Albinism is characterized by a variety of abnormalities of the visual system. Ophthalmic characteristics of albinism include nonprogressive reduced visual acuity, delayed maturation of the visual system, nystagmus, iris translucency, foveal hypoplasia, fundus hypopigmentation, and an abnormal pattern of decussation at the optic chiasm, the so called chiasmal misrouting. When all clinical signs are present, a diagnosis of albinism is evident. However, subjects may have a very mild phenotype, and on the other hand, some other ocular conditions may have overlapping features. Therefore, major and minor diagnostic criteria were recently introduced.
1 Major criteria are ocular hypopigmentation, foveal hypoplasia grade 2 or more, and misrouting. Misrouting in albinism is characterized by a majority of the optic nerve fibers crossing at the chiasm and projecting to the contralateral hemisphere, resulting in a reduced or delayed signal in the ipsilateral hemisphere.
2,3 This is in contrast to normal routing, where the visual information of each eye projects equally to both hemispheres. Misrouting can be detected by multichannel visually evoked potential (VEP) recordings. The interhemispheric difference potential has been quantified by use of an asymmetry index, Pearson's correlate, or chiasm coefficient.
4–7 Soong et al.
5 showed that the Pearson's correlate was more accurate than the asymmetry index in assessing misrouting. The Pearson's correlate compared the interhemispheric difference potential waveforms from right eye (OD) and left eye (OS) stimulation measured in a window of 0–200 ms.
5 Jansonius et al.
6 introduced an improved correlate, the chiasm coefficient, that was calculated in a window of 60–300 ms.
7 The difference between the chiasm coefficient and the Pearson's correlate is that the calculation of the chiasm coefficient includes a high-pass filter to cope with drift.
5–7 For both Pearson's correlate and chiasm coefficient, a negative value indicates a predominantly anticorrelation between the interhemispheric difference potential waveforms. This may be caused by an excessive amount of optic nerve fibers projecting to the contralateral hemisphere, as in albinism, or to the ipsilateral hemisphere, as seen in achiasmia. The correlations can take a value from −1 to +1; −1 indicates complete asymmetry and +1 complete symmetry. The more noise the signals contain, the more the value will shift toward 0.
Figure 1 shows simulated examples of the effect on the level of correlation for offset, amplitude difference, drift, and noise on the chiasm coefficient and Pearson's correlate. The chiasm coefficient appears less sensitive to drift, although with a nonlinear drift even the chiasm coefficient may deteriorate severely (
Fig. 1g). Previous studies concluded that flash VEPs (fVEPs) should be used for the detection of misrouting in subjects under the age of 3 years, pattern-onset VEP (poVEP) in subjects from 6 years of age onward, and both fVEP and poVEP in toddlers between 3 and 6 years. Misrouting could be detected only sporadically with poVEP in subjects younger than 3 years of age. The pattern reversal and hemifield stimulation proved to be unreliable.
2,4,8–12 Therefore, the International Society for Clinical Electrophisiology of Vision (ISCEV) guide recommends for multichannel VEP recordings to use fVEP in young children and poVEP in children ≥6 years and adults.
13 Earlier studies compared phenotypically evident albinism subjects to controls without ocular pathology, except for idiopathic nystagmus.
2,4,7–12,14