Ocular Manifestations of HIV Infection

Emmett T. Cunningham, Jr., M.D., Ph.D., M.P.H., and Todd P. Margolis, M.D., Ph.D. N Engl J Med 1998; 339 !3"#!$$Jul% !3, 1998D&' 1(.1()"*NEJM1998(+!3339($(" ,hare -rti.le The human immunode/i.ien.% 0irus 1H'23 has in/e.ted nearl% 9((,((( 4ersons in North -meri.a and more than 3( million 5orld5ide.1,! ,in.e the initial des.ri4tion o/ e%e a6normalities in H'2#4ositi0e 4atients more than 1) %ears ago,3 numerous re4orts ha0e des.ri6ed the s4e.trum and natural histor% o/ H'2#asso.iated e%e disorders, 5hi.h a//e.t +( to 8( 4er.ent o/ all 4atients at some 4oint during their illness.$ 7e 4resent here the 8e% .lini.al /eatures o/ the most .ommonl% en.ountered o.ular mani/estations o/ H'2 in/e.tion, as 5ell as the main issues in their management. CD4+ T-Lymphocyte Count as a Predictor of is! 9or %ears, the CD$: T#l%m4ho.%te .ount 4ro0ed a relia6le 4redi.tor o/ the ris8 o/ o.ular .om4li.ations o/ H'2 in/e.tion 1Ta6le 1Ta6le 1

CD$: T#;%m4ho.%te Counts in Patients Presenting 5ith Common H'2#-sso.iated Disorders 'n0ol0ing the E%es.3.) <e.entl%, ho5e0er, the use o/ highl% a.ti0e antiretro0iral thera4%" has allo5ed su6stantial and sustained, al6eit in.om4lete, re4o4ulation o/ T l%m4ho.%tes to o..ur in man% 4atients.+ ,u.h o6ser0ations ha0e raised the =uestion o/ 5hether re.onstituted T#l%m4ho.%te 4o4ulations are in /a.t /un.tional and, more s4e.i/i.all%, 5hether the .urrent or the lo5est CD$: T#l%m4ho.%te .ount is a 6etter 4redi.tor o/ the ris8 o/ H'2#asso.iated disorders.8 &ne 5ould ho4e that in.reases in .ir.ulating CD$: T l%m4ho.%tes indu.ed 6% highl% a.ti0e anti#retro0iral thera4% 5ould 6e 4rote.ti0e, and re4orts o/ s4ontaneous resolution o/ .%tomegalo0irus retinitis in 4atients 5ith in.reased CD$: .ounts as a result o/ su.h thera4% are no5 6eginning to a44ear.9,1( Ho5e0er, the re.o0er% o/ CD$: T l%m4ho.%tes ta8es months to %ears,+ and 4atients ha0e 4ermanent or long#lasting de4letion o/ T# l%m4ho.%te re4ertoires.11 - re.ent re4ort1! on .%tomegalo0irus retinitis in 4atients 5ho 5ere re.ei0ing highl% a.ti0e antiretro0iral thera4% and 5hose

CD$: .ounts 5ere higher than !(( .ells 4er .u6i. millimeter suggests that re.onstituted CD$: .ells ma% /ail to 4ro0ide 4rote.ti0e immunit%, although the 4ossi6ilit% that the onset o/ .%tomegalo0irus retinitis 4re.eded the re.o0er% o/ CD$: T l%m4ho.%tes 5as not ruled out.8 >i0en these un.ertainties, 5e ha0e de.ided to monitor other5ise as%m4tomati. H'2# 4ositi0e 4atients on the 6asis o/ the lo5est CD$: T#l%m4ho.%te .ount,8 at least until antigen#s4e.i/i. tests o/ T#l%m4ho.%te /un.tion 6e.ome more 5idel% a0aila6le.13 "dne#al Manifestations The o.ular adne?a in.lude the e%elids, .on@un.ti0a, and la.rimal drainage s%stem. The most .ommon .om4li.ations a//e.ting these stru.tures are her4es Aoster o4hthalmi.us, Ba4osiCs sar.oma, mollus.um .ontagiosum, and .on@un.ti0al mi.ro0as.ulo4ath%.1$ Herpes $oster Ophthalmicus Her4es Aoster o4hthalmi.us is a 0esi.ulo6ullous dermatitis .aused 6% 0ari.ellaDAoster 0irus. The in/e.tion in0ol0es the o4hthalmi. distri6ution o/

the trigeminal ner0e 19igure 1-9igure 1 H'2#-sso.iated E%e Disorders.3,1) and 4ain ma% 6e se0ere. The o..urren.e o/ 0ari.ellaDAoster 0irus dermatitis in a 4erson less than )( %ears old is un.ommon and should suggest the 4ossi6ilit% o/ an immunosu44ressi0e .ondition.1) Her4es Aoster o4hthalmi.us a//e.ts ) to 1) 4er.ent o/ H'2#4ositi0e 4atients.$ Con.urrent or dela%ed 8eratitis, s.leritis, u0eitis, retinitis, or en.e4halitis ma% also o..ur.1) Treatment .onsists o/ intra0enous a.%.lo0ir 11( mg 4er 8ilogram o/ 6od% 5eight three times a da% /or se0en da%s3 /ollo5ed 6% an oral maintenan.e regimen 18(( mg three to /i0e times a da%3, 5hi.h redu.es the /re=uen.% o/ re.urren.es. 9am.i.lo0ir 1)(( mg three times a da%3 o//ers the ad0antage o/ /e5er dail% doses, 6ut /or long#term maintenan.e thera4%, its e//i.a.% as .om4ared 5ith that o/ a.%.lo0ir is still under stud%. 9or 4atients 5ith 4oor res4onses to a.%.lo0ir or /am.i.lo0ir, a trial o/ intra0enous /os.arnet should 6e .onsidered. %aposi&s 'arcoma Ba4osiCs sar.oma is a highl% 0as.ulariAed, 4ainless mesen.h%mal tumor a//e.ting the s8in and mu.ous mem6ranes in u4 to !) 4er.ent o/ H'2# 4ositi0e 4atients.1" -44ro?imatel% !( 4er.ent o/ su.h 4atients ha0e

as%m4tomati. Ba4osiCs sar.oma o/ the e%elids or .on@un.ti0a 19igure 1E3,1+ 5hi.h ma% mimi. a .halaAion or su6.on@un.ti0al hemorrhage, res4e.ti0el%. <adiation thera4% is e//e.ti0e /or e%elid and .on@un.ti0al Ba4osiCs sar.oma, 6ut it is e?4ensi0e and ma% .ause loss o/ lashes, s8in irritation, and .on@un.ti0itis.18 E?.ision o/ .on@un.ti0al lesions .an 6e 4er/ormed 5ith little di//i.ult%, 5hereas surgi.al remo0al o/ e%elid lesions is o/ten .om4li.ated 6% su6stantial 6leeding. -lternati0e thera4ies /or 6oth e%elid and .on@un.ti0al lesions in.lude lo.al .r%othera4% and intralesional .hemothera4% 5ith 0in6lastine. &.ular lesions a..om4anied 6% s%stemi. Ba4osiCs sar.oma are o/ten 6est treated 5ith s%stemi. .hemothera4%. Molluscum Conta(iosum Mollus.um .ontagiosum is a highl% .ontagious dermatitis .aused 6% a 4o?0irus. Eoth the s8in and the mu.ous mem6ranes ma% 6e a//e.ted, 5ith multi4le, small, 4ainless, um6ili.ated lesions. Mollus.um .ontagiosum is more .ommon and tends to 6e more se0ere in H'2#4ositi0e 4ersons than in H'2#negati0e 4ersons, 5ith larger, more numerous, and more ra4idl% gro5ing lesions.1" 'n0ol0ement o/ the e%elids 19igure 1C3 o..urs in u4 to ) 4er.ent o/ H'2#in/e.ted 4atients.19 -sso.iated /olli.ular .on@un.ti0itis and su4er/i.ial 8eratitis ha0e 6een re4orted in immuno.om4etent 4atients 6ut are un.ommon in H'2#in/e.ted 4ersons. Treatment o4tions in.lude .r%othera4%, .urettage, in.ision, and e?.ision. Con)uncti*al Micro*asculopathy ,e0ent% to 8( 4er.ent o/ H'2#4ositi0e 4atients e0entuall% ha0e as%m4tomati. .on@un.ti0al mi.ro0as.ular .hanges, in.luding segmental 0as.ular dilatation and narro5ing, mi.roaneur%sm /ormation, the a44earan.e o/ .omma#sha4ed 0as.ular /ragments, and FsludgingG o/ the 6lood .olumn.!(,!1 These .hanges, 5hi.h are 6est seen 5ith a slit#lam4 6iomi.ros.o4e near the lim6us 19igure 1D3, are .orrelated 5ith the o..urren.e o/ retinal mi.ro0as.ulo4ath%. The .ause o/ .on@un.ti0al mi.ro0as.ular .hanges is un8no5n, although in.reased 4lasma 0is.osit%, H'2#related immune#.om4le? de4osition, and dire.t in/e.tion o/ the .on@un.ti0al 0as.ular endothelium 6% H'2 ha0e 6een 4ro4osed as 4ossi6le .auses.!1 No treatment is indi.ated. "nterior-'e(ment Manifestations The anterior segment in.ludes the .ornea, anterior .ham6er, and iris. More than hal/ o/ H'2#4ositi0e 4atients ha0e anterior#segment .om4li.ations.1$ The most .ommon 0isuall% im4ortant .om4li.ations

in.lude dr% e%es 18erato.on@un.ti0itis si..a3, .orneal in/e.tion 18eratitis3, and anterior#.ham6er in/lammation 1irido.%.litis3. -lthough 6est seen 5ith a slit lam4, anterior#segment .om4li.ations are o/ten dete.ta6le 5ith a 4enlight. Common s%m4toms in.lude irritation, 4ain, sensiti0it% to light, and de.reased 0isual a.uit%. %eratocon)uncti*itis 'icca Berato.on@un.ti0itis si..a o..urs in 1( to !( 4er.ent o/ 4atients 5ith H'2 in/e.tion, t%4i.all% at later stages o/ illness.!! -6normal results on ,.hirmerCs testing and inter4al4e6ral rose#6engal staining hel4 esta6lish the diagnosis. The .ause is 4ro6a6l% related to H'2#mediated in/lammation and destru.tion o/ the 4rimar% and se.ondar% la.rimal glands. '/ en.e4halo4ath% is also 4resent, in.om4lete lid .losure 1lago4hthalmos3, a de.reased 6lin8 rate, or 6oth ma% e?a.er6ate the .ondition. Treatment 5ith arti/i.ial tears and long#a.ting lu6ri.ating ointments usuall% 4ro0ides s%m4tomati. relie/. Infectious %eratitis -lthough .orneal in/e.tions o..ur in less than ) 4er.ent o/ H'2#in/e.ted 4atients, the% ma% result in 4ermanent loss o/ 0ision.1$ 2ari.ellaDAoster 0irus 19igure 1E3 and her4es sim4le? 0irus are the most .ommon .auses o/ 8eratitis. De.reased .orneal sensation and ele0ated intrao.ular 4ressure 4ro0ide .lues to the diagnosis. Beratitis related to 0ari.ellaDAoster 0irus in/e.tion is o/ten .hara.teriAed 6% the 4resen.e o/ her4es Aoster o4hthalmi.us, although the dermatitis ma% 6e mild or e0en a6sent.1),!3 Eoth 0ari.ellaDAoster 0irus 8eratitis and her4es sim4le? 0irus 8eratitis ma% re.ur more /re=uentl% and in some .ases 6e more resistant to treatment in H'2#4ositi0e 4atients than in other 4atients.!$,!) Treatment o/ 0ari.ellaDAoster 0irus 8eratitis is similar to that o/ her4es Aoster o4hthalmi.us, 5hereas her4es sim4le? 0irus 8eratitis usuall% res4onds to lo5er doses o/ oral a.%.lo0ir 1$(( mg /i0e times a da%3 or /am.i.lo0ir 11!) to )(( mg three times a da%3. ;ong#term thera4% ma% 6e ne.essar% /or 6oth 0ari.ellaDAoster 0irus 8eratitis and her4es sim4le? 0irus 8eratitis. Ea.terial and /ungal .orneal in/e.tions do not a44ear to 6e more .ommon in H'2#4ositi0e 4ersons than in others 6ut do tend to 6e more se0ere.1$ Numerous .ausati0e organisms ha0e 6een re4orted, although .andida s4e.ies are 4arti.ularl% .ommon in intra0enous drug users.!" >ramCs staining and .ultures should 6e 4er/ormed to hel4 guide thera4%. Mi.ros4oridia are o6ligate intra.ellular 4arasites 8no5n to .ause gastroenteritis, sinusitis, and 4neumonitis in H'2#4ositi0e 4atients.!+ &.ular mi.ros4oridiosis is un.ommon 6ut .an 4rodu.e a 4un.tate su4er/i.ial

8erato4ath% 19igure 193, o/ten 5ith a mild 4a4illar% .on@un.ti0itis.!8 The organism is e?tremel% di//i.ult to .ulture 6ut .an 6e readil% seen 5ithin .orneal or .on@un.ti0al e4ithelial .ells 5ith the use o/ either Masson tri.hrome or >iemsa staining. Treatment o4tions in.lude oral itra.onaAole, to4i.al /umagillin, and oral al6endaAole. Iridocyclitis Mild irido.%.litis is .ommon in H'2#4ositi0e 4atients and is usuall% o6ser0ed in asso.iation 5ith retinitis .aused 6% .%tomegalo0irus!9 or 0ari.ellaDAoster 0irus.3( ,e0ere in/lammation o/ the anterior .ham6er is un.ommon 6ut .an o..ur in asso.iation 5ith to?o4lasmi. retino.horoiditis,31 s%4hiliti. retino.horoiditis,3! or rarer /orms o/ 6a.terial or /ungal retinitis.$ Medi.ations used to treat o44ortunisti. in/e.tions in H'2#4ositi0e 4atients, su.h as ri/a6utin33 and .ido/o0ir,3$ ma% also .ause irido.%.litis. ;astl%, irido.%.litis ma% 6e 4art o/ a more generaliAed autoimmune and endogenous u0eitis, su.h as <eiterCs s%ndrome, 5hi.h ma% 6e more .ommon in 4atients 5ith H'2 in/e.tion than in those 5ithout it.3) 'denti/i.ation o/ irido.%.litis re=uires high#4o5er slit#lam4 e?amination. Treatment should 6e dire.ted at a s4e.i/i. in/e.tious .ause. '/ to?i.it% is sus4e.ted, the dose should 6e ta4ered or the o//ending drug 5ithdra5n. To4i.al .orti.osteroid dro4s are o/ten indi.ated 6ut should 6e used 5ith e?treme .aution and onl% 5ith a44ro4riate antimi.ro6ial treatment 5hen in/e.tion is sus4e.ted. Posterior-'e(ment Manifestations The 4osterior segment in.ludes the retina, .horoid, and o4ti.#ner0e head. More than hal/ o/ H'2#4ositi0e 4atients ha0e disorders in0ol0ing these stru.tures. T%4i.al s%m4toms in.lude /loaters, /lashing lights 14hoto4sias3, 0isual#/ield de/e.ts, and de.reased 0isual a.uit%. -n a//erent 4u4illar% de/e.t .onstitutes strong e0iden.e o/ e?tensi0e retinal or o4ti.#ner0e in0ol0ement, and e0er% 4atient 5ith 0isual loss should 6e tested /or su.h a de/e.t. Diagnoses are usuall% 6ased on .hara.teristi. .lini.al /indings o6ser0ed on dilated#/undus e?amination 5ith the use o/ either a dire.t or an indire.t o4hthalmos.o4e. etinal Micro*asculopathy <etinal mi.ro0as.ulo4ath%, also termed a.=uired immunode/i.ien.% s%ndrome 1-'D,3 or H'2 retino4ath%, o..urs in )( to +( 4er.ent o/ H'2# in/e.ted 4ersons. The most .ommonl% o6ser0ed mani/estations in.lude .otton#5ool s4ots, intraretinal hemorrhages, and retinal mi.roaneur%sms 19igure 1>3.3",3+ These /indings in.rease in /re=uen.% 5hen the CD$: T# l%m4ho.%te .ount /alls 6elo5 1(( .ells 4er .u6i.

millimeter.$,3",3+ H%4otheses a6out the 4athogenesis o/ retinal mi.ro0as.ulo4ath% 4arallel those suggested /or .on@un.ti0al 0as.ular .hanges.!1 H'2#asso.iated retinal mi.ro0as.ulo4ath% is t%4i.all% as%m4tomati. and transient 6ut ma% 4la% a 4art in 4rogressi0e o4ti.#ner0e atro4h%, 5ith loss o/ .olor 0ision, .ontrast sensiti0it%, and 0isual#/ield de/e.ts.38 The role o/ retinal mi.ro0as.ulo4ath% in the de0elo4ment o/ .%tomegalo0irus retinitis remains un.lear.3",39,$( Infectious etinitis Cytome(alo*irus etinitis C%tomegalo0irus retinitis a//e.ts 3( to $( 4er.ent o/ H'2#4ositi0e 4atients in de0elo4ed .ountries,$,!9 t%4i.all% o..urring 5hen the CD$: T# l%m4ho.%te .ount has /allen 6elo5 1(( .ells 4er .u6i. millimeter. -//e.ted 4atients usuall% re4ort /loaters, 4hoto4sias, 0isual#/ield loss, or 6lurred 0ision. Classi.all%, anterior#.ham6er and 0itreous e?aminations re0eal little in/lammation, and /undus e?amination sho5s /ull#thi.8ness retinal 5hitening, o/ten asso.iated 5ith intraretinal hemorrhages 19igure 1H3. The o4ti. ner0e is in0ol0ed in u4 to ) 4er.ent o/ 4atients. The use o/ highl% a.ti0e antiretro0iral thera4% has .hanged the natural histor% o/ H'2#asso.iated .%tomegalo0irus retinitis in t5o im4ortant 5a%s. 9irst, sin.e /e5er 4atients ha0e CD$: T#l%m4ho.%te .ounts 6elo5 1(( .ells 4er .u6i. millimeter, /e5er 4atients are at ris8 /or the de0elo4ment o/ .%tomegalo0irus retinitis. -s a .onse=uen.e, the in.iden.e o/ .%tomegalo0irus retinitis in .ountries 5here highl% a.ti0e antiretro0iral thera4% is a0aila6le has de.reased dramati.all%.8 ,e.ond, 4atients re.ei0ing su.h thera4% 5ho ha0e earl% or 4artial re.onstitution o/ CD$: .ell 4o4ulations ma% ha0e other5ise un.ommon /eatures o/ .%tomegalo0irus in/e.tion, in.luding moderate#to#se0ere anterior#.ham6er or 0itreous in/lammation$1 and s4ontaneous healing in the a6sen.e o/ s4e.i/i. anti.%tomegalo0irus thera4%.9,1( The treatment o/ .%tomegalo0irus retinitis is a ra4idl% e0ol0ing /ield that has 6een thoroughl% .o0ered in se0eral re.ent re0ie5s 1Ta6le !Ta6le !

Treatments /or C%tomegalo0irus <etinitis.3.!9,$!,$3 The .hoi.e o/ an a44ro4riate anti0iral agent and the route o/ deli0er% should 6e 6ased on the lo.ation and e?tent o/ disease, 4otential drug#related side e//e.ts, and the e//e.ti0eness o/ 4rior treatments.

Varicella+$oster Virus etinitis 2ari.ellaDAoster 0irus is the se.ond most .ommon .ause o/ ne.rotiAing retinitis in H'2#4ositi0e 4ersons, a//e.ting 1 to $ 4er.ent o/ 4atients.!1 ;i8e .%tomegalo0irus, 0ari.ellaDAoster 0irus 4rodu.es retinal 5hitening, o/ten a..om4anied 6% intraretinal hemorrhages 19igure 1'3. Ho5e0er, 0ari.ellaD Aoster 0irus retinitis is usuall% distinguished 6% ra4id 4rogression, multi/o.al lesions, and the initial in0ol0ement o/ dee4 retinal la%ers. - .on.urrent or re.ent her4es Aoster dermatitis 4ro0ides additional su44ort /or the diagnosis. The ris8s o/ retinal deta.hment and in0ol0ement o/ the other e%e are high.$$ -lthough rare, her4es sim4le? 0irus retinitis .an also .ause ra4id and 4ro/ound 0isual loss in H'2#4ositi0e 4atients.$) Control o/ retinitis .aused 6% 0ari.ellaDAoster 0irus or her4es sim4le? 0irus is di//i.ult and o/ten re=uires .om6ination thera4% 5ith intra0enous a.%.lo0ir and intra0enous as 5ell as intrao.ular gan.i.lo0ir or /os.arnet.$) ;ong#term thera4% is o/ten ne.essar%. To#oplasmic etinochoroiditis &.ular to?o4lasmosis a//e.ts 1 to ! 4er.ent o/ H'2#4ositi0e 4atients.$ -lthough the 4resentation ma% 6e at%4i.al, to?o4lasmi. .horioretinitis is o/ten distinguished 6% the o..urren.e o/ a moderate#to# se0ere anterior#.ham6er and 0itreous in/lammation, a relati0e a6sen.e o/ retinal hemorrhage, and 4igmented .horioretinal s.ars 19igure 1J3.31 'n .ontrast to immuno.om4etent 4ersons 5ith o.ular to?o4lasmosis, H'2# in/e.ted 4atients tend to ha0e multi/o.al or 6ilateral disease. Testing should in.lude serologi. assa%s /or 'g> and 'gM anti6odies against to?o4lasmosis, although the results ma% 6e negati0e in 4ro/oundl% immunosu44ressed 4atients. 9rom 3( to )( 4er.ent o/ 4atients 5ith o.ular to?o4lasmosis ha0e .entral ner0ous s%stem in0ol0ement. Treatment .onsists o/ 4%rimethamine in .om6ination 5ith a sul/onamide or .lindam%.in, or 6oth. ;ong#term or re4eated thera4% is o/ten ne.essar%. -to0a=uone has 6een used su..ess/ull%$" 6ut is e?4ensi0e and has %et to 6e sho5n to 6e su4erior to standard thera4%. ,acterial and -un(al etinitis &.ular s%4hilis is the most .ommon intrao.ular 6a.terial in/e.tion in H'2# 4ositi0e 4ersons, a//e.ting 1 to ! 4er.ent o/ 4atients.$,3! Patients ma% 4resent 5ith either an irido.%.litis or more di//use intrao.ular in/lammation. ;a6orator% testing should in.lude a s4e.i/i. tre4onemal#anti6od% assa%. 'n rare .ases, tests are negati0e des4ite the 4resen.e o/ a.ti0e disease. 'ntra0enous 4eni.illin > 1!$ million units 4er da% /or + to 1( da%s3 is the indi.ated treatment. <e.urren.es ma% o..ur des4ite ade=uate thera4%. &ther 6a.terial and /ungal .auses o/ retinitis or endo4hthalmitis are un.ommon in

4atients 5ith H'2 in/e.tion 6ut should 6e .onsidered in intra0enous drug users and 4atients 5ith s%stemi. 6a.terial or /ungal in/e.tion.$ Infectious Choroiditis 'n/e.tious .horoiditis a..ounts /or less than 1 4er.ent o/ o.ular disorders in most series o/ H'2#4ositi0e 4atients.$,$+ The in/e.tious agent is usuall% Pneumocystis carinii 19igure 1B3, although other organisms ha0e 6een identi/ied. Most o/ the re4orted .ases ha0e 6een identi/ied at auto4s%, re/le.ting the o/ten serious nature o/ the underl%ing s%stemi. in/e.tions.$+ Or.ital Manifestations &r6ital .om4li.ations o/ H'2 in/e.tion are un.ommon. &r6ital l%m4homa$8 and or6ital .ellulitis, usuall% due to as4ergillus in/e.tion,$9 ha0e 6een re4orted most /re=uentl%. ;%m4homa res4onds 5ell to radiation and .hemothera4%, 5hereas or6ital .ellulitis is treated 5ith s%stemi. antimi.ro6ial agents. /euro-Ophthalmic Manifestations Neuro#o4hthalmi. .om4li.ations o..ur in 1( to 1) 4er.ent o/ H'2#in/e.ted 4atients.)(#)! The most /re=uent /indings in.lude 4a4illedema /rom ele0ated intra.ranial 4ressure, .ranial#ner0e 4alsies, o.ular#motilit% disorders, and 0isual#/ield de/e.ts 1Ta6le 13. 2irtuall% an% in/e.tious or neo4lasti. 4ro.ess .an 4rodu.e these .hanges, 6ut .r%4to.o..al meningitis 19igure 1;3, meningeal and 4aren.h%mal l%m4homa, neuros%4hilis, and to?o4lasmosis are the most /re=uent .auses. Patients 5ith more di//use en.e4halo4athies related either to the dire.t e//e.ts o/ H'2 in/e.tion 1H'2 en.e4halo4ath%3 or to se.ondar% in/e.tion 5ith the JC 4ol%oma0irus, 5hi.h .auses 4rogressi0e multi/o.al leu8oen.e4halo4ath%,)3 ma% ha0e similar .om4li.ations. E0aluation usuall% in.ludes magneti. resonan.e imaging /ollo5ed 6% a lum6ar 4un.ture to o6tain .ere6ros4inal /luid /or a .ell .ount, .%tologi. studies, .ulture, and anti6od% and antigen testing. Treatment in.ludes radiation and .hemothera4%, in the .ase o/ l%m4homa, and s4e.i/i. antimi.ro6ial thera4%, in the .ase o/ identi/ied in/e.tions. There is .urrentl% no treatment /or H'2 en.e4halo4ath% or 4rogressi0e multi/o.al leu8oen.e4halo4ath%. Ocular Manifestations in Children Children are less li8el% than adults to ha0e o.ular mani/estations o/ H'2 in/e.tion, and the 4re0alen.e o/ .%tomegalo0irus retinitis is es4e.iall% lo5 in .hildren 1estimated at ) 4er.ent in one stud%)$3. The reason /or this di//eren.e is un8no5n 6ut ma% 6e related to an altered immune res4onse to

H'2 or to a lo5er 4re0alen.e o/ .%tomegalo0irus sero4ositi0it% in .hildren. H'2#in/e.ted .hildren are, ho5e0er, at in.reased ris8 /or neurode0elo4mental dela%,)) a .ondition o/ten asso.iated 5ith neuro# o4hthalmi. disorders. - /etal -'D,#asso.iated em6r%o4ath% 5ith do5n5ard o6li=uit% o/ the e%es, 4rominent 4al4e6ral /issures, h%4ertelorism, and 6lue s.lerae has also 6een des.ri6ed.)" Ocular Manifestations in De*elopin( Countries Ninet% 4er.ent o/ H'2#in/e.ted 4ersons li0e in de0elo4ing .ountries, 4arti.ularl% those in su6#,aharan -/ri.a and ,outheast -sia.1,! The /e5 studies o/ o.ular .om4li.ations o/ H'2 in/e.tion in these 4arts o/ the 5orld suggest that .%tomegalo0irus retinitis o..urs less /re=uentl% than in de0elo4ed .ountries and that o.ular .om4li.ations o/ to?o4lasmosis and tu6er.ulosis, her4es Aoster o4hthalmi.us, and 4a4illoma0irus#asso.iated .on@un.ti0al s=uamous#.ell tumors are more 4re0alent.)+ The reasons /or su.h an altered s4e.trum o/ o.ular disease in 4atients in de0elo4ing .ountries are almost assuredl% related to higher /re=uen.ies o/ e?4osure to .ausati0e in/e.tious agents and higher rates o/ death earl% in the .ourse o/ H'2 in/e.tion.) Ocular To#icity in HIV-Infected Patients 'ntrao.ular in/lammation, or u0eitis, o..urs in u4 to one third o/ 4atients treated 5ith high#dose ri/a6utin, 4arti.ularl% 5hen an anti/ungal aAole is used .on.urrentl%.33 Cido/o0ir3$ .auses u0eitis in !) to 3( 4er.ent o/ 4atients and ma% also .ause lo5 intrao.ular 4ressure, or h%4oton%, in u4 to 1( 4er.ent o/ 4atients. Mild u0eitis is usuall% managea6le 5ith to4i.al .orti.osteroid dro4s, 6ut more se0ere u0eitis and h%4oton% .an .ause 4ermanent 0isual loss and should there/ore 4rom4t a .hange in medi.ation. There ha0e also 6een isolated re4orts o/ 4atients 5ith a6normalities o/ retinal 4igment e4ithelium asso.iated 5ith high#dose didanosine,)8 .orneal e4ithelial in.lusions asso.iated 5ith intra0enous gan.i.lo0ir and a.%.lo0ir,)9 and .orneal su6e4ithelial de4osits asso.iated 5ith ato0a=uone."( Ea.h o/ these e//e.ts a44ears to 6e dose#related and, 5ith the e?.e4tion o/ a6normalities o/ retinal 4igment e4ithelium, tends to resol0e on.e the drug has 6een dis.ontinued. ,u44orted 6% a grant /rom <esear.h to Pre0ent Elindness. Dr. Margolis is the re.i4ient o/ a ;e5 7asserman Merit -5ard /rom <esear.h to Pre0ent Elindness. 'ource Information

9rom the 9ran.is '. Pro.tor 9oundation and the De4artment o/ &4hthalmolog%, Hni0ersit% o/ Cali/ornia, ,an 9ran.is.o, Medi.al Center, ,an 9ran.is.o. -ddress re4rint re=uests to Dr. Cunningham at the 9ran.is '. Pro.tor 9oundation, HC,9 Medi.al Center, ,an 9ran.is.o, C- 9$1$3#(9$$. <e/eren.es eferences 1. 1 H4date trends and -'D, in.iden.e, deaths, 4re0alen.e ## Hnited ,tates, 199". MM7< Mor6 Mortal 78l% <e4 199+;$" 1")#1+3 Medline !. ! HN-'D,*7H& re4ort on the glo6al H'2*-'D, e4idemi.. >ene0a 7orld Health &rganiAation, De.em6er 199+. 3. 3 Holland >N, >ottlie6 M,, Iee <D, ,.han8er HM, Pettit TH. &.ular disorders asso.iated 5ith a ne5 se0ere a.=uired .ellular immunode/i.ien.% s%ndrome. -m J &4hthalmol198!;93 393#$(! 7e6 o/ ,.ien.e J Medline $. $