Digital Exclusive: The whys and wherefores of ophthalmic electrophysiology in inflammatory retinal and optic nerve disorders

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Ophthalmic electrophysiology is crucial for evaluating and managing inflammatory disorders of the retina and optic nerve. It complements the standard clinical assessments of visual acuity, color vision, contrast sensitivity, and visual field testing.

Combined with optical coherence tomography, electrophysiologic testing provides valuable insights for diagnosis, monitoring disease progression, and assessing treatment response, according to Minzhong Yu, PhD, MMed. In a recent article, Yu reviewed the benefits and limitations of various electrophysiologic technologies in a diverse group of inflammatory conditions affecting the retina and optic nerve, a perspective endorsed by Shree K. Kurup, MD.¹

Yu is from the Department of Ophthalmology, University Hospitals, Case Western Reserve University School of Medicine; Department of Ophthalmic Research, Cleveland Clinic; and Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, all in Cleveland, Ohio. Kurup is from the Department of Ophthalmology, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Full-field electroretinography

This diagnostic test can globally assess retinal function to provide a picture of the overall health, function, and activity of different retinal cell types, including photoreceptors and inner retinal cells. Full-field electroretinography (ffERG) involves recording electrical responses generated by the retina in response to light flashes presented to the eye that vary in intensity, duration, and color, Yu explained.

The main ffERG components are the a- and b-waves and oscillatory potentials. Respectively, these components reflect the hyperpolarization of photoreceptor cells in response to light stimulation, reflect bipolar cell activity, and provide information about the reciprocal synapses between the rod bipolar cells and AII and A17 amacrine cells in the inner retina.² ffERG is recorded under dark-adapted and light-adapted conditions to assess the function of the rod and cone pathways, respectively.

ffERG is valuable for assessing retinal function in acute posterior multifocal placoid pigment epitheliopathy (APMPPE), which shows marginal reductions in a- and b-wave amplitudes, reflecting photoreceptor and bipolar cell dysfunction.³

In acute zonal occult outer retinopathy (AZOOR), ffERG pinpoints characteristic abnormalities such as attenuated or absent photopic and scotopic responses, indicating dysfunctional cone and rod photoreceptors. The test results show more severe amplitude reduction than the implicit time prolongation, indicating primary photoreceptor dysfunction⁵ and spontaneous recovery or stabilization in some patients.

In Behçet disease (BD), ffERG may show reduced amplitude and prolonged implicit time. These abnormalities result from direct retinal inflammation, retinal pigment epithelium (RPE) involvement, or photoreceptor cell damage. The BD findings correlate with the severity and activity of ocular inflammation and provide valuable insights into disease progression and treatment decision-making.⁴

In autoimmune retinopathy (AIR) and neuroretinopathy (AINR), classified into paraneoplastic (pAIR/AINR) and nonparaneoplastic (npAIR/AINR) forms, ffERG shows decreased function in the rod and cone photoreceptors and bipolar cells, which can recover after treatment.

In birdshot chorioretinopathy (BSCR), ffERG can aid diagnosis, especially when clinical findings are inconclusive or atypical. “The characteristic ERG pattern of generalized retinal dysfunction helps distinguish BSCR from other uveitic entities, guiding the appropriate management strategies. The ffERG often demonstrates a reduction in the rod and cone responses, reflecting generalized retinal dysfunction,” the authors said, noting that the extent of involvement varies from subclinical to severe. Notably, abnormalities in ffERG, particularly an electronegative mixed response, are common even with the characteristic lesions.

In acute multiple evanescent white dot syndrome (MEWDS), ffERG often shows reduced a- and b-wave amplitudes in rods and cones, indicating dysfunctional photoreceptors and bipolar cells and delayed implicit times, which reflects impaired retinal processing. With progression, the abnormalities tend to resolve, suggesting that the primary insult in MEWDS affects retinal function, with the potential for recovery over time.⁵

In Vogt-Koyanagi-Harada (VKH) disease, ffERG is key to evaluation and treatment and typically shows reduced rod and cone responses, reflecting widespread retinal dysfunction. A significant reduction in rod and cone ERG amplitudes and mild increases in the a- and b-wave implicit times are correlated with the severity of ocular inflammation and the extent of retinal involvement, and these parameters can be recovered in treatment.^6,7

Multifocal electroretinography

Multifocal electroretinography(mfERG), performed to assess the functionality of different retinal regions, facilitates simultaneous localized evaluation of retinal responses to light stimuli across multiple retinal areas. It enables clinicians to detect and localize abnormalities with greater precision. Following the presentation of light stimuli to 61 or 103 discrete areas of the retina, the resulting waveform includes a response array corresponding to specific retinal regions that provide information about photoreceptor and inner retinal cell function in each region.

mfERG can pinpoint abnormalities in specific retinal regions, such as cone-mediated responses in areas of residual photoreceptor function, and assess function loss in the macular and peripheral retina. The technique can also monitor changes in retinal function longitudinally, thus facilitating early disease progression; assess treatment efficacy; and monitor therapeutic efficacy.

The value of mfERG in acute APMPPE is like that of ffERG; mfERG shows decreased response density of the central retina, corresponding to the extent of retinal involvement by the placoid lesions. mfERG findings also show improvement in the scar stage, indicating partially recovered retinal function. “The ability of mfERG to localize and quantify retinal dysfunction makes it a tool for monitoring disease progression and treatment response in APMPPE,” the investigators commented.

In AZOOR, mfERG can locally assess retinal function. The presence of localized amplitude reductions or delays in mfERG responses corresponds to the distribution of visual field defects, facilitating the precise localization of retinal pathology⁸ and treatment strategies.

In BD, mfERG shows focal or diffuse abnormalities corresponding to active inflammation or retinal damage, facilitating early detection and complication management. In pAIR and npAIR, mfERG shows functional retinal change in the tested field in some patients who presented different abnormalities.⁹

In acute MEWDS, mfERG may reveal reduced response densities in the affected areas, corresponding to the location of the white dot lesions. With disease resolution, mfERG responses typically return to baseline, indicating restored retinal function. The ability of mfERG to localize and quantify retinal dysfunction makes it a valuable tool for monitoring disease progression and treatment response in MEWDS.^5,10,11

In VKH disease, mfERG can show localized dysfunction corresponding to active retinal inflammation or damage, an ability that can detect subclinical disease activity and provide valuable information for treatment monitoring.¹² mfERG also shows gradual recovery of response densities during treatment with corticosteroids and other immunosuppressive agents, and there is delayed recovery of macular function compared with visual acuity after treatment with immunosuppressive agents.

Visual-evoked potentials

Visual-evoked potentials (VEPs), electrical signals recorded from the visual cortex in response to visual stimuli, are crucial in neuroscience and clinical neurology for evaluating the functional integrity of the visual pathway from the retina to the visual cortex.¹³

During VEP testing, scalp electrodes are positioned at specific locations corresponding to different visual cortex regions. Analysis of the subsequent electrical signals extracts the VEP waveform, which typically consists of components that reflect different visual processing stages. These include negative component 1, the initial neural response to the visual stimulus originating primarily from the primary visual cortex; positive component 1, which reflects further processing in the visual cortex, including feature extraction and pattern recognition; negative component 2, possibly reflecting additional processing in the visual cortex or feedback from higher-order visual areas; and positive component 2, which may represent more complex cognitive processing related to attention and perception. The implicit time and amplitude of these components can provide valuable information about the integrity and efficiency of the visual pathway, the authors explained.

VEPs can assess optic neuritis, multiple sclerosis, amblyopia, glaucoma, and cortical blindness, and the changes in the latency or amplitude can indicate visual processing abnormalities and help diagnose and monitor these conditions. This technology also is used during research to investigate visual perception, attention, and cognition to determine how the brain processes visual information and study the effects of aging, development, and neurologic disorders on visual function.

Electro-Oculography

Electro-oculography (EOG) is a technique that measures the eye’s electrical activity by recording the standing potential, defined as the negative charge of the posterior eye relative to the cornea that is correlated with the transepithelial potential (TEP) of the RPE. The TEP changes with dark and light adaptation. During the dark phase, the electrical potential remains low, while in the light phase, it gradually increases, helping to evaluate RPE function.¹⁴ The light peak reflects the peak amplitude of the EOG signal after stimulus; conversely, the dark trough reflects the lowest signal point during the dark phase. The light peak to dark trough ratio is the main index of EOG. In the actual recording of TEP, a potential difference between the inner and outer canthus during ocular movement is recorded. EOG is commonly used in ophthalmology to assess the function of the RPE.

A higher light peak to dark trough ratio indicates a more robust RPE response to light and a healthier retinal function, as the amplitude of the response to light should ideally exceed the baseline activity during darkness. This ratio has clinical relevance in the assessment of various retinal disorders, particularly those affecting the RPE. Changes in the EOG light peak to dark trough ratio can provide early indications of RPE dysfunction, allowing for the timely intervention and monitoring of disease progression.

The EOG light peak to dark trough ratio is reduced in patients with antibestrophin autoantibodies,autoantibodies against bestrophin in a patient with vitelliform pAIR, and a metastatic choroidal malignant melanoma. The ratio also can be used to evaluate pharmacologic or gene therapies targeting RPE function, and longitudinal changes allow adjustment of treatments as needed.

In BSCR, aberrations in EOG parameters, including a reduced light peak and light peak to dark trough ratio, suggest the inflammatory involvement of the RPE at the chorioretinal interface.¹⁵

In acute MEWDS, EOG evaluates the RPE functional integrity and may demonstrate abnormalities, reflecting RPE dysfunction. However, with disease resolution, EOG recordings tend to normalize, suggesting recovery of RPE function. Given the RPE’s role in maintaining retinal homeostasis, EOG provides insights into the pathophysiology of MEWDS and may aid in predicting visual outcomes.

References

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