Korean J Ophthalmol Vol.25, No.3, 2011 Table 3. Correlation between parameters of multifocal electroretinography and total macular volume (TMV) Ring 1 - 0.36 0.26 P1 amplitude Ring 2 - 0.03 0.93 Ring 3 0.38 0.23 Ring 1 implicit time N1 P1 0.46 0.26 0.13 0.42 Ring 2 implicit time N1 P1 - 0.04 0.36 0.91 0.25 Ring 3 implicit time N1 P1 0.05 - 0.01 0.88 0.97 TMV (correlation coefficient)* TMV (p-value) *Spearman’s Rho, p < 0.05. treatment, but no statistically significant differences were found (ring 1, p = 0.18; ring 2, p = 0.27; ring 3, p = 0.55) (Fig. 3A). The amplitude of P1 in rings 1 to 3 increased after injection with statistical significance (ring 1, p = 0.03; ring 2, p = 0.04; ring 3, p = 0.02) (Fig. 3B). From ring 1 to 3, the implicit time of N1 and P1 decreased after injection compared with base- line, and statistical analysis revealed significant difference (P1: ring 1, p = 0.02; ring 2, p = 0.01; ring 3, p = 0.03; N1: ring 1, p = 0.01; ring 2, p = 0.02; ring 3, p = 0.01) (Fig. 4). There appeared to be a linear relationship between changes of N1 implicit time in ring 1 and the BCVA however, other factors had no significant difference (Table 1). The correla- tion between CMT and mfERG values was not significant (Table 2). The TMV correlated with the implicit time of N1 and P1 in ring 1, P1 in ring 2, and N1 in ring 3, but without statistical significance. A reverse correlation was seen be- tween TMV and amplitude in rings 1 and 2, but not at a sig- nificant level (Table 3). Discussion Bevacizumab is a recombinant humanized monoclonal an- tibody to human VEGF that binds to VEGF and blocks it from binding to its receptors in tumor tissues. Intravitreal bevacizumab injection is increasingly used as an off-label therapy in ophthalmology, and shows benefits in the im- provement of visual acuity and anatomical changes of many eye diseases [8-14,16]. As we hypothesized, visual acuity and anatomical changes were associated with functional changes of the retina, thus we used mfERG, which assesses retinal function, to confirm functional changes after injection. The use of mfERG en- ables topographic mapping of retinal function in the central 30° of the retina. Recent studies revealed that the human mfERG response is dominated by cells of the outer retina, such as the photoreceptors and the ON- and OFF-bipolar cells, than cells from the inner retina [17,18]. Accordingly, mfERG response is useful in evaluating cone cells in pro- portion to bipolar cells, while the amplitude and implicit time show retinal functions principally [19]. Any damage to the receptor that destroys the cell or reduces its responsiveness will lead to a decrease in the mfERG response amplitude. The result showed that intravitreal bevacizumab injection has clinical benefit in CNV secondary to AMD in terms of visual acuity, CMT, TMV, and mfERG response. These find- ings are similar to those of previous studies [8-14,16]. Before injection, the amplitude of P1 and N1 decreased to less than 164 normal values, representing impaired retinal function. The amplitude of P1 increased in rings 1, 2, and 3 after injection, and the changes of amplitude were significantly different. On the other hand, the amplitude of N1 showed no significant change after injection. The changes of the P1 amplitude were more significant than those of N1. The P1 amplitude is be- lieved to be linked to the number and function of photo- receptor cells [19-22]. Damage of the photoreceptor outer segment will reduce the P1 amplitude and result in delays of its implicit time [18]. In this study we assumed that bipolar and other outer retina cells have more of an effect on P1 waveforms than N1 waveforms [22,23]. Unlike previous studies [12-14], we evaluated not only the change of the am- plitude, but the change of the implicit time after intravitreal bevacizumab injection. The implicit times of P1 and N1 were prolonged before and after injection compared with normal values. The delayed P1 implicit time was due to delay in bi- polar cell response of the outer retina [19]. It is also possible that the delay in the N1 implicit time reflected damage to the inner retinal layers, as well as the outer retina [22]. In our study the implicit times of P1 and N1 in rings 1, 2, and 3 showed statistically significant improvement compared with amplitude. Implicit time has been shown to be more sensitive than amplitude in CNV as well as other conditions, such as diabetes [24], retinitis pigmentosa [25,26], and macular dys- trophy [27]. The implicit time is thought to be more susceptible than the amplitude to injury of photoreceptors and the outer plexiform layer [19,22,23,28]. Although mfERG responses after injection improved compared with the baseline, the am- plitude and implicit time were in the sub-normal range. Analysis showed that intravitreal bevacizumab injection contributed to improvement of retinal function, but did not result in complete recovery. In a study on 18 eyes with AMD by Moschos et al. [13], there was improvement of visual acuity, mfERG response, and OCT parameters after intravitreal bevacizumab in- jection, but there was no correlation between values. Maturi et al. [14] studied nine patients with AMD after injection and found patients to have significantly higher amplitude com- pared with baseline, but no correlation was found between amplitude and visual acuity or CMT. Also, these findings show that BCVA, CMT, TMV, the amplitude, and implicit time of mfERG had no obvious correlation, except for the implicit time of N1 in ring 1 and the BCVA. From the results, we observed less correlation between mfERG responses and improvement of visual acuity and ana- tomical changes, as mfERG waveforms reflect not only the