a smooth rather than granular leading edge
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32. Toxoplasma retinochoroiditis
• usually bilateral and multifocal and may be associated with central
nervous system (CNS) involvement.
 Pyrimethamine and Sulfadiazine combination plus folinic acid
 Cotrimoxazole, Clindamycin alternative drugs as effective as
pyrimethamine/sulfadiazine for lesions outside fovea.
 At least 6 weeks treatment needed
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33. Toxoplasma retinochoroiditis Recurrence over an old scar
Old scar
(pigmented)
Active
recurrent
lesion(white)
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34. Orbital and Neuro-Ophthalmic
Manifestations of HIV infection
Orbital Neuro-ophthalmic
Orbital lymphoma Papilledema
Orbital cellulitis Optic neuritis
Orbital Kaposi's sarcoma Optic atrophy
Cranial nerve palsies
Ocular Motility disorders
Visual field defects
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35. The Impact of HAART on Ophthalmic manifestations
• HAART has changed the face of HIV /AIDS by leading to dramatic
decreases in HIV-related morbidity and mortality.
• Since the introduction of HAART, the incidence of ocular opportunistic
infections causing retinitis such as cytomegalovirus (CMV), varicella
zoster virus (VZV), tuberculosis, and toxoplasmosis, has dramatically
decreased.
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36. Ocular toxicities
• may develop in patients receiving medications for HIV or opportunistic
infections.
• These include uveitis with Cidofovir and Rifabutin,
retinal pigment epithelial abnormalities with high dose
Didanosine,
corneal epithelial inclusions with intravenous Cidofovir or
Acyclovir, and
corneal subepithelial deposits with Atovaquone.
• Patients with CMV retinitis on HAART may suffer from a condition called
immune recovery uveitis which causes diminution of vision and is
characterized by cataract, vitritis, macular edema, optic disc edema, and
epiretinal membrane.
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37. Immune Recovery Uveitis/IRU/
• Since the advent of HAART, immune recovery uveitis (IRU) has
become an ocular manifestation described in patients with inactive
CMV retinitis from prior lesion.
• It has become a major visually-threatening condition and occurs in
10% of patients with inactive CMV retinitis and on HAART.
• It is believed to be a result of the restored immune system to mount an
exuberant inflammatory response.
• Immune reconstitution syndrome can cause posterior segment
inflammation in a patient with prior inactive CMV retinitis and can
lead to visual morbidity in patients with AIDs.
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