Elsevier

American Journal of Ophthalmology

Volume 156, Issue 6, December 2013, Pages 1285-1296.e2
American Journal of Ophthalmology

Original article
Development and Validation of an Associative Model for the Detection of Glaucoma Using Pupillography

https://doi.org/10.1016/j.ajo.2013.07.026Get rights and content

Purpose

To develop and validate an associative model using pupillography that best discriminates those with and without glaucoma.

Design

A prospective case-control study.

Methods

We enrolled 148 patients with glaucoma (mean age 67 ± 11) and 71 controls (mean age 60 ± 10) in a clinical setting. This prototype pupillometer is designed to record and analyze pupillary responses at multiple, controlled stimulus intensities while using varied stimulus patterns and colors. We evaluated three approaches: (1) comparing the responses between the two eyes; (2) comparing responses to stimuli between the superonasal and inferonasal fields within each eye; and (3) calculating the absolute pupil response of each individual eye. Associative models were developed using stepwise regression or forward selection with Akaike information criterion and validated by fivefold cross-validation. We assessed the associative model using sensitivity, specificity and the area-under-the-receiver operating characteristic curve.

Results

Persons with glaucoma had more asymmetric pupil responses in the two eyes (P < 0.001); between superonasal and inferonasal visual field within the same eye (P = 0.014); and smaller amplitudes, slower velocities and longer latencies of pupil responses compared to controls (all P < 0.001). A model including age and these three components resulted in an area-under-the-receiver operating characteristic curve of 0.87 (95% CI 0.83 to 0.92) with 80% sensitivity and specificity in detecting glaucoma. This result remained robust after cross-validation.

Conclusions

Using pupillography, we were able to discriminate among persons with glaucoma and those with normal eye examinations. With refinement, pupil testing may provide a simple approach for glaucoma screening.

Section snippets

Subjects and Eye Examinations

In this prospective case-control study, we enrolled a total of 243 participants, including 165 patients with glaucoma and 78 normal subjects. All participants were enrolled between March 2011 and June 2012. To be eligible for participation, participants had to be 40 years old or older at enrollment, to have presenting visual acuity better than 20/100 in both eyes, and to have not had ocular surgery within 3 months. All subjects provided informed consent to participate in the study, and the

Results

A total of 236 eligible participants were enrolled in our study, and 219 (93%) of them completed the pupillographic examination. Of the 17 incomplete examinations, 4 were due to frequent blinking, 3 were due to software errors, and the pupil waveforms of the other 10 were unanalyzable. Among the 219 subjects who successfully completed the pupillographic test, 148 cases had glaucoma in at least 1 eye (93% primary open-angle glaucoma, 3% primary angle-closure glaucoma, and 4% secondary glaucoma),

Discussion

The asymmetry of the pupillary light reflex between eyes (a surrogate for an RAPD) differed significantly when comparing patients with glaucoma to those without evidence of retinal or optic nerve disease. However, nearly half of those with glaucoma were missed when comparing only the between-eye responses. Noting this limitation, we compared the pupil responses for corresponding superonasal vs inferonasal fields and observed greater within-eye asymmetry in patients who did not have an RAPD.

Dolly S. Chang, MD, MPH, PhD, received her medical degree from National Taiwan University and subsequently earned her MPH and PhD in epidemiology from Johns Hopkins University Bloomberg School of Public Health. Her areas of research interest include the screening, prevention, and interventions of eye diseases, the methodology and conduct of clinical trials and systematic reviews, and pupil pathophysiology.

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  • Cited by (0)

    Dolly S. Chang, MD, MPH, PhD, received her medical degree from National Taiwan University and subsequently earned her MPH and PhD in epidemiology from Johns Hopkins University Bloomberg School of Public Health. Her areas of research interest include the screening, prevention, and interventions of eye diseases, the methodology and conduct of clinical trials and systematic reviews, and pupil pathophysiology.

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