HIV AND ITS OCULAR MANIFESTATION This presentation is about HIV and what are its clinical ocular changes which we in these patients

1. HIV AND ITS OCULAR
MANIFESTATIONS
Presented by: L.Tarun Kumar
Boptom(final year)
BVDUMC school of optometry pune

2. INTRODUCTION
• Hiv is a virus that attacks the body's immune system. If HIV
is not treated, it can lead to AIDS (acquired
immunodeficiency syndrome
•The human immunodeficiency virus (HIV) is grouped
to the genus Lentivirus
•On the basis of genetic characteristics and differences
in the viral antigens, HIV is classified into the types 1
and 2 (HIV-1, HIV-2).
•HIV was introduced into the human population around
1920 to 1940.

3. EPIDEMIOLOGY
• The spread of HIV started at the beginning of the 20th
century .
• Zoonotic transmission of SIVcpz from chimpanzees (Pan
troglodytes troglodytes) occurred for HIV-1 group M and
group O around 1920 and for HIV-1 group N around 1960 in
West Central Africa.
• HIV-2 was transmitted zoonotically from sooty mangabey
(Cercocebus atys) to human in West Africa around 1940
• Globally, an estimated 35 million people were living with
HIV in 2013

4. ASIA
• cambodia, China and India are the countries with the
highest proportion of new hiv diagnosis.
• In western India, the HIV-2 epidemic originated
from the former Portuguese Goa
• The HIV-1 epidemic in India began with repatriates
from Eastern and Southern Africa
• In Asia, about 1.7 million people are living with
HIV, approximately 50% of whom receive
antiretroviral therapy. The number of newly
diagnosed HIV infections has decreased from 2001
to 2012 by about 26%

5. Genome Structure
•The HIV genome consists of two single stranded
RNA molecules that are enclosed within the core of
the virus particle.
•The genome of the HIV provirus also known as
proviral DNA is generated by the reverse
transcription of the viral RNA genome into DNA,
degradation of the RNA and integration of the
double-stranded HIV DNA into the human
genome.

6. • A) two envelope glycoproteins gp120 (surface protein,
SU) and gp41 (transmembrane protein, TM) are
derived
• B) Regulatory proteins
Tat (transactivator protein) and Rev (RNA splicing-
regulator) are necessary for the initiation of
replication.

7. Nef (negative regulating factor), Vif (viral infectivity factor), Vpr (virus
protein r) and Vpu (virus protein unique) have an impact on viral
replication, virus budding and pathogenesis.

8. Particle structure
•The mature HIV particle is round, measures
approximately 100 nm in diameter, with an outer lipid
membrane as its envelope
•The envelope contains 72 knobs, composed of trimers
of the Env proteins.
•The trimers of gp120 surface protein (SU) are
anchored to the membrane by the trimers of the
transmembrane protein gp41 (TM) .
•The viral envelope is composed of a lipid bi-layer .

10. • . It covers the symmetrical outer capsid membrane which is
formed by the matrix protein (MA, p17).
• . The conical capsid is assembled from the inner capsid
protein p24 (CA)
• Two identical molecules of viral genomic RNA are located
inside the capsid and several molecules of the viral enzymes
RT/RNase H and IN bound to the nucleic acid.
• Additional regulatory proteins are Vif, Vpr and Vpu which
influence the rate of the production of virus particles.

11. Pathogenesis
• The surface glycoprotein gp120 of the mature HIV particle binds to
the CD4 receptor on the host cell.
• All CD4-positive cells such as T helper cells, macrophages, dendritic
cells and astrocytes are susceptible to HIV.
• After attachment , a conformational change in CD4 and gp120 occurs,
opening up an additional site for gp120 to enable binding to the co-
receptor, i.e. chemokine receptor 5 (CCR5) or chemokine receptor 4
(CXCR4 or fusin) on the cell surface .
• The N-terminus of gp41 is presented on the viral membrane, forms a
channel and, due to its high hydrophobicity, inserts into the plasma
membrane of the target cell.

12. • Fusion of the viral and cellular membranes leads to translocation of
the viral capsid into the cytoplasm
• The capsid is taken up by an endosome, and a change in the pH value
in the phagosome induces the release of the capsid contents into the
cytoplasm.
• HIV RT transcribes the single-strand HIV RNA genome into DNA .
• In parallel to DNA synthesis, the RNA strand is degraded
enzymatically by RNase H, followed by conversion of single-stranded
cDNA into double-stranded DNA (proviral DNA) by the DNA-
dependent DNA polymerase activity of RT

14. • This proviral DNA is transported via nucleopores into the cell nucleus
in the form of a complex consisting of the integrase (IN) and linear or
circular proviral DNA.
• The integrase then inserts at random the proviral genome into the
human host cell genome
• The proviral genome can be replicated together with and as part of the
host cell genome during cell division.
• However, after activation of infected cells the LTR promotor of the
proviral genome can serve as attachment site for cellular DNA-
dependent RNA polymerases and a variety of transcription factors
initiating the synthesis of viral mRNA and genomic RNA.

15. SYMPTOMS
• With the onset of the humoral immune response against HIV after 3-6 weeks,
variable clinical symptoms can be observed in the majority of infected persons.
• Fever
• Lymph node enlargement
• Fatigue
• Headache
• Joint pains
• Sweating during night
• Diarrhea
• Malaise
• Red Rashes on skin.
• Gastrointestinal Symptoms

17. • The symptoms persist for 2-6 weeks. This initial symptomatic
phase is usually followed by an asymptomatic phase or one
with occasional symptoms which can last for many years.
• . A person with HIV often experiences no symptoms, feels healthy,
and appears healthy.

18. Transmission
• HIV is able to enter the body via intact mucous membranes,
eczematous or injured skin or mucosa and by parenteral inoculation.
• The majority of new HIV infections are still transmitted sexually
• parenteral administration of drugs .
• Transmission of HIV via blood or transplanted organs, including
bone, is possible from about days 5-6 after infection of the donor.
• Mother-to-child transmission has been demonstrated from the 12th
week of gestation, but transmission occurs predominantly (>90%)
in the final trimester and particularly shortly before or during birth.

19. • Sharing needles ,syringes, other equipments
• Contaminated blood transfusions and organ/ tissue transplant.
• Certain body fluids- Blood, semen,Rectal fluid ,vaginal fluid, and
breast milk.

21. Diagnosis
• A general distinction can be made between two principles of detection:
antibody and virus detection.
• Antibodies
• HIV antibody screening tests are used for the primary diagnosis
followed by a confirmation test in the case of a reactive result in the
screening assay.
• ELISA TEST
1. the blood sample will be sent to a laboratory for analysis.
2. A lab technician will add the sample to a device that contains HIV
antigen and anti-HIV antibodies

22. 3. An automated process will add an enzyme to the device.
4. The enzyme helps speed up chemical reactions.
5 .Afterward, the reaction of the blood and the antigen will be
mmonitored
6. If the blood contains antibodies to HIV or antigens of HIV, it will
bind with the antigen or antibody in the device.
7. If this binding is detected, the person may have HIV.
8. However, there can be false positives with the ELISA test.

23. ELIISA TEST

24. 9 . Sometimes, HIV doesn’t show up on the
ELISA test even though a person has an HIV
infection. This can happen if someone is in
the early stages of the infection, and their
body hasn’t produced enough antibodies (in
response to the virus) for the tests to detect

25. Western blot test
Western blot test Western blot HIV tests usually
look for antibodies against the following HIV
proteins:
• Proteins from the HIV envelope: gp41, and
gp120/gp160.
• Proteins from the core of the virus: p17, p24, p55
• Enzymes that HIV uses in the process of
infection: p31, p51, p66

26. Western blot test

27. • Virus Detection
• Virus isolation in cell culture takes approximately 6 weeks and is
often unsuccessful and costly
• The p24 protein forms the inner capsid. Each virus particle contains
approximately 2,000 p24 molecules
• ELISA test
Detection of p24 antigen is performed using a combination of
polyclonal or monoclonal antibodies, following the principle of the
sandwich ELISA technique.

28. • Nucleic Acid Amplification
Diagnosis of an HIV infection can be performed by
determining proviral DNA in cells or of viral RNA
genome in plasma.
Genome detection can be done either via direct
amplification of defined target sequences or through the
use of probes with subsequent signal amplification
• Polymerase chain reaction (PCR)

29. Treatment
• Drugs with different spectra of activity are applied: nucleoside
(NRTIs), nucleotide (NtRTIs) and non-nucleoside analogues
(NNRTIs), reverse transcriptase inhibitors combined with protease
inhibitors (PI or PRI) and/or additionally a fusion or integrase
inhibitor (INI)
• The initial therapy of HIV infection should be started with a highly
effective and at the same time safe and well-tolerated combination of
two NRTIs with one NNRTI
• A combination of different active substance groups of antiviral drugs
should delay the development of resistant HIV in the patient as long as
possible.

30. • Common side-effects include diarrhoea, insomnia, lack of
concentration and inability to gain weight despite adequate food
intake; also diabetes, anaemia and neurologic disorders are observed

31. Ocular Manifestations Of HIV
• Ocular manifestations are common in HIV patients
• Ocular involvement in HIV can be caused by opportunistic
infections, vascular abnormalities, neoplasms, neuro-
ophthalmic conditions, or adverse effects of medications.
• Studies suggest that between 5 to 25% of all HIV patients in
developing countries may become blind in their lifetime
• The ocular structures affected by HIV include the adnexa,
anterior segment, posterior segment, and orbit.
Neuroophthalmological manifestations also may be seen.

32. Herpes Zoster Ophthalmicus
• HZO is a vesiculobullous dermatitis in the course of the ophthalmic
division of the trigeminal nerve caused by the Varicella zoster virus
(VZV).
• It is seen in 5% to 15% of HIV patients and may be associated with a
simultaneous occurrence of keratitis, scleritis, uveitis, retinitis, or
encephalitis.
• It include severe chronic pain and vision loss.
• Typically, patients then develop a painful unilateral dermatomal rash
in the distribution of one or more branches of V1: supraorbital,
lacrimal, and nasocilliary.

33. • Viral culture, direct immunoflourescence assay, or PCR may also be
used to confirm the diagnosis
• Treatment consists of local wound care, pain control, initiation of
antiviral medication, and antibiotics if needed.
• Treatment with seven to 10 days of oral acyclovir at a dose of 800mg
five times.
• Topical steroids may be helpful in the initial management of pain due
to uveitis or scleritis

35. Kaposi Sarcoma
• Kaposi’s sarcoma (KS) is the most common cancer in HIV-infected
untreated individuals
• Kaposi’s sarcoma-associated herpesvirus (KSHV; also known as
human herpesvirus 8 (HHV8)) is the infectious cause of this
neoplasm.
• Oral transmission through saliva is considered the most common route.
• Kaposi sarcoma is a highly-vascularized, mesenchymal tumor.
• It may present as painless, violaceous lesions on the eyelid skin or
conjunctiva.

36. • Treatment available is radiation and/or
cytotoxic chemotherapy
• In severe cases of KS that are localized
to the limbs amputation is indicated.

37. Molluscum Contagiosum
• Molluscum contagiosum (MC) is a very common benign self-
limiting cutaneous viral infection caused by molluscum
contagiosum virus
• Molluscum contagiosum is a dermatitis caused by a poxvirus
and characterized by multiple, small, painless umbilicated
lesions on the eyelid skin.
• Surgical methods, such as, curettage, electrodessication,
cryotherapy, and laser surgery are used.
• Cytodestructive methods include use of cantharadin, iodine,
lactic acid, phenol, salicylic acid, silver nitrate, tretinoin, and
trichloroacetic acid.

39. Conjunvtival Microvasculopathy
• . Seventy percent to 80% of HIV patients may present with
conjunctival microvasculopathy
• characterized by segmental dilatation and narrowing of blood
vessels, comma-shaped vascular segments, and sludging of
blood column
• The cause is thought to be either immune complex deposition,
increased plasma viscosity or direct infection of hiv in
conjunctival vascular endothelium.
• Conjunctival Microvasculopathy presents as asymptomatic
microvascular changes and no treatment is necessary

40. Conjunctival Microvasculopathy

41. Conjunvtival Squamous Cell Carcinoma.
• The exact cause of squamous cell carcinoma is not known,
but the human papilloma virus (HPV) has been implicated.
• The growth is located on the nasal conjunctiva near the
limbus or mid-way between the limbus and the caruncle.
• Typically, the lesion is gelatinous, greyish white on surface
which vary in size from 2–3mm, and cover the nasal one
third of the cornea
• While most of these lesions slough off the cornea, some are
embedded to underlying sclera.

42. •We often see tumours invading 2–3mm into the
cornea, from 7 o'clock to 10 o'clock.
•This is diagnosed by excision biopsy.
• Management is to excise with a margin of at least
2mm of normal looking conjunctiva, as well as remove
as much of the base of the tumour as possible.
•Enucleation is performed routinely in our clinics for
recurrent squamous cell carcinoma

43. Squamous Cell Carcinoma
• Chemotherapy, in the form of
mitomycin application to the
tumour bed, has been
suggested to reduce recurrence.

44. Trichomegaly
• Trichomegaly or hypertrichosis
is an exaggerated growth of the
growth of the eye lashes eye lashes
found in the later stages of the disease
• Direct effects of the virus on the hair
follicle, immune dysregulation, and a
multifactorial pathogenesis are discussed.
• When symptomatic or for cosmetic
reasons the eyelashes can be trimmed .

45. Keratoconjunctivitis Sicca.
•About 20% of people with HIV have dry eyes
•Keratoconjunctivitis sicca ( dry eye syndrome)
results from deficiency of any of the tear film
layers.
•It is likely caused by both the destruction of
primary and secondary lacrimal glands and
inflammation mediated by the HIV virus.
• Symptoms may include foreign body sensations,
photophobia and decreased visual acuity.
• Treatment is artificial tears and eye lubricants.

46. Keratitis
• Keratitis in HIV is rare, seen in less than 5% of cases, but can lead to loss
of vision.
• Herpes simplex virus and varicella-zoster virus are the most common
causes.
• Herpes simplex keratitis is a painful condition of peripheral cornea with
longer course and higher recurrences in AIDS patients.
• Corneal scarring and iritis may be
seen.
• Varicella-Zoster Virus Keratitis present with elevated intraocular pressure
• Microsporidia are protozoa which can cause a punctuate epithelial
keratopathy.

47. Management for viral keratitis by oral acyclovir or famciclovir;
microsporidial keratitis by oral itraconazole, topical fumagillin, and oral
albendazole; bacterial and fungal keratitis with appropriate
antimicrobial therapy.
A) Herpes simplex
keratitis
B) Varicella zoster keratitis

48. Iridocyclitis
• Iridocyclitis is fairly common in HIV
• An HIV infected patient complaining of photophobia and
red eye may have iridocyclitis.
• Mild iridocyclitis may be seen in association with VZV or
CMV retinitis
• Severe iridocyclitis in association with toxoplasmosis,
syphilis, tuberculosis, and bacterial or fungal retinitis.
• Medications, like Rifabutin and Cidofovir, prescribed for
HIV patients also may cause iridocyclitis
• It may reveal KPs, cells in AC, patches of iris necrosis,
posterior synechiae, and hypopyon.

49. • Treatment with topical corticosteroids started only after instituting
appropriate antimicrobial therapy if an infection is suspected
B ) varicella zoster virus acute anterior uveitis, showing a
small area of stromal keratitis (arrow), diffuse, medium-
size keratic precipitates, and an irregular pupil due to
iridoplegia.
A) Anterior uveitis

50. Posterior Segment
• Posterior segment involvement in HIV is quite common and
can cause visual loss.
• The posterior segment of the eye (retina, choroid and optic
nerve head) is affected in more than 50% of AIDS patients by
either infectious causes or non infectious causes.
• They include Retinal microangiopathy, CMV retinitis, VZV
retinitis, toxoplasma retinchoroiditis, and bacterial and fungal
retinitis.
• Patients may complain of floaters, flashes of light, decreased
visual acuity or visual field defects

51. Retinal microvasculopathy
•Retinal microangiopathy is the most common
ophthalmic manifestation seen in 40-60% of
HIV patients .
•It is characterized by the cotton wool spots,
retinal hemorrhages, and microaneurysms
especially when CD4+ T lymphocyte count is
lower than 100/µl.
•Most patients are usually asymptomatic and does
not require any treatment.

52. HIV RETINOPATHY
A) Numerous cotton wool spots

53. CMV Retinitis
• CMV retinitis affects nearly 30% to 40% of HIV-infected
individuals and is usually seen with CD4 counts less than
100/microliters.
• Fundus examination reveals full thickness intraretinal opacification
associated with retinal hemorrhages.
• There is minimal AC reaction, and the vitreous is generally clear.
• Loss of vision can occur due to the direct involvement of macula or
optic nerve, retinal detachment and immune recovery uveitis.
• CMV retinitis is treated with drugs such as valganciclovir, oral or
intravenous ganciclovir, ganciclovir implant, fomivirsen, foscarnet,
and cidofovir, and immune recovery uveitis.

54. CMV Retinitis

55. Acute Retinal Necrosis
•Varicella zoster virus has been associated with acute
retinal necrosis
•It is characterized by peripheral retinal whitening, often
accompanied by intraretinal hemorrhages associated
with rapidly progressing necrosis over several days.
• Asociated with marked anterior uveitis and vitritis.
• Pain is usually seen, associated with blurred vision and
floaters.
•ARN is managed with systemic acyclovir, followed by
barrage laser photocoagulation after resolution of retinitis
to prevent retinal detachment

56. Acute Retinal Necrosis

57. Progressive Outer retinal Necrosis
• Progressive outer retinal necrosis (PORN) syndrome is
a form of the Varicella zoster virus (VZV) chorioretinitis
found almost exclusively in people with the acquired
immunodeficiency syndrome (AIDS).
•IT may lead to no light perception in affected eyes
within days or weeks.
• Unlike ARN, which affects immunocompetent patients,
PORN is a disease of the immunocompromised.
• Characterized by Multifocal, deep retinal infiltrates, with
minimal vitritis

58. Progressive Outer Retinal Necrosis
• Treatment is intravitreal injections
of ganciclovir or foscarnet in
addition to IV antiviral therapy.

59. Toxoplasma Retinchoroiditis
• It is usually bilateral and multifocal and may be associated with
central nervous system (CNS) involvement.
• Patients usually complain of seeing floaters, pain and decrease
in visual acuity.
• Retinochoroidal scars and retinal hemorrhage may be absent.
• PCR of the ocular fluid may be helpful in distinguishing between
toxoplasmic retinochoroiditis.
• Intravitreous clindamycin with dexamethasone seems to be
as effective as systemic treatments.

61. Syphilis Retinitis
• Ocular syphilis is seen in 2% of patients and may present as
anterior segment inflammation or diffuse intraocular
involvement
• Characterized by a deep yellow lesion along with retinal
vasculitis and intraocular inflammation , vitritis .
• The diagnosis can be confirmed by the serum fluorescent
treponema antibody absorption test (FTA ABS) and
microhemagglutination assay (MHA-TP).
• For late latent syphilis, treatment with 3 weekly IM
injections of 2.4 million units of benzathine penicillinG is
recommended.

62. Ocular syphilis

63. Candida Albicans Endopthalmitis.
• Candidal endophthalmitis generally presents as a focal
white infiltrate in the choroid, and may break through
the retina into the vitreous.
• Usually, an overlying vitritis is present
• Detection of C. albicans DNA in intraocular fluid can
be
• carried out using PCR assay
• Combination therapy with high-dose fluconazole
and intravenous amphotericin B was performed

64. Candida Albicans Endophthalmitis.

65. Neurophthalmic Manifestations
•Neurophthalmic manifestations are seen in 10% to 15 % of
patients with HIV.
•Include papilloedema, cranial nerve palsies, ocular motility
disorders, and visual field defects. Cryptococcal meningitis,
CNS lymphoma, neurosyphilis
•Intracerebral toxoplasma cysts cause intracranial
manifestations.
•secondary to elevated intracranial pressure
•Progressive multifoca leukoencephalopathy (PML),
•Intracerebral infection with herpes virus

66. Orbital Manifestations
•Orbital manifestations of HIV infection
are not seen very often.
•However, some cases of orbital cellulitis and
orbital
lymphoma have been reported.
•It is usually caused by Aspergillus