1. Case Study Toolkit
For general ophthalmologists and specialists treating non-anterior non-infectious uveitis
Date of preparation: February 2019 | ALL-IMMU

2. Case Study 2
Developed with Prof. Soon-Phaik Chee | Singapore National Eye Centre, Singapore
This case study represents the speaker's experience and is not intended to be a representative example. Off-label therapy may have been used, but this does not constitute a recommendation.

3. Background Given BCG vaccine for tuberculosis at birth.
No history of tuberculosis in immediate family.
Red eyes.
Blurring of vision in both eyes for three months.
Taken to general ophthalmologist at optometrist’s recommendation.
Patient profile
Other relevant medical history
Presenting complaint
AGE
5 years
SEX
Male
ETHNICITY
Singaporean Malay
OCCUPATION
Student
BCG, Bacillus Calmette-Guérin
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4. Background Given BCG vaccine for tuberculosis at birth.
No history of tuberculosis in immediate family.
Red eyes.
Blurring of vision in both eyes for three months.
Taken to general ophthalmologist at optometrist’s recommendation.
Patient profile
Other relevant medical history
Presenting complaint
AGE
5 years
SEX
Male
ETHNICITY
Singaporean Malay
OCCUPATION
Student
BCG, Bacillus Calmette-Guérin
CLICK ON BUTTONS TO VIEW CONTENT

5. Initial treatment details
Standard uveitis workup was done (details unknown).
Mantoux test for tuberculosis was done.
> RESULT: Positive (15 mm)
Presumed bilateral ocular tuberculosis-associated panuveitis
Started on anti-tuberculosis medication
Rifampicin 225 mg + isoniazid 150 mg + pyrazinamide 450 mg
Oral administration
Investigations
Diagnosis
Management
Consider: Do you agree with the diagnosis & treatment decision given the patient’s history? ?

6. Initial treatment details
Standard uveitis workup was done (details unknown).
Mantoux test for tuberculosis was done.
> RESULT: Positive (15 mm)
Presumed bilateral ocular tuberculosis-associated panuveitis
Started on anti-tuberculosis medication
Rifampicin 225 mg + isoniazid 150 mg + pyrazinamide 450 mg
Oral administration
Investigations
Diagnosis
Management
Consider: Do you agree with the diagnosis & treatment decision given the patient’s history? ?

7. Let’s assess… ?
Was the treatment decision adequate? ?
How could the treatment decision be supported further?
Further testing for M. tuberculosis: interferon-γ release assay, polymerase chain reaction (vitreous biopsy).
Improvement of uveitis after six weeks of treatment if the condition was related to tuberculosis.
Anti-tuberculosis treatment was given based on the positive Mantoux test.
However, the positive test result may have been caused by a latent tuberculosis infection unrelated to the eye inflammation.
We also know that the patient received a BCG vaccination at birth.

8. Let’s assess… ?
Was the treatment decision adequate? ?
How could the treatment decision be supported further?
Further testing for M. tuberculosis: interferon-γ release assay, polymerase chain reaction (vitreous biopsy).
Improvement of uveitis after six weeks of treatment if the condition was related to tuberculosis.
Anti-tuberculosis treatment was given based on the positive Mantoux test.
However, the positive test result may have been caused by a latent tuberculosis infection unrelated to the eye inflammation.
We also know that the patient received a BCG vaccination at birth.

9. Events leading to referral to uveitis specialist
Uveitis and visual function did not improve after 3 months.
Patient continued to be treated with anti-tuberculosis medication – treatment was not reviewed.
Regular check-ups included visual acuity, intraocular pressure and slit lamp examination.
Parents sought second opinion from an infectious disease physician.
Interferon-γ release assay was done.
> RESULT: Negative
Outcome
Investigations
Lack of improvement in visual function and negative interferon-γ release assay led to referral to a uveitis specialist.

10. Events leading to referral to uveitis specialist
Uveitis and visual function did not improve after 3 months.
Patient continued to be treated with anti-tuberculosis medication – treatment was not reviewed.
Regular check-ups included visual acuity, intraocular pressure and slit lamp examination.
Parents sought second opinion from an infectious disease physician.
Interferon-γ release assay was done.
> RESULT: Negative
Outcome
Investigations
Lack of improvement in visual function and negative interferon-γ release assay led to referral to a uveitis specialist.

11. Assessments by uveitis specialist
Posterior segment exam
Other information
Ocular exam
Investigations
VITREOUS HAZE
Moderate in both eyes
ICG
Extensive choroidal large vessel leakage in both eyes
OCT (EDI)
Choroidal thickness OD 409 mm, OS 390 mm (bilateral thickening)
Multiple small choroidal scars scattered over peripheral fundus
Sunset glow appearance of fundus
No retinal vasculitis or macular edema
CHEST X-RAY
Normal
T-SPOT TUBERCULOSIS TEST
Negative
SYPHILIS SEROLOGY
BLOOD COUNTS, RENAL & LIVER PANEL
Vitiligo on upper eyelids, left temple, chin, cheek and back
Poliosis
No high-tone deafness
VISUAL ACUITY
OD 6/120, OS 6/120
INTRAOCULAR PRESSURE
OD 21 mmHg, OS 27 mmHg
ANTERIOR CHAMBER CELL GRADE
OD 2+, OS 2+
Extensive posterior synechia, iris stromal nodules and posterior subcapsular cataracts in both eyes
Consider: How would you manage this patient? ?
EDI, enhanced depth imaging; ICG, indocyanide green; OCT, optical coherence tomography; OD, oculus dexter; OS, oculus sinister

12. Assessments by uveitis specialist
Posterior segment exam
Other information
Ocular exam
Investigations
VITREOUS HAZE
Moderate in both eyes
ICG
Extensive choroidal large vessel leakage in both eyes
OCT (EDI)
Choroidal thickness OD 409 mm, OS 390 mm (bilateral thickening)
Multiple small choroidal scars scattered over peripheral fundus
Sunset glow appearance of fundus
No retinal vasculitis or macular edema
CHEST X-RAY
Normal
T-SPOT TUBERCULOSIS TEST
Negative
SYPHILIS SEROLOGY
BLOOD COUNTS, RENAL & LIVER PANEL
Vitiligo on upper eyelids, left temple, chin, cheek and back
Poliosis
No high-tone deafness
VISUAL ACUITY
OD 6/120, OS 6/120
INTRAOCULAR PRESSURE
OD 21 mmHg, OS 27 mmHg
ANTERIOR CHAMBER CELL GRADE
OD 2+, OS 2+
Extensive posterior synechia, iris stromal nodules and posterior subcapsular cataracts in both eyes
Consider: How would you manage this patient? ?
EDI, enhanced depth imaging; ICG, indocyanide green; OCT, optical coherence tomography; OD, oculus dexter; OS, oculus sinister

13. New diagnosis, treatment regimen and disease progression
Panuveitis associated with chronic Vogt-Koyanagi- Harada syndrome (incomplete)
The patient’s treatment was changed multiple times due to inadequately controlled disease.
Started on subcutaneous injections of adalimumab (40 mg, every two weeks) with oral methotrexate (25 mg, every two weeks).
Over the next three years, patient was placed on infliximab with oral methotrexate.
Attempts to taper infliximab failed.
Patient currently on intravenous abatacept (125 mg, every four weeks) with oral mycophenolate mofetil (1 g, every other day).
Over three years, patient developed uveitic cataracts and advanced uveitic glaucoma in both eyes.
Patient underwent lens aspiration, surgical iridectomy, synechiolysis and anterior vitrectomy, then Ahmed glaucoma valve surgery, Tutopatch® and anterior vitrectomy.
Choroidal neovascularization was detected in the left eye 1.5 years after starting abatacept and treated with three intravitreal doses of bevacizumab.
Diagnosis
Management
Outcome

14. New diagnosis, treatment regimen and disease progression
Panuveitis associated with chronic Vogt-Koyanagi- Harada syndrome (incomplete)
The patient’s treatment was changed multiple times due to inadequately controlled disease.
Started on subcutaneous injections of adalimumab (40 mg, every two weeks) with oral methotrexate (25 mg, every two weeks).
Over the next three years, patient was placed on infliximab with oral methotrexate.
Attempts to taper infliximab failed.
Patient currently on intravenous abatacept (125 mg, every four weeks) with oral mycophenolate mofetil (1 g, every other day).
Over three years, patient developed uveitic cataracts and advanced uveitic glaucoma in both eyes.
Patient underwent lens aspiration, surgical iridectomy, synechiolysis and anterior vitrectomy, then Ahmed glaucoma valve surgery, Tutopatch® and anterior vitrectomy.
Choroidal neovascularization was detected in the left eye 1.5 years after starting abatacept and treated with three intravitreal doses of bevacizumab.
Diagnosis
Management
Outcome

15. Final patient outcome OD OS
After five years on biologics, vision improved significantly and stabilized.
Disease appears quiescent on indocyanide green angiography.
Posterior segment shows multiple peripheral choroidal scars and left choroidal faint scar at macula.
Outcome OD OS
VISUAL ACUITY
OD 20/25, OS 20/100
INTRAOCULAR PRESSURE
OD 12 mmHg, OS 12 mmHg
The patient is now being seen regularly by a pediatric rheumatologist and an ophthalmologist.
OD, oculus dexter; OS, oculus sinister

16. Final patient outcome OD OS
After five years on biologics, vision improved significantly and stabilized.
Disease appears quiescent on indocyanide green angiography.
Posterior segment shows multiple peripheral choroidal scars and left choroidal faint scar at macula.
Outcome OD OS
VISUAL ACUITY
OD 20/25, OS 20/100
INTRAOCULAR PRESSURE
OD 12 mmHg, OS 12 mmHg
The patient is now being seen regularly by a pediatric rheumatologist and an ophthalmologist.
OD, oculus dexter; OS, oculus sinister

17. ? Let’s assess… How could this patient’s outcomes have been improved?
The patient should have been referred earlier.
Delayed referral led to the Vogt-Koyanagi Harada disease becoming chronic, resulting in irreversible visual loss and development of complications (secondary cataract, secondary glaucoma, choroidal neovascularization).
Persistent poor vision that did not respond to treatment, especially in a pediatric patient, should have triggered the referral.

18. ? Let’s assess… How could this patient’s outcomes have been improved?
The patient should have been referred earlier.
Delayed referral led to the Vogt-Koyanagi Harada disease becoming chronic, resulting in irreversible visual loss and development of complications (secondary cataract, secondary glaucoma, choroidal neovascularization).
Persistent poor vision that did not respond to treatment, especially in a pediatric patient, should have triggered the referral.