Fuchs uveitis

Ilknur Tugal-Tutkun

Istanbul University, Istanbul Faculty of Medicine

Department of Ophthalmology

Fuchs’ heterochromic cyclitis

Fuchs’ heterochromic iridocyclitis

Fuchs’ heterochromic uveitis

Fuchs uveitis syndrome

FUCHS UVEITIS

5-10% of all uveitis cases

Mostly unilateral

Chronic low-grade uveitis

(1851-1930)

Zeitschrift für Augenheilkunde 1906; 15:191–212

First description by Fuchs in 1902 Heterochromia, cataract and chronic cyclitis with

precipitates always in the eye with the lighter color

15th edition of Fuchs’ book in 1926 Absence of ciliary injection, vitritis, favorable results of

cataract surgery, chorioretinal scars

Fuchs uveitis

Frequently misdiagnosed because of

variable clinical spectrum,

overemphasis of heterochromia,

description as a nongranulomatous uvetis,

classification as an anterior uveitis,

underrecognition of vitreous infiltration.

Misdiagnosis leads to unnecessary and

potentially harmful treatment

Referral patterns Tugal-Tutkun et al N=172

Bouchenaki&Herbort N=105

Study period 1995-2007 1995-2008

Proportion of referral cases 67% 92.4%

Misdiagnosis N=105 (61%) N=75 (71%)

Mean diagnostic delay 31 months 36 months

Previous diagnoses Undefined (86%)

Behçet disease (8.7%)

Intermediate uveitis (2%)

HLA-B27 uveitis (2%)

Herpetic AU (2%)

Intermediate uveitis (56.8%)

Other anterior uveitis (22.3%)

Pauveitis (12.2%)

Posterior uveitis (8.1%)

Previous treatment

Topical corticosteroids

Periocular injections

Systemic corticosteroids

Immunosupp agents

Antiviral

Antibiotic

54%

3%

26%

6%

1%

-

41.9%

7.6%

27.6%

4.7%

2.8%

2.8%

Tugal-Tutkun I, et al. Am J Ophthalmol 2009; 148:510-5

Bouchenaki N, Herbort CP. Middle East Afr J Ophthalmol 2009;16:239-44

Fuchs uveitis is a clinical diagnosis

Presence of Diffuse microgranulomatous stellate KPs

Diffuse iris stromal atrophy with/without heterochromia

Low-grade anterior chamber reaction

Cells and condensations in the vitreous

Subclinical mild flare by LFP

Small nonsticky iris nodules

Chorioretinal scars

Posterior subcapsular cataract

Abnormal vessels in the angle

Paracentesis -hyphema (Amsler sign)

Glaucoma

Absence of Posterior synechiae

Macular edema

Acute symptoms of pain, redness, photophobia

Marked flare

Demogr.

features

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P

et al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

Mean age

(range)

< 16 years

31

(5-80)

35

(15-75)

37

(19-57)

29.5

(10-75)

9.9%

34

(6-75)

35.2

(10-70)

30.1

(10-51)

3.8%

M/F

37 / 31 49 / 55 21 / 33 75 / 97 52 / 53 92 / 74 97 / 86

Bilateral 10.3% 13.5% 6% 5.2% 11.4% 4.8% 8.2%

15 y/o girl with Fuchs uveitis,OD

Presenting

Symptoms

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P

et al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-

Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

Visual blurring 94% 82.6% 24% 61% 35.2% 79.9% 93.9%

Floaters 8% 14.4% 54% 17.4% 49.5% 8.6% 25.2%

Ocular pain

discomfort NA 15.4% 2% NA 3.8% 11.5% -

Redness NA 13.5% 2% NA NA 4.6% 19.7%

Routine exam NA NA 2% 9.9% 7.6% NA 1%

Heterochromia NA NA NA 2.3% NA NA NA

Arellanes Garcia L, et al. Ocul Immunol Inflamm 2002;10:125-31.

Yang P, et al. Ophthalmology 2006;113:473-80.

Norrsell K, Sjödell L. Acta Ophthalmol 2008;86:58–64.

Tugal-Tutkun I, et al. Am J Ophthalmol 2009;148:510-5.

Bouchenaki N, Herbort CP. Middle East Afr J Ophthalmol 2009;16:239-44.

Al-Mansour YS, et al. Int Ophthalmol 2010;30:501-9.

Clinical

features

Arellanes-

Garcia et

al

(2002)

Mexico

N=68

Yang P et al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S. Arabia

N=166

Tandon

et al

(2012)

India

N=183

KPs 90% 100% 100% 97% 95% 90% 92.4%

Jones NP. Eye 1991;5:649-661

Jones NP. Eye 1991;5:649-661

In vivo confocal microscopy

Clinical

features

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P et al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

Saudi Arabia

N=166

AC cells

None

1-2+

≥ 3+

NA

86%

NA

12%

85%

3%

NA

NA

NA

26%

58%

17%

NA

NA

NA

52%

43%

5%

Mean LFP flare

(ph/ ms) NA 6.4 ± 2.3 NA 8.4 ± 3.1

(3.6 to 17.1)

9.85 ± 6.28 NA

Nguyen NX et al. Ophthalmologica 2005;219:21-5.

Tugal-Tutkun I, et al. Am J Ophthalmol 2009; 148:510-5

Bouchenaki N, Herbort CP. Middle East Afr J Ophthalmol 2009;16:239-44

Laser flare photometry studies have shown a mild BAB disruption that

remained stable even after cataract surgery

Laser flare levels and cell counts correlated with the number of keratic

precipitates and degree of iris depigmentation Fang W, et al.Eye 2009;23, 79–84

Clinical

features

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P et

al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-

Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

Saudi Arabia

N=166

Tandon

et al

(2012)

India

N=183

Iris atrophy

Heterochromia 89%

25%

100%

14%

100%

76%

88%

40%

NA

43%

100%

14%

39%

9.6%

Bilateral Fuchs Uveitis

Bilateral hypochromia?

Clinical

features

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P et

al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

Koeppe

Busacca 31%

17%

26%

2%

NA

NA

26%

8%

13%

NA

K+B=13.8% 14.6%

5.5%

Iris crystals 1%

The pupil is slightly larger

Pupillary ruff is lost

Complications

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P et

al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

Cataract

Pseudophakia 69%

NA

71%

NA

80%

7%

62%

7%

47%

12%

86%

NA

70.2%

9.1%

3 wks

Steroid

drops

risk of cataract development:

42% at 4 years

56% at 8 years

Tugal-Tutkun I, et al. Am J Ophthalmol 2009;148:510-5.

Complications

Arellanes-

Garcia et

al

(2002)

Mexico

N=68

Yang P

et al

(2006)

China

N=104

Norrsell

&

Sjödell

(2008)

Sweden

N=54

Tugal-

Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

High IOP

Glaucoma

31%

4%

23%

1%

13%

11%

13%

1%

13%

16%

26%

13.6%

1%

Angle vessels NA NA NA 6/35 (17%) 13/25 (52%) 13/60 (22%) 4/27(15%)

risk of IOP elevation: 17% at 4 years

Tugal-Tutkun I, et al. Am J Ophthalmol 2009;148:510-5.

Spontaneous hyphema

* IOP is typically lower than the fellow eye if there is no OHT

Clinical

features

Arellanes-

Garcia et al

(2002)

Mexico

N=68

Yang P

et al

(2006)

China

N=104

Norrsell

&

Sjödel

(2008)

Sweden

N=54

Tugal-Tutkun

et al

(2009)

Turkey

N=172

Bouchenaki

&

Herbort

(2009)

Switzerland

N=105

Al-Mansour

et al

(2010)

S.Arabia

N=166

Tandon

et al

(2012)

India

N=183

Vitreous cells

Condensation 47%

74%

93%

7%

72%

50%

97%

15%

NA

50%

61.1%

45.5%

Chorioretinal

scars 1% 0% 11% 8% 6% 4% 2%

Fluorescein

angiography

Yang P et al

(2006) China

N=25

Tugal-Tutkun

et al

(2009) Turkey

N=24

Bouchenaki &

Herbort

(2010) Switzerland

N=44

Tandon et al

(2012) India

N=49

Optic disc staining

Peripheral leakage

CME

68%

60%

0%

22%

0%

0%

98%

14%

9%(post-surgery)

77.5%

18.3%

2% (post surgery)

absence of angiographic macular edema confirms Fuchs

Differential diagnosis

Intermediate uveitis

Viral anterior uveitis

Ocular toxoplasmosis

Sarcoid uveitis

MS-associated uveitis

Primary vitreoretinal lymphoma

Other causes of iris depigmentation

VKH

MS

MS

Toxo

PVRL

HSV

Favorable visual prognosis in Fuchs uveitis

Initial visual acuity Number of eyes (%)

0.6 – 1.0 118 (65.2)

0.1 – 0.5 51 (28.2)

< 0.1 12 (6.6)

The rate of decreased visual acuity by 2 lines or more was 0.06/eye-year.

Tugal-Tutkun I, et al. Am J Ophthalmol 2009;148:510-5.

Quentin & Reiber Am J Ophthalmol 2004;138:46-54

Intraocular synthesis of rubella antibodies in

100% of 52 patients with Fuchs uveitis,

73% of 15 patients with MS-associated uveitis, none of the patients with ocular toxoplasmosis, HSV or

VZV iritis, or acute anterior uveitis

Rubella genome in 18% of patients with Fuchs uveitis

A sharp decline in the prevalence of Fuchs uveitis with

the introduction of population-wide rubella virus

vaccination programs

Brinbaum AD, et al. Am J Ophthalmol 2007;144:424-8.

Intraocular synthesis of rubella antibodies in

100% of 63 patients with Fuchs uveitis,

none of the controls with HSV or VZV uveitis,

HLA-B27-uveitis or Possner-Schlossman syndrome.

Rubella genome in 2/20 (10%) of patients with Fuchs uveitis

Additional antibodies (HSV, VZV, CMV) in 11 patients (17%)

Ruokonen PC, et al. Graefes Arch Clin Exp Ophthalmol 2010;248:565-71

Comparison of Rubella Virus- and Herpes Virus-Associated Anterior Uveitis

Clinical Manifestations and Visual Prognosis

Wensing B, et al. Ophthalmology 2011

Characteristics Rubella virus (N=57) HSV (N=39) VZV (N=10)

Mean age (years) 35 43 53

Unilateral 86% 97% 80%

Acute course 37% 61% 60%

Corneal edema 1.8% 54% 30%

Previous keratitis 3.6% 33% 2.5%

KPs present 84% 76% 70%

Cells ≥2+ 14% 54% 20%

Heterochromia 23% 0% 0%

Focal iris atrophy 5.5% 48.6% 10%

Vitreous cells 88% 43% 83%

Cataract 47% 15% 30%

IOP > 30mmHg 25% 46% 50%

Focal chorioretinal scars 22% 0% 11%

CMV-positive patients with Fuchs features are more

likely to be male, older at diagnosis, and have nodular

endothelial lesions accompanied by pigmentation

Chee SP, Jap A. Am J Ophthalmol 2008;146:883-9

62 year-old woman

Hx of unilateral AU with secondary glaucoma

Relapses despite oral valacyclovir

3+ cells, flare 16ph/ms,

Diffuse iris atrophy like Fuchs uveitis

No vitreous cells

PCR+ for CMV

Responded to Rx with valganciclovir

Fellow eye

37 year-old woman

Hx of unilateral AU with IOP rise at relapses

1+ cells, flare 5.6 ph/ms, IOP 48mmHg

Diffuse iris atrophy with transillumination defects

No vitreous cells

5 relapses in 1 year despite oral acyclovir

PCR+ for CMV

Responded to Rx with valganciclovir

25 year-old man

Hx of unilateral AU with IOP rise at relapses

0.5+ cells, flare 19.8 ph/ms, IOP 30mmHg

Subtle loss of iris details, anisocoria

No vitreous cells

Unresponsive to oral acyclovir

RT PCR+ for CMV

Responded to Rx with oral valganciclovir

Conclusions

RV and CMV are not the only infectious triggers

Toxoplasma, Toxocara, HSV, ophthalmomyiasis,

chikungunya, ..as well as noninfectious triggers

such as trauma and hereditary retinopathies

The role of genetic susceptibility?

Recently reported gene polymorphisms (ICAM-1,

IL23R, CTLA-4)

Fuchs uveitis is still a clinical diagnosis

Misdiagnosis and potentially harmful treatment can be avoided by prompt recognition of confirmatory signs

Iris stromal atrophy - Absence of posterior synechiae

Vitreous infiltration - Absence of macular edema

The risk of glaucoma is low in patients who are not exposed to the side-effects of corticosteroids

Patients with OHT and features resembling Fuchs uveitis except for vitreous infiltration should be checked for CMV infection

Conclusions