GLAUCOMA PATIENTS SHOW INCREASED NONLINEAR ERG COMPONENTS UNDER DOUBLE SINEWAVE STIMULATION

Aim: To investigate how nonlinear ERG response components, potentially originating in retinal ganglion cells (RGCs) are altered in Glaucoma patients with RGC loss using a novel double sinewave stimulation.
Methods: ERG recordings were obtained from glaucoma patients (n=8) and healthy controls (n=9). Stimuli consisted of two sinewaves presented simultaneously, with frequencies 5Hz apart, each modulated at 50% contrast around a mean luminance of 100cd/m². Frequency combinations ranged from 3Hz & 8Hz to 31Hz & 36Hz. Signals were Fourier transformed to extract amplitudes at the stimulating frequencies (fundamentals), doubled frequencies (2^nd harmonics) and at interaction frequencies (5Hz difference and the additions of the fundamentals). Standard perimetry data were obtained. One eye per participant (typically the eye with worse perimetry result) was used for the average per group. Group differences were evaluated using linear mixed-effects models, and correlations with perimetry were examined.
Results: Glaucoma patients exhibited significantly larger response amplitudes than controls for fundamentals and interaction frequencies. The nonlinear 5Hz difference component was particularly enhanced (p<0.0001 across all frequency combinations). No significant correlation was observed between the 5Hz component and perimetry measures.
Conclusion: Unexpectedly, nonlinear ERG components were increased in glaucoma patients. We hypothesize that RGC loss reduces feedback inhibition onto bipolar cells, resulting in increased bipolar cell activity. The findings highlight a novel aspect of retinal dysfunction in glaucoma and suggest that nonlinear ERG responses may provide complementary information beyond standard structural and functional assessments. Further experiments are needed to test this mechanism and clarify its relevance for early glaucoma detection.