Grand Rounds

Shivani V. Reddy, M.D.3/6/2014

University of LouisvilleDepartment of Ophthalmology and

Visual Sciences

Patient Presentation CC: blurry vision OU

HPI: 12 year old white male presents with 1 week history of blurry vision OU. He denies any pain, photophobia, flashes or scotomas.

He had a similar episode 4 months prior with associated pain and photophobia. Patient denies any associated malaise, nausea or flank pain during these episodes.

HistoryPOHx and PMHx

1 year ago: patient presented to KCH with fever, malaise, flank pain

and 2 weeks of frothy urine

renal biopsy: tubular interstitial nephritis

treatment: prednisone 40 mg daily

4 months ago: patient developed blurry vision OU with pain and photophobia – diagnosed with acute anterior uveitis

treatment: topical Pred Forte, Cyclogyl

12 week course of methotrexate

FAM Hx none

ROS cushingoid features

MEDS prednisone 20 mg QOD, Cellcept 500mg PO BID

ALLERGIES NKDA

VA cc P TTP

EOM: Full OU CVF: Full OU

20/20-3 ( -0.75 + 1.00 x 015) 4 3 mm

4 3 mm

16

16

no RAPD20/20 (-1.50 + 0.25 x

165)

Exam

Ext WNL WNL

L/L WNL WNL

C/S 1+ injection 1+ injection

K few fine KP WNL

AC 2+Cell, 1+ Flare 1+ Cell, 1+ Flare

I/L posterior synechiae posterior synechiae

NO VITREOUS CELLS OU

OD OS

Anterior Segment

Fundus Exam OD

2 + disc edema, normal macula, normal vesselsmultiple choroidal inflammatory foci on peripheral exam

Fundus Exam

1 + disc edema with mild peripapillary NFL edema, normal macula, normal vessels. Multiple choroidal inflammatory foci (arrows)

OCT

mild ILM gliosis, normal foveal contour

OS

OD

normal foveal contour

FA/ICG

29 seconds: few areas of choroidal leakage on ICG

FA/ICG

54 seconds: foci of choroidal hypofluorescence on ICG

Summary

DDx:• TINU syndrome (tubular interstitial nephritis

and uveitis)• Infectious mononucleosis• Sarcoidosis • Other Infections (syphilis, herpesviridae) • Systemic lupus erythematosus

12 y/o WM with h/o tubular interstitial nephritis diagnosed 1 year prior and an episode of bilateral anterior uveitis 4 months prior presents with blurry vision OU while taking oral prednisone and Cellcept. Exam reveals anterior uveitis , optic disc edema and multiple foci of outer retinal and choroidal inflammation OD > OS.

Treatment Given patient’s cushingoid features and long term prednisone use, prednisone dose was decreased to 10 mg every other day and Cellcept was increased to 1.5 gm daily

Follow-up pending

TINU Syndrome A predominantly bilateral non-

granulomatous anterior uveitis found in a subset of patients with tubular interstitial nephritis (TIN)

First described in 1975 by Dobrin et.al.

relatively rare with reported incidence 1-2%

Uveitis occurs in approximately 65% of TIN patients

TINU Syndrome Epidemiology

- young females (teens – 30)- younger age groups with more male

patients

No racial affinity

Some HLA associations with HLA-DQA1*01, HLA-DQB1*01 HLA-DQB1*05

TINU Syndrome Pathogenesis not well understood

Autoantigen to both uveal and renal tubular cells (mCRP)

Inflammation is T- lymphocyte driven

Risk factors found in only 50% - antibiotics for URIs, NSAIDS, autoimmune diseases, Chlamydia and EBV concurrent infection

Ocular Symptoms Patients present with anterior uveitis

symptoms (pain, redness, photophobia, decreased vision)

Other findings: optic nerve edema, retinal infiltrates, vitreous opacities

ocular symptoms follow TIN in 65%, are concurrent in 15%, precede by up to 2 months in 20%

TIN Findings Increased serum creatinine

Abnormal urinalysis ( no definitive markers)- increased B2- microglobulin- urinary eosinophilia, pyuria,

hematuria- glucosuria

Renal biopsy for definitive diagnosis- Interstitial edema, mononuclear

infiltrate, eosinophils and noncaseating granulomas

Interstitial edema, mononuclear infiltrate, eosinophils and noncaseating granulomas

Treatment renal disease very responsive to

corticosteroids - typically treated for 3 to 6 months with slow taper

Uveitis treated with corticosteroids (topical and systemic)

Even though TIN typically is self limited, uveitis can be recurrent requiring immunomodulator therapy (IMT)• mycophenolate mofetil , methotrexate,

cyclosporine

Prognosis

Long term complication are rare

Uveitis often persists longer than TIN but treatment rarely lasts over 1 year

Uveitis recurs in up to 40% of patients within a few months of therapy cessation but nephritis rarely recurs

retrospective case series of 4 patients with TINU

Gender: 3 female, 1 male Age range: 10 -31 years

All patients presented with acute anterior uveitis. 3/4 patients with vitritis

2 patients presented with TIN before uveitic symptoms: Pt 1 – 4 months prior, Pt 2 - 3 years prior.

2 patients presented with TIN concurrent with uveitic symptoms

10 year old caucasian female presenting with blurred vision,

floaters. Elevated ESR, creatinine. Anterior uveitis, vitritis and lesions

seen below

31 year old caucasion female with pain, redness, photophobia and floaters. Elevated creatinine.

Exam with anterior uveitis, vitritis chorioretinal lesions

11 year old half- asian male with concurrent TIN and pain, redness and

photophobia. Elevated creatinine. Exam with anterior uveitis, vitritis and punctate

chorioretinal lesion

References 1. BSCS Section 9: Intraocular Inflammation and Uveitis2. BSCS Section 12: Retina and Vitreous3. Mandeville et al. The tubulointerstitial nephritis and uveitis

syndrome.Surv Ophth. 2001,46(3):195-208. 4. Suzuki H, Yoshioka K, Miyano M, et al. Tubulointerstitial

nephritis and uveitis (TINU) syndrome caused by the Chinese herb "Goreisan". Clin Exp Nephrol 2009; 13:73.

5. Mackensen et al Br J Ophth. 2011,95:971-976. 6. Birnbaum, et. al. Arch Ophthalmol. 2012;130(11):1389-

1394.7. Mandeville JT, Levinson RD, Holland GN. The

tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001; 46:195.

8. Reddy et al. HLA-DR, DQ class II DNA typing in pediatric panuveitis and tubulointerstitial nephritis and uveitis. Am J Ophthalmol. 2014 Mar;157(3):678-86

9. Ali A, Rosenbaum JT. TINU (tubulointerstitial nephritis uveitis) can be associated with chorioretinal scars.Ocul Immunol Inflamm. 2014 Jun;22(3):213-7.