Electroretinography

Electroretinography records the electrical response of the retina to light. It measures the function of the photoreceptors (rods and cones) and the cells that connect to them, such as the bipolar cells, and it detects disease of the retina before changes are visible on examination. It is an objective test that does not depend on the patient's response.

Light flashes of set intensity and colour are presented to the eye, and the response is recorded with electrodes on the cornea or lower lid (contact lens, thread or foil electrodes) and skin electrodes near the eye. The test has several parts.

The full field electroretinogram measures the response of the whole retina, and is done after 20 to 30 minutes of dark adaptation for rod and combined responses, and after light adaptation for cone responses and flicker. The pattern electroretinogram measures the function of the macula and retinal ganglion cells, using a reversing checkerboard.

The multifocal electroretinogram maps the responses from about 100 small areas of the central retina. The electro oculogram measures the function of the retinal pigment epithelium. Visual evoked potentials may be added to test the visual system as far as the brain.

The test takes 30 to 90 minutes. The main waves are the a-wave (from photoreceptors), the b-wave (from bipolar and supporting glial cells), and oscillatory potentials (from inner retinal cells). Full field electroretinography is abnormal when more than about 20 to 30% of the retina is damaged, so a focal macular disease may be missed. The test confirms the diagnosis in inherited retinal dystrophies in most patients, and separates rod cone from cone rod patterns.

Indications.

• Suspected inherited retinal dystrophy: retinitis pigmentosa, cone rod dystrophy, Leber congenital amaurosis, congenital stationary night blindness, achromatopsia, and Stargardt disease.
• Unexplained visual loss with a normal appearing fundus, night blindness, and poor vision in infants and young children.
• Suspected toxic retinopathy (hydroxychloroquine, vigabatrin, other drugs) and retinal damage after poisoning.
• Retinal inflammation and degeneration with unclear cause, including autoimmune retinopathy and paraneoplastic retinopathy.
• Vascular disease: central retinal vein and artery occlusion (to assess ischaemia), and diabetic retinopathy in research.
• Before gene therapy, and to document baseline function.
• Media opacity (dense cataract, vitreous haemorrhage) when the retina cannot be seen, to assess retinal function before surgery.
• Medico legal documentation of retinal function, and suspected non-organic visual loss.

Not indicated for diseases that are clear on examination and imaging, and not sensitive to small, focal lesions.

Contraindications and precautions.

• Corneal abrasion, infection, or a very fragile cornea: the corneal electrode is avoided or a skin electrode is used.
• Open globe injury or recent eye surgery: delayed until healed.
• Allergy to topical anaesthetic or electrode gel or adhesive.
• Photosensitive epilepsy: caution with flashes.
• Pupil dilation is needed, with the cautions for narrow angles.
• Infants and young children need sedation or anaesthesia, which affects the response, so the same anaesthetic and a controlled setup are used.
• Patients taking drugs that affect the response (some anticonvulsants, anaesthetic agents) need notes made.

Preparation and technique.

The pupils are dilated fully, and the patient is dark adapted for 20 to 30 minutes. Corneal anaesthetic drops are given, and electrodes are placed: an active electrode on the cornea, a reference near the outer corner of the eye, and a ground on the forehead or earlobe. The patient sits in front of a stimulator bowl and looks at a fixation point.

Flashes of increasing intensity are given to record the rod response, then the maximal combined response. The patient is then light adapted for 10 minutes, and cone responses and 30 Hz flicker are recorded. Several responses are averaged, and artefacts from blinks and movements are rejected. The recording is repeated to confirm reproducibility.

Results are compared with the laboratory's age matched normal values.

Normal appearances.

In a dark adapted eye, a dim flash gives a rod driven b-wave, and a bright flash gives a combined response with a clear a-wave and larger b-wave, with amplitudes of several hundred microvolts (the b-wave is about 300 to 500 microvolts, depending on the laboratory). In the light adapted state, the cone response and 30 Hz flicker have smaller amplitudes and shorter timing. The two eyes give similar results. Amplitudes fall with age and with high myopia, and the timing (implicit time) is constant.

Interpretation.

• Rod cone dystrophy (retinitis pigmentosa): early loss or extinction of the rod response and reduced combined and cone responses, with delayed timing. The test is abnormal before the fundus changes in many patients.
• Cone rod and cone dystrophies: reduced or absent cone and flicker responses, with preserved or later reduced rod responses.
• Congenital stationary night blindness: a negative waveform in the combined response (a normal a-wave with a reduced b-wave), with normal fundus.
• Achromatopsia: absent cone responses with normal rod responses.
• Stargardt disease and macular dystrophies: normal or mildly reduced full field response in early disease, and an abnormal pattern or multifocal electroretinogram.
• Toxic retinopathy: hydroxychloroquine shows reduced multifocal responses in the parafovea. Vigabatrin shows reduced cone flicker.
• Central retinal artery occlusion: a negative waveform with a reduced b-wave. Central retinal vein occlusion: a reduced b-wave and delayed flicker, which shows ischaemia and risk of neovascularisation.
• Autoimmune and paraneoplastic retinopathy: an abnormal response with a negative waveform, in a patient with rapid vision loss.
• Optic nerve disease: normal full field responses, with an abnormal pattern response in ganglion cell disease.
• Non-organic loss: a normal electroretinogram and visual evoked potentials with poor reported vision.

Critical values and findings needing immediate action.

• There are no emergency values for the test itself.
• A negative electroretinogram or a reduced response in a patient with subacute visual loss: urgent search for paraneoplastic or autoimmune retinopathy, which may precede cancer.
• Toxic retinopathy: urgent discussion with the prescriber about stopping the drug.
• Absent responses in an infant with poor vision: urgent referral to a paediatric ophthalmologist and genetic services for diagnosis and counselling.
• Ischaemic pattern in vein occlusion: urgent review for neovascularisation treatment.

Limitations and artefacts.

• Results are affected by incomplete dilation, inadequate dark adaptation, poor electrode contact, movement, blinks, and noise. Small pupils lower the amplitude.
• Corneal electrodes are uncomfortable, and results can differ between electrode types. Sedation and anaesthesia change results in children.
• Normal values depend on the laboratory, the equipment, and age, so the laboratory's own normal range is used.
• The full field electroretinogram does not detect small macular or localised lesions, which need pattern or multifocal recordings.
• Responses fall with high myopia, cataract, and media opacity, and in the elderly, and a low response is not always due to retinal disease.
• Variation between visits can mimic progression, and results are compared with care.
• The test is expensive, needs specialists, and is available in few centres.

Special groups.

• Infants and children: tests are done with sedation or anaesthesia, with skin electrodes, in specialist centres, and early diagnosis helps with counselling and gene therapy planning.
• Patients on hydroxychloroquine, vigabatrin or similar drugs: baseline and regular monitoring with multifocal electroretinography and other imaging.
• Patients with dense media opacity: a normal result predicts the potential for visual gain after cataract surgery.
• Families with inherited retinal disease: testing of relatives, genetic counselling and genetic testing.
• Patients with unexplained visual loss, and normal examination: the test often finds the diagnosis.
• Regions: electroretinography is available in few specialist centres, and the diagnosis of inherited retinal disease depends on history (night blindness, family history, consanguinity), examination of the fundus with pigment changes, and visual fields. Vitamin A deficiency causes night blindness and an abnormal rod response that recovers with treatment, and is common in some regions.

Follow up tests.

• Optical coherence tomography, fundus photography, and fundus autofluorescence.
• Visual field testing, and dark adaptation tests.
• Genetic testing with a retinal disease gene panel, and genetic counselling.
• Visual evoked potentials for function of the optic nerve and visual areas of the brain.
• Serum vitamin A, and antiretinal antibodies, with cancer screening when paraneoplastic retinopathy is suspected.
• Review of the drugs.
• Repeat electroretinography at planned intervals for progression, in the same laboratory.