Algorithm for Work-Up of Panuveitis

Luca Cimino

Contents The term panuveitis (PU) should be reserved

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 for those situations in which there is no predom-
inant site of inflammation, but where it is distrib-
Laboratory Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Scenario . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
uted among the anterior chamber, vitreous, and
Unilateral Panuveitis (UPU) . . . . . . . . . . . . . . . . . . . . . . . . . . 3 retina and/or choroid (i.e., retinitis, choroiditis, or
Exclude Acute Endogenous Endophthalmitis . . . . . . . . 4 retinal vasculitis).
Unilateral Acute Granulomatous Panuveitis . . . . . . . . . . 4 A comprehensive ocular and systemic history
Bilateral Non-granulomatous Panuveitis with Retinal
Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
is the most important component of the PU clini-
Bilateral Panuveitis Often Granulomatous . . . . . . . . . . . 15 cal approach. The review of systems should be
Bilateral Chronic Panuveitis with Moderate Response oriented toward identifying systemic signs or
to Steroids: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 symptoms of general diseases. For example, sar-
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 coidosis can cause lymphadenopathy and skin
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 changes, Vogt-Koyanagi-Harada (VKH) is asso-
ciated with meningism, and Behçet’s disease
(BD) includes oral and/or genital aphthous ulcers,
Introduction skin lesions (erythema nodosum), and reactive
arthritis (Fig. 1).
Uveitis can occur either as a co-manifestation of Demographic information such as gender, age
various autoimmune disorders and infections or as at presentation, and ethnic group (people from
a side effect of medications and toxins, or it can Silk Route in Behçet’s, blacks in sarcoidosis,
arise as a purely idiopathic ocular inflammation Asians in VKH) may suggest certain types of
(Table 1). uveitis.
It is essential to rule out infectious etiology,
especially in acute, unilateral PU. In fact, do not
hesitate to repeat the work-up (even if negative
before) in cases of strictly unilateral disease; in
cases of chronic, long-standing, and recalcitrant
uveitis; and in case of resistance to the therapy.

L. Cimino (*)
Ocular Immunology Unit, Arcispedale S.M. Nuova
IRCCS, Reggio Emilia, Italy
e-mail: l.cimino64@gmail.com

# Springer (India) Pvt. Ltd. 2016 1

V. Gupta et al. (eds.), The Uveitis Atlas,
DOI 10.1007/978-81-322-2506-5_92-1
2 L. Cimino

A temporary, intermittent, or incomplete Patients with PU may follow an acute (some-

response to steroids should raise also suspicion of
masquerade syndromes (neoplastic or non-
neoplastic) that may clinically simulate PU, such
as necrotic tumors, retinoblastoma, Coats’ disease,
tapetoretinal degenerations, disease leukemia,
juvenile xanthogranuloma, lymphoma, and others.
If the standard work-up for infectious and non-
infectious panuveitis is negative, the diagnosis of
idiopathic PU is made.
times hyperacute) course, while others may have a
slowly progressive debilitating course. For this
reason it is important to obtain information
regarding the integrity of the immune system
and/or to evaluate some predisposing conditions
(e.g., recent major gastrointestinal surgery,
indwelling catheters, organ transplantation, and
undergoing chemotherapy – see association with
Candida endogenous endophthalmitis).

Table 1 IUSG clinical classification of uveitis

Laboratory Tests
Infectious Bacterial
Viral
Fungal Extensive work-up is not necessary. We propose
Parasitic the following tests:
Others Full blood cells; serum AST-ALT, creatinine,
Noninfectious Known systemic associations and glucose, serum angiotensin-converting
No known systemic associations
Masquerade Neoplastic
Nonneoplastic

Fig. 1 Flowchart of clinical approach to patient with panuveitis

Algorithm for Work-Up of Panuveitis
enzyme (ACE) and lysozyme, and serology (IgM
and IgG) for herpes simplex 1–2, VZ, CMV
Serology (IgM and IgG) for Toxoplasma,
QuantiFERON-TB Gold and/or Mantoux skin test
Serology for syphilis: specific (TPHA) and non-
specific (RPR). “Always include HIV serology”.
When suspected: human leukocyte antigen
(HLA) typing B51 for Behçet’s disease (BD),
A29 for birdshot retinochoroiditis, and DR4
for VKH syndrome. Always bear in mind the pre-
test probability: for example, around 20% of the
Italian general population is HLA-B51 positive.
Do not hesitate to repeat the work-up in cases
where laboratory tests are negative or not supportive
for the suspected clinical diagnosis. Also consider
revaluation in monolateral disease; in chronic, long-
standing, and recurrent uveitis; and in case of resis-
tance to therapy. Suspect infection when the uveitis
remains strictly unilateral during its course. Choose
the correct evaluation criteria for monitoring and
prognosis. Recognize and treat in emergency,
according to clinical suspicion, when you are faced
with acute retinal necrosis (ARN) or in other critical
situations (infectious endophthalmitis). In selected
cases, anterior chamber paracentesis can provide
important diagnostic evidence to support a specific
infective diagnosis. In fact, polymerase chain reac-
tion (PCR) is a molecular technique for evaluation
of very small amounts of DNA in anterior chamber
fluids. It can be a simple, rapid, sensitive, and spe-
cific tool for the diagnosis of infection and also to
monitor the efficacy of treatment (including
Goldmann-Witmer coefficient or antibody index).
Cultures of intraocular fluids (especially vitre-
ous) in conjunction with bloods are important to
diagnose endogenous endophthalmitis.
Scenario
After having reviewed the clinical, laboratory, and
other exams, we propose here a list of possible
scenarios that we might face in panuveitis, along
with the most appropriate work-up for that sce-
nario (Fig. 2). In some cases there are no specific
clinical manifestations useful to diagnosis. For
this reason a comprehensive, multifactorial
assessment is necessary that takes into
3
consideration the clinical history, clinical presen-
tation, any extraocular clinical signs, clinical
course, and diagnostic work-up (laboratory,
instrumental ocular, and systemic tests) (Table 2).
Unilateral Panuveitis (UPU)
For UPU with occlusive vasculitis and +/ vitre-
ous involvement, accompanying with anterior
chamber inflammation, consider the differential
diagnosis (DD) between Behçet’s disease (see
extraocular signs, HLA-B51, always
non-granulomatous PU), tuberculosis (see positive
Mantoux and/or QuantiFERON-TB Gold), sar-
coidosis (negative Mantoux and/or
QuantiFERON-TB Gold, presence of elevated
serum ACE and/or lysozyme), and syphilis (pres-
ence of specific and nonspecific tests) (Fig. 3).
For UPU with diffuse retinochoroidal lesions
with vitreous involvement, consider DD between
sarcoidosis, tuberculosis, and syphilis (Figs. 4 and
5).
UPU: In patients with atypical forms of uveitis
(presumed autoimmune), nonresponsive to con-
ventional therapy (corticosteroid-resistant forms)
is important to exclude viral origin. Molecular
analysis (PCR and local antibody production for
HSV-1–2, VZ, CMV, EBV) can confirm the diag-
nosis of non-necrotizing herpetic retinopathies
(Fig. 6).
Sometimes, the more frequent granulomatous
PU (sarcoidosis, TBC, syphilis) could be
non-granulomatous at presentation. Before
starting a systemic steroid therapy, you must
ensure to exclude an infectious etiology.
Acute UPU with Hypopyon
• Information regarding the integrity of immune
system
• Risk factors: recent major surgery, indwelling
catheters, organ transplantation, intravenous
drug abuse
• Look at systemic symptoms: fever, malaise
• Eye involvement: mono-/bilateral
• Acute onset (blurred vision)
Differential Diagnosis:
4 L. Cimino
Fig. 2 Most frequent clinical presentations of panuveitis. Blue mostly unilateral, yellow bilateral, or green mono- or
bilateral
1. Severe HLA-B27 uveitis can mimic infection
(look at history, vitreous involvement, includ-
ing eco B-scan for better evaluation; see the
patient after 1 day of intense topical therapy
with steroids and mydriatic agents).
2. Behçet’s disease with retinal infiltrates and
hemorrhages.
Exclude Acute Endogenous
Endophthalmitis
• Blood culture
• Vitreous tap for microbiology
• Cardiological investigation (echocardiography)
(Figs. 7 and 8)
Unilateral Acute Granulomatous
Panuveitis
With retinal necrosis, recognize and treat in
emergency:
• Immunocompetent patients. Known to occur
also in immunocompromised individuals.
• Impaired cellular immunity in apparently
immunocompetent ARN patients suggesting
that it may develop in association with an
imbalance of immune system.
• Sometimes no typical presentation.
• Positive serum-specific serology is only
confirmatory.
• Anterior TAP for herpes virus (PCR for
HSV-1–2, VZ, EBV, CMV).
• Consider immunodeficiency in atypical case
(intraocular fluid analysis including PCR and
GW coefficient) (Figs. 9 and 10).
Unilateral acute granulomatous panuveitis
with a retinochoroidal lesion:
• Look at Toxoplasma etiology.
• Focal necrotizing retinitis resulting in charac-
teristic atrophic scars.
• Reactivation frequently situated adjacent to an
old scar.
• Anterior uveitis (may be granulomatous) and
secondary rise in IOP.
Retinal vasculitis near to or distant from focus
of active retinochoroiditis (Figs. 11, 12 and 13)
Algorithm for Work-Up of Panuveitis 5

Table 2 Targeted approach to the diagnosis

Diagnosis Instrumental
Clinical setting suspicion Targeted investigation exams
Mono- or bilateral, usually Endogenous Vitreous and blood culture B-scan
non-granulomatous panuveitis endophthalmitis echography
History and immune status
Clinical findings: hypopyon, vitreous
infiltration, retinitis foci
Monolateral often granulomatous panuveitis Herpes virus Anterior TAP (PCR and I/A) OCT, fundus
History and immune status (including CMV) Anti-herpes IgM and IgG color image,
Clinical findings: acute retinal necrosis  HS 1–2, VZ, EBV, CMV FA
vitreitis
Monolateral granulomatous panuveitis Toxoplasmosis Anti-Toxoplasma IgG and OCT, fundus
History and immune status IgM color image,
Clinical findings: vitreitis + retinochoroiditis Anterior chamber TAP (PCR) FA-ICGA
adjacent to a pigmented scar
Non-granulomatous panuveitis with retinal Behçet’s disease HLA-B51 OCT, fundus
vasculitis history of oral and/or genital color image,
aphthous, skin lesions FA
Clinical findings: recurrent anterior uveitis
with or without hypopyon
Cellular infiltration and opacification of
vitreous retinal infiltrates and hemorrhages,
cystoid macular edema, disc hyperemia
Retinal vasculitis and recurrent
vasoocclusive episodes are the major cause
of visual morbidity
Bilateral granulomatous panuveitis with VKH Lumbar puncture: pleocytosis OCT
exudative retinal detachment associated (mostly lymphocytes) in EDI-OCT
with neurological and auditory signs (more cerebrospinal fluid FA-ICGA
evident in acute phase) and vitiligo, HLA-DR4
alopecia, poliosis (frequently in
convalescent phase)
Clinical findings: hallmark, in acute, is
bilateral multifocal exudative retinal
detachments and papillitis. Peripheral well-
circumscribed yellow-white lesions (clinical
equivalent of Dalen-Fuchs nodules, a
histological term)
In convalescent phase, the fundus exhibits
an orange-red discoloration (“sunset glow”)
Bilateral granulomatous panuveitis Sympathetic Retinal imaging OCT
insidious onset, history of ocular penetrating ophthalmia EDI-OCT
trauma or intraocular surgery (exciting eye) FA-ICGA
Clinical findings: similar to VKH
Bilateral granulomatous panuveitis, with Sarcoidosis Serum ACE and lysozyme, OCT
multisystem disease, mediastinal skin test for anergy to EDI-OCT
lymphadenopathy, skin lesions (erythema tuberculin FA-ICGA
nodosum)
Clinical findings: presence of endothelial
large mutton-fat keratic precipitates,
choroiditis and/or retinal vasculitis, vitreitis,
retinal vasculitis (“candle-wax” vascular
sheathing)
Bilateral panuveitis characterized by Birdshot HLA-A29 (100% presence) OCT
posterior segment with dual, independent retinochoroiditis FA-ICGA
retinal, and choroidal inflammation VF
(continued)
6 L. Cimino

Table 2 (continued)
Diagnosis Instrumental
Clinical setting suspicion Targeted investigation exams
The disease has no known extraocular
inflammation sites
Adjunctive clinical findings: vitreous
involvement and possible presence of
granulomatous endothelial precipitates
Reemerging multisystem granulomatous TBC, often TBC tests (Mantoux and/or OCT
infectious disease with ocular involvement presumed IGRA tests) EDI-OCT
Clinical findings: bilateral panuveitis (often Intraocular TB FA-ICGA
asymmetric), partially steroid responsive, Similar to
diagnostic delay, usually old scars sarcoidosis
Peculiarity of multifocal lesions
noncontiguous to the optic disc showing
serpiginous spread
Chronic bilateral panuveitis (often Syphilis Syphilis serology (specific and Color picture
asymmetric) due to Treponema pallidum Three stages: nonspecific) OCT
(sexually transmitted infection), skin lesions primary, secondary, CFS analysis FAF
(e.g., hand palm), neurological signs and tertiary syphilis FA-ICGA
Diagnostic findings: intraocular
inflammation is considered to be a risk factor
for the presence of asymptomatic
neurosyphilis
Bilateral eye involvement resembling Vitreoretinal Diagnostic vitrectomy Color
panuveitis (masquerade syndrome) lymphoma including cytology, cytokines, picture
History, immune status, and partially steroid gene rearrangements, biopsy FAF
responsive OCT
Clinical findings: sheets of cells and dense
vitreitis + subretinal infiltrates
TAP anterior chamber paracentesis, FA fluoroangiography, ICGA indocyanine green angiography, FAF fundus auto-
fluorescence, OCT optical coherence tomography, EDI-OCT enhanced depth imaging optical coherence tomography, VFT
visual field test, ACE angiotensin-converting enzyme, HRCT high-resolution chest tomography, RPE retinal pigment
epithelium, CSF cerebrospinal fluid

Bilateral Non-granulomatous
Panuveitis with Retinal Vasculitis

Remember that sometimes even classical,

more frequent granulomatous panuveitis in sar-
coidosis, tuberculosis, and syphilis may be
non-granulomatous at onset or during follow-
up! Always keep in mind the differential diag-
nosis (looking at the diagnostic work-up)
between these three entities and Behçet’s
disease:

• Most frequently panuveitis with involved pre-

dominantly veins
• Behçet’s disease, tuberculosis, sarcoidosis
Fig. 3 UPU with dense vitreitis and retinal vasculitis in
Behçet’s disease
Discrimination between infectious (Tb) and
noninfectious etiology is important.
Algorithm for Work-Up of Panuveitis 7

Fig. 4 UPU with vitreitis and diffuse chorioretinal scars in sarcoidosis

Fig. 5 UPU with diffuse, peripapillary infiltrate involving the optic nerve (neuroretinitis): (a, b) acute phase, (c, d)
convalescent phase
8 L. Cimino

Fig. 6 UPU with non-necrotizing retinitis due to HSV-2 (PCR positive in aqueous humor): (a) acute, (b, c) post-acute
phase

Fig. 7 Acute endogenous endophthalmitis due to Candida albicans: (a) intense vitreitis, in acute phase, (b) inferior dense
vitreous infiltrates, (c) after vitrectomy + silicone oil

Fig. 8 (a) Acute endogenous endophthalmitis with hypopyon, (b) intense and diffuse vitreitis in acute phase,
(c) convalescent phase after systemic and local therapy

Behçet’s Disease (Looking at Diagnostic
Criteria)
• Italy: HLA-B51 positive in 18% of normal
controls and in 60% of BD patients.
• Extraocular involvement: oral and genital
aphthae, erythema nodosum, others.
• Laser flare photometry (LFP) is a method used to
detect flare in the anterior chamber (AC). LFP
results should always be interpreted in conjunc-
tion with the usually clinical observations. There
is some evidence that worsening of the flare on
two consecutive visits is predictive of a relapse,
especially in patients with Behçet’s disease.
Algorithm for Work-Up of Panuveitis 9

Fig. 9 Granulomatous PU after a severe bronchial pneu- retinal active lesion, (c, d) FA showing retinal ischemic
monia, at presentation (a-c); note the possible DD between lesion, (e, f, g) follow-up visits after 7, 14 (acyclovir i.v.),
HSV and Toxoplasma (anterior chamber TAP showed PCR and 40 days (oral valacyclovir)
positive for HSV-1): (a) anterior granulomatous uveitis, (b)

Fig. 10 Bilateral acute retinal necrosis in pt. HIV+. LE anterior TAP confirmed a positive PCR for Toxoplasma.
Importance of intraocular fluid analysis when the clinical diagnosis is not clear (in this case the possible DD with CMV)

Fig. 11 (a, b) LE acute retinochoroidal lesion in UPU: typical toxoplasmosis (see the new lesion adjacent the old scar).
(c) The same healed lesion after 1 month of anti-Toxoplasma therapy. The diagnosis is confirmed by fundus exam
10 L. Cimino

Fig. 12 Peridiscal toxoplasmic lesion (see the utility of OCT during the follow-up) first episode in 42 y.o.

Fig. 13 (a) Toxoplasma

retinochoroidal lesion,
active phase, (b) healed
lesion after specific therapy,
(c) progressive
improvement of visual field
test (VFT) during the
follow-up
Algorithm for Work-Up of Panuveitis
Fig. 14 Mobile hypopyon (seeing with the head movement) to differentiate with HLA-B27 hypopyon
Fig. 15 Attention to the extraocular signs: erythema nodosus, oral and genital aphthae
• Pathognomonic of Behçet’s disease: transient
white patches of retinitis, small adjacent hem-
orrhages in patients with active uveitis, silent
on FA.
• FA is more sensitive than clinical examination.
• Active vasculitis: leakage of dye due to break-
down of inner blood-retinal barrier and
staining of blood vessel wall.
• Leakage may be focal or more frequently
diffuse.
• Diffuse capillary leakage (Figs. 14, 15, 16 and
17).
Bilateral panuveitis with papillitis and serous
retinal detachment:
• Not always bilateral serous retinal detachment
• Differential diagnosis of choroidal folds +
papillitis
11
• Vogt-Koyanagi-Harada disease (see diagnostic
criteria)
• If previous ocular penetrating trauma or
intraocular surgery: sympathetic ophthalmia
(SO)
• Posterior scleritis (looking at eco B-scan show-
ing sclera thickening and pain during eye
movement) (Fig. 18)
VKH: chronic, bilateral, granulomatous
panuveitis associated with central nervous sys-
tem, auditory, and integumentary manifestations:
• Always treat VKH aggressively (preventing
sunset glow fundus).
• Importance of ICGA EDI-OCT: to monitor
choroidal thickness.
• FA-ICGA: disc hyperfluorescence (acute
phase).
12 L. Cimino

Fig. 16 Behçet’s disease-related bilateral PU in 24 M with full visual acuity and therapy incomplete control. In optic
nerve neovessels (color photos), FA is more sensitive than fundus exam

Fig. 17 The same case after 1 month of more aggressive systemic therapy

Fig. 18 Posterior scleritis (confirmed by eco B-scan) with papillitis and after the resolution of the acute phase
Algorithm for Work-Up of Panuveitis 13

• FA in acute: diffuse hyperfluorescent, pin- • ICGA in acute: fuzzy and indistinct choroidal
points, and dye pooling (late phase); chronic vessels, diffuse hyperfluorescent dots
phase, window and blocking effect due to RPE (granuloma), hyperfluorescent pinpoints (exu-
disorders. dation) (Figs. 19, 20 and 21).

Sympathetic Ophthalmia (SO)

Rare bilateral granulomatous panuveitis that
occurs as a complication of a penetrating injury
that involves the uvea of one eye:

• Major sight-threatening disorder.

• High index of suspicion must be maintained
whenever inflammation occurs in fellow eye
(sympathizing eye) of an eye (exciting eye)
that has suffered penetrating trauma or intraoc-
ular surgery.
• Infection should be carefully ruled out.
• Diagnosis is made clinically: histological proof
is not required.

Fig. 19 To confirm the diagnosis, lumbar puncture to

obtain the presence of pleocytosis (mostly lymphocytes)

Fig. 20 (a) Bilateral PU

with papillitis and serous
retinal detachment in acute
phase, (b) quasi-complete
resolution of inflammation
after 1-month therapy
14 L. Cimino

Fig. 21 Sometimes, in
recurrent bilateral PU, we
can see bilateral papillitis
(a) without serous retinal
detachment. Consider the
extraocular signs (e.g.,
vitiligo) (b) and headache.
Perform FA (c) and ICGA
(d) to see more specific
lesions
Algorithm for Work-Up of Panuveitis
• Injured eye which has potential vision should
not be enucleated in an attempt to prevent or
lessen SO or to provide confirmatory pathology
(Figs. 22, 23 and 24).
Bilateral Panuveitis Often
Granulomatous
Sarcoidosis and tuberculosis, similar instrumental
Fig. 22 Perforating trauma
work-up:
Fig. 23 Sympathetic ophthalmia: active inflammation in a
diagnostic delay case. The right eye is the exciting (past
perforating trauma), and the left eye is the sympathizing.
Note the presence of bilateral vitreitis and papillitis. In the
15
Multimodal imaging: nonspecific signs may be
helpful in establishing the diagnosis but are useful
for assessing the extent of inflammation.
FA: retinal vasculitis, disc hyperfluorescence,
and cystoid macular edema
ICGA: diffuse hypofluorescent dark dots (gran-
uloma), fuzzy choroidal vessels in intermediate
phase, and diffuse hyperfluorence due to cho-
roidal staining in the late phase
Sarcoidosis
Elevated serum lysozyme and angiotensin-
converting enzyme (ACE). Attention: the children
show normally elevated serum ACE.
Radiology: high-resolution (HR) CT scan bet-
ter than chest X-ray to detect hilar and mediastinal
lymphadenopathy.
Lesion biopsy: when possible, mediastinal
lymph nodal biopsy is important to have a specific
diagnosis of sarcoidosis (in differential diagnosis
with TBC or lymphoma when the clinical
left eye, the more inflamed eye, are visible diffuse small
yellow lesions (Dalen-Fuchs nodules). In the right eye are
present depigmented scars (representing the loci of previ-
ous Dalen-Fuchs nodules)
16
Fig. 24 The sympathizing eye (a–c) in acute phase
looking at ICGA (hyperfluorescence of optic disc and
diffuse hypofluorescent dots indicating active
Fig. 25 High-resolution CT scan is more sensitive to show lymphadenopathy chest X-ray
manifestations and work-up are not exhaustive)
and also to ensure a good therapeutic approach,
avoiding potential side effects (e.g., regarding the
use of anti-TNF agents not recommended in case
of TBC).
Exclude birdshot retinochoroiditis (vitreitis,
retinal vasculitis, stromal choroiditis that can
L. Cimino
inflammation) is more sensitive than FA (A). OCT (c)
shows exudative retinal detachment. Figures (d, e) resolu-
tion of inflammation after therapy
show granulomatous keratic precipitates, pres-
ence of HLA-A29) (Figs. 25 and 26).
Tuberculosis
This can be due to direct infection or indirect
immune-mediated hypersensitivity response to
mycobacterial antigens.
Algorithm for Work-Up of Panuveitis
Fig. 26 Choroidal granuloma well seen at EDI-OCT at the beginning and during the follow-up
• In recent years, ocular involvement due to TB
has reemerged associated with an increasing
prevalence of TB.
• High index of clinical suspicion is essential for
early diagnosis.
• Diagnosis should be considered when
unexplained chronic uveitis with the character-
istic clinical signs occurs that promptly recurs
upon tapering corticosteroid and/or immuno-
suppressive therapy.
• Most patients with ocular involvement have no
history of pulmonary or other systemic forms.
• The absence of clinically evident pulmonary
TB does not rule out the possibility of ocular
TB as about 60% of patients with extra-
pulmonary TB has no evidence of
pulmonary TB.
• In most cases diagnosis of intraocular TB is
only presumptive.
• Diagnostic criteria for presumed tuberculosis
uveitis.
17
• Ocular findings consistent with possible TB
with no other causes of uveitis suggested by
history, symptoms, or ancillary testing.
• QuantiFERON-TB positive and/or a strongly
positive tuberculin skin test result.
• Response to antituberculosis therapy with the
absence of recurrences (Fig. 27).
Syphilis
• Extraocular manifestations.
• Serology: nonspecific and specific tests.
• Specific tests are more sensitive in all stages
than nonspecific tests.
• Nonspecific type of uveitis.
• Considerations: partially steroid responsive,
diagnostic delay. Therapy of choice is penicil-
lin (Figs. 28 and 29).
18 L. Cimino

Fig. 27 Bilateral granulomatous panuveitis in ocular TBC. (a–d) acute phase: (a) color fundus, (b) FA, (c) OCT. (e, f)
Convalescent phase: (e) color fundus, (f) OCT
Algorithm for Work-Up of Panuveitis
Bilateral Chronic Panuveitis
with Moderate Response to Steroids:
Vitreoretinal Lymphoma (VRL)
Suspect in cases of uveitis in which infectious
forms have been ruled out and which do not
Fig. 28 Attention at extraocular signs: maculopapular
eruption on the palm in a patient with secondary syphilis
Fig. 29 Placoid choroidal infiltration in syphilis. (a) Color fundus, (b) FAF, (c) FA, (d) ICGA early phase, (e) ICGA late
phase, (f) OCT acute phase, (g) OCT convalescent phase
19
respond completely to steroid therapy. In fact, in
the presence of dense vitreal involvement with
diffuse subretinal infiltrates, suspicion of VRL is
strong.
Intraocular lymphomas are one of the most
critical entities to take into consideration in the
differential diagnosis of patients with panuveitis.
Careful ophthalmic examination, appropriate
consideration of past medical history, and a diag-
nostic vitrectomy timely performed could lead to the
correct (early) diagnosis of intraocular lymphoma.
(Figs. 30, 31, 32 and 33)
20
Fig. 30 Vitreoretinal lymphoma: (a, b) dense cellular infiltration in the vitreous, (c) the same case after chemotherapy
(local and systemic)
Fig. 31 Large multifocal but coalescing subretinal masses
and dense cellular vitreous infiltration are typical for
vitreoretinal lymphoma
Conclusions
• Diagnostic evaluation should be focused
guided by history and ophthalmic and physical
examinations.
• A detailed history, review of systems, and
physical examination allow for a differential
diagnosis.
• The absence of any diagnostic clues from his-
tory makes idiopathic panuveitis most likely.
L. Cimino
• If medical history, review of systems, or ocular
examination suggests an underlying systemic
disease, then diagnostic work-up should be
tailored for that disease.
• Discrimination between infectious and non-
infectious etiology is important.
• Possibility of a masquerade syndrome (malig-
nancy) should be kept in mind.
• Specific antimicrobial therapy is indicated for
infectious causes.
• Specific immunosuppressive agents may be
useful in immunologic-mediated disorders but
contraindicated in infectious causes without
specific antimicrobial treatment.
• Malignancy must be ruled out. It should
be considered if disease becomes refractory
to treatment after an initial improvement.
Not only sight threatening but could be the
first sign of potentially lethal systemic
disease.
• Prompt diagnosis and institution of appropriate
therapy will help to control ocular disease and
systemic disease.
• PU often involves an interdisciplinary
approach, essential in evaluation and treatment
and laboratory investigation.
Algorithm for Work-Up of Panuveitis 21

Fig. 32 Secondary choroidal lymphoma: patient with (b) B-scan ecography: choroidal thickening, (c) OCT
choroidal involvement secondary to marginal lymphoma showing irregularly choroidal profile due to lymphoma
in the lung. In (a) color picture, you can appreciate vitreitis, infiltration, (d) lung histology

Fig. 33 The same case after radiotherapy. The (a) color fundus, (b) eco B-scan, (c) OCT photos show the complete
resolution of lymphoma choroidal infiltration
22
Suggested Reading
Abu El-Asrar AM, Al-Kharashi AS, Aldibhi H,
Al-Fraykh H, Kangave D. Vogt-Koyanagi-Harada dis-
ease in children. Eye (Lond). 2008;22(9):1124–31.
Al-Mezaine HS, Al-Muammar A, Kangave D, Abu
El-Asrar AM. Clinical and optical coherence tomo-
graphic findings and outcome of treatment in patients
with presumed tuberculous uveitis. Int Ophthalmol.
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