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population has this allele versus 18–22% in
Japan, 7.6–8.13% in India, 2.2–8.8 in different
regions of China, and only 0.5% in Zimbabwe
[209]. Notably, anecdotal cases have been
reported from people of West African and AfroCaribbean origin living for several years in the
UK [209]. The exact aetiology remains unknown,
but infectious antigen(s) (environmental factors)
probably precipitate the disease in genetically
predisposed people [210]. In the Japanese population, the frequency of HLA-B*51 varies according to the cluster of the symptom complex, with
50–52% in the dominant mucocutaneous, mucocutaneous arthritis, ocular, and CNS clusters
compared to only 33% in the GI dominant BS
[210]. Notably, with the rising number of women
in their population, the HLA-B*51 frequency is
decreasing.
Pathology ofBehçet’s Syndrome
The hallmark of Behcet’s syndrome is the activation of neutrophils and expression of intercellular
adhesion molecules on the endothelial cell lining
of the blood vessels prompting the activated neutrophils and RBCs to extravasate from the vessels. Practically, all involved organs in BS show a
signicant inltration with neutrophils. The other
characteristic feature is the venous occlusions,
likely related to the factor V Leiden mutation,
which is seen more frequently in patients of BS
with venous thrombosis [211].
There is a 14-fold rise in the risk of venous
thrombosis in Behçet’s syndrome compared to
the normal controls [212]. All BS lesions in different organs show almost similar pathological
changes. There is upregulation of cytokines like
TNF-α, IL-Iβ, and Il-8 that are known to activate
neutrophils. There are also increased levels of
myeloperoxidase, which is generated by the neutrophils [208].
Systemic Signs ofBehçet’s Syndrome
The BS is characterized by recurrent panuveitis
and oral and genital aphthous ulcers. Till 2018,
Behçet’s syndrome was known as Behçet’s disease when the nomenclature was changed from a
disease to a syndrome. The experts believe that
Behçet’s is not a single disease but a symptom
complex with great variations in organ involvement in various regional and familial clusters
[213]. There are fewer gastrointestinal symptoms
in the Mediterranean basin, increased frequency
of arthritis and skin ulcers in the familial cohorts
in Japan, and less severe eye disease in the BS
patients in the US and North European countries
[214]. It is essentially a heterogeneous multisystem vasculitis affecting both the arteries (involvement of the vasa vasorum of large arteries leads
to arterial aneurysms) and the veins (venous
thrombosis) of all sizes. It runs a relapsing and
remitting course and, besides the eye, involves
skin (papulopustular or acne-like lesions, erythema nodosum and leg ulcers), joints (nondeforming acute mono- or poly-polyarthritis),
gastrointestinal tract (inammatory bowel disease), and central nervous system (parenchymal
disease or venous thrombosis). It is predominantly seen in men in their early 20s to 30s who
also carry a worse outcome than women. The
involvement of the various organs may occur
over several years. Besides, it runs a variable
course and may sometimes show spontaneous
remission. For these reasons, the treatment has to
be organ-specic and individualized depending
upon the severity of involvement. In general, the
involvement of the skin, mucosa, and joints carries a much better prognosis than the involvement
of the eyes, GI tract, and CNS [213]. It is now
believed that the HLA-B*51 haplotype, which is
closely associated with this syndrome, determines the clinical spectrum of the disease.
Recurrent, painful oral ulcers on the tongue,
buccal, or labial mucosa, lasting for 7–10days,
are almost always present during the disease and
may precede the onset of BS in other organs by
years. Genial ulcers are seen on the scrotum and
penis in men and the vulva in women, and anal
ulcers may occur in both sexes. These are recurrent, painful, and larger than in the oral cavity.
Genital ulcers usually heal with scarring, unlike
oral ulcers, which do not leave behind any scarring. Other systemic involvement includes supercial venous thrombosis in the legs and arms,
erythema nodosum, pseudofolliculitis, acneiform
lesions, and ulceration [207]. Large joints may be
involved as non-deforming mono- or polyarthri-
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10 Retinal andChoroidal Infections andInammation
a
Fig. 10.16 Hypopyon (blue arrow) in a patient with Behcet’s disease (a), which is shifting in nature (b), who had oral
ulcers (black arrow; c)
tis. Patients may have inammatory bowel disease (IBD) that mimics ulcerative colitis or
Crohn’s disease and present with diarrhoea or
even GI perforation. HLA typing, the phenotype
of uveitis and GI biopsy, may help distinguish the
BS from other causes of IBD.A variety of nervous system symptoms, including meningitis,
meningoencephalitis, venous thrombosis and
brainstem involvement, may be seen in some
patients. Neuropsychiatric symptoms ultimately
lead to symptoms of dementia.
b
or manifestation of the BS in about 20% of the
cases. It is important to recognize this entity at
the outset to prevent the long-term consequences
of the disease (Tugal-Tutkun, 2022). BS uveitis
may present as a painless, recurrent, and mobile
hypopyon in one-third of the patients. In BS uveitis, the level of the hypopyon shifts with head
tilting (Fig.10.16). It is due to a lack of brin in
the BS uveitis, unlike the painful acute anterior
uveitis associated with HLA-B27 disease, in
which the most dominant sign is a severe brin-
c
ous reaction and a non-shifting streak hypopyon.
Ocular Signs ofBehçet’s Syndrome
In our single-centre experience in India from
1990 to 2006, BS was seen in 53 (1.25%) of the
4214 patients with uveitis [215]. It was seen as
nearly three times more common in men than
women at the mean age of 27 years (range
10–62years). Ocular involvement was the most
common in 92.4%, followed by oral ulcers in
88.7%, genital ulcers in 61.2%, skin lesions (erythema nodosum, acne, and folliculitis), and
arthritis in 28.3% each. In our cohort, GI tract,
CNS, and epididymis involvement was rare and
seen only in two (3.7%) patients each.
In our experience, presenting ocular signs
were panuveitis (57.1%), followed by posterior
uveitis (26.5%) and anterior uveitis (16.3%)
[215]. Although our cohort was much smaller
than the Turkish report of 880 patients with BS,
the ocular and systemic involvement was almost
similar in the two cohorts [216]. The ocular
involvement usually follows oral aphthous
ulcers. However, it may be important to note that
ocular involvement may be the rst presentation
The anterior uveitis in BS is non-granulomatous.
Granulomatous reactions, such as mutton fat
keratic precipitates, rule out the BS.The vitreous
inammatory reaction is variable. The most
sight-threatening complication of BS uveitis is
retinal vasculitis, which involves all retinal
veins, capillaries, and retinal arterioles
(Fig.10.17). The complications include cystoid
macular oedema (55.1%), occlusive vasculitis
(44.8%), and optic atrophy (26.5%) [215]. There
is a signicant vitreous haze due to inammatory cell inltration of the vitreous gel, which
may settle down as pearls. The retinal signs
include transient greyish-white retinitis patches,
which resolve without leaving any scarring. The
vessels show perivascular inltrates and a variable amount of haemorrhages. Retinal branch
vein occlusions are more common than arterial
occlusions. The retinal perivascular leakage and
staining of the vessel walls of all types of small
or large vessels characterize the fundus uorescein angiography (FFA) in BS uveitis
(Fig.10.17). The ‘fern-like’ pattern of the retinal
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a
c
b
d
Fig. 10.17 A patient with Behcet’s disease presented with hypopyon (blue arrows; a), which was shifting in nature (b).
Fluorescein angiography showed leakage from vessels in fern pattern suggestive of active vasculitis in both eyes (c, d)
capillary leakage highly suggests subclinical
inammatory activity. Along with laser are
photometry, it is an important sign in apparently
quiescent eyes, as these signs indicate an
impending recurrence [217]. The FFA is also
helpful in detecting and monitoring retinal vascular occlusions, capillary non-perfusion, and
the development of new vessels. In recent years,
ultra-wide-eld FFA has been used to monitor
the response to therapy [218]. Optical coherence
tomography (OCT) helps detect cystoid macular
oedema, frequently complicating Behçet’s uveitis. It may also show defects in the ellipsoid
zone, which may serve as a predictive sign for
the nal visual outcome. The OCT additionally
may show defects in the external limiting membrane, RPE and epiretinal membrane disruption,
and macular atrophy [219]. The role of OCT
angiography is limited in BS uveitis as the most
sensitive parameter of the disease activity; i.e.,
the retinal capillary leaks cannot be seen on
OCTA.However, a recent meta-analysis showed
that OCTA might be a valuable tool to monitor
BS activity as it shows a decreased retinal capillary density in the supercial and deep capillary
plexus in the macula, fovea, and parafovea [220].
The role of indocyanine green angiography
(ICG) and fundus autouorescence is limited as
these do not provide any helpful information.
Notably, Behçet’s disease does not cause choroiditis, and if choroiditis is seen in BS suspects
patients, we need to rule out syphilis and sarcoidosis as possible aetiology. See Box 10.9 for
the classication criteria of Behcet’s disease.
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Box 10.9 Classication Criteria for Behςet’s
Uveitis
Criteria
1 Compatible uveitis syndrome
(a) Anterior uveitis
(b) Anterior and intermediate uveitis
(c) Posterior uveitis with retinal vasculitis
and/or focal retinal inltrates
(d) Panuveitis with retinal vasculitis and/
or focal retinal inltrates
2
A diagnosis of Behςet’s disease using ISG
for Behςet’s disease criteria
Recurrent oral ulcers observed by physician
or patient at least three times in one
12-month period
Plus any of the two criteria
(a) Recurrent genital ulceration or
scarring observed by physician or
patient
(b) Uveitis (anterior uveitis, posterior
uveitis, or vitreous cells on slit-lamp
examination or retinal vasculitis
observed by physician)
(c) Skin lesions (EN observed by patient
or physician; pseudofolliculitis or
papulopustular lesions or acneiform
nodules observed by the physician in
post-adolescent patients, not on
corticosteroid treatment
(d) Positive pathergy test read by
physician at 24–48h
Behςet’s uveitis is diagnosed when criteria 1 and
2 are met
ISG International study group for
Behςet’s disease, EN erythema nodosum
a
Presence of choroiditis rules out
Behςet’s uveitis
Source:
1. Adapted from Standardization of
Uveitis Nomenclature (SUN)
Working Group. Classication
Criteria for Behçet Disease Uveitis,
2021. With permission from the
publishers
2. Adapted from Criteria for diagnosis
of Behçet’s disease. International
Study Group for Behçet's Disease,
1990. With permission from the publishers [221]
10 Retinal andChoroidal Infections andInammation
Therapy ofBehçet’s Uveitis
The BS is a highly heterogeneous syndrome;
hence, a multidisciplinary approach is required to
diagnose, treat, and monitor response to therapy.
Depending on the severity, as various systems
may get affected over a considerable period, the
therapy will usually be directed to the affected
a
system. In the past, the treatment consisting of
oral corticosteroids combined with immunomodulatory agents like cyclosporine or azathioprine has been used to control acute inammation
rapidly. The treatment goals in BS have been to
achieve a temporary remission of inammation,
prevent recurrences and minimize complications.
In recent years, increasingly biological agents
like interferon-α and TNF-α blocking agents (infliximab or adalimumab) are being used to treat,
especially the refractory cases of BS [222].
Tocilizumab has been used in patients who fail to
respond to the anti-TNF-α antibodies. Although
highly effective in uveitis, vascular and neurological disease is ineffective in many cases with
oral or genital ulceration, arthritis, and skin and
GI lesions. It worsened some of these patients’
skin and oro-genital ulcers [223]. More recently,
in a small pilot study of refractory Behçet’s uveitis, cases have been successfully treated with
tofacitinib, a JAK1/3 inhibitor, which targets
both the innate and adaptive immune responses.
It was suggested that being a small molecule, it
can cross the blood-retinal barrier more efciently than other biological agents. However,
previously it failed to control the GI involvement
in the BS [224]. These experiences strengthen the
treatment philosophy of BS that being a highly
heterogeneous disease, multiple inammatory
mechanisms may be involved in various systems,
and therapeutic options should be chosen, keeping this fact in mind.
Visual Outcome ofBehçet’s Syndrome
BS is one of the most sight-threatening panuveitis. Thirty-eight per cent of the eyes in our own
experience had less than 6/60 visual acuity at the
nal follow-up [215]. Likewise, most patients
had panuveitis and bilateral involvement in a
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large international cohort with BS.At the nal
follow-up, 23–25% of these patients had less
than 20/200 in the better eye. Men who were
HLA-B 51 positive disease had more severe and
blinding disease compared to women [225].
10.7.2 Organ-Specic (Ocular)
Immune-Mediated Panuveitis
withMultisystem Involvement
10.7.2.1 Vogt-Koyanagi-Harada
(VKH) Disease
VKH disease is one of the most common causes
of panuveitis and posterior uveitis in Asian and
Hispanic populations and is distinctly uncommon
in Caucasians. Although cases had been described
independently in Japan by Vogt, Koyanagi, and
Harada in the early decades of the twentieth century, it was only in the 1950s that a commonality
was found in these cases, and the term VKH syndrome was coined. Its description as a ‘syndrome’ was replaced by ‘disease’ by the rst
international workshop on VKH disease held in
1999, which met to dene its diagnostic criteria
[226].
The VKH disease is characterized by an
autoimmune T-cell response to tyrosinase family proteins contained in the melanocytes
[227]. An experimental rat model of VKH dis-
ease has been successfully created by immunizing rats with tyrosinase family proteins
[228]. Melanocytes are responsible for the
colour of the skin and hair and also present in
the meninges, choroid, and inner ear, and
hence, the symptoms and signs in the VKH disease relate to these tissues. In the skin, the
melanocytes are destroyed by an autoimmune
response leading to the formation of vitiligo
patches. Skin biopsy from skin vitiligo patches
in patients with VKH disease revealed HLA-DR
expressing T cells and CD4+ dominating over
CD8+ T cells in a ratio of 3:1 [229]. In a rat
model, electron microscopy showed an accumulation of lymphocytes and epithelioid cells
around choroidal melanocytes [230]. In several
populations, it has been associated with HLA-
DRB1*0405, indicating a racial and genetic
predilection. The exact trigger that causes loss
of tolerance to the melanocytes is unknown.
Exceptional cases of minor skin abrasions
precipitating VKH have been reported [122,
124, 231]. VKH has followed vaccinations
against BCG, hepatitis B and yellow fever, and
viral infections such as the inuenza A virus
[232]. COVID-19 infection has led to the acute
onset of VKH disease [233]. Even the administration of inactivated COVID-19 vaccine has
not only led to the occurrence of the VKH disease [234] but an exacerbation of the existing
VKH disease [235].
Interestingly, immune checkpoint inhibitors
(ICIs) in patients with malignant melanoma have
led to a picture mimicking VKH disease, including patients who developed alopecia, vitiligo,
poliosis, exudative retinal detachment, and
chronic uveitis [232]. The retinal detachment
responded to the use of corticosteroids. The
development of VKH-like disease following the
use of CII was associated with regression of the
melanomas and is considered an indicator of a
good prognosis for the outcome of melanoma
[236].
Clinical Presentations ofVKH Disease
VKH disease has no specic diagnostic laboratory test; hence, clinical signs and symptoms are
used to diagnose and classify VKH disease.
Because of its spectrum of involving multiple
systems has been classied as a complete, incomplete, or probable VKH disease [230]. See Box
10.10.
Box 10.10 Revised Diagnostic Criteria for
Vogt-Koyanagi-Harada Disease
1. No history of penetrating trauma or
intraocular surgery before the onset of
intraocular inammation
2. No clinical or laboratory evidence of any
other disease
3. Bilateral involvement (a) OR (b) must be
met
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(a) Early Manifestation:
I. Fundus examination: diffuse
choroiditis, focal areas of SRF,
bullous SRD
OR If fundus exam is equivocal
II. FFA signs of focal areas of delayed
choroidal perfusion, pinpoint focal
leakage, large placoid
hyperuorescence, and pooling of
dye AND
III. Diffuse choroidal thickening on
USG.Rule out posterior scleritis
(a) Late manifestations: History
suggestive of prior disease as in (a).
I. Sunset glow fundus; Sugiura’s sign
II. Nummular chorioretinal
depigmented scars; recurrent or
chronic anterior uveitis
4. Neurological sSymptoms: meningismus,
tinnitus or CSF pleocytosis (may have
resolved)
5. Integumentary sSigns: Must appear
after the onset of ocular inammation
Vitiligo, poliosis, or alopecia
Complete VKH Disease: All the ve criteria
are present
Incomplete VKH Disease: criteria 1, 2, and 3
with either 4 or 5
Probable VKH Disease: criteria 1 to 3 are
met
Adapted from: O’Keefe GA, Rao
NA.Vogt-Koyanagi-Harada disease. Surv
Ophthalmol. 2017 Jan-Feb;62(1):1–25.
https://doi.org/10.1016/j.survophthal.2016.05.002. Epub 2016 May 27.
PMID: 27241814 with permission of the
publishers
In a review of 120 patients with VKH disease
seen in 10years in our clinic from 2003–2012, it
predominantly affected young women (W:M:2:1)
at an average age of 35years (range of 6–70years)
(unpublished data). We reached a diagnosis of
probable VKH disease in 61% of the patients,
incomplete VKH in 34%, and complete VKH disease only in 5% of the patients. The most differentiating features of VKH from other panuveitis
are the nearly universal presence of bilateral exudative retinal detachment in the acute stage and
sunset glow fundus in the chronic stage. The
positive predictive value (PPV) of bilateral exu-
10 Retinal andChoroidal Infections andInammation
dative retinal detachment in non-traumatic settings is 100% and the negative predictive value
(NPV) of 88.4%. The PPV of sunset glow fundus
was 94.5% and the NPV of 89.4% [237].
Irrespective of whether the VKH disease has
been classied as complete, incomplete, or probable, it runs through a course of four stages [230].
These are (1) prodromal; (2) acute uveitic; (3)
convalescent; and (4) chronic recurrent.
Prodromal Stage ofVKH Disease
The prodromal stage of the VKH disease is
characterized by symptoms suggestive of meningismus and includes headache, neck stiffness,
nausea, and dysacusis (inability to perceive
higher frequencies), which lasts for several days
or weeks. The neck stiffness and headache
symptoms may be so severe to land the patient
in a neurology clinic. In a Japanese study, 84%
of the patients in the prodromal stage showed
lymphocytic pleocytosis in the cerebrospinal
uid (CSF), and 74% showed dysacusis [238].
However, being an invasive procedure, experts
in many regions of the world do not currently
insist on doing a CSF tap in patients suspected
of the VKH disease. A simpler test is doing pure
tone audiometry, which reveals loss of highfrequency sounds in nearly third-fourth of
patients in the prodromal stage. The CSF
changes and the audiometry changes persist
well into the next stage, which brings the
patients to the ophthalmologists.
Acute Uveitic Stage ofVKH Disease
Some patients may not develop the prodromal
stage and directly present with an acute uveitic
stage characterized by multifocal exudative retinal detachments, which are always simultaneously bilateral. If unilateral, the contralateral eye
may follow a few days later (Fig. 10.18a, b).
There may be a presence of inammatory cells in
the anterior chamber and the vitreous cavity. This
sign has 100% PPV for the diagnosis of VKH
disease. The FFA shows the presence of initial
patchy delayed lling of the choroid followed by
numerous pinpoint leaks from the RPE and pooling of uorescein dye in the subretinal space
(Fig.10.18c, d). A large majority of patients also
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a
e
b
f
Fig. 10.18 Multifocal exudative retinal detachment in
the acute uveitic stage of VKH disease in the right eye (a).
The left eye looks clinically normal (b). Fluorescein angiography of the right eye shows hypouorescent granulo-
show optic disc hyperuorescence. The ICG
angiography shows hypouorescent spots in the
early frames and remains hypouorescent even in
the late frames, suggestive of full-thickness stromal granulomas in the VKH disease (Fig.10.18e,
f) [239]. With aggressive therapy, these dark
spots disappear only to appear later as the dose of
corticosteroids is tapered, suggesting a subclinical recurrence of the disease [239].
mas in the early phase (c), with pinpoint leaks in the late
phase (d). ICG angiography shows hypocyanescent spots
in the right (e) and left (f) eyes
Ultrasonography, if done at this stage, will show
highly pathognomonic thickening of the choroid,
which is maximum in the peripapillary choroid
and shows progressive tapering towards the
periphery [65, 66]. It corresponds to the distribution of the melanocytes in the choroid, which are
found maximum in the peripapillary choroid and
progressively decrease towards the periphery.
The enhanced depth imaging in OCT (EDI-OCT)
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10 Retinal andChoroidal Infections andInammation
shows choroidal thickening along with pockets of
serous subretinal uid. The EDI-OCT can also be
used to monitor the response to treatment and for
regular follow-up [240]. Even before the patient
becomes symptomatic with visual disturbance or
return of inammation, the EDI-OCT may indicate a disease recurrence by showing a thickening of the choroid. The swept-source OCT reveals
bacillary layer detachment in more than 90% of
the eyes, indicating a split in the myoid zone of
the inner segments of the photoreceptors, a sign
of inammatory uid collection [132–134].
Choroidal striations may be seen in the acute
uveitic stage of the VKH disease due to choroidal
thickening, which on FFA are seen as hypouorescent lines. On OCT 3D mapping, undulations
of the RPE are seen, which correspond to the
choroidal striations [241]. Nearly 50% of older
a
women may also develop a rise in intraocular
pressure in the acute uveitic stage.
Convalescent Stage ofVKH Disease
The eye enters a convalescent stage several weeks
after the acute uveitis phase. During this time, the
eye loses pigment in the choroid and appears
orange-red, a highly sensitive and specic sign of
the VKH disease termed the ‘sunset’ glow fundus
(Fig.10.19). Patients also develop integumentary
changes during this stage, namely vitiligo (common site is the lower back) of the skin, poliosis
(greying of the eyelashes), and patchy alopecia
(Fig.10.20a, b). The retinal periphery also shows
nummular scars (Fig. 10.20c, d). Since most
patients are treated with intensive corticosteroids
and immunomodulatory therapy during the acute
uveitis phase, the integumentary changes are not
b
Fig. 10.19 Optic disc oedema (black arrows) with subclinical choroidal granulomas in acute presentation of VKH
disease (a and b). Five years later, the patient developed sunset glow fundus and peripapillary atrophy (c, d)
cd
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a
b
Fig. 10.20 Integumentary changes in chronic recurrent VKH, seen as vitiligo (blue arrows) and poliosis (inset), with
sunset glow fundus (a, b). Nummular scars are seen in the periphery (c, d)
seen as frequently as recorded in the past. In our
experience with the following 120 patients, only
5% developed integumentary changes. Nearly
31% of the patients who presented to us in the
chronic recurrent phase may develop subretinal
brosis within a median time of 6.5months from
the diagnosis in Hispanic population versus
6.5years in the non-Hispanic population [242].
acute uveitic stage developed sunset glow
fundus.
Complications ofAcute Versus Late
Presentation ofVKH
Chronic Recurrent Stage ofVKH Disease
After several months, especially in those who
have either early withdrawal or quick tapering of
corticosteroids, patients enter into a chronic
recurrent stage characterized by granulomatous
anterior uveitis with keratic precipitates and
development of posterior synechiae. During this
stage, the patient may develop pigmentary
changes and peripapillary atrophy, which may
get complicated by the development of juxtapapillary CNV. Uncommonly, VKH eyes in the
Patients of VKH disease need early and highly
aggressive therapy. Patients with aggressive therapy can be prevented from entering the chronic
recurrent stage of VKH disease. Starting aggressive therapy when the patients have already
reached the recurrent stage does not help in the
further progression of various complications.
Nearly one-third of the VKH disease patients
presented to us in the chronic recurrent stage of
VKH disease (unpublished data). The sunset
glow fundus was already present in 67% of the
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10 Retinal andChoroidal Infections andInammation
eyes, and by the end of the follow-up, 79% of the
eyes had developed this sign.
Further, 44% of eyes already had peripapillary
atrophy, which increased to 62% of the eyes by
the end of the follow-up. Nummular scars were
present in 56% and increased to 76%. CNV had
already complicated 5% of the eyes, and by the
end of follow-up, 15% of these eyes had developed CNV.In contrast, in patients who reached
us in the acute uveitic stage, no eye had sunset
glow fundus, peripapillary atrophy or nummular
scars at presentation. By the end of the follow-up,
these patients who were intensively treated by us
using induction therapy with intravenous methylprednisolone, followed by high-dose oral corticosteroids with slow tapering and institution of
steroid-sparing immunomodulatory therapy, signicantly less number of eyes developed sunset
glow fundus (31%), peripapillary atrophy (27%),
nummular scars (7%) and CNV (3%). With
aggressive therapy, nearly 75% of the eyes
attained 6/12 or better visual acuity.
10.7.2.2 Sympathetic Ophthalmia
Epidemiology ofSympathetic
Ophthalmia(SO)
Sympathetic ophthalmia (SO) in the present
times is extremely rare. A bilateral organ-specic
autoimmune granulomatous pan uveitis follows
penetrating ocular injuries or intraocular surgery.
It is potentially a blinding disorder in one or both
eyes if not detected, prevented, and treated appropriately. SO is a highly uncommon complication
of penetrating ocular trauma and intraocular surgeries, especially glaucoma incisional and pars
plana vitreous surgery. Intraocular surgery, especially vitreoretinal procedures, has become the
dominant cause of SO in recent years. In a prospective surveillance study, the incidence of SO
was 0.03/100,000 population [243]. Of the 18
patients for whom data were available, 11 followed surgery, and half followed retinal surgeries. Only seven patients of SO followed
penetrating trauma. It is in sharp contrast to the
earlier reports that suggested that 14–50% of all
eye injuries sustained in the nineteenth-century
wars developed SO [244]. In the pre-operating
microscope era, Allen did not nd a single case of
SO among cataract surgeries done from 1933 to
1965in his hospital. However, he did nd 0.07%
of all glaucoma surgeries, specically 0.4% of
the iris inclusion surgery (then a popular incisional glaucoma surgery) and 0.3 of all ocular
injuries to develop SO [244]. Gass reported that
over 5years, every 2 of the 1000 enucleated eyeballs in the US pathology laboratories had evidence of SO [245]. Of the 53 eyes harbouring
SO, 55% had sustained trauma, and 45% had
undergone surgery [245]. In the National Eye
Institute, Bethesda, USA, 32 cases of SO were
seen over 10years, of whom 23 followed trauma
and nine followed surgery [246]. Prompt and
meticulous repair of open globe injuries using
modern microsurgical techniques has signicantly reduced the risk of SO following trauma.
However, it remains high at 0.24% in children
who sustain open globe injuries [247]. Among all
the ocular surgical procedures, the risk of repeat
surgeries on the same eye is maximum with the
vitreoretinal procedures with an attendant
increasing risk of SO.Gass calculated that 0.06
of all vitreous surgeries were complicated by SO
[245]. While only 0.008% of patients developed
SO after a single vitreoretinal surgery, the risk of
developing SO increased to 6.67% with seven
procedures on the same eye [248].
Pathogenesis andPathology ofSO
The intraocular compartments lack lymphatics.
Thus, the most critical step is the leakage of
sequestrated soluble retinal antigens into the subconjunctival space following penetration of the
ocular coats from where these are drained to the
regional lymph nodes [249] followed by a T-cellmediated immune response in both the exciting
and sympathizing eyes. When injected in the subconjunctival space with a bacterial adjuvant, the
soluble retinal antigen produced granulomatous
uveitis but not when injected directly into the eye
[249]. It also explains why the delay in repairing
an open penetrating wound of the eye increases
the risk of SO compared to those repaired within
24h. Not only are the surfaces of the injured eye
contaminated with bacteria, but the cell walls of
the dead commensal bacteria may also act as
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