Unusual anterior Uveitis
in a Child
Ocular History
 10 year old boy
 1/2001: OD>OS
 red eyes
 iris thickening,
 endothelial precipitates, hyphema
 topical corticosteroids
 IOP: OD: 40mmHg
 YAG-iridotomy: unsuccessfull
First Diagnosis

Anterior uveitis of unknown origin
Treatment

topical corticosteroids every hour
Ocular History at Presentation
 6 weeks after first symptoms
 VA OD 8/20; OS 12/20
 IOP: 18/16mmHg
 slitlamp OD:
 iris thickening,
 endothelial precipitates, hyphema
 Fundus: unremarkable
First Presentation - OD
First Presentation - OD

massive granulomatous precipitates
Ocular History at Presentation
 slitlamp OS
 iris prominence at 11 o´clock
 mild anterior chamber cells 1+
 fundus: unremarkable
First Presentation - OS
General History
unclassified malformation syndrome
with anal atresia, insufficiency of the
pituitary gland
 heart transplantation at the age of 3 due
to dilative cardiomyopathy with
endocardial fibrosis
 several transplant rejections (2000)
 Immunosuppression at the moment
 Cyclosporin A, Azathioprin

Second Diagnosis
 CMV induced uveitis
 based on:
 CMV mismatch at transplantation
 leading to high IgG- and IgMantibody titers against CMV
Change of Treatment

systemic ganciclovir in addition
repeated negative PCR and PP-65 ruled
out active CMV, leading to
 stop of ganciclovir
 clinically and serologically no evidence
for sarcoidosis, toxoplasmosis, toxocara
or HIV-infection

Follow up – After 3 Months
 angle closure - peripheral iridectomy
 severe hyphema
 systemic corticosteroids
Histology of Irisbiopsy
 first view
 lymphocytes
 no lymphoma
 severe inflammation
 second view:
 very few mitotic cells
 probably low malignant non
Hodgkin-lymphoma
Irisbiopsy – HE-Staining
 polymorphic lymphocytic infiltration (brown)
Rohrbach et al. Graefe´s Arch Clin Exp Ophthalmol 2004
Immunohistology of Irisbiopsy
 CD
20 +/ CD3 - lymphocytes
Irisbiopsy- Immunostainig
Rohrbach et al. Graefe´s Arch Clin Exp Ophthalmol 2004
Irisbiopsy - EBV
 irisbiopsy:
positive PCR for EBNA-1
 EBV-load: 5,6 x 10-3 (20 x elevated)
 monoclonal rearrangement in the
CD2 region of Ig heavy chain gene in
cells of the tumour (IgH-gene)
Gel-Electrophoresis
 PCR with primers
for the Ig heavy
chain gene,
hypervariable
region
 A,B: tumour
 L: length marker
 P: pos. control
 lane 5, 6: neg.
control
A
B
P
L
Rohrbach et al. Graefe´s Arch Clin Exp Ophthalmol 2004
Diagnosis
 Posttransplantation-Lymphoproliferative
Disease (PTLD)
 localized NH-lymphoma in children
after severe immunosuppression
 nearly exclusively associated to EBV
 interpretation of histology known to be
difficult
Follow up – After 5 Months
 low dose CsA, azathioprine stopped
 ganciclovir orally
 OS: iris tumor regressed slightly
 OD: iris tumor progressed
 high EBV-replication rate in
mononuclear blood cells
Follow Up – After 6 Months
Follow up - After 6 Months
 radiation (5 x 2.0 Gy/week)
 well tolerated
 at the end of the radiation
 mild conjunctivitis
 partial remission of the tumor
Follow up - After 8-12 Months
complete remission of the ocular tumor
 hypotonic situation
 cataract with convergent squint
 still very high EBV titers

Follow Up- After 8 Months OD
Follow Up – After 13 Months
 viral load half of the beginning
 still consistant with persistant active EBVinfection
 foscarnet started
 after a few weeks:
 viral load even higher than before begin of
the foscarnet therapy
 probably high risk for more lymphoma
Follow Up – After 17 Months
 collection of EBV-infected B-cells
from the patient
 generation of patients own specific
cytotoxic anti-EBV T-cells
 Center for Gene and Cell Therapy
Houston TX, USA
Follow Up – After 22 Months
 anti-EBV Treatment
 reinfusion of the T-cells in 3
portions
 reduction of the EBV load
 free of cells in the anterior
chamber
Last Control – After 32 Months
 VA: OD: hand movements, OS: 16/20
 OU:
 clear cornea, no AC cells
 no iris tumors
 IOP 5 and 10 mmHg
 OD: dense cataract, surgery planned
 then lost for follow-up
Posttransplantation
Lymphoproliferative Disorder





all age groups
after transplantation of kidney, liver, heart,
lung or bone marrow
incidence ca. 2-3 %
latency few weeks to 3 years
highest incidence probably in the first year
after transplantation
Posttransplantation
Lymphoproliferative Disorder
 special entity, no simple lymphoma
 3 variants
 circumscribed lesion, typically later than 1 year
after tranplantation, often localized in the CNS,
gastrointestinal tract or salivary glands
 benign, selflimiting disease resembling
mononucleosis
 malignant widespread lymphoproliferation with
high mortality
Ocular PTLD
 Brodsky et al 1991
 until now 14 cases (50% with syst. disease)
 7 with iris nodules
 2 with iris nodules and subretinal mass
 1 with widespread disease (uvea, retina,
optic nerve,orbit)
 1 vitritis,1chorioretinitis,1 anterior uveitis
 1 orbital mass
Histology of Ocular PTLD
 proliferation
of B-cells and/or
plasma cells
 proliferation of T-cells in 10%
 polyclonal or monoclonal
Role of EBV






most PTLD caused by a chronic EBV-infection
EBV negativ recipients are at higher risk than
positive
detectable in the tumor and blood monocytes
anti-T-cell treatment especially dangerous
CMV-infection elevates risk for PTLD
therapy: reduction of IS, increase antivirals
Conclusion
 PTLD incidence ca. 2-3%
 diagnosis: history of solid organ transplantation
 can affect the eye
 iris nodules
 uveitis
 therapy:
 reduction of immunosuppresion
 virustatics
 generation of own anti-EBV cytotoxic T-cells