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INVESTIGATIONS IN
UVEITIS
Dr . Mamata Subhakar . R
Assistant professor ,
Department of Ophthalmology,
ACSMCH
• Competency : 6.4
The learning objectives of
todays class
• REASONS TO INVESTIGATE UVEITIS
• INDICATIONS FOR INVESTIGATIONS
• SELECTION OF INVESTIGATION
• WHAT INVESTIGATIONS
• HEMATOLOGICAL INVESTIGATIONS WHEN?
• IMMUNOLOGICAL INVESTIGATIONS WHEN?
• Some of the important serological
investigations
• Regardless of the choice of laboratory tests,
a thorough history and physical examination
are essential as it may give you a clue to the
underlying disease.
• Many systemic manifestations may either
precede or appear much later that the uveitic
episode.
Investigations can lead you somewhere, anywhere or nowhere
Investigation not indicate •
• A single episode of unilateral mild/moderate
non granulomatous Uveitis
• Typical clinical feature
• A systemic diagnosis compatible with
clinical feature has already been confirmed
Investigation indicate in
• Recurrent Uveitis
• Bilateral uveitis
• Granulomatous sign
• Associated with Intermediate or posterior
uveitis
REASONS TO INVESTIGATE
UVEITIS
• Come to a specific diagnosis.
• Infection
• Auto Immunity
• Allergy
• Systemic Disease Associations.
REASONS TO INVESTIGATE
UVEITIS
• Confirm a clinical diagnosis, so as to institute
appropriate treatment and avoid dangerous
drug side effects.
REASONS TO INVESTIGATE
UVEITIS
• Commence anti-metabolite or
immunosuppressive therapy.
REASONS TO INVESTIGATE
UVEITIS
• Identify complications
REASONS TO INVESTIGATE
UVEITIS
• To explain cause of poor vision.
• Rule out masquerade syndromes/infections.
• For academic and research purposes.
INDICATIONS FOR
INVESTIGATIONS
• To exclude the diagnosis of tumor, infection
and presumed autoimmune disease.
INDICATIONS FOR
INVESTIGATIONS
• To evaluate the capacity of the eye to respond
to therapy;
INDICATIONS FOR
INVESTIGATIONS
• To identify why the vision has not improved,
i.e. non-responders, poor responders and
early recurrences; irreversible changes e.g.
subretinal fibrosis.
INDICATIONS FOR
INVESTIGATIONS
• Atypical presentation.
SELECTION OF
INVESTIGATION
• Following points need to be considered
before ordering the investigations.
• a) Age, sex and ethnic character of the
subject.
• b) Type of uveitis i.e. anterior, posterior, and
intermediate or pan-uveitis.
SELECTION OF
INVESTIGATION
• Specific eye findings like iris nodules, keratic
precipitates, extent of fundus involvement,
evidence of vasculitis and macular
involvement.
SELECTION OF
INVESTIGATION
• Response of eye to treatment i.e. the extent of
visual loss.
SELECTION OF
INVESTIGATION
• Whether the condition is active or healed i.e.
change is reversible or not; typical example is
toxoplasmic scar or inactive toxocara
granuloma.
• Even if the diagnosis is confirmed, it will not
benefit the patient as no treatment can
improve the vision.
CHOOSING THE
INVESTIGATION
This depends on :
• * Age, Sex and ethnicity.
• * Type of uveitis
(anterior/intermediate/posterior)
• * Associated ocular and extraocular
signs/symptoms.
• * Nature of uveitis (acute/chronic;
unilateral/bilateral; active/healed)
WHAT INVESTIGATIONS
• Hematological
• Immunological
• Microbiological
• Cytological
• Histopathological
• Radiological
• HLA typing
• Dermatological (skin tests)
• Ultrasonography
• ICG Angiography
• Systems review
HEMATOLOGICAL INVESTIGATIONS
WHEN?
• Commencing antimetabolite or
Immunosuppressive therapy.
• Suspicion of parasitic infestation
• Suspicion of leukemia
• ACE estimation in Sarcoidosis
• Factor V leiden mutation
• IgE levels
IMMUNOLOGICAL INVESTIGATIONS
WHEN?
• Toxoplasma Retinochoroiditis (Active)
• AIDS
• Other Infectious Diseases CMV, HSV, VZV,
Bartonella, Toxocara etc.
• Collagen Vascular Diseases
• ANA, ANA profile ( Scleritis and secondary
infections)
• ANCA ( Scleritis )
. Serological tests for syphilis
• Rapid plasma regain (RPR) for syphilis
showing clumping of the antigenic particles
(left) after 4 minutes;
• positive fluorescent treponema antibody test
(FTA-ABS) for syphilis
Some of the important
serological investigations
are
Rheumatoid Factor
• It is an antibody against the Fc portion of IgG,
which is itself an antibody. RF and IgG join to
form immune complexes which contribute to the
disease process.
• Has no role in the diagnosis of uveitic
entities.
• However it forms the basis of dividing
arthropathies into seropositive and
seronegative.
Antinuclear Antibodies
• Presence of ANA in the serum shows that
there is possibility of an existing autoimmune
disease and hence further investigations are
warranted to identify the specific type.
Antinuclear Antibodies
• Type of testing alters sensitivity and
specificity of result (i.e. ELISA versus
fluorescent detection on cellular substrates)
• Positive ANA is helpful in evaluating risk for
uveitis in pauciarticular chronic arthritis and
has an almost universal presence in SLE.
ANA alone is not a very good
screening or
diagnostic test
• Deane, Liard, Siegel, Baum: Pediatrics 1995,
95:892-5
• • ANA is positive in 113/500 consecutive children
• seen in clinic
• • 72/113 children have a clear, objective diagnosis
• • 31/113 with +ANA and no diagnosis remain
• without a diagnosis over mean f/u of 37 months
• Low titer ANA has poor positive predictive
power for diagnosis of rheumatic diseases
Anti-DNA Antibodies
• Antibodies against ds-DNA are found in 40-80%
cases of SLE and only rarely in other connective
tissue disorders.
• Hence, it is considered to be relatively specific
for SLE and the American Rheumatoid Arthritis
Association considers it a criterion in the
diagnosis of this disease.
• The normal reference range is 0.00-0.05 IU/ml or
70-200 units.
• They may also be useful in monitoring disease
activity in these patients.
• A combination of positive ANA test, ds-DNA
antibodies and hypocomplementaemia is said to
have a diagnostic specificity of 100% for SLE.
Anti-Neutrophil Cytoplasmic
Antibodies (ANCA)
• ANCA are a group of autoantibodies that
occur in a large majority of patients with
systemic small vessel vasculitis.
• Most common conditions in which they are
positive are Wegener's granulomatosis and
microscopic polyarteritis nodosa.
• c-ANCA has a greater specificity than p-
ANCA.
Anti-Neutrophil Cytoplasmic
Antibodies (ANCA)
• Diseases like PAN ,MPO or Wegener's
Granulomatosis can very rarely cause retinal
vessel inflammation.
• These diseases primarily affect sclera and
adnexa.
• Manifestations are secondary to the
associated renal induced hypertension
(PAN,MPO).
• Direct infiltration of retina and optic nerve in
case of Wegener‘s granulomatosis.
Angiotensin Converting Enzyme
(ACE)
• Serum ACE levels are elevated in 85% of
patients with active pulmonary disease due to
sarcoidosis.
• However, it may also be increased in diabetes
mellitus (24%), leprosy (53%),
hyperthyroidism (81%), chronic renal disease,
cirrhosis, amyloidosis and tuberculosis.
Angiotensin Converting Enzyme
(ACE)
• As it has a false positive rate of 2-4%, it is not
considered a diagnostic test but a useful
parameter to monitor disease activity and
treatment response.
• SACE level is considered to be elevated if the
value is above 35 U/ml in adults and 50U/ml in
those below 19 years. (8 – 52 U/L)
•
Serum Globulin
• 75% of patients with sarcoidosis have elevated
serum globulin levels.
• Due to this serum protein increases and
albumin/globulin ratio decreases.
• Alterations in the serum protein values may act
as the first clue to diagnosis of sarcoidosis in
some patients. Subsequent serum
electrophoresis may also reveal a characteristic
"sarcoid-step" pattern. (Normal total serum
protein = 6-8.6gm/dl; globulins = 2.3-3.5gm/dl).
•
Serum Lyzozyme
• Sarcoidosis, serum lyzozyme is found to be
elevated in 70% cases irrespective of whether
the disease is active or inactive.
• However, increased levels may also be
present in tuberculosis.
Serum C-reactive Protein
(SCRP)
• The values of SCRP generally parallel that of
ESR but the former is not influenced by
anemia.
• It is a non-specific indicator of inflammatory
activity in the body.
• It increases earlier and declines faster than
ESR at the onset and resolution respectively
of inflammation.
• Following steroid suppression in completely
disappears.
MIDDLE
PATH
TOTALLY LAB
DEPENDENT
APPROACH
TOTALLY
EMPIRICAL
APPROACH
2491
Thank You

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40-INVESTIGATIONS-IN-UVEITIS.serology pp t

  • 1. INVESTIGATIONS IN UVEITIS Dr . Mamata Subhakar . R Assistant professor , Department of Ophthalmology, ACSMCH
  • 3. The learning objectives of todays class • REASONS TO INVESTIGATE UVEITIS • INDICATIONS FOR INVESTIGATIONS • SELECTION OF INVESTIGATION • WHAT INVESTIGATIONS • HEMATOLOGICAL INVESTIGATIONS WHEN? • IMMUNOLOGICAL INVESTIGATIONS WHEN? • Some of the important serological investigations
  • 4. • Regardless of the choice of laboratory tests, a thorough history and physical examination are essential as it may give you a clue to the underlying disease. • Many systemic manifestations may either precede or appear much later that the uveitic episode.
  • 5. Investigations can lead you somewhere, anywhere or nowhere
  • 6. Investigation not indicate • • A single episode of unilateral mild/moderate non granulomatous Uveitis • Typical clinical feature • A systemic diagnosis compatible with clinical feature has already been confirmed
  • 7. Investigation indicate in • Recurrent Uveitis • Bilateral uveitis • Granulomatous sign • Associated with Intermediate or posterior uveitis
  • 8. REASONS TO INVESTIGATE UVEITIS • Come to a specific diagnosis. • Infection • Auto Immunity • Allergy • Systemic Disease Associations.
  • 9. REASONS TO INVESTIGATE UVEITIS • Confirm a clinical diagnosis, so as to institute appropriate treatment and avoid dangerous drug side effects.
  • 10. REASONS TO INVESTIGATE UVEITIS • Commence anti-metabolite or immunosuppressive therapy.
  • 11. REASONS TO INVESTIGATE UVEITIS • Identify complications
  • 12. REASONS TO INVESTIGATE UVEITIS • To explain cause of poor vision. • Rule out masquerade syndromes/infections. • For academic and research purposes.
  • 13. INDICATIONS FOR INVESTIGATIONS • To exclude the diagnosis of tumor, infection and presumed autoimmune disease.
  • 14. INDICATIONS FOR INVESTIGATIONS • To evaluate the capacity of the eye to respond to therapy;
  • 15. INDICATIONS FOR INVESTIGATIONS • To identify why the vision has not improved, i.e. non-responders, poor responders and early recurrences; irreversible changes e.g. subretinal fibrosis.
  • 17. SELECTION OF INVESTIGATION • Following points need to be considered before ordering the investigations. • a) Age, sex and ethnic character of the subject. • b) Type of uveitis i.e. anterior, posterior, and intermediate or pan-uveitis.
  • 18. SELECTION OF INVESTIGATION • Specific eye findings like iris nodules, keratic precipitates, extent of fundus involvement, evidence of vasculitis and macular involvement.
  • 19. SELECTION OF INVESTIGATION • Response of eye to treatment i.e. the extent of visual loss.
  • 20. SELECTION OF INVESTIGATION • Whether the condition is active or healed i.e. change is reversible or not; typical example is toxoplasmic scar or inactive toxocara granuloma. • Even if the diagnosis is confirmed, it will not benefit the patient as no treatment can improve the vision.
  • 21. CHOOSING THE INVESTIGATION This depends on : • * Age, Sex and ethnicity. • * Type of uveitis (anterior/intermediate/posterior) • * Associated ocular and extraocular signs/symptoms. • * Nature of uveitis (acute/chronic; unilateral/bilateral; active/healed)
  • 22. WHAT INVESTIGATIONS • Hematological • Immunological • Microbiological • Cytological • Histopathological • Radiological • HLA typing • Dermatological (skin tests) • Ultrasonography • ICG Angiography • Systems review
  • 23. HEMATOLOGICAL INVESTIGATIONS WHEN? • Commencing antimetabolite or Immunosuppressive therapy. • Suspicion of parasitic infestation • Suspicion of leukemia • ACE estimation in Sarcoidosis • Factor V leiden mutation • IgE levels
  • 24. IMMUNOLOGICAL INVESTIGATIONS WHEN? • Toxoplasma Retinochoroiditis (Active) • AIDS • Other Infectious Diseases CMV, HSV, VZV, Bartonella, Toxocara etc. • Collagen Vascular Diseases • ANA, ANA profile ( Scleritis and secondary infections) • ANCA ( Scleritis )
  • 25. . Serological tests for syphilis • Rapid plasma regain (RPR) for syphilis showing clumping of the antigenic particles (left) after 4 minutes; • positive fluorescent treponema antibody test (FTA-ABS) for syphilis
  • 26. Some of the important serological investigations are
  • 27. Rheumatoid Factor • It is an antibody against the Fc portion of IgG, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. • Has no role in the diagnosis of uveitic entities. • However it forms the basis of dividing arthropathies into seropositive and seronegative.
  • 28. Antinuclear Antibodies • Presence of ANA in the serum shows that there is possibility of an existing autoimmune disease and hence further investigations are warranted to identify the specific type.
  • 29. Antinuclear Antibodies • Type of testing alters sensitivity and specificity of result (i.e. ELISA versus fluorescent detection on cellular substrates) • Positive ANA is helpful in evaluating risk for uveitis in pauciarticular chronic arthritis and has an almost universal presence in SLE.
  • 30. ANA alone is not a very good screening or diagnostic test • Deane, Liard, Siegel, Baum: Pediatrics 1995, 95:892-5 • • ANA is positive in 113/500 consecutive children • seen in clinic • • 72/113 children have a clear, objective diagnosis • • 31/113 with +ANA and no diagnosis remain • without a diagnosis over mean f/u of 37 months • Low titer ANA has poor positive predictive power for diagnosis of rheumatic diseases
  • 31. Anti-DNA Antibodies • Antibodies against ds-DNA are found in 40-80% cases of SLE and only rarely in other connective tissue disorders. • Hence, it is considered to be relatively specific for SLE and the American Rheumatoid Arthritis Association considers it a criterion in the diagnosis of this disease. • The normal reference range is 0.00-0.05 IU/ml or 70-200 units. • They may also be useful in monitoring disease activity in these patients. • A combination of positive ANA test, ds-DNA antibodies and hypocomplementaemia is said to have a diagnostic specificity of 100% for SLE.
  • 32. Anti-Neutrophil Cytoplasmic Antibodies (ANCA) • ANCA are a group of autoantibodies that occur in a large majority of patients with systemic small vessel vasculitis. • Most common conditions in which they are positive are Wegener's granulomatosis and microscopic polyarteritis nodosa. • c-ANCA has a greater specificity than p- ANCA.
  • 33. Anti-Neutrophil Cytoplasmic Antibodies (ANCA) • Diseases like PAN ,MPO or Wegener's Granulomatosis can very rarely cause retinal vessel inflammation. • These diseases primarily affect sclera and adnexa. • Manifestations are secondary to the associated renal induced hypertension (PAN,MPO). • Direct infiltration of retina and optic nerve in case of Wegener‘s granulomatosis.
  • 34. Angiotensin Converting Enzyme (ACE) • Serum ACE levels are elevated in 85% of patients with active pulmonary disease due to sarcoidosis. • However, it may also be increased in diabetes mellitus (24%), leprosy (53%), hyperthyroidism (81%), chronic renal disease, cirrhosis, amyloidosis and tuberculosis.
  • 35. Angiotensin Converting Enzyme (ACE) • As it has a false positive rate of 2-4%, it is not considered a diagnostic test but a useful parameter to monitor disease activity and treatment response. • SACE level is considered to be elevated if the value is above 35 U/ml in adults and 50U/ml in those below 19 years. (8 – 52 U/L) •
  • 36. Serum Globulin • 75% of patients with sarcoidosis have elevated serum globulin levels. • Due to this serum protein increases and albumin/globulin ratio decreases. • Alterations in the serum protein values may act as the first clue to diagnosis of sarcoidosis in some patients. Subsequent serum electrophoresis may also reveal a characteristic "sarcoid-step" pattern. (Normal total serum protein = 6-8.6gm/dl; globulins = 2.3-3.5gm/dl). •
  • 37. Serum Lyzozyme • Sarcoidosis, serum lyzozyme is found to be elevated in 70% cases irrespective of whether the disease is active or inactive. • However, increased levels may also be present in tuberculosis.
  • 38. Serum C-reactive Protein (SCRP) • The values of SCRP generally parallel that of ESR but the former is not influenced by anemia. • It is a non-specific indicator of inflammatory activity in the body. • It increases earlier and declines faster than ESR at the onset and resolution respectively of inflammation. • Following steroid suppression in completely disappears.