Approach to a case of uveitis, work-up and management

2. FLOW OF SEMINAR
1. WORKUP & NAME UVEITIS
2. TARGETED APPROACH FOR OCULAR AND SYSTEMIC INVESTIGATIONS
3. TREATMENT OF UVEITIS

3. INTRODUCTION
uva = grapes
Uvea comprises of iris, ciliary body and choroid
Inflammation of uveal tract is called uveitis.
Uveitis, the fifth commonest cause of visual loss in the developed world.
In the US, the disease accounts for 10% of the blindness.
Am J Opthalmol. 2008;146:890-96.

4. WORKUP AND NAME
UVEITIS

5. HISTORY TAKING IN UVEITIS

6. SUN CLASSIFICATION : DESCRIPTORS OF
UVEITIS
Category Descriptors Description
Onset Sudden Acute onset
Insidious Slow onset
Duration Limited <3 months duration
Persistent >3 months duration
Course Acute Episode characterized by sudden
onset and limited duration
Recurrent Repeated episodes separated by
periods of inactivity without
treatment <3 months in duration
Chronic Persistent uveitis with relapse in
<3 months after discontinuing
treatment
Am J Opthalmol. 2005;140(3):509-16..

7. SUN CLASSIFICATION
Type Primary site of inflammation Includes
Anterior uveitis Anterior chamber Iritis
Iridocyclitis
Anterior cyclitis
Intermediate uveitis Vitreous Pars planitis
Posterior planitis
Hyalitis
Posterior uveitis Retina/Choroid Choroiditis
Retinochoroiditis
Retinitis
Neuroretinitis
Panuveitis Anterior chamber, vitreous and
Retina or Choroid
Am J Opthalmol. 2005;140(3):509-16..
Classify patient on the basis of anatomy and pathology of uveitis

8. CLINOPATHOLOGICAL / WOOD’S
CLASSIFICATION
GRANULOMATOUS UVETIS NON-GRANULOMATOUS UVETIS
Insidious onset and chronic course Sudden onset and acute course
Absent or mild congestion Severe episcleral congestion
Iris nodules (Koeppe’s and Bussaca’s) common Iris nodules uncommon
Medium to large keratic precipitates (Muttonfat
KP’s)
Small fine keratic precipitates
Posterior segment involvement common Posterior segment involvement uncommon

9. Detailed Slitlamp
examination
And dilated fundus
examination (+90D
and+20D)
Sarcoid granuloma

12. NAMING & MESHING : TARGET
APPROACH : GOALS OF TESTING
Will the results of the test provide a definitive etiology ?
Will the results of the test confirm or reject a possible diagnosis ?
Will the results of the test identify any underlying systemic disease process or association ?
Will the results of the test help in the management of the patient ?
Will the results of the test study a possible iatrogenic complication ?
Will the results of the test help to study the sequlae of the disease
Will the results of the test play Prognostic indicator ?
Am J Ophthalmol. 2013;156:228–36.

13. PRINCIPLES OF DIAGNOSTIC TESTING
Bayes’ theorem :
Post test probability of a disease = pretest probablity x sensitivity____________________
pretest probablity x sensitivity + (1-pretest probability)(1-specificty)
Arch Ophthalmol 1990; 108: 1291–1293
In India for a case of uveitis pretest probability is high for TB and sarcoidosis

14. GENERAL IVESTIGATIONS IN INDIAN
SCENARIO
CBC
ESR
CXR
Mantoux
VDRL / TPHA
Due to high incidence of TB & Sarcoidosis in India and syphilis being great mimicker
J Pathol. 2006 Jan;208(2):224-32

17. 20 year old male with D/V and lower back pain, stiffness; cells ++, flare, hypopyon,
small sized KPs
Name the uveitis : Acute anterior nongranulomatous uveitis
ESR, Mx, CXR, VDRL, and
Xray sacroiliac joint
Investigations

18. HLA B-27

21. 18 year-old-girl with RE normal VA 6/6 OD
OS VA 6/9
AS cells +
Vitritis +++
Dilated fundus exam shows peripheral vasculitis
H/o fever+ numbness in hands for 2 weeks
INVESTIGATION
ESR
CXR
VDRL Normal
Mx

22. MRI Brain

24. South India , J Clin Ophthalmol Res 2017;5:73-6

25. 10-year-old-female
Decreased vision left eye for 2 – 3 days.
VA 20/200, A/S cells +2, Vitritis +3
ESR
VDRL
CXR
Mx 5X7mm
TORCH IgG
– Toxoplasma IgG 2.49 Positive
IgM 2.06 Positive
– Rubella IgG 2.82 +
– CMV IgG 2.04 +
– CMV IgM 0.7 _
– HSV-2 IgG 0.20 _
– HSV-2 IgM 0.95 Equivocal
– HIV Serology Negative
Tt
Intravitreal Inj. CLINDAMYCIN (1 mg) and
dexamethasone (0.4 mg)

26. VA 20/200
VA 20/120

27. 34-year-old healthy male sudden painful decrease in vision OS x7 days
associated with watering, redness
OD OS
VA 20/20 CFCF
AC cells - +3
AC flare - +3
Lens clear Pigment on ant surface
Vitreous - Cells++

28. Retrospective history : History of fever 9 days before presentation when
the patient was given i.v dextrose (and antipyretics?) by a local
practitioner
Direct KOH mount +
1 week post PPV with i/ntravitreal
Amphotericin B (5mcg/.1ml) +
dexamethasone 360 µg/0.1ml
Final Diagnosis:
Metastatic
Endophthalmitis
after single iv infusion
VA 20/20

29. Panuveitis causes

30. South India , J Clin Ophthalmol Res 2017;5:73-6

31. 35 year male with D/V RE
Granulomatous uveitis, granuloma
Cells+++ flare+++
Mx test: necrotic

33. A 48 year male with the chief complaint of decrease in vision and floaters OS of 8
months duration. On examination periphlebitis and neovascularisation elsewhere OD
and a granulomatous mass lesion on the optic nerve head with surrounding serous
detachment OS.

34. 40 year male
Granulomatous uveitis with BSK
Mx test –ve,
CXR s/o B/L Hilar lymphadenopathy

35. Careful examination reveals skin lesions

36. Careful examination of axillae and lower back
Audiometry
CSF pleocytosis

37. hypopyon uveitis with occlusive vasculitis

38. Major criteria :
•Oral ulceration(recurrent-97%)
•Genital ulceration(83%)
•Cutaneous lesion(75%)
•Ocular lesions(48%)
•Posterior segment more often and more severe
Minor criteria
•Arthritis
•Epididymitis
•Gastrointestinal lesions
•CNS involvement
Investigations :
•Pathergy test
•HLA B51 typing

40. The general goals of medical management are:
Relief of pain and photophobia
Elimination of inflammation
Prevention of structural complications such as synechiae, secondary cataract
and glaucoma
Preservation or restoration of good visual function.
Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 11–19

41. •Anti inflammatory
•Mydriatics/cycloplegics
•Non steroidal anti-inflammatory drugs
•Immunosuppressants (steroid sparing)
•Corticosteroids (first line)
1.Topical
2.Periocular
3.Systemic
Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 11–19
• Corticosteroids
• T cell inhibitors
• Anti- metabolites
• Alkylating agents
• Anti TNF
• Other biologic agents
• Atropine, 1%, 2%
• Homatropine, 2%,
• Cyclopentolate, 0.5%, 1%, 2%.
• Phenylephrine, 2.5%

42. MYDRIATICS/CYCLOPLEGICS :
 To relieve pain by immobilizing the iris
 To prevent adhesion of the iris to the anterior lens capsule (posterior
synechia), which can lead to iris bombe and elevated IOP
 To stabilize the blood-aqueous barrier and help prevent further protein
leakage (flare).
Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 11–19

43. TOPICAL CORTICOSTEROIDS
Medication Concentration (%) Formulation
Dexamethasone sodium
phosphate
0.1 Solution
Dexamethasone alcohol 0.1 Suspension
Fluorometholone acetate 0.1 Suspension
Fluorometholone alcohol 0.1-0.125 Suspension
Loteprednol 0.2-0.5 Suspension
Betamethasone 0.1-0.5 Solution
Prednisolone acetate (LS) 0.12-0.125 Suspension
Prednisolone acetate 1 Suspension
Difluprednate 0.05 Emulsion
Rimexolone 1 Suspension

44. The choice of topical steroid should be based on the severity of
uveitis :
 severe Anterior uveitis : topical steroid with strong potency
(prednisolone acetate)
 mild anterior uveitis : weak topical steroid (betamethasone or
dexamethasone)
 In steroid responders, avoid steroid as far as possible and use
topical non-steroidal anti-inflammatory drugs (NSAIDs) like
flubriprofen or weak steroids or steroids with least propensity
to raise IOP such as rimexolone 1%.
Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 11–19

45. Side effects of Topical Steroids
Side effects of topical administration of steroids
Elevation of IOP
Susceptibilty to infections
CSCR
Eyelid edema
Impaired corneal or scleral wound healing
Subconj h’age
Corneal epithelial toxicity
Crystalline keratopathy

46. SYSTEMIC STEROIDS :
 when the anterior uveitis is not responding to topical drugs
alone
 disease is recurrent and bilateral
 In posterior uveitis
The guidelines for oral corticosteroids therapy are:
 Start with high dose and then taper according to response of
disease
Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 11–19

47. Side effects of Systemic Steroids
Common Intravenous
Cushingoid changes :
Moon facies, buffalo hump, weight gain, increased
acne
Rapid administration :
Cardiac arrthymias, cardiovascular changes, MI
Infections
Hypertension
DM
Fluid retention
Hyperlipidemia
Atherosclerosis
Osteoporosis
Anxiety, mood changes

48. PERIOCULAR STEROIDS
Indications Advantages
Moderate to severe or recurrent uveitits Higher local and
sustained drug delivery
to the eye with greater
posterior segment
penetration
Cystoid macular oedema
Anterior chamber inflammation not adequately
responding to topical corticosteroids
Nussenblatt RB, Whitcupp SM. Fundamentals and Clinical Practice. 4th ed. Uveitis; pp. 76–113.

49. PERIOCULAR STEROIDS
Medication Concentration Approximate duration of action
Dexamethasone sodium
phosphate
4, 10 and 24 mg/ml solution 1-2 days
Triamcinolone acetonide 40 mg/ml suspension 2-4 months intraocular,
<3 months periocular
Betamethasone phosphate 3 mg/ml solution 1-2 days
Betamethasone acetate/
phosphate
3.6 mg/ml suspension 7-10 days
Side effects
Increased IOP and glaucoma, ptosis, cataract, and inadvertant globe perfortion
Can J Ophthalmol. 2010 Aug; 45(4):352-8.

50. INTRAVITREAL STEROIDS
Indications
Non infectious intermediate and posterior uveitis
Cystoid macular edema
Triamcinolone acetonide : 4mg in 0.1 ml
Duration of action : 6-8 weeks
Side effects
Cataract, increased IOP, glaucoma, retinal detachment, vitreous hemorrhage, and endophthalmitis.
Surv Ophthalmol. 2008 Mar-Apr; 53(2):139-49.

51. INTRAVITREAL STEROIDS
Ophthalmology. 2010 Jun; 117(6):1134-1146.e3.
OZURDEX
, Allergan, Inc., Irvine, CA : 0.7 MG DEXAMETHASONE intravitreal implant
biodegradable implant
sustained release of approximately 3 m
delivers a sustained release of dexamethasone over 3–6 months through the Novadur solid polymer
delivery system, which is given intravitreally via an injector.

52. INTRAVITREAL STEROIDS
Ophthalmology. 2000 Nov; 107(11):2024-33.
RETISERT
(Bausch and Lomb, Rochester, NY) : FLUOCINOLONE ACETONIDE 0.59 MG
requires a surgical procedure to suture the implant to the scleral wall
sustained release of approximately 2.5 years

53. IMMUNOSUPPRESSANTS :
• Used mainly in corticosteroid-resistant cases or as steroid-sparing agents
• Classification :
T cell inhibitors (CYCLOSOPORINE, TACROLIMUS)
Anti-metabolites (METHOTREXATE, AZATHIOPRINE, MYCOPHENOLATE
MOFETIL)
Alkylating agents (CYCLOPHOSPHAMIDE, CHLORAMBUCIL)
Biologic agents (ADALIMUMAB, CERTOLIZUMAB, RITUXIMAB)
Clin Ophthalmol. 2014; 8: 1891–1911

54. Commonly used immunosuppressants :
CYCLOSPORINE : T cell inhibitor
 Dose : 2.5-5 mg/kg/day BD
 PeakEfficacy : within 7-15 days
 Side effects : Hypertension,
nephrotoxicity, gingivitis, hirsutism
AZATHIOPRINE
Dose : 1 mg/kg/day
Peak Efficacy : 4-12 days
Side effects :, myelosuppression
Clin Ophthalmol. 2014; 8: 1891–1911
METHOTREXATE : antimetabolite
 Dose : 2.5 – 10 mg/ week with max dose
of 50 mg/week
 Peak Efficacy : 3 to 6 weeks
 Side effects : Hepatotoxicity,
myelosuppression

55. •Cyclophosphamide :
 Dose : i/v infusion at an initial dose of 15 mg/kg at 2, 4, 7, 10, and 13
weeks (2 weekly), with monthly infusions thereafter to a maximum
of nine pulses
 Peak efficacy : 2-8 weeks
 Side effects : leucopenia, hemorrhagic cystitis, secondary
malignancy, sterility
Clin Ophthalmol. 2014; 8: 1891–1911

56. TUBERCULOSIS
ATT : HRZE for a minimum of 2 months (up to 3–4 months), with
subsequent administration of HR for a minimum of 4 months (up
to 15 months)
 H : Isoniazid (5mg/kg/day -300mg)
 R : Rifampicin (450 mg/day if BW </= 50 kg, or 600 mg/day if
BW > 50 kg)
 Z : Pyrazinamide (25-30 mg/kg/day – 1500 mg/day)
 E : Ethambutol (15 mg/kg/day – 800 mg)
Surv Ophthalmol. Author manuscript; available in PMC 2017 Sep 1

57. VA 20/100, A/S cells+ Koeppe’s nodule,
vitreous cells +
45-year-old-male presents with decreased vision LE since 1 week
and gives history of contact with TB patient
Investigations- Mantoux – 14x18mm, X-ray chest- wnl, PCR for TB negative
QuantiFERON – TBGOLD positive

58. Initial presentation
3wks after oral steroids+ATTVA 20/120
VA 20/200

59. SYPHILIS
High-dose i/v penicillin G -12 to 24 million units/day for 10 to 14 days
 HIV-positive : full 14 days of high-dose i/v penicillin G + i/m benzathine
penicillin 2.4 million units weekly for three weeks
Ann Ophthalmol. 1992 Apr;24(4):134-8.

60. 22-year-old-male presenting with decreased vision RE
ESR – 2 mm/hr, Mx – 3 x 3 mm, VDRL- NR, CXR -N
VA CFCF, AC cells +
Vitreous cells +

61. Genital lesion resemble that of healed chancre
Rest of genital lesions were warts for which electrocautery was done
TPHA +ve

62. Tt i/m procaine penicillin 2.4 million units weekly
for 3 weeks

63. TOXOPLASMOSIS :
 Intravitreal clindamycin (1.5 mg) injection and dexamethasone
Trimethoprim/sulfamethoxazole plus oral prednisolone
Korean J Parasitol. 2013 Aug; 51(4): 393–399.

64. IgM toxo titres positive
Tt i/vitreal clindamycin with
dexamethasone
18-year-old-boy
esr unremarkable
mxtest
cxr
vdrl
Worsening at 1 wk
Pan fungal PCR(+ve) and PCR for toxo(-
ve) Courtesy PGIMER
6 days after intravitreal voriconazole and
oral itraconazole

65. OD OS
BCVA 20/100 20/20
PUPILS Normal size, normal reaction Normal size, normal reaction
EOM Full and free Full and free
OCULAR ADNEXA
Eyebrow
Eyelid
eyelashes
Within normal limits
no evidence of any granuloma, patches of depigmentation, scar marks
Intraocular pressure
(GAT, mm of Hg)
14 16
 Circumcorneal
congestion
Fresh KPs
AC cells 2+ (SUN
classification)
Anterior segment
45-year-old-man with sudden onset decrease in RE vision

66. Vitritis haze- 3+(NIH Grading
System)
History of chicken pox
Lab invg unremarkable

67. Acute Retinal necrosis arn
Tt :
Intravenous acyclovir (15 mg/kg body wt. divided 8 hourly) for 14 days
Oral prednisolone 1.5 mg/kg body weight started after 48 hours
Topical- Prednisolone acetate 1% 4/d, G. Atropine 1% 3/d
Intravitreal ganciclovir 2 mg/0.1 ml given biweekly for 2 weeks from 2nd week
onwards
8 weeks follow up
after PPV and SB
2 wks fu
VA 20/60

68. Am J Ophthalmol. 2011 Nov; 152(5):857-63.e2
In tropical countries, fungal infection is commonly seen.
Voriconazole (oral dose 200 mg twice a day)
Intravitreal voriconazole (50–100 ug in 0.1 ml)
In ocular tuberculosis, there may be paradoxical worsening of inflammation following
antitubercular therapy and systemic steroids.
If the inflammation is progressing inspite of addition of oral steroids, immunosuppressives may
be added with close monitoring of liver function.
In viral uveitis, ganciclovir gel (0.15%) is used topically to control the cytomegalovirus anterior
uveitis and intravitreal ganciclovir implants can be used to treat cytomegalovirus retinitis.

69. BIOLOGICS
Indian J Ophthalmol.2013 Jun; 61(6): 277–283.

70. (ANTI –TNF Αlpha) THERAPY
Indian J Ophthalmol.2013 Jun; 61(6): 277–283.

71. CONCLUSION
EYE IS WINDOW TO SYSTEMIC DISEASES.
DETAILED HISTORY TAKING AND METICULOUS SYSTEMIC AND OCULAR EXAMINATION CLINCHES DIAGNOSIS
Sometimes we cannot 'pin down' the exact diagnosis
The aim then is to IDENTIFY AND TREAT SIGHT THREATENING INFLAMMATION IN UVEITIS :
◦ Macular oedema
◦ Vasculitis
◦ Vitritis
◦ Sub-retinal neovascularisation
It is must to RULE OUT INFECTIVE UVEITIS