1. Uveitis classification, diagnosis,Management (Out lines)
April 2010
Uveitis classification, diagnosis,Management (Out lines)

2. Standardization of Uveitis Nomenclature (SUN)
Classification
Standardization of Uveitis Nomenclature (SUN)
International workshop was held NOV,2004 in Baltimore,Maryland,USA.
Participants: 50 individuals,35 center ,13 countries
American Uveitis Society (AUS) & International Uveitis Study Group(IUSG) endorsed the workshop

3. Sun 3 things were addressed Terminology
Grading inflammation & document complications
Outcome & results reporting

4. SUN: Consensus reached 1)Grading A/C cells A/C flare Retinal Haze
Acute, Chronic, Recurrent
Anterior/intermediate,
Posterior, panuveitis
6)Grading disease activity
7) How to record complications

5. sun Iritis Iridocyclitis Anterior Cyclitis Anterior Uveitis
Anterior Chamber
Intermediate
Pars planitis
Posterior Cyclitis
Vitreouus
Focal,Multifocal,diffuse,
Chorioretinitis,Retinochoroiditis
Retinitis,Neuroretinitis
Posterior
RETINA/CHORIOD

6. Anterior Chamber+Vitreous+
Terminology
Primary site of inflammationm inflammation
(No predominant)
Panuveitis
Anterior Chamber+Vitreous+
Retina/choriod

7. SUN:GRADING INFLAMMATION
Grade A/C
Cells in Field
< 1
0.5+(trace)
1---5 1+
6---15 2+
16--25 3+
26--50
4+ (plastic aqeous)
>50
N.B. hypopyon recorded separately
SUN:GRADING INFLAMMATION
1*1mm
Neutrophils& lymphocytes
Flare Grading
Non 1+
Faint 2+
Moderate (iris&lens details clear) 3+
Marked(Iris & lens details hazy) 4+
Intense(fibrin or plastic aqueous)

8. SUN: Grading
No consensus reached on standard grading system for vitreous cells.
National Eye Institute System for the grading vitreous haze was adopted both for the severity & evaluating the uveitis.
Haze is better indicator of active inflammation( cells+protein leak).
Grading haze: +20D, optic disc,posterior pole, correct for the lens opacities,A/S inflammation, corneal disease.
Best to use photos to compare then subjective by 20D
Grade: 0,TR,+1,+2,+3,+4

9. sun Grading of Vitreous cells by use Hruby Lens
Not agreed as a classification by SUN
Vitreous Cells:( 0, TR,+1, +2, +3, +4)
, 20, 50,100,250,251
Presence of vascular sheathing & macular edema should NOT change the classification, but to be recorded separately.

10. SUN: retinal Vasculitis
The retinal vasculitis was addressed:
No consensus was reached on retinal vascular changes leading to the Dx of vasculitis.
Though the group agreed to consider 3 things as a evidence of retinal vascular disease.

11. retinal Vasculitis: It was agreed to consider: Pervascular sheathing
Vascular leaks
Vascular occlusion Vasculitis
(active?)

12. Retinal vasculitis
It was agreed that vasculitis classification needs more workup.
Unresolved issue in vasculitis:
e.g. Vascular sheathing, Leaks ,Oclusion
Needs further workup to reach an agreement

13. Acute vs chronic Onset sudden or insidious Duration:
Acute----Limited(<3/12)
Chronic—Persistant (>3/12)
Recurrent: repeated episodes separated by period(3/12) of inactivity without treatment.
Chronic: Relapse in < 3/12 after D/C RX
Chronic: Reactivation( on maintance RX)

14. SUN & KP’s
No consenus could be reached either on how to describe keratic precipitates or on the use of the term “granulomatous” vs Non
But terms reached to describe KP’s (small,medium,Large,Stellate )
KP’s 3 dimentional structures helping in Dx of Uveitis?? Coming up soon!
Grade
Cells in field
<1
TR(0.5+(
1---5

15. KP’s

16. Role of KP’s in DX coming up soon
James Rosenbaum M.D.
Yale University, 1975
Professor, Medicine and Ophthalmology
Why a Rheumatologist needs to Understand Uveitis.
Johns Hopkins Arthritis center.
Neutrophils: inflammatory response is photographed, there are lots of white cells that line up along these vessels uvea
KP’s 3 dimensional structure to Dx Uveitis

17. Role:Neutrophils & KP’s in uveitis

18. Record complication ( SUN)
Macular edema reported as present or absent clinically & confirmed by FFA/OCT
Epiretinal membrane +/- , confirmed by OCT/photo
Neovascularization: +/- confirmed by FFA

19. Record complication
Raised IOP due corticosteroid use should be >10mm Hg(base line)
No consensus reached for raised IOP,but the choices were narrowed to 3 options
1)IOP >21mmHg(traditional upper limit normal)
2) >30mm Hg (levels most Ophthalmologist Rx.)
2)IOP > 24mm Hg
There was consensus—term glaucoma should not be considered based on elevated IOP only in uveitis, but reserved only if accompanied by disc damage or VF defect

20. Sun: grading the disease acitivity
Inactive
Grade 0 cells
Worsening activity
2 step increase in level inflammation(A/C cells,Vitreous haze only) from +3 to +4
Improved activity
2 step decrease inflammation or to grade 0
Remission
Inactive disease >3months after D/C RX
0 cells or trace (1 cell per HPF) 0.5+(TR)

21. Formulating DX
Anterior Uveitis mild first episode most agreed no workup.
Our aim is to first rule out infections Why???
1)infection can be treatable
2)If you are thinking of starting steroids oral/Injection.
3)Some infection if missed early, can lead loss of the eye (ARN)
4)Some infection if left untreated probably better then to start on steroids alone and loss the eye (Toxo)

22. Systemic disease
Systemic diseases most commonly associated with retinal vasculitis
Sarcoidosis
Behçet’s disease
Multiple sclerosis
Vogt-Koyanagi-Harada syndrome

23. Anterior Uveitis
Idiopathic (37.8%);
HLA-B27-associated arthropathies (21.6%),(AS,Reiter’s.IBD,Psoriatic)
Behect
Juvenile Rheumatoid Arthritis (10.8%)(ANA+ve +/-B27+ve)
Herpetic uveitis (9.7%) (Clincial)( iris atrphy sectorial,loss corneal sensation)
Sarcoidosis (5.85%) (ACE,serum Ca,CXR) H/o difficulty breathing
Fuchs' heterochromic iridocyclitis (no redness, diffuse Kp’s,stelate,loss iris archetec, heterochromia not common in brown eyes, light color iris need time to observe.
Syphilis
Intraocular lens-induced persistent uvietis (1.2%)
Posner-Schlossman syndrome (0.9%),
TINU (B/L Ant Uveitis) Urine analysis----Renal Biopsy before cortisone Rx
Tuberculosis ?? (PPD,CXR, Goldman Quatefron)

24. Intermediate Uveitis
The most common causes of intermediate uveitis are
idiopathic (69.1%)
sarcoidosis (22.2%)
IBD
Multiple sclerosis (8.0%)
Syphilis
Lyme disease
PIOL

25. Hypopyon?? Acute Hypertensive Uveitis: 1)HSV 2)Sarciodsis
Anterior Uveitis: With hypopyon
Behect,HLA-B27(AS,Rieters) must R/O Pseudohypopyon(S/P IV Kenalog,Phacolytic glaucoma)
Endophthalmitis
Acute Hypertensive Uveitis:
1)HSV
2)Sarciodsis
,3)Toxopalsmosis
,4)Fuch’s iridocyclitis,
5)Posner-Schlossman Syndrome)

26. Hypopyon vs pesudohypopyon

27. Posterior uveitis The most common causes of posterior uveitis are :
Toxoplasmosis
SYPHILIS
SARCOIDOSIS
T.B
Behect
ARN
CMV
Candida
Birdshot retinochoroidopathy (7.9%) West
Serpiginous choroidopathy (1.65%).
Other causes of posterior uveitis include
White dot syndromes
presumed ocular histoplasmosis (POHS)
Primary Intra ocular Lymphoma PIOL or (PCNSL) , leukemia.(Masquarde)
Ideopathic

28. Panuvitis
Syphilis
Sarciodosis
VKH
Endophthalmitis
Behect
Ideopathic

29. Masquerade syndrom
Group of disorders –intraocular inflammation & misdiagnosed as chronic idiopathic uveitis.
Malignant disorders:
PIOL or PCNCL (Non-Hodgkin’s)
Leukemia
Ca: metasrasis to eye (Lung,Renal,Breast etc)
Uveal melanoma

30. Masquerade Syndromes Childhood malinancies: Retinoblastoma
Medulloepithelioma
JXG
Paraneoplastic Syndromes etc

31. Masquerade Nonmalignant disorsers: Intraocular foreign body
Retinal detachment (Swartz Syndrome)
Myopic degenration
Pigment dispersion syndrome
Postoperative infections:Fungal, P. acnes
Postvaccination & drug reaction: Rifabutin etc

32. DDx (Summary) Always think of 2 S(Syphilis,Sarciodosis)
2T’s (Toxoplasmosis,T.B.)
2H’s (HSV,HIV)
1 B (Behect)
1F (Fungal)

33. Investigations:

34. Investigations CBC,ESR,CRP LFT,RFT, Serum ACE,Lysosyme,Ca, PPD
CXR (Sarciodosis,TB)
Syphilis(VDRL,ELISA)
Xray (Sacroilac joint, if back pain +)
CT scan chest if CXR ?

35. investigations UA,(proteins, R/O TINU) ANA,RA HIV Others ?????
Serology (HSV1,2, CMV) ????in healthy person not in HIV.
There is many other valuble test better to leave it for the uveitis team.

36. Role of Hla typing
Only 2 types of HLA typing are very useful in formulating the DX and planning management
1)HLA B27 ( To plan RX)
2)HLA A % ( help’s confrim DX ) (BSCR)
Others
HLA B 5, B51, DR ??????????????????????? Not used much for DX.
Because not so specific nor sensitive

37. Goal rx
To limit the tissue damage and to restore vision quickly by starting Rx early and effective manner.
In case chronic uveitis on immunosuppressive drugs therapy, our goal is to limit prednisone use to 10mg per day or less in (successful corticosteroid sparing)

38. Managment Medical: Steriods Topical: Perdnisolone,Dexam-,Fluoro
Periocular: Triam,betameta
Systemic: Prednisone
“Use enough soon enough”
Start higher dose taper before stopping
Investigate before start systemic Rx.
Cycloplegic: cyclogel ??.Trop,HA,AT
Immunosuppressive: Steroid sparing agent

39. RX:

40. RX;Uveitis vs oculopasty/derma

41. Thanks

44. Panuveitis The most common causes of panuveitis : Idiopathic (22.2%),
Sarcoidosis (14.1%),
Multifocal choroiditis and panuveitis (12.1%), (MFCPU)
BEHECT (11.6%),
Systemic lupus erythematosus (9.1%),
Syphilis (5.5%)??
Vogt-Koyanagi-Harada syndrome (5.5%),
HLA-B72 associated (4.5%),
Sympathetic ophthalmia (4.0%),
Tuberculosis (2.0%),
Fungal retinitis (2.0%).

45. Figures???
The above-mentioned percentages and figures were obtained from a study of 1237 uveitis patients referred to the Uveitis and Immunology Service of the MEEI, Harvard Medical School, from 1982 to These figures were found to be similar to the results of other studies of tertiary referral centers from different parts of the world., especially those of developed countries.

46. PEDIATRIC UVEITIS
Uveitis starting before the age of 16 years represent 5% to 10% of the total uveitis population.
In children is associated with unique problems.
The manner of initial presentation and treatment options differ significantly from those of adults.
Children with uveitis may be asymptomatic due to the preverbal age of the child, or they may actually be asymptomatic because of the insidious nature of the disease.
Consequently, the child may already have serious complications of chronic uveitis at initial presentation to the ophthalmologist.
Furthermore, the adverse effects of prolonged topical steroid use and the risks of systemic treatment must be considered carefully in young patients who have developing skeletal and reproductive systems.
The causes of uveitis is as follows:
Juvenile rheumatoid arthritis-associated uveitis (41.5%),
Idiopathic uveitis (21.5%)
Pars planitis (15.3%).
Toxoplasmosis 7.7%;
Toxocariasis (3.1%),
Sarcoidosis (2.3%),
Vogt-Koyanagi-Harada syndrome (2.0%),
Acute retinal necrosis syndrome (2.0%),
HLA-B27+ associated uveitis (1.0%),
Reiter's syndrome (2.0%),
Systemic lupus erythematosus, 1.0%
Others
Adamantiades-Bechet's disease, Fuchs' heterochromic iridocyclitis, tubulointerstitial nephritis and uveitis syndrome (TINU), and chickenpox).

47. JRA only a minority(13 to 34%) develop uveitis ( Iridocyclitis).
Risk Factors:
ANA(+), female and young age at onset,family history of psoriasis
. The peak age of onset of arthritis in this group is age 2 to 5 years,
subsequent development of uveitis within the next 5 to 7 years.
The incidence is highest among those with pauciarticular(</=4) forms of the illness (fewer than 5 joints affected)
.Children with JRA should be screened routinely for eye involvement, starting immediately upon diagnosis of JRA because JRA children who go on to develop uveitis most commonly do not report symptoms (screening guidelines).
The majority of children have a relatively good visual prognosis if the uveitis is detected and treated early, and if inflammation (even so-called "low grade" inflammation)

48. Managment Medical: Steriods Topical: Perdnisolone,Dexam-,Fluoro
Periocular: Triam,betameta
Systemic: Prednisone
“Use enough soon enough”
Start higher dose taper before stopping
Investigate before start systemic Rx.
Cycloplegic: cyclogel ??.Trop,HA,AT
Immunsuppressive: Steriod sparing agent

49. Labs:

50. Labs in ocular sarciodosis
(1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive tuberculin skin test previously.
(2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme,
(3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL)
(4) abnormal liver enzyme tests.
(5) chest CT scan in patients with a negative chest x-ray
(6)Bx: biopsy-supported diagnosis (+)

51. DX Oculr sarcoidosis: 4 DX cariteria
(1) Biopsy (BX) : (+ve ) labeled as definite ocular sarcoidosis;
(2) if biopsy was not done but chest x-ray was positive showing BHL associated with a uveitis, the condition was labeled as (presumed ocular sarcoidosis
(3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular sarcoidosis;
(4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2 positive laboratory investigations were present, the condition was labeled as possible ocular sarcoidosis.
CONCLUSION: Various clinical signs, laboratory investigations, and biopsy results provided four diagnostic categories of sarcoid uveitis. The categorization allows prospective multinational clinical trials to be conducted using a standardized nomenclature, which serves as a platform for comparison of visual outcomes with various therapeutic modalities.

52. Ocular Sarcoidosis
Multisystem granulomatous disease ---first described by Jonathan Hutchinson in I
Clinical manifestations -- variable in different ethnic groups.
Organs : lungs, skin and eyes.
The frequency of ocular involvement ranges from 26% to 50%.
May co-exist with asymptomatic systemic disease
can precede systemic involvement by several years. Most patients present between the ages of 20 to 40 years; however, children and the elderly can be affected. Cases of familial sarcoidosis, including monozygotic twins, and husband-wife pairs have also been reported.
Diagnosis relies on demonstration of non caseating granuloma by tissue biopsy. In cases of suspected sarcoidosis where no affected tissue amenable to biopsy is identifiable, supportive evidence of the diagnosis can be obtained through non-invasive investigations including measurement of serum angiotensin converting enzyme (ACE) and lysozyme, chest x-ray, chest computerized tomography (C-T), gallium scintillography, pulmonary function tests, bronchoalveolar lavage, and measurement of serum and urinary calcium.
Ocular manifestations
Anterior segment
Conjunctival involvement has been reported in 6.9%-70% of patients with ocular sarcoidosis (Figure 1). Sarcoidosis granulomas are described as solitary, yellow "millet-seed" nodules. Anterior uveitis occurs in 22%-70% of patients with ocular sarcoidosis, and is usually granulomatous and chronic. Iris nodules have been reported in up to 12.5% of patients with sarcoidosis associated uveitis. Exacerbations of granulomatous uveitis are often associated with an appearance of fresh iris or fundus nodules. Posterior synechiae, cataract and glaucoma are common complications. Corneal band keratopathy develops in a few patients and is usually associated with hypercalcemia.

54. The goal of treatment is to preserve long-term vision
The goal of treatment is to preserve long-term vision. Treatment must be started immediately. Treatment must be directed to preventing structural damage to the eye such as glaucoma, macular edema, cataract and hypotony(CB atrophy/fibrosis).
JRA/JIA-associated uveitis is chronic.

55. 1)Nodule, Conjectiva,Lacrrmal gland ares

56. Posterior uveitis

57. Sarcoidosis in childhood
Early onset or pre-school sarcoidosis seen in children is relatively rare. The classic triad of symptoms consists of skin, eye and joint lesions; pulmonary involvement is rare, at least initially. It can be easily misdiagnosed as juvenile rheumatoid arthritis, as the latter also presents with symptoms from the joints and eyes.

58. Bilateral symmetrical hilar lymphadenopathy and lung infiltration
Bilateral symmetrical hilar lymphadenopathy and lung infiltration. Gallium (67GA) scan

59. Figure 7. Bilateral symmetrical gallium uptake by the lacrimal, parotid, and submandibular glands (Panda sign).

60. Ddx: vkh
• Uveal Effusion Syndrome • Posterior Scleritis • Primary Intraocular Lymphoma • Sarcoidosis • Syphilis • Tuberculosis