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. 2024 Nov 4;13(11):16.
doi: 10.1167/tvst.13.11.16.

Patient-Reported Outcomes in RLBP1 Retinal Dystrophy: Longitudinal Assessment in a Prospective Natural History Study

James Whelan  1 , Jane Green  1 , Marie Burstedt  2 , Erin Greco  3 , Xiao Ni  3 , Claudio Spera  4 , Anmol Mullins  4 , Jean-Yves Deslandes  4 , Zhenzhong Su  5 , Michael Wald  3 , Cynthia L Grosskreutz  3 , Guillaume Normand  6 , Arnaud Charil  3 , Darlene Lu  4 , Kalliopi Stasi  3 , Karen Holopigian  6
Affiliations

Patient-Reported Outcomes in RLBP1 Retinal Dystrophy: Longitudinal Assessment in a Prospective Natural History Study

James Whelan et al. Transl Vis Sci Technol. .

Abstract

Purpose: To evaluate the performance of two non-disease-specific patient-reported outcome (PRO) instruments, the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and the Low Luminance Questionnaire (LLQ), in patients with retinaldehyde-binding protein 1 retinal dystrophy (RLBP1 RD).

Methods: PROs were assessed using the VFQ-25 and LLQ. Rasch analysis was conducted to estimate person and item measures of the VFQ-25 and LLQ questionnaires to determine the association between the two PROs. In addition, the association between these two instruments and their correlations to weighted measures of visual function and disease progression were analyzed in this three-year PRO-focused sub-study of a five-year prospective natural history study.

Results: Forty-two patients participated, with most of them having completed at least two PRO follow-up visits at least one year apart. The mean VFQ-25 scores were lowest for distance activities (39.2-49.0) and peripheral vision (37.5-52.4), with mean LLQ subscale scores generally low (<41), except for the emotional distress subscale. Using Rasch analysis, calibrated item and person measures along with their standard errors were estimated for both ePROs. This indicated that the distribution of the VFQ-25 and LLQ item measures well covered the distribution of person function in this group. This suggests that the item difficulties well cover the person-level performance in this population. As well, the two PROs showed a strong and significant correlation at all assessed time points as assessed with Pearson correlation coefficient (0.81, 0.91, 0.81 and 0.87 at baseline, 1/1.5, 2/2.5 (P < 0.001) and 3/3.5 years (P = 0.002)). The composite scores of both PRO questionnaires strongly correlated with clinical measures of visual function. At 2 to 2.5 years of follow-up, meaningful statistically significant declines in peripheral vision (both VFQ-25 and LLQ), distance vision (VFQ-25), and extreme lighting in dark and bright light (LLQ) subscales were noted.

Conclusions: This study demonstrated a strong association between VFQ-25 and LLQ scores and their association with clinical measures of visual function.

Translational relevance: PRO instruments can provide insights into the specific disabilities of this unique patient population and help to guide appropriate outcome measures for future clinical trials.

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Conflict of interest statement

Disclosure: J. Whelan, Novartis (F, R), Bayer (R), Alcon (R), Sentrex (R), Roche (C); J. Green, Novartis (C), Memorial University, Newfoundland, Canada (R); M. Burstedt, Novartis (F, R); E. Greco, Novartis (E), PHASTAR (E); X. Ni, Novartis (E), Sarepta Therapeutics (E); C. Spera, Novartis (E); A. Mullins, Takeda Pharmaceuticals (E), Novartis (E); J.-Y. Deslandes, Blue Companion (E), Novartis (E); Z. Su, Shanghai Luoxin Pharmaceutical Co. Ltd. (E), Novartis (E); M. Wald, Biogen (F), Novartis (E, F); C.L. Grosskreutz, Novartis (E); G. Normand, Novartis (E); A. Charil, Eisai Inc. (E), Novartis (E, I); D. Lu, None; K. Stasi, Saliogen Therapeutics (E); K. Holopigian, Novartis (E)

Figures

Figure 1.
Figure 1.
Mean (SD) scores over time (PRO baseline, years 1/1.5, 2/2.5, and 3/3.5 PRO sub-study visits) of all 42 RLBP1 RD patients are represented as bar graphs for composite* and subscale scores for VFQ-25 (A) and LLQ (B). N, number of patients per PRO sub-study visit. *Composite score of all PRO (VFQ-25 or LLQ) subscale scores.
Figure 2.
Figure 2.
Wright construct map for VFQ-25Ca,b (A) and LLQa (B). aPlots the distributions of estimated item and person measures for the VFQ-25/LLQ whereby the axis origin is set to the mean item measure (defined to be 0 logit). bHigher person measure has better performance. Higher item measure is an item with greater difficulty.
Figure 3.
Figure 3.
Scatter plot analysis revealed strong and statistically significant positive correlation between VFQ-25 and LLQ composite* scores during all PRO sub-study visits: (A) PRO baseline (N = 42); (B) Year 1/1.5 (N = 41); (C) Year 2/2.5 (N = 37); and (D) Year 3/3.5 (N = 8) and between VFQ-25 and LLQ Rasch analysis Person Measures scores during all PRO sub-study visits: (E) PRO baseline (N = 42); (F) Year 1/1.5 (N = 41); (G) Year 2/2.5 (N = 37); and (H) Year 3/3.5 (N = 8). *Composite score of all PRO (VFQ-25 or LLQ) subscale scores.
Figure 4.
Figure 4.
Correlation of PRO composite* scores with visual function measures: (A) VFQ-25 with wVA (N = 42); (B) VFQ-25 with wvMD (N = 14); (C) VFQ-25 with wCS (N = 35); (D) LLQ with wVA (N = 42); (E) LLQ with wvMD (N = 14); and (F) LLQ with wCS (N = 35). Correlation of PRO Rasch analysis Person Measures scores with visual function measures: (G) VFQ-25 with wVA (N = 42); (H) VFQ-25 with wvMD (N = 14); (I) VFQ-25 with wCS (N = 35); (J) LLQ with wVA (N = 42); (K) LLQ with wvMD (N = 14); and (L) LLQ with wCS (N = 35). Scatter plot analysis revealed strong and statistically significant correlation of VFQ-25 and LLQ composite* scores with weighted visual function measures (wVA, wvMD, and wCS) at the PRO baseline visit and with the Rasch analysis Person Measures. *Composite score of all PRO (VFQ-25 or LLQ) subscale scores.
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