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……..