An electroretinogram (ERG) is a diagnostic test that measures the electrical activity of the retina in response to light stimulation. It records potential changes generated by currents from retinal neurons and contributions from glial cells using electrodes on the cornea. It is a non-invasive objective indicator of retinal function and provides diagnostic information for various hereditary and acquired retinal diseases.
It is also used for monitoring disease progression, evaluating retinal toxicity of drugs, and assessing the effects of retained intraocular foreign bodies.
1967: Ragnar Granit received the Nobel Prize for research on dark-adapted cat retina
The International Society for Clinical Electrophysiology of Vision (ISCEV) established standard protocols for electroretinography in 1989, updated in 2015.
QWhat eye diseases can be diagnosed with electroretinography?
Electroretinogram findings vary by disease. Representative patterns are shown below.
Rod-Dominant Dysfunction
Retinitis pigmentosa / Rod-cone dystrophy: Amplitude reduction begins in the scotopic response, and eventually the electroretinogram disappears.
Vitamin A deficiency (VAD) night blindness: Loss of scotopic response at DA 0.01, reduced a-wave and b-wave amplitudes at DA 3.0/DA 10.0, and marked reduction of oscillatory potentials. Cone responses show delayed implicit time. Rods are affected earlier and more extensively than cones. 1)
Complete congenital stationary night blindness (CSNB): b-wave is absent at DA 0.01. In ffERG, it is subclassified into Riggs type and Schubert-Bornschein type (complete/incomplete). 4)
Mixed type / cone dysfunction
Autoimmune retinopathy (AIR): Both rod and cone responses are reduced to absent. The AAO Task Force (2025) diagnostic criteria include reduced rod and cone responses on ffERG. 3)
Cone dystrophy: Cone responses and 31 Hz flicker responses are absent. Some cases cannot be diagnosed without an electroretinogram.
Negative-type electroretinogram: Normal a-wave with reduced b-wave. Seen in CSNB, melanoma-associated retinopathy, and juvenile X-linked retinoschisis. Photoreceptors are normal, but signal transmission beyond the inner nuclear layer is impaired.
Other important findings:
Leber congenital amaurosis (LCA): The electroretinogram is often non-recordable. Prevalence 1:80,000 to 1:200,000, accounting for about 5% of inherited retinal dystrophies (IRD) 4)
Metabolic disease (cblC type methylmalonic acidemia): Reduced amplitude of scotopic and photopic components. Useful for monitoring progression of maculopathy 2)
Mucopolysaccharidosis (MPS): Rod-mediated retinopathy progresses to rod-cone dystrophy on ERG over 7 years. ERG abnormalities precede fundoscopic findings 6)
Mitochondrial disease (MIDD): ffERG is typically abnormal but milder than fundus phenotype. Pattern ERG and multifocal ERG are highly sensitive for detecting macular lesions 4)
Records the summed response from multiple retinal sources. It is useful for detecting widespread retinal dysfunction (rod/cone dystrophies, cancer-associated retinopathy, toxic retinopathy) but is not suitable for detecting small retinal lesions.
Five basic recording conditions of the ISCEV standard protocol:
Dark-adapted weak flash (DA 0.01): Records the b-wave originating from ON bipolar cells
Dark-adapted strong flash (DA 3.0/DA 10.0): Mixed rod and cone response with a-wave (rod + cone) and b-wave
Light-adapted strong flash (LA 3.0): Cone pathway a-wave and b-wave
31 Hz flicker: Selectively evaluates cone pathway function
Oscillatory potentials (OPs): Small waves on the ascending limb of the b-wave. Derived from amacrine cells. Reduced amplitude and delayed latency suggest retinal blood flow impairment
Simultaneously records local responses from 61 to 103 locations within the central 30 degrees. Allows detailed evaluation of macular dysfunction. Used for hydroxychloroquine toxicity assessment.
Evaluates macular retinal ganglion cell (RGC) activity. Consists of three components: N35, P50, and N95. Transient pERG is recorded with 4 reversals per second.
Photopic Negative Response (PhNR): Derived from RGC. Attracts attention as an ffERG component reflecting RGC function
c-wave: Derived from RPE + photoreceptors. Not evaluated in ISCEV standard
d-wave: Derived from OFF bipolar cells. Positive potential following light offset
QWhat is the difference between ffERG and mfERG?
A
ffERG records the summed response of the entire retina and is suitable for detecting widespread dysfunction (e.g., retinitis pigmentosa, toxic retinopathy). mfERG simultaneously records local responses from 61 to 103 loci within the central 30 degrees and is specialized for evaluating localized dysfunction within the macula. Small lesions undetectable by ffERG can be detected by mfERG.
Avoid strong illumination such as fundus photography or fluorescein angiography (FAG) before the test (if unavoidable, ensure at least 30 minutes of recovery under room lighting)
Perform maximum pupil dilation and record pupil diameter before the test. Refractive correction is not required.
Dark adaptation for 20 minutes, light adaptation for 10 minutes
Insert contact lens electrode after dark adaptation under dim red light, then ensure an additional 5 minutes of dark adaptation
In infants and uncooperative patients, selection of recording electrodes and recording under sedation are important.
In infants, skin electrodes and recording under sedation improve diagnostic feasibility 4)
The diagnostic workflow for pediatric inherited retinal diseases (IRD) incorporates ffERG ± pattern/mfERG 4)
In the differential diagnosis of nystagmus, electroretinography is useful for distinguishing inherited retinal dystrophy from other causes (neurological, anatomical, motor) 5)
QHow is electroretinography performed in children?
A
In infants and uncooperative children, skin electrodes (placed on the lower orbital rim) or recording under sedation can improve diagnostic feasibility. Infants can also be examined while lying supine on a parent’s lap. Skin electrodes have limitations such as small amplitude and high noise, but they offer excellent tolerability. 4)
5. Clinical Applications of Electroretinography and Treatment Monitoring
The effect of vitamin A supplementation therapy for vitamin A deficiency night blindness can be evaluated over time using electroretinography.
Poornachandra et al. (2022) reported serial electroretinograms before and after vitamin A supplementation (intramuscular 100,000 units/day for 3 days → oral 50,000 units/day for 2 weeks) in two cases: a 20-year-old man with intestinal lipofuscinosis and a 50-year-old man with alcoholic liver disease (both with serum vitamin A 0.02 mg/mL, normal 0.3–0.6 mg/mL) 1). Pre-treatment electroretinograms showed absent scotopic responses at DA 0.01, reduced a-wave and b-wave amplitudes at DA 3.0/DA 10.0, and markedly reduced oscillatory potentials. Improvement in scotopic responses began after 1 week of treatment, and nearly normalized after 1 month.
A case of cblC type methylmalonic acidemia detected by newborn screening has been reported2). Treatment was started at 8 days of age (OHCbl 1 mg intramuscular injection/day, betaine 100 mg × 3/day, folic acid 5 mg × 2/week), but at 7 months, ffERG showed reduced amplitudes of scotopic and photopic components, and bull’s eye maculopathy appeared around the same time. Retinal degeneration progressed despite treatment.
Implications for management of cblC patients:
Electroretinography is recommended in cblC patients even when maculopathy is not apparent2)
High-dose OHCbl (6.5 ± 3.3 mg/kg/day) has been reported to be associated with better ocular outcomes2)
Electroretinography in the diagnosis of autoimmune retinopathy (AIR)
A negative-type electroretinogram, in which a normal a-wave is combined with a reduced b-wave, indicates that signal transmission from the inner nuclear layer onward is impaired even though photoreceptors are normal. In cCSNB, the b-wave disappears in DA 0.01 due to ON bipolar cell dysfunction 4).
Mechanism of the effect of vitamin A deficiency on the retina
MMACHC protein deficiency → impaired conversion of vitamin B12 to adenosylcobalamin and methylcobalamin → accumulation of methylmalonic acid (MMA) and homocysteine (Hcy)2)
Photoreceptors, RPE, and Müller cells in the outer retina have high-density mitochondria and are vulnerable to metabolic impairment2)
Foveal development progresses from birth to early childhood, making it vulnerable to toxic accumulation of Hcy and MMA during this period2)
The retinal protective effect of high-dose hydroxocobalamin (OHCbl) therapy in cblC-type methylmalonic acidemia is being investigated.
High-dose OHCbl (0.4–2.7 mg/kg/day) has been reported to potentially prevent the onset of maculopathy and retinopathy 2). In particular, cases where high-dose treatment (mean 6.5±3.3 mg/kg/day) was initiated within 5 months showed favorable ophthalmological and cognitive outcomes 2).
The AAO Task Force (2025) established guidelines for the diagnosis, management, and research of AIR, positioning reduced rod and cone responses on ffERG as one of the diagnostic criteria 3). Standardization of anti-retinal antibody (ARA) detection methods remains a future challenge 3).
Poornachandra B, Jayadev C, Sharief S, et al. Serial 網膜電図 monitoring of response to therapy in vitamin A deficiency related night blindness. BMJ Case Rep. 2022;15:e247856.
Michieletto P, Baldo F, Madonia M, Zupin L, Pensiero S, Bonati MT. Retinal Changes in Early-Onset cblC Methylmalonic Acidemia Identified Through Expanded Newborn Screening: Highlights from a Case Study and Literature Review. Genes. 2025;16(6). doi:10.3390/genes16060635. PMID:40565527; PMCID:PMC12193327.
Chen Y, Zhang Y, Luo J, Liu M, Lin M, Zhu W, et al. Autoimmune retinopathy in patients with myasthenia gravis: cases series and literature review. BMC ophthalmology. 2025;25(1):521. doi:10.1186/s12886-025-04357-5. PMID:41029312; PMCID:PMC12487295.
Mordà D, et al. Pediatric inherited retinal dystrophies: a comprehensive review. Prog Retin Eye Res. 2025;109:101405.
Gurnani B, et al. Nystagmus in children: a comprehensive review. Clin Ophthalmol. 2025;19:1617-1637.
Collin RJ, et al. Retinopathy in mucopolysaccharidoses. Ophthalmology. 2025;132(4):470-.
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