Results in patients showed that the function relating the FERG to
stimulus modulation depth was significantly altered, compared with that
of control subjects, with a different pattern of abnormalities
depending on the severity of macular lesions. Response gain losses and
modulation depth-dependent phase delays, with normal thresholds, were
associated with early lesions. Increased thresholds, in addition to
gain and phase abnormalities, were found in more advanced lesions. In
the past, the FERG-versus-modulation depth function has been used to
test retinal flicker threshold, gain, or both, in physiologic
experiments
13 15 17 20 22 and in patients with retinitis
pigmentosa or hereditary macular degeneration.
14 19 26 However, changes in these FERG parameters have not been investigated in
ARM. The present results suggest a pathophysiological sequence in
which, in association with early Bruch’s membrane and RPE changes
(i.e., soft drusen), there are already some signs of retinal
dysfunction involving response gain. Indeed, amplitude gain losses and
modulation depth–dependent phase delays could be the expression of the
same altered control mechanism. These abnormalities may result from
early degenerative changes
3 of cone photoreceptors, whose
number at this stage is presumably normal or near normal. Shortening of
cone outer segments, by reducing quantum catch and therefore the
effective retinal intensity of the stimulus, and altered photoreceptor
membrane properties (i.e., time constants
26 36 ) by
delaying reestablishment of equilibrium, may both affect retinal gain.
As the disease spreads to larger areas, with a spatially dependent
loss
2 of photoreceptors, retinal dysfunction becomes more
marked and manifests itself with an increase in threshold. It has been
indeed suggested
14 that FERG sensitivity losses may
result from photoreceptor dropout, either spatially dependent or
independent, assuming that detection depends on the pooled contribution
of underlying retinal elements. A simpler explanation of the present
findings may be that different degrees of severity of cone system
dysfunction, independent of the number of remaining photoreceptors, are
reflected first by changes in response gain and phase and then by an
increased threshold. Clearly, the proposed sequence of FERG
abnormalities, whatever the underlying mechanism would be, should be
validated by longitudinal studies with clinical evaluations and serial
recordings in the same ARM patients.