Heterogeneity of patient-reported outcome measures in clinical research.

BACKGROUND: The use of patient-reported outcome measures (PROMs) in clinical research increases and use of heterogeneous instruments reflects how well diverse traits are captured by a medical specialty. In order to reflect the heterogeneity of current PROM use in ophthalmology, we reviewed the available literature. METHODS: The medical literature database Web of Science was searched for the most cited articles in clinical ophthalmology. Titles, abstracts and full text articles were reviewed for the use of PROMs and a list of the 100 most cited articles using PROMs was obtained and stratified by year of publication. RESULTS: A total of 1,996 articles were screened. Seventy-seven out of the 100 articles identified included one PROM, and the average number of instruments was 1.5 ± 1.1. The most widely used PROMs were the National Eye Institute Visual Function Questionnaire (33%), the Ocular Surface Disease Index (14%) and the Medical Outcomes Study Short Form (13%). A simulation analysis suggested that the distribution of PROM use in ophthalmology study did not significantly differ from a power law distribution. Twenty-two percent and fifteen percent of articles did not reference and did not specify the PROM used, respectively. This rate decreased in the more recently published articles (p = 0.041). CONCLUSIONS: Our data suggest that the heterogeneity of PROMs applied in ophthalmology studies is low. The selection of PROMs for clinical studies should be done carefully, depending on the research goal.

Evaluation of the test-retest and inter-mode comparability of the Impact of Vision Impairment questionnaire in people with chronic eye diseases.

PURPOSE: The main objective of this study is to assess the test-retest and inter-administration mode reliability of the Impact of Vision Impairment profile (IVI), a common patient-reported outcome measure (PROM) for people with chronic eye diseases. METHODS: The IVI was administered to adult patients with stable, chronic eye diseases two to four times per participant (average intervals between administrations 12 to 20 days; maximum two phone interviews, paper administration, electronic administration) by two trained interviewers. Rasch models were fit to the data. Intra-class correlation coefficients (ICCs), mean differences and Cronbach's alpha between test-retest administrations (two phone interviews) and inter-mode comparisons were calculated. RESULTS: Two hundred-sixteen patients (mean age 67 ± 12 years, 40% male) were included in the study. The IVI met all psychometric requirements of the Rasch model, and the division into the domains of functional items (IVI_F) and emotional items (IVI_E) corresponded to the German validation study. ICCs (all for IVI_F and IVI_E, respectively) for the retest administrations were 0.938 and 0.912, and 0.853 and 0.893 for inter-mode comparisons phone/paper, 0.939 and 0.930 for phone/electronic, and 0.937 and 0.920 for paper/electronic (all p < 0.01). Mean differences (all for IVI_F and IVI_E, respectively) for the retest administrations were 2.8% and 0.7% and ranged from 2.0% to 6.2% and from 0.4 % to 4.9% between administration modes. Cronbach's alpha ranged from 0.886 to 0.944 for retest and inter-mode comparisons. CONCLUSION: Due to the high test-retest reliability and the almost equally high comparability of different modes of administration of the IVI, the study endorses its use as a robust PROM to capture vision-related quality of life. Our results further support the use of the IVI as an endpoint in clinical trials and may simplify implementing it in both clinical trials or real-world evidence generation by offering multiple administration modes with high reliability.

Knowledge about age-related eye diseases in the general population in Germany.

BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions. METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations. RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011). CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

Patient-reported vision impairment in low luminance predicts multiple falls.

BACKGROUND: Visual impairment is an independent risk factor for falling. Whether this extends to patient-reported visual difficulties has not been assessed to date. We have evaluated whether patient-reported visual difficulties in low-contrast and low luminance situations are a risk factor for falls and concerns about falling. METHODS: Baseline assessments in outpatients with varying degrees of visual impairment aged ≥ 60 years included the Vision Impairment in Low Luminance (VILL) questionnaire and socio-demographic data; prospective follow-up assessments included falls over 12 months, the Falls Efficacy Scale (FES-I) and the VILL. The VILL was scored using Rasch models, and the FES-I was categorized following published guidelines. Associations were investigated using logistic regression analysis, controlling for age, visual acuity and known risk factors of falling. RESULTS: We included 112 participants (74 women, mean age 70 ± 7 years). Twenty-seven participants recalled any falls and eleven recalled multiple falls at follow-up. Higher VILL reading subscale and mobility subscale scores at baseline were significantly associated with reporting less multiple falls at follow-up (OR 0.559 [0.333-0.936], p = 0.027 and OR 0.595 [0.377-0.940], p = 0.026). VILL scores were significantly associated with concerns about falling (high versus low: p ≤ 0.004, reading, mobility and emotional subscales; high versus moderate: p = 0.004, emotional subscale). CONCLUSIONS: Patient-reported visual difficulties under low illumination and in low-contrast conditions are predictive of multiple falls in the future, have an additional predictive value over established risk scores, and are associated with concerns to fall. Current fall risk assessments may benefit from the inclusion of such assessments, e.g. the VILL questionnaire.

Properties of Patient-Reported Outcome Measures in Recessive Stargardt Disease.

INTRODUCTION: The study aimed to explore the psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI VFQ) and Impact of Vision Impairment (IVI) profile in recessive Stargardt disease (STGD1). METHODS: The NEI VFQ-25 and IVI-28 were administered to individuals with STGD1. Responses were analyzed following psychometrically established dimension structures of the NEI VFQ (visual function [VF] subscale; socioemotional [SE] subscale) and of the IVI (functional [F] subscale; emotional [E] subscale). We analyzed internal consistency, dimensionality, item fit, and differential item functioning (DIF), using latent trait models. Criterion validity was assessed using Pearson correlation coefficients. RESULTS: Seventy-one participants (42 females, 29 males; mean age, 44 ± 19 years) were included. Self-reported difficulty levels were lower than the mean difficulty of items in both instruments. Person reliability and person separation index of the instruments were 0.85 and 2.40 (NEI VFQ-VF), 0.69 and 1.49 (NEI-VFQ-SE), 0.88 and 2.77 (IVI-F), and 0.72 and 1.62 (IVI-E). No items showed misfit at a level distorting the measurement system. One IVI item showed DIF by gender but was retained as person measures were largely unaffected by its removal. NEI VFQ-VF and IVI-F as well as NEI VFQ-SE and IVI-E were positively correlated (r = 0.79 and 0.64, respectively). CONCLUSION: The NEI VFQ and IVI have acceptable psychometric properties in STGD1 with the IVI allowing more sensitive person stratification. Targeting of questionnaires to individuals with STGD1 might be improved by including additional content domains specific to the disease.

Challenges, facilitators and barriers to screening study participants in early disease stages-experience from the MACUSTAR study.

BACKGROUND: Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD). METHODS: Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data. Only participants with intermediate AMD were considered. RESULTS: A total of 766 individual screenings within 87 weeks were available for analysis. The mean screening rate was 0.6 ± 0.9 screenings per week among all sites. The participation at investigator teleconferences (relative risk increase 1.466, 95% CI [1.018-2.112]), public holidays (relative risk decrease 0.466, 95% CI [0.367-0.591]) and reaching 80% of the site's recruitment target (relative risk decrease 0.699, 95% CI [0.367-0.591]) were associated with the number of screenings at an individual site level. CONCLUSIONS: Careful planning of screening activities is necessary when recruiting early disease stages in multi-centre observational or low-interventional studies. Conducting teleconferences with local investigators can increase screening rates. When planning recruitment, seasonal and saturation effects at clinical site level need to be taken into account. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017.

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions.

The slow progression of early age-related macular degeneration (AMD) stages to advanced AMD requires the use of surrogate end points in clinical trials. The use of combined end points may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite end points as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite end points used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite end point categories were: combined structural and functional end points, combined structural end points, combined functional end points and combined multicategorical end points. The majority of the studies included binary composite end points. There was a lack of sensitivity analyses of different end points against accepted outcomes (i.e., progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined end points in clinical studies of early stages of AMD exists, and no surrogate end points have been accepted for AMD progression.

Prevalence of Retinal Vein Occlusion in Europe: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this study was to examine the prevalence and incidence of retinal vein occlusions (RVO) in Europe. METHODS: A systematic review and meta-analysis of the prevalence and incidence of RVO in Europe according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines was performed in the databases PubMed, Embase and Web of Science. Based on Eurostat data, the total number of affected individuals in the EU was calculated and projected to the year 2050. RESULTS: The random-effects pooled prevalence of RVO in Europe was 0.7% (95% CI: 0.5-0.9%) in persons aged 55 years and older based on the examination of 25,002 individuals from 4 prevalence studies. No European incidence studies were identified. The total number of affected individuals in the EU was estimated to rise by almost 20% from 900,000 today to 1.1 million in 2050. CONCLUSION: Published articles on the prevalence and incidence of RVO in Europe are limited. With the expected increase in affected persons, further epidemiological research is warranted for adequate healthcare planning.

[Vision-related Quality of Life with Low Vision - Assessment and Instruments]. / Visuelle Lebensqualität bei starker Sehbehinderung ­ Messung und Messinstrumente.

Patient-reported outcome measures have been met with increasing interest, particularly in clinical research. They are used to capture the patient-relevant impact of an intervention or a loss of function. In patients with loss of vision, vision-related quality of life is assessed in order to quantify the impact of visual impairment in everyday life. When using quality of life instruments, psychometric characteristics - such as reliability, validity and responsiveness - are of great importance to ensure that the collected data are robust. There are various questionnaires to assess health-related quality of life, vision-related quality of life or visual function, but not all of these are suitable for patients with very low vision. The IVI and NEI VFQ questionnaires are available in German and can be used to assess vision-related quality of life. However, additional studies to evaluate these instruments and refinement or development of novel tools are needed to better meet the growing interest in using patient-reported outcomes as clinical study endpoints.

Predictors of shoulder level after spinal fusion in adolescent idiopathic scoliosis.

BACKGROUND: For patients with adolescent idiopathic scoliosis, shoulder balance influences their treatment satisfaction and psychological well-being. Several parameters are known to affect postoperative shoulder balance, but few prognostic models are as yet available. PURPOSE: This study aimed to identify independent predictive factors that can be used to assess preoperatively which patients are at risk of postoperative shoulder elevation, and to build a linear prediction model. METHODS: N = 102 patients with all Lenke types were reviewed radiographically before surgery and 1 year afterward. The outcome measures were coracoid height difference (CHD), clavicular angle (CA), and clavicle-first rib intersection difference (CiRID). Predictive factors commonly used in the literature were investigated using correlation analysis and statistical testing. Significant contributing factors were included in three multiple linear regression models (for CHD, CA, and CiRID). RESULTS: The mean shoulder level (CHD) significantly changed from a lower left shoulder value of -8.5 mm before surgery to 3.3 mm at the follow-up examination. A high preoperative left shoulder level by CiRID, a large amount of Cobb angle correction of the distal thoracic curve, a low preoperative Cobb angle in the lumbar curve, and a structural proximal thoracic curve proved to be determinants and thus risk factors for left-sided shoulder elevation after surgery. The three models predicting CHD, CA, and CiRID at the follow-up examination included these four risk factors and were significant. CONCLUSIONS: Preoperative variables have the strongest influence on shoulder level after spinal instrumentation. Additionally, extensive correction of the distal thoracic curve can cause elevation of the left shoulder.

German validation of the quality of life profile for spinal disorders (QLPSD).

BACKGROUND: The Quality of Life Profile for Spine Deformities (QLPSD) is a self-reporting questionnaire designed for studying patients with spinal deformities. PURPOSE: The aim of the present study was to systematically translate the QLPSD into German (G-QLPSD) and to test its reliability and validity. Special emphasis was intended to be given to patients with different Cobb angles and ages. METHODS: The QLPSD was systematically translated into German and was responded to in a web-based online survey by patients with idiopathic scoliosis and by healthy control individuals to carry out a matched-pair analysis. Participants aged 14 years and older were included. All participants answered a battery of validated questionnaires (SRS 22-r, PHQ-9, PANAS, FKS, WHO-5, BFI-S, PTQ). Reliability testing included Cronbach's alpha and test-retest reliability (retest 8 weeks after initial testing). Factorial, convergent, divergent, concurrent, and discriminant validity were calculated. RESULTS: A total of 255 scoliosis patients (age 30.0 ± 16.7 years, Cobb angle 43.5° ± 20.9°) and 189 matched healthy control individuals were finally included. Cronbach's alpha for the G-QLPSD total score was 0.93 and the test-retest reliability was 0.84. The G-QLPSD total score correlated with the SRS 22-r total score (r = -0.86). All concurrently applied scores showed strong correlations with the G-QLPSD (e.g., depression score PHQ-9: r = 0.70). The matched-pair analysis of 189 pairs showed strong discriminant validity (Cohen's d = 0.78). Patients with more severe Cobb angles (≥40°) and those ≥18 years of age had significantly poorer results than patients with minor curves and younger patients. CONCLUSION: The G-QLPSD proved to be a highly reliable and valid instrument that can be recommended for clinical use in scoliosis patients.

German validation of the BIDQ-S questionnaire on body image disturbance in idiopathic scoliosis.

PURPOSE: The Body Image Disturbance Questionnaire-Scoliosis (BIDQ-S) is a seven-item questionnaire inquiring into patients' worries about back shape and associated problems at school, at work, with friends or family, and whether the patients are avoiding certain activities. The aim of this study was to translate the BIDQ-S into German (G-BIDQ-S), test its reliability, and establish its convergent, divergent, concurrent, and discriminant validity. METHODS: In a prospective cohort study, 259 patients with idiopathic scoliosis (mean age 30.2; 221 female; mean Cobb angle 43.8°) completed the G-BIDQ-S; Scoliosis Research Society 22-r (SRS 22-r); Patient Health Questionnaire (PHQ-9); Positive and Negative Affect Schedule (PANAS); Questionnaire on Body Dysmorphic Symptoms (FKS); and WHO-5 Well-Being Index. Healthy control individuals matched by age, sex and BMI (n = 149; mean age 36.1; 133 female; BMI = 23.0) answered the same questions to establish discriminant validity. Discriminant statistics, and Pearson and Spearman correlations were calculated. RESULTS: The G-BIDQ-S proved to be one-factorial, internally consistent (Cronbach alpha = 0.87), and stable over time (total score 2.22 vs. 2.21 during retest; retest reliability r = 0.79, P < 0.001). It correlated significantly with the mean SRS 22-r (r = -0.72, P < 0.001) and with Cobb angles (r = 0.30, P < 0.001)-convergent validity; much less with body mass index (r = 0.19, P < 0.001)-divergent validity; and with the PANAS (r = 0.55, P < 0.001), PHQ-9 (r = 0.53, P < 0.001), FKS (r = 0.67, P < 0.001), and WHO-5 (r = -0.54, P < 0.001)-concurrent validity. The G-BIDQ-S also showed discriminant validity, with a strong difference between the scoliosis group (total score 2.19) and the control group (total score 1.13; P < 0.001). CONCLUSIONS: The G-BIDQ-S showed good internal consistency, reliability, and convergent, divergent, concurrent, and discriminant validity. This questionnaire is the first one inquiring into patients' body image disturbances that has been validated and is available in German.

Piloting Rasch model scoring of the National Eye Institute Visual Function Questionnaire in uveitis.

INTRODUCTION: The National Eye Institute Visual Function Questionnaire (NEI VFQ) is a common patient-reported outcome measure (PROM) in uveitis trials. Its psychometric properties using state-of-the-art scoring based on Rasch models, a latent trait model that improves accuracy of PROMs assessment, has not yet been investigated. METHODS: The study participants were recruited online from uveitis patient organizations, where individuals self-reported their uveitis diagnosis and visual acuity level. These participants then completed the NEI VFQ-25. The visual function (VF) and socioemotional (SE) subscales were psychometrically analysed in terms of item fit, targeting, internal consistency, dimensionality, and differential item functioning (DIF), using Rasch models. Criterion validity was examined based on associations between NEI VFQ person measures and recent visual acuity (VA) levels. RESULTS: Ninety-nine participants recruited online from uveitis patient organizations (68 women, 31 men; mean age 50 ± 15 years; 46.5% self-reported receiving systematic therapy for uveitis, 0.6% NEI VFQ-25 missing data) were included. The mean difficulty of items was lower than the average person ability. None of the items demonstrated misfit to an extent that would induce noise into the measurement. The consistency metrics person reliability and person separation index of the subscales were 0.85 and 2.34 (NEI VFQ-VF), 0.86 and 2.52 (NEI VFQ-SE), respectively. There was no evidence of multidimensionality and none of the items showed DIF by gender. The differences between item and person measures were 1.44 (NEI VFQ-VF) and 1.03 (NEI VFQ-SE). NEI VFQ-25 person measures were significantly lower in participants with visual impairment (all p values ≤ 0.007). CONCLUSION: Rasch model-based scoring of the re-engineered NEI VFQ-25 demonstrates acceptable internal consistency, item fit and construct validity for assessing two key domains of quality of life in individuals self-reporting uveitis. The PROM was targeted at a higher level of difficulty than present in our heterogeneous sample.

Modifications in ocular microperfusion after transcatheter aortic valve implantation.

Cerebral embolization is a known complication of transcatheter aortic valve implantation (TAVI) but the effect of the procedure on the ocular perfusion is currently unclear. Thus, we investigated post-procedural morphologic and perfusion changes of the retina and choroid, using optical coherence tomography angiography (OCTA) and color fundus photography (CFP) in a prospective cohort study. Ophthalmic examinations were conducted pre- and post-TAVI. OCTA images were analyzed quantitatively based on vessel density and skeleton density of the superficial and deep retinal plexus as well as the signal intensity and flow deficits in the choriocapillaris. CFP images were assessed for presence of acute retinal ischemia, optic nerve swelling, vessel emboli, hemorrhages and cotton wool spots. Data was analyzed using linear mixed models. Twenty patients (9 women; 11 men) at a mean age of 81 ± 6 years were included. Pre- and post-interventional ocular imaging data were available for 32 eyes. The analysis revealed a significant impairment of the choriocapillaris perfusion after TAVI with an increased proportion of flow deficits (p = 0.044). When controlling for blood pressure, the average size of choriocapillaris flow voids was significantly increased (systolic and diastolic, p = 0.039 and 0.029). Qualitatively, focal areas of retinal ischemia were detected on OCTA in 33% of participants. Silent emboli or cotton wool spots were identified on CFP in 21%. Our findings indicate a reduced choroidal perfusion as well as areas of retinal ischemia and embolization in a considerable proportion of patients following TAVI. Pending confirmation in a larger sample, these complications merit monitoring as well as inclusion in consent procedures for TAVI.

Disease-specific assessment of Vision Impairment in Low Luminance 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 (VRQoL) 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 subset of participants (n=301), test-retest reliability (intraclass correlation coefficient (ICC) and coefficient of repeatability (CoR)) and construct validity were assessed. RESULTS: Four items were removed from the VILL with 37 items due to misfit. The resulting Vision Impairment in Low Luminance with 33 items (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 Vision Impairment in Low Luminance Reading Subscale (VILL-R), 0.87 and 2.58 for the Vision Impairment in Low Luminance Mobility Subscale (VILL-M), and 0.78 and 1.90 for the Vision Impairment in Low Luminance 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 VRQoL 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.

Instrumental Activities of Daily Living Tools in Very-Low Vision: Ready for Use in Trials?

Traditional endpoints assessing visual function are limited by their responsiveness to interventions restoring or maintaining vision. An alternative concept is assessing instrumental activities of daily living (IADL). Herein, we review all available vision-specific IADL instruments relevant for vision restoration trials and report data for the most promising instrument. Six relevant instruments exist: The Low Vision Functional Status Evaluation (LVFSE), Timed IADL (TIADL), Melbourne Low-Vision Activities of Daily Living Index (MLVAI), Assessment of Disability Related to Vision (ADREV), Functional Low-Vision Observer Rated Assessment (FLORA), and Very Low Vision IADL (IADL-VLV). Both internal consistency and test-retest data were available for the LVFSE, MLVAI, and IADL-VLV. In a sample from a low-vision clinic (n = 51; age 57 ± 16 years), we report additional validation data on the IVI-VLV including test-retest reliability (intraclass correlation coefficient 0.981 [0.961; 0.991]). The LVSFE was noticeably less reliable than the MLVAI and the IADL-VLV. Content and construct validity data were available for the LVFSE, TIADL, MLVAI, ADREV, and IADL-VLV, but only the MLVAI and IADL-VLV were developed for an ultra-low vision context. Ceiling effects were present across instruments. Thus, of all appropriate IADL instruments related to vision, the IADL-VLV and MLVAI best meet existing requirements for use in vision restoration trials, e.g., in gene therapies or visual prostheses in inherited retinal diseases, but require further validation.

Interviewer Administration Corresponds to Self-Administration of the Vision Impairment in Low Luminance (VILL) Questionnaire.

Purpose: To quantify the impact of the mode of administration (MOA) on scores of the Vision Impairment in Low Luminance (VILL) questionnaire. Methods: The VILL questionnaire was implemented using different MOAs (paper, interview, electronic), in addition to a demographical survey of adult participants recruited at an outpatient eye clinic, with the initial MOA being either paper or interview. Polytomous Rasch models were used to generate person measure scores for the three subscales of the VILL questionnaire (reading, VILL_R; mobility, VILL_M; and emotional, VILL_E). Measures of agreement among the different MOAs were calculated (self-administered paper/interview, self-administered paper/self-administered electronic, and interview/self-administered electronic). An age-matched analysis was performed to control for the impact of the initial MOA, administration interval, visual acuity, and self-reported hearing difficulties. Results: We included 309 participants (mean age, 63 ± 14 years; 61% female). Intra-class correlation coefficients were 0.930, 0.919, and 0.799 for paper versus interview assessment; 0.951, 0.959, and 0.916 for paper versus electronic; and 0.967, 0.955, and 0.907 for interview versus electronic assessment (VILL_R, VILL_M, and VILL_E, respectively). Mean differences were 0.35, 0.41, and 1.74 logits; 0.32, 0.18, and 0.68 logits; and 0.08, 0.22, and 0.63 logits, respectively. None of the mentioned factors significantly affected the results (corrected P ≥ 0.11). Conclusions: Paper, interview, and electronic MOAs of the VILL can be considered equivalent. Reporting across the main MOAs of self-administration (paper) and interviewer-administration was unaffected by better eye visual acuity and self-reported hearing difficulties. Translational Relevance: The results support use of the VILL questionnaire with flexible modes of administration.

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.Trial registration: ClinicalTrials.gov NCT03349801. Registered on 22 November 2017.

Automated quantification of posterior vitreous inflammation: optical coherence tomography scan number requirements.

Quantifying intraocular inflammation is crucial in managing uveitis patients. We assessed the minimum B-scan density for reliable automated vitreous intensity (VI) assessment, using a novel approach based on optical coherence tomography (OCT). OCT volume scans centered on the macula were retrospectively collected in patients with uveitis. Nine B-scans per volume scan at fixed locations were automatically analyzed. The following B-scan selections were compared against the average score of 9 B-scans per volume scan as a reference standard: 1/3/5/7 central scans (1c/3c/5c/7c), 3 widely distributed scans (3w). Image data of 49 patients (31 females) were included. The median VI was 0.029 (IQR: 0.032). The intra-class-correlation coefficient of the VI across the 9 B-scans was 0.923. The median difference from the reference standard ranged between 0.001 (7c) and 0.006 (1c). It was significantly lower for scan selection 3w than 5c, p(adjusted) = 0.022, and lower for selection 7c than 3w, p(adjusted) = 0.003. The scan selections 7c and 3w showed the two highest areas under the receiver operating curve (0.985 and 0.965, respectively). Three widely distributed B-scans are sufficient to quantify VI reliably. Highest reliability was achieved using 7 central B-scans. Automated quantification of VI in uveitis is reliable and requires only few OCT B-scans.