Download - Occular manifestations of HIV
Occular Manifestations of HIVDr.Asif imran
Eye A ward
Hollywood **** industry shuts as star contracts HIVBy Guy Adams in Los Angeles
Wednesday, 31 August 2011
• Hollywood's "other" movie industry has ordered its cameras to
stop rolling after an adult film star tested positive for HIV,
prompting renewed soul-searching about its safety standards.
• An unnamed performer was found to have contracted the virus,
during a routine examination on Saturday. Studios were notified
on Monday morning and agreed to an immediate shutdown of
production until further medical tests were completed
• Source: The Independent news
• www.independent.co.uk
HIV/AIDS in Pakistan
• Population, 2009 180,800,000
• People living with HIV/AIDS, 2009 98,000
• Women (aged 15+) with HIV/AIDS, 2009
28,000
• Children with HIV/AIDS, 2009 no data
• Adult HIV prevalence (%), 2009 0.1
• AIDS deaths, 2009 5,800
HIV/AIDS in United States
• Population, 2009 306,800,000
• People living with HIV/AIDS, 2009
1,200,000
• Women (aged 15+) with HIV/AIDS,
2009 310,000
• Children with HIV/AIDS, 2009 nd
• Adult HIV prevalence (%), 2009 0.6
• AIDS deaths, 2009 17,000
BACKGROUND…
• Human immunodeficiency virus (HIV) is a blood-borne, sexually
transmissible virus (see the image below.)
• The virus is typically transmitted via sexual intercourse, shared
intravenous drug paraphernalia, and mother-to-child
transmission (MTCT), which can occur during the birth process
or during breastfeeding.
ROUTE…
• The most common route of infection varies from
country to country and even among cities, reflecting
the population in which HIV was introduced initially
and local practices.
• Co-infection with other viruses that share similar
routes of transmission, such as hepatitis B, hepatitis
C, and human herpes virus 8 (HHV8; also known as
Kaposi sarcoma herpes virus [KSHV]), is common.
Types…..
• Two distinct species of HIV (HIV-1 and HIV-2) have been
identified, and each is composed of multiple subtypes, or
clades.
• All clades of HIV-1 tend to cause similar disease, but the global
distribution of the clades differs.
• This may have implications on any future vaccine, as the B
clade, which is predominant in the developed world (where the
large pharmaceutical companies are located), is rarely found in
the developing countries that are more severely affected by the
disease.
Type 1…
• HIV-1 probably originated from one or more cross-
species transfers from chimpanzees in central
Africa. HIV-2 is closely related to viruses that infect
sooty mangabeys in western Africa.
• Genetically, HIV-1 and HIV-2 are superficially
similar, but each contains unique genes and its own
distinct replication process.
Type 2…
• HIV-2 carries a slightly lower risk of transmission, and HIV-2
infection tends to progress more slowly to acquired immune
deficiency syndrome (AIDS).
• This may be due to a less-aggressive infection rather than a
specific property of the virus itself.
• Persons infected with HIV-2 tend to have a lower viral load than
people with HIV-1, and a greater viral load is associated with
more rapid progression to AIDS in HIV-1 infections
• HIV-2 is rare in the developed world. Consequently, most of the
research and vaccine and drug development has been
(perhaps unfairly) focused on HIV-1
Pathophysiology…
• HIV produces cellular immune deficiency
characterized by the depletion of helper T
lymphocytes (CD4+ cells).
• The loss of CD4+ cells results in the
development of opportunistic infections and
neoplastic processes
Phases of HIV infection…
Clinical HIV infection undergoes 3 distinct
phases:
• Acute Seroconversion,
• Asymptomatic infection,
• and AIDS
Figure showing the phases of HIV...
OCCULAR MANIFESTATIONS
IN HIV……
Overview..
• Ocular manifestations of human immunodeficiency virus (HIV) infection are
common. Approximately 70-80% of HIV-infected patients will be treated for an HIV-
associated eye disorder during the course of their illness.
• In general, the CD4+ T-lymphocyte count has been used to predict the onset of certain
ocular infections in patients who are HIV positive. A CD4+ T-cell count below 500/mL is
associated with Kaposi sarcoma, lymphoma, and tuberculosis. A CD4+ T-cell count below
250/mL is associated with pneumocystosis and toxoplasmosis. A CD4+ T-cell count less
than 100/mL is associated with the following:
• Retinal or conjunctival microvasculopathy
• Cytomegalovirus (CMV) retinitis
• Varicella-zoster virus (VZV) retinitis
• Mycobacterium avium complex infection
• Cryptococcosis
• Microsporidiosis
• HIV encephalopathy
• Progressive multifocal leukoencephalopathy
Overview….
• The predictive value of the CD4+ T-cell count for ocular complications in HIV
infection has been called into question by reports of CMV retinitis in patients
with CD4+ cell counts higher than 200 cells/mL.
• These patients reportedly were taking highly active antiretroviral therapy
(HAART). While such findings may argue against the protective effect of an
increased CD4+ cell count, the possibility that the CMV retinitis preceded the
recovery of CD4+ cell count was not ruled out.
• Thus, whether a reconstituted T-cell count will serve as a better predictor of
specific ocular infection is under active evaluation.
• Despite these uncertainties, the CD4+ cell count has remained the
predicting parameter for the occurrence of specific ocular infection in
patients who are HIV positive, at least until antigen-specific tests of T-
lymphocyte function become widely available.
Consequences of Ocular
Manifestations….
• The consequences of ocular manifestations of HIV infection can result from any of the following 3
processes:
• Inflammation (infectious or noninfectious)
• Nerve damage
• Tissue scarring
• Inflammation
• Inflammatory changes can affect almost all adnexal, ocular, and orbital tissues. The
infectious/noninfectious inflammatory process may manifest as a keratitis or vasculitis, iritis, ischemic
papillitis or retrobulbar optic neuritis, and orbital vasculitis. Other complications may include retinitis or
encephalitis.
• Nerve damage
• Nerve damage may be associated with neurotrophic keratitis. Cranial nerve palsies have been reported in
as many as 33% of cases of herpes zoster ophthalmicus, with the third cranial nerve being the most
frequently affected. The cranial nerve involvement may take place within the orbit or the cavernous sinus.
• Tissue scarring
• Tissue scarring may result in eyelid deformities, including marginal notching, loss of cilia, trichiasis, and
cicatricial entropion. Scarring and occlusion of the lacrimal puncta or canaliculi may occur.
• Some of the complications of ocular Kaposi sarcoma include trichiasis and entropion formation. Untreated
ocular Kaposi sarcoma may lead to obstructive disruption of the visual axis.
• Chronic follicular conjunctivitis frequently is present with occasional associated punctate epithelial erosions
and/or superficial vascular pannus on the cornea. Severe keratitis due to molluscum contagiosum tends to
mimic chlamydial keratoconjunctivitis. It is uncommon to find conjunctivitis and superficial keratitis in HIV-
positive patients.
• With conjunctival microvasculopathy, there is no reported morbidity or mortality.
Classification…(Kanski)
1.Eyelid :
– Blepharitis,
– Kaposi sarcoma
– Multiple molluscum lesions
– Severe herpes zoster ophthalmicus
2. Orbital:
– Cellulitis
– B cell lymphoma
3. Anterior Segment:
– Kaposi sarcoma, SCC and
microangiography
– Keratitis due to microsporidium,
Herpes simplex and Herpes
zoster
– Keratoconjunctivitis sicca
– Anterior uveitis
4. Posterior Segment
– HIV retionopathy,
– CMV retinitis
– Progressive outer retinal necrosis
– Toxoplasmosis frequently atypical
– Choroidal cryptococcosis
– Choroidal cryptocystosis
– B cell intraocular lymphoma
Ophthalmic Manifestations of HIV
Infection...
• AROUND THE EYE
– Molluscum Contagiosum
– Herpes Zoster
Ophthalmicus
– Kaposi’s Sarcoma
– Conjunctival Squamous
Cell Carcinoma
– Trichomegaly
• FRONT OF THE EYE
– Dry Eye
– Anterior Uveitis
• BACK OF THE EYE
– Retinal Microvasculopathy
– CMV Retinitis
– Acute Retinal Necrosis
– Progressive Outer Retinal
Necrosis
– Toxoplasmosis
Retinochoroiditis
– Syphilis Retinitis
– Candida albicans
endophthalmitis
• NEURO-OPHTHALMIC
Molluscum Contagiosum
• Molluscum contagiosum is a viral
infection of the skin.
• Affects up to 20% of symptomatic
HIV infected patients.
• Clinically appears like painless, small,
umbilicated nodules, which produce a
waxy discharge when pressured.
• Treatment consists on excision of the
lesion, curettage or cryotherapy
Herpes Zoster Ophthalmicus
Kaposi’s Sarcoma
• Kaposi’s sarcoma is a vascular neoplasm which is almost
exclusively seen in patients with AIDS.
• KS is the commonest anterior segment lesion seen in AIDS;
appears as a violaceous non-tender nodule on the eyelid or
conjunctiva.
• Typically KS involves only the skin but when there is a reduced
CD4 count it can progress rapidly to other sites such as the
gastrointestinal tract and CNS
• Treatment of ocular adnexal KS may be necessary for
cosmesis and to relieve functional difficulties. The mainstay of
treatment is radiotherapy. Other options include cryotherapy or
chemotherapy.
Conjunctival Squamous Cell Carcinoma
• Squamous cell carcinoma (SCC) is the third most common neoplasm associated to HIV infection.
• This may be due to an interaction between HIV, sunlight and Human Papilloma Virus infection.
• SCC appears as a pink, gelatinous growth, usually in the interpalpebral area. Often an engorged blood vessel feeding the tumour is seen.
• It may extend onto the cornea, but deep invasion and metastasis are rare.
• The treatment of choice is local excision and cryotherapy but the presence of orbital invasion is an indication of exenteration
Trichomegaly...
• Trichomegaly or
hypertrichosis is an
exaggerated growth of the
eye lashes found in the
later stages of the disease
• The cause is not known
• When symptomatic or for
cosmetic reasons the
eyelashes can be trimmed
or plucked
Dry Eye….
• Sicca syndrome is common with HIV infection
• Patients complain of burning uncomfortable red eyes.
• There are several causes of dry eye in HIV infection from blepharitis to destruction of the lacrimal glands.
• Treatment is with tear supplements
Anterior Uveitis..
• HIV related anterior uveitis can be:
– Direct manifestation of the HIV
infection
– autoimmnune in origin
– drug induced ie: rifabutin, secondary
to direct toxic effect upon the non-
pigmented epithelium of the ciliary
body.
– Any of the different infections
associated with AIDS :-
Herpes Zoster Virus,
Herpes Simplex Virus,
Cytomegalovirus,
Toxoplasma gondii
Syphilis
Rifabutin induced Anterior uveitis..
•Rifabutin (Rfb) is bactericidal antibiotic drug
primarily used in the treatment of tuberculosis.
The drug is a semi-synthetic derivative
of rifamycin S.
•Rifabutin is now recommended as first-line
treatment for tuberculosis. Rifampicin is more
widely used because of its cheaper cost.
•Rifabutin is well tolerated in patients with HIV-
related tuberculosis (TB), but patients with low
CD4 cell counts have a high risk of treatment
failure or relapse due to acquired rifamycin
resistance, a new study found.
•Its main usefulness lies in the fact that it has
lesser drug interactions than rifampicin therefore
HIV infected patients on HAART are given
rifabutin for treatment of TB
Retinal microvasculitis
• Retinal microvasculopathy occurs in more than half of the
patients with HIV
• It is seen as transient cotton wool spots (CWS), intra-retinal
haemorrhages and microaneurysm,
• Occurs in 50-70% of patients. It is usually asymptomatic.
• Unclear pathogenesis,but thought to be HIV infection of retinal
vascular cells.
• Serological test for HIV will confirm the diagnosis.
• Treatment is based in delaying the progression of the disease
associated with HIV.
Cotton Wool spots….
CMV Retinitis…
• Introduction
– CMV Retinitis is the commonest intraocular ocular
opportunistic infection seen in patients with AIDS
– Antibodies are found in almost 95% of adults, causing a
trivial illness in immunocompetent adults, however severe
immunosuppression causes viral reactivation and tissue
invasive disease
• Pathogenesis
– Reactivation from extraocular sites leads to seeding in other
sites such as the retina
• Epidemiology
– The number of newly diagnosed cases of CMVR has
decreased since the introduction of the HAART
CMV Retinitis…
Acute Retinal Necrosis…
• ARN is a confluent peripheral whitening of the retina with
marked vitritis and blood vessel closure. Optic neuritis and
retinal detachment are frequent complications.
• ARN is usually due to Varicella-Zoster infection, but it can also
be caused by Herpes Simplex virus or Cytomegalovirus.
• Initially described in the immunocompetent, it has also been
described in the immunosuppressed.
• The diagnosis is mainly clinical and is confirmed by PCR
assays on vitreous samples.
• Patients are treated with high doses of intravenous aciclovir or
famciclovir, combined with laser treatment to prevent retinal
detachment.
Toxoplasma Retinochoroiditis..
• Toxoplasmosis retinochoroiditis is an uncommon infection of
the eye in AIDS.
• Ocular toxoplasmosis in HIV positive patients is different in
appearance from immunocompetent patients.
• HIV infected patients often have bilateral and multifocal
disease associated with anterior uveitis and vitritis
• No pigmented scars adjacent to the areas of retinal necrosis.
(unlike in immunocompetent patients)
• Retinochoroiditis is not self-limiting as it is in imunocompetent
patients.
Toxoplasma Retinochoroiditis..
• When testing patients for antibodies to toxoplasmosis both IgG and IgM levels may be raised, but in immunocompromised patients these tests may be negative.
• Often associated with toxoplasma lesions in the Central Nervous System.
• Treatment in immunocompromised patients sulphadiazine or clindamycin +/- pyrimethamine and folinic acid (triple therapy).
• Long term maintenance to prevent relapses
MRI T1 showing an uniformly
enhancing lesion in the
midbrain
One week later, the lesion
showing ring enhancement
Immunocompetent Immunocompromised
Candida albicans endophthalmitis
• Infection with candida albicans is rare. Candida albicans is the
commonest cause of fungal endophthalmitis
• Affected patients usually have a history of drug abuse or
indwelling central lines or immuno-compromised.
• In the initial stages, floaters are the main symptom. As the
condition progresses, whitish “puff-balls” and vitreous strands
develop (‘string of pearls’)
• The treatment depends on the severity of the ocular
involvement and systemic disease. The original foci should be
removed. The drugs of choice are Amphotericin B and
Fluconazole
Candida albicans endophthalmitis
Lack of resources could undermine gains
made in the HIV response in Pakistan05 February 2010
• Pakistan’s capacity to effectively respond to the HIV epidemic could be hindered due to the
lack of resources to implement its revised National Strategic Framework. The framework,
endorsed by partners involved in the response, provides evidence-based strategic direction
to urgently address the increasing levels of HIV infection amongst injecting drug users
(IDUs) and other populations through sexual transmission and avoid a spillover to the
general population.
• Despite having an HIV prevalence of less than 0.1% among its general population,
Pakistan’s HIV epidemic has transitioned from low to a concentrated one as the overall
prevalence among IDUs has steadily increased from 10.8% in 2005 to nearly 21% in 2008.
• In part, the region’s comparatively heavy burden of injecting drug use stems from the
presence of long-standing trafficking routes for illicit opium. Opiates are the drug of choice
for 65% of Asia’s drug rehabilitation patients, although drug use patterns vary greatly within
the region. There are an estimated 91, 000 injecting drug users in Pakistan of which nearly
one in four in large urban settings are infected with HIV.
• Thankyou for listening……..