Intersession Test-Retest Variability of Microperimetry in Type 2 Macular Telangiectasia

Abstract

Purpose: Microperimetry is used as an endpoint in type 2 macular telangiectasia (mactel) trials. The change required for defining disease progression depends on measurement error. We determined the threshold of test-retest variability (TRV) of microperimetry in mactel.

Methods: A prospective study was done of 24 patients with stable mactel enrolled in a tertiary eye clinic. Each patient underwent three sessions of microperimetry separated by a median of 28 days. An identical testing protocol was used: 4-2 staircase algorithm at 37 loci radial grid covering central 6°. Microperimetry variables were compared across three visits. TRV was quantified by calculating the coefficients of repeatability (CRs) for mean and median foveal sensitivity and the number of loci with dense scotoma (DS) or normal sensitivity (NS). The 95% confidence intervals (CIs) for CRs were calculated.

Results: Mean and median foveal sensitivity increased from first to second testing sessions. Test duration, visual acuity, number of loci with DS, and fixation stability remained stable through the three test sessions. The intersession CRs for mean and median foveal sensitivity were 2.6 (95% CI, 1.8-3.3) and 2.4 (95% CI, 1.7-3.1) dB, respectively. CRs for the number of DS and NS loci were 5 and 12 loci. CR for both logBCEA63 and logBCEA95 was 1.0 (95% CI, 0.8-1.2).

Conclusions: The first microperimetry examination should be discarded due to learning effects. TRV in foveal sensitivity may be as high as 3.3 and 3.1 dB (∼0.3 log unit; 2× change) for its mean and median.

Translational relevance: Our results have implications for the design of clinical trials in mactel.

Keywords: MAIA microperimetry; fixation stability; measurement error; repeatability; retinal sensitivity; scotoma.

Figure 1

The 37 test loci grid pattern covers the central 6° region of the retina with 1° separation between each of the 3 rings. In MAIA, light stimuli created by a white LED light are projected directly onto the retinal surface at specific locations. Subsequent measurements re-examines the same anatomical locations by using the follow-up retest protocol.

Figure 2

A Bland-Altman plot of within-subject standard deviation (SD) against mean shows increasing variability of the BCEA with magnitude for 63% (A) and 95% (B) of fixation loci. After logarithm (base 10) transformation, variability became independent of mean for logBCEA 63% (C) and logBCEA 95% (D). Bland-Altman plots of difference against mean show similar measurement error between logBCEA 63% (E) and logBCEA 95% (F). The mean difference (test 3–test 2) is marked as dashed line (- - - ) and the 95% limits of agreement (2 × SD above and below mean) are marked as dotted lines (. . . ).

Figure 3

A Bland-Altman plot of within-subject SD against mean shows variability of the number of loci with dense scotoma (A) and normal sensitivity (B) did not increase with magnitude. Bland-Altman plot of difference against mean show dense scotoma loci mapping (C) is slightly more reliable than normal sensitivity loci mapping (D). The mean difference (test 3–test 2) is marked as dashed line (- - -) and the 95% limits of agreement (2 × SD above and below mean) are marked as dotted lines (. . .). Floor effects were removed during calculation of limits of agreement.

Figure 4

Three examples of interpolated sensitivity maps for three visits illustrating a subject with no scotoma and stable fixation (A–C), a subject with scotoma but stable fixation (D–F), and a subject with scotoma and relatively unstable fixation (G–I). They illustrate the variability in dense scotoma and normal sensitivity loci mapping.

Figure 5

Bland-Altman plots of absolute difference against mean show no change in variability of mean (A) and median (B) foveal sensitivity across a range of measurement magnitude. Bland-Altman plots of difference against mean show similar extent of measurement error between mean (C) and median (D) foveal sensitivity. The mean difference (test 3–test 2) is marked as dashed line (- - -) and the 95% limits of agreement (2 × SD above and below mean) are marked as dotted lines (. . .).

Figure 6

Scatter graphs show some consistency in pointwise sensitivity measurements between Tests 2 and 3 in pooled analysis (A, all loci across all patients = 888 pairs of measurements) and foveal center locus (B, one locus across all patients = 24 pairs of measurements). Variability is most marked in retinal loci with a mean retinal sensitivity of less than 20 dB in pooled analysis (C) but this was not obvious at foveal center locus (D) because of foveal sparing lesions in macular telangiectasia. Bland-Altman plots of differences against mean show that measurement error is driven by certain retinal loci with poorer mean sensitivity in pooled analysis (E) but not at foveal center locus (F). The mean difference (Test 3–Test 2) is marked as dashed line (- - -) and the 95% limits of agreement (2 × SD above and below mean) are marked as dotted lines (. . .). Floor effects were removed during calculation of limits of agreement.