Disease-specific assessment of Vision Impairment in Low Luminance (VILL) in age-related macular degeneration – a MACUSTAR study report

Background/Aims: To further validate the Vision Impairment in Low Luminance (VILL) questionnaire, which captures visual functioning and vision-related quality of life under low luminance, low contrast conditions relevant to age-related macular degeneration (AMD). Methods: The VILL was translated from German into English (UK), Danish, Dutch, French, Italian and Portuguese. Rasch analysis was used to assess psychometric characteristics of 716 participants (65% female, mean age 72±7 years, 82% intermediate AMD) from the baseline visit of the MACUSTAR study. In a sub-set of participants (n=301), test-retest reliability (intra-class correlation coefficient, ICC; coefficient of repeatability, CoR) and construct validity were assessed. Results: Four items were removed from the VILL-37 due to misfit. The resulting VILL-33 has three subscales with no disordered thresholds and no misfitting items. No differential item functioning and no multidimensionality were observed. Person reliability and person separation index were 0.91 and 3.27 for the reading subscale (VILL-R), 0.87 and 2.58 for the mobility subscale (VILL-M) and 0.78 and 1.90 for the emotional subscale (VILL-E). ICC and CoR were 0.92 and 1.9 for VILL-R, 0.93 and 1.8 for VILL-M and 0.82 and 5.0 for VILL-E. Reported visionrelated quality of life decreased with advanced AMD stage (p<0.0001) and was lower in the intermediate AMD group than in the no AMD group (p≤0.0053). Conclusion: The VILL is a psychometrically sound patient-reported outcome instrument and the results further support its reliability and validity across all AMD stages. We recommend the shortened version of the questionnaire with three subscales (VILL-33) for future use. Trial registration number NCT03349801

Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability

Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991–0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757–0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD

Development and valuation of a preference-weighted measure in Age-Related Macular Degeneration from the Vision Impairment in Low Luminance (VILL) questionnaire – A MACUSTAR report

Objective: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD), and valued to generate UK and German preference weights. Methods: A PWM consists of a classification system to describe health; and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the UK and German public. Responses were modelled to generate utility values for all possible health states. Results: The classification system has 5 items across the three domains of VILL-33: reading and accessing information; mobility and safety; and emotional wellbeing. The DCE samples (UK: n=1004, Germany: n=1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. Conclusion: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both UK and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD where generic preference-weighted measures typically lack sensitivity