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10.6 Infectious Uveitis
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a
Fig. 10.12 (A) Tubercular retinal vasculitis (blue arrows)
with periphlebitis, retinal haemorrhages, and perivascular
cufng (a). Fluorescein angiography shows extensive
capillary non-perfusion (*) (b). (B) A 46-year-old man
underwent successful pars plana vitreous surgery for the
vitreous haemorrhage in the left eye (a) and recovered
20/20 visual acuity (b). Four years later, he returned with
fresh symptoms. He showed multifocal choroiditis lesions
along the retinal vessels (c). The FFA showed initial hypouorescent (not shown) and intense uorescein staining of
recurrent vitreous haemorrhage in young people
has been erroneously labelled as Eales’ disease, a
misnomer for vitreous haemorrhage resulting
from retinal periphlebitis, seen most commonly
in TB-endemic countries like India. Biswas etal.
[150], after an extensive review of the literature,
suggested that this disease should be described as
presumed tuberculous retinal periphlebitis.
Patients rst present with vitreous haemorrhage and not earlier due to the mildly symptomatic or even asymptomatic nature of the
peripheral retinal periphlebitis that may go
unnoticed by young people. It is a bilateral but
asymmetric disease. Examination of the contralateral eye in those presenting with vitreous
haemorrhage will often reveal active periphlebitis or healed white thread-like occluded vessels
in the peripheral retina. Acute-stage tubercular
retinal vasculitis was characterized in patients
b
the discrete chorioretinal lesions and retinal vessel wall
staining nasal to the optic disc (d). His tuberculin skin test
was positive at 13×15mm. CT scan chest showed brotic
opacities at the lung apices. Axillary glands were enlarged
and were biopsied. On histopathology of the lymph node
biopsy showed central areas of caseation necrosis, peripherally palisaded histiocytes along with epithelioid cell
granulomas with Langhans giant cells. Stain for AFB was
positive (e)
who were PCR- positive for the MTB genome.
These patients were treated with oral corticosteroids combined with anti-TB therapy and were
followed up to monitor the course of the disease
[122, 124]. In the acute stage, TB-periphlebitis
is characterized by segmental exuberant perivenous inltrates that involve one or more peripheral quadrants. Vitreous inammatory cells,
retinal haemorrhages, exudates, and macular
oedema often accompany it. The most characteristic feature of this periphlebitis is the occlusion
of the affected segments of the retinal veins
resulting in extensive capillary non-perfusion
(CNP) in the retinal periphery (Fig. 10.12).
Nearly half of the patients may show perivascular discrete active or healed patches of chorioretinitis, which differentiates it from other causes
of retinal vasculitis like Behcet’s disease.
Extensive CNP areas ultimately lead to the
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10 Retinal andChoroidal Infections andInammation
a
d
Fig. 10.12 (continued)
b
c
e
a
b
c
Fig. 10.13 Vitreous haemorrhage as the presentation of
tubercular retinal vasculitis in a young man (a).
Fluorescein angiography showed a large NVD (optic disc
development of retinal neovessels elsewhere in
the retina, which burst to cause sudden loss of
vision from vitreous haemorrhage (Fig.10.13).
The new vessels are always accompanied by
supporting connective tissue, which contracts
and may lead to peripheral tractional retinal
detachment. Undiluted vitreous samples from
57% of patients with the so-called Eales’ disease
neovascularization, blue arrow) (b). Vitreous surgery with
laser photocoagulation led to clearing of media and restoration of vision (c)
genome, with copies varying from 1.52×104 to
1.01×106 [151]. Earlier, using the nested PCR
technique, nearly 21% of the vitreous samples
from patients with Eales’ disease were positive
for the MTB genome versus 4% from the control
samples [152]. See Boxes 10.4 and 10.5 for clinical characteristics and the classication criteria
of TB uveitis.
were positive by quantitative PCR for the MTB
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Box 10.4 Case Denitions for the Diagnosis
of Tubercular Uveitis (TBU)
Proposed case denitions for diagnosing TBU
A. Clinical signs consistent with TBU
1. Broad posterior synechiae
2. Retinal periphlebitis with or without
discrete chorioretinal lesions/scars
3. Multifocal serpiginoid choroiditis or SLC
4. Choroidal granuloma
5. Optic disc granuloma
6. Optic neuropathy
B. History of documented or undocumented
exposure to TB within 48months
C. Immunological tests—interferon gamma
release assay or tuberculin skin test
D. Radiological evidence of active or past
pulmonary TB
E. Histopathological evidence or AFB on smear
or culture from extraocular sites
F. PCR or smear or culture+for MTB from
ocular uids
G. Response to treatment with anti-TB therapy
assessed at 2months after initiation
serpiginous-like choroiditis, TB
SLC
tuberculosis, AFB acid-fast bacilli, PCR
polymerase chain reaction, MTB
Mycobacterium tuberculosis
Ref. Adapted from Gupta etal. [99, 100]
with permission of the publishers
Box 10.5 Classication Criteria for
Tubercular Uveitis
Classication of TBU
Clinical
diagnostic group Case denition criteria
Conrmed
TBU (1 and 2)
1. At least one clinical sign
suggestive of TBU
2. Microbiological
conrmation of MTB from
ocular uids/tissues
Classication of TBU
Clinical
diagnostic group Case denition criteria
Probable TBU
(1, 2, and 3
together)
Possible TBU
(1, 2, and 3) or
(1 and 4)
1. At least one clinical sign
suggestive of TBU (other
aetiologies excluded)
2. Radiological evidence
consistent with TB
infection or clinical
evidence of extraocular TB
or microbiological
conrmation from sputum
or extraocular sites
3. At least one of the
following
(a) Documented exposure
to TB
(b) Immunological
evidence of TB
1. At least one clinical sign
suggestive of TBU (other
aetiologies excluded)
2. Radiology not consistent
with TB and no evidence of
extraocular TB
3. A least one of the following
(a) Documented exposure
to TB
(b) Immunological
evidence of TB
4. Radiological evidence of
TB but no documented
exposure or immunological
evidence of TB
TBU tubercular uveitis, TB tuberculosis,
MTB Mycobacterium tuberculosis
Adapted from: Gupta A, Sharma A,
Bansal R, Sharma K. Classication of
intraocular tuberculosis. Ocul Immunol
Inamm. 2015 Feb;23(1):7–13. doi:
10.3109/09273948.2014.967358. Epub
2014 Oct 14. PMID: 25314361 with permission of the publishers
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10 Retinal andChoroidal Infections andInammation
10.6.6.4 Laboratory Diagnosis
ofInfectious Uveitis
Pathogen-Directed
Polymerase Chain Reaction
(PCR)
Necrotizing infections of the retina, especially in
immunosuppressed individuals, are challenging
to clinically differentiate, whether caused by herpes viruses, toxoplasmosis, or syphilis, as these
often present with atypical features. Most organisms contain either DNA or RNA. Nonnecrotizing infections by the herpes viruses in
immunocompetent patients, although rare, may
pose a diagnostic challenge [153]. Prespecied
pathogen-directed polymerase chain reaction
(PCR) from the ocular uids has been a mainstay
for more than three decades for detecting infections of the retina caused by HSV, VZV, and
CMV with more than 95% sensitivity and nearly
100% specicity. [154–161]. The Ebola virus
was found persisting in the aqueous humour of a
patient who had recovered from the infection in
the past [162]. More recently, a strip multiplex
PCR to simultaneously test for 24 common eye
infections produced comparable results to the
conventional real-time PCR (RT-PCR) tests
[163]. Suboptimal sensitivity of various PCR
techniques in TBU, perhaps due to its paucibacillary pathology, has yet to nd favour for these
techniques for routine use in the clinics [151,
164, 165]. However, these have helped in charac-
terizing the phenotypes of TBU.Moreover, the
detection of a multidrug-resistant MTB genome
by gene sequencing of the amplied DNA from
the vitreous uid helped successfully treat
patients with non-responding TBU ([147, 149];
Sharma etal. 2019). Further, using mRNA multiplex PCR, viable MTB was reported from the
vitreous uid in over 40% of the suspected TBU
cases [166], justifying the use of anti- tuberculosis
drugs.
The yield of PCRs is higher from the vitreous
uid because of the proximity of the sampling
site to the focus of infection. Micro-incisional
pars plana vitreous surgery using either 23/25 or
27 gauge is a safe and effective procedure in
patients with uveitis, especially infectious uveitis, where relatively larger volumes of uid are
required for carrying out many laboratory investigations [167, 168].
10.6.6.5 Next-Generation
Sequencing (NGS)
Nearly 30years after Sanger [169] introduced a
technique, albeit slow and expensive, to identify
the exact sequence of nucleotides in a genome,
the introduction of NGS, a high-throughput technology capable of sequencing Gb size sequences
of DNA by running millions of parallel sequences
of 100–500 base pairs bits, it has begun to nd its
way into clinics to diagnose infections. Most of
the sequenced DNA would be human, but an
overabundance of microbial DNA indicates
infection [170]. The major challenge is getting a
sample not contaminated by bystander
environmental organisms. It helps in detecting
hitherto known or even unknown microbes.
Deshmukh etal. [171] reported positivity rates of
almost 88% from patients with endophthalmitis
versus only 44% using conventional cultures.
10.6.6.6 Metagenomics Deep
Sequencing (MDS)
An unbiased, comprehensive technique of NGS
that can detect all species of microbes (viruses,
bacteria, fungi and parasites) without any selection bias [172] led to the detection of organisms
from 8 of the 36 (22%) archived vitreous samples
that were negative by the conventional pathogendirected PCR techniques. The technique has been
validated by obtaining highly concordant results
with the conventional pathogen-directed PCR
[173]. The long-suspected rubella infection in
patients of Fuchs’ uveitis was conrmed by the
MDS technique [172]. RNA-sequencing techniques have detected common and rare pathogens
from the ocular uids of patients with uveitis
[173]. Using metagenomics sequencing, the
same authors detected Tropheryma whipplei from
the aqueous humour of a patient with Whipple’s
disease who presented with uveitis [174].
Arunasri etal. [175] found dysbiosis in the ocular
microbiome in the vitreous uid from patients
with post-fever retinitis. Relapsing uveitis due to
human T-lymphotropic virus type 1 in a patient
living with HIV was diagnosed by metagenomic
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deep sequencing [176]. MDS has been one of the
most exciting developments in microbial diagnostics. In the coming times, we expect to see a
more extensive application of these techniques to
detect offending microbes in the eld of infectious uveitis and the yet-unknown microbes that
drive non-infectious uveitis.
10.7 Non-infectious Choroiditis
andRetinitis
Many rare non-infectious organ-specic immunemediated disorders cause inammation of the
retina, choroid, or both. They include multiple
evanescent white dot syndrome (MEWDS),
punctate inner choroidopathy (PIC), multifocal
choroiditis with panuveitis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE),
acute zonal occult outer retinopathy (AZOOR),
and Birdshot chorioretinopathy. Commonly,
Vogt-Koyanagi-Harada’s (VKH) disease and
sympathetic ophthalmia start rst in the choroid
and, during the disease, evolve into panuveitis
involving both the anterior segment and the posterior segment. Retina and choroid often get
involved in multisystem immune-mediated disorders such as systemic lupus erythematosus,
Behcet’s disease, and sarcoidosis.
10.7.1 Systemic Immune-Mediated
Disorders
10.7.1.1 Systemic Lupus
Erythematosus (SLE)
Retinopathy
Rheumatological diseases are autoimmune multisystem inammatory disorders, generally classied into arthritides, connective tissue disorders,
and vasculitides. All three have signicant, albeit
variable, ocular involvement in different disorders. Of the major connective tissue disorders,
namely SLE, scleroderma, polymyositis, dermatomyositis, and relapsing polychondritis, SLE is
the most common affecting the eye. SLE predominantly affects young female patients in a
ratio of 9:1. The incidence of SLE is ~5/100,000.
It is 4–5 times higher in black and Asian ethnic
groups than in the white races. The most characteristic feature of SLE is the development of
autoantibodies years before the onset of clinical
symptoms. The basic pathogenesis of SLE lies in
the failure to handle the intracellular antigens
(nucleosomes) from the apoptotic and necrotic
cells. The macrophages take up these intracellular antigens and present them to the T and B lymphocytes to activate innate and adaptive immune
responses to autoantigens [177]. Antinuclear
antibodies are present in all patients with SLE,
the highly specic anti-double stranded (ds)
DNA antibodies are present in 70% of patients
with SLE and only 0.5% of normal or even rheumatoid arthritis patients [178]. The level of the
anti-ds DNA antibodies reects the disease activity [179].
The anti-DS antibodies react with the released
extracellular nucleosomes and activate complements that get deposited on the basement membrane and can involve any tissue, most commonly
the kidneys, blood, and the brain. Any women
presenting from 15 to 50years of age with arthritis, skin rash, anaemia, thrombocytopenia,
nephritis, seizures, or psychosis need to have
SLE as a differential diagnosis [179]. The most
common external feature of the disease is a skin
malar rash. Nearly 33% of SLE patients have
ocular involvement [180]. Before the availability
of corticosteroids, nearly 50% of patients developed SLE retinopathy, but now the estimates vary
from 3% in the well-controlled disease to 29% in
the active disease [181]. SLE retinopathy is
caused by immune complex deposition. Using
immunouorescent techniques, on the autopsy of
a patient who had resolved SLE retinopathy,
immune complexes were found deposited on the
vascular walls of the entire choroidal vasculature,
arterioles in the ciliary processes, and basement
membrane of the bulbar conjunctiva [182]. SLE
retinopathy is characterized by bilateral multiple
cotton wool spots resulting from occlusion of the
precapillary arterioles and manifests as SLE
microangiopathy (see Chap. 3, Fig. 3.11).
SLE microangiopathy results from vascular
endothelial injury from the deposition of immune
complexes, leading to thrombosis. There may or
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10 Retinal andChoroidal Infections andInammation
may not be associated linear retinal haemorrhages. These changes are independent of hypertension, which is often present due to the
involvement of kidneys by lupus. In addition,
there may be infarcts in the visual pathways,
ischaemic optic neuropathy, and internuclear
ophthalmoplegia. There may be external eye
involvement in keratoconjunctivitis sicca,
episcleritis, or scleritis. There may also be small
retinal arteriolar occlusion and venous thrombosis. Vision-threatening para macular acute middle maculopathy (PAMM) reecting occlusion
of deep retinal capillary plexus in the macula
may be seen [183]. The retinal lesions in SLE
indicate active disease and are a marker for poor
survival. Nearly 75% of patients with SLE retinopathy have neuropsychiatric involvement
[184]. On FFA, the retinal arterioles show stump-
ing, indicating an obstruction to blood ow.
Extensive occlusion of the vessels may rarely
lead to the formation of new vessels on the optic
disc and elsewhere, termed proliferative SLE
retinopathy.
SLE may uncommonly present with choroidopathy, mostly bilateral, and presents with
multifocal serous detachments of the retina that
may mimic central serous chorioretinopathy
[185, 186]. Usually, they are associated with
active SLE disease. Choroidopathy may result
from the deposition of immune complexes, antibodies against the RPE, or micro-thrombotic
occlusion of choroidal vessels due to APLA.Most
reported patients had associated systemic associations such as nephritis, CNS lupus, and hypertension. There is pinpoint leakage of uorescein
dye on FFA, and the ICG angiography shows
non-lling of some of the choroidal vasculature.
The OCT shows thickening of the choroid with
loss of structural details and irregularities of the
overlying of the RPE along with a collection of
uid under the retina and cystoid spaces in the
outer plexiform layer [187].
Primary antiphospholipid syndrome (APS)
is an autoimmune disorder caused by developing antiphospholipid antibodies (APLA),
termed Lupus anticoagulant (LA), associated
with arterial, venous thrombosis, and recurrent
abortions. Secondary APLA is commonly asso-
ciated with other autoimmune diseases like
SLE and Sjogren’s syndrome. Arterial and
venous occlusions are signicantly more common in primary or secondary APLA than SLE
alone. While antinuclear antibodies (ANA)
may be equally common in APS and SLE, LA
is present in nearly two-thirds of the APS and
very rare in SLE alone. Moreover, anti-cardiolipin antibodies are present in APS, not SLE
[188]. It is essential to rule out APS if a retinal
arterial or venous occlusion or any retinopathy
is observed in a patient with SLE, as nearly
77% of patients of SLE who had retinopathy
had associated APS [189]. See Box 10.6 for the
classication criteria of SLE.
Box 10.6 Classication criteria for diagnosis
of SLE
Entry criteria
ANA + >1:80 on HEp-2 cells or equivalent
If ANA is absent, do not classify it as SLE
If present, apply additive criteria
Do not apply additive criteria if there is a more
likely explanation than SLE.Criteria
occurrence on even one occasion is sufcient.
They need not occur simultaneously. SLE
classication requires at least one clinical
criteria and >10 points. Within each domain,
only the highest weighted criteria are counted
Clinical domains and
criteria Weight
Constitutional 2
Fever
Haematologic
Leukopenia 3
Thrombocytopenia 4
Autoimmune
haemolysis 4
Neuropsychiatric
Delirium 2
Psychosis 3
Seizure 5
Immunological
domain and
criteria Weight
Antiphospholipid
antibodies
Anti-cardiolipin
antibodies OR
Anti-β2GP1
antibodies OR
Lupus
anticoagulant 2
Complement
proteins
Low C3 or Low
C4 3
Low C3 and C4 4
SLE-specic
antibodies
Anti-dsDNA
antibody Or
Anti-Smith
antibody 6
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Mucocutaneous
Non-scarring
alopecia 2
Oral ulcers 2
Subacute cutaneous or
discoid lupus 4
Acute cutaneous
lupus 6
Serosal
Pleural or pericardial
effusion 5
Acute pericarditis 6
Musculoskeletal
Joint involvement 6
Renal
Proteinuria
>05g/24h 4
Renal biopsy class II
OR 4
V lupus nephritis
Renal biopsy class III
OR
IV lupus nephritis 8
Classify as SLE with a score of 10 or more if
entry criterion is fullled
Adapted from Fig. 2 by Aringer etal.
[190] with permission of the publishers
10.7.1.2 Sarcoidosis
Sarcoidosis is a systemic multiorgan granulomatous inammatory disease that often involves the
lungs, lymph nodes and skin. It affects people
younger than 40years of age. The pathogenesis
of sarcoidosis is unknown, but as many as 2% of
people of Afro-American ancestry have a lifetime
risk of developing this disease. Compared to
Caucasians, Blacks suffer more severe diseases.
There are no denitive autoantibodies or markers
for diagnosing or monitoring this disease. The
granulomas are formed due to a Th1-type T-cell
oligoclonal immune response to a poorly degradable antigen. Many triggers, including viruses
(herpes, CMV, EBV, and retroviruses) or bacteria
(MTB, Propionibacterium acnes, and Borrelia
Burgdorferi), aluminium, zirconium, talc, pine
tree pollens, or even soil, have been incriminated
[191]. Sarcoidosis may mimic connective tissue
disorders, vasculitis, or even a simultaneous
autoimmune disease. Patients with sarcoidosis
235
may have subtle constitutional symptoms, like
low-grade fever, fatigue, cough, or breathlessness. Uncommonly, acute sarcoidosis may present as Lofgren syndrome characterized by fever,
hilar lymphadenopathy, erythema nodosum, and
ankle arthritis [192]. The lungs are involved in
>90% of patients, lymph nodes in ~33%, the liver
in 50–80%, eyes in 11–80%, CNS ~10%, skin
~25%, and less commonly may involve the heart
and muscles [191]. In a series of 364 patients
with sarcoid uveitis, more than 50% of patients
had lung parenchymal disease, cutaneous
involvement in 27% (lupus pernio, plaque-like,
or nodular skin lesions), ~and arthritis and CNS
in ~16%. Liver and cardiac involvement were
seen involvement in 5–6%. Caucasian patients
were older and had less granulomatous uveitis
and less skin involvement [193].
Patients with sarcoidosis may present rst to
the ophthalmologist with visual symptoms. There
are several, bilateral in nearly 90%, ocular signs
that suggest a granulomatous inammation of the
eye, including mutton fat keratic precipitates,
nodular iris granuloma in the inferior angle of the
anterior chamber with a tent-like peripheral anterior synechiae (Berlin’s nodule) [194, 195].
Koeppe’s nodules at the pupillary border, broad
posterior synechiae, vitritis with a string of pearls
snowball opacities in the inferior vitreous gel,
optic disc oedema, and focal nodular perivascular
inltrates like candle wax dripping, retinal arterial macroaneurysms, and choroidal granulomas
(Fig.10.14). In the external eye, they may also
present with a dry eye due to lacrimal gland sarcoidosis. The age of presentation of sarcoidosis is
shifting to a higher age in Western countries.
Notably, patients above 65 present have fewer
ocular signs than younger patients [196]. Taches
de bougie lesions (candle wax spots) may be seen
in nearly one-third of the ocular sarcoidosis as
yellowish white streaks or discreet white spots in
the inferior or inferonasal retina that may mimic
birdshot chorioretinopathy or multifocal chorioretinitis [197]. Taches de bougie is present in the
choroid in contrast to the perivascular candle wax
drippings in the retina. In a large series of sarcoid
uveitis, nearly two-thirds presented rst to the
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10 Retinal andChoroidal Infections andInammation
c
d
Fig. 10.14 Optic disc oedema (black arrow) and choroidal granulomas (blue arrows) in right (a) and left (b) eyes of a
patient with sarcoidosis. Peripheral examination also revealed choroidal granulomas in right (c) and left (d) eyes
ophthalmologist. Granulomatous anterior uveitis
was seen in ~48%, snowballs in vitreous ~46%,
multifocal choroiditis in 43%, periphlebitis in
21%, and isolated optic nerve or choroidal granuloma in 11% [193]. In a study of 48 patients with
multifocal choroiditis, 17% had retinal arteriolar
macroaneurysms, and half had histopathologically proven sarcoidosis. Arterial macroaneurysms in sarcoidosis are associated with severe
cardiovascular disease [198]. Most of these macroaneurysms are exudative [199].
Less commonly, sarcoid granuloma may be
located on the optic disc and consists of epithelioid cells [200]. The choroid is thickened in sarcoidosis, and a disproportionate enlargement of
the Sattler’s layer (medium vessels layer of the
choroid) in sarcoidosis can help differentiate it
from TB choroiditis [201]. Choroidal granulomas on OCT are uniformly hyporeective and
may occupy the choroid’s total or partial thickness (Fig. 10.15). Increased light transmission
posterior to these hyporeective spaces is a
unique sign in sarcoid granulomas. The OCT also
helps monitor the treatment response [202].
Sarcoidosis granulomas need to be differentiated
from tubercular choroidal granulomas. The latter
are often solitary, larger, lobulated, intense yellow in colour, perivascular inlocation, and vascularized (Fig. 10.11). Sarcoid granulomas are
often multiple, oval in shape, dull yellow, and do
not show retinal haemorrhages (Fig.10.14). They
remain under the RPE layer, unlike the TB granu-
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c
Fig. 10.15 A 59-year-old man, known case of skin sarcoidosis and calcied mediastinal lymph nodes, presented
with bilateral choroidal granulomas (black arrows; a, b).
On OCT, the sarcoid choroidal granulomas are uniformly
lomas that, on OCT, show hyperreectivity in the
outer retina indicative of the inltrative nature of
the TB granuloma [132–134].
d
hyporeective (blue arrows) and occupy the choroid’s
total or partial thickness (c, d). Increased light transmission is seen posterior to these hyporeective spaces
remains a histopathological demonstration of
non-caseating epithelioid cell granuloma from
any available disease site. In recent years, a minimally invasive technique of endobronchial
Diagnostic Criteria forOcular Sarcoidosis
An international workshop for ocular sarcoidosis
(IWOS) suggested criteria for making a diagnosis of conrmed ocular sarcoidosis (biopsy
proven); presumed—compatible uveitis with
bilateral hilar lymphadenopathy (BHL) but
biopsy not done; probable, no biopsy or BHL but
three clinical signs and two laboratory tests positive; and possible, no biopsy, no BHL but four
clinical signs and two laboratory tests [203].
However, in a large series of uveitis patients,
37% of those suspected to have sarcoidosis did
not meet these IWOS criteria, and except for
BHL, all clinical signs had low sensitivity [204].
The gold standard for diagnosing sarcoidosis
ultrasound- guided trans-bronchial needle aspiration (EBUS-TBNA) biopsy has been used with a
diagnostic accuracy of almost 80%. It is recommended as a routine for diagnosing sarcoidosis
wherever this facility is available [205]. The
IWOS revised their criteria once again [206].
More recently, using machine learning algorithms, the Standardization of Uveitis
Nomenclature (SUN) Working Group gave a new
classication for sarcoidosis-associated uveitis
with very high sensitivity and specicity for
diagnosing sarcoidosis-associated uveitis. [60–
63]. See Box 10.7 for investigations in a case of
sarcoidosis and Box 10.8 for SUN classication
criteria for diagnosis of sarcoidosis.
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10 Retinal andChoroidal Infections andInammation
Box 10.7 Investigation in a Patient with a
Suspected Diagnosis of Sarcoidosis or
Autoimmune Disease
Laboratories CBC; liver enzymes; creatinine;
BUN; uric acid; creatine kinase;
calcium; albumin; CRP
Protein-electrophoresis
ACE; sIL-2R
Urine analysis for proteinuria,
haematuria, and hypercalciuria
RF; ACPA; ANA or ENA; IgG4
25(OH)D, 1,25(OH)D3
Imaging tests X-ray chest; USG abdomen; CT
chest
Imaging studies of affected joints
if required
PET scan optional
Others Pulmonary function tests
ECG
Biopsy Mediastinal lymph nodes,
extrapulmonary nodes; skin lesion;
liver; kidney
CBC complete blood counts, BUN blood
urea nitrogen, CRP C-reactive proteins,
ACE angiotensin-converting enzyme, sIL-
2R soluble interleukin-2 receptor, RF rheu-
matoid factor, ACPA anti-citrullinated
peptide antibodies, ANA antinuclear antibodies, ENA extractable nuclear antigen
Adapted from Korsten P, Tampe B, Konig
MF, Nikiphorou E.Sarcoidosis and autoimmune diseases: differences, similarities and
overlaps. Curr Opin Pulm Med. 2018
Sep;24(5):504–512. https://doi.org/10.1097/
MCP.0000000000000500. PMID: 29985181
with permission of the publishers
Box 10.8 SUN Classication Criteria for
Diagnosis of Ocular Sarcoidosis
Criteria
Clinical Compatible uveitis
(a) Anterior
(b) Intermediate or anterior-
intermediate uveitis
(c) Posterior uveitis either
paucifocal or multifocal
choroiditis
(d) Panuveitis with choroiditis or
retinal vascular sheathing or
retinal vascular occlusion
Criteria
Evidence
Exclusion
1. Tissue biopsy demonstrating
non-caseating granuloma OR
2. BHL
1. Positive serology for syphilis
2. Evidence of infection with MTB
(a) Histological or microbiological
evidence of MTB OR
(b) Positive IGRA OR
(c) Positive tuberculin skin test
(>10mm induration)
SUN standardization of Uveitis
Nomenclature, BHL bilateral hilar lymphadenopathy, MTB mycobacterium tuberculosis, IGRA interferon-γ release assay
Adapted from Standardization of
Uveitis Nomenclature (SUN) Working
Group. Classication Criteria for
Sarcoidosis-Associated Uveitis, 2021.
With permission of the publishers
10.7.1.3 Behçet’s Syndrome
Epidemiology andGenetic Predisposition
ofBehçet’s Syndrome
Behçet’s syndrome (BS) is a multisystem autoinammatory disorder seen worldwide, although
its prevalence varies widely across regions. It is
the most common cause of blinding panuveitis in
regions along the old trading ‘silk route’ that
extends from the countries around the
Mediterranean Sea to the Middle East and the Far
East. Its prevalence progressively decreases from
a high of ~400 people per 100,000 population in
North Turkey to 13.5 to 20/100,000 population in
Saudi Arabia, Iran, China, and Japan and still
lowers in the UK (0.64/100,000) and is least
common in the USA (0.12–0.33/100,000). In
Germany, its prevalence is estimated at
21/100,000 in people of Turkish origin versus
0.42–0.55/100,000 native Germans [207]. There
is no single test to diagnose BS, but there is a
strong association of BD with HLA-B*5101, and
the prevalence of BS in the population runs parallel with the prevalence of this allele [208]. The
highest prevalence of the HLA-B*51 allele is
seen in Turkey and Saudi Arabia, where 24–26%
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