Accuracy of Pupil Assessment for the Detection of Glaucoma: A Systematic Review and Meta-analysis

doi:10.1016/j.ophtha.2013.04.012

Ophthalmology

Volume 120, Issue 11, November 2013, Pages 2217-2225

https://doi.org/10.1016/j.ophtha.2013.04.012 Get rights and content

Objective

To assess the accuracy of using pupillary light reflex (PLR) in detecting glaucoma.

Clinical Relevance

Glaucoma is a specific disease of the optic nerve and is often more severe in 1 eye. When large enough, this asymmetry in disease severity can cause a relative afferent pupillary defect (RAPD). Better detection of RAPDs may be one way to identify persons with glaucoma.

Methods

We searched Medline and Embase through June 2012 and searched bibliographies for relevant studies for additional references. Two authors independently reviewed all articles and selected studies that assessed PLRs in patients with glaucoma. We analyzed data using mixed-effect bivariate summary receiver operating characteristic meta-analysis models.

Results

A total of 30 studies were included in this review. An RAPD was observed in 9% to 82% of patients with glaucoma. Eleven studies with a total of 7271 participants were included in the analysis, and the pooled estimate corresponded to a sensitivity of 0.63 (95% confidence interval [CI], 0.43–0.80) and a specificity of 0.93 (95% CI, 0.85–0.97). After excluding 2 studies that used the swinging flashlight test, the sensitivity increased to 0.74 (95% CI, 0.59–0.85) with a specificity of 0.85 (95% CI, 0.77–0.90). Study designs and different pupil measurement techniques explained part of the heterogeneity between studies.

Conclusions

Patients with glaucoma frequently have an abnormal PLR and comparing the responses between the 2 eyes can in part distinguish between those with glaucoma and those without the disease. Newer instruments and analytic approaches to assess pupil function may improve the performance of pupil screening.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Data Sources and Search Strategy

We searched Medline (literature from 1951) and Embase (from 1947) to identify potentially relevant articles. Our search included combined controlled vocabulary search terms (MeSH and EMTREE) and text words for glaucoma, visual field defect, optic neuropathy, retinal nerve fiber layer thickness (study population) and RAPD, SFT, pupillography, pupillometer, pupil perimetry, and PLR (techniques) (Appendix 1, available at http://aaojournal.org). All searches were last updated on June 22, 2012, and

Search Results and Study Characteristics

The electronic database searches identified 1258 citations. We deleted duplicates and assessed the bibliographies of included studies and articles that cited the included studies. A total of 31 articles from 30 studies met inclusion criteria (Fig 1).4, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 Studies were conducted in more than 11 countries and published in different languages. We did not translate non-English

Discussion

This review of the literature shows that an RAPD is present in patients with glaucoma, but estimates range widely in the literature. The severity of an RAPD correlates with the amount of visual field loss and the extent of optic nerve damage. Furthermore, assessing pupil function to detect glaucoma seems highly specific (>90%). On the basis of a meta-analysis of the reported data, pupillography has a sensitivity of approximately 75% with a specificity of 85% in clinic-based studies.

The SFT is

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Cited by (46)

Assessment of a pupillometric method for the screening of glaucoma
2023, Journal Francais d'Ophtalmologie
Le glaucome est une neuropathie optique progressive et longtemps asymptomatique, ce qui rend difficile un diagnostic précoce. Le champ visuel est aujourd’hui l’examen de référence mais il comporte des défauts. L’objectif de cette étude est d’évaluer un test pupillométrique soumis passivement au sujet pendant 1 minute, pour déterminer sa sensibilité et sa spécificité dans le classement des yeux sains et des glaucomes, ainsi que sa tolérance par rapport au champ visuel.
Quarante-cinq participants ont été inclus dans cette étude interventionnelle, monocentrique et prospective. Il leur a été soumis 3 tests pupillométriques monoculaires (6 enregistrements) au cours desquels les réponses pupillaires à un stimulus lumineux ont été enregistrées : stimulation multifocale champ large (test doublé) et étude du cycle d’oscillation pupillaire.
Les puissances spectrales et les variables pupillaires enregistrées lors de la stimulation champ large permettent d’obtenir une sensibilité de 0,94 et une spécificité de 0,88, voire une discrimination parfaite pour les stades précoces de la maladie. L’analyse du cycle d’oscillation pupillaire offre une sensibilité de 0,92 et une spécificité de 0,88 pour les stades précoces. L’acceptabilité de ces tests est meilleure que celle du champ visuel.
Les résultats indiquent que les variables dérivées de nos tests pupillométriques permettent une bonne classification des yeux sains et des glaucomes, et doivent être confirmés sur une population plus importante.
Glaucoma is a progressive optic neuropathy, remaining asymptomatic for a long time, which makes its early diagnosis difficult. Visual field testing is still the gold standard but is less than ideal. The goal of this study is to assess a pupillometric test, administered passively to the subject for one minute, to measure its sensitivity and specificity in the classification of healthy eyes and glaucomatous eyes, and to evaluate its tolerability compared to visual field testing.
Forty-five participants were included in this single-center, interventional, prospective study. They underwent 3 monocular pupillometric tests with light stimulation: 6 pupillary responses were recorded during full-field multifocal stimulation (performed twice) and pupillary hippus cycle study.
Analysis of spectral power and pupillary measurements with full-field multifocal stimulation provides a 0.94 sensitivity and a 0.88 specificity, a virtually perfect discrimination for early stages of glaucoma. Analysis of pupil cycle time provides a 0.92 sensitivity and a 0.88 specificity for early stages. Acceptability of this test by patients is superior to visual field testing.
These results show that data from our pupillometric recordings provide a good classification of healthy and glaucomatous eyes and must be confirmed on a larger population.
Temporal Raphe Sign for Discrimination of Glaucoma from Optic Neuropathy in Eyes with Macular Ganglion Cell–Inner Plexiform Layer Thinning
2019, Ophthalmology
Citation Excerpt :
Although temporal raphe sign positivity in severe-stage glaucoma was lower than overall (73.3% vs. 91.0%), it was still significantly larger than that of severe-stage NGON and might be a useful clue for discrimination. In previous reports, the presence of RAPD in GON ranged from 9% to 82%.48 Relative afferent pupillary defect is detectable once the RNFL has been thinned to 83% compared with the fellow eye.49
To evaluate the potential of the temporal raphe sign on the macular ganglion cell–inner plexiform layer (mGCIPL) thickness map for discriminating glaucomatous from nonglaucomatous optic neuropathy (NGON) in eyes with mGCIPL thinning.
Cross-sectional study.
A total of 175 eyes of 175 patients with mGCIPL thinning on Cirrus (Carl Zeiss Meditec, Dublin, CA) high-definition OCT were retrospectively included. Glaucoma specialists and neuro-ophthalmology specialists evaluated the patients’ medical records for diagnosis of glaucomatous optic neuropathy (GON) or NGON. Finally, by consensus, 67 eyes with GON and 73 eyes with NGON were enrolled.
A positive temporal raphe sign was declared in patients in whom there was a straight line longer than one-half of the length between the inner and outer annulus in the temporal elliptical area of the mGCIPL thickness map. Decision tree analysis was performed to formulate a diagnostic model.
Area under receiver operating characteristic curve (AUC) with sensitivity and specificity.
The temporal raphe sign was observed in 61 of 67 GON eyes (91.0%), but in only 21 of 73 NGON eyes (28.8%) (P < 0.001; chi-square test). On this basis, the diagnostic ability of the temporal raphe sign for discriminating GON from NGON was judged to be good (AUC, 0.811; 95% confidence interval, 0.749–0.874; sensitivity, 91.0%; specificity, 71.2%). The diagnostic performance of the decision tree–based model (AUC 0.879; 95% confidence interval, 0.824–0.933; sensitivity, 88.1%; specificity, 87.7%) was better than that of the temporal raphe sign or the relative afferent pupillary defect (RAPD) alone (P = 0.005, P < 0.001, respectively; DeLong’s test). The decision tree model revealed the following: (1) If the temporal raphe sign is positive and the RAPD is absent, the case should be diagnosed as GON; (2) if the temporal raphe sign is absent regardless of the presence or absence of the RAPD, or both the temporal raphe sign and the RAPD are present, the case should be diagnosed as NGON.
In clinical practice, determining whether the temporal raphe sign appears on OCT macular scans can be a useful tool for discrimination of glaucomatous from nonglaucomatous mGCIPL thinning.
The long-term effects of topical latanoprost 0.005% treatment on pupillary functions: A 2-year longitudinal study
2024, European Journal of Ophthalmology
Evaluation of the Glaucomatous Macular Damage by Chromatic Pupillometry
2023, Ophthalmology and Therapy
Detection of Relative Afferent Pupillary Defect and Its Correlation with Structural and Functional Asymmetry in Patients with Glaucoma Using Hitomiru, a Novel Hand-Held Pupillometer
2023, Journal of Clinical Medicine
Handheld chromatic pupillometry can accurately and rapidly reveal functional loss in glaucoma
2023, British Journal of Ophthalmology

View all citing articles on Scopus

: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: Funding: D.S.C. received a training grant from the National Institute on Aging (2T32AG000247-16).

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Original articleAccuracy of Pupil Assessment for the Detection of Glaucoma: A Systematic Review and Meta-analysis

Objective

Clinical Relevance

Methods

Results

Conclusions

Financial Disclosure(s)

Section snippets

Data Sources and Search Strategy

Search Results and Study Characteristics

Discussion

Surv Ophthalmol

Am J Ophthalmol

Ophthalmology

J Clin Epidemiol

Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data

Invest Ophthalmol Vis Sci

Interocular asymmetry of visual field defects in primary open angle glaucoma and primary angle-closure glaucoma

Eye (Lond)

Spatial pattern of glaucomatous visual field loss obtained with regionally condensed stimulus arrangements

Invest Ophthalmol Vis Sci

Relative afferent pupillary defect in glaucoma: a pupillometric study

Acta Ophthalmol Scand

Electronic pupillography; a new instrument and some clinical applications

AMA Arch Ophthalmol

The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

BMC Med Res Methodol [serial online]

A simple method for the early diagnosis of abnormalities of the pupillary reaction

Br J Ophthalmol

Edge-light pupil cycle time

Br J Ophthalmol

A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations

Stat Med

metandi: meta-analysis of diagnostic accuracy using hierarchical logistic regression

Stata J

The utility of relative afferent pupillary defect as a screening tool for glaucoma: prospective examination of a large population-based study in a south Indian population

Br J Ophthalmol

The Ibadan glaucoma study

Afr J Med Med Sci

Comparative study of 3 techniques to detect a relative afferent pupillary defect

J Glaucoma

The usefulness of a new method of testing for a relative afferent pupillary defect in patients with ocular hypertension and glaucoma

Trans Am Ophthalmol Soc

Retinal nerve fiber layer loss in glaucoma patients with a relative afferent pupillary defect

Invest Ophthalmol Vis Sci

The afferent pupillary defect in asymmetric glaucoma

Arch Ophthalmol

Quantification of retinal nerve fiber layer thickness reduction associated with a relative afferent pupillary defect in asymmetric glaucoma

Br J Ophthalmol

Associating the magnitude of relative afferent pupillary defect (RAPD) with visual field indices in glaucoma patients

Br J Ophthalmol

Relative afferent pupillary defect in glaucoma

Klin Monbl Augenheilkd

Relative afferent pupillary defects in primary open-angle glaucoma–five years' experience

J Natl Med Assoc

Cardiovascular reflex testing and pupil cycle time in open-angle glaucoma

Ophthalmologica

Original article
Accuracy of Pupil Assessment for the Detection of Glaucoma: A Systematic Review and Meta-analysis