THE LANCET

HIV series

AIDS and the eyes

David Sarraf, J Terry Ernest

The eye is affected in 50–75% of adult AIDS patients. This rate of ocular involvement is much higher than that in
symptom-free HIV-seropositive patients, and seems to increase in incidence with severity of disease. These
observations indicate that regular screening of HIV-positive patients is warranted to allow early identification of
potential vision and life threatening disease.

Since the first report of the ocular manifestations of AIDS
by Holland et al,1 subsequent studies have documented
numerous AIDS-related conditions in the eye and orbit.
50–75% of adult AIDS patients will experience an ocular
complication. Whilst AIDS is a fatal disease, proper
diagnosis and treatment of its ocular manifestations may
help to maintain vision and prolong life. A balance must
be struck between survival expectations, quality of life,
and cost of interventions, which may be as high as
$50 000.2 This review outlines the wide-ranging
ophthalmological presentations of AIDS and the
therapeutic options available to practitioners.
Eyelids
Any individual under the age of 50 years who presents
with herpes zoster ophthalmicus (HZO) should be
suspected of harbouring HIV. Although not an AIDS-
defining illness, HZO may be the initial presentation of
HIV infection and may predict an increased risk for the
development of AIDS.3,4 HZO also occurs in AIDS
patients. Clinical characteristics include a vesicular rash in
the region of the ophthalmic division of the trigeminal
nerve, which may be associated with a conjunctivitis and
dendriform keratitis. Treatment with oral acyclovir is
required.
Kaposi’s sarcoma may present as flat or very slightly
raised purple papules of the eyelid. These lesions are
sometimes part of a multifocal presentation including
visceral involvement, and can also present within the
conjunctiva or orbit.3–6 Some patients have isolated eyelid
lesions, which can be treated with excision, intralesional
chemotherapy, or radiation. If there is associated systemic
involvement, systemic chemotherapy may be all that is
indicated.
Molluscum contagiosum is a DNA pox virus that causes
raised lesions with umbilicated centres that can present
along the eyelid. These growths may be associated with a
follicular conjunctivitis from viral shedding into the
adjacent conjunctival fornix. Molluscum contagiosum
tends to behave much more aggressively in AIDS patients,
who therefore present with more numerous and larger
lesions.6 Moreover, treatment with excision, curettage, or
cryotherapy may be less successful than in
immunocompetent patients.
Conjunctiva
As many as 10% of AIDS patients develop non-specific
conjunctivitis.3,7 Cultures tend to be negative and
treatment is therefore conservative, with cool compresses,
good lid hygiene, and topical antibiotics to prevent
bacterial superinfection. About 10% of AIDS patients
experience a dry-eye syndrome;8 the aetiology is unclear,
but may relate to systemic malabsorption of nutrients
essential for maintenance of a healthy tear film, or to
toxicity from systemic medication.5 Therapy consists of
appropriate tear substitutes in the form of drops and/or
ointments. The microvasculopathy present within the eye
of AIDS patients has been well documented. Different
theories of pathogenesis have been proposed, including
immune complex disposition within vascular walls and
endothelial damage as a result of HIV infection.9,10
Conjunctival manifestations include dilated capillary
segments, microaneurysmal formation, and sludging of
blood flow similar to that seen in sickle-cell patients.
Conjunctival Kaposi’s sarcoma, which affects 1% or less
of AIDS patients, presents as a reddish plaque that can
mimic a subconjunctival haemorrhage (figure 1) or
chalazion.10,11 Lesions are usually located in the cul-de-sac.
Treatment is as previously discussed.

Lancet 1996; 348: 525–28

Department of Ophthalmology and Visual Science, University of

Chicago, Visual Sciences Center, 939 East 57th Street, Chicago,
Illinois 60637, USA (D Sarraf MD, Prof J T Ernest MD)
Correspondence to: Prof J T Ernest
Figure 1: Conjunctival Kaposi’s sarcoma
The appearance resembles a subconjunctival haemorrhage. (Courtesy of
Dr J A Shields.)

Vol 348 • August 24, 1996 525

THE LANCET
Figure 2: Cotton wool spot along the inferior temporal retinal
vascular arcade
The CWS is an area of occlusion of the precapillary arteriole with
infarction of the nerve fibre layer of the retina.
Cornea
AIDS patients seldom develop bacterial or fungal corneal
ulcers: rates of occurrence are not appreciably different
from those in immunocompetent patients. Herpes simplex
keratitis has been documented in AIDS patients, but
whether there is an increased risk of such infection is
uncertain. Lesions tend to have a predilection for the
peripheral cornea and may respond to conventional
topical trifluorothymidine therapy. However, a lengthy
course of disease with multiple recurrences has been noted
in AIDS patients.4,6
Anterior segment
An AIDS patient complaining of a red, photophobic eye
may have iritis; this presentation necessitates a thorough
ocular examination to rule out anterior or posterior
segment infection. Posterior segment conditions include
cytomegalovirus (CMV) retinitis, acute retinal necrosis,
toxoplasma retinochoroiditis, and syphilitic
retinochoroiditis. Flare (protein in the aqueous) is present
in eyes with CMV retinitis although it does not seem to
predict the development of the retinitis.12
There have been several reports of anterior uveitis
associated with the rifabutin treatment of atypical
mycobacterial infection in AIDS patients.13,14 This iritis
may be severe and associated with hypopyon. Intensive
topical corticosteroid therapy is needed. If unsuccessful,
lowering the dose of rifabutin is effective.
Lens
There are few published accounts of refractive changes in
AIDS patients, although Newsome5 noted increasing
myopia and premature presbyopia (accommodation loss).
Retinovitreous
The most common ocular manifestation of AIDS is cotton
wool spots (CWS), which occur in about 50% of
patients.7,10,15–17 CWS are another manifestation of the
microvasculopathy that is well documented in AIDS
patients. These superficial fluffy retinal lesions (figure 2),
which result from occlusion of precapillary arterioles,
generally do not compromise visual acuity and do not
require treatment. Nevertheless, CWS may indicate a
greater risk for the onset of CMV retinitis.7,9 Moreover, the
appearance of CWS is sometimes confused with CMV
retinitis; the former are evanescent whereas the lesions of
CMV invariably progress. These factors highlight the
526
Figure 3: Cytomegalovirus retinitis along the superior temporal
retinal vascular arcade
Note the characteristic haemorrhagic, necrotic appearance.
importance of close follow-up of AIDS patients with
CWS.
Various types of intraretinal haemorrhages, including
Roth spots, are commonly seen in AIDS patients. Like
CWS, they are usually due to non-infectious
microvascular retinopathy. These haemorrhages may
present posteriorly or peripherally, within different layers
of the retina, and are generally innocuous.
Retinal infections in patients with AIDS include
syphilis, toxoplasmosis, candida, varicella zoster,
tuberculosis, and herpes simplex. There may be multiple
organisms in the same retina.18 CMV retinitis (figure 3) is
the most common intraocular infection in AIDS, affecting
about 25% of patients.7,10 This relentless process presents
as haemorrhagic necrosis, often extending along the
vascular arcade, and may be associated with a mild
anterior and vitreal inflammation. Other retinal
manifestations include granular infiltration along the
vascular arcade or perivascular sheathing. CMV can also
cause a papillitis. CMV retinitis tends to affect patients
with CD4 counts of less than 100/␮L, and survival after
the initial diagnosis ranges from 8 to 12 months.19
Treatment options include intravenous ganciclovir
(figure 4), which can lead to myelosuppression, or
intravenous foscarnet, which is associated with renal
insufficiency. Ganciclovir can be given by direct injection
into the vitreous cavity but multiple injections are
necessary.20 A sustained intravitreal ganciclovir-releasing
device, which is surgically implanted, can also be used;21
even in patients who are resistant to intravenous
ganciclovir, an implant may be beneficial.22 Moreover, a
second implant can be used, although in some cases
fibrosis prevents removal of the first implant. This local
therapy can be combined with oral ganciclovir to cover the
systemic CMV disease that often accompanies ocular
infection. In resistant cases, cidofovir therapy may be used
but the dose-dependent complications are iritis and
hypotonia and a safe protocol remains to be devised.23
Relapses and recurrences necessitate life-long treatment of
this condition, which can be further complicated by retinal
detachment. Prophylactic laser coagulation of the retina
has been used to prevent subsequent retinal detachment.24
Syphilis has various intraocular presentations including
uveitis, choroiditis, retinitis, papillitis, and papilloedema.
The retinitis manifests as a deep yellow lesion, sometimes
associated with intraocular inflammation or retinal
vasculitis. Serological tests for syphilis should be done in
patients with any of these presentations; if positive,
Vol 348 • August 24, 1996

neurosyphilis should be ruled out. Since syphilis follows a
more aggressive course in AIDS patients, vigorous therapy
should be initiated with intravenous penicillin.25,26
Toxoplasma retinochoroiditis comprises 1–3% of ocular
infections in AIDS patients,3 the manifestation being deep
yellow-white intraretinal lesions. In contrast to
immunocompetent patients, there are no associated
retinochoroidal scars, nor is dense vitritis invariably
present. Lesions may be bilateral and/or multifocal.
Treatment is with oral pyrimethamine, sulphadiazine, and
folinic acid.
Candidal endophthalmitis, like toxoplasma, does not
seem to be any more prevalent in AIDS patients than in
the normal population.3 However, AIDS patients with
predisposing factors for fungal infection—eg, intravenous
drug use or the presence of a long-term indwelling
catheter—may be at greater risk of ocular candidosis,
which presents as a focal white choroidal infiltrate that
may break through the retina into the vitreous causing an
overlying vitritis. If this disease is strongly suspected,
intravenous amphotericin can be given. Vitrectomy with
culture and cytological testing of the vitreous specimen
and subsequent intravitreal injection of amphotericin may
also be required.
Acute retinal necrosis is an infectious condition that
may affect immunocompetent as well as
immunosuppressed individuals. Patients present with
progressive peripheral retinal whitening or necrosis, in
conjunction with arteriolitis and severe vitritis. As the
infection spreads to the posterior pole, a path of retinal
scarring is left behind. At the junction of scarred and
infected retina there is a high incidence of retinal
detachment. Aetiological factors include herpes zoster and
simplex, so acyclovir should be given intravenously if the
clinical picture accords with this diagnosis.
Choroid
Choroidal infiltrates, which present as deep yellow or
white lesions, have several possible aetiologies including
tuberculosis, syphilis, Pneumocystis carinii, Candida,
cryptococcus, and lymphoma. Many of these entities,
including lymphoma, may break through into the vitreous
causing a dense vitritis.
Orbit
AIDS patients presenting with unilateral, painless, and
progressive proptosis, with or without diplopia and
periorbital lymphoedema, must be suspected of
harbouring an orbital infection or mass. Initial
investigation should be with computed tomography or
magnetic resonance imaging. If a mass lesion is found and
the diagnosis remains unclear, biopsy is required. Possible
aetiologies include Kaposi’s sarcoma, which seldom
affects the orbit, as well as Burkitt’s lymphoma.5 The latter
was previously believed to be endemic to central Africa
but has been seen with increasing frequency in AIDS
patients. Lesions may respond to irradiation or
chemotherapy.
Neuro-ophthalmology
Isolated or combined cranial nerve palsies affecting the
eye, as well as gaze palsies, are usually the result of one of
the various intracranial manifestations of AIDS, most
commonly cryptococcal meningitis and intracerebral
toxoplasma cysts. Other causes include intracranial
lymphoma, progressive multifocal leucoencephalopathy,
Vol 348 • August 24, 1996
THE LANCET
Figure 4: Treated CMV retinitis
Same patient as in figure 3 after initiation of intravenous ganciclovir
therapy. The haemorrhages have decreased and there is less whitish
necrosis.
and intracerebral infection with herpes virus or Treponema
pallidum.10,27–29 These lesions may also result in
papilloedema due to increased intracranial pressure or an
optic neuropathy from infiltrative disease. Each of these
neuro-ophthalmological presentations in AIDS patients
warrants emergency intracranial and orbital imaging so
that appropriate systemic therapy can be initiated to treat
potential life-threatening, as well as ocular disabling,
disease.
Paediatric AIDS
The incidence of ocular manifestations in paediatric AIDS
patients, especially non-infectious microvasculopathy and
CMV retinitis, seems to be significantly less than in
adults.30 Kaposi’s sarcoma is also much less frequent in
this age group. The reason for these differences is unclear.
This work was partly supported by Research to Prevent Blindness Inc.
References
1 Holland GN, Gottlieb MS, Yee RD, et al. Ocular disorders associated
with a new severe acquired cellular immunodeficiency syndrome.
Am J Ophthalmol 1982; 93: 393–402.
2 Steinberg EP, Griffiths RI, Bleecker GC. Costs and outcomes of
alternative approaches to treating cytomegalovirus (CMV) retinitis in
persons with AIDS (PWA). Invest Ophthalmol Vis Sci 1996; 37: S899.
3 Kreiger AE, Holland GN. Ocular involvement in AIDS. Eye 1988; 2:
496–505.
4 Palestine AG, Palestine RF. External ocular manifestations of the
acquired immunodeficiency syndrome. Ophthalmol Clin N Am 1992; 5:
319–24.
5 Newsome DA. Noninfectious ocular complications of AIDS. Int
Ophthalmol Clin 1989; 29: 95–97.
6 Shuler JD, Engstrom RE, Holland GN. External ocular disease and
anterior segment disorders associated with AIDS. Int Ophthalmol Clin
1989; 29: 98–104.
7 Holland GN, Pepose JS, Pettit TH, et al. Acquired immune deficiency
syndrome: ocular manifestations. Ophthalmology 1983; 90: 859–72.
8 Khadem M, Kalish SB, Goldsmith J, et al. Ophthalmologic findings in
acquired immune deficiency syndrome (AIDS). Arch Ophthalmol 1984;
102: 201–06.
9 Pepose JS, Holland GN, Nestor MS, et al. Acquired immune
deficiency syndrome: pathogenic mechanisms of ocular disease.
Ophthalmology 1985; 92: 472–84.
10 Jabs DA, Green WR, Fox R, et al. Ocular manifestations of acquired
immune deficiency syndrome. Ophthalmology 1989; 96: 1092–99.
11 Palestine AG, Rodrigues MM, Macher AM, et al. Ophthalmic
involvement in acquired immunodeficiency syndrome. Ophthalmology
1984; 91: 1092–99.
12 Althaus C, Best J, Hintzmann A, et al. Flare measurement in AIDS
patients with and without cytomegalovirus retinitis. Invest Ophthalmol
Vis Sci 1996; 37: S370.
13 Shafran SD, Deschenes J, Miller M, et al. Uveitis and pseudojaundice
during a regimen of clarithromycin, rifabutin, and ethambutol. N Engl
527
THE LANCET
J Med 1994; 330: 438–39.
14 Saran BR, Maguire AM, Nichols C, et al. Hypopyon uveitis in patients
with acquired immunodeficiency syndrome treated for systemic
Mycobacterium avium complex infection with rifabutin. Arch
Ophthalmol 1994; 112: 1159–65.
15 Rosenberg PR, Uliss AE, Friedland GH, et al. Acquired
immunodeficiency syndrome: ophthalmic manifestations in ambulatory
patients. Ophthalmology 1983; 90: 874–78.
16 Freeman WR, Lerner CW, Mines JA, et al. A prospective study of the
ophthalmologic findings in the acquired immune deficiency syndrome.
Am J Ophthalmol 1984; 97: 133–42.
17 Humphry RC, Weber JN, Marsh RJ. Ophthalmic findings in a group
of ambulatory patients infected by human immunodeficiency virus
(HIV): a prospective study. Br J Ophthalmol 1987; 71: 565–69.
18 Rummelt V, Rummelt C, Jahn G, et al. Triple retinal infection with
human immunodeficiency virus type 1, cytomegalovirus, and herpes
simplex virus type 1: light and electron microscopy,
immunohistochemistry and in situ hybridization. Ophthalmology 1994;
101: 270–79.
19 Studies of Ocular Complications of AIDS Research Group. Mortality
in patients with the acquired immunodeficiency syndrome treated with
either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J
Med 1992; 326: 213–20.
20 Heinemann M-H. Long-term intravitreal ganciclovir therapy for
cytomegalovirus retinopathy. Arch Ophthalmol 1989; 107: 1767–72.
21 Anand R, Nightingale SD, Fish RH, et al. Control of cytomegalovirus
retinitis using sustained release of intraocular ganciclovir. Arch
Viewpoint
QED: quick and early diagnosis
M J Kendall, V Toescu, D M A Wallace
Many patients are evaluated by Health Services in a way
which seems designed to be slow and inefficient. The
delay between onset of symptoms which might suggest
that the patient has a serious disease and the making of a
diagnosis often causes uncertainty and anxiety and allows
the disease to progress.
For example, a 65-year-old man with recent onset of
indigestion may try to ignore his symptoms and his
primary-care doctor, who sees many patients with this
type of problem, takes a reassuring line. If symptoms
persist, the patient may be referred by post to an
outpatient clinic for history taking, physical examination,
and blood tests. This may be followed by further visits to
view test results and check what was found at the first
visit. Eventually, an upper gastrointestinal endoscopy is
done and a gastric cancer is found.
Could we not offer a more efficient approach to the
patient with indigestion described above or to patients
with haematuria, young people with pigmented skin
lesions, or men with a testicular swellings? Is quick and
early diagnosis (QED) an achievable goal?
QED: the concept
The concept has four components:
● a hospital unit where specialised clinics are run by
consultants;
Lancet 1996; 348: 528–29
Quick and Early Diagnosis Unit, Queen Elizabeth Hospital,
Edgbaston, Birmingham B15 2TH, UK (M J Kendall MD,
V Toescu MD, D M A Wallace FRCS)
Correspondence to: Dr M J Kendall
528
Ophthalmol 1993; 111: 223–27.
22 Kupperman BD, Gordon JF, the Ganciclovir Implant Study Group. A
multicenter study to evaluate the safety and efficacy of an intravitreal
ganciclovir implant in patients with CMV retinitis. Invest Ophthalmol
Vis Sci 1996; 37: S898.
23 Taskintuna I, Rahhal FM, Arevalo JF, et al. Low dose intravitreal
HPMPC (Cidofovir) therapy for CMV retinitis in patients with AIDS.
Invest Ophthalmol Vis Sci 1996; 37: S669.
24 Schimkat M, Althaus C, Sundmacher R. Prophylactic argon-laser
coagulation for rhegmatogenous retinal detachment in AIDS patients
with cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 1996; 37:
S370.
25 Katz DA, Berger JR. Neurosyphilis in acquired immunodeficiency
syndrome. Arch Neurol 1989; 46: 895–98.
26 McLeish WM, Pulido JS, Holland S, et al. The ocular manifestations
of syphilis in the human immunodeficiency virus type 1-infected host.
Ophthalmology 1990; 97: 196–203.
27 Keane JR. Neuro-ophthalmologic signs of AIDS: 50 patients.
Neurology 1991; 97: 196–203.
28 Hamed LM, Schatz NJ, Galetta SL. Brainstem ocular motility and
AIDS. Am J Ophthalmol 1988; 106: 437–42.
29 Friedman DI. Neuro-ophthalmic manifestations of human
immunodeficiency virus infection. Neurol Clin 1991; 9: 55–72.
30 Dennehy PJ, Warman R, Flynn JT, et al. Ocular manifestations in
pediatric patients with acquired immunodeficiency syndrome. Arch
Ophthalmol 1989; 107: 978–82.
● patient selection by primary-care doctors;
● support staff for the medical team (nurses) and clinical
organisation (administrator and reception staff);
● patient assessment in a one-stop visit to the unit within
2 weeks of referral.
The hospital unit
Reception office and waiting area The referral centre
receives all telephone requests for appointments.
Receptionists take down details of the patient and
referring doctor and give an appointment date and time.
At reception, patients are greeted by someone who is
expecting them and knows what is to happen.
Outpatient consulting offices These contain desk, chairs,
couch, and diagnostic equipment.
Endoscopy suite To be efficient, three or four endoscopy
rooms should be close together and each fully equipped to
allow endoscopists to move rapidly from room to room.
There must be enough endoscopes to ensure that time is
not wasted when instruments are cleaned. Each
endoscopy room should have a computer terminal so that
patient details can be displayed on the screen and findings
recorded directly into the system. After investigation, the
patient needs to have a place to rest and recover, and to
be given further information and support. Throughout,
the patient should be accompanied by a named nurse who
explains, assists, and helps.
Patient selection
Usually, the primary-care physician knows what is needed
from a referral. For a woman with a breast lump,
Vol 348 • August 24, 1996