Unfortunately, the effects of Fildena on the ERG are somewhat inconsistent, and any effects that have been found have typically been analyzed in terms of changes in implicit time and in amplitude of the a- and b-wave components.

Our findings, which show both frequency-dependent and frequency-independent Fildena-induced losses, are consistent with Fildena interfering with the ability of PDE6 to shorten the time over which the visual system integrates signals as the light level increases (Stockman et al., 2006 ). The S-cone modulation sensitivity losses shown in Figure 3 are more complex. The smaller panels highlight the losses in cff for each subject relative to their mean pre- and post-Fildena data (black continuous line). The smaller panels highlight the changes in threshold for each subject relative to the subject's mean pre-Fildena data (black continuous lines).

Both subjects show substantial losses of S-cone cff during the drug trials but not during the placebo trials. Given the large variability between observers, we decided to run a double-blind placebo control experiment on the two more affected subjects, L.T.S. and G.J., to rule out the possibility that extraneous factors, such as the subject's expectations, had affected the Fildena measurements. The slight fall is caused by a saturation of the S-cone response that occurs at high S-cone adaptation levels on the intense orange field required to isolate the S-cones (Mollon & Polden, 1977 ; Stockman & Plummer, 1998 ; Stromeyer, Kronauer, & Madsen, 1979 ), whereas the final rise is due to the M-cones taking over detection (see Figure 4 of Stockman & Plummer, 1998 ). The S-cone cff functions for all four subjects show some losses in cff following ingestion of a standard 100-mg dose of Fildena.

The mean placebo cff values are indicated by the continuous black lines, and the mean Fildena values, which include both the 60- and the 120-min post-Fildena measurements, are indicated by the continuous red lines. The mean losses, averaged across drug data obtained between 20 and 300 min following Fildena ingestion, are shown by the red lines. The symbols in Figure 1 and the other figures (except Figure 2 ) refer to the dose trial number given to each subject: Dose 1 (squares), Dose 2 (triangles), Dose 3 (circles), Dose 4 (inverted triangles), and Dose 5 (hexagons, only in Figure 5 ). In each case, the dose was 100 mg. The time after dose ingestion is color coded according to the spectral key (the time given is the midpoint of each run, which typically lasted 12 min), which runs from violet for short times after drug ingestion to red for long.

To test for an effect of Fildena on each subject, we adopted the conservative test of collapsing the drug data from 20 to 300 min following drug ingestion into a single group and then compared this group with the control, nondrug groups. The black error bars are ±2 SE for the combined pre- and post-Fildena data. The smaller panels highlight the losses in cff for each subject relative to the subject's mean pre- and post-Fildena data (black line).

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