The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings

Abstract

Purpose To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma. Methods A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, L max 100 cd/m 2 , L min \1 cd/m 2 ), followed by two global flashes (L max 200 cd/m 2 ) at an interval of 26 ms (VERIS 6.0 TM , FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain = 50 K) and bandpass filtered at 1-300 Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15°and 4 adjoining quadrants) as well as 8 smaller response averages (central 10°and 7 surrounding response averages of approximately 7°radius each). Three epochs were analyzed: the direct component at 15-45 ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC-1) and at 75-105 ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age. Results Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10°t han for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10°with an area under the ROC curve of 0.78. With a cutoff value of 12.52 nV/deg 2 , 80 % of the POAG patients (100 % HTG, 69 % NTG) were correctly classified as abnormal, while 77 % of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field. Conclusion When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma further.

Wavelet decomposition analysis in the two-flash multifocal ERG in early glaucoma: a comparison to ganglion cell analysis and visual field

“…The multifocal electroretinogram (mfERG, two-flash pattern) technology which allows topographic examination of retinal function is an objective method shown to be sensitive in glaucoma [ 2 – 8 ]. Also, it complements visual field information and may be more sensitive in some patients, especially in cases where defects are seen in OCT but not yet in the visual field (poster ARVO 2014: IOVS.…”

The effect of filtering on the two-global-flash mfERG: identifying the optimal range of frequency for detecting glaucomatous retinal dysfunction

“…In our most recent study, we applied a two-global-flash mfERG with a focal flash of 100 cd/m 2 Lmax and global flashes of 200 cd/m 2 Lmax, filter setting: 1-300 Hz. Here, glaucoma patients differed significantly from healthy subjects in the central 10° [7]. In the present paper, we report on the effect of digital filter settings on those recordings.…”

“…In the present paper, we studied the influence of the filter setting on the two-global-flash mfERG, in order to identify the range of frequency that might detect most glaucomatous retinal dysfunction in the mfERG. With the two-global-flash paradigm used, POAG differed most from control in the central 10° [7]. Therefore, we focused our analysis on the response average of the central 10°.…”

“…Three response epochs were analysed: the response to the focal flash, at 15-45 ms (DC), and the following two response components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC1) and at 75-105 ms (IC2). Under these stimulus parameters, glaucoma patients differed most from control subjects in the response average of the central 10°(for more details, see also Kramer et al [7]). Therefore, we analysed the response averages from the central 10°.…”

M-sequences in ophthalmic electrophysiology

“…Reduced amplitudes are associated with visual field defects as well as nerve fiber layer thickness and can even be found before manifest glaucoma occurs (Bach, 2001;Bach & Hoffmann, 2008;Bach & Poloschek, 2013;Bach et al, 2006;Rao, Singh, Mukherjee, & Chowdhury, 2015). Various modifications of the mfERG stimulation such as fast flicker, low contrast, slow sequence, global flash, two flash, and luminance modulation have been developed in recent years in order to improve validity and effectiveness in the diagnosis of glaucoma (Chan, 2005;Chu, Chan, & Brown, 2006Chu et al, 2012;Kramer et al, 2013;Ledolter, Monhart, Schoetzau, Todorova, & Palmowski-Wolfe, 2015;Palmowski-Wolfe, Allgayer, Vernaleken, Schötzau, & Ruprecht, 2006;Palmowski-Wolfe, Todorova, Orguel, Flammer, & Brigell, 2007).…”