Grand Rounds
Shivani V. Reddy, M.D.
3/6/2014
University of Louisville
Department 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.
History
POHx 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
Exam
4  3 mm
20/20-3 ( -0.75 + 1.00 x 015)
VA cc
20/20
(-1.50 + 0.25 x 165)
EOM:
Full OU
CVF:
Full OU
P
no RAPD
4  3 mm
16
TTP
16
Anterior Segment
OD
Ext
L/L
C/S
K
AC
I/L
OS
WNL
WNL
WNL
WNL
1+ injection
1+ injection
few fine KP
WNL
2+Cell, 1+ Flare
1+ Cell, 1+ Flare
posterior synechiae
posterior synechiae
NO VITREOUS CELLS OU
Fundus Exam OD
2 + disc edema, normal macula, normal vessels
multiple 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
OD
mild ILM gliosis, normal foveal contour
OS
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
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.
DDx:
• TINU syndrome (tubular interstitial nephritis and uveitis)
• Infectious mononucleosis
• Sarcoidosis
• Other Infections (syphilis, herpesviridae)
• Systemic lupus erythematosus
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
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
31 year old caucasion female with pain, redness, photophobia
and floaters. Elevated creatinine. Exam with anterior uveitis,
vitritis chorioretinal lesions
References
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BSCS Section 9: Intraocular Inflammation and Uveitis
BSCS Section 12: Retina and Vitreous
Mandeville et al. The tubulointerstitial nephritis and uveitis syndrome.Surv
Ophth. 2001,46(3):195-208.
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.
Mackensen et al Br J Ophth. 2011,95:971-976.
Birnbaum, et. al. Arch Ophthalmol. 2012;130(11):1389-1394.
Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and
uveitis syndrome. Surv Ophthalmol 2001; 46:195.
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
Ali A, Rosenbaum JT. TINU (tubulointerstitial nephritis uveitis) can be
associated with chorioretinal scars.Ocul Immunol Inflamm. 2014
Jun;22(3):213-7.