Application of Multifocal Electroretinogram in Early Detection of Inner Retinal Changes in Experimental Glaucoma



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Purpose: Glaucoma is a multifactorial disease that causes structural and functional damage to retinal ganglion cells (RGCs) and their axons (retinal nerve fiber layer, RNFL). Early diagnosis is critical to preserving vision. The electroretinogram (ERG) is a noninvasive technique of assessing retinal function. The goal of this dissertation was to explore the utility of two ERG techniques (multifocal, mfERG and full field) in detecting early functional changes and to compare the changes with early structural changes in retina and optic nerve head (ONH) in an experimental model of glaucoma.

Methods: All experiments were conducted on nonhuman primates (Mucaca Mulatta). In Experiment 1, using a slow sequence mfERG protocol, the stimulus consisted of a 19 hexagon array subtending angles of 35o X 34o on the retina. The protocol was modified by adding up to six initial focal flashes in a 30 frame sequence to increase the amplitude of the multifocal photopic negative response (mfPhNR). mfPhNR and multifocal oscillatory potentials (mfOPs) using the modified mfERG protocol were recorded in experimental (Exp) and fellow control (Con) eyes of seven monkeys with unilateral experimental glaucoma. Structural measures including RNFL thickness (RNFLT), macular ganglion cell inner plexiform layer thickness (m-GCIPLT) and deep ONH structures, minimum rim width (MRW) and anterior lamina cribrosa depth (ALCSD) were obtained concurrently. All parameters were measured globally (g) and locally (sectoral, s and macular, m). Time points of first significant changes in structural and functional measures were compared. In Experiment 2, mfPhNR was measured from a slow sequence protocol with a 103 hexagon array and a m-sequence of one focal flash followed by 14 dark frames (F14). Time points of change in the mfPhNR-F14 were compared with the corresponding structural changes and with mfPhNRs from Experiment 1. In Experiment 3, longitudinal changes in the full field PhNR (FF-PhNR) were measured and the time point of change in the FF-PhNR amplitude was compared with the structural measures.

Results: Experiment 1: mfPhNR amplitude increased with increasing number of focal frames and saturated at 5 focal frames (F30-5), corresponding to an approximate duration of 53 ms. In Exp eyes, mfERG measures showed early reductions as cumulative IOP increased. g-mfPhNR amplitude was linearly related to MRW (R2=0.66, P<0.01) and ALCSD (R2=0.54, P<0.01) but showed an exponential relationship with g-RNFLT (R2=0.58, P<0.01). ONH structural changes either preceded or coincided with functional losses (mfPhNR) and g-RNFLT was the last parameter to change (K-M survival, P<0.05, log rank test). Reductions in m-mfPhNR amplitude occurred prior to m-GCIPL thinning in half of the monkeys. s-RNFL showed thinning prior to g-RNFL (P<0.05, paired t-test). Experiment 2: The coefficient of variation (CV) was significantly lower for the F30-5 (9.1%) protocol compared to the F14 (14.1 %) (P<0.05, paired t test). In Exp eyes, the mfPhNR-F14 amplitude changed early along with the ONH measures but prior to RNFL thinning. Time points for changes in the mfPhNR amplitudes from the two mfERG protocols were similar. Experiment 3: Early reduction in FF-PhNR amplitude occurred concurrently with the ONH changes but prior to g-RNFL and m-GCIPL thinning (P<0.05, log rank test). Time points for changes in mfPhNR-F30 and FF-PhNR were similar.

Conclusion: Functional changes in mfPhNR and FF-PhNR amplitudes and changes in the ONH structures (MRW and ALCSD) occurred prior to structural changes in the inner retina (RNFLT and m-GCIPLT) in experimental glaucoma. Local RNFLT showed changes prior to global. While the FF-ERG can be used as a screening tool to detect early functional changes, mfERG can used to track changes in function related to local structural changes in the inner retina in glaucoma.



Glaucoma, Electroretinogram, Optical coherence tomography (OCT), Structure-function, Vision sciences