1. Sarcoid-Associated Uveitis: Comparison of a Single-Centre Diagnostic System with the International Workshop on Ocular Sarcoidosis (IWOS) Diagnostic Criteria
Ramandeep (Romi) Chhabra, Robyn Troutbeck, Rajitha Ajit, Nicholas Jones
Manchester Royal Eye Hospital, Oxford Road, Manchester, M13 9WL, UK

2. Introduction Sarcoidosis
Multisystem disease with protean manifestations1
Ocular involvement reported in up to 60, usually as the initial manifestation
IWOS: International Workshop on Ocular Sarcoidosis 20062
Aims:
To help clinicians in suspecting sarcoidosis based on clinical signs
To aid diagnosis by establishing relevant investigations
To establish criteria for the diagnosis of ocular sarcoidosis
4 diagnostic categories of sarcoid-associated uveitis proposed
Using 7 ocular clinical signs:
and 5 laboratory investigations:

3. Laboratory Investigations
Clinical Signs
Mutton-fat/granulomatous KPs and/or iris nodules
TM nodules and/or tent-shaped PAS
Snowballs or strings of pearls in vitreous
Multifocal peripheral chorioretinal lesions
(active or atrophic)
Nodular and/or segmental periphlebitis and/or macroaneurysm in an inflamed eye
Optic disc nodule and/or solitary choroidal nodule
Bilateral inflammation
Laboratory Investigations
Negative tuberculin skin test in a BCG- vaccinated patient or in a patient with previously (+)ve tuberculin test
Raised serum ACE or lysozyme
Chest X-ray : Bilateral hilar lymphadenopathy
Abnormal Liver function tests
Chest CT showing changes indicative of sarcoidosis (if CXR normal)

4. Sign 1a: Granulomatous KP

5. Sign 1b: Iris nodules

6. Sign 5a: Segmental periphlebitis

7. Sign 5b: Retinal artery macroaneurysm

8. Sign 6: Optic nerve head granuloma

9. Lab 3: Bilateral hilar lymphadenopathy

10. Lab 5: Peribronchial nodules on CT

11. “Barndoor” sarcoidosis:
multifocal choroiditis, patchy periphlebitis,
vitreous snowballs and papillitis

12. IWOS Sarcoid Classification
Biopsy confirmation with compatible Uveitis
Biopsy not done
Bilateral Hilar lymphadenopathy compatible Uveitis
Presumed Ocular Sarcoidosis
Hilar adenopathy (-)ve or more intraocular signs or more investigational tests
Probable Ocular Sarcoidosis
Biopsy negative
Hilar adenopathy (-)ve or more intraocular signs or more investigational tests
Possible Ocular Sarcoidosis
Definite Ocular Sarcoidosis

13. Purpose
To compare the IWOS diagnostic criteria for sarcoid-associated uveitis with the Manchester Uveitis Clinic (MUC) diagnostic system and to identify discrepancies.

14. Patients and methods
MUC has prospectively entered patients into diagnostic database for 21yrs:
260 patients diagnosed with sarcoid-associated uveitis
MUC Diagnostic Protocol for Ocular Sarcoidosis:
Confirmed: Biopsy (+)ve or Kveim (+)ve with consistent uveitis
Presumed: Raised ACE and/or hilar lymphadenopathy with consistent uveitis
Possible: Uveitis strongly suggestive of sarcoid, with other diagnoses excluded, but ACE and CXR normal
100 randomly-selected MUC patients reviewed

15. Results Comparison of MUC and IWOS diagnostic systems
100 MUC records reviewed:
Male 59:41 female
Age range at presentation (mean 52)
Lab test
MUC
Kawaguchi* (IWOS)
Raised ACE
78%
35%
Abnormal CXR
54%
48%
Clinical sign
MUC
Kawaguchi* (IWOS)
KP (granulomatous)
62% (67%)
52%
Snowballs
72%
69%
C/R lesions
58%
76%
Periphlebitis
39%
45%
ON/single nodule
10% 6%
Bilateral
91%
98%

16. Results Diagnosis MUC IWOS Matches Confirmed(MUC) Definite (IWOS) 2625
Presumed 50 38 34
Possible (MUC)
Probable (IWOS) 24 6 2
Possible (IWOS)
N/A
Unclassifiable 31
(Total)
100 61

17. Comparison of MUC and IWOS systems:
Category: Confirmed/Definite
MUC (Confirmed) 26 vs. IWOS (Definite) 25; Excellent correlation but:
MUC “confirmed” classification permits (old) Kveim Biopsy +ve as a surrogate for tissue biopsy (not considered by IWOS)
Category: Presumed
Presumed: MUC 50 vs. IWOS 38
Of the 12 discordant patients (MUC+ve, IWOS –ve):
All had uveitis compatible with sarcoid
All had ACE levels >55 IU, but normal CXR
Category: Possible/Probable
MUC (Possible) 24 vs IWOS (Probable) 6;
Of the 18 discordant patients (MUC+ve, IWOS –ve) the pattern of uveitis was highly suspicious of sarcoid and with no evidence of other causes
But normal CXR, normal ACE
Poor correlation at this level
Category 4: IWOS possible: MUC no category

18. Results: Summary MUC vs. IWOS systems
There was generally good correlation between the IWOS and MUC systems but:
Using the IWOS system, 31/100 MUC patients were unclassifiable because:
Despite each one exhibiting >2 IWOS eye signs:
only 0 or 1 lab investigations were positive, and biopsies were not performed
Under the MUC system, all 31 patients were classifiable
Kawaguchi3 and colleagues found 81% positivity for TM nodules or Tent-shaped PAS, but these findings (although included by IWOS) do not have widespread support and the evidence base is poor
Abnormal liver enzyme tests have been included as an indicator in the IWOS system, but the evidence base for this is weak
IWOS includes 4 categories, which we feel is unnecessary

19. Conclusions Recommendations to amend the IWOS system:
The MUC diagnostic system is clinically-orientated and simple
The IWOS diagnostic system was designed to standardise nomenclature and to facilitate research, but in our view shows the following faults:
ACE levels do not require quantification, but high levels (>100IU) have very high specificity for sarcoidosis
The evidence base for the following IWOS indicators of sarcoid is inadequate:
Raised liver enzymes
Tent-shaped PAS
Kveim biopsy +ve was not included as a tissue biopsy surrogate
Four IWOS categories of diagnoses are superfluous; 3 should be sufficient
Recommendations to amend the IWOS system:
Permit ACE >100 to carry additional diagnostic weight
Exclude raised liver enzymes and tent-shaped PAS as diagnostic indicators
Include (historical) +ve Kveim biopsy as a surrogate for tissue biopsy
Reduce categories to 3 by merging 3 and 4

20. References
Jones N , Mochizuki M. Sarcoidosis: Epidemiology and clinical features. Ocu Imm & Inflam. 18(2), 72-79, 2010.
Herbort Carl et al. International criteria for the diagnosis of ocular sarcoidosis: Results of the first International Workshop on Ocular Sarcoidosis (IWOS). Ocu Imm & Inflam, 17, , 2009.
Kawaguchi T et al. Evaluation of characteristic ocular signs and systemic investigations in ocular sarcoidosis patients. Jpn J Ophthalmol 2007 Mar-Apr;51(2):121-6.

21. Choroidal Nodule