How practical is it to use spectral stimuli for non-invasive dissection of the human visual system in health and disease? The rods and the three classes of cone photoreceptor have broadly-tuned, overlapping spectral sensitivities that peak at different wavelengths in the visible spectrum. No single light can be used to target only one receptor class but, if two lights differ only in the stimulation they offer to the target receptor class and their exchange is silent for the remaining receptors, the response of the target receptor can be isolated--a technique known as silent substitution. Calculation of the required spectral composition of the two lights requires estimates of the spectral sensitivities of the receptors. Photopigment spectral sensitivities are well known but there are polymorphisms within the normal population, and the light that reaches the photoreceptors must travel through ocular media whose optical densities vary substantially between individual observers. Silent substitution methods have therefore typically required lengthy observer calibration routines.

In this paper, Huchzermeyer and Kremers use silent substitution without observer calibration to derive S-cone and rod-driven sensitivity to flickering lights. Importantly, they calculate the expected "splatter" in other receptor classes, and use measurements after a rod bleach and from an S-cone monochromat to validate their measurements. The method permits good separation of the responses of the target photoreceptor types under specific conditions, but also allows identification of conditions under which isolation fails. In the clinic, the method is attractive, particularly as it forgoes the long periods of dark adaptation that are typically used to assess rod function, and opens the way to routine monitoring of the functional effects of diseases such as retinitis pigmentosa and evaluation of novel therapies.

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