Rapid Objective Testing of Visual Function Matched to the ETDRS Grid and Its Diagnostic Power in Age-Related Macular Degeneration

Abstract

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade.

Design: Evaluation of a diagnostic technology.

Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure-function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA).

Main outcome measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size.

Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well.

Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.

Keywords: AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; AUC, area under the receiver operating characteristic curve; BCVA, best-corrected visual acuity; ETDRS-grid OCT; OFA, Objective FIELD Analyzer; PD, pattern deviation; ROC, receiver operating characteristic; SD, standard deviation; TD, total deviation; abs(DelayDiff), delay difference; macular function; mfPOP, multifocal pupillographic objective perimetry; mfVEP, multifocal visual evoked potential; multifocal pupillography; objective perimetry; rapid perimetry.

Figure 1

The Objective FIELD Analyser (OFA) device. A, Illustration of a test participant seated and looking into the OFA objective lenses. B, Diagram showing the dichoptic stimulus arrangement inside the OFA. The pseudorandomly sequenced brief-onset stimuli are presented on 2 displays. Cold mirrors direct the eyes to the 2 displays. Infrared video cameras capture images of the 2 pupils. The record of the pupil diameters and the stimulus histories are used to extract the responses to each of the up to 44 stimulus test regions per eye. See Figure 2.

Figure 2

Representations of the 3 Objective FIELD Analyser (OFA) stimulus types. All stimuli shown are those for the left eye (OS); stimuli for the right eye (OD) were mirror image. A, Contours of the 44 stimulus regions of the widefield P129 stimulus. The transiently presented (33 ms) stimuli were delivered pseudorandomly, with a mean per-region interval of 4 s. In practice, overlapping regions are never presented concurrently. B, Stimuli from the left and right halves of the 5 rings of P129 stimuli showing their relative intensities. C, Same as for (B), but for the 44-region P131 macular stimulus array. D, M18 stimulus array. E, Numbering scheme of the M18 stimuli as presented in visual space to OS. F, The projection of the M18 stimuli onto the retina showing the relationship to the ETDRS grid (cyan).