Ophthalmic Manifestations of HIV Infection

Digital Journal of Ophthalmology 2004

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reno !ocha "ima# M$D$ % &ni'ersity of Miami (chool of Medicine ) *illiam J$
Harrington Medical +raining Programs
ABSTRACT INTRODUCTION DISCUSSION ACKNOWLEDGEMENTS REFERENCES CLINICAL PICTURES
,-stract
Objective
+his re'ie. is intended to descri-e the most common ophthalmic manifestations of HIV
infection$ It is estimated that more than /00 of adult ,ID( patients .ill e1perience an
ocular complication at some point of the disease$ Or-ital and adne1al manifestations
include tumors of the periocular tissues and e1ternal infections$ ,nterior segment findings
consist of 2eratitis# 2eratocon3uncti'itis sicca# iridocyclitis# and other complications$
Posterior segment findings include a HIV associated retinopathy and a num-er of
opportunistic infections of the retina and choroid$ HIV has also -een related to neuro)
ophthalmic manifestations such as 'isual field defects and papilledema$
Methods
+he author performed a search of Medline# using Pu-Med$ (earch .ords included HIV#
cytomegalo'irus retinitis# retinal micro'asculopathy# herpes 4oster ophthalmicus#
5aposi6s sarcoma# immune reco'ery u'eitis# or-ital lymphoma# to1oplasmosis# herpes
simple1 'irus# pneumocystis carinii# microsporidia# syphilis# molluscum contagiosum#
ganciclo'ir and 2eratocon3uncti'itis sicca$ ,rticles .ere selected -ased on clinical
importance$ ,dditional references of 2ey articles .ere also included$ ,rticles .ere
e1cluded if they had non)7nglish a-stracts$
Ke!o"ds
HIV# 8ytomegalo'irus 98MV: retinitis# !etinal micro'asculopathy# Herpes ;oster
Ophthalmicus# 5aposi6s (arcoma# Immune !eco'ery &'eitis# +o1oplasmic
!etinochoroiditis
top
Introduction
+he human immunodeficiency 'irus 9HIV: infection has spread .orld.ide# .ith 'arious
ad'erse health and economic implications# particularly in the de'eloping .orld$9<: ,
glo-al summary of the HIV=,ID( epidemic from Decem-er 200> -y the Joint &nited
?ations Programee on HIV=,ID( 9&?,ID(: and *orld Health Organi4ation 9*HO:
estimates that there are 40 million people .orld.ide li'ing .ith HIV=,ID($
,ppro1imately @ million people .ere infected .ith HIV and there .ere a-out > million
,ID( deaths in 200>$92: ,t present# around A00 of HIV)infected persons li'e in
de'eloping countries# particularly those in su-)(aharan ,frica and (outheast ,sia$92# >:
&nless a cure is found or life prolonging therapy can -e made more .idely a'aila-le# the
ma3ority of people .ill remain suffering the profound impacts the disease has on their
Buality of life$94:
?umerous ophthalmic manifestations of HIV infection may in'ol'e the anterior or
posterior segment of the eye$ (ince the first report of the ocular manifestations of ,ID(
-y Holland et al$ in <AC2#9@# D: su-seBuent studies ha'e descri-ed se'eral ,ID( related
conditions in the eye and or-it$ /0EC00 of adult ,ID( patients .ill e1perience an ocular
complication at some point of their illness$9@# /: Or-ital and adne1al findings include
tumors of the periocular tissues and e1ternal infections$ ,nterior segment manifestations
consist of 2eratitis# 2eratocon3uncti'itis sicca# iridocyclitis# and other complications$
Posterior segment findings include a HIV associated retinopathy and a num-er of
opportunistic infections 9OI: of the retina and choroid$ HIV has also -een related to neuro)
ophthalmic manifestations# such as 'isual field defects# papilledema# and diplopia$ +he
occurrence of ophthalmic complications associated .ith HIV infection is significantly
lo.er in the pediatric age group$ ,ll patients .ith HIV disease should undergo routine
ophthalmologic e1aminations# since proper diagnosis and treatment may help to maintain
'ision and prolong life$ (ome retinal OI may ha'e a rapid and de'astating course$
8D4F + "ymphocyte pro'ed to -e a relia-le predictor of ocular complications of HIV
infection$9/# C: +he use of highly acti'e antiretro'iral therapy 9H,,!+:# .hich consists
of a com-ination of nucleoside re'erse transcriptase inhi-itors# HIV protease inhi-itors
and non nucleoside re'erse transcriptase inhi-itors# has decreased plasma le'els of HIV
!?, and increased 8D4F + lymphocytes counts# impro'ing the immune function of
patients .ith HIV infection$9A# <0# <<: +he clinical presentation of HIV related diseases
may -e modified -y H,,!+# .hich has dramatically impro'ed the prognosis of HIV
infection$ efore the introduction of H,,!+# patients .ith cytomegalo'irus retinitis
commonly had 8D4F counts less than @0 cells=Gl .ith minimal ocular inflammation$9A:
+here are some reports of spontaneous resolution of cytomegalo'irus retinitis in patients
.ith increased 8D4F counts related to such therapy# although the reco'ery in +
lymphocytes may ta2e many months$9<2# <># <4: ?e'ertheless# su-stantial intraocular
inflammation in patients .ith healed cytomegalo'irus retinitis recei'ing H,,!+ has
-een reported# .hich is 2no.n as immune reco'ery u'eitis$9A#<0@:
top
Discussion
II E Or-ital Manifestations
Or-ital manifestations of HIV infection are not seen 'ery often$ Ho.e'er# some cases of
or-ital cellulitis and or-ital lymphoma ha'e -een reported$ +he cases of or-ital cellulitis
.ere related to ,spergillus infection most times# -eing treated .ith systemic
antimicro-ial drugs$ Other organisms reported in the literature that caused or-ital
infections in patients .ith HIV include !hi4opus arrhi4us# +o1oplasma gondii# and
Pneumocystis carinii$ 8hildren may present .ith recurrent episodes of or-ital=peri)or-ital
cellulitis$9<@# <D: Primary non)Hodg2in6s lymphoma 9?H": of the or-it and ocular
adne1a is a rare disease$ It accounts for only <0 of all ?H"$ In general# the ris2 of
de'eloping ?H" is higher in HIV infected patients$ +he reported cases of lymphoma
responded .ell to radiotherapy$ Ho.e'er# high doses may -e correlated to late ocular
complications$9</# <C:
III E ,dne1al Manifestations
+he most common adne1al manifestations in patients .ho ha'e HIV infection are
5aposi6s sarcoma# herpes 4oster ophthalmicus# moluscum contagiosum and con3uncti'al
micro'asculopathy$9<A: 8on3uncti'al sBuamous)cell carcinoma is a rare finding$
5aposi6s (arcoma
5aposi6s sarcoma .as a rare tumor$ ,fter the spread of HIV# the incidence mar2edly
increased$ It is a highly 'asculari4ed# painless mesenchymal tumor that affects the s2in
and mucous mem-ranes and occurs in up to 2@0 of HIV infected patients$ ,round 200
of these patients ha'e asymptomatic 5aposi6s sarcoma of the eyelids# con3uncti'a and
rarely the or-it$9/# 20:
Ho.e'er# a study -y is.as et al$# .ho follo.ed <00 HIV positi'e indi'iduals in India#
did not o-ser'e a single case of 5aposi6s sarcoma of the eye$ +he lo. pre'alence of this
tumor in India may -e attri-uted to the lo.er proportion of cases associated .ith
homose1ual -eha'ior in that country$ D?, seBuences of human herpes 'irus C ha'e -een
detected in patients .ith 5aposi6s sarcoma either .ith or .ithout HIV infection$ +he lo.
incidence of human herpes 'irus C in India may also contri-ute to the lo. occurrence of
this tumor in that country$9># 2<:
5aposi6s sarcoma may present as purple papules in the eyelids# .hich may -e either flat
or slightly raised$ (ometimes# these lesions are part of a multifocal presentation# .hich
may include 'isceral in'ol'ement$9@# 22:
8on3uncti'al 5aposi6s sarcoma may occur in up to <0 of patients .ith HIV infection$ +he
classic presentation is a reddish plaBue that may mimic a su-con3uncti'al hemorrhage or
chala4ion$ +his lesion is often located in the cul de sac$ 7'en small lesions can cause
important cosmetic and functional discomfort# .hich may -e related to mass effect or
secondary corneal changes$9@# 2>:
5aposi6s sarcoma does not in'ade the eye$ Most lesions are slo.ly progressi'e and
respond to systemic drug therapy 9<0D:$ !adiation therapy may -e effecti'e .hen
functional discomfort is reported$ ?e'ertheless# it is e1pensi'e and can cause s2in
irritation and con3uncti'itis$ Doses of 20 Hy may -e sufficient to produce shrin2age of the
tumor$ 71cision and intralesional chemotherapy .ith 'in-lastine are other treatment
options$ If there is systemic in'ol'ement# systemic chemotherapy may -e indicated$9/# 2>:
+here are some reports of regression in patients treated .ith H,,!+ containing a
protease)inhi-itor$ (aBuina'ir# indina'ir# ritona'ir and nelfina'ir may affect angiogenesis#
cell sur'i'al# tumor gro.th and in'asion$924:
Herpes ;oster Ophthalmicus
!eacti'ation of latent 'aricella 4oster 'irus in the ophthalmic di'ision of the trigeminal
ner'e causes herpes 4oster ophthalmicus$ +he ophthalmic di'ision -ranches into the
lacrimal# nasociliary and frontal ner'es$ In'ol'ement of the frontal ner'e is common$
*hen the nasociliary ner'e is affected# the patients may present .ith 'esicles at the tip of
the nose# 2no.n as Hutchinson6s sign$ (tudies ha'e sho.n ophthalmic in'ol'ement in
AA0 of patients .ith this sign$92@:
Herpes 4oster occurs in patients .ith HIV infection as .ell as other patients .ith
depressed cellular immunity such as lymphoma patients and patients recei'ing
immunosuppressi'e therapy$ 8haracteristic prodromal symptoms include headache#
generali4ed malaise and fe'er$92D:
In younger indi'iduals# it may -e the initial manifestation of HIV infection$92/: ,ny
patient younger than @0 years of age .ho presents .ith herpes 4oster ophthalmicus is
suspect of ha'ing HIV infection or any other immunosuppressi'e condition$9@# 2C: ,
study -y Hodge et al$ sho.ed a relati'e incidence ris2 ratio of D$D=< in HIV positi'e
patients compared to HIV negati'e patients$92A:
!eports suggest that it affects @E<@0 of HIV positi'e patients and may ha'e a high rate of
painful and sight threatening complications$9/# 2/: Forty one percent of the patients
studied -y "e.allen in Mala.i de'eloped corneal perforation and se'enteen percent of
the patients studied -y (ellitti et al$ in Miami de'eloped necroti4ing retinitis$ Ocular
complications result from inflammation# ner'e damage and tissue scarring$9>0# ><:
Herpes 4oster ophthalmicus presents as 'esico-ullous rash and may -e associated .ith
2eratitis# scleritis# u'eitis# retinitis or encephalitis$92/: +he se'erity of the s2in rash is an
important prognostic parameter of su-seBuent ocular in'ol'ement$9>2:
(ignificant entropion or trichiasis may result from herpes 4oster# -ecause the 'irus can
cause permanent contraction scars of the deep dermal tissues of the eyelids$92@:
Patients should -e treated .ith intra'enous acyclo'ir 9<0 mg per 2ilogram of -ody .eight
three times a day for se'en days: follo.ed -y an oral maintenance regimen 9C00 mg >E@
times a day:$ Other options are famciclo'ir# .hich reBuires long term maintenance
therapy# and 'alaciclo'ir$9/# 2@:
Molluscum 8ontagiosum
Molluscum contagiosum is caused -y a D?, po1'irus and affects the s2in and mucous
mem-ranes as translucent papules .ith a central um-ilication$ In HIV patients it occurs
commonly and lesions may -ecome Buite large and are often more numerous and more
rapidly gro.ing$ In'ol'ement of the eyelids may occur in up to @0 of HIV infected
patients$ +hey are usually multiple# -ilateral# confluent# and tend to recur .ithin D to C
.ee2s after remo'al$9>:
+reatment options are cryotherapy# incision# curettage and e1cision$ +he use of
podophylloto1in cream as an ad3unct to cryotherapy may -e helpful$ "esions may recur
particularly .hen 8D4F counts decrease$9>># >4:
8on3uncti'al Micro'asculopathy
Patients .ith HIV infection may present .ith asymptomatic micro'ascular changes#
.hich is correlated .ith retinal micro'asculopathy$ +he se'erity of the micro'asculopathy
has -een correlated to increased 4eta sedimentation ratios and fi-rinogen le'els$9>@:
&sually# no treatment is necessary$ +hose patients may ha'e microaneurysms and
segmental 'ascular dilatations and narro.ings$9/: +he cause of these 'ascular changes is
not clear yet# -ut it is pro-a-ly associated .ith the deposition of immune comple1es
related to HIV or the direct infection of HIV in the con3uncti'al 'ascular endothelium$9>D:
8on3uncti'al (Buamous)8ell 8arcinoma
, study -y ,ga-a in &ganda sho.ed a correlation -et.een an increase in cases of
con3uncti'al sBuamous)cell carcinoma and HIV infection$ +hese tumors ha'e also -een
related to e1posure to ultra'iolet light and con3uncti'al papilloma'irus infection and
usually arise in the lim-us of the eye$9>/:
IV),nterior (egment Disease
+he anterior segment of the eyes 9cornea# anterior cham-er and iris: may also suffer
changes related to HIV infection$ !eports indicate that more than @00 of HIV infected
patients ha'e anterior segment manifestations$9>C: 5eratitis# 2eratocon3uncti'itis sicca
and iridocyclitis are among the most common complications in the anterior segment of the
eyes$ Ho.e'er# studies ha'e sho.n no difference in the ocular flora -et.een HIV)
negati'e patients and patients .ith ,ID($9>A:
Herpes (imple1 5eratitis
Herpes simple1 2eratitis has -een reported in ,ID( patients# -ut .hether there is an
increase ris2 of this disease is still un2no.n$ +he infection has a predilection for the
peripheral cornea and may cause corneal ulcerations# -eing usually painful$ In general# the
course of the disease is longer in ,ID( patients and the rate of recurrences is also higher$
It is associated .ith corneal scarring and iritis$ +he treatment of choice for epithelial
2eratitis consists of topical trifluridine si1 to eight times a day during the first se'eral
days$ Orally administered acyclo'ir is also effecti'e$922# 40:
Varicella);oster Virus 5eratitis
,s mentioned -efore# the 'aricella 4oster 'irus may -e associated .ith 2eratitis in ,ID(
patients$ +he patients may present .ith ele'ated intraocular pressure$ 8ommonly# the
patients ha'e herpes 4oster ophthalmicus as .ell# although the dermatitis may -e mild$ ,s
in herpes simple1 2eratitis# the course of the disease tends to -e longer in ,ID( patients$
+he treatment is similar to that of 4oster ophthalmicus$ 92@# 2C# ><:
acterial and Fungal 8orneal Infections
acterial and fungal infections are generally more se'ere in HIV infected patients$
(pontaneous fungal 2eratitis secondary to 8andida al-icans has -een reported in patients
.ith ad'anced HIV disease$94<: 8andida species are particularly common in intra'enous
drugs users$ ,lthough uncommon# Microsporidia is associated .ith a -ilateral diffuse
punctate epithelial 2eratopathy and con3uncti'itis$ +he treatment consists of oral
itracona4ole# oral al-enda4ole or topical fumagillin$942# 4># 44:
Posterior Intracorneal Infiltrates
Posterior intracorneal infiltrates ha'e -een reported in HIV infected hosts .ith
concomitant cytomegalo'irus retinitis and in children .ho ha'e -een treated .ith
prophylactic rifa-utin$ +hose infiltrates tend to -e distri-uted primarily in the inferior
cornea$ +he cause of those corneal infiltrates is still under in'estigation$ +hey may -e
caused -y direct deposition of immune comple1es or 'iral particles# to1icity of medication
or e'en the direct effect of opportunistic infections$94@:
5eratocon3ucti'itis (icca
More than 200 of patients .ith HIV infection may ha'e 2eratocon3uncti'itis sicca# also
called dry eye syndrome# .hich results from deficiency of any of the tear film layers$
,pparently# it is not related to 8D4F counts or associated .ith the se'erity of HIV$94D:
(ymptoms may include foreign -ody sensations# photopho-ia and decreased 'isual acuity$
It is li2ely caused -y -oth the destruction of primary and secondary lacrimal glands and
inflammation mediated -y the HIV 'irus$ +he treatment is -ased on the administration of
artificial tears# often si1 to eight times a day# and lu-ricating ointments$94/:
Iridocyclitis
,n HIV infected patient complaining of photopho-ia and red eye may ha'e iridocyclitis$
+his presentation reBuires a thorough ocular e1amination in order to rule out anterior or
posterior segment infection$9@: It may -e associated .ith retinal or choroidal infection
.ith multiple opportunistic organisms# such as cytomegalo'irus# herpes simples 'irus#
'aricella 4oster 'irus# 8andida species# 8ryptococcus species# +o1oplasma gondii#
+reponema pallidum and Myco-acterium species$94C:
In the differential diagnosis of acute iridocyclitis in a patient .ith ,ID(# infection .ith
syphilis or to1oplasmosis should al.ays -e considered$ Immunocompromised hosts may
ha'e +$ gondii infection -ilaterally and ha'e multiple infectious foci$ 7ncysted +$ gondii
organisms ha'e -een found in an iris -iopsy specimen from an ,ID( patient presenting
.ith iridocyclitis$94A:
P8! of the aBueous humor or 'itreous of those patients may -e used for identification of
those organisms$ Vitreous samples ha'e a higher sensiti'ity$94A#<0/#<0C:
(ome medications# such as rifa-utin and cidofo'ir# ha'e also -een associated .ith
iridocyclitis$9@0# @<:$ !ifa-utin is also related to ocular hypotony# and cidofo'ir may
cause an endophthalmitis)li2e manifestation$
Iridocyclitis may also -e associated .ith !eiter6s syndrome# .hich is defined -y the
classic triad of arthritis# urethritis# and con3uncti'itis$ +his syndrome appears to -e more
common in patients .ith HIV infection$
+he treatment of iridocyclitis depends on the specific infectious agent$ In the cases
associated .ith medications# the dose should -e tapered or the drug should -e
discontinued$ +opical corticosteroids are usually indicated# -ut must -e used carefully
.hene'er a infectious cause is suspected$9/:
V E Posterior (egment Disease
+he posterior segment of the eye 9retina# choroid and optic ner'e head: is affected in more
than @00 of ,ID( patients$ +hose disorders may -e either associated .ith infectious
causes or non infectious causes$ Decreased 'isual acuity# 'isual field defects and
photopsias are among the most common symptoms$9A/:
!etinal Micro'asculopathy
+he micro'ascular changes in the retina are the most common retinal manifestations of
HIV infection$ ?e'ertheless# they are generally asymptomatic and transient$ +hese
changes may occur in up to /00 of ,ID( patients at some point of the disease$ +he
patients presenting .ith HIV retinopathy may ha'e cotton).ool spots 98*(: in the retina#
intraretinal hemorrhages# and retinal microaneurysms# especially .hen 8D4F +
lymphocyte count is -elo. <00 cells=mm>$ Forty fi'e percent of the patients .ith HIV
related retinopathy ha'e 8DF cell counts -elo. @0 cells=mm>$ 9@# @2:
+he 8*( result from occlusion of precapillary arterioles# normally do no affect 'isual
acuity and do not reBuire treatment$ +hey appear as small# .hite# superficial retinal
opacities and are mainly locali4ed on the posterior pole$ Pathologically# the 8*( are
ner'e fi-er layer infarcts# related to accumulations of a1oplasmic de-ris# su-seBuent to
o-struction of a1oplasmic flo.$9@>: +hey may represent an increased ris2 for
cytomegalo'irus 98MV: retinitis$ +he appearance of 8*( is sometimes similar to 8MV
retinitis$ 8*(# ho.e'er# tend to -e smaller# do not progress# are not characteristically
associated .ith retinal hemorrhage and resol'e o'er .ee2s to months$ ,ID( patients .ith
8*( should ha'e close follo. up$9@2:
Intraretinal hemorrhages# including !oth6s spots# may -e present in ,ID( patients$ +hey
are commonly innocuous in the setting of HIV retinopathy and may occur .ithin different
layers of the retina$9@:
+he pathogenesis of retinal micro'asculopathy is pro-a-ly similar to that of con3uncti'al
micro'asculopathy$9>D: Hypothesis including hemorheologic a-normalities# li2e
increased plasma 'iscosity and fi-rinogen le'elsI circulating immune comple1es and
infectious damage of the retinal 'asculature ha'e -een postulated$
(chmetterer and colleagues studied the ocular -lood flo. in patients infected .ith HIV$
+hey detected a decreased macular leu2ocyte density in HIV infected persons$ +he study
also suggested that a-normal retinal hemodynamics in this group may -e in'ol'ed in the
pathogenesis of HIV)related micro'asculopathy$ ?o correlation -et.een antiretro'iral
treatment and ocular -lood flo. parameters .as found$9@>:
ranch retinal artery and retinal 'ein o-structions ha'e -een seen in HIV infected
patients$ 9@4# @@: +here are some reports of ischemic maculopathy associated .ith HIV
infection# .hich can -e se'ere# ho.e'er the condition is apparently uncommon$ +he
presence of opacification of the superficial retina# resulting in a cherry red spot# or
intraretinal hemorrhages near the fo'ea may suggest the diagnosis# although some patients
may not present .ith these findings$ ilateral in'ol'ement of the eyes# .ith an a-rupt
onset often occurs$ Fluorescein angiography should -e done on HIV infected patients .ith
une1plained 'ision loss$9@2:
, study -y 8unningham and associates suggested the possi-ility that occult herpetic
infection may -e a contri-uting factor to ischemic maculopathy# as .ell as alterations in
-lood flo. in the setting of micro'ascular a-normalities$9@2:
8hronic Multifocal !etinal Infiltrates
"e'inson and associates descri-ed a distinct syndrome in HIV infected su-3ects that .as
characteri4ed -y the presence of sta-le or slo.ly progressi'e multifocal peripheral
infiltrates# often in association .ith inflammatory reactions in the 'itreous humor and
anterior cham-er and lac2 of retinal necrosis$ +hose infiltrates do not seem to -e related to
drug to1icity or to opportunistic infections$ Henerally# they .ere round or irregular in
shape# and typically less than 200 Gm in the greatest dimension$ Floaters .ere the most
freBuent complaint among the patients studied# follo.ed -y -lurred 'ision$ ,n auto
immune phenomenon associated .ith immune response to the presence of HIV in the
ocular tissue has -een suspected to cause these inflammatory reactions$ +he long term
effect of this syndrome on 'isual function remains un2no.n$9@D:
Infectious !etinitis
!etinal infections in HIV infected patients may result from different pathogens# .hich
may affect the retina at the same time$9@/: (yphilis# candida# 'aricella)4oster#
to1oplasmosis# herpes simple1 and cytomegalo'irus retinitis are among the most common
ones$ ,lthough these infectious may also occur in immunocompetent hosts# the course
tends to -e longer in ,ID( patients# and the rate of recurrences is also higher$
Varicella ;oster Virus and Herpes (imple1 !etinitis
Varicella 4oster 'irus has -een associated .ith acute retinal necrosis# .hich affects <E40
of HIV infected patients$ It is characteri4ed -y peripheral retinal .hitening# often
accompanied -y intraretinal hemorrhages associated .ith rapidly progressing necrosis
o'er se'eral days$ Multifocal lesions are commonly seen$ !etinal detachment .ith
proliferati'e 'itreoretinopathy as .ell as the in'ol'ement of the other eye may also occur$
9@C# @A: 8entral retinal 'ein occlusion as the initial presentation of herpes 4oster
ophthalmicus has also -een reported$9D0:
,lthough not freBuently seen# herpes simple1 'irus has also -een related to retinitis in
HIV)positi'e patients$ It has -een associated .ith a rapid progressing 'isual loss$
+he treatment for these t.o pathogens is normally long$ Intra'enous acyclo'ir and
intraocular ganciclo'ir or foscarnet are commonly reBuired$9@A# D<:# and long)term
treatment .ith acyclo'ir pre'ents recurrences and is important in prophyla1is of the
fello. eye 9<02#<0>:
8ytomegalo'irus !etinitis
Human cytomegalo'irus 9H8MV: is part of the -eta su-group of herpes 'iruses 9Herpes
'iridae: and has strong species specificity$ ,lthough the infection .ith 8MV is usually
su-clinical in immunocompetent hosts# there may -e a life long persistence in @0EA00 of
the population$ In immunocompromised hosts# such as patients infected .ith HIV# 8MV
may lead to se'eral complications$9D2# D>:
8ytomegalo'irus 98MV: retinitis is the most common intraocular infection related to HIV
infection# affecting around 2@0 of patients according to reports of the past decade and
may cause progressi'e loss of 'ision and -lindness$9@: +he pre'alence of 'isual
impairment at the time of 8MV retinitis diagnosis is high and is related to demographic
characteristics$9D4:
, study performed -y Doan et al$ sho.ed a decrease in the incidence and pre'alence of
8MV retinitis after the ad'ent of H,,!+$ +he relapses of 8MV retinitis .ere less
freBuent 9>D0 -efore H,,!+ 's$ </0 after H,,!+: and ne.ly diagnosed 8MV
retinitis also decreased 9D$<0 -efore H,,!+ to <$20 after H,,!+:$ !emission
durations from recurrent 8MV retinitis ha'e increased in patients recei'ing H,,!+#
.hich is associated .ith decreased progression of retinal necrosis# and to lo.er ris2 of
retinal detachment$ ?e'ertheless# it does not restore the retina .here such damage has
already occurred$9D@# <0<:
5empen et al$ follo.ed up @CA patients to e'aluate the relationship of anti)8MV
treatment and immune reconstitution in response to H,,!+ on the mortality ris2 of
patients .ith ,ID( and 8MV retinitis$ +he use of H,,!+ reduced the ris2 of mortality
-y C<0I it .as AD0 lo.er for those .ho de'eloped immune reco'ery and 4A0 lo.er for
those .ho did not$9DD:
Vision related Buality of life 9JO": may still -e compromised -y 8MV retinitis e'en
.hen general health related JO" has impro'ed in response to H,,!+$ +herefore#
pre'ention of 8MV .ith anti)8MV medications may -e .arranted in high ris2 su-3ects$
9D/: +he study -y Doan et al$ also suggested that a 8D4F cell count a-o'e @0 cells=mm>
or a lo. 'iral load does not fully protect from 8MV disease$ Immune response
reconstitution may -e only partial after H,,!+# -ecause lac2 of pathogen specific 8D4F
+ cell response may persist e'en in the presence of a significant rise in the a-solute 8D4F
+ cell counts$
+herefore# HIV)infected patients still reBuire close ocular follo. up e'en if they are -eing
treated .ith H,,!+$ Moreo'er# 'irologic resistance to H,,!+ is -ecoming more
freBuent$9D># D@# DC:
Occasionally# H,,!+ may cause 'ision loss 'ia the mechanism of immune reco'ery
u'eitis$9D/: It may -e characteri4ed -y 'itritis and optic disc and macular edema$ Ocular
neo'asculari4ation at the optic disc and the retinal periphery may also occur$ 8linically
important complications of immune)reco'ery u'eitis may include cataract# epiretinal
mem-rane formation# and cystoid macular edema$ +he mechanism of this condition
remains unclear$ Henerally# su-stantial inflammation does not occur in eyes .ithout prior
8MV retinitis$ +herefore# immune reco'ery u'eitis may -e caused -y an immune
response related to the persistence of 8MV antigen in the eye$ +here are some reports
sho.ing that protease inhi-itors may -e associated .ith increased cytomegalo'irus)
specific lymphocyte proliferation and production of inflammatory cyto2ines$9A# DA: (ong
et al$ sho.ed that the ris2 of immune reco'ery u'eitis .as strongly correlated .ith prior
use of cidofo'ir$ It .as not clear .hether continuing noncidofo'ir anti)8MV therapy after
immune reco'ery .ould reduce the ris2 of immune reco'ery u'eitis$9/0:
!ecent reports sho. that 8MV retinitis progression does not necessarily correlate .ith
'iral 8MV loads# .hich is different from other 8MV diseases# such as colitis and
pneumonitis$9D>:
Henerally# 8MV retinitis is characteri4ed -y hemorrhagic necrosis that may e1tend along
the 'ascular arcade# as .ell as retinal .hitening$ 9Figure <-: +he lesion tends to enlarge
o'er time$ +he patients may also present .ith mild 'itreal inflammation# anterior u'eitis#
and up to @0 of them may ha'e in'ol'ement of the optic disc$ Visual field loss# -lurred
'ision and photopsias are common complaints -y the patients$9/# D@:
+he administration of systemic anti)8MV medication may pre'ent the occurrence of
retinitis in the fello. eye$
+he choice of a drug for the treatment of 8MV retinitis should -e -ased on the response to
pre'ious treatments# side effects as .ell as e1tension and se'erity of the disease$
In patients on chronic suppressi'e# maintenance therapy# 8MV resistant to the treatment
-eing used may de'elop$ +he identification of resistant 'irus in the -lood or urine may
ha'e an association .ith ad'erse clinical outcomes of the 8MV retinitis$ +here may -e an
increased ris2 of retinitis progression# as .ell as an increase in the amount of retinal area
affected -y 8MV$ Patients treated .ith ganciclo'ir implant alone pro-a-ly ha'e a higher
rate of contralateral ocular or 'isceral disease than the ones recei'ing concomitant oral
ganciclo'ir$ +he detection of 8MV 'iral load in the -lood or direct seBuencing of -lood
specimens for 8MV &"A/ gene mutations may -e important in the clinical setting# in
order to determine the patients .ith resistant 'irus$9/<:
Intra'enous ganciclo'ir may -e indicated .hen there is -ilateral retinitis or .hen systemic
treatment is reBuired$9/2: Ho.e'er# it may cause myelosuppression$ Intra'itreal
ganciclo'ir in3ection is another option# though freBuent in3ections are reBuired and the
fello. eye and distant organs are not protected$ (tandard doses range from 200 Gg to 400
Gg administered t.ice a .ee2# for up to > .ee2s# follo.ed -y .ee2ly maintenance
in3ections$ , report presented -y Vele4 et al$ suggested that higher doses of ganciclo'ir
may -e tolerated -y the eye# and .hen associated .ith intra'itreous foscarnet# they may
-e effecti'e in controlling 8MV retinitis in patients .ho do not respond to con'entional
treatment$9/># /4# /@: , controlled trial of 'alganciclo'ir -y Martin et al$ sho.ed that it
appears to -e as effecti'e as intra'enous ganciclo'ir for induction treatment and is
effecti'e for long)term management of 8MV retinitis$9/D:
, ganciclo'ir intra'itreal implant has -een de'eloped as a local treatment option that does
not in'ol'e intra'itreal in3ections and a'oids systemic side)effects$9//: It is a non)
eroda-le drug deli'ery de'ice# .hich can pro'ide therapeutic le'els of ganciclo'ir to the
posterior segment of the eye$ +he implants are designed to release ganciclo'ir o'er a
period of months$ Factors in the decision to use the ganciclo'ir implant include the
location and se'erity of 8MV retinitis# the patientKs potential for immunologic
impro'ement# and the ris2s and costs associated .ith implantation and concomitant oral
ganciclo'ir therapy$ 7ndophthalmitis is an uncommon complication of ganciclo'ir
implant surgery$9/C:
Intra'enous foscarnet is another treatment optionI ne'ertheless# it is associated .ith renal
insufficiency$9/2:
8om-ined intra'enous ganciclo'ir and foscarnet offers the ma1imal protection of other
eye and distant organs disease# though long daily infusions are reBuired and the side
effects are com-ined$9/A:
In resistant cases# cidofo'ir therapy may -e used$ Ho.e'er# it has -een associated .ith
iritis and hypotonia and has the potential for nephroto1icity# particularly in patients .ith
history of 2idney disease$9/2# /A:
Other treatment alternati'es are formi'irsen in3ected into the 'itreous or oral
'alganciclo'ir$9/2:
(yphilis !etinitis
(yphilis may affect the retina in HIV positi'e patients$ ,s +reponema pallidum and HIV
may -e -oth transmitted se1ually# it is not uncommon to detect -oth pathogens in the
same patient$ +he retinitis is characteri4ed -y a deep yello. lesion$ !etinal 'asculitis and
intraocular inflammation may -e present$ +he diagnosis can -e confirmed -y the serum
fluorescent treponema anti-ody a-sorption test 9F+, ,(: and microhemagglutination
assay 9MH,)+P:$ *hen the diagnosis is confirmed# 'igorous treatment should -e started
.ith <2)24 million units of intra'enous penicillin H for /)<0 days$9C0: +etracycline#
erythromycin and chloramphenicol are options for patients allergic to penicillin$ (ome
authors -elie'e that HIV positi'e patients may reBuire maintenance therapy# -ecause
ocular symptoms may recur$9C<# C2: FreBuently# there may -e atypical presentations of
ocular syphilis in these patients# such as 'itritis$9C2:
8andidal 7ndophthalmitis
8andidal endophthalmitis generally presents as a focal .hite infiltrate in the choroid# and
may -rea2 through the retina into the 'itreous$ &sually# an o'erlying 'itritis is present$
Vitreous a-scesses may also -e seen$ Once the diagnosis is confirmed# the patients should
recei'e intra'enous amphotericin$9@:
+o1oplasmic !etinochoroiditis
,round <E20 of HIV infected patients may present .ith to1oplasmic retinochoroiditis$
+he pre'alence of +$ gondii infection 'aries -et.een geographic regions and -et.een
population groups$ +o1oplasmic retinochoroiditis still has a high pre'alence in regions
such as southern ra4il# .here it may -e as high as C0 9<04:$ Ocular lesions may first
de'elop many years after +$ gondii infection$ It is usually -ilateral and presents multifocal
sites of infection# .hich is not common in immunocompetent persons$ !etinochoroidal
scars and retinal hemorrhage may -e a-sent$ +he appearance of the lesions 'aries .ith
intensity of inflammation and duration of acti'e retinal infection$ Patients usually
complain of seeing floaters# pain and decrease in 'isual acuity$ (erologic studies should
-e performedI ho.e'er they may -e negati'e e'en in the presence of disease$ P8! of the
ocular fluid may -e helpful in distinguishing -et.een to1oplasmic retinochoroiditis and
other ocular diseases$
+he treatment consists of oral sulfadia4ine# com-ined .ith pyrimethamine or
clindamycin# or -oth$ +rimethoprim)sulfametho1a4ole may also -e effecti'e$ ,to'aBuone
may -e used in immunocompromised patients .ho are at increased ris2 of -one marro.
to1icity from sulfonamides$ +he patients may ha'e fe.er relapses .hen recei'ing
maintenance sulfadia4ine or trimethoprim)sulfametho1a4ole$ !ecent studies ha'e sho.n
that a half)dosage regimen is also effecti'e in pre'enting recurrences# .hich are -elie'ed
to -e caused either -y the release of parasites from tissue cysts in the retina or
dissemination of parasites from non)ocular sites$ 9C>)CD# <04:
Infectious 8horoiditis
Myco-acterium tu-erculosis# 8andida species# 8ryptococcus species# Pneumocystis
carinii and +reponema pallidum are among the most common entities related to infectious
choroiditis# .hich is seen in less than <0 of HIV positi'e patients$ Multiple# -ilateral#
round or o'oid# yello.).hite lesions characteri4es Pneumocystis carinii choroiditis$ +hese
lesions are usually slo.ly progressi'e and are not associated .ith iritis# 'itritis# or
'asculitis$ +he treatment is the same for Pneumocystis carinii pneumonia$9C/)CA# AC:
VI)?euro)Ophthalmic Manifestations of HIV Infection
Optic neuropathies in HIV positi'e patients may -e related to compression# infiltration#
infection# 'aso occlusion or inflammation$ 8ryptococcal meningitis and intracere-ral
to1oplasma cysts# .hich are intracranial manifestations associated .ith HIV# can affect
the eyes# causing ner'e palsies$ ?euro ophthalmic complications of HIV ha'e also -een
reported in the a-sence of associated opportunistic infections$ Optic neuritis associated
.ith a multiple sclerosis li2e illness in the presence of HIV has also -een descri-ed$9A0:
Other neuro ophthalmic complications are 'isual field defects# papilledema# secondary to
ele'ated intracranial pressure and ocular motility disorders# occurring in up to <@0 of
HIV)infected patients$9@# A<: HIV may also cause diplopia due to palsies of cranial 'er'es
III# IV# and VI$ ?eurosyphilis# progressi'e multifocal leu2oencephalopathy 9PM":# .hich
is caused -y J8 polyoma'irus# meningeal and parenchymal lymphoma# and intracere-ral
infection .ith herpes 'irus ha'e also -een related to neuro)ophthalmic manifestations$
+he diagnosis of PM" should -e considered in immunocompromised patients .ith neuro)
opthalmic findings# especially in those presenting .ith homonymous hemianopia and
nystagmus$9A2: Herpes 'irus may present .ith papilledema and e1traocular muscle
palsies$
Micro'ascular oculomotor ner'e palsies may occur in association .ith HIV$ Premature
atherosclerosis is commonly seen in HIV)infected patients due to an un2no.n
mechanism$9A>:
"um-ar puncture and magnetic resonance imaging are usually reBuired in order to
determine the pathogen causing the neuro ophthalmic symptoms# and to start the proper
treatment$ Henerally# intracranial lymphoma is treated .ith radiation and chemotherapy$
+he infections are treated .ith specific antimicro-ial drugs$9/:
+he optic ner'e may -e affected -y HIV due to direct infection$ ,nother e1planation is
related to HIV 'iral proteins$ +at and gp <20# .hich are 'iral proteins# may ha'e direct
and indirect to1ic effects on neurons$ Moreo'er# HIV may induce the production of +?F
alpha# I" I and arachidonic acid meta-olites# .hich may cause neuroto1icity$ (ome
studies suggest that non)nucleoside and nucleoside re'erse transcriptase inhi-itors
9?!+Is: may impair mithocondrial function$9A0:
HIV infected persons differ in measures of the retinal ner'e thic2ness# cross sectional area
and cup shape$ Most defects are found in patients .ith associated 8MV retinitis$ , study
-y Plummer et al$ demonstrated that HIV positi'e patients .ithout 8MV retinitis still
ha'e statistically significantly a-normal measures in retinal fi-er layer thic2ness# rim
'olume# retinal fi-er layer area and dis2 area# indicating that there may -e destruction of
the retina as a complication of HIV infection# .ith or .ithout 8MV retinitis$9A4# A@:
VII E Ocular Manifestations in the Pediatric Hroup
+he first reports of HIV infection in children are from <AC2# after the description of the
disease in intra'enous drug a-users and homose1ual men$9AD: , glo-al summary of
HIV=,ID( epidemic dating from Decem-er 200> from &?,ID(=*HO estimates that
there are 2$@ million children under <@ years .orld.ide li'ing .ith HIV=,ID(# and
/00#000 .ere ne.ly infected .ith HIV in 200>$ ,ppro1imately @00#000 children died
from the disease in 200>$92:
+he most freBuent mode of transmission of HIV in the pediatric group is mother to child
transmission$ +he incu-ation period tends to -e shorter in children$ (ome -acterial
infections are more common in this age group than in adults# .hereas cryptococcosis and
to1oplasmosis are less freBuent$ +herefore# HIV infection may -e different in children in
se'eral .ays$
+he occurrence of ophthalmic complications associated .ith HIV infection is
significantly lo.er in the pediatric group$ +he first reports of eye complications in
children related to HIV infection are from <AC2$ 5aposi6s sarcoma# as .ell as 8MV
retinitis are not as common as in the adult population$ +he reason for this fact is still
unclear# -ut may -e related to an altered immune response to HIV in children$ +he most
freBuent manifestation in the pediatric group is dry eye syndrome# .hich occurs in
appro1imately 200 of patients$ (ome authors descri-ed peri'asculitis of the peripheral
fundus 'essels as a common finding in children .ith ,ID($9AD# AA:
, report -y 5estelyn et al$# .ho follo.ed <D2 HIV infected children in ,frica# sho.ed a
high incidence 9>C0: of peri'asculitis and=or sheathing of the peripheral retinal 'essels$
ilateral in'ol'ement .as 'ery common and the se'erity tended to -e symmetrical$ Veins
.ere affected more often than arteries$ +he lesions freBuently originated in the periphery#
sometimes e1tending to.ards the posterior pole .ithout in'ading it$ +he authors also
descri-ed a possi-le lin2 -et.een lymphocitic interstitial pneumonia# parotitis# lacrimal
gland in'ol'ement# and peri'asculitis of the retinal 'essels as the e1pression of the same
immunopathological process in different sites$ 8MV retinitis and cotton).ool spots# the
most freBuent ocular finding in adult HIV infection# as .ell as e1ternal lesions# such as
herpes 4oster ophthalmicus and 5aposi6s sarcoma of the eyelids .ere rare in the ,frican
pediatric group$9AD:
Purdy et al$ reported three cases of -ilateral progressi'e outer retinal necrosis due to
'aricella)4oster 'irus in children .ith HIV infection$ ,ll three lost 'ision in -oth eyes$
9<00:
top
,c2no.ledgements
+he author .ishes to than2 the ?ational 7ye Institute# ?ational Institutes of Health for
pro'iding the clinical pictures and the anonymous re'ie.ers for their constructi'e
comments$
top
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8linical Pictures
Figure <a$ ?ormal fundus
Figure <-$ Fundoscopic changes seen in 8MV retinitis
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Fi#$"e %&
?ormal fundus
Fi#$"e %b
Fundoscopic changes seen in 8MV retinitis