
<div className="bg-blue-200 px-4 rounded-md shadow-lg dark:text-gray-700">
  <table>
    <tbody>
      <tr>
        <td>
          <strong>DNA</strong>
        </td>
        <td>
          <strong>RNA</strong>
        </td>
        <td>
          <strong>Oncogenic</strong>
        </td>
      </tr>
      <tr>
        <td>Adenovirus&nbsp;</td>
        <td>Rotavirus</td>
        <td>HBV- hepatocellular carcinoma</td>
      </tr>
      <tr>
        <td>Parvovirus&nbsp;</td>
        <td>Enterovirus</td>
        <td>Papovavirus&nbsp;</td>
      </tr>
      <tr>
        <td>Herpesviruses (HSV, VSV, EBV, CMV)</td>
        <td>HCV</td>
        <td>EBV- Burkitt&rsquo;s lymphoma, nasopharyngeal neoplasia</td>
      </tr>
      <tr>
        <td>Pox viruses including Molluscum</td>
        <td>MMR viruses</td>
        <td>HPV: E6 protein inactivates p53</td>
      </tr>
      <tr>
        <td>HBV</td>
        <td>RSV</td>
        <td>HTLV-1</td>
      </tr>
      <tr>
        <td>HPV</td>
        <td>Influenza</td>
        <td>&nbsp;</td>
      </tr>
      <tr>
        <td>Papovavirus</td>
        <td>LCMV</td>
      </tr>
      <tr>
        <td>&nbsp;</td>
        <td>HIV (retrovirus)</td>
      </tr>
      <tr>
        <td>Dengue and yellow fever</td>
      </tr>
      <tr>
        <td>HTLV-1 (retrovirus)</td>
        <td>(NB: HIV is non-oncogenic)</td>
      </tr>
    </tbody>
  </table>
</div>
<ul>
  <li>Acellular: enter cells to &lsquo;borrow&rsquo; metabolism</li>
  <li>Viral genome composed of capsids enclosed in a protein shell</li>
  <li>Capsids are icosahedral or helical</li>
  <li>Replication:</li>
  <ul>
    <li>Adsorption: attach to cell via electrostasis or cell receptors</li>
    <li>Penetration</li>
    <li>
      Cell enzymes remove the capsid and nucleic acid replication occurs (varies depending on DNA or
      RNA)
    </li>
    <ul>
      <li>DNA: mostly use host cell enzymes in the nucleus to make mRNA</li>
      <li>
        RNA: replication occurs in the cytoplasm. Cannot borrow host enzymes but use reverse
        transcriptase to make DNA from RNA
      </li>
    </ul>
    <li>Maturation</li>
    <li>New particles released by cell lysis or budding</li>
  </ul>
  <li>Transmission:</li>
  <ul>
    <li>Vertical: maternal to offspring</li>
    <ul>
      <li>CMV</li>
      <li>Rubella</li>
      <li>HSV</li>
    </ul>
    <li>Horizontal: from one individual to another</li>
    <ul>
      <li>HSV (again)</li>
    </ul>
  </ul>
  <li>Chronic infections</li>
  <ul>
    <li>Persistence: replication occurs at a slow rate</li>
    <li>Latency: no replication occurs but the viral genome integrates into host DNA</li>
  </ul>
  <li>Malignant and teratogenic change</li>
  <li>Evasive strategies</li>
  <ul>
    <li>Change antigens via point mutations or antigen shift</li>
    <li>
      Dodge complement: HSV produces a C3b binding molecule and EBV binds to complement receptors
    </li>
  </ul>
</ul>

## HSV-1: Herpes stromal keratitis
<ul>
  <li>DNA</li>
  <li>Most common cause (globally) of ocular viral infection</li>
  <li>Life cycle</li>
  <ul>
    <li>Entry into host and replication at peripheral site</li>
    <li>Spread to axonal terminals of sensory neurones</li>
    <li>Retrograde intra-axonal transport to neuronal cell bodies in ganglia</li>
    <li>Latency in trigeminal ganglia</li>
    <li>Reactivation: antegrade transport of virus to the periphery</li>
    <li>The lytic pathway leads to cell lysis and particle release</li>
  </ul>
  <li>Infection often asymptomatic</li>
  <li>Oral and genital lesions</li>
  <li>Reactivation:</li>
  <ul>
    <li>UV radiation</li>
    <li>Fever</li>
    <li>Stress</li>
    <li>Menstruation</li>
    <li>Trauma&nbsp;</li>
  </ul>
  <li>Primary infection: TLR9 involved in initial activation</li>
</ul>
<ClinicalCorrelate>
  <>
    <p>Angiogenesis and lymphangiogenesis of normally avascular cornea occurs&nbsp;</p>
    <ul>
      <li>Allows an adaptive immune response but impairs corneal transparency</li>
      <li>Ring infiltrates in the corneal stroma represent antigen-antibody complexes</li>
    </ul>
  </>
</ClinicalCorrelate>

## VZV
<ul>
  <li>DNA</li>
  <li>Causes chicken pox: highly infectious, respiratory spread</li>
  <li>
    Becomes latent in ganglia especially the trigeminal (but also thoracic, lumbar and cervical)
  </li>
  <li>Reactivation (shingles):</li>
  <ul>
    <li>
      Immunosuppression (cell-mediated immunity is essential to maintain the virus in the latent
      state)
    </li>
    <li>X-ray</li>
  </ul>
</ul>

## Viral retinitis
<ul>
  <li>Important cause of visual loss in immunosuppressed patients</li>
  <li>Most common:</li>
  <ul>
    <li>HSV</li>
    <li>VZV</li>
    <li>CMV</li>
    <li>LCMV: lymphocytic choriomeningitis virus</li>
    <li>EBV</li>
    <li>Rubella</li>
    <li>Measles</li>
    <li>West Niles</li>
    <li>Dengue</li>
  </ul>
  <li>Further explored in Part 2 package</li>
</ul>

## CMV
<ul>
  <li>Extremely common but usually subclinical</li>
  <li>Double stranded DNA virus of the herpes family</li>
  <li>Primary infection: CD8 T-cell mediated (the virus becomes latent in lymphocytes)</li>
  <li>
    Most pathogenic after congenital infection and fetal abnormalities (due to infection DURING
    pregnancy. Infection prior to pregnancy may lead to reactivation but only an asymptomatic fetal
    infection)
  </li>
  <li>Owl&rsquo;s eye inclusion bodies are a specific histopathological sign</li>
  <li>Clinical features:</li>
  <ul>
    <li>Chorioretinitis (in immunocompromised)</li>
    <ul>
      <li>Necrotizing retinitis can lead to retinal detachment</li>
      <li>Affects the posterior pole mostly</li>
      <li>Full thickness retinal necrosis seen histologically</li>
    </ul>
    <li>Keratitis</li>
    <li>Optic atrophy</li>
    <li>Cataract&nbsp;</li>
    <li>Hydrocephalus</li>
    <li>Cytomegalic inclusion disease: strabismus</li>
    <li>Microcephaly and microphthalmia</li>
    <li>Jaundice (hepatitis), hepatosplenomegaly</li>
    <li>Intracranial calcification</li>
  </ul>
  <li>Treatment: oral ganciclovir</li>
</ul>

## Hepatitis B virus
<ul>
  <li>DNA virus</li>
  <li>Oncogenic&nbsp;</li>
  <li>Average incubation period is 60-90 days</li>
  <li>
    Outer coat: HBsAg (&ldquo;Australia antigen&rdquo;) raised in acute illness and in carriers
  </li>
  <ul>
    <li>Persistence of HbsAg increases the risk of chronic liver disease</li>
  </ul>
  <li>
    Inner core: HBeAg indicates acute infection or supercarrier status (increased infectivity)
  </li>
  <li>
    Anti-HBsAg: indicates previous infection or immunity (appears late). Reliable measure of
    non-infectivity.
  </li>
  <li>Anti-HB core (IgM/IgG): previous infection</li>
  <li>Primarily horizontal transmission via parenteral or sexual route</li>
  <li>HBeAg positive mothers can transmit vertically</li>
  <li>Vaccination uses HBsAg</li>
</ul>

## HPV
<ul>
  <li>dsDNA</li>
  <li>More than 60 types</li>
  <li>Target epithelial cells</li>
  <li>A minority insert themselves into the genome and cause malignant change</li>
  <li>E2 gene contributes to HPV proliferation</li>
  <li>
    The E6 protein of HPV 16 and 18 causes p53 protein degradation (these are high-risk associated
    with conjunctival carcinoma)
  </li>
  <li>E7 protein inactivates the product of retinoblastoma tumour suppressor gene</li>
  <li>HPVs 6 and 11 cause conjunctival papillomata</li>
</ul>

## Kaposi&rsquo;s sarcoma
<ul>
  <li>Malignant tumour of the vascular endothelium</li>
  <li>
    Associated with Herpes hominis virus type 8 infection (<strong>HHV-8</strong>)
  </li>
  <li>More common in sexually transmitted HIV</li>
  <li>Usually seen when CD4 count &lt;500 cells/microlitre</li>
  <li>Skin and palate are common sites</li>
  <li>Radiosensitive (cutaneous and lymph nodes) and chemosensitive (systemic)</li>
  <li>
    May be mistaken for subconjunctival haemorrhage (bright red, fleshy, violaceous nodular mass,
    commonly in the fornix).
  </li>
  <li>
    Ocular adnexal Kaposi&rsquo;s typically presents as a pink-red conjunctival mass or blue-purple
    eyelid mass
  </li>
</ul>

## Molluscum contagiosum
<ul>
  <li>Poxvirus: DNA</li>
  <li>Grows in the cytoplasm</li>
  <li>Possess enzymes allowing replication independent of the host</li>
  <li>Pearly white lesions of the skin (epidermal hyperplasia)</li>
  <li>Transmission by direct contact or sexually</li>
</ul>

## Adenoviruses
<ul>
  <li>Numerous serotypes (dsDNA)</li>
  <li>No envelope</li>
  <li>
    Transmission by direct contact with virus in ocular secretions, instruments, eye drops etc.
  </li>
  <li>Can be cultured on HeLa cell lines</li>
  <li>A single infected cell can product 10000 virions every 30-36 horus</li>
  <li>Avoid immune defences:</li>
  <ul>
    <li>Disrupt MHC presentation by infected cells</li>
    <li>Suppress transcription encoding class I MHC</li>
    <li>Inhibition of cell lysis by TNF</li>
  </ul>
  <li>Can interact with retinoblastoma and p53 genes</li>
  <li>Serotypes 8, 19, 35 and subgroup D: epidemic keratoconjunctivitis (EKC)</li>
  <ul>
    <li>May be a severe follicular conjunctivitis with punctate keratitis</li>
    <li>Delayed presentation 7-10 days after inoculation</li>
    <li>True and pseudomembranes</li>
    <li>Subconjunctival hemorrhage</li>
    <li>Subepithelial infiltrates</li>
  </ul>
</ul>
<HotTopic>
  <p>
    Management is supportive and topical steroids should only be used for vision threatening
    subepithelial infiltrates or conjunctival membranes
  </p>
</HotTopic>
<ul>
  <li>Steroids may prolong the disease course</li>
</ul>
<ul>
  <li>Contagious: while still hyperaemic and tearing</li>
</ul>
<ul>
  <li>Serotypes 3 and 7: pharyngoconjunctival fever</li>
  <ul>
    <li>Flu-like symptoms</li>
  </ul>
  <li>Skin papilloma</li>
</ul>

## LCMV
<ul>
  <li>Single stranded RNA arenavirus and retrovirus</li>
  <li>
    Sources: ingestion of particles contaminated by mouse faeces, urine or saliva (rodent borne)
  </li>
</ul>

## Measles
<ul>
  <li>Paramyxovirus (RNA)</li>
  <li>Clinical features (never subclinical):</li>
  <ul>
    <li>Fever</li>
    <li>Prodromal cough</li>
    <li>Coryza</li>
    <li>Conjunctivitis</li>
    <li>Rarely corneal scarring (typically with vitamin A deficiency)</li>
  </ul>
  <li>Can cause secondary bacterial infection</li>
  <ul>
    <li>Usually respiratory</li>
    <li>Rarely encephalitis</li>
    <li>More rarely: subacute sclerosing panencephalitis (SSPE).</li>
    <ul>
      <li>
        Slowly progressive and fatal encephalitis associated with chorioretinitis and maculopathy.
      </li>
    </ul>
  </ul>
</ul>

## Rubella
<ul>
  <li>Togavirus (RNA)</li>
  <li>Transmission: droplet</li>
  <li>Subclinical in 80% of small children and 10% of adults</li>
  <li>The fetus is infected transplacentally, highest risk within the first 10 weeks</li>
  <li>
    Congenital abnormalities if infection during first trimester (when fetal organs developing)
  </li>
  <ul>
    <li>Transplacental spread to fetus</li>
    <li>Miscarriage or stillbirth</li>
    <li>
      <strong>Cataracts </strong>(2nd most common eye finding): pearly white nuclear opacifications
    </li>
    <ul>
      <li>Live virus particles can persist in the lens for many years</li>
      <li>
        They may be released after cataract surgery leading to a vigorous inflammatory response
      </li>
    </ul>
    <li>Microphthalmia</li>
    <li>
      <strong>Chorioretinitis </strong>leading to bilateral pigmentary retinopathy (most common
      ocular findings, &lsquo;salt-and-pepper&rsquo; fundus. Not visually significant and ERG is
      normal)
    </li>
    <li>Corneal hydrops/clouding, keratoconus</li>
    <li>
      <strong>Glaucoma </strong>(3rd most common finding in eyes): does <strong>not </strong>occur
      simultaneously with cataract in congenital rubella! For some reason.
    </li>
    <li>Strabismus&nbsp;</li>
    <li>Neural deafness</li>
    <li>Congenital heart defects eg. PDA</li>
  </ul>
  <li>Raised IgM indicates recent infection (IgG indicates previous infection)</li>
</ul>

## Mumps
<ul>
  <li>Paramyxovirus (RNA)</li>
  <li>Clinical features</li>
  <ul>
    <li>Fever</li>
    <li>Parotitis</li>
    <li>Orchitis</li>
    <li>Pancreatitis</li>
    <li>Meningoencephalitis</li>
    <li>Dacroadenitis</li>
    <li>Extraocular palsies</li>
  </ul>
  <li>Recent infection: antibody to S antigen</li>
  <li>Previous infection: antibody to V antigen</li>
</ul>

## Enteroviruses
<ul>
  <li>RNA viruses with icosahedral capsid</li>
  <li>Faecal-oral spread, direct contact, droplet</li>
  <li>Acute haemorrhagic conjunctivitis</li>
</ul>

## HIV
<ul>
  <li>
    Single stranded RNA virus containing reverse transcriptase (exogenous virus ie. do not contain
    conserved cellular genes)
  </li>
  <li>Non-oncogenic cytocidal retrovirus</li>
  <li>HIV-1 and HIV-2 have different glycoprotein envelopes</li>
  <ul>
    <li>Type 1: urban centres, mainly transmitted via homosexuals and IVDUs</li>
    <li>Type 2: African, mainly heterosexually transmitted</li>
  </ul>
  <li>Weak virus: killed by strong acid and alkali, bleach and ethanol</li>
  <li>Pathogenesis</li>
  <ul>
    <li>
      CD4 receptors on T-helper cells act as receptors (although HIV can bind to macrophages,
      monocytes, microglia&hellip;)
    </li>
    <li>Binds to CD4 receptors with CCR5 or CXCR4 as co-receptors</li>
    <li>gag gene encodes the core nucleocapsid polypeptides</li>
    <li>Viral reverse transcriptase transcribes the ssRNA to DNA</li>
    <ul>
      <li>This is highly error prone, so new strains can be made</li>
    </ul>
    <li>The complementary DNA becomes part of the host genome: provirus</li>
    <li>Multinucleate cells form after infection leading to cell death (destroying CD4 cells)</li>
    <li>Cell mediated immune response fails (increased risk of infection and neoplasia)</li>
    <li>Decreases T cell dependent immunoglobulins</li>
    <li>
      Becomes latent in monocytes and macrophages (which also possess CD4 receptors) becoming
      invisible to immune defences
    </li>
    <li>Frequent mutations lead to changing glycoprotein envelopes and changing antigenicity</li>
  </ul>
  <li>ELISA (enzyme-linked immunosorbent assay) is a common diagnostic test in use</li>
  <ul>
    <li>Plate-based assay with quantitative and qualitative properties</li>
    <li>Can detect antigen or antibody, peptides, hormones, proteins</li>
    <li>Highly sensitive and specific</li>
    <li>
      Antigen or antibody is labelled with an enzyme which induces a colour change in a substrate
    </li>
  </ul>
  <li>
    Antibody profile varies depending on stage of disease eg. AIDS-related complex compared to
    full-blown AIDS
  </li>
  <ul>
    <li>ARC and AIDS: antibodies to gp41, gp120 and gp160 envelope glycoproteins</li>
    <li>Transition from ARC to AIDS: increase in p24 (a core protein) and reduced CD4:CD8 ratio</li>
    <li>NB: presence of p24 in the blood is one of the earliest signs of infection</li>
  </ul>
</ul>

## Human T-lymphotropic virus type 1 (HTLV-1)
<ul>
  <li>Single stranded RNA</li>
  <li>
    Oncogenic retrovirus: T cell leukaemia, lymphoma (mycosis fungoides, Sezary syndrome),
    progressive myelopathy, uveitis
  </li>
  <li>Immortalises peripheral T cells in vitro via the tax gene</li>
  <li>Transmission: vertical and horizontal (sexual transmission or parenteral)</li>
  <li>Endemic in Japan, Africa, Caribbean&nbsp;</li>
</ul>

## TORCH viruses causing fetal abnormalities
<ul>
  <li>Toxoplasmosis</li>
  <li>Other (syphilis, HIV-1, Listeria)</li>
  <li>Rubella</li>
  <li>CMV</li>
  <li>Herpes viruses</li>
</ul>

## Live vaccines
<ul>
  <li>Polio</li>
  <li>Yellow fever</li>
  <li>MMR</li>
</ul>


Microbiology

Viral Infections

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Cornea

Corneal Structure And Development

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Pathology

Collagen

Tissue Damage

Inflammation

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Free Radicals And Antioxidants

Immunology

Ocular Immunology

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Antimicrobials

Genetics

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Chromosome Defects

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance