Response of the Pupil to Tropicamide Is Not a Reliable Test for Alzheimer Disease

Abstract

No evidence of pupillary hypersensitivity to an anticholinergic mydriatic drug was found in patients with Alzheimer disease or any evidence that this putative hypersensitivity could be used as an early, simple diagnostic test for Alzheimer disease.

Why patients with Alzheimer’s disease may show increased sensitivity to tropicamide eye drops: role of locus coeruleus

“…The use of absolute values eliminates a possible error of interpretation resulting from using percentage change. In the original paper by Scinto et al (1994) and also in a number of subsequent studies (Gomez-Tortosa et al 1996;Treloar et al 1996;FitzSimon et al 1997;Robles et al 1999), the response to tropicamide was expressed as a percentage of pre-treatment pupil size without any reference to the absolute value of the baseline. Therefore, if patients in the AD group had smaller pupil diameters than subjects in the control group, which indeed can be the case as reported by Prettyman et al (1997), the conclusion of an increased response to tropicamide in the AD group may have been based on a computational artefact.…”

Ocular Biomarkers for Early Detection of Alzheimer's Disease

“…Alternative explanations more consistent with the dual hypersensitivity include AD related damage to the locus coeruleus brain region which is involved in pupillary control [80] or increased corneal penetration of the cholinergic eyedrops. One study using a fluorescent marker to evaluate corneal penetration of tropicamide found no difference between AD and controls [81], but further studies are required to confirm this result. It should also be noted that not all studies controlled for medications with anticholinergic effects.…”

“…Some studies found no significant hypersensitivity in AD [81][82][83][84][85][86][87][88][89][90][91], or a hypersensitive response in APOE-ε4 allele carriers rather than AD [78,92], affecting carriers of this allele who are cognitively normal (although at increased risk of progressing to AD). A similar hypersensitivity has been reported in Down's syndrome subjects -who develop AD as a result of an extra copy of the AβPP gene [93], yet also in healthy young adults [87].…”

Neuro-ophthalmology of pupillary function - practical guidelines

“…Patients with other dementias and normals were said not to respond [44]. These results could not be confirmed by other investigators, and the "tropicamide test for Alzheimer's disease" cannot be recommended [13,15,23,28,31,34,43]. Pupils of patients with myotonic dystrophy are hypersensitive to tropicamide as well, and show additional pupillographic abnormalities [55].…”