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. 2023 Jun 1;12(6):4.
doi: 10.1167/tvst.12.6.4.

Microperimetry as an Outcome Measure in RPGR-associated Retinitis Pigmentosa Clinical Trials

Laura J Taylor  1   2 , Amandeep S Josan  1   2 , Jasleen K Jolly  3 , Robert E MacLaren  1   2
Affiliations

Microperimetry as an Outcome Measure in RPGR-associated Retinitis Pigmentosa Clinical Trials

Laura J Taylor et al. Transl Vis Sci Technol. .

Abstract

Purpose: To explore which microperimetry sensitivity index (pointwise sensitivity, mean sensitivity, and volume sensitivity) is suitable as a microperimetry outcome measure in patients with X-linked RPGR-associated retinitis pigmentosa (RP).

Methods: Microperimetry data from patients with RPGR-associated RP were collected and analyzed retrospectively. Fourteen participants completed triplicate microperimetry testing, across 2 consecutive days for the repeatability analyses. Longitudinal data was obtained from 13 participants who completed microperimetry testing at two separate visits.

Results: The test-retest coefficients of repeatability (CoR) for pointwise sensitivity were ±9.5 dB and ±9.3 dB, in the right and left eyes, respectively. The mean sensitivity CoR for the right and left eyes was ±0.7 dB and ±1.3 dB. Volume sensitivity CoR was ±144.5 dB*deg2 and ±324.2 dB*deg2 for the right and left eyes, respectively. The mean sensitivities were positively skewed toward zero in those with a high number of nonseeing points (arbitrarily assigned to -1.0 dB) and just seen points (0.0 dB). Volume sensitivities were unaffected by the averaging effects of skewed data.

Conclusions: Clinical trials should report population-specific test-retest variability to determine a clinically significant change. Pointwise sensitivity indices should be used with caution as outcome measures in clinical trials owing to high levels of test-retest variability. Global indices seem to be less prone to variability. Volume sensitivity indices seem to be superior for use in RPGR-associated RP clinical trials compared with mean sensitivity because they are unaffected by the averaging effects of highly skewed data.

Translational relevance: Careful selection of sensitivity indices (VA) is required when using microperimetry as a clinical trial outcome measure.

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Conflict of interest statement

Disclosure: L.J. Taylor, None; A.S. Josan, None; J.K. Jolly, None; R.E. MacLaren, None

Figures

Figure 1.
Figure 1.
The pointwise repeatability for the right (A) and left eyes (B). The Bland–Altman plots illustrate the test–retest variability of individual microperimetry loci for participants with RPGR-associated RP. The pointwise CoR for the right and left eyes were ±9.5 dB and ±9.3 dB respectively. LLoA, lower limit of agreement; ULoA, upper limit of agreement.
Figure 2.
Figure 2.
Longitudinal pointwise sensitivity changes for a single test pair: (A) and (B) show MAIA pointwise sensitivity threshold plots from a single participant, for visit one and two, respectively. (C) Details visit two minus visit one pointwise sensitivity differences. The red points highlight any loci with absolute changes of ≥7.0 dB, in this instance two loci that gained ≥7.0 dB and three loci dropped <7.0 dB.
Figure 3.
Figure 3.
(A) The median mean sensitivity for the right eyes visit one was 5.7 dB (IQR, 0.2–9.2 dB) and for visit two it was 3.2 dB (IQR, 0.3–8.5 dB). Left eye median mean sensitivity for visit one was 6.9 dB (IQR, 2.8–9.2 dB), for visit two it was 4.3 dB (IQR, 0.5–9.3 dB). (B) The volume sensitivity data for visits one and two for each eye. The median volume sensitivity for the right eye was 1497.4 dB*deg2 (IQR, 272.3–2460.2 dB*deg2) for test one and 893.7 dB*deg2 (IQR, 223.3–2217.8 dB*deg2) for test two. Left eye median volume sensitivity was 1748.2 dB*deg2 (IQR, 860.9–2435.3 dB*deg2) for visit one and 1143.1 dB*deg2 (IQR, 284.8–2322.0 dB*deg2) for visit two. (C and D) Frequency distribution plots for microperimetry pointwise sensitivity values, from visit one and two, showing a non-normal positively skewed distribution, with −1.0 dB containing the highest number of values for the right and left eyes, respectively. (E and F) Scatter plots showing the relationship between the number of unseen points and sensitivity, for mean sensitivity and volume sensitivity, respectively. Right eye (RE); left eye (LE).
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