

## Electroretinogram
<ul>
  <li>
    A measurement of the retina&rsquo;s electrical mass response to a light stimulus (a summation of
    photoreceptor and bipolar cell activity)
  </li>
  <li>Affected by:</li>
  <ul>
    <li>Adaptive state of the eye eg photopic (cone ERG) vs scotopic (rod ERG)</li>
    <li>Type of stimulus</li>
  </ul>
  <li>Electrode placed in contact with cornea and reference electrode on forehead</li>
  <li>
    The ERG is <span className="font-semibold">unaffected by small localised lesions</span> and will therefore be normal
    in disease confined to the macula and will also not detect disease of the ganglion cell layer or
    optic nerve
  </li>
  <li>
    Does <span className="font-semibold">not </span>measure VA
  </li>
</ul>
<h4>Waveforms</h4>
<ul>
  <li>Two main waves in response:</li>
  <ul>
    <li>
      Negative A wave, arising from the <span className="font-semibold">photoreceptors</span>
    </li>
    <ul>
      <li>A1 originates in cones</li>
      <li>A2 originates in rods</li>
    </ul>
    <li>
      Positive B wave, caused by bipolars but magnified by Muller cells (which act as a sink for
      potassium ions released by depolarising bipolar cells):{' '}
      <span className="font-semibold">surrogate for bipolar cell function</span>
    </li>
    <li>
      Oscillatory potentials are superimposed on b wave and increase with stimulus intensity.
      Represent amacrine cell function.
    </li>
    <li>
      C wave (occasionally present): slow positive wave generated by RPE but also depends on
      photoreceptor integrity. Can be used to represent the function of these two structures and
      their interactions
    </li>
    <li>
      D wave: only seen when using stimulus of long duration which is then stopped (ie. cessation of
      constant illumination)
    </li>
  </ul>
  <li>Implicit time: time from stimulus to peak of b wave</li>
  <li>
    In a constant subject, increasing the intensity of the stimulus will first cause increase in the
    b wave amplitude followed by development of the preceding a wave which also increases in size
    and both waves become faster.&nbsp;
  </li>
  <ul>
    <li>
      Pupil size and media opacity will affect the intensity of light stimuli entering the eye
    </li>
  </ul>
  <li>
    Colour of stimulus: rod responses peak at the blue-green region of spectrum while cones
    responses vary with types of cones but average peak is at orange light (high end).
  </li>
  <ul>
    <li>Rod system is more sensitive across the whole spectrum compared to cones.</li>
  </ul>
  <li>
    Frequency of stimulation: the critical fusion frequency (CFF) represents the maximum frequency
    that can be perceived as flickering
  </li>
  <ul>
    <li>
      Highest CFF for rod vision is 15-28Hz (hence a higher frequency flicker will only elicit a
      cone response)
    </li>
    <li>Highest CFF for cone vision is 50Hz</li>
  </ul>
  <li>
    Bright white flash (standard stimulus): both a and b wave amplitudes are maximal in scotopic
    (dark adapted) conditions
  </li>
  <li>Dim white or blue flash: response is generated only by rods</li>
  <li>
    Bright background (saturates rods) or high frequency flickers elicit a pure cone response (since
    rods have poor temporal resolution): low amplitudes but very fast kinetics (time to peak is
    30-32ms)
  </li>
</ul>
<h4>Examples</h4>
<ul>
  <li>
    Reduced b wave (with preserved a wave implying normal photoreceptors but abnormal{' '}
    <span className="font-semibold">bipolar cells</span>) ie. an &ldquo;<span className="font-semibold">electronegative response</span>&rdquo;,
    occurs in many conditions including
  </li>
  <ul>
    <li>Inner retinal process</li>
    <ul>
      <li>CRAO/CRVO</li>
      <li>Toxicity: iron (siderosis), quinine, methanol</li>
      <li>Juvenile X-linked retinoschisis</li>
    </ul>
    <li>Bipolar cell or photoreceptor-bipolar synapse process</li>
    <ul>
      <li>Melanoma associated retinopathy</li>
      <li>Congenital stationary night blindness</li>
      <li>Autosomal dominant neovascular inflammatory vitreoretinopathy</li>
    </ul>
    <li>Miscellaneous&nbsp;</li>
    <ul>
      <li>Duchenne/Becker muscular dystrophies</li>
      <li>Birdshot chorioretinopathy</li>
    </ul>
  </ul>
  <li>
    Reduced or absent photopic response: cone dystrophies (which show a normal or subnormal but
    present scotopic ERG)
  </li>
  <ul>
    <li>Achromatopsia&nbsp;</li>
    <li>Cone dystrophies</li>
  </ul>
  <li>No response (extinguished):</li>
  <ul>
    <li>Batten&rsquo;s disease</li>
    <li>Leber&rsquo;s congenital amaurosis</li>
    <li>Rod-cone dystrophies like RP</li>
    <li>Total RD</li>
    <li>Cancer associated retinopathy</li>
    <li>Advanced siderosis</li>
  </ul>
  <li>Increased a wave: albinism</li>
  <li>Reduced oscillatory potentials: vigabatrin toxicity</li>
</ul>
<HotTopic>
  <p>
    Siderosis (eg. retained intraocular iron foreign body): increasingly negative a wave
    (supranormal) followed (in late stage) by decreasing b wave amplitude. Advanced siderosis leads
    to extinguished ERG.
  </p>
</HotTopic>

## Pattern electroretinogram
<ul>
  <li>
    Retinal electrical response to a patterned stimulus and represents{' '}
    <span className="font-semibold">central retinal and ganglion cell function</span>
  </li>
  <li>Objective assessment of macular function</li>
  <li>
    Reference electrode must be place on ipsilateral temple or outer canthus to avoid interference
    from cortical-evoked potential
  </li>
  <li>
    Stimulus is usually a <span className="font-semibold">reversing chequerboard</span>
  </li>
</ul>
<h4>Indications</h4>
<ul>
  <li>Macular dystrophies eg. Stargardt&rsquo;s</li>
  <li>Differentiating macular and optic nerve dysfunction</li>
  <li>Assessment of unexplained visual loss</li>
</ul>
<h4>Waveform</h4>
<ul>
  <li>
    Three responses (N=negative and P=positive. The subscript refers to the timing in miliseconds of
    the response&rsquo;s peak):
  </li>
  <ul>
    <li>Negative N35 wave</li>
    <li>Positive P50 wave (macular photoreceptors)</li>
    <li>Second negative N95 wave (ganglion cell layer)</li>
  </ul>
  <li>
    Therefore the P50 component is abnormal in macular disease (but a full field ERG would also be
    needed to exclude a generalised retinal dysfunction)
  </li>
  <li>Abnormal N95 component suggests optic nerve/ganglion cell disease</li>
  <ul>
    <li>
      The PERG will only be abnormal in optic neuropathy if there is sufficient damage to cause
      retrograde degeneration of the ganglion cells
    </li>
    <li>
      Eg. optic nerve demyelination, ischaemic optic neuropathy, tobacco-alcohol amblyopia,
      compressive lesions, LHON and dominant optic atrophy
    </li>
  </ul>
</ul>

## Multifocal ERG
<ul>
  <li>Useful to detect outer retinal disease&nbsp;</li>
  <li>Provides a topographic representation that can be mapped to patient&rsquo;s visual field</li>
</ul>
<h4>Waveform</h4>
<ul>
  <li>N1: initial negative deflection</li>
  <li>P1: positive peak</li>
</ul>

## Electro-oculogram
<ul>
  <li>
    Measures the &lsquo;corneoretinal standing potential&rsquo;: ie. the electrical mass response to
    the eye, but primarily reflecting the metabolic activity of the RPE
  </li>
  <li>The cornea is positively charged compared to the RPE</li>
  <li>The resting potential of the eye is: 60mV</li>
  <li>Uses fixed excursion lateral eye movements under conditions of varying luminance</li>
  <li>
    Electrodes are placed at the outer and inner canthi during dark adaptation and followed by
    bright light
  </li>
</ul>
<h4>Waveform&nbsp;</h4>
<ul>
  <li>
    The &lsquo;dark trough&rsquo; is measured when the eyes make saccadic movements in the dark
  </li>
  <li>The &lsquo;light peak&rsquo; is measured when the move against a steady light background</li>
  <li>
    The amplitude should increase markedly during light adaptation compared to a trough in the dark
  </li>
  <li>
    The ratio of the light peak to dark trough is known as the Arden ratio and is normally expressed
    as a percentage
  </li>
  <li>Arden is usually &gt;180% in normal eyes (&gt;1.8). &lt;1.4 is considered abnormal</li>
  <li>
    The EOG reflects<span className="font-semibold"> retinal pigment epithelium (and outer retina) activity</span>
  </li>
  <li>
    Results tend to correlate with the ERG (except in{' '}
    <span className="font-semibold">Best&rsquo;s vitelliform macular dystrophy </span>where the ERG is normal and the EOG
    light peak is much reduced)
  </li>
</ul>
<HotTopic>
  <p>
    Patients with Best&rsquo;s and carriers of Best&rsquo;s disease both show a diminished Arden
    ratio
  </p>
</HotTopic>
<ul>
  <li>EOG can be used to distinguish local from diffuse retinal disease</li>
  <li>Note: requires pupillary dilatation</li>
</ul>

## Visual evoked potential
<ul>
  <li>
    Measurement of occipital cortical electrical response to retinal stimulation via flash or
    pattern stimuli (pattern is preferred as it has better inter-subject reliability)
  </li>
  <ul>
    <li>Reflects the activity of the whole visual pathway</li>
    <li>The wave pattern of flash VEP shows great variability between people</li>
    <li>The pattern VEP arises from the V1 area of the cortex</li>
    <li>The flash VEP arises from the V2 area of the cortex</li>
  </ul>
  <li>
    Primarily represents optic nerve function and useful to quantify function between the retina and
    the cortex
  </li>
</ul>
<Note>
  <p>VEP cannot localise pathology</p>
</Note>
<ul>
  <li>
    <span className="font-semibold">Can approximate to visual acuity</span>: loss of amplitude approximates to reduced VA.
    may provide indication of visual function in infants
  </li>
  <li>Electrodes placed over occipital scalp areas</li>
  <li>
    Pupils must not be dilated as accommodation is lost, and refractive error must be corrected
    (except for flash VEPs)
  </li>
  <ul>
    <li>
      Flash VEPs do not require as much cooperation from the patient and so can be useful in
      children or unconscious patients
    </li>
  </ul>
</ul>
<h4>Waveform&nbsp;</h4>
<ul>
  <li>N75</li>
  <li>
    P100: this is the major component and is very reliable between subjects and generally stable
    from age 5 to 60 (time to peak only slows 1ms across this age gap). The p100 is predominantly a
    macular response
  </li>
  <li>N135</li>
  <li>P100 latency is the most useful measurement but amplitude is also useful</li>
  <ul>
    <li>The amplitude approximates to visual acuity</li>
  </ul>
  <li>
    Monocular stimuli evoke responses from both cortices representing the degree of chiasmal
    crossover
  </li>
  <li>Any abnormalities of the visual pathways or visual cortex can affect the VEP</li>
</ul>
<h4>Examples&nbsp;</h4>
<ul>
  <li>
    Multiple sclerosis: delayed P100 component in affected eye (presentation is usually unilateral
    therefore asymmetric retrobulbar neuritis).
  </li>
  <ul>
    <li>Over time both nerves tend to be involved and amplitudes are diminished</li>
  </ul>
  <li>
    Trauma: visual pathway compression may initially lead to no VEP response being found but as
    inflammation subsides it may return so progress can be monitored
  </li>
  <li>
    Tumours: eg in patients with NF1. VEPs may show prolongation and eventually diminished
    amplitudes then obliteration
  </li>
  <li>Quantification and monitoring of progression in patients with atrophic/pale optic discs</li>
  <li>
    Drug toxicities: slow P100 components eg ethambutol, amiodarone, methanol, carbon monoxide,
    isoniazid, linezolid, sildenafil, infliximab
  </li>
</ul>
<HotTopic>
  <p>
    Albinism: enhanced chiasmal cross-over (a larger proportion of retinal ganglion cell fibres
    cross at the chiasm in albino patients). Stimulating the left eye produces predominantly right
    occipital lobe response
  </p>
</HotTopic>
<ul>
  <li>Amblyopia: flash VEP is normal but pattern VEP is abnormal</li>
</ul>
<Note>
  <p>
    VEP abnormalities are symptomatic but not diagnostic. Retinal disease alone will significantly
    affect VEP and so they cannot distinguish optic neuropathy from retinal disorders
  </p>
</Note>


Clinical Techniques

Electrodiagnostics

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

Microbiology

Viral Infections

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