Electroretinogram (ERG)

Definition

Principle & Recording Setup

• An active (corneal) electrode — placed on or near the cornea (contact lens electrode)
• A reference electrode — placed on the forehead or earlobe
• A ground electrode — placed elsewhere on the body
• The potential difference between the two electrodes is amplified and displayed

Components of the Normal ERG Waveform

• Amplitude of b-wave — measured from the a-wave trough to the b-wave peak
• Latency — time from stimulus to commencement of the a-wave
• Implicit time — time from stimulus to b-wave peak
• b:a ratio — a reduced ratio indicates inner retinal dysfunction

Types of ERG

1. Full-field ERG (Ganzfeld ERG)

• Standardised by the International Society for Clinical Electrophysiology of Vision (ISCEV)
• Uses diffuse stimulation of the entire retina
• Consists of 6 standard recordings (ISCEV 2022 update)
• Assesses generalised retinal disorders; cannot detect localised pathology

• Dim flash (0.01 cd·s/m²) → rod-only response: small b-wave, barely visible a-wave
• Bright white flash → combined rod-cone response: prominent a-wave and b-wave
• Oscillatory potentials → bright flash with modified recording parameters

• Bright single flash → cone a- and b-wave
• 30 Hz flicker → isolates cones (rods cannot follow >20 Hz); measures cone b-wave amplitude and implicit time

2. Multifocal ERG (mfERG)

• Produces topographical maps of retinal function across the macular region
• Patient fixates on an array of flickering hexagons (scaled for photoreceptor density — smaller stimulus at the fovea where density is high)
• Results displayed as a 3D plot resembling the hill of vision
• Used in: early cone-rod dystrophies (occult macular dystrophy), autoimmune retinopathies (normal fundal appearance), macular RP

3. Pattern ERG (PERG)

• Uses pattern-reversal stimulus (same as VEP)
• Targets retinal ganglion cell function
• Used to detect subtle optic neuropathy and early glaucoma

4. Focal ERG

• Assesses macular function specifically
• Rarely used clinically

Interpretation Patterns

Clinical Applications

1. Diagnosis of inherited retinal dystrophies — retinitis pigmentosa, cone-rod dystrophy, CSNB, Leber congenital amaurosis
2. Monitoring disease progression in dystrophies and uveitis (e.g., birdshot retinopathy)
3. Drug toxicity monitoring — e.g., hydroxychloroquine, vigabatrin toxicity
4. Detecting retinal ischaemia — CRAO, CRVO, diabetic retinopathy
5. Paraneoplastic retinopathies — CAR (extinguished ERG), MAR (electronegative ERG)
6. Intraocular foreign body (IOFB) — serial ERGs to monitor for siderosis
7. Screening before surgery — assessing retinal function when media are opaque (dense cataract, vitreous haemorrhage) before vitreoretinal surgery
8. Neonatal/paediatric evaluation — visual function in infants unable to cooperate with subjective tests

Comparison: ERG vs EOG

Important Points for Examination

• ERG is a mass retinal response — cannot detect localised disease
• The b-wave is larger than the a-wave under normal conditions
• Dark adaptation for 30 min is required before scotopic testing; 10 min light adaptation for photopic testing
• An electronegative ERG (b/a ratio <1) is a critical diagnostic clue for CSNB, MAR, CRAO
• Retinitis pigmentosa → rods affected first → scotopic ERG reduced earlier than photopic
• Pattern ERG assesses ganglion cells; mfERG maps macular function
• Standardised by ISCEV (International Society for Clinical Electrophysiology of Vision)

Cystoid Macular Edema (CME)

Definition

Pathophysiology

• Disruption of tight junctions in retinal vascular endothelium (inner BRB) or RPE (outer BRB)
• Accumulation of fluid in the perifoveal Henle fibre layer (OPL), which has an oblique orientation — this causes the characteristic petaloid pattern on fluorescein angiography
• Müller cells initially buffer excess fluid; when overwhelmed, intracellular oedema ruptures to form extracellular cystic spaces
• Prostaglandins and VEGF are key mediators of vascular permeability

Etiology / Causes

Postoperative (most common overall)

• Irvine-Gass syndrome — after cataract extraction (peak incidence 6–10 weeks post-op)
  • Risk factors: vitreous loss, vitreous incarceration in the wound, iris prolapse, anterior chamber IOL, secondary IOL, diabetes, uveitis, topical prostaglandin use
• After laser photocoagulation, cryotherapy, vitreoretinal surgery

Retinal Vascular Disease

• Diabetic macular oedema (most common cause of CME globally)
• Central retinal vein occlusion (CRVO) and branch RVO (BRVO)

Inflammatory

• Intermediate uveitis (pars planitis) — particularly associated
• Severe or chronic uveitis of any type
• Retinal vasculitis: Eales disease, Behçet syndrome, sarcoidosis, MS, CMV retinitis

Drug-induced

• Topical prostaglandin analogues (latanoprost, bimatoprost)
• Topical epinephrine / dipivefrin
• Nicotinic acid (high dose)
• Taxane chemotherapy drugs

Retinal Dystrophies

• Retinitis pigmentosa (RP)
• Dominant cystoid macular oedema (inherited form)

Vitreomacular Traction

• Epiretinal membrane (ERM)
• Vitreomacular traction syndrome

Others

• AMD (neovascular / MNV)
• Retinal telangiectasias (Coats disease, idiopathic macular telangiectasia)
• Fundus tumours (retinal capillary haemangioma)
• Systemic conditions: chronic renal failure, hypertension, collagen vascular disease
• Subfoveal choroidal neovascularisation

Symptoms

• Decreased central visual acuity (especially for near tasks)
• Metamorphopsia (distortion of straight lines)
• Micropsia (objects appear smaller)
• Central scotoma on Amsler grid testing
• Subtle CME may be asymptomatic

Signs

On Slit-lamp / Fundoscopy

• Irregularity and blunting of the foveal light reflex
• Macular thickening with or without small intraretinal cysts in the foveal region (best seen with red-free light using a fundus contact lens)
• Loss of the foveal depression
• Multiple cystoid (honey-comb) areas in the sensory retina
• Optic disc swelling may be present (especially in Irvine-Gass)
• A lamellar hole may be visible in advanced cases
• Vitreous cells, dot haemorrhages depending on etiology

Investigations

1. Histology

2. Fluorescein Angiography (FA/IVFA)

• Early phase: leakage from perifoveal capillaries
• Late phase: classic "flower-petal" (petaloid) pattern of hyperfluorescence — dye accumulates in microcystic spaces in the OPL arranged around the fovea
• Optic nerve head leakage in Irvine-Gass syndrome
• No fluorescein leakage in pseudo-CME (X-linked retinoschisis, nicotinic acid maculopathy)

3. Optical Coherence Tomography (OCT) — Gold Standard

• Retinal thickening with cystic hyporeflective spaces (dark lacunae)
• Loss of the foveal depression (flat or dome-shaped foveal profile)
• Can quantify macular thickness and monitor treatment response
• May demonstrate lamellar hole in advanced cases

4. Other

• Amsler grid: central blurring and distortion
• ERG may be abnormal in RP-associated CME
• Fasting blood glucose / HbA1c for diabetic aetiology

Differential Diagnosis

Treatment

Step 1 — Address Causative Factors

• Discontinue topical prostaglandin analogues, epinephrine, dipivefrin, or nicotinic acid
• Vitrectomy/YAG laser lysis of vitreous wick if present (Irvine-Gass with vitreous traction)
• Control diabetes, manage uveitis

Step 2 — Topical Therapy (first-line for post-surgical CME)

Step 3 — Periocular / Intravitreal Injections

• Sub-Tenon triamcinolone 40 mg/mL (0.5–1 mL)
• Intravitreal triamcinolone 1–4 mg
• Intravitreal anti-VEGF (bevacizumab 1.25 mg) — especially for diabetic/RVO-related CME
• Intravitreal dexamethasone implant (Ozurdex 0.7 mg)
• Intravitreal ranibizumab / aflibercept for diabetic macular oedema and RVO

Step 4 — Systemic Therapy

• Systemic steroids — prednisolone 40 mg/day for 5 days, then taper
• Systemic NSAIDs — indomethacin 25 mg TID × 6 weeks
• Carbonic anhydrase inhibitors (CAIs) — dorzolamide 2% TID topically or acetazolamide 500 mg PO (particularly useful in RP-related CME and uveitic CME)

Step 5 — Surgical

• Pars plana vitrectomy — for tractional CME (ERM, VMT), refractory cases, or vitreous wick incarceration
• Grid laser photocoagulation — for diabetic macular oedema (largely superseded by anti-VEGF)

Complications

• Foveal lamellar hole — from coalescence of cystic spaces → irreversible visual loss
• Chronic CME → photoreceptor atrophy → permanent central scotoma
• Secondary epiretinal membrane formation

Key Points for Exam