SYMPOSIUM

Year : 2010 | Volume : 58 | Issue : 1 | Page : 45-54

Current approach in the diagnosis and management of panuveitis
Reema Bansal !ishali "upta #mod "upta
$epartment of %phthalmolog& #dvanced '&e Centre (ost "raduate )nstitute of *edical
'ducation and Research Chandigarh )ndia
$ate of +u,mission 04-+ep-2008
$ate of #cceptance 14-#pr-200-
$ate of .e,
(u,lication
22-$ec-200-
Correspondence Address:
!ishali "upta
(ost "raduate )nstitute of *edical 'ducation and Research Chandigarh-1/0 012
)ndia
5
3
DOI: 100410120101-4318058431
PMID: 2002-145

#,stract
(anuveitis is a generali4ed inflammation of not onl& the 5hole of the uveal tract ,ut also
involves the retina and vitreous humor0 )t differs from other anatomical sites of inflammation
in terms of causes as 5ell as distri,ution0 6he common causes of panuveitis in our population
are tu,erculosis !ogt-7o&anagi-8arada s&ndrome s&mpathetic ophthalmia Behcet9s disease
and sarcoidosis0 # large num,er of cases still remain idiopathic0 # step5ise approach is
essential 5hile evaluating these patients to ,e a,le to identif& and treat the disease timel& and
correctl&0 #ncillar& tests can ,e appropriatel& applied once the anatomic site of inflammation is
identified0 #n e:haustive approach comprising a full ,atter& of tests is o,solete0 %nl& specific
tailored investigations are ordered as suggested ,& the preliminar& clinical and ocular
e:amination0 6he mainsta& of the treatment of uveitis is corticosteroids0 )mmunosuppressive
agents are administered if the inflammation is not ade;uatel& controlled 5ith corticosteroids0
%ne of the recent ,rea<throughs in the treatment of refractor& uveitis includes the introduction
of immunomodulating drugs: 6umor necrosis factor-alpha antagonist and )nterferon-alpha0
!itrectom& has ,een used in uveitis for over a fe5 decades for diagnostic and therapeutic
purposes0 .hen compared to other anatomical sites of inflammation panuveitis has poor visual
outcome due to more 5idespread inflammation0 6he side-effects of the chronic treatment that
these patients receive cannot ,e overloo<ed and should ,e specificall& monitored under the
supervision of an internist 5ith special interest in inflammator& diseases0
Keywords: $iagnosis management panuveitis
ow !o c"!e !#"s ar!"cle:
Bansal R "upta ! "upta #0 Current approach in the diagnosis and management of panuveitis0
)ndian = %phthalmol 2010>58:45-54
ow !o c"!e !#"s U$%:
Bansal R "upta ! "upta #0 Current approach in the diagnosis and management of panuveitis0
)ndian = %phthalmol ?serial online@ 2010 ?cited 2014 =un /@>58:45-540 #vaila,le
from: http:225550iAo0in2te:t0aspB201025821245258431 $%):100410120101-4318058431
Cveitis is one of the maAor causes of ,lindness in the 5orld0
?1@
#ccording to anatomical
location the )nternational Cveitis +tud& "roup D)C+"E defines panuveitis as generali4ed
inflammation of all three parts of the uvea i0e0 iris ciliar& ,od& and the choroid0
?2@
)t covers a
large group of diverse diseases 5hich affect not onl& the uvea ,ut also the retina and vitreous
humor0 $iagnosis of panuveitis is esta,lished in the presence of the follo5ing clinical signs:
'vidence of choroidal or retinal inflammation such as choroiditis Dfocal multifocal or
serpiginousE choroidal granuloma retinochoroiditis retinal vasculitis su,retinal
a,scess necroti4ing retinitis or neuroretinitis> 5ith
evidence of vitreous inflammation Dvitreous cells or vitritisE> and
presence of signs of anterior uveitis Dcells and flare in the anterior cham,er <eratic
precipitates or posterior s&nechiaeE0
6he distri,ution of uveitis according to the anatomical site of inflammation and its causes are
influenced ,& diverse geographic racial nutritional and socioeconomic differences0
?1@
7no5ledge of the epidemiolog& of uveitis helps the clinician to ,etter predict the li<elihood of
a s&stemic association and to order appropriate diagnostic testing0
?4@
(anuveitis is relativel&
more common in #sia #frica and +outh #merica as compared to Forth #merica 'urope and
#ustralia0
?5@
6u,erculosis D6BE and !ogt-7o&anagi-8arada D!78E s&ndrome are the most
common causes of panuveitis in )ndia0
?1@?/@

6his article highlights the current clinical approach to the diagnosis and management of
panuveitis 5ith special emphasis on the most common causes of panuveitis in our setting0
Clinical approach
Classification and standardi4ation of uveitis is important as it enhances the precision and
compara,ilit& of clinical e:amination0 6his helps in developing a complete picture of the
course of the disorders and their response to treatment0 6he most 5idel& used classification of
uveitis is the one devised ,& the )C+" in 1-83 ,ased on anatomical location of inflammation0
6he standardi4ation of uveitis nomenclature 5or<ing group in 2005 standardi4ed the approach
to reporting clinical data Ddiagnostic terminolog& grading of inflammation and outcome
measuresE in uveitis research0
?3@
*ore recentl& the )C+" in 2008 designed a simplified
classification of uveitis into infectious non-infectious and mas;uerade ,ased on etiological
criteria0
?8@

6o recogni4e a specific entit& 5e use the follo5ing step-ladder approach 5hen evaluating a
patient 5ith uveitis:
10 # detailed ocular histor& is elicited regarding the s&mptoms duration Dacute or
chronicE num,er of episodes DrecurrentE and lateralit& of the s&mptoms0
20 6horough ocular e:amination is done to assess the anatomic location of the uveitis t&pe
of inflammation Dgranulomatous or non-granulomatousE to recogni4e an& t&pical entit&
Dsuch as Guchs9 heterochromic c&clitisE0
10 %nce the naming and meshing of the disease is done s&stemic histor& Dtargeted
;uestionsE is as<ed to <no5 an& associated conditions or s&ndromes causing uveitis0
40 %nl& selective investigations are ordered0
)nvestigations
Fearl& all cases of uveitis re;uire investigations for correct diagnosis Dor la,elE and guidance
for treata,le conditions DinfectionsE to <no5 the natural histor& and prognosis of the disease to
provide reassurance to the patient as 5ell as doctor to identif& groups at particular ris<
?antinuclear anti,od& D#F#E status in Auvenile idiopathic uveitis@ and to avoid unnecessar&
treatments0 Clinicall& uveitis can ,e classified into granulomatous and non-granulomatous
uveitis0 #natomic approach is essential in the diagnosis of uveitis for proper application of
ancillar& tests0
Ancillary tests
.hereas anterior segment inflammations involving the iris are routinel& pic<ed up ,& slit-lamp
e:amination ciliar& ,od& involvement can ,est ,e confirmed ,& ultrasound ,iomicroscop&
DCB*E0 Baseline color fundus photograph& serves as an e:tremel& good clinical reference
5hen monitoring the fundus changes during follo5-up periods0 $igital color fundus
photograph& allo5s eas& storage and retrieval of fundus images0 # composite montage of the
retina can ,e made to document ,etter the lesions in the peripheral fundus0
?-@

Gundus fluorescein angiograph& DG#E is mandator& for retinal and choroidal lesions0 6he G#
allo5s identification of active inflammation of the retinal vessels as seen in vasculitis due to
sarcoidosis tu,erculosis Behcet9s disease and s&philis0 6he pattern of staining and lea<age
provides diagnostic clues0 !ascular occlusions can also ,e detected0 Clinicall& a,sent macular
edema or optic disc edema can ,e revealed on G#0 Besides the active lesions complications of
uveitis that are ,est studied on G# include c&stoid macular edema DC*'E neovasculari4ation
of retina capillar& dropout su,retinal neovasculari4ation and retinal pigment epithelium DR('E
changes0 ':udative retinal detachment in the earl& stage of !78 ,egins as ,ilateral multifocal
points in the posterior pole0 *ultifocal lea<s at the level of R(' 5ith pooling of the d&e in the
areas of e:udative detachment are t&picall& seen on the G# in !78 patients0 +imilar lesions on
G# ma& also ,e seen in s&mpathetic ophthalmia0 +taining of a h&pofluorescent lesion starting
at the ,order and then progressing to the center is t&pical of to:oplasmic retinochoroiditis0
)ndoc&anine green angiograph& D)C"#E is the techni;ue of choice for imaging the choroid0 6he
alteration of the normal choroidal )C"# ,ac<ground fluorescence is the main parameter
studied and information is o,tained mostl& from late angiographic phases 5hen choroidal
inflammator& lesions ma& appear as areas of decreased or a,sent fluorescence0 Csing )C"#
choroidal vasculitis in posterior uveitis can ,e characteri4ed and su,divided into t5o main
patterns: D1E primar& inflammator& choriocapillaropath& and D2E stromal inflammator&
vasculopath&0
?10@
6he first pattern consists of h&pofluorescent areas up to the late phase of
angiograph& characteristic of choriocapillaris non-perfusion and includes entities such as
multiple evanescent 5hite dot s&ndrome acute posterior multifocal placoid pigment
epitheliopath& multifocal choroiditis ampiginous choroiditis and serpiginous choroiditis0 6he
second pattern consists of fu44& indistinct appearance of vessels in the intermediate
angiographic phase and diffuse choroidal h&perfluorescence in the late phase indicating
inflammator& vasculopath& of larger choroidal vessels0 6his pattern has ,een descri,ed in
active !78 disease ocular sarcoidosis and tu,erculosis and ,irdshot chorioretinopath&0 )n
BehHet9s uveitis of recent onset choriocapillaris perfusion dela& and fu44& choroidal vessels
5ithout diffuse late choroidal h&perfluorescence has ,een descri,ed0 Cltrasound is a safe
noninvasive d&namic tool for the evaluation of the posterior segment 5hen direct visuali4ation
of the fundus is o,scured due to severe inflammation or its complications0 )t is useful also for
the evaluation of inflammator& infiltration of the choroids in !78 s&ndrome or s&mpathetic
ophthalmia D+%E0
?11@
)t is especiall& helpful in differentiating choroidal thic<ening associated
5ith choroiditis from posterior scleritis 5hich ma& mimic posterior or even panuveitis0 )t is
also useful 5hen evaluating patients prior to the use of intraocular drugs or surger&0 CB*
allo5s an o,Aective ;uantitative evaluation of the ciliar& ,od&0
?12@
)t can ,e of great help in
deciding the course of treatment ,& detecting the underl&ing structural a,normalities in ocular
h&poton& associated 5ith uveitis0
?11@

%ptical coherence tomograph& D%C6E is a noncontact and noninvasive imaging tool0 #lthough
certain complications of uveitis such as C*' neovasculari4ation of retina epiretinal
mem,rane or vitreomacular traction s&ndrome can ,e demonstrated e:tremel& 5ell on the
%C6 its use in panuveitis ma& ,e restricted ,& ha4& media0 Recentl& our e:perience 5ith the
use of %C6 in uveitic e&es has revealed that high-definition D8$E spectral-domain %C6 ?+$-
%C6@ DCirrus 8$-%C6> Carl Ieiss $u,lin California C+#E has an advantage over time-
domain %C6 ?6$%C6@ D+tratus version 4> Carl IeissE for imaging macula in patients of uveitis
,& providing ,etter identification of normal and pathologic structure in patients 5ith poor
media clarit&0
?14@

Laboratory tests
Recent advances in the understanding of the pathogenetic mechanisms of uveitis have changed
the diagnostic and therapeutic approach to these patients0 )n most te:t,oo<s the e:haustive
approach is presented0 +uch lists are not ver& useful0 Random screening 5ith a full ,atter& of
tests is needless0 %ne should concentrate on a limited num,er suggested ,& naming-meshing0
.e routinel& order the follo5ing la,orator& tests:
Gull ,lood counts
'r&throc&te sedimentation rate
*antou: test
Chest J-ra& DComputed tomograph& if re;uiredE
+&philis serolog& DTreponema pallidum hemagglutination testE
6he follo5ing tests are ordered onl& in relevance to the particular disorder:
+erum #ngiotensin-Converting-'n4&me D#C'E levels for sarcoidosis
8uman leu<oc&te antigen D8K#E t&ping DB 51 $R4E for Behcet9s disease DB$E or !78
s&ndrome
D#lthough B$ is associated 5ith the

8K#-B51 locus not all patients have this genot&pe
?15@
E
#F# for Auvenile rheumatoid arthritis and antineutrophil c&toplasmic anti,od& for
vasculitis associated 5ith .egener granulomatosis
J-ra& of sacro-iliac Aoint for an<&losing spond&litis
#nti,odies against Toxoplasma gondii
# repeat evaluation and follo5-up is re;uired in cases 5here la,orator& test results do not &ield
an& positive information0 Cases that remain undiagnosed ,& the routinel& availa,le la,orator&
tests are la,eled as idiopathic0
?1@

)n some of the etiologies Dinfectious endophthalmitis acute retinal necrosisE a clinical
diagnosis can ,e made and therap& can ,e immediatel& started 5hile the specific confirmation
tests are ,eing ordered or carried out0 .hereas culture still remains the gold standard for
diagnosing micro,ial infections definitive diagnosis of intraocular inflammation due to
infectious agents is difficult to o,tain from ocular fluids or tissue specimens in routine clinical
practice0 %ur a,ilit& to detect infectious agents has ,een strengthened ,& the use of pol&merase
chain reaction D(CRE0 )t has ,een used to diagnose uveitis including viral uveitis
m&co,acterial intraocular infections infectious endophthalmitis and proto4oal e&e diseases0
?1/@
(CR is a po5erful molecular techni;ue for evaluation of ver& small amounts of
$eo:&ri,onucleic acid and Ri,onucleic acid0 )t can ,e a simple rapid sensitive and specific
tool for the diagnosis of infection autoimmunit& and mas;uerade s&ndromes in the e&e0
Certain tests such as liver function and renal function tests are ordered onl& during the course
of treatment 5hile evaluating a patient ,efore considering immunosuppressive therap& or 5hile
evaluating the adverse effects of these drugs or certain antimicro,ial drugs0
*anagement of (anuveitis
6he treatment of uveitis has three main goals: to prevent vision-threatening complications to
relieve the patient9s complaints and 5hen feasi,le to treat the underl&ing disease0
?13@
)t can ,e
divided into follo5ing steps:
$iagnosis and treatment of the specific causative agent0
Fonspecific treatment0
6reatment of related conditions0
+upportive therap&0
Cveitis due to infectious agents is treated ,& specific antimicro,ial therap& Danti,iotic
antiparasitic or an antiviralE for appropriate duration 5ith or 5ithout corticosteroids0 6he
mainsta& of treatment of noninfectious uveitis is anti-inflammator& therap&0 +evere or
refractor& panuveitis needs immunosuppressive agents0
Cor!"cos!ero"ds
Corticosteroids are the drugs of choice in most t&pes of uveitis0 6he& inhi,it the inflammator&
process ,& suppressing the arachidonic acid meta,olism and activation of complement0
?13@

)n panuveitis ,oth topical and s&stemic corticosteroids are needed0 $epending upon the
severit& of the disease oral prednisolone is started in a loading dose of 1 mg2<g2da&0 #s the
inflammation su,sides tapering of corticosteroids ,& 5-10 mg per 5ee< is ,egun 5ithin t5o to
four 5ee<s of initiating therap&0 %nce the e&e is completel& ;uiescent the patient is follo5ed
on a maintenance dose ranging from 205-10 mg dail& of prednisolone0 # reasona,l& long
period of lo5-dose corticosteroids is re;uired as maintenance therap& in !78 s&ndrome and
+%0
6he normal response to the corticosteroid therap& ma& ,e interrupted ,& recurrence of uveitis
in 5hich case the fre;uenc& of instillation of topical drops is increased ,esides raising the oral
corticosteroid to the initial high-dose levels0 Cnilateral cases ma& ,e given a trial 5ith
periocular inAection of depot corticosteroids into the posterior su,tenon space0 6he side-effects
and complications of topical or s&stemic corticosteroids must ,e loo<ed for at ever& follo5-up
visit of the patient0 6hese include secondar& glaucoma posterior su,capsular cataract
increased suscepti,ilit& to infection Docular or s&stemicE h&pertension gastric ulcer dia,etes
o,esit& gro5th retardation osteoporosis and ps&chosis0
Suppor!"&e !#erapy
C&cloplegics are administered to relieve pain due to ciliar& spasm0 (osterior s&nechiae
formation is prevented ,& instilling a m&driatic agent0 #tropine is used in acute attac<s 5hile
intermediate acting agents DhomatropineE are used to maintain pupillar& dilatation0
Immunosuppress"&e agen!s
6he three main classes of immunosuppressives that are 5idel& used toda& in addition to
glucocorticosteroids are antimeta,olites 6 cell inhi,itors and al<&lating agents0
#ntimeta,olites include a4athioprine methotre:ate and m&cophenolate mofetil D**GE0 6 cell
inhi,itors include c&closporine and tacrolimus0 #l<&lating agents include c&clophosphamide
and chloram,ucil0 .hen corticosteroid therap& is insufficient to control ocular inflammator&
disease immunosuppressive agents are given0 6he& e:ert their ,eneficial effects ,& actuall&
<illing the rapidl& dividing clones of l&mphoc&tes that cause the inflammation0 )ndications of
immunosuppressive therap& in panuveitis are: severe inflammation that is sight-threatening>
chronic inflammation that is not responding to the primar& conventional corticosteroid therap&>
multiple relapses of uveitis> or intolerance or contraindications to s&stemic corticosteroids0 6he
clinician should discuss e:tensivel& 5ith the patient regarding the side-effects of such therap&0
6hese drugs have to ,e used onl& after ruling out a possi,le infectious agent as the cause of
uveitis0 !78 s&ndrome and +% are the uveitis conditions that are usuall& resistant to
corticosteroids or re;uire long-term treatment 5ith corticosteroids0 )n such conditions
immunosuppressive agents are initiated as immediate second line therap& or as steroid-sparing
agents as first-line therap&0 #ll patients are evaluated for hemoglo,in ,lood cell counts
Dleucoc&tes and plateletsE liver and renal function tests to rule out contraindications to
treatment ,efore starting an& immunosuppressive drug and ever& four 5ee<s 5hile receiving
these medications0 Ko5-dose immunosuppressive drugs such as a4athioprine or methotre:ate
D*6JE are also initiated ,efore an& intraocular surger& to control the inflammation for a
prolonged time and sustain it after surger& for a favora,le outcome0
?18@?1-@

C&closporine
?20@
and a4athioprine
?21@
have ,een found to ,e effective in the treatment of
Behcet9s disease in randomi4ed controlled trials 5hereas the efficac& of other agents is sho5n
,& uncontrolled case series0
'ewer s!ra!eg"es
Biologic drugs 5ere introduced as an alternative mode of therap& for recalcitrant uveitis a,out
15 &ears ago 5ith encouraging outcomes0 6hese are therapeutic agents 5ith ,iologic
properties including monoclonal anti,odies and solu,le c&to<ine receptors0 6he main ,iologics
in current use include anti-tumor necrosis factor-L D6FG- LE c&to<ine receptor anti,odies and
interferon-L D)GF-LE0 6hese are ,elieved to have a superior anti-inflammator& potential than the
conventional immunosuppressives and have ,een proposed as a second-line strateg& after
failure 5ith conventional immunosuppressants for the treatment of refractor& uveitis
especiall& 5ith ocular B$0
?22@

Anti-tumor necrosis factor-
6FG-L is an inflammator& c&to<ine found in animal models of uveitis as 5ell as the a;ueous of
e&es 5ith uveitis0 6he three currentl& commerciall& availa,le anti-6FG-L agents are infli:ima,
adalimuma, and etanercept0 )nfli:ima, and adalimuma, are monoclonal immunoglo,ulin "1
D)g"1E anti,odies against 6FG-L0 6he& ,oth form sta,le ,onds 5ith the solu,le and
transmem,rane forms of 6FG-L0 'tanercept is a dimeric solu,le form of the p35 6FG-L
receptor lin<ed to )g"1 and forms less sta,le ,onds mainl& 5ith the transmem,rane form0
#nti-6FG(L agents are increasingl& proving to ,e effective in the control of uveitis0 )nfli:ima,
in particular has ,een found to ,e effective in reducing inflammation in a,out 80M of
refractor& uveitis 5ith relativel& fe5 serious adverse reactions0
?21@?24@?25@
8o5ever repeated
infusions ever& four to eight 5ee<s are often re;uired to prevent recurrences0 )n B$ the
response to infli:ima, is especiall& rapid occurring as earl& as 24 h after the infusion even in
patients 5ho have recurrences despite ,eing heavil& immunosuppressed0
?2/@?23@
#dalimuma, is
given as a su,cutaneous inAection of 40 mg at 5ee<l& to t5o-5ee<l& intervals> hence it can ,e
self-administered and ,ecause it is full& humani4ed there is less li<elihood of formation of
anti,odies0 6here has ,een onl& one report on its use in three adult patients 5ith B$ and three
small studies in childhood uveitis0 #ll three Behcet9s patients had achieved remission 5ith
infli:ima, ,ut 5ere s5itched to adalimuma, as it could ,e self-administered0
?28@
'tanercept is
given t5ice 5ee<l& also as a su,cutaneous inAection of 25 mg and is consistentl& found to ,e
less effective than the other t5o agents in uveitis0 6his is attri,uted to its relativel& 5ea<
,inding mainl& to the transmem,rane form of 6FG-L0
?21@?24@
%ne potentiall& fatal complication
of anti-6FG-L therap& is disseminated tu,erculosis0 +creening for latent tu,erculosis ma& ,e
compromised ,& the fact that these patients are usuall& alread& on other immunosuppressants
5hich ma& result in a false-negative purified protein derivative test and the primar& focus ma&
,e e:trapulmonar&0
Cytokine receptor antibodies
$acli4uma, is a humani4ed monoclonal anti,od& that targets the C$25 su,unit of the human
interleu<in-2 receptor of 6 l&mphoc&tes0 )t is given as an intravenous infusion of 1 mg2<g at
t5o to four-5ee< intervals0 # su,cutaneous form is currentl& still undergoing trials ,ut sho5s
promise as a more accessi,le route of administration0
?2-@
$acli4uma, has ,een found to ,e
clinicall& ,eneficial in controlling the inflammation and hence preserving vision in ,irdshot
chorioretinopath& ,ut is &et to ,e proved to ,e efficacious in the treatment of B$0
)nterferon-L2a
)GF-L2a is a c&to<ine released in viral infections and has ,een used mainl& for the treatment of
B$ as it is thought to have a possi,le viral origin0 )t is given as a su,cutaneous inAection at a
dose of 1-- million units2da& dail& or thrice a 5ee<0
?22@?10@

Biologic agents are effective and comparativel& 5ell-tolerated options in the treatment of
refractor& uveitis in ,oth adults and children in the short term e:cept for etanercept0 6he
predominant side-effects of antimeta,olites are ,one marro5 suppression and hepatoto:icit&>
that of 6 cell inhi,itors is renal to:icit& and that of al<&lating agents are ,one marro5
suppression and the development of malignancies0 6he uncertaint& of their long-term results
their high costs as 5ell as the necessit& for repeated intravenous infusions in the case of
infli:ima, limit their 5idespread use0
?11@
*&cophenolate mofetil is another efficacious fairl&
5ell-tolerated and less costl& immunosuppressant0 )t has the additional advantage of an oral
formulation0
V"!rec!omy "n panu&e"!"s
!itrectom& for uveitis ,egan in the late 1-30s for diagnostic purposes and for treating
infections0 $iagnostic vitrectom& com,ined 5ith (CR can significantl& improve diagnostic
&ield in other5ise idiopathic uveitis and can fre;uentl& ma<e a diagnosis in cases complicated
,& media opacit& or other features that ma<e traditional e:am-,ased diagnosis difficult or
impossi,le0 !itrectom& ma& ,e considered as a therapeutic option 5hen uveitis persists despite
ma:imum tolera,le medical treatment 5ith corticosteroids and2or other immunosuppressants0 )t
ma& also ,e indicated 5hen visual loss occurs due to complications of longstanding
inflammations such as a densel& opacified vitreous scar tissue pulling on the ciliar& ,od&
causing h&poton& c&stoid macular edema an epiretinal mem,rane a dense posterior lens
capsule opacification or a tractional retinal detachment0
?12@
!itrectom& removes the lodged
l&mphoc&tes in the vitreous inflammator& de,ris immune comple:es and autoantigens0 )t also
increases the uveal penetration of anti-inflammator& cells0
?11@
Besides providing a ,etter access
for complete removal of the cataractous lens material along 5ith posterior capsule the
com,ined approach of pars plana lensectom& and vitrectom& allo5s eas& performance of
intraocular maneuvers and prevents formation of c&clitic mem,rane0
?14@

Complications of vitrectom& ma& ,e mild or severe and include ,leeding cataract glaucoma
infection retinal detachment or ,lindness0
+ome of the common uveitis entities seen in our population causing panuveitis are discussed0
)u*erculos"s
6u,erculosis D6BE-related uveitis is ,eing increasingl& reported from +outheast #sian .estern
(acific and 'astern *editerranean regions0
?1@?15@?1/@
6he true prevalence of tu,ercular uveitis
remains a maAor concern especiall& in 6B-endemic areas and ,ecause of lac< of definite
diagnostic criteria0 6B can affect an& part of the e&e and patients present 5ith a spectrum of
clinical signs0 #lthough it ma& mimic other clinical entities a positive tu,erculin s<in test
healed lesions on chest J-ra& or associated s&stemic 6B corro,orates the diagnosis of
presumed intraocular 6B0 #dministration of anti-tu,ercular therap& Disonia4id 5 mg2<g2da&
rifampicin 450 mg2da& if ,od& 5eight is N 50 <g and /00 mg2da& if ,od& 5eight is O 50 <g
etham,utol 15 mg2<g2da& and p&ra4inamide 25 to 10 mg2<g2da& initiall& for three to four
months> thereafter rifampicin and isonia4id are used for another nine to 14 monthsE in addition
to the standard corticosteroids significantl& reduces recurrences of uveitis in these patients0
?13@
)n our e:perience the most common presentation of tu,ercular uveitis is posterior uveitis
follo5ed ,& anterior uveitis0 (anuveitis and intermediate uveitis are less common0 6he recentl&
introduced immune-,ased rapid ,lood tests ?PuantiG'R%F-6B "old test DPG6-"E and 6+(%6
DTB testE@ seem to ,e a significant upgrade of the centur&-old tu,erculin s<in test for
diagnosing latent 6B infection0 PG6-" assa& measures the amount of interferon-gamma D)GF-
QE released ,& the patient9s sensiti4ed 6-cells 5hen his 5hole ,lood is incu,ated 5ith t5o
s&nthetic peptide antigens '+#6-/ and CG(-100 6hese antigens are present in *&co,acterium
tu,erculosis ,ut not in the Bacilli-Calmette-"uerin DBC"E or at&pical m&co,acteria0 6he
advantages of these tests over the routine tu,erculin s<in test are that these are not affected ,&
the previous BC" vaccination or at&pical m&co,acteria the results are availa,le 5ithin 24 h
5ithout an& need for a second visit to the hospital and the& are free from an& ,ooster effect0
?18@
?1-@
6he maAor limitation of these tests is that the& are e:pensive0
VK syndrome
!78 is a severe ,ilateral granulomatous panuveitis associated 5ith various e:traocular
manifestations involving the central nervous auditor& and integumentar& s&stem0
?40@
6his
s&ndrome usuall& affects adults ,et5een 20-50 &ears of age0 'vidence suggests that it involves
a 6-l&mphoc&te-mediated autoimmune process directed against an as &et unidentified antigen
Dor antigensE associated 5ith melanoc&tes0
?41@?42@?41@
6he mechanism that triggers this
autoimmune attac< is un<no5n ,ut sensiti4ation to melanoc&tic antigens ,& means of
cutaneous inAur& or viral infection have ,een proposed as possi,le factors in some cases0
#lthough the e:act target antigen has not ,een identified candidates have ,een proposed0 6he&
include t&rosinase or t&rosinase-related proteins an unidentified 35 <$a protein o,tained from
cultured human melanoma cells D"-1/1E and the +-100 protein0 !78 disease is t&picall&
characteri4ed as affecting primaril& those of more pigmented groups such as 8ispanics
D*esti4osE #sians Fative #mericans *iddle 'asterners and #sian )ndians ,ut not ,lac<s of
su,-+aharan #frican descent0 6his finding in com,ination 5ith the evidence of an increased
ris< among those 5ith certain 8K# genot&pes points to a geneticall& determined suscepti,ilit&
to the triggering event for !78 disease0
?44@?45@?4/@?43@?48@?4-@
%nce diagnosed multiple therapeutic
regimens have ,een used in the treatment of !78 disease including regional oral and
intravenous corticosteroids c&closporine antimeta,olites and al<&lating agents0 6he diagnosis
of !78 is clinical and several criteria have ,een proposed in the past such as the #merican
Cveitis +ociet& D#C+E criteria
?50@
and +ugiura9s criteria0
?51@
6he revised diagnostic criteria
su,divide patients into complete incomplete or pro,a,le categories according to the presence
of e:traocular manifestations0
?52@
!78 disease is a single entit& 5ith ver& different clinical
manifestations depending on the stage at 5hich the patient is e:amined0 6hus patients
presenting soon after the onset of the disease ma& complain of auditor& and neurological
manifestations Dsevere headache and meningismusE follo5ed ,& the onset of decreased vision
5ith the finding of e:udative retinal detachments and optic disc h&peremia0 Conversel& a
patient presenting months to &ears after the initial episode 5ill more t&picall& have the signs
and s&mptoms of an anterior uveitis 5ith photopho,ia and cell and flare in the a;ueous humor
?Gigure 1@ along 5ith the possi,le additional manifestations of cutaneous and ocular
h&popigmentation0 6he ocular manifestations are divided into those occurring earl& and those
occurring late in the course of the disease0 )n its earl& stages there is the occurrence of a
diffuse choroiditis manifested ,& a num,er of findings including diffuse choroidal
inflammator& signs and e:udative detachment of the retina the latter of 5hich ma& appear as
focal areas of su,retinal fluid accumulation development of larger ,ullous detachments or
,oth0 .hen the patient presents months to &ears after the initial episode he must demonstrate
an& of the late findings such as sunset glo5 fundus or +ugiura sign Dperilim,al vitiligoE 5ith
nummular chorioretinal depigmentation scars Dalso sometimes erroneousl& referred to as
$alen-Guchs nodulesE generali4ed R(' clumping or migration and recurrent or chronic
anterior uveitis0 6he disease is t&picall& characteri4ed ,& e:acer,ations and remissions0 6he
clinical course is varia,le: some patients ma& have limited inflammator& activit&> 5hile others
have recurrent episodes of severe intraocular inflammation causing rapid visual loss0
?51@
!78
disease is a multis&stem disorder0 Cne;uivocal diagnosis therefore re;uires evidence of the
involvement of more than the ocular s&stem0 .hen the patient presents at disease onset
evidence of meningeal inflammation in the form of malaise fever headache nausea
a,dominal pain stiffness of the nec< and ,ac< or a com,ination of these features Dcommonl&
referred to as meningismusE or auditor& involvement in the form of tinnitus is re;uired0 )f
neither meningismus nor tinnitus is present pleoc&tosis on cere,rospinal fluid e:amination is
re;uired0 Cutaneous findings such as vitiligo poliosis or alopecia are late manifestations of this
disease0
#part from routine fundus photograph& and G# )C"# has an immense role in diagnosing and
follo5ing !78 patients0 6he maAor )C"# signs descri,ed in an acute initial uveitis episode
include D1E earl& choroidal stromal vessel h&perfluorescence and lea<age D2E h&pofluorescent
dar< dots D1E fu44& vascular pattern of large stromal vessels and D4E disc h&perfluorescence0
?54@
)n the a,sence of an )C"# follo5-up undetected smoldering su,clinical disease ma& persist0
+o !78 disease should ,e follo5ed ,& )C" angiograph& and in the case of choroidal
su,clinical reactivation a reversal of therap& tapering and an e:tension of therap& duration
should ,e considered0
6raditionall& !78 disease has ,een treated 5ith high-dose corticosteroids often 5ith
immunosuppressive drug therap& reserved for patients 5ith disease that is refractor& to
corticosteroid therap&0 6reatment for !78 disease often is aimed at treating individual
e:acer,ations of inflammation00 6he t&pical treatment for !78 disease is high-dose
corticosteroid therap& follo5ed ,& a slo5 tapering of the drug over three to si: months0 6he
course of treatment of uveitis in such patients is usuall& aggressive increasing the chances of
sight-threatening complications li<e cataract glaucoma and choroidal neovascular mem,rane0
%ur initial approach to the treatment of !78-associated panuveitis includes fre;uent topical
and s&stemic corticosteroids D1 mg2<g2da&E along 5ith c&cloplegics ?Gigure 2@0 #cute
e:acer,ations re;uire admission of the patient in the hospital and are controlled ,& intravenous
meth&l prednisolone inAection D1 g2da&E for three consecutive da&s follo5ed ,& oral
prednisolone D100-105 mg2<g2da&E0 )mmunosuppressive agents Da4athioprine 200-205 mg2<g2da&E
are added as and 5hen indicated0 6he& are also started 5hen a prolonged period of ;uiescence
of inflammation is desired in the e&e ,efore undergoing an intraocular surger& Dcataract
glaucoma vitrectom&E0
%nce the inflammation is ade;uatel& controlled the corticosteroids are tapered ver& graduall&
over months and &ears ?Gigure 1@ and ?Gigure 4@0 6he patients are follo5ed on lo5-dose topical
and s&stemic corticosteroid 5ith or 5ithout immunosuppressive agent as the maintenance
therap&0 Ko5-dose a4athioprine therap& has ,een found to ,e effective as corticosteroid-
sparing agent in !78 disease0
?55@

#lthough relativel& a rare cause of uveitis in children !78 has ,een reported in children
,elo5 1/ &ears of age during the last 50 &ears0
?54@?5/@?53@?58@?5-@?/0@?/1@?/2@?/1@
6he course of !78-
associated uveitis is more aggressive in children than adults0 'arl& use of corticosteroid-sparing
agents has ,een recommended in pediatric patients ,ecause of ha4ards of cataract glaucoma
and gro5th retardation 5ith long-term and high-dose corticosteroids0
?/4@

Sympa!#e!"c Op#!#alm"a
+% is an autoimmune

condition in 5hich inAur& to one e&e De:citing e&eE causes sight-
threatening

inflammation in the other5ise normal contralateral e&e Ds&mpathi4ing e&eE0
?/5@
)t
t&picall& presents as ,ilateral granulomatous panuveitis0 )t is a rare disease 5ith an incidence of
000121000000
?//@
6he classical description of signs include granulomatous mutton fat <eratic
precipitates anterior cham,er and vitreous inflammation 5ith or 5ithout &ello5 -5hite lesions
in the retinal peripher&0 %ther fundus lesions li<e retinal detachment papillitis optic atroph&
and vasculitis are reported uncommonl& and are generall& seen in conAunction 5ith anterior
segment inflammation0
?/3@?/8@
6here are no definite tests for confirming the diagnosis of +%0 #
histor& of an intraocular surger& or an ocular trauma com,ined 5ith the clinical signs of
inflammation support the diagnosis of +%0 8o5ever routine la,orator& and ancillar& tests are
performed in the clinical practice to rule out the possi,ilit& of other granulomatous panuveitis
conditions that mimic +% such as !78 s&ndrome or sarcoidosis0 6he mainsta& of treatment is
aggressive use of corticosteroids0 #ll patients seen in the acute phase of disease in our clinic
receive s&stemic corticosteroids 5ith a starting dose of 105-2 mg2<g ,od& 5eight that is tapered
slo5l& to a maintenance dose ,et5een 5 and 10 mg2da& over the ne:t four to si: months 5hich
is then continued for a period of t5o to five &ears0
?/-@
)n case of recurrences the dose of oral
corticosteroids is increased to 105-2 mg2<g ,od& 5eight if the patient has ne5 fundus lesions or
severe anterior segment inflammation0 6he maintenance dose this time is not reduced ,elo5
the level at 5hich the recurrence has occurred0 6opical corticosteroids and c&cloplegics are
given as per re;uirement0 +evere or recurrent cases re;uire additional therap& including more
than one immunosuppressive agent0 (atients seen in the chronic recurrent form receive oral
a4athioprine in a dosage of 100-150 mg2da& to ,egin 5ith 5hich is graduall& reduced over the
ne:t /-12 months0 (atients 5ho initiall& respond to ,ut are una,le to continue corticosteroids
due to either side-effects Dfive patientsE or recurrence Dthree patientsE also receive
immunosuppressive therap&0 )ntravenous c&clophosphamide D350 mg2 5ee< ever& three to four
5ee<s 5ith a ma:imum of seven dosesE is given for managing acute recurrences 5hile oral
a4athioprine D100-150 mg2da&E or methotre:ate D305-1000 mg2da&E is used as steroid sparer0
+e#ce!,s d"sease
B$ is a multis&stem disorder characteri4ed ,& recurrent e&e inflammation oral ulcers and
genital ulcers0 '&e involvement 5hich affects /0-80M of B$ patients is characteri4ed ,&
unilateral

or ,ilateral acute episodes of iridoc&clitis 5ith or 5ithout

h&pop&on and2or
panuveitis0
?30@?31@?32@
6he maAorit&

of patients 5ith ocular B$ present 5ith recurrent panuveitis0
?31@
6here is evidence that the disease is more severe 5ith the ris< of losing useful

vision higher
in men than in 5omen0
?34@
'&e disease in B$ patients is mostl& a recurrent nongranulomatous
uveitis 5ith necroti4ing o,literative retinal vasculitis 5hich ma& ,e found either in the anterior
or the posterior segment or ,oth0
?35@?3/@?33@?38@
)t affects the posterior e&e segment more often
and more severel& than the anterior one0 $iagnosis of B$ is mostl& ,ased on several sets of
diagnostic criteria0 6oda& the most 5idel& used are the criteria of the international stud& group
for B$0
?3-@
8o5ever these 5ere developed as classification and not as diagnostic criteria so
especiall& in earl& stages of the disease the diagnosis of B$ is often ver& difficult0
?80@
%lder
sets of criteria most commonl& those ,& *ason and Barnes
?81@
%9$uff&
?82@
and $ilsen et al.
?81@
and in #sia the =apanese
?84@
are therefore still in use0
+&stemic corticosteroids are 5idel& used in the therap& of ocular B$0 6he& are usuall&
administered as oral prednisolone at an initial dose of 1-2 mg2<g2da& follo5ed ,& a gradual
tapering ,& 5-10 mg25ee<0 8o5ever the& are not al5a&s suita,le as a monotherap& for
maintaining remission of uveitis due to adverse side-effects0 )n such cases it ,ecomes
necessar& to add an immunosuppressive drug as a steroid-sparing agent0
C&closporine # is the onl& immunosuppressant approved for uveitis therap& in several
countries and is <no5n to ,e the most commonl& used immunosuppressive drug for ocular B$0
#long 5ith lo5-dose corticosteroids it has ,een proved to ,e effective and safe for treating
acute uveitis episodes as 5ell as for reducing recurrence rates of uveitis in ocular B$ at a dose
of 1-5 mg2<g2da&0
?85@?8/@?83@
#4athioprine in a dose of 205 mg2<g2da& has also ,een sho5n to
effectivel& control intraocular inflammation to maintain visual acuit& and to prevent onset or
progression of e&e disease in ocular B$0
?88@

$espite aggressive immunosuppressive treatment the visual prognosis of ocular B$ remains
generall& poor0 %pen-la,el clinical trials in =apan and 6ur<e& have sho5n infli:ima, to ,e
effective in improving the prognosis of the disease in ocular B$0
?8-@?-0@
)GF-L has antiviral
antiproliferative and various immunomodulator& effects0
?-1@
Cnfortunatel& these ne5 drugs are
ver& e:pensive and therefore the& ma& ,e not universall& availa,le in countries 5ith a lo5
economic status0
6he treatment of B$ has to follo5 a multidisciplinar& approach ,ecause of possi,le
involvement of multiple organs 5hich necessitates earl& referral of patients to speciali4ed
internists 5ith e:perience in diagnosis and treatment of this disorder0 6he fact that no
standardi4ed treatment regimens e:ist complicates the treatment of ocular B$0
Sarco"dos"s
6he organs affected more often are the lungs s<in and e&es0 6he fre;uenc& of ocular
involvement ranges from 2/-50M0
?-2@
#nterior segment involvement has ,een reported to ,e
the most common0 (anuveitis occurs in /-11M of patients 5ith sarcoidosis0
?-1@?-4@?-5@?-/@
(resence of panuveitis is considered as a poor prognostic factor in patients 5ith sarcoidosis0
?-1@
?-3@?-8@
6he gold standard in the diagnosis of sarcoidosis is histopathological evidence of
noncaseating granuloma0
?--@
6he routine clinical tests for diagnosing sarcoid uveitis include
*antou: test chest J-ra& serum angiotensin converting en4&me levels er&throc&te
sedimentation rate0 .hen suspecting e:traocular sarcoidosis ,iops& of the involved organ is
performed to confirm the diagnosis0 %ther5ise in all suspected cases of sarcoid uveitis the
diagnosis remains presumptive0 # negative *antou: test that corro,orates the clinical
diagnosis of sarcoidosis can ,e e:plained ,& a preponderance of suppressor cells in the
peripheral ,lood leading to depletion of 6-helper cells and monoc&tes that actuall& cause the
dela&ed h&persensitivit& response0
+arcoid uveitis is uncommon in the #sian )ndian population and its diagnosis often remains
clinical0
?1@?5@?/@
)n a series of histologicall& confirmed s&stemic sarcoidosis 5ith ocular
involvement in )ndia anterior and intermediate uveitis have ,een found to ,e the commonest
sites0
?-2@?100@

Besides topical corticosteroid and c&cloplegic e&e drops for anterior uveitis s&stemic
corticosteroids Dprednisolone 1 mg2<g2da&E are the mainsta& of treatment for intermediate
posterior or panuveitis0 Cnilateral cases ma& ,enefit from posterior su,tenon inAection of
triamcinolone acetonide D20 mgE0 6he oral corticosteroids are tapered over 8-10 5ee<s ,& 5-10
mg per 5ee< depending upon the clinical response in consultation 5ith the pulmonologist0
#lthough immunosuppressive agents in general have had ver& limited use in the treatment of
ocular sarcoidosis a state of controlled inflammation has ,een achieved and reported ,& a fe5
authors using lo5-dose *ethotre:ate in the other5ise difficult-to-treat patients of panuveitis0
?1-@?101@
Beneficial effect of *ethotre:ate in patients undergoing cataract surger& has also ,een
o,served ,& a fe5 authors in controlling the preoperative inflammation Dthat 5as other5ise
persistent on corticosteroids aloneE and sustaining improved visual acuit& after surger&0
?1-@
Because sarcoidosis is a multis&stem disorder the immunosuppressive drugs also help in
managing the non-ocular manifestations of the disease0 Certain side-effects ma& ,e seen 5ith
lo5-dose *ethotre:ate ,ut the& are ,etter tolerated than those 5ith long-term corticosteroids0
?102@

Conclusion
# s&stematic tailored approach in ma<ing accurate diagnosis is central to emplo&ment of
specific more effective treatment for all t&pes of uveitis irrespective of the anatomical site of
inflammation0
?1@
.hat 5e prefer not to do is the e:haustive approach0
Cveitis 5ill continue to ,e increasingl& more important as a group of potentiall& sight-
threatening inflammator& e&e diseases that have a significant impact on ,oth the visual and
s&stemic health of the generall& &oung adult population that is affected0
?5@
6he use of a
prospective anal&sis in a colla,orative multi-center approach 5ould facilitate therapeutic trials
and provide valua,le ,rea<through in managing some of the most refractor& sight-threatening
t&pes of panuveitis0 6herapeutic decisions are dictated ,& disease location and severit&0
#s uveitis often afflicts the &oung adult population in their most productive &ears of life the
personal and population ,urden of this sight-threatening disease is significant0
?5@
)rrespective of
the cause visual mor,idit& is poor in panuveitis0 6here is an increased ris< of development of
cataract secondar& glaucoma and c&stoid macular edema as a result of more 5idespread
inflammation and more aggressive treatment 5ith corticosteroids0 .hile identif&ing the causes
of ,lindness in patients 5ith intraocular inflammation Rothova et al0 found that panuveitis had
the 5orst visual outcome as far as the anatomical site of involvement 5as concerned0
?-8@

6he aim to treat a patient of panuveitis is to achieve a successful outcome in terms of
;uiescence of inflammation in ,oth anterior as 5ell as posterior segments prevent recurrences
of inflammation minimal or no side-effects of chronic treatment 5hich these patients receive
and favora,le visual recover& in the long term0 #lthough uveitis 5or<up is team5or< re;uiring
an accurate description of uveitis t&pe and etiolog& a selective approach to general
investigations and an internist to monitor s&stemic treatment an ophthalmologist pla&s a
crucial role in the diagnosis and management of these patients0
Panu&e"!"s
+&mpathetic ophthalmia ma& present as a multifocal choroiditis ,ut more commonl& is a
,ilateral granulomatous panuveitis that presents several 5ee<s to months after either surger& or
penetrating trauma0
?-8R100@
)t is ,elieved that the inflammation is actuall& a 6-cell response to
choroidal melanoc&tes 5hich e:plains its ,ilateral nature0 6here is usuall& accompan&ing
vitritis and 5hite choroidal lesions0 6his condition is rare ,ut should ,e considered 5hen there
is a histor& of intraocular surger& trauma and other causes of uveitis have ,een ruled out0
?100101@
!ogtR7o&anagiR8arada disease is a s&stemic inflammator& condition characteri4ed ,& a
panuveitis often granulomatous of sudden onset 5hich ma& ,e associated 5ith neurologic
dermatologic and auditor& involvement0
?1/102101@
6he disease is more common in individuals
from #sian 8ispanic or #mericanR)ndian heritage0 6he ophthalmologic findings include a
,ilateral granulomatous panuveitis0 !78 disease is ,ro<en into four phases 5hich ma&
overlap:
S (rodromal in 5hich the patients ma& often e:perience flu and2or meningitis-li<e
s&mptoms0 8eadache is a common complaint even 5ithout meningismus>
#cute uveitic during 5hich patients present 5ith anterior cell2flare e:udative retinal
detachments diffuse choroiditis and optic disc edema>
Chronic 5ith regression of active inflammation and appearance of the hallmar< 9sunset-
glo59 fundus appearance0 #lthough some patients continue to have chronic ,ilateral
#C posterior segment recurrences are rare e:cept 5hen treatment is 5eaned too
rapidl&0 (atients ma& often demonstrate poliosis or vitiligo during this stage of the
disease>
Recurrent in 5hich anterior inflammation is more prominent than posterior0
#ssociated s&mptoms or signs are often helpful in diagnosing !78 disease0 Feurologic
s&mptoms ma& ,e multiple and severe including ,ut not limited to meningeal s&mptoms and
signs headache confusion cranial nerve palsies and inner ear disorders although this is rare0
6he presence of neurologic s&mptoms ma& re;uire ,rain neuroimaging and C+G anal&sis to
rule out other etiologies0 %ften in !78 there 5ill ,e cellular pleioc&tosis of the C+G0
Gluorescein angiograph& 5ill confirm choroiditis at the time of disease onset 5ith multiple
areas of lea<age at the level of the retinal pigment epithelium0 Cltrasonograph& t&picall&
demonstrates a thic<ened choroid0 #n important differential diagnosis to !78 is s&mpathetic
ophthalmia0
%ther causes of panuveitis include BehTet9s disease sarcoidosis and infectious endophthalmitis0
?1141341488-104105@
)nfectious endophthalmitis ma& initiall& present 5ith vitritis ,ut t&picall& a
severe inflammation involving all ocular structures is o,served0 (ostoperative endopthalmitis is
usuall& suspected 5hen the inflammation occurs after surger& and can ,e acute or chronic0 )n
the latter case it ma& partiall& respond to corticosteroids0 Kate-onset postoperative
endophthalmitis even &ears after surger& must ,e suspected in patients after glaucoma surger&
5ith ne5-onset inflammation especiall& after use of mitom&cin0 'ndogenous endopthalmitis
often is suspect 5hen there are ris< factors such as recent ,o5el perforation or surger&
ind5elling lines intravenous drug use or <no5n recent infections else5here0 )f endogenous
endophthalmitis is suspected vitreous sampling 5ith culture and potentiall& 5ith molecular
diagnostics is indicated0
?11@
)f there is no prior histor& of trauma or e&e surger& then
echocardiograph& CJR and ,lood cultures should also ,e performed0 8)! testing should also
,e considered in other5ise health& individuals presenting 5ith suspected endogenous
endophthalmitis0 %ther important considerations in the differential diagnosis are mas;uerade
s&ndromes and primar& intraocular B-cell l&mphoma0
?103/-4@

Multifocal Choroiditis and Panuveitis (MCP)
Case $epor!
# /4 - &ear old 5hite 5oman e:periencing ,lurr& vision in ,oth e&es presented in +eptem,er
1--10 8er past ocular histor& revealed ,ilateral uveitis 5hich 5as diagnosed 4 &ears
previousl&0 +he had had 4 flare-ups since then 5hich improved 5ith s&stemic corticosteroids0
+he 5as ta<ing (rednisone 10 mg2 ever& other da& at her presentation0 8er past medical
histor& 5as significant 5ith muscular aches sinus pro,lems chills night s5eats and fatigue0
8er visual acuit& 5as 20225 %C0 +lit-lamp e:amination sho5ed trace flare and no cells in the
anterior cham,er of ,oth e&es0 %phthalmoscopic e:amination sho5ed vitreous opacities and
mild epiretinal mem,ranes D'R*E in ,oth maculae as seen in the figures ,elo50
Ka,orator& 5or<-up0 including G6#-#B+ serum l&so4&me and angiotensin converting en4&me
D#C' E (($ and chest J-ra& 5as normal0
%n follo5-up 1 &ear later the patient came complaining of decreased vision in ,oth e&es more
so in the right e&e0 !# at that time 5as 20240 %$ and 20210 %+0 6here 5ere flare 1U and
cells1U in the anterior cham,er of ,oth e&es0 6here 5ere vitreous cells D1UE in the right e&e and
'R*9s %C0 6opical steroid ever& 2 hours 5as started and transseptal 7enalog 40 mg 5as
administered to the right e&e0 %ne month later fundus e:amination revealed decreased vitreous
reaction Dcells 1UE %C c&stoid macular edema DC*' E %$ and multiple round &ello5
chorioretinal infiltrates in the peripheral retina of the right e&e0
Because the 5or<-up including for s&philis sarcoidosis and tu,erculosis 5as negative
diagnostic vitrectom& 5as done in the right e&e on 112212-40 C&tologic e:amination of the
vitreous specimen 5as negative for malignant cells0 65o months laterD122-4E similar round
&ello5 chorioretinal lesions appeared in the posterior and peripheral retina of the left e&e and
there 5as C*' %C as seen ,elo50
Gluorescein angiograph& DG#E sho5ed significant C*' %C and earl& h&perfluorescence of the
chorioretinal lesions and staining of the small vessels0 D+ee G# ,elo5E0
(rednisone 40 mg2d 5as started 5ith slo5 tapering0 6he patient had cataract e:traction 5ith
posterior cham,er )%K implantation in her right e&e on 32132-50 (rior to her operation she had
no active inflammation in ,oth e&es and after surger& she had ,een doing 5ell 5ith (red-Gorte
;id and (rednisone 10 mg2d0
%n her last e:amination in 10282-/ her !# 5as 20210 %$ and 20250 %+0 +lit-lamp
e:amination revealed trace flare and rare cells %C posterior su,capsular cataract %+ and
vitreous cells 1U %C0 Gundus e:amination sho5ed multiple round atrophic punched-out
chorioretinal lesions %C0 +he 5as in sta,le condition 5ith onl& $olo,id 500 mg2d> ,& mouth0
6his case is an e:ample of multifocal choroiditis and panuveitis D*C(E 5ho 5as follo5ed-up
closel& 5ith a relativel& good response to s&stemic corticosteroids and 5ith a good prognosis0

MU%)I-OCA% CO$OIDI)IS A'D PA'UV.I)IS / MCP 0
)n 1-31 Fo4i< and $orsch descri,ed 2 patients 5ith ,ilateral anterior uvetis associated 5ith a
chorioretinopath& resem,ling the presumed ocular histoplasmosis s&ndrome D(%8+E D1E0 )n
1-84 $re&er and "ass presented their series of 28 patients 5ith uveitis and similar lesions at
the level of the retinal pigment epithelium DR('E and choriocapillaris and called the s&ndrome
multifocal choroiditis and panuveitis D2E0 )n 1-85 $eutsch and 6essler descri,ed 28 patients
5ith a similar condition 5hich the& called inflammator& pseudohistoplasmosis ,ut most of
these patients had findings to suggest s&stemic diseases such as sarcoidosis s&philis or
tu,erculosis D1E0 Ginall& in 1-8/ *organ and +chat4 reported 11 similar cases of a condition
the& called recurrent multifocal choroiditisD4E0 6hese four reports all descri,e a condition 5ith
fundus lesions that mimics (%8+ ,ut 5ith the addition of vitritis and often an anterior
uveitis0 *C( is one of the most common 5hite dot chorioretinal inflammator& s&ndromes
D124E
Clinical features
Patient characteristics and symptoms
*ultifocal choroiditis and panuveitis primaril& affects 5omen D35M-100ME0 6he ages have
varied from / to /- &ears ,ut most patients are in their thirties0 6here appears to ,e no racial
predilection0 *ost patients give no histor& of living in areas endemic for (%8+ nor do the&
have affected famil& mem,ers0 *ost patients have ,ilateral involvement D45M-3-ME ,ut there
ma& ,e as&mmetric involvement and man& of the involved second e&es ma& ,e completel&
as&mptomatic0 (atients usuall& present su,acutel& 5ith decreased central vision or
metamorphpsia0 %ther less common presenting complaints include paracentral scotomata
floaters photopsias mild ocular discomfort and photopho,ia0 )nitial visual acuit& is highl&
varia,le ranging from 20220 to light perception0
Anterior ueitis
#nterior uveitis in *C( D4/M-8-ME ma& consist of mild to moderate cellular reaction in the
anterior cham,er nongranulomatous <eratic precipitates and posterior s&nechia0 )n (%8+ the
anterior cham,er is nota,l& clear0
!itritis
*C( differs from (%8+ clinicall& in a num,er of 5a&s the most important ,eing the
presence of vitritis in one or ,oth e&es0 )n fact the presence of vitreous cells in an e&e
effectivel& eliminates the diagnosis of (%8+0 !itritis 5as o,served in all of the patients in the
series of Fo4i< and $orsch and $re&er and "ass and in 8-M of the patients in $eutsch and
6essler9s series0 6he vitritis ranges from mild to moderate and ma& ,e as&mmetrical0 Kittle
vitreous de,ris is seen once the active inflammation ;uiets do5n0
Chorioretinal lesions
6he <e& finding in *C( is the chorioretinal lesions scattered in the fundus0 #cutel& several to
several hundred &ello5 D sometimes gra&E lesions are seen at the level of the R(' and
choriocapillaris 0 *ost lesions are 50 to 150 mm in diameter ,ut occasionall& ma& ,e larger0 )n
contrast the lesions in (%8+ tend to ,e larger D100 to 1000 mmE and fe5er Dless than 10E D5E0
6he lesions are usuall& round or oval in shape and ma& ,e seen in the posterior mid-peripheral
or peripheral retina0 6he& ma& ,e seen singl& in clusters or arranged in a linear configuration
Dlinear strea<sE in the e;uatorial region D/E0 6hese lesions eventuall& ,ecome deep round and
atrophic 5ith varia,le degrees of pigmentation and scarring DGigure -E0 Fe5 chorioretinal
lesions ma& ,e seen in conAunction 5ith old scars in recurrences0
6&picall& most patients develop peripapillar& scarring similar to that seen in (%8+D5hite
nap<in-ring li<eE0 D-"gure 10E %ptic disc pallor and narro5ing of the retinal vessels is much
less fre;uentl& seen0 C&stoid macular edema DC*'E occurs in 10M to 20M of patients0
#,out 25M to 1-M of patients 5ith *C( develop macular and peripapillar& choroidal
neovascular mem,ranes DCF!*9sE 5hich ma& ,e the presenting cause for decreased vision0
*acular CF!* 5ith e:tensive scarring is the maAor cause of visual loss in *C(0
)n fluorescein angiograph& acute lesions h&perfluoresce earl& and lea< latel&0 %ld scars
t&picall& act as 5indo5 defects 5ith earl& h&perfluorescence and late fading0
)n $re&er and "ass9s series electroretinograph& has ,een reported to ,e normal or ,orderline
D41ME moderatel& reduced D13ME or severel& reduced D21ME D2E0
!isual field testing ma& reveal ,lind spot enlargement scotomata corresponding to the
chorioretinal lesions or large temporal field defects 5hich do not necessaril& have
corresponding fundus lesions0
Clinical course
*C( tends to ,e a chronic disorder lasting several months to &ears0 Recurrent ,outs of
inflammation are the rule and ma& occur in one or ,oth e&es either separatel& or
simultaneousl&0 Fe5 lesions can occur an&5here in the fundus0 CF!*9s ma& ,e present
initiall& or develop late in the follo5-up0 Because of the chronic and recurrent nature of *C(
patients need to ,e follo5ed closel&0 6he visual prognosis in *C( is guarded mostl& due to
choroidal CF!*9s 5hich occur in a,out one third of the patients0
'tiolog&
6he cause of *C( is not full& understood0 6iedeman suggested a viral etiolog& 5hen he found
serologic evidence of chronic or persistent 'pstein-Barr virus D'B!E infection in 10 patients
5ith *C( 5hich he did not find in 8 control patientsD3E0 # su,se;uent stud& ,& +paide et al0
did not support this h&pothesisD8E0 *oreover patients 5ith *C( do not have s&stemic signs of
chronic 'B! infection0 )n another recent stud& 3 cases of *C( 5ere evaluated0 6he presence
of specific anti,odies in the a;ueous and serum suggested recent infection 5ith herpes 4oster in
2 cases and herpes simple: in 2 cases D-E0 )t is possi,le that an e:ogenous pathogenDsE 5hether
viral ,acterial or fungal initiall& triggers an immune response 5hich can lead to su,se;uent
e:acer,ations in the a,sence of the inciting pathogen0 6his is clearl& true in (%8+0 #dditional
5or< is needed to more clearl& define the cause of *C(0
$ifferential diagnosis
6he most important condition to consider in the differential diagnosis of *C( is (%8+ since
the fundus appearance in ,oth entities including peripapillar& scarring chorioretinal lesions
Dsometimes as linear strea<sE and CF!* can ,e ver& similar0 *C( differs from (%8+ in the
follo5ing aspects : D1E !itreous cells are present often 5ith anterior uveitis> D2E active ne5
choriretinal lesions ma& develop in the follo5-up> D1E most patients come from nonendemic
histoplasmosis areas and have negative histoplasmin s<in tests> D4E lac< of 8K#-$R2
specificit& 5hich is often present in (%8+ D10E> D5E a female se: predilection in *C(and it
ma& occur in children> D/E the 'R" ma& ,e a,normal in *C(0
(atients 5ith ,irdshot chorioretinopath& are usuall& older have more often ,ilateral
involvement and distinctive discrete cream colored or depigmented spots stre5n throughout
the fundus 5hich are rather distinct from the chorioretinal lesions seen in *C(0)n addition
8K#-#2- specificit& in BCR helps greatl& in the differential diagnosis0
*ultiple evanescent 5hite dot s&ndrome D*'.$+E primaril& affects &oung 5omen ,ut the
presentation is more often acutel& it is usuall& unilateral the small gra&-5hite lesions are at
R(' level and usuall& confined to the posterior retina there is t&pical orangish macular
granularit&0)t is self-limited Daverage 8 5ee<sE 5ith a return of visual acuit& to 20220-20240
and it rarel& recurs0
(unctuate inner choroidopath& D()CE descri,ed ,& .at4<e et al0 resem,les closel& *C( D11E0
(atients 5ith ()C are &oung moderatel& m&opic 5omen and usuall& present acutel& 5ith
,lurred central vision flashing lights and small central or paracentral scotomas0 6here is
usuall& no intraocular inflammation chorioretinal lesions appear all at one timeare confined to
the posterior and mid-peripheral retina and it does not usuall& recur unli<e *C(0 !isual
prognosis is good and no treatment is needed e:cept for the 25M of e&es that develop a
CF!*0
%ther diseases that should ,e considered in the differential diagnosis of *C( include
sarcoidosis s&philis K&me disease miliar& tu,erculosis intraocular l&mphoma herpes virus
infection inflammator& ,o5el disease and outer retinal to:oplasmosis0 6hese diseases usuall&
have other characteristic clinical and2or la,orator& findings that help in differentiation0
6reatment
(eriocular or s&stemic corticosteroids have ,een used to treat *C( although the ,est therap&
for *C( is still not clear0 )n $re&er and "ass9s report / of 18 patients had improvement of
vision 5ith steroid therap& and 2 additional patients ,elieved that the steroids halted a rapid
loss of vision0 6here 5as no change in - patients D2E0 *organ and +chat4 reported that all of the
patients in their series 5hom the& treated 5ith s&stemic or periocular steroids responded 5ell
and in one patient 5ith a macular CF!* shrin<age of the mem,rane and improvement in
visual acuit& 5as o,served D4E0$re&er and "ass treated a similar patient 5ith oral steroids ,ut
5ithout an& effect on the CF!* D2E0 Fussen,latt and (alestine o,served a moderatel& good
response to steroids ,ut noted that the disease can ,e stu,,ornl& chronic and in such cases the&
recommend consideration of other immunosuppressive drugse0g0 c&closporine D12E0 Clinicians
should avoid the mista<e of continuing corticosteroids 5hen there appears to ,e little effect0
':trafoveal mem,ranes can ,e treated 5ith laser along 5ith oral corticosteroids0 Cnli<e those
of (%8+ macular CF!*9s in *C( have often e:tensive fi,rosis ma<ing the surgical removal
of su,macular neovascular nets most difficult D11E