16Fuchs’ Uveitis and

Posner-Schlossman Syndrome

INTRODUCTION AND HISTORICAL ASPECTS

In 1906 Ernst Fuchs described a condition includingheterochromia, unilateral inflammatory signs such asfine “microgranulomatous” keratic precipitates (KPs)as well as unilateral degenerative signs including irisatrophy and vitreous strands. He called the diseaseheterochromic cyclitis, more precisely his words were“cyclitis associated with heterochromia”, which wouldlater be known by the eponym of Fuchs’ heterochromiccyclitis or iridocyclitis1 (Figures 1A and B).

In the 15th edition of Fuchs’ ophthalmologytextbook the full clinical picture is described includingthe very prominent vitreous involvement andinfiltration2 (Figure 2).

Because the disease was described in Vienna, in aCaucasian population, the most striking clinical sign,heterochromia, was included in the eponym of thedisease called until today Fuchs’ heterochromiccyclitis. It is thought that in the past the disease wasprobably underdiagnosed in areas where irises arenearly exclusively brown and heterochromia is notpart of the disease picture. The disease should there-fore simply be named “Fuchs’ uveitis”. The diseasepattern with onset mostly from the second to the fifthdecade, points towards an external, probably infectioustrigger that is at the origin of the subsequently auto-entertained disease in persons that are probablygenetically predisposed.3

EPIDEMIOLOGICAL ASPECTS

The disease seems to be occuring in most parts of theworld with similar frequencies. In European reports,the percentage of cases in uveitis series is going from2.2% in Portugal,4 5.0% in the Netherlands,5 5.4% inSwitzerland6 to even 8.32% in Italy.7 Around theworld, the proportion of Fuchs’uveitis (FU) in uveitispatient series is 6.6% in Iran,8 3.5% in Saudi Arabia,9

2% in Japan,10 5.7% in a recent study performed insouthern China11 and 4.2% in African Americanpatients.12 As can be concluded from this sample ofepidemiological data, the disease seems to beubiquitous and seems nowadays to be diagnosed withequal performance in brown iris population countriesas shown by the recent chinese series.11

CLINICAL SYMPTOMS AND SIGNS

In contradiction to what is written in many textbooksand articles, Fuchs’ uveitis is a granulomatous disease.It has several clinical features such as Koeppe nodulesand granulomatous keratic precipitates (KPs) thatmake up the definition of granulomatous uveitis. Itshould be remembered that the term granulomatousis a misnomer as terminology coming from pathologyis used to describe a clinical entity or group of diseases.This term however serves very well clinical purposesas the definition of granulomatous uveitis is veryprecise and useful, including KPs that are more than

Carl P Herbort, Nadia Bouchenaki

A. Fuch’s Uveitis

Imaging in Uveitis322

just dust on the endothelium, Koeppe nodules at thepupillary margin and Busacca nodules on or withinthe iris. It is worthwile to clearly specify here that assoon as KPs can be individually identified, meaningthat they have already an “architecture”, they shouldbe termed as granulomatous, which is not alwaysclearly stated in textbooks. This is at the origin of theerroneous misclassification of Fuchs’ uveitis as a nongranulomatous uveitis. In Fuchs’ uveitis the granulo-

Figure 1A: 15th edition of ErnstFuchs’ ophthalmology textbook

Figur 1B: Title page of 15th edition ofFuchs’ ophthalmology textbook

Figures 1A and B: View of of the 15th edition of Fuchs’ textbookon ophthalmology (1926) where the exact description of“hetrochromia and cyclitis” is given (A) and view of 1st page oftextbook (B)

Figure 2: Original text on Cyclitis associated with heterochromiain the 15th edition of Ernst Fuchs’ ophthalmology textbook

matous KPs have usually a quite specific aspect withfluffy edges taking sometimes a stellate appearancewith fine spicules extending from the body of the KP

Fuchs’ Uveitis and Posner-Schlossman Syndrome 323

with a diffuse distribution on the endothelial surface(Figure 3).

SYMPTOMS

Most often floaters as well as blurred vision and visualdeterioration is pushing patients to consult. Very oftenhowever the unilateral inflammation is a chancediscovery during a routine ophthalmological exami-nation. If anterior involvement is not prominent it canbe missed and the attention of the ophthalmologist isattracted by the more obvious vitreal involvementoften causing the diagnosis to be missed in favour ofintermediate uveitis or other diagnoses such as the nonspecific diagnosis of “granulomatous uveitis”, “poste-rior uveitis” or “panuveitis”.

SIGNS (TABLE 1)

The signs that have mostly been put forward in theliterature is heterochromia because it is the mostspectacular sign as well as stellate granulomatous KPsthat are also very characteristic.This is at the origin ofthe idea in the practitioner’s mind that Fuch’s uveitisis a purely anterior uveitis. If series coming fromEuropean countries are analysed, heterochromia isreported in 82% in the Netherlands,13 in 87% in aEuropean study,14 in 80% in a North-American study15

and 70% in a United Kingdom study.16 When analys-ing studies coming from predominantly brown eyedpopulation countries the proportion of heterochromiais by far lower and goes down to 14% in China17 andto 23% in Japan.10 Instead of focussing on hetero-chromia, the iris signs to search for are iris atrophicchanges with or without heterochromia. In some seriesatrophic iris changes are present in close to 100% ofcases (Figure 3).

The proportion of patients for whom characteristicKPs were described do not differ among Caucasianand brown eyed populations representing respec-tively 88% (Netherlands),13 96% (Belgium),14 81%(UK)16 and 96% in a North American study15 which isnot sensibly different for Asian series where thepercentage is respectively 91.5% for China17 and 97%for Japan10 (Figures 4A-C). See proportion of signs intable one.18-20

Another set of signs is seen less consistently as thetwo previous signs but is very helpful to make thediagnosis more certain. This includes posterior polarsubcapsular cataract (Figure 5), iris (Koeppe > Bussaca)nodules (Figure 6) and abnormal vessels in the irido-corneal angle. The latter sign is not always reportedin Fuchs’ uveitis series. These abnormal angle vesselsare also at the origin of the classically reported“Amsler’s sign” consisting of occurence of a hyphemawhen an anterior chamber puncture or tap isperformed. Similarly these vessels are also at the originof hyphema during cataract surgery.

One of the most neglected signs is vitreous infil-tration which is even not reported in some series,although it is one of the signs described originally byFuchs (Figure 7).

The degree of vitreous involvement may vary fromthe presence of a few cells to an infiltration with densevitreous fibrous strands and condensations which mayexplain an erroneous diagnosis such as intermediateor posterior uveitis. In rare cases the heavily infiltratedvitreous may be at the origin of peripheral retinal tearsand retinal detachment.

Finally absence of some clinical signs are almostdiagnostic and may be excluding signs if present butare rarely reported. This is the case of “absence ofcystoid macular oedema” (CMO) and “absence ofposterior synechiae” on the crystalline lens which arepresent if reported in a proportion of over 95%. In the

Figure 3: Iris atrophy. This patient with Fuch’s uveitis had nofrank heterochromia. However the iris is clearly atrophic. Notesparsly distributed KPs visible on the cornea in front of the wholepupillary area

Imaging in Uveitis324

Tabl

e 1

Cou

ntry

Sw

itzer

land

Net

herla

nds

Bel

gium

U.K

. (1)

U.K

. (2)

Spa

inU

SA

Bra

sil

Japa

nC

hina

Yea

r20

0719

9119

8419

9519

9120

0119

8219

8919

8220

06

Nam

e 1s

t aut

hor

Bou

chen

aki

La H

eyD

erno

ucha

mps

Fear

nley

Jone

sV

elill

aLi

eseg

ang

Silv

aH

iguc

hiY

ang

Nbr

of C

ases

8851

550

7710

326

5413

243

104

Nam

e gi

ven

to u

veiti

sFu

chs’

uve

itis

FHC

FHC

FHC

FHU

FHC

Fuch

s’ u

veiti

sFH

CFH

CFu

chs’

syn

d-

Ref

eren

ce23

1314

1619

20sy

ndro

me

1518

10ro

me

17

Vitr

itis

98%

84%

69%

84%

66.6

0%14

.80%

55%

N/D

88%

73.8

Fuch

s K

Ps

85%

88%

96%

81%

83.8

0%10

0%96

%99

%98

%92

%

Het

eroc

hrom

ia43

%82

%82

%70

%90

.30%

70.4

0%80

%34

%23

%14

%

Iris

chan

ges

(atro

phy)

N/D

100%

N/D

94%

100%

14.8

0%98

%18

%10

0%10

0%

Cat

rarc

t55

%82

%84

%73

%80

.10%

77.8

0%90

%70

%93

%70

.70%

Gla

ucom

a / H

yper

t.9%

22%

19%

21.3

0%26

%14

.80%

59%

19%

12.1

0%23

%

Abn

. ang

le v

esse

ls13

%N

/DN

/DN

/DN

/D70

%N

/D33

%N

/D

Iris

nodu

les

13%

10%

N/D

32%

20%

7.40

%N

/DN

/D83

%28

%

Bila

tera

lity

12%

4%8%

15.8

0%7.

80%

4%0%

21%

0%13

.50%

Abs

ence

of C

MO

100%

98%

N/D

N/D

N/D

N/D

N/D

N/D

98%

N/D

Abs

ence

of s

ynec

hiae

100%

100%

N/D

98.7

0%10

0%N

/DN

/D94

%81

%N

/D

FHC

= F

uchs

’ Het

eroc

hrom

ic C

yclit

isFH

U =

Fuc

hs’ H

eter

ochr

omic

Uve

itis

N/D

= n

ot d

one

Fuchs’ Uveitis and Posner-Schlossman Syndrome 325

absence of the characteristic signs of heterochromiaand Fuchs’ KPs and the presence of vitritis these signshave almost determining diagnostic value. Howeverboth these signs are reliable only in patients that havenever undergone intraocular surgery. Fuchs’ uveitispatients having had intraocular surgery are no moreprotected against CMO nor irido-lenticular synechiae.The proportion of any given sign in Fuchs’ uveitisseries is shown on Table 1, indicating some diversityin the proportion of reported signs from one study toanother.

Figure 4A: Microgranulomatous FuchsKPs that do not cluster inferiorly

Figure 4B: Macroscopic view of Fuchs KPs showing spiculesor extentions from the “body” of the KP

Figure 4C: Macroscopic view of Fuchs KP showing fluffyborders and extensions (yellow arrows)

Figures 4A-C: Fuchs’ typical microgranulomatous KPs withdiffuse spread-out disposition on whole endothelium (A) andmacroscopic view (B and C)

Figure 5: Fuchs KPs and posterior polar cataract. Pictureshowing two planes; towards the right typical Fuchs KPs;towards the left of the picture white posterior subcapsularcataract

Figure 6: Koeppe nodules. Fuchs uveitis in a brown eye. TwoKoeppe nodules on the iris border (yellow arrows). Note alsoatrophic changes in the iris with loss of intensity of brown colour

Imaging in Uveitis326

LASER FLARE PHOTOMETRY

Laser flare photometry (LFP) is measuring backscattered photons from anterior chamber proteinswhen a laser light beam is shone into the anteriorchamber. Its principle is identical to slit-lamp anteriorchamber examination except that in LFP the lightsource is monochromatic and quantified rather thanpolychromatic. Also the light detector is objectivemade of a photomultiplyer and photodetector ratherthan the subjective human eye.21 This methodtherefore allows to measure objectively the disruptionof the blood-aqueous barrier and hence the exact levelof intraocular inflammation.22 When we measuredflare in our Fuchs’ uveitis patients at presentation themean flare value was 8.62 ± 4.3 photons per milli-second (ph/ms) which is only slightly above normalvalues (4-6 ph/ms). This showed that in most Fuchs’cases there is minimal disruption of the blood-aqueousbarrier, hence minimal anterior chamber inflam-mation.23 Moreover, at the end of follow-up this valueremained stable at 8.45 ± 4.3 ph/ms in our patientsand did not increase, showing that inflammation doesnot progress in the absence of treatment. This hasrecently been confirmed by a chinese study reportingsimilar values.24

It is however in every day practice that LFP hasproved especially useful for Fuchs’ uveitis. In thoseFuchs cases that have been misdiagnosed and areunder topical and sometimes even systemiccorticosteroid therapy, LFP allowed to show that, afterdiscontinuation of therapy, there is no rebound flareincrease or minimal flare increase indicating to thepatient and to the referring doctor that it is safe towithdraw potentially harmful therapy that has noimpact on inflammation in this disease.

ANGIOGRAPHIC FINDINGS

In case of a clinically sure diagnosis of Fuchs’ uveitisthere is no need to perform fluorescein angiography.Very often however diagnosis is missed initially andfluorescein angiography happens to be performed. Weanalysed a series of 23 patients that had a fluoresceinangiography performed for diagnostic purposes.23

In all but one of these patients was there a slight tomoderate and sometimes pronounced disc hyperfluo-rescence (Figure 8). The only patient who had no dischyperfluorescence was a case that was known to havedisc atrophy previous to the diagnosis of Fuchs’uveitis. In 4 patients slight mid-peripheral retinalvascular leakage was seen. No cystoid macularoedema could be seen in any of the 21 patients thathad never had intraocular surgery even after verylongstanding inflammation. Cystoid macular oedemawas present in two patients both of whom hadundergone cataract surgery.

Being aware of these results it might be helpful andjustified to use fluorescein angiography as a diagnosticprocedure in some cases where Fuchs’ uveitis is thepresumed diagnosis but where some of the principalsigns are missing. In such cases with longstandinguveitis with prominent vitreous infiltration, theabsence of an angiographic CMO together with dischyperfluorescence can be considered confirmatory ofFuchs’ uveitis.

DIFFERENTIAL DIAGNOSIS, EVOLUTION,THERAPY AND PROGNOSIS

In the paragraphs on differential diagnoses given forFuchs’ uveitis, textbooks usually only cite otheranterior uveitis entities such as herpetic uveitis, zosteruveitis, Posner Schlossman syndrome, etc. Only one

Figure 7: Vitritis, the misleading sign. This young ladyconsulted her ophthalmologist because of a suboptimal vision.The presence of a dense vitritis rendering the fundus imageblurred was interpreted by the ophthalmologist as anintermediate uveitis. He introduced systemic steroids followed6 months later by cyclosporin that still had no effect. After seeingthe patient for a second opinion, inflammation suppressivetherapy was progressively withdrawn under laser flarephotometry monitoring without rebound inflammation and stableevolution

Fuchs’ Uveitis and Posner-Schlossman Syndrome 327

textbook cited intermediate uveitis as a possibledifferential diagnosis.25 This shows how strong theidea is, even among textbook authors, that Fuchs’uveitis is a purely anterior uveitis, making abstractionof the vitreous involvement. In real ophthalmologicpractice the situation is quite different. In our seriesin which 84% of patients werw referred, the list oferroneous diagnoses, hence diagnoses that should belisted in the differential diagnosis for Fuchs’uveitis,was headed by intermediate uveitis in 37/59 (63%) ofnon diagnosed cases followed by panuveitis in 11/59(19%), posterior uveitis in 6/59 (10%) patients andgranulomatous uveitis in 5/59 (8%). The nature ofthese diagnoses indicates that the clinician tends to ruleout Fuchs’ uveitis in the presence of inflammatoryvitreous involvement.

Evolution of Fuchs’ uveitis is mostly benign as thesensitive structures such as the macula is nearly neverinvolved despite substantial and prolonged vitritis.Therefore no therapy is necessary. Neverthelessregular follow-up examinations are necessary in orderto detect complications such as intraocular hyper-tension or glaucoma as well as cataract which may bepart of the natural course of the disease but which areoften favoured by the abusive and/or long term useof steroids. Prognosis is rather good because even ifcataract is present, it is operated with success becausethese eyes tolerate surgery very well as was noted inFuchs’ original descriptions. Among the 10 to 20 % ofpatients that develop glaucoma, some are difficult to

stabilise despite surgery and prognosis is reserved onlyin this portion of Fuchs patients.

Despite the fact that about 15-20% of Fuchs’ eyesdevelop hypertension, the mean pressure of the Fuchseye is lower than the fellow eye (12.04 ± 4 versus 12.87± 4.2 mmHg), indicating that, as a rule, the affectedeye has a lower pressure than the normal eye.

Although corticosteroid therapy is not supposed tobe used because of absence of impact, there are raresituations where inflammatory bouts occur that mightbenefit from short courses of topical steroids.

WHY IS FUCHS’ UVEITIS SO OFTENMISDIAGNOSED OR DIAGNOSED WITHSUBSTANTIAL DELAY? / DIAGNOSTICCRITERIA OF FUCHS’ UVEITIS

The reasons why Fuchs’ uveitis is so often misdiag-nosed or underdiagnosed are several, includingbilaterality usually not associated with the disease butwhich occurs in about 10%, search for heterochromiawhich is often absent especially in brown eyedcountries and absence of the characteristic KPs. Themain reason however, as stated earlier, is the presenceof inflammatory vitreous involvement that, in themind of the practitioner, is usually not associated withFuchs’ uveitis when in reality it is a major diagnosticsign. This leads to diagnostic delay which in our seriesoccured in 59/79 (75%) cases with a mean duration ofdelay of 3.67± 4.34 years. Unawareness that vitritis is

Figure 8: Disc hyperfluorescence on the side of Fuchs’ uveitis (lef eye on the right side of the picture)

Imaging in Uveitis328

part of Fuchs’ clinical picture is also at the origin ofinadequate, useless and potentially harmful therapysuch as systemic coricosteroids and/or even systemicimmunosuppressants that were given in 34/79 (43%)patients in our study.

Therefore diagnostic criteria of Fuchs’ uveitis haveto be reconsidered. The most striking clinical signssuch as heterochromia and characteristic KPs are ofcourse very useful for the diagnosis when they arepresent. However the diagnosis has to be made moresecure by considering also less spectacular signs albeithighly consistent that put together allow to make thediagnosis of the condition even without the moreobvious signs. A very high, almost 100% degree ofcertainty is obtained when triad consisting ofheterochromia, typical KPs and vitritis is present. Theneglected or more discrete signs that are recorded witha proportion of close to 100% in Fuchs’ series are, whengoing antero-posteriorly (1) atrophic iris changes,(2) absence of posterior irido-crystalline synechiae,(3) vitritis or vitreous strands and (4) absence of cystoidmacular edema. The occurence of the combination ofthese signs probably allows to reach an almostidentical degree of certainty. The association of “ minorsigns“ such as (1) iris nodules, (2) cataract and(3) stromal pseudo-neovessels apparent because of irisatrophy or abnormal iridocorneal angle vessels withor without Amsler’s sign (hyphema following anteriorparacentesis) add to the degree of certainty of thediagnosis.

PATHOGENESIS OF FUCHS’ UVEITISAND CONCLUSION

Fuchs’ uveitis typically has the profile of a diseasecaused by an infectious triggering factor (probablymore than one) at the origin of an immune auto-entertained disease in genetically susceptible patients.Most cases are diagnosed between the 2nd and the 5thdecade, the period during which individuals areexposed to most of the infectious agents encounterthroughout life including the agent(s) that can triggerFuchs’uveitis.13,15,19 Above the age of sixty the diseaseis less frequently diagnosed as the probability toencounter the infectious trigger is much less. HLA-B27related acute anterior uveitis has an identicalepidemiological profile. For this disease the triggeringagents are known to be debris from gram-negative

bacteria and the genetical predisposition is thepresence of the HLA-B27 antigen.

The evidence accumulated so far indicatingimmune dysfunction in Fuchs’ patients and Fuchs’eyes is sufficient to allow us to consider immunemechanisms as the common effector pathway causinglesions in Fuchs’ uveitis. Very early, when immuno-logical investigations were still very rough, increasedIgG in aqueous humour was found.26 This was laterconfirmed by PI Murray et al who also found increasedinterleukin-6 in the aqueous humour.27,28 Other studiesshowed the presence of autoimmunity to cornealantigens, a possible explanation of the spread-outdisposition of Fuchs KPs.29 Immunohistochemicalanalysis of iris biopsy specimens from patients withFuchs’ heterochromic cyclitis showed evidence of aninflammatory cell infiltrate, which was a mixture ofinterleukin-2 receptor-negative T helper and suppres-sor cells, B lymphocytes, and plasma cells.30 Morerecently Labalette and colleagues showed the presenceof CD8-positive CD28-negative T cell clonotypesindicating an antigen-driven process involving thesecells at the origin of Fuchs’ uveitis.31 In addition acellular autoimmune response to S antigen was foundin patients with Fuchs’ uveitis, a possible explanationof posterior segment involvement,32 which seems tohave received clinical support by a study that showedsubclinical retinal damage using electroretinography.33

As far as the infectious trigger in Fuchs’ uveitis isconcerned, several agents have been put forward. Forsome time toxoplasma Gondii had the favours.34,35

only to be seriously put in doubt some years later.36

Recently the detection of an intraocular synthesis ofanti-rubella antibodies in all tested patients as well asthe rubella genoma itself in 20% of eyes, representeda very strong argument for Fuchs’ uveitis being arubella virus driven uveitis.37 Similar results were alsofound in another group.38 Although there are presentlyquite convincing arguments for rubella to be a triggerfor Fuchs’ uveitis, other possible triggers might alsoplay a role.

In conclusion, Fuchs’ uveitis is an ubiquitousdisease involving the vitreous and the anterior uvea.The inflammatory nature does make no doubt and thepresently favoured pathogenetic mechanism is animmune process triggered by an infectious agentthought to be in many cases rubella virus, other agents

Fuchs’ Uveitis and Posner-Schlossman Syndrome 329

not being completely excluded. The disease is oftenmisdiagnosed because of the textbook generatedunawareness of the quasi 100% rate of association ofvitritis with the disease. Anti-inflammatory treatmenthas mostly no or minimal impact but evolution isfavourable unless complications such as glaucoma orcataract occur.

KEY POINTS

• Fuchs’ uveitis is a mostly unilateral uveitis involving theanterior segment and the vitreous body.

• It is usually diagnosed between the second and fifthdecade, a disease pattern indicating the association ofan external trigger associated with susceptibility to thedisease.

• Moderate decrease of visual function and floaters arethe main symptoms but very often the disease isdiagnosed by chance during a routine visit.

• The main signs of Fuchs’uveitis with a proportion ofpresence between 90-100% are (1)characteristic Fuchs’KPs, (2) iris atrophic changes, (3) vitritis, (4)absence ofsynechiae, (5) absence of CMO, (6) unilaterality

• Complications include cataract formation (> 60%,depending on lenght of follow-up) and glaucoma(12-20%)

• No treatment is necessary for the primary disease.

REFERENCES1. Fuchs E. Ueber Komplikationen der Heterochromie. Z.

Augenheilk 1906;15:191-212.2. Fuchs E. Aetiologie und Formen der Iridozyklitis. In Fuchs

E, (Ed): Lehrbuch der Augenheilkunde. Leipzig und Wien:Franz Deuticke; 1926, p.463-71.

3. Jones NP, Read AP. Is there a genetic basis for Fuchs’heterochromic uveitis? Discordance in monozygotic twins.Br J Ophthalmol 1992;76:22-4.

4. Palmares J, Coutinho MF, Castro-CorreiraJ. Uveitis innorthern Portugal. Curr Eye Res 1990;27(suppl):31-4.

5. Kijlstra A, Rothova A, Baarsma GS, Zaal MJM, Fortuin ME,Schweitzer C, et al. Computer registration of uveitispatients. Doc Ophthalmol 1987;102:234-5.

6. Tran VT, Auer C, Guex-Crosier Y, Pittet N, Herbort CP.Epidemiology of uveitis in Switzerland. Ocular ImmunolInflamm 1994;2:169-76.

7. Pivetti-Pezzi P, Accorinti M, La Cava M, Collobelli GisoldiRA, Abdulaziz MA. Endogenous uveitis: an analysis of1417 cases. Ophthalmologica 1996;210:234-8.

8. Soheilian M, Heidari K, Yazdani S, Shahsavari M,Ahmadieh H, Dehghan MH. Pattterns of uveitis in atertiary eye care center in Iran. Ocular Immunol Inflamm2004;12:297-310.

9. Islam SM, Tabbara KF. Causes of uveitis at the Eye Centerin Saudi Arabia: a retrospective study. Ophthalmic Epi-demiology 2002;9:239-49.

10. Higuchi M, Ohno S, Matsuda H. Clinical characteristicsof Fuchs’ heterochromic iridocyclitis. Rinsho Ganka 1982;36:1275-80.

11. Yang P, Zhang Z, Zhou H, Li B, Huang X, et al. Clinicalpatterns and characteristics of uveitis in a tertiary centerfor uveitis in China. Curr Eye Res 2005;30:943-8.

12. Tabbut BR, Tessler HH, Williams D. Fuchs’ heterochromiciridocyclitis in Blacks. Arch Ophthalmol 1988;106:1688-90.

13. La Hey E, Baarsma GS, De Vries J, Kijlsra A. Clinicalanalysis of Fuchs’ heterochromic cyclitis. Doc Ophthalmol1991;78:225-35.

14. Dernouchamps JP. Fuchs’ heterochromic cyclitis : an IUSGstudyabout 550 cases. In: Saari Km, (Ed). Uveitis update.Amsterdam : Elsevier Science Publishers, 1984;129-35.

15. Liesegang TJ. Clinical features and prognosis in Fuchs’uveitis syndrome. Arch Ophthalmol 1982;100:1622-6.

16. Fearnley IR, Rosenthal AR. Fuchs’ heterochromic irido-cyclitis revisited. Acta Ophthalmol Scand 1995;73:166-70.

17. Yang P, Fang W, Jin H, Chen X, Kijlstra A. Clinical featuresof Chinese patients with Fuchs’ syndrome. Ophthal-mology 2006;113:473-80.

18. Silva HF, Orefice F, Piheiro SRA. Fuchs’ heterochromiccyclitis: clinical study of 132 cases. In: Belfort Jr R, PetrilliAMN, Nussenblatt R, (Eds). Proceedings first worlduveitis symposium, Guaruja, Sao Paulo: Livraria Roca,1989;215-22.

19. Jones NP. Fuchs hetrochromic uveitis : a reappraisal of theclinical spectrum. Eye 1995;649-61.

20. Velilla S, Dios E Herreras JM, Calonge M. Fuchs’heterochromic cyclitis. Ocul Immunol Inflamm 2001;9:169-75.

21. Herbort CP, Guex-Crosier Y, De Ancos E, et al. Use of laserflare photometry to assess and monitor inflammation inuveitis. Ophthalmology 1997;104:64-72.

22. Guex-Crosier Y, Pittet N, Herbort CP. Sensitivity of laserflare photometry to monitor inflammation in uveitis of theposterior segment. Ophthalmology 1995;102:613-21.

23. Herbort CP, Bouchenaki N. Neglected and unrecognisedsigns in Fuchs’ uveitis. Ophthalmic Res 2005;37S:96.

24. Fang W, Zhou H, Yang P, Huang X, Wang L, Kijlstra A.Aqueous flare and cells in Fuchs’ syndrome. Eye 2007;Epub ahead of print.

25. Kanski J. Fuchs’ uveitis syndrome. In Uveitis, a colourmanual of diagnosis and treatment. Butterworths, London;1987, pp 68-70.

26. Dernouchamps JP. The proteins of the aqueous humour.Doc Ophthalmol 1982;53:193-248.

27. Murray PI, Hoekzema R, Luyendijk L, Koenings S, KijlstraA. Analysis of aqueous humour immunoglobulin G inuveitis by enzyme-linked immunosorbent assay, isoelectricfocussing, and immunoblotting. Invest Ophthalmol Vis Sci1990;31:2129-35.

28. Murray PI, Hoekzema R, van Haren MAC, de Hon FD,Kijlstra A. Aqueous humour interleukin-6 levels in uveitis.Invest Ophthalmol Vis Sci 1990;31:917-20.

29. van der Gaag R, Broersma L, Rothova A, Baarsma S,Kijlstra A. Immunity to a corneal antigen in Fuchs’ hetero-chromic cyclitis patients. Invest Ophthalmol Vis Sci 1989;30:443-8.

Imaging in Uveitis330

30. Murray PI, Mooy CM, Visser-deJong E, Baarsma GS, deVries J, de Jong PTVM, et al. Immunohistochemicalanalysis of iris biopsy specimens from patients with Fuchs’heterochromic cyclitis. Am J Ophthalmol 1990 ; 109 :394-9.

31. Labalette P, Caillau D, Grutzmacher C, Dessaint JP,Labalette M. Highly focussed clonal composition ofCD8(+)CD28(neg) T cells in aqueous humnour of Fuchs’heterochromic cyclitis. Exp Eye Res 2002;75:317-25.

32. La Hey E, Broersma L, van der Gaag R, Baarsma GS,Rothova A, Kijlstra A. Does S Antigen play a role in Fuchs’heterochromic cyclitis ? Br J Ophthalmol 1993;77:436-9.

33. Murray DC, Stavrou P, Good PA, Murray PI.Electroretinographic findings in Fuchs’ heterochromicCyclitis. Eye 1997;11:102-8.

34. De Abreu MI, Belfort R, Hirata PS. Fuchs’ heterochromiccyclitisand ocular toxoplasmosis. Am J Ophthamol 1982;93:739-44.

35. Saraux H, Laroche L, Le Hoang P. Secondary Fuchs’heterochromic cyclitis: a new approach to an old disease.Ophthalmologica 1985;190:193-8.

36. La Hey E, Rothova A, Baarsama GS, de Vries J, vanKnapen F, Kijlstra A. Fuchs’ hetrochromic cyclitis is notassociated with ocular toxoplasmosis. Arch Ophthalmol1992;110:806-11.

37. Quentin CD, Reiber H. Fuchs’ heterochromic cyclitis :rubella virus antibodies and genoma in aqueous humour.Am J Ophthalmol 2004;138:46-54.

38. de Groot-Mijnes JD, de Visser L, Rothova A, Schuller M,van Loon AM, Weersink AJ. Rubella virus associated withFuchs’ heterochromic iridocyclitis.

Bechir Jelliti, Moncef Khairallah

B. Posner-Schlossman Syndrome

INTRODUCTION

Posner Schlossman syndrome (PSS) as originallydescribed in 1948 by Posner and Schlossman is a self-limiting and benign condition characterized byunilateral, recurrent attacks of mild, granulomatousiritis with elevated intraocular pressure (IOP) duringthe acute attack, open angle, normal visual field andoptic disc.1

It is classified as an inflammatory glaucomabecause it is by definition always accompanied byuveitis.1 The inflammation may follow the acute risein intraocular pressure (IOP) by some days or be somild as to be overlooked, so the etiology of the rise inpressure may not be clear at first presentation.

EPIDEMIOLOGY AND PATHOGENESIS

PSS tends to affect patients between 20 and 50 yearsof age. Males are more often affected. There is noreported ethnic or racial predilection. Recent reportssuggest an association with the human leukocyteantigen (HLA) Bw54.2,3 Recurrence is common and canbe in either eye but intervals between attacks tend toincrease during the course of the disease.4

The etiology of PSS is uncertain and no recognizedassociated systemic conditions have been reported. Themechanism responsible for glaucomatocyclitic crisis is

unclear. Cytomegalovirus (CMV), varicella-zostervirus and herpes simplex virus (HSV) may be linkedto the disease.5 The trabecular meshwork is innervatedby the trigeminal nerve and is a conduit for HSV. Onepostulated mechanism for the syndrome is that HSVcauses an inflammation of the trabecular meshwork,impeding aqueous outflow and increasing IOP.

The allergic response is also under investigation.High levels of prostaglandin E have been found in theaqueous humor during attacks. These levels have beenobserved to return to normal during remissions.2,6

CLINICAL FEATURES

Typically, patients describe a history of intermittentepisodes of mild visual blurring, colored haloes aroundlights, and minimal discomfort in one eye. Somepatients have no symptoms.

The hallmark feature of PSS is that the IOP (often45 mmHg or higher) does not correspond to theamount of ocular inflammation. The affected eyetypically appears white and quiet on gross inspection,but a small amount of inflammation can usually bedetected. The anterior chamber is deep. A few, small,round non-pigmented keratic precipitates (KPs) tendto accumulate on the lower one third of the cornealendothelium within three days of onset (Figure 1).

Fuchs’ Uveitis and Posner-Schlossman Syndrome 331

A common finding is that the pupil is slightly dilatedin the affected eye compared to the unaffected eye.Gonioscopy reveals normal, open angles withoutabnormal pigmentation.7 Posterior and anteriorsynechiae do not develop in this condition. Signs maybe present for a month or longer without producingsubstantial symptomatology.

PSS is a self-limiting condition that lasts a fewweeks to a month. During the acute and remissionphases of PSS, anterior chamber angles are typicallyopen with normal pigmentary density and noassociated synechiae. Although attacks are self limited,glaucomatous cupping and field loss may occur.

Recurrent attacks characterize the illness; howeverthe frequency of such attacks is highly variablebetween patients. Usually only one eye is affected;rarely however, a patient may experience subsequentepisodes in either eye.8

Posner-Schlossman syndrome does not alwaysfollow a completely uncomplicated course.

Repeated episodes of elevated intraocular pressurecan cause long-term sequelae such as glaucoma. In astudy of 53 cases of PSS, 14 (26.4%) were found to haveglaucomatous optic nerve damage.9

DIAGNOSIS

There are no specific laboratory tests for this entity anda presumptive diagnosis of PSS was made based onthe following findings: recurrent episodes of mild iritis

associated with elevated IOPs, diffuse epithelial edemaof the cornea, and a few fine keratic precipitates . TheIOP is normal between attacks and the angles areopen.10

DIFFERENTIAL DIAGNOSIS

When diagnosing PSS, we must rule out other condi-tions that could cause unilateral or bilateral uveitis.These include Fuchs’ uveitis, acute angle-closureglaucoma, pigmentary glaucoma, herpes simplex virusinfection, uveitic glaucoma, neovascular glaucoma,and secondary angle-closure glaucoma due toperipheral anterior synechiae.11

History, biomicroscopy, tonometry and dilatedfundoscopy are essential for the differential diagnosis.Past ocular, systemic, social and family histories arenecessary to rule out suspected underlying etiologies.

TREATMENT

The treatment for PSS focuses on lowering IOP andreducing inflammation. Therapy may include topicalbeta blockers, topical alpha agonists topical/oralcarbonic anhydrase inhibitors and even hyperosmoticagents.2 Myotic agents are contra-indicated for thetreatment of PSS and uveitic glaucoma because theyenhance the risk for the formation of posterior syne-chia, cause discomfort to the patient by aggravatingciliary muscle spasm and increase inflammation in theeye by amplifying the breakdown of the blood aqueousbarrier. Pain and discomfort may be addressed withcycloplegic agents such as atropine 1%, homatropine5%, or scopolamine 0.25%. Inflammation can be treatedwith topical steroidal preparations, every two hoursdepending on the severity of the episode. Prophylacticanti-inflammatory therapy is somewhat controversial.Most practitioners do not feel that it preventsrecurrences.2,5

KEY POINTS

• PSS is a condition characterized by unilateral attack ofmild, granulomatous iritis with elevated IOP during theacute attack, white eye, open angle, normal visual fieldand optic disc.

• The etiology of PSS is uncertain, but several viruses,including CMV,VZV, and HSV have been suggested aspotential causes of the syndrome

Figure 1: Isolated KPs towards (arrows) and in the irido-corneal angle (not shown) in a case of PSS

Imaging in Uveitis332

• Recurrent attacks characterize the illness. PSS is a self-limiting condition, but glaucomatous optic nerve damagemay occur as consequence of repeated episodes ofelevated IOP

• The treatment for acute attacks of PSS focuses onlowering IOP and reducing inflammation. Prophylacticanti-inflammatory therapy does not seem to preventrecurrences.

REFERENCES1. Moorthy RS, Mermoud A, Baerveldt G, Minckler DS, Lee

PP, Rao NA. Glaucoma associated with uveitis. SurvOphthalmol 1997;41:361-94.

2. Chandler PA, Grant WM. Glaucoma due to intraocularinflammation. In: Glaucoma, Lea and Febinger,Philadelphia, 1986;363-3775.

3. Hirose S, Ohno S, Matsuda H. HLA-Bw54 and glauco-matocyclitic crisis. Arch Ophthalmol 1985;103: 1837-9.

4. Kanski JJ. Clinical Ophthalmology. A SystematicApproach, 5th ed. London: Butterworth Heinemann, 2003.p 238.

5. Geurds EA, Gurwood AS. Anterior uveitis, IOP, signalPosner Schlossman syndrome. Review of Optometry 1998;135(3):114-9.

6. Kanski J, McAllister J, Salmon J. Inflammatory glaucomas.In: Glaucoma, A Colour Manual of Diagnosis andTreatment. Butterworth Heinemann, Boston, 1989;88-9.

7. Narang SK, Shah SJ. Glaucomatocyclitic crisis (Posner-Schlossman syndrome) case report. Indian J Ophthalmol1972;20:25-7.

8. Sangha SS. Posner Schlossman syndrome. Ophthalmology2002;109(3):409.

9. Jap A, Sivakumar M, Chee SP. Is Posner-Schlossmansyndrome benign? Ophthalmology 2001;108:913-8.

10. Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH.Clinical features of cytomegalovirus anterior uveitis inimmunocompetent patients. Am J Ophthalmol 2008;145(5):769-71.

11. Goldberg I. Ocular Inflammatory and Steroid-InducedGlaucoma. In: Yanoff M, Duker JS, (Eds): Ophthalmology.2nd ed. St. Louis: Mosby, 2004;1211:1516-7.