Next Generation PERG Method: Expanding the Response Dynamic Range and Capturing Response Adaptation

Abstract

PurposeTo compare a new method for steady-state pattern electroretinogram (PERGx) with a validated method (PERGLA) in normal controls and in patients with optic neuropathy.MethodsPERGx and PERGLA were recorded in a mixed population (n = 33, 66 eyes) of younger controls (C1; n = 10, age 38 ± 8.3 years), older controls (C2; n = 11, 57.9 ± 8.09 years), patients with early manifest glaucoma (G; n = 7, 65.7 ±11.6 years), and patients with nonarteritic ischemic optic neuropathy (N; n = 5, mean age 59.4 ± 8.6 years). The PERGx stimulus was a black-white horizontal grating generated on a 14 × 14 cm LED display (1.6 cycles/deg, 15.63 reversals/s, 98% contrast, 800 cd/m2 mean luminance, 25° field). PERGx signal and noise were averaged over 1024 epochs (∼2 minutes) and Fourier analyzed to retrieve amplitude and phase. Partial averages (16 successive samples of 64 epochs each) were also analyzed to quantify progressive changes over recording time (adaptation).ResultsPERGLA and PERGx amplitudes and latencies were correlated (Amplitude R2 = 0.59, Latency R2 = 0.39, both P < 0.0001) and were similarly altered in disease. Compared to PERGLA, however, PERGx had shorter (16 ms) latency, higher (1.39×) amplitude, lower (0.37×) noise, and higher (4.2×) signal-to-noise ratio. PERGx displayed marked amplitude adaptation in C1 and C2 groups and no significant adaptation in G and N groups.ConclusionsThe PERGx high signal-to-noise ratio may allow meaningful recording in advanced stages of optic nerve disorders. In addition, it quantifies response adaptation, which may be selectively altered in glaucoma and optic neuropathy.Translational RelevanceA new PERG method with increased dynamic range allows recording of retinal ganglion cell function in advanced stages of optic nerve disorders. It also quantifies the response decline during the test, an autoregulatory adaptation to metabolic challenge that decreases with age and presence of disease.

Neurovascular Changes Associated With the Water Drinking Test

“…WDT consisted on drinking 1 liter of bottled water at room temperature within 5 minutes [5]. Study outcome measures were IOP (Reichert PT-100), time-integrated mean brachial blood pressure [MAP=Diastolic +0.42 × (Systolic-Diastolic)] [6,7], heart rate (HR), (Welch-Allyn Vital Signs Monitor 300 series), and steady state pattern electroretinogram (PERG, Jorvec Corp)[8], which were assessed before WDT and every 15 minutes thereafter over one hour. The same protocol was repeated in the same subjects without WDT (Control) in a different session about one week thereafter.…”

“…PERG waveforms were Fourier analyzed to isolate the frequency component at the reversal rate (15.63 Hz) whose amplitude (μV) and phase (degrees) were evaluated. Phase values were converted in latency (ms), which corresponded to the time-to-peak of the positive wave of the PERG waveform [8]. This also corresponds to the peak-latency of the P50 waveform component of the standard transient PERG [10].…”

“…Noise signals had a very small amplitude (mean 0.08 μV) across conditions and will not be further discussed. Further details are reported elsewhere [8].…”

Adaptation of retinal ganglion cell function during flickering light in the mouse

“…The magnitude of steady-state PERG adaptation is of the order of 30% in healthy subjects 25 and is reduced in early glaucoma 26 and optic neuritis 27 . As the human PERG is also recordable from non-corneal electrodes 28 , combined assessment of flicker-induced neural and vascular dynamics is possible by adapting available imaging instruments.…”

Compartmental Differences in Macular Retinal Ganglion Cell Function

“…Here, we use the steady-state pattern electroretinogram (SS-PERG) in healthy subjects to noninvasively record responses from partitions of the macular region, using a recently developed method that takes advantage of light-emitting diode (LED) displays with high luminance and high temporal resolution 22 , 23 to generate response with high signal-to-noise ratio (SNR). Analysis of local SS-PERGs will include assessment of response amplitude, amplitude temporal dynamics (adaptation), latency, and oscillatory potentials (OPs), which represent different functional aspects of RGCs and inner retinal neurons impinging on them.…”