Electroretinography and idiopathic intracranial hypertension

Electroretinography and IIH Research

ERG technology continues to advance in the ways it can be used to help diagnose and track optic nerve dysfunction and neuropathies. We at LKC Technologies are proud to see our technology being used at the frontier of this research.

Here are some relevant studies that have been recently published.

Moss HE, Park JC, McAnany JJ. 'Electroretinography in idiopathic intracranial hypertension: comparison of the pattern ERG and the photopic negative response.'

In Doc Ophthalmol. 2018 Feb;136(1):45-55.

Purpose: To evaluate the relationship between electrophysiological measures of retinal ganglion cell (RGC) function in patients who have idiopathic intracranial hypertension (IIH).

Methods: The pattern electroretinogram (pERG) and photopic negative response (PhNR) were recorded from 11 IIH patients and 11 age-similar controls. The pERG was elicited by a contrast-reversing checkerboard. The PhNR, a slow negative component following the flash ERG b-wave, was recorded in response to a long-wavelength flash presented against a short-wavelength adapting field. The PhNR was elicited using full-field (ffPhNR) and focal macular (fPhNR) stimuli. Additionally, Humphrey visual field mean deviation (HVF MD) was measured and ganglion cell complex volume (GCCV) was obtained by optical coherence tomography.

Results: The ffPhNR, fPhNR, and pERG amplitudes were outside of the normal range in 45, 9, and 45% of IIH patients, respectively. However, only mean ffPhNR amplitude was reduced significantly in the patients compared to controls (p < 0.01). The pERG amplitude correlated significantly with HVF MD and GCCV (both r > 0.65, p < 0.05). There were associations between ffPhNR amplitude and HVF MD (r = 0.58, p = 0.06) and with GCCV (r = 0.52, p = 0.10), but these did not reach statistical significance. fPhNR amplitude was not correlated significantly with HVF MD or GCCV (both r < 0.40, p > 0.20).
Conclusions: Although the fPhNR is generally normal in IIH, other electrophysiological measures of RGC function, the ffPhNR and pERG, are abnormal in some patients. These measures provide complementary information regarding RGC dysfunction in these individuals.

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Moss HE, Park JC, McAnany JJ. ‘The Photopic Negative Response in Idiopathic Intracranial Hypertension’

In Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3709-3714.

Purpose: To evaluate the photopic negative response (PhNR) as an index of retinal ganglion cell (RGC) function in idiopathic intracranial hypertension (IIH).


Methods: Amplitude and implicit time of the PhNR, as elicited by full-field, brief-luminance flashes, was measured in IIH (n = 10) and visually normal control (n = 15) subjects. Visual function was assessed in IIH subjects using standard automated perimetry mean deviation (SAP-MD) scores. Optic nerve structure was evaluated using the Frisén papilledema grading scale (FPG). Macula ganglion cell complex volume (GCCV) was extracted from optical coherence tomography images to assess RGC loss.

Results: Median PhNR amplitude was significantly lower in IIH subjects compared with control subjects (P = 0.015, Mann-Whitney Rank Sum [MW]), but implicit time was similar (P = 0.54, MW). In IIH subjects, PhNR amplitude and SAP-MD were correlated (Pearson’s r = 0.78, P = 0.008). Ganglion cell complex volume was correlated with both SAP-MD (r = 0.72, P = 0.019) and PhNR amplitude (r = 0.77, P = 0.009). Multivariate linear regression models demonstrated that the correlation between GCCV and PhNR amplitude was improved by accounting for FPG in the model (r = 0.94, P < 0.0001), but the correlation between GCCV and SAP-MD was not (r = 0.74, P = 0.009).
Conclusions: Photopic negative response amplitude, which can be decreased in IIH subjects, correlates well with a clinical measure of visual function (SAP-MD). In multivariate models, it correlated with both an imaging measure of chronic ganglion cell injury (GCCV) and a clinical measure of acute optic nerve head pathology (FPG). Further studies are needed to determine the clinical utility of PhNR as a marker for diagnosis and monitoring of IIH.

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Moss HE, Park JC, McAnany JJ. ‘The Pupillary Light Reflex in Idiopathic Intracranial Hypertension’

In Invest Ophthalmol Vis Sci. 2016 Jan; 57(1): 23–29.

Purpose: To evaluate the effects of idiopathic intracranial hypertension (IIH) on rod-, cone-, and melanopsin-mediated pupillary light reflexes (PLRs).


Methods: Pupillary light reflexes elicited by full-field, brief-flash stimuli were recorded in 13 IIH patients and 13 normal controls. Subjects were dark-adapted for 10 minutes and the PLR was recorded in response to short-wavelength flashes (0.001 cd/m2: rod condition; 450 cd/m2: melanopsin condition). Subjects were then exposed to a rod-suppressing field and 10 cd/m2 long-wavelength flashes were presented (cone condition). Pupillary light reflexes were quantified as the maximum transient constriction (rod and cone conditions) and the post-illumination pupil constriction (melanopsin condition), relative to the baseline pupil size. Diagnostic power was evaluated using receiver operating characteristic (ROC) analysis.

Results: The IIH patients had significantly smaller PLRs under the melanopsin (P < 0.001) and rod (P = 0.04) paradigms; a trend for reduced cone-mediated PLRs was also found (P = 0.08). Receiver operating characteristic analysis indicated areas under the curves (AUC) of 0.83 (melanopsin-meditated; P = 0.001), 0.71 (rod-mediated; P = 0.07), and 0.77 (cone-mediated; P = 0.02). The AUC (0.90, P < 0.001), sensitivity (85%), and specificity (85%) were high for ROC analysis performed on the mean of the rod, cone, and melanopsin PLRs.
Conclusions: Pupillary light reflex reductions in IIH patients indicate compromised RGC function. PLR measurement, particularly under rod- and melanopsin-mediated conditions, may be a useful adjunct to standard clinical measures of visual function in IIH.

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Moss HE, Bindiganavale MP. ‘ Development and Implementation of a Handheld Pupillometer for Detection of Optic Neuropathies’

Curr Eye Res. 2021 Feb 5;1-4. 

Purpose: Quantitative pupillometry has utility in research settings for measuring optic nerve and autonomic function. We configured a portable device to perform quantitative pupillometry with application to detecting unilateral optic neuropathies in the clinical setting.

Materials & methods: Light stimuli were delivered, and pupil diameter responses recorded using customized software implemented on a commercial portable electroretinography device. Increasing pupillary constriction occurred with increasing duration and intensity of full-field blue light (470 nm) stimuli in healthy subjects. Flashes of 1 s dim (50 cd/m2) and bright (316 cd/m2) blue light were administered to both eyes of subjects with unilateral optic neuropathies (n = 10) and controls (n = 5). Maximum pupillary constriction (Cmax) for each stimulus was compared between control eyes and optic neuropathy eyes. Cmax for the inter-eye difference curve (Cdiffmax) was compared between control and optic neuropathy subjects.

Results: The pupil protocol lasted 15 minutes and was well tolerated by subjects. Cmax for bright and dim stimuli was reduced in eyes with optic neuropathy compared to fellow and control eyes (p < .0005 for all). Inter-eye Cdiffmax was larger in optic neuropathy subjects than control subjects for both dim and bright stimuli (p = .002, <0.0005). There was no overlap between groups for Cmax and Cdiffmax for either stimulus. Conclusions: A portable pupillometer was implemented on a commercial portable electroretinography platform and applied in a pilot manner to subjects with and without unilateral optic neuropathies. Optic neuropathy eyes were distinguished from non-optic neuropathy eyes both within and between subjects.

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