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a
Fig. 10.2 On OCT, the retinitis lesion shows the retinal
layers’ hyperreectivity and disorganization (red arrows)
(a). Choroiditis lesions (granulomas) are associated with
exudative subretinal uid (blue arrow) with a bumpy ele-
a
b
vation of the (yellow arrow) of the RPE-Bruch’s complex
(b). Note inltration of the outer retina from the choroidal
granuloma in (b)
b
Fig. 10.3 Retinitis lesions (a) heal with only minimum pigmentary changes, whereas the choroiditis lesions (b) heal
with heavily pigmented scars (blue arrow)
tomography (OCT) can easily differentiate
between retinitis, retinochoroiditis, choroiditis,
and chorioretinitis.
10.6 Infectious Uveitis
10.6.1 Toxoplasmic Retinochoroiditis
10.6.1.1 Prevalence
Toxoplasmosis, a zoonotic disease, is acquired
by humans by consumption of raw/undercooked
meat or contamination of food with oocysts
passed in the cats’ litter box. Contaminated
municipal water supplies have led to an outbreak
of toxoplasmosis epidemic [10]. The infection
may also be acquired via the transplacental route
from the mothers who get infected during pregnancy or rarely through organ transplants.
Contrary to the long-held popular belief that
toxoplasmosis is a congenital infection, most
cases are now believed to be acquired after birth.
This obligate unicellular parasite poses a
global challenge, with nearly 25–30% of the
world’s population seropositive for toxoplasmosis. It remains the most common cause of infectious uveitis in Brazil, France, and most of the
Western world [11]. It is one infection that is preventable by taking appropriate hygienic measures while handling cats’ litter, not eating raw
meat, and ensuring clean drinking water. Its prevalence in uveitis clinic patients in different
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10 Retinal andChoroidal Infections andInammation
regions and periods in the USA has shown a
declining trend from 10 to 2.8% [12–16]. It is
estimated to cause nearly 20,000 cases of ocular
infection in the US population yearly [17]. In
European and certain Asian countries, toxoplasma rates have varied from a high of 39% [18]
to a low of 2. 3% [19], while the majority have
reported the prevalence of toxoplasmic retinochoroiditis in the uveitis clinic to vary from 6 to
10% ([20–30].
From India, the rates have varied from 12% in
East India [31] and 8.6–2.5% in South India [32,
33]. In single-centre prevalence studies, a signi-
cant decline has been noted in both South India
(8.6–5.12%; [34]) and North India (1.69–0.66%;
[35, 36]). Very low toxoplasmic retinochoroiditis
was also noted in New Delhi, India (0.91%; [37]).
10.6.1.2 Mechanisms ofToxoplasma
gondii Infection
Toxoplasma gondii is the subject of intensive
studies to address some of the most fundamental
questions—how does it reach the eyes, what cells
play host to the parasite, how does it remain
sequestrated in the retina and other organs, and
what leads to egress of the parasites from the host
cells to cause inammation. Following ingestion,
the oocysts (from the faeces) or the tissue cysts,
the bradyzoites (undercooked meat), and the sporozoites (highly infectious dormant forms of T.
gondii) are released from the oocysts that invade
the epithelial lining of the intestines and multiply
to form the motile tachyzoites (fast replicating).
Once released from the tissue cysts (bradyzoites),
the tachyzoites enter the circulation either as free
or riding in the leucocytes and get widely disseminated to various tissues (muscles, brain, and
heart), including the retina [38]. Recently, the
pathogenesis of ocular toxoplasmosis was extensively reviewed [39]. The tachyzoites released in
the gut must breach the gut epithelial barrier,
where they rst adhere and then transmigrate
through the epithelium into the lamina propria
[40]. The T. gondii release nanoparticle-sized
exosomes containing HSP 70, a chaperone protein, and CD63 protein along with surface marker
protein, the P30, and induce expression of IL-12
and TNF-α, which leads to macrophage activa-
tion [41]. In the eye, T. gondii primarily attacks
the retina, where it rst adheres and traverses the
retinal capillary endothelium through a transcellular or an intercellular path [42]. Unlike in the
brain, where the neurons are the preferred host, in
the retina, the most preferred cell for sequestration is Muller glial cells. It also infects the RPE
cells and leads to the proliferation of the uninfected RPE cells [39].
10.6.1.3 Clinical Diagnosis
ofToxoplasma
Retinochoroiditis
Of all the infectious uveitis, diagnosis of toxoplasma retinochoroiditis is the least challenging
when presenting in immunocompetent patients.
The retinal lesion in such patients is characterized by intense focal retinitis, usually smaller
than one-disc size, with an overlying intense vitreous reaction leading to the ‘lamp in the fog’
appearance (Fig.10.1a). There have been recent
developments that facilitate making a clinical
diagnosis of this infection. The unique focal vitreous reaction seen in toxoplasma retinochoroiditis can be appreciated by structural OCT
that shows the hyperreective dots in front of
the retinitis lesion. There is complete disorganization and thickening of the affected neurosensory retinal layers (Fig. 10.2) and choroidal
swelling with hyporeective spaces under the
retinal lesion. The presence of hyporeective
spaces in the retina due to liquefactive necrosis,
if present, suggests a poor visual outcome [43].
Coagulative necrosis is a hallmark of the pathology of toxoplasmic retinitis. In fulminant cases,
there may be complete necrosis of the neurosensory retina with sparing of the ILM, as is also
observed in cases of subacute sclerosing panencephalitis (SSPE) [44, 45]. Even the retinal arterioles away from the lesion may show highly
characteristic peri-arterial plaques called the
Kyrieleis (Fig.10.4). On FFA, the retinal vessels within the retinitis lesion tend to show
intense staining (Fig.10.1b). These lesions may
be isolated when acquired, but the recurrences
are often seen next to a healed pigmented atrophic chorioretinal scar (Fig. 10.5) [46]. In
patients with HIV infection, the toxoplasmosis
ab
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lesions are often bilateral, multifocal, and extensive and may mimic other retinal infections
caused by the herpes viruses [47].
10.6.1.4 Laboratory Diagnosis
ofToxoplasmic
Retinochoroiditis
Laboratory diagnosis of toxoplasmic retinochoroiditis has remained clinical, aided by a positive
serology for IgG or IgM antibodies. A negative
serology helps to rule out the toxoplasmic aetiology of focal retinitis. Circulating tachyzoites of the
T. gondii have been detected in the blood of
Fig. 10.4 In toxoplasmic retinal infection, the retinal
arterioles (blue arrows) away from the retinitis lesion
(black arrow) show highly characteristic peri-arterial
plaques called the Kyrieleis plaques
patients with acute or chronically infected patients
with or without toxoplasmic retinochoroiditis,
suggesting that they may be responsible for the
reactivation of the retinal lesions [48]. In immunocompetent individuals, the sensitivity of PCR for
detecting T. gondii from the ocular uids (24%)
and blood samples (1.4–16%) has remained unacceptably low and is not recommended. However, it
may be valuable in immunocompromised patients
where PCR may be positive up to 61.5% from the
ocular uids and 16–45% from the blood.
Goldmann-Witmer coefcient to demonstrate a
threefold increase in the ocular uids in immunocompetent patients has remained the standard
diagnostic criteria with a sensitivity of nearly 70%
irrespective of the immune status [49].
10.6.1.5 The Standard ofCare
forToxoplasmic
Retinochoroiditis
For several decades, the standard of care for
toxoplasmic retinochoroiditis has remained oral
pyrimethamine, sulphadiazine, and leucovorin,
which is highly effective in reducing the size of
the toxoplasmic retinochoroiditis lesions compared to the intravitreal clindamycin but cannot
be administered in pregnant women due to potential teratogenicity of pyrimethamine besides the
risk of myelosuppression, haematological disturbances, and Stevens-Johnson syndrome. Acute
toxoplasmic infection, if detected during preg-
Fig. 10.5 Right eye fundus photograph showing vitreous haze (a). Another patient showing a recurrence of retinitis
lesion (blue arrow) next to a healed pigmented atrophic chorioretinal scar (black arrow) (b)
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10 Retinal andChoroidal Infections andInammation
nancy and managed with oral anti-toxoplasma
drugs, prevents the transplacental migration of
the infection to the foetus. Spiramycin, a potent
macrolide, can be used for a suspected or conrmed toxoplasma infection in pregnancy as it
gets concentrated in the placenta but is not transmitted. So far, no antimicrobial agents are available that target the bradyzoites, the tissue cysts of
toxoplasma gondii. While extensive research is
underway to identify or repurpose drugs that target tachyzoites, the search is still on for a strategy
to eliminate the cystic stage of toxoplasma [50].
There is a ray of hope from animal experiments
following observations that orally bioavailable
endochin-like quinolones, especially the ELQ316 administered as ELQ-334, were effective
against both the acute and latent toxoplasma
infection and showed a signicant reduction in
the brain cysts in a mouse model [51].
10.6.1.6 Mechanism ofLatency
inToxoplasma gondii
Infection
Tachyzoites of T gondii are surrounded by a membranous vacuole and convert easily within the
nucleated cells into an impenetrable tissue cyst
(Bradyzoites), allowing for their latency and persistence. Given an opportunity, these cysts rupture
and release numerous tachyzoites, creating another
cycle of active inammation. Recently, the mechanisms that make the toxoplasma hibernate and
evade the host’s innate immunity have been
explored. It was shown that while invading the
cell, the parasite injects rhoptry and microneme
proteins into the host cell that trafc to the parasitophorous vacuole membrane, nucleus, and cytoplasm [52]. Additionally, once the tachyzoites
enter the cell, it transports an inhibitory protein
(IST), an inhibitor of the STAT1 transcription, to
the host cell to suppress immune signals. It turns
off type 1 interferon signalling on the infected cell
and is thus successful in evading the innate
immune response of the host [53]. As the tachyzoites differentiate into bradyzoites, a change in the
transcriptional prole prevents host cell death via
apoptotic or necroptotic pathways. Under what
conditions the tachyzoites leave the host cell to
infect other permissive host cells is probably not a
simple cell wall rupture. Still, highly intricate
mechanisms facilitate the egress of the tachyzoites
from the infected host cell [54].
10.6.2 Infectious Herpes Simplex
andVaricella Zoster Virus
Retinitis
10.6.2.1 Clinical Signs
The prevalence of anterior and posterior herpes
uveitis is rising in clinics worldwide. Unlike tuberculosis, recognized more than 150years ago, and
toxoplasmosis retinochoroiditis more than
70years ago, acute retinal necrosis (ARN) by the
herpes viruses was rst reported over 50years ago
in the Japanese literature. In the English literature,
Young and Bird [55] described four elderly
patients with dense bilateral opacication of the
peripheral retina and macula, retinal haemorrhages, and occlusion of vessels in the area of the
sloughing retinitis. They called it bilateral acute
retinal necrosis [55]. Five of the eight eyes ended
up with retinal detachment. The lesions that healed
left behind an atrophic retina with sheathed vessels. They suspected it to be caused by the herpes
virus, as a similar picture had been described in
infants who suffered from herpes viral fever. Using
electron microscopy and immunocytopathology
techniques, VZV was demonstrated in eyes
blinded by ARN [56]. Since then, ARN has been
increasingly reported from across the world. In a
population-based survey in the UK, the incidence
of ARN was reported as 1 case per 1.6 to 2 million
population per year [57], and 56% of all those
tested were positive for VZV.
In HIV-negative patients, two-thirds of the
ARN cases are caused by VZV and less than 25%
by HSV [58]. Next to toxoplasmosis, herpes
viruses are the commonest cause of infectious uveitis in most parts of the world. Herpes viruses may
cause anterior uveitis or necrotizing retinitis. In the
posterior segment, varicella zoster virus (VZV),
more commonly in the older and the herpes simplex virus (HSV) in the younger individuals,
causes blinding necrotizing retinitis irrespective of
the immune status. The immunocompetent and the
immunocompromised individuals often present
with tongue-like areas of necrotic retinal opacication in the periphery that rapidly advance poste-
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riorly and circumferentially (Fig. 10.6). The
vitreous reaction is contingent on the immune status of the person being very aggressive in immunocompetent persons but practically shows no
reaction in patients living with HIV infection. It
remains one of the rare uveitis emergencies that
necessitate intravenous acyclovir. Till recently, the
diagnosis of ARN was made using the diagnostic
criteria by the American Uveitis Society (Box
10.1) [59]. More recently, using machine learning
tools from a large database of infectious posterior/
pan uveitis (803 cases including 186 of ARN), a
fresh set of classication criteria for diagnosis of
a
ARN was developed with an overall accuracy of
~90% (Box 10.2) [60–63]. A distinctive form of
highly aggressive ARN, progressive outer retinal
necrosis, was described in patients with acquired
immune deciency syndrome, malignancy, or
organ transplants. The vitreous inammatory reaction in these eyes can vary from almost minimum
to moderate depending upon the severity of the
immunosuppression. They have extensive multifocal deep retinal necrosis and absent retinal haemorrhages, and the retina’s characteristic perivenous
sparing gives it a mud crack appearance (Fig.10.7).
There appears to be no involvement of the retinal
b
Fig. 10.6 Tongue-like areas (red arrows) of necrotic retinal opacication in the periphery of right eye (a) with vitreous
haze, suggestive of acute retinal necrosis (ARN). Fellow (left) eye is normal (b)
a
b
c
Fig. 10.7 Progressive outer retinal necrosis (in a patient
with renal transplant) characterized by multifocal deep
retinal necrosis lesions and absent retinal haemorrhages
(a). The retina’s characteristic perivenous sparing gives it
a mud crack appearance (b, c)
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10 Retinal andChoroidal Infections andInammation
Box 10.1 American Uveitis Society Criteria
for Diagnosis of Acute Retinal Necrosis
A. Umbrella term necrotizing herpetic
retinopathies be used when the involvement of
HSV, VZV, or CMV is suspected but not proven
B. Diagnosis of ARN is clinical. All the
following criteria must be met
(a) Lesions and
location
(b) Spread Circumferential and
(c) Progression Rapid
(d) Vessels Occlusive vasculopathy,
(e) Vitreous Prominent inammatory
Supportive evidence is not essential for
diagnosing ARN
(a) Optic neuropathy/atrophy
(b) Scleritis
(c) Pain
Note: Diagnosis of ARN does not depend upon
the age, gender, or immune status or isolation
of the offending virus
One or more areas of
retinal necrosis beyond
the temporal retinal
vascular arcades.
Involvement of macular
does not rule out ARN
posterior
especially the arterioles
reaction in the vitreous
and AC
HSV herpes simplex virus, VZV varicella zoster virus, CMV cytomegalovirus,
ARN acute retinal necrosis, AC anterior
chamber
Adapted from Holland [59] with permission of the publishers
Box 10.2 Classication Criteria for Acute
Retinal Necrosis Standardization of Uveitis
Nomenclature (SUN) Working Group
Criteria
1. Peripheral necrotizing retinitis
2. PCR from intraocular uids positive
3. Characteristic clinical appearance of
Clinical characteristics or laboratory
test
for HSV, VZV
circumferential or conuent
necrotizing retinitis, retinal vascular
sheathing, and/or occlusion and more
than minimum vitritis
Criteria
Diagnosis of ARN is made if criteria 1 and
either 2 or 3 are met
Clinical characteristics or laboratory
test
PCR polymerase chain reaction, HSV
herpes simplex virus, VZV varicella zoster
virus, ARN acute retinal necrosis
Adapted from Standardization of
Uveitis Nomenclature (SUN) Working
Group. Classication Criteria for Acute
Retinal Necrosis Syndrome 2021.With permission of the publishers
vessels. The macula and the optic disc get affected
early in the course. All of them have antecedent or
concomitant skin zoster lesions [64–67]. Scanning
laser ophthalmoscope (SLO) ultra-wide-led fundus imaging is a valuable tool for detecting and
characterizing the extent of peripheral necrotizing
retinitis and associated vascular occlusions, retinal
haemorrhages even in the presence of media haze
[68]. Retinal detachment is present in 2% of the
cases of ARN at presentation, but by the time they
nish the course of the disease, it may be seen in
up to 47% of the eyes [69]. More than one quadrant involvement in ARN is signicantly associated with the development of retinal detachment
and consequent poor visual outcome. Retinal
detachment develops due to sieve-like retinal
breaks that develop in the necrotic retina after
about 3 weeks of the onset of the ARN and is
prompted by the development of posterior vitreous
detachment [58]. All eyes with >2 quadrants of
retinal involvement had associated optic disc
involvement [70]. Systemic antiviral therapy and
prophylactic vitreous surgery may substantially
reduce the incidence of retinal detachment from
67 to 43% and 45 to 22%, respectively [69, 71].
While in the past, laser photocoagulation had been
used to prevent the occurrence of retinal detachment, there appears to be no advantage of this procedure [69]. The second eye gets involved in
nearly one-third of the patients within several
weeks, although there may be a delay of years
between the involvements of the second eye.
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Interestingly, PCR reveals the same virus (most
often HSV-1) in the two affected eyes [72].
10.6.2.2 Recurrences andLatency
inHSV andVZV Retinitis
Recurrences of herpes zoster in immunocompetent individuals, unlike herpes simplex, are rarely
reported, and of those reported cases, the clinical
diagnosis may have been mistaken [73]. More
than 30 cases of ARN have been reported weeks
to years following herpes simplex encephalitis
(HSE) [74]. More often, ARN develops within
2 years of HSE. Hence, there is a need for
increased awareness among both neurologists
and ophthalmologists [75]. Rarely, recurrences of
ARN in the same eye may be spread over several
years following HSV encephalitis [76]. Herpes
virus encephalitis following ARN is a rarity [77].
In any case, oral corticosteroids administered to
control inammation in the treatment of ARN
must be stopped before discontinuing antiviral
therapy. Recurrence of the ARN in the same eye
due to VZV is rare [78]. However, ARN due to
HSV may reactivate in the same eye years later
[79, 80].
The Herpesviridae family consists of at least
nine viruses that infect humans and are further
subdivided into three subgroups, α-herpesvirus
(HSV-1, HSV-2, and VZV); β-herpesvirus (CMV,
HHV-6, HHV-7, and HHV-8); and γ-herpesvirus
(EBV and Kaposi sarcoma herpes virus). Almost
all people worldwide are infected with at least
one of these viruses. The primary target of both
the HSV and VZV are the epithelial cells
exploited to replicate and spread the virus. The
HSV and the VZV are unique as they establish a
life-long presence/latency in the cranial nerve
ganglia’s neuronal cells and get activated occasionally. The viral DNA in these cells is stored as
circular episomes in the nucleus of the infected
cells. The viral proteins help the episomes tether
to the chromosomes enabling the viral episomes
to pass onto the daughter cells. The CMV targets
monocytes and lymphocytes, where this virus
can establish latency [81].
The herpes viruses evade immune recognition
by producing non-coding microRNA that suppresses lytic gene expression and limits the
expression of proteins, thus disabling the host’s
innate immune mechanisms to eliminate the
infected host cells. While the VZV reactivates
only once, the HSV shows frequent reactivation
and shedding of the virus. However, since not all
the infected cells show activation simultaneously,
clinical disease may not become apparent every
time the virus is shed [82]. HSV predominantly
causes frequent recurrences of epithelial keratitis
and anterior uveitis. However, acute retinal
necrosis (ARN) caused by the VZV most often
does not show recurrences. Extensive basic science research in the last 30years is focused on
the mechanism of latency and reactivation to
develop effective strategies [82, 83].
10.6.2.3 Treatment ofHSV andVZV
Retinitis
Acyclovir is the drug of choice, which is highly
effective for the reactivated virus but does not target the latent virus and thus cannot prevent reactivation. However, there is a role for long-term
antiviral therapy to prevent the involvement of
the other eye, especially if the rst eye has had a
poor visual outcome. However, for preventing the
recurrence of ARN in the same eye, the risks certainly outweigh the advantages, especially since
long-term antiviral therapy is fraught with
acyclovir- resistant strains of HSV. The virusspecic IFN-γ producing CD8+ T lymphocytes
keep the HSV in check. Glutamine, a nonessential amino acid, is an essential ingredient for
the proliferation of lymphocytes. Oral glutamine
supplements effectively upregulate several IFN-γ
producing genes in the ganglia of HSV-1-infected
mice and HSV-2-infected guinea pigs. Oral use
of glutamine appears to be a promising strategy
to prevent the recurrence of HSV infection [84].
10.6.3 CMV Retinitis
10.6.3.1 Risk Factors forCMV
Retinitis
CMV retinitis (CMV-R) is one of the 20 lifethreatening or opportunistic severe infections
that are listed by WHO as dened as an advanced
stage of HIV infection when it is labelled as
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10 Retinal andChoroidal Infections andInammation
acquired immune deciency syndrome (AIDS).
These opportunistic infections usually occur
when the CD4+ T-cell counts go below 200 per
μL.There is minimal risk of developing CMV-R
until CD4+ T-cell count 100/μL. Before the
advent of highly active antiretroviral drugs
(HAART) in the 1990s, the median time to survival after developing CMV retinitis was
10 months. After rst developing CD4+ T-cell
count <100/μL, the incidence of CMV-R rose
from 9% by the end of rst year to 25% by the
end of the fourth year. The risk of CMV-R rose
by 3× after the CD4+ T-cell count fell <50/μL.By
the fourth year, two-thirds of the patients had
died [85].
With the universal availability of HAART
therapy, CMV-R has become highly uncommon
in people living with HIV. Its incidence was
noted to be 0.36/100 person-years, the single
most risk factor being CD4+ T-cell count <50/μL
in the immediately prior visit. The CMV-R in
patients with HIV may be asymptomatic and is
usually detected on fundus examination of these
patients. There are two types of retinitis lesions,
(1) chronic indolent granular and peripheral perivascular lesions and perivenous inltrate with
fewer retinal haemorrhages or (2) more fulminant
haemorrhagic necrotizing retinitis. In HIV
patients, there is either minimal or no vitreous
reaction. However, once the patients are put on
HAART therapy, a severe vitreous inammatory
reaction may occur due to immune reconstitution. The lesions heal with atrophy of the retina
and may develop sieve-like retinal holes.
Currently, CMV-R is increasingly reported in
patients with organ transplants, bone marrow
transplants, leukaemias, lymphomas, or connective tissue disorders who are on immunosuppressive therapy. Intraocular and periocular
corticosteroids may account for nearly 20% of all
CMV retinitis in non-HIV patients [86]. Without
any of these non-HIV risk factors, diabetes
should be ruled out.
The patients who develop CMV-R without
HIV infection tend to be older, all have signicant vitreous inammation and, besides the nec-
rotizing haemorrhagic retinitis, have retinal
vasculitis, especially the retinal arteriolar occlusions (Fig. 10.8) [87, 88]. It contrasts sharply
with HIV+ patients with CMV-R, in which retinal vascular involvement is limited to only nonocclusive perivenous sheathing [89]. The
arteriolar occlusion may be much larger than suspected by the size of the retinitis lesion. Extensive
capillary non-perfusion areas exist [87, 89].
Moreover, if a PCR test for detecting CMV DNA
from the intraocular uids has not been done, the
CMV-R in non-HIV patients may be mistaken for
ARN [90, 91]. Notably, CMV-R in non-HIV
patients is unilateral. Also, the favourite sites for
CMV infection include the gastrointestinal tract,
the brain, and the eyes. See Box 10.3 for the diagnostic criteria of CMV-R.
On optical coherence tomography, the CMV-R
shows posterior hyaloid thickening, retinal swelling, retinal hyperreectivity, retinal disruption,
interruption of the IS/OS junction, and hyporeective spaces (empty spaces) in the outer nuclear
layer. Hyperreective vertical strips (bridges) are
seen in the outer nuclear layer [92, 93].
10.6.3.2 Pathogenesis andPathology
ofCMV Retinitis
The CMV is latent in the bone marrow CD34+
progenitor cells, the precursors of the monocytes.
The monocytes get released into the peripheral
blood and have a short life span of 1–3days. In
patients with HIV microangiopathy, the bloodretinal barrier breakdown allows the CMV to
infect the retinal cells. In immunocompetent individuals, the circulating pro-inammatory cytokines (TNF-α and IL-1β) cause endothelial cells
to express adhesion molecules (V-CAM, CD106),
letting the virus-infected monocytes adhere and
enter the capillary endothelial cells. It is recognized that the CMV-R starts near the retinal vessels. Ultrastructural and immunohistochemical
studies of CMV-R have shown the presence of
viral particles in the Muller cells and the perivascular glial cells in the necrotic retina. These were
also seen in the neuronal cells and the RPE cells.
In the area of necrosis, there was a complete loss
A
cd
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a
b
Fig. 10.8 (A) A 36-year-old woman presented with bilat-
eral CMV retinitis (a). She had pancytopenia and had
been diagnosed 9months earlier dyskeratosis congenita,
although without conclusive evidence of the disease. Her
white cell counts were 1620/mL. Quantitative PCR for
CMV was positive. She was treated with intravitreal and
oral ganciclovir. Lesions started healing at follow-up (b,
c) and at 3months (d). (Images courtesy of Dr. Anuradha
V. K., Head of uveitis Services, Aravind Eye Hospital,
Coimbatore. India). (B) A 38-year-old woman with HIV+
with a CD4+ count of 48mm3 presented as frosted branch
angiitis in the right eye. She had light perception (LP)
vision in this eye (a). On HAART and systemic ganciclovir, the retinitis and vasculitis improved, but she remained
LP+ vision 3months later (b). (Images courtesy of Prof
Ramandeep Singh, Advanced Eye Centre, Post Graduate
Institute of Medical Education and Research, Chandigarh,
India)
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10 Retinal andChoroidal Infections andInammation
a
Fig. 10.8 (continued)
Box 10.3 Classication Criteria for CMV
Retinitis Standardization of Uveitis
Nomenclature (SUN) Working Group
1. Necrotizing retinitis with indistinct borders
2a. Systemic immune compromise due to
AIDS, organ or bone marrow transplant,
IMT for CTD
2b. Ocular immunosuppression due to
periocular or intraocular depot
corticosteroids
3. Clinical characteristics:
a. Wedge-shaped retinitis or
b. Haemorrhagic retinitis or
c. Granular retinitis AND
d. Absent or minimal vitritis
4. PCR+ from intraocular uid
Diagnosis of CMV-R requires criteria 1, 2, and
either 3 or 4
Exclusion Criteria
+ for HSV or VZV or toxoplasma from the
intraocular uid
Adapted from Standardization of
b
: Tests for syphilis +; PCR
a
Uveitis Nomenclature (SUN) Working
Group. Classication Criteria for
Cytomegalovirus Retinitis, 2021. With permission of the publishers
CMV cytomegalovirus, AIDS acquired
immune deciency syndrome, IMT immunosuppressive therapy, CTD connective tissue disorders, PCR polymerase chain
reaction, HSV herpes simplex virus, VZV
b
varicella zoster virus, CMV-R cytomegalo-
virus retinitis
a
In non-HIV patients, the vitreous reac-
tion is severe
b
In immunocompromised patients,
more than two infections may co-exist in
the eye
of the endothelial lining of the retinal vessels.
However, at the advancing edge of the retinitis,
endothelial cells showed the presence of viral
proteins establishing that the CMV rst spreads
to the endothelial cells and then spreads to the
other retina cells [94].
10.6.3.3 Treatment ofCMV Retinitis
Systemic therapy is preferred in HIV+ CMV-R as
it frequently involves both eyes. The standard
therapy is intravenous ganciclovir (5mg/kg body
weight to be modied in renal pathology).
Induction therapy is given twice daily for
2–3 weeks, followed by maintenance therapy
once a week. The treatment is continued till, following the HAART therapy, the CD4+ T-cell
count rises >100/μL. Ganciclovir has a broad
range of activity against CMV, HSV, VZV, and
HHV-6 to HHV-8. Acyclovir, the drug most
effective against HSV and VZV, needs thymidine
kinase for its phosphorylation which the human
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