DR. CHRISTINA SAMUELPG- M.S OPHTHALMOLOGYMMCH & RI

GENERAL PROPERTIES OF VIRUS

Virus is the smallest known micro organism

[10nm-300nm]

It consists of a nucleic acid core(RNA/DNA)

surrounded by a protein coat.

They are metabolically inert and hence requires

living cells to survive and replicate.

The protein coat which is antigenic in nature is

called a ‘Capsid’ and together with the nucleic

acid is termed as ‘Virion’. The capsid is made up

of protein subunits called as ‘Capsomeres’

VIRUS

ADENO VIRUS

HERPES SIMPLEX

HERPES ZOSTER

CYTOMEGALOVIRUS

PAPOVA VIRUS

POX VIRUS- VARIOLA, VACCINIA, MOLLUSCUM

PICORNA VIRUS

PARAMYXO VIRUS

RUBEOLA

RUBELLA

HIV

ADENOVIRUS- ADENOVIRAL CONJUNCTIVITIS

Family- Adenoviridae

Double stranded DNA virus without an envelope

70-90nm in diameter, icosahedral symmetry, 252 capsomeres.

Has an affinity for mucous surfaces and hence infect the

conjunctiva, pharynx and small intestine.

Humoral immunity plays a major role in combating adenovirus

infections and aslo a long lasting immunity is conferred against

reinfection.

Mode of transmission- hand to eye transfer, unsterilized instruments,

fomites, water borne(swimming pool)

ADENOVIRUS

Syndrome Adenovirus type

- Pharyngo conjunctival 3,4,7,14,21

fever, ARD

- Follicular conjunctivitis 1,2,3,5,6,7

- Epidemic

keratoconjunctivitis 8,19,37

(Shipyard eye)

SIGNS:

Conjunctiva- Eyelid edema, pre auricular lymphadenopathy,

conjunctival congestion, follicles, chemosis, rarely membranes

or pseudo membranes leaving a mild scar after resolution.

Cornea- Non staining epithelial microcysts, punctate epithelial

keratitis, focal subepithelial/anterior stromal infiltrates.

Mild anterior uveitis in some cases.

DD:-

Acute haemorrhagic conjunctivitis- enterovirus/coxsackievirus

Follicular conjunctivitis- HSV, varicella, mumps, measles,HIV

LAB DIAGNOSIS

- Giemsa stain- mononuclear cells

- Electron microscopy

- Virus isolation from conjunctival swab

- Cell line- primary human embryonic kidney cells, human epithelial

cells and MRC-5 cells( observe cytopathic effect) = ‘plaques’

- Complement fixation test

- ELISA & Enzyme Immunoassays

- PCR

ADENOVIRAL CONJUNCTIVITIS

FOLLICULAR CONJUNCTIVITIS

TREATMENT

Topical antibiotics

Lubricants

Topical steroids

Discontinue contact lens

Warm compressions

Hygiene- hand wash

HERPES VIRUS

Family- Alpha herpes virus

Double stranded DNA virus with a capsid and envelope.

150-200nm in diameter, 162 capsomeres

2 subtypes- HSV 1 & HSV 2

It multiplies in the nuclei of infected cells and produces

intracellular inclusion bodies “Lipschutz inclusion bodies”

Virus proliferates in the cells of the stroma and keratocytes and

sets up an inflammatory reaction.

It remains latent in the trigeminal ganglion- recurrent infection.

Primary infection- face, eye, mouth( 6mth-5yrs/newborns through

mother)

Latent infection-reactivation. May not involve the eye

CLINICAL FEATURES

Epithelial dendritic/geographic keratitis causing ulcer which stains

well with fluorescein dye.

Ends of the ulcer has terminal buds staining with rose bengal

Decreased corneal sensation. Scarring and vascularization in

prolonged cases. Disciform keratitis, necrotizing stromal

keratitis, neurotrophic ulceration

Keratoconjunctivitis and anterior uveitis

Preauricular lymphadenopathy, vesicular eruptions on the skin.

Fever and malaise

DD:-

Herpes zoster keratitis

Acanthaemoeba keratitis

CORNEAL ULCER

LAB DIAGNOSIS

Direct demonstration by electron microscopy/immunofluorescence.

Corneal scrappings- Giemsa/papanicola stain and intra nuclear

eosinophilic inclusion bodies can be demonstrated.

Cytology of infected tissue for multinuclear giant cells,

polymorphonuclear cells and monocytes.

Conjunctival fluid for virus culture- human embryo lung cells,BHK-

21,MRC-5 cells.

CPE occurs within 24-48hrs which is characterised by rounding of

cells and plaque formation.

ELISA

HERPES ZOSTER

Same group as HSV, but antigenically distinct.

It travels in a retrograde manner to the dorsal route and

cranial nerve sensory ganglia, where it remains dormant

for decades and gets reactivated when VZV-specific cell

mediated immunity fades.

HZO describes Shingles involving the dermatome supplied

by trigeminal nerve.

FEATURES:

Direct viral invasion- conjunctivitis, epithelial keratitis

Secondary inflammation with episcleritis, scleritis, keratitis,

uveitis, optic neuritis, cranial nerve palsy and cicatrizing

complications of eyelids.

Inflammation and destruction of the peripheral nerves or

central ganglia maybe responsible for post herpetic

neuralgia.

Reactivation causes necrosis and inflammation in the sensory

ganglia, corneal anaesthesia causing neurotrophic keratitis.

Skin vesicles occur which doesn’t cross the midline.

SHINGLES AROUND THE EYE

TREATMENT

Oral/ointment/topical Acyclovir.

Acyclovir Cream for skin lesions too.

Ganciclovir 0.15% gel

Oral valaciclovir/ famciclovir

Interferon monotherapy

Prostaglandins for IOP control

Topical/ oral steroids

CYTOMEGALOVIRUS

Family – Beta Herpes viridae

Double stranded DNA virus with icosahedral capsid and envelope.

Indistinguishable from HSV/VZV by electron microscopy.

Transmission is through placenta, intimate contact, blood

transfusion.

CMV has a profound immunosuppressive effect on the host and

has a tendency to persist in a latent state in the cellular

components of the blood.

Mononuclear phagocytes and natural killer cells play a role in

combating CMV infection.

FEATURES:

Keratitis

Cataract

Glaucoma

Microphthalmia

Retinal detachment

Optic atrophy

Chorioretinitis- multiple foci with a peripheral location

Retinal haemorrhages

DD:-

Toxoplasmosis

CMV- RETINITIS

LAB DIAGNOSIS:

Cytology – “OWL’S EYE” scanty cytoplasm and large nucleus with

acidophilic inclusion bodies.

Culture – human fibroblast cell lines. CPE shows rounding up of cells

in 2-3 weeks.

Serology – complement fixation test, ELISA and radio immuno

assays

PCR

TREATMENT:-

I.V Ganciclovir, Foscarnet, Cidofovir

Intravitreal vitrasert( ganciclovir slow release device)

CMV-VZV-HSV-TOXO

PICORNA VIRUS

RNA virus. A large family

27nm in diameter.

Icosahedral symmetry

Further sub divided

Enterovirus

poliovirus Rhinovirus

coxsachie

echovirus

enterovirus types 68-72

OCULAR LESIONS

ACUTE HAEMORRHAGIC CONJUNCTIVITIS-

Coxsackie A24, Enterovirus type 70

Transmission – fomites, faecal oral route, Direct inoculation into

the conjunctiva (contaminated fingers).

Incubation period – 2 days

It multiplies in the conjunctival epithelium and causes

haemorrhagic conjunctivitis.

LAB DIAGNOSIS

Virus Isolation: conjunctival swab inoculated into cell lines

like primary monkey kidney cell lines, Vero, HeLa. This

virus produces typical cytopathic effect.

Coxsackie: Isolated by suckling mice inoculation

Serology: Neutralization tests

TREATMENT:

Topical antibiotics

POX VIRUS

VARIOLA –

Commonly known as small pox virus. Brick shaped. 230-400nm.

Has an envelope.

Genome is a double stranded DNA and contains DNA dependent

RNA polymerase.

Causes Catarrhal purulent conjunctivitis, lid abscess, corneal pustule

and albinotic spots on the iris.

Lab diagnosis:-

Growth on Chorioallantoic membrane of yolk sac produces pocks.

Cytoplasmic eosinophilic Guarinieri bodies- light microscopy

Complement fixation test

Gutstein’s methyl violet stain

POX VIRUS

GUARINIERI INCLUSION BODIES

VACCINA VIRUS

Used as a small pox vaccine( induces immunity)

Transmission either by contamination or auto innoculation.

Signs :-

Lids – swelling, pustules, Ulcerative blepharitis

Purulent conjunctivitis

Marginal/disciform keratitis. Corneal pustule.

Pseudo retinitis pigmentosa

LAB:-

Growth on cell lines- HeLa, MRC-5

TREATMENT:-

Vidarabine and Iodoxuridine.

Topical and i.m use of vaccina immunoglobulin

PARAMYXO VIRUS

RNA virus, spherical in shape, pleomorphic, 150-300nm.

Enveloped virus having a hemagglutin(HN) and fusion(F)

glycoprotein spikes. HN is responsible for the host cell attachment

of the virus and F for fusion of viral envelope with host cell

plasma membrane.

Transmitted by droplet infection, humans being their only host.

Spreads to salivary glands.

Incubation period= 7-25 days

Ocular signs- Dacryoadenitis, optic neuritis, conjunctivitis, unilateral

stromal disciform keratitis.

LAB DIAGNOSIS

Immunofluorescence technique

Virus isolation by monkey kidney cell lines- rounding and giant cell

syncytium formation. Confirm by hemadsorption and

hemagglutination inhibition test using mumps virus specific

antiserum and immunofluorescence.

Complement fixation test

Haemagglutination inhibition test

Single radial hemolysis

ELISA

TREATMENT:- Oral supportive therapy

MEASLES- RUBEOLA

Enters the host via respiratory route and spreads to the lymph nodes.

Incubation period= 1-3 weeks

Both humoral and cell mediated immunity take part in combating

infection, has a life long immunity.

OCULAR MANIFESTATIONS-

Conjunctivitis, Koplik’s spots, SPK

LAB:-

Virus isolation from conjunctival biopsy

Direct immunofluorescence- microscopy

Culture- Cell lines- primary monkey kidney, human fibroblast cells

Serology- Hemagglutination inhibition test, complement fixation test,

neutralisation test.

RUBELLA- GERMAN MEASLES

RNA virus.

Family- Togaviridae.

Genus- Rubivirus

Spherical virus

70nm in diameter

Has a lipid envelope which has virus specific hemagglutinin spikes.

It Causes-

Post natal Rubella

Congenital Rubella syndrome{CRS}

CRS

Viremia occuring in pregnant women results in infection of

placenta and the differentiating cells of the foetus.

These children who are born secrete the virus in pharyngeal

secretions, urine and CSF fluid, which is detectable for 12-18

months.

Clinical triad of CRS=

Congenital heart disease+ Total/partial blindness(cataract,

glaucoma, chorioretinitis)+ Neurosensory deafness

Demonstration of IgM rubella antibody in infants is the Diagnostic

of CRS.

LAB DIAGNOSIS

Virus isolation from the specimen- Cell lines: Vero, RK-13

derived from rabbit, SRIC. In these cell lines it produces a

non specific cytopathic effect.

The virus can be demonstrated by- immunofluorescence with

specific antibody, interference method(using Coxsachie

antigen as challenge virus)

Serology- Hemagglutination Inhibition test: agglutinates

erythrocytes of 1day old chick, pigeon and sheep.

ELISA for IgG & IgM: Rise in IgG antibody titre should be

demonstrated in 2 serum samples and obtained at an interval

of 10-14 days. Else rubella specific IgM should be

demonstrated in a single specimen.

PREVENTION & CONTROL

MMR= Mumps, Measles, Rubella vaccine in a combined

form between 12-18 months of age.

Live attenuated MMR vaccine-

Routine vaccination of children < 12yrs

Immunisation of adolescents and children of child bearing

age.

Screening all pregnant women and immunising them

RETRO VIRUS

HIV belongs to the family Retrovirus and the genera Lentivirus.

Etiologic agent of Acquired Immuno Deficiency Syndrome.

It is a linear single stranded RNA virus. It is an enveloped Spherical

virus, 100-140nm in diameter, has a cylindrical bar shaped

nucleoid. Has the enzyme ‘Reverse Transcriptase’

HIV infects the T4 cells, monocytes, macrophages. As the disease

progresses T4 cells are destroyed and leads to reversal of T4:T8

ratio.

There is a decrease in production of Interleukins and Lymphokines,

abnormal activation of B-cells, Decreased natural killer cell activity

and impaired lymphocyte and macrophage functions.

PATHOGENESIS

Exposure to HIV

Pt is asymptomatic Symptomatic

Persistent glandular lymphadenopathy

AIDS

Immunosuppression

Opportunistic infection

Lymphoma

Kaposi’s sarcoma

ROUTES OF TRANSMISSION

Sexual route

Trans placental route

Contaminated blood and its products

HIV AND THE EYELIDS

Kaposi’s sarcoma

Multiple molluscum lesions

Severe herpes zoster ophthalmicus

HIV AND THE ORBIT

CELLULITIS:

From contiguous sinus infection

B-CELL LYMPHOMA

HIV AND THE CONJUNCTIVA

Kaposi Sarcoma

Squamous Cell Carcinoma

HIV AND THE CORNEA

KERATITIS - Due to

Microsporidium

Herpes Simplex

Herpes zoster

HIV AND THE EYE -

UVEA AND POSTERIOR SEGMENT

Anterior Uveitis

HIV Retinopathy

Asymptomatic

Multiple cotton wool spots

Retinitis - Due to

CMV-Vasculitis, Vitritis, Haemorrhages.

VZV-Progressive outer Retinal necrosis

Toxoplasmosis-Retinitis

Choroiditis:

Pneumocystis

Cryptococcus

B-cell Intraocular lymphoma

OCULAR MANIFESTATIONS IN AIDS

Ocular adnexal Kaposi sarcoma

Molluscum contagiosum follicular conjunctivitis

Herpes zoster ophthalmicus

Keratitis due to Microsporidia and HSV

Infectious conjunctival granulomas due to cysticercosis, TB and fungus

CMV retinitis

Acute retinal necrosis syndrome due to HZV

Toxoplasma chorioretinitis

Syphilitic chorioretinitis

Ocular histoplasmosis

HIV retinopathy

DIAGNOSTIC TESTS FOR HIV

Non specific tests to detect immuno compromised state

Leucocyte count< 2000/mm3

Total CD4 count <200/mm3

Reversal of CD4: CD8 ratio

Raised IgG and IgA levels

Decreased platelet counts- thrombocytopenia

Diminished CMI by skin tests

Specific Tests:

Antigen detection P24 is the earliest viral marker.

IgM followed by IgG disappears within 4-8weeks.

Virus isolation - Tissue culture in embryonic kidney cells/ MRC-5.

PCR- DNA PCR / RNA PCR

Antibody detection

Screening with ELISA

Western Blot test- Confirmatory

TREATMENT

I.V Ganciclovir and Foscarnet are used in the treatment of CMV

retinitis.

Zidovudine and Didanosine are presently available, they block the

enzyme Reverse transcriptase.

Thank you