HIV and the eye
In an area of high HIV prevalence, HIV-related ocular lesions are relatively common.
L Visser, MB ChB, MMed (Ophth), FCS (Ophth) SA
Head, Department of
Ophthalmology, University of KwaZulu-Natal, Durban, South
Africa
Correspondence to: L Visser
(visser@ukzn.ac.za)
It is estimated that there are 5.6 million people in South Africa living with the human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS).1 A relatively small percentage of them are on highly active antiretroviral therapy (HAART) although numbers are steadily increasing. As their CD4 cell counts decrease, these people will become more likely to develop certain opportunistic infections, immune-related diseases and tumours. A large number (70 - 75%) of them will develop ocular disease sometime during the course of their illness and it may be the first sign of HIV infection.
Ophthalmic manifestations are usually due to
underlying microvasculopathy, opportunistic infections,
neoplasms or autoimmune/hyperallergic reactions. For ease of
discussion these will be classified according to clinical
presentation into external eye (orbital and adnexal) disease,
anterior segment, posterior segment and neuro-ophthalmic
manifestations. Only the entities that are more commonly seen
will be discussed.
External eye (orbital and adnexal) manifestations
External eye manifestations are quite common
and range from the innocuous trichomegaly (long eye lashes) to
proptosis caused by orbital cellulitis or lymphoma
(life-threatening if not managed appropriately).
Allergic conjunctivitis
When a patient with no previous history of ocular allergies presents with new-onset allergic conjunctivitis after the age of 18 years, underlying HIV disease should be excluded, especially if this patient falls within the high-risk groups for HIV. The appearance is similar to vernal conjunctivitis (Fig. 1) and patients usually respond to treatment with weak steroid drops (such as fluoromethalone).
Keratoconjunctivitis sicca (dry eyes)
Dry eyes can be due to the auto-immune
destruction of lacrimal gland tissue, or secondary to lid
infections or Stevens-Johnson syndrome. Artificial tear
supplementation is often necessary.
Blepharitis
Recurrent lid infections are common and often
associated with dry eyes and recurrent Meibomian cysts or styes.
Lid hygiene is important and topical antibiotic ointment is
often indicated.
Trichomegaly/hypertrichosis
Exaggerated eyelash growth is sometimes seen
quite late in the course of the disease. The exact cause is not
known but an autoimmune response is suspected.
Molluscum contagiosum
Molluscum contagiosum virus infection presents as small, elevated, umbilicated lesions of the eyelid. These are often multiple and bilateral in AIDS patients. It is a DNA virus of the pox virus family. Treatment could include:
• surgical excision
• curettage
• cryotherapy
• liquid nitrogen
• topical phenol or
trichloroacetic acid.
Immune reconstitution with HAART will also result in resolution of the lesions, but this may take up to 6 months.2
Kaposi’s sarcoma of the lid or conjunctiva
Almost 30% of AIDS patients develop Kaposi’s sarcoma (KS). Oculocutaneous KS may precede, follow or develop concurrently with the visceral form and may involve the eyelid skin, conjunctiva, plica semilunaris, caruncle, lacrimal sac and rarely the lacrimal gland and orbit. They are more malignant when associated with HIV and can disseminate. They present as red/purple subepidermal/subepithelial nodules, which can be flat to elevated (Fig. 2).
Indications for treatment of ocular disease include loss of eyelid function, cosmesis and discomfort. The type of treatment depends on the size and location of the tumour and includes:
• local treatment:
• radiotherapy
• cryotherapy or laser therapy
• surgical excision
• intralesional chemotherapy (vinblast-in) and subconjunctival interferon-α-2a
• systemic treatment (usually for non-ocular disease):
• combination chemotherapy (adria-mycin, vinblastine, bleomycin, dacti-nomycin, vincristine, dacarbazine)
• immunotherapy (interferon-alpha).2
Fig. 2. Kaposi’s sarcoma of the left upper lid (photo courtesy of Dr E Siolo).
Proptosis (orbital cellulitis or lymphoma)
This is fortunately rare and usually a result of infection, inflammation or neoplasms arising from the paranasal sinuses and spreading to the orbit, but on occasion the orbital tissues may be primarily involved in lymphoma.
Anterior segment manifestations
Anterior segment manifestations are also
common and include potentially blinding and life-threatening
conditions outlined below.
Stevens-Johnson syndrome
Stevens-Johnson
syndrome is a complex immunological syndrome characterised by
acute blistering of the skin and at least 2 mucous membranes
(conjunctival involvement resulting in acute membranous
conjunctivitis). It is caused by an idiosyncratic reaction to
infections (HIV, herpes simplex, Streptococcus
species) or drugs (antiretrovirals (ARVs) or sulfonamides) and
can lead to severely dry eyes, conjunctival vascularisation
and keratinisation. If not managed appropriately it can result
in bilateral blindness.
Uveitis associated with arthritis in children
Arthritis-associated uveitis is an entity seen in HIV-positive children.3 They have a clinical picture similar to juvenile idiopathic arthritis (JIA), but the arthritis is polyarticular rather than pauciarticular, there is no female preponderance and all patients are antinuclear antibody (ANA) negative (Figs 3 and 4).
Anterior uveitis in adults
Adults can present with an anterior uveitis caused by HIV itself or secondary to other viral infections (herpes or cytomegalovirus (CMV)) or bacterial infections (syphilis or tuberculosis). The signs and symptoms are:
• pain and redness
• decrease in vision
• mild inflammation
• anterior chamber activity.
Treatment is with steroid eye drops together
with treatment of the underlying infection with the appropriate
antiviral or antibiotic drug.
Herpes zoster ophthalmicus (HZO)
Patients under the age of 40 years who present with HZO (ocular shingles) must be investigated for HIV. They have a worse clinical course than HIV-negative patients with the same condition. The infection can occur early or late in the course of the HIV disease and ocular involvement may be severe.
Patients present with a painful, vesicular dermatitis localised to the dermatome supplied by the trigeminal nerve (usually VI or the ophthalmic division). The vesicles become pustules in 3 - 4 days, then dry and crust in 10 - 12 days. It involves deep layers of the skin and may resolve with scarring and pigmentation. Neuralgia in the dermatome can continue for months or years.
Ocular involvement is common (>70%). A vesicle on the tip of the nose (Hutchinson’s
sign) is a sign of globe involvement. This can
manifest as conjunctivitis, keratitis (either dendritic or
neurotrophic), episcleritis, scleritis or uveitis. Secondary
bacterial infection often occurs which compounds the scarring
and leads to cicatricial entropion or ectropion. Chronic
inflammation may lead to corneal vascularisation, corneal
opacification, lipid keratopathy, thinning and even perforation
of the cornea (Fig. 5).
Treatment is with systemic antivirals within 72 hours of the rash developing:
• acyclovir 800 mg 5 x/day or
• valaciclovir 1 g 3 x/day
• analgesics for acute pain
• non-steroidal anti-inflammatory/topical lidocaine cream
• amitriptyline at night for neuralgia.2
Herpes simplex keratoconjunctivitis
Herpes simplex virus (HSV) is one of the leading causes of chronic infectious ocular disease in immunocompetent patients. Keratoconjunctivitis, keratitis (dendritic ulcers) or keratouveitis can occur. In HIV disease the presentation and course are similar, but there may be more frequent recurrences of the ulcers and dendrites are often located more peripherally on the cornea. Patients may need systemic and topical acyclovir treatment due to a relative resistance to treatment.2
Keratitis
In HIV-positive patients, corneal infections can occur in otherwise healthy corneas (compared with immune-competent pa-tients, where there is almost invariably an underlying corneal problem). Corneal infections are caused by bacteria or fungi (the latter generally after injury with vegetable matter). In the immune-suppressed patient the ulcers tend to be larger and more aggressive and often respond slowly to treatment (Fig. 6).
Treatment is with appropriate antibiotic or antifungal eye drops following a corneal scrape for microscopy, culture and sensitivity.
Ocular surface squamous neoplasia (OSSN)
As many as 70 - 80% of patients under the age of 50 years with OSSN are HIV positive.2 Clinically it presents as an elevated, well-demarcated grey to red mass, usually in the interpalpebral area. It often straddles the nasal or temporal limbus and may have prominent feeder vessels and surface keratin. It is more aggressive in HIV-positive patients (Fig. 7).
Treatment includes:
• surgery:
• complete local excision with or without lamellar dissection into sclera or corneal stroma
• enucleation of the globe or exenteration of the orbit in neglected cases with tumour invading the eye or orbit
• adjuvant cryotherapy or chemotherapy at the time of surgery
• radiotherapy
• topical
chemotherapy (mitomycin-C, 5-fluorouracil or interferon α-2a).2
Posterior segment manifestations
Posterior segment
manifestations are often bilateral and can lead to bilateral
blindness if not diagnosed timeously. They include retinal,
choroidal or chorioretinal infections as well as HIV
microangiopathy, an indicator of advanced HIV disease.
Cytomegalovirus retinitis (CMVR)
CMVR is the most common cause for loss of vision in patients with AIDS. It is typically seen in advanced stages of AIDS when the CD4 count is less than 50 cells/mm³. Approximately 25% of patients not on HAART who have a CD4 count below 100 cells/mm³ will develop CMVR within 1 year. The clinical appearance can vary but usually consists of:
• full-thickness retinal opacification with or without haemorrhage (Fig. 8)
• minimal overlying vitritis except where large areas of retina are involved or where there is partial immune recovery from HAART
• retinal
vasculitis/periphlebitis.
Loss of vision occurs as a result of involvement of the optic nerve or macula, retinal detachment or immune recovery uveitis with cystoid macular oedema (CME), vitreous opacity or epiretinal membrane (seen only in patients on HAART).
Readily available treatment includes oral, intravenous or intravitreal ganciclovir. Because of its cost-effectiveness, intravitreal ganciclovir is the preferred method of treatment in the public sector.4 , 5
Progressive outer retinal necrosis (PORN)
PORN is caused by
infection with herpes simplex virus (HSV) or varicella zoster
virus (VZV). Patients often have a history of cutaneous zoster
infection, recent chicken pox infection or HSV ulcer on the
lip or eye. There is rapid progression of retinal necrosis in
a circumferential fashion with relative sparing of retinal
vasculature early in the course (Figs 9 and 10). The outcome
is often poor, with 67% of the patients becoming blind within
1 month – mainly due to rhegmatogenous retinal detachment.
Treatment is with intravitreal ganciclovir injections
and oral acyclovir, but once
retinal detachment occurs, surgery is needed.6
Fig. 9. Early PORN with lesions starting to coalesce but the vessels spared.
Toxoplasmosis chorioretinitis
Infection with Toxoplasma gondii results in intense, white, focal areas of retinal necrosis. These can be solitary, multifocal or in a miliary pattern. The lesions are usually larger than in immunocompetent individuals and there may be no pre-existing retinal scar. There is always substantial inflammation in the vitreous and invariably the patient will have concomitant central nervous system (CNS) involvement.
Treatment is with megadose co-trimoxazole or the combination of pyrimethamine (50 - 100 mg loading, then 25 - 50 mg daily orally) plus folinic acid (5 mg 3 times a week orally) and either:
• sulfadiazine 1 g qid
• clindamycin 300 - 450 mg qid
• azithromycin 250 mg daily or
• atovaquone 750 mg tid.
Prednisone (high dose, short course) must be given if the vision is threatened.7
Tuberculous choroiditis/choroidal granulomas
Tuberculosis is a common infection seen in HIV patients. Tuberculous uveitis is seen occasionally but, surprisingly, tuberculous choroiditis/TB choroidal granulomas are not seen as often as expected. The reason for this is not known. In most cases where choroidal lesions are seen, the patient is quite ill. Lesions are usually centrally located, either associated with the major vascular arcades or the macula (Fig. 11).
Syphilitic chorioretinitis
Syphilitic chorioretinitis presents as a
vitritis associated with bilateral, large, solitary, placoid,
pale yellow subretinal lesions with central fading and stippled
retinal pigment epithelial (RPE) hyperpigmentation. When this
diagnosis is made, the patient needs to be given the full
neurosyphilis course of penicillin.
HIV microangiopathy
Nerve fibre layer
infarcts or ‘cotton-wool spots’ are part of HIV
microangiopathy. The CD4 count is usually below
50 cells/mm³ when these
occur. They can be seen at the posterior
pole or around the optic disc and may be associated with a
small intraretinal haemorrhage similar to a small focus of
CMVR, which may make them difficult to distinguish from early
CMVR (Fig. 12). They spontaneously resolve over several months. A
repeat examination must be done every 2 weeks to distinguish
them from CMVR.
Neuro-ophthalmic manifestations
Optic neuritis
In immunocompromised
patients, optic neuritis can be due to the HIV disease per se or associated with neurosyphilis,
tuberculous meningitis, cryptococcal meningitis, toxoplasmosis
or viral (CMV or HSV) encephalitis. Unilateral or bilateral
occurrence is possible. Severe decrease in vision is typical.
As vision can be lost permanently, systemic steroids are
indicated in severe cases (high dose, short course). A lumbar
puncture is needed to aid with diagnosis.
Cranial nerve palsies
Cranial nerve palsies usually occur due to central nervous system (CNS) lymphoma or CNS infections, e.g. neurosyphilis, but can also be secondary to microvasculopathy or HIV infection per se. Often multiple cranial nerves are involved simultaneously. Investigation in the form of neuro-imaging with or without lumbar puncture is essential to make the diagnosis.
Papilloedema
Patients can present with papilloedema as a result of raised intracranial pressure secondary to:
• cryptococcal meningitis
• TB meningitis
• CNS toxoplasmosis
• neurosyphilis
• CNS lymphoma or other
intracranial tumours.
Vision may still be retained unless
papilloedema is chronic. Neuro-imaging is essential and
neurosurgical intervention may be needed.
References
1. UN AIDS info database: http://www.unaids.org/en/regionscountries/countries/southafrica/ (accessed 4 February 2013).
2. Jeng BH, Holland GN, Lowder CY, et al. Anterior segment and external ocular disorders associated with human immunodeficiency virus disease. Surv Ophthalmol 2007;52(4):329-354. [http://dx.doi.org/10.1016/j.survophthal.2007.04.010]
3. Zaborowski AG, Parbhoo D, Chinniah K, et al. Uveitis in children with HIV-associated arthritis. J AAPOS 2008;12(6):537-538. [http://dx.doi.org/10.1016/j.jaapos.2008.04.011]
4. Morlet N, Young S, Naidoo D, et al. High dose intravitreal ganciclovir injection provides a prolonged therapeutic intraocular concentration. Br J Ophthalmol 1996;80:214-216.
5. Laher F, Ashford G, Cescon A, et al. Held to ransom – CMV treatment in South Africa. SAJHIVMed 2010;11(1):31-34.
6. Gore DM, Gore SK, Visser L. Progressive outer retinal necrosis – outcomes in the intravitreal era. Arch Ophthalmol 2012;130(6):700-706.[http://dx.doi.org/10.1001/archophthalmol.2011.2622]
7. Yanoff M, Duker JS. Ophthalmology, 2nd ed. New York: Mosby, 2004:1170.
In a nutshell
• The incidence of HIV/AIDS in South Africa has started to decline, but as patients are living longer with the disease, the prevalence is still on the increase.
• More than 70% of patients will develop ocular complications at some stage during their illness.
• Sometimes the ocular disease will prompt the diagnosis of HIV.
• This article discusses clinical presentation divided into external eye (orbital and adnexal) disease, anterior segment, posterior segment and neuro-ophthalmic manifestations.
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