The purpose of this study was to assess which visual function measures are most strongly associated with vision-related quality of life (VRQoL) in age-related macular degeneration (AMD). A cross-sectional study of subjects with early AMD (n = 10), intermediate AMD (n = 42) and late AMD (n = 38) was conducted. Subjects were interviewed with the Impact of Vision Impairment (IVI) questionnaire. Functional tests performed included best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), visual acuity measured with the Moorfields Acuity Charts (MAC), contrast sensitivity, reading speed, mesopic and dark-adapted microperimetry. The relationship between VRQoL and visual function was assessed with multiple regressions controlling for confounders. Rasch analysis demonstrated the validity of the IVI to assess VRQoL through three subscales: reading and accessing information, mobility and independence, and emotional well-being. Subjects with late AMD had significant lower IVI scores on all subscales compared with intermediate and early AMD (p < 0.011). In the overall cohort, IVI subscales were associated with BCVA, LLVA, MAC-VA and contrast sensitivity (all p < 0.001). Among the subgroup of early and intermediate AMD subjects, reading and mobility subscales were significantly associated with MAC-VA (p < 0.013). These results suggest that MAC-VA is a useful, patient-relevant measure of visual impairment in AMD.

Background: There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials. Methods: The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part's primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part's primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities. Discussion: The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition.

Data Availability Statement: The data proving the main findings of the study are contained within the manuscript. The Optical Coherence Tomography Angiography images of all participants cannot be made publicly available as public availability of the data might compromise participant privacy. All participants consented to scientific analysis of the data by the researchers involved but not to public data sharing (according to the consent form approved by the Ethics committee, University of Bonn). As subjects might be identifiable by the higher for the Mean algorithm compared to the manual approach with respect to the superficial retinal layer. Conclusions Automated thresholding algorithms yield a higher reproducibility of OCTA parameters and allow for a more sensitive diagnosis of macular pathology. However, different algorithms are not interchangeable nor results readily comparable. Especially the Mean algorithm should be investigated in further detail. Automated thresholding algorithms are preferable but more standardization is needed for clinical use.

Hypertensive crisis causes end-organ damage through small-vessel damage as described histologically. Noninvasive optical coherence tomography angiography (OCTA) makes it possible to image retinal and choroidal capillaries on a microscopic level in vivo. We quantified eye vessel perfusion changes in hypertensive crisis using OCTA. Methods: Patients with hypertensive crisis (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg) and age-matched healthy controls were included in the study. OCTA en face 3 × 3-mm images of the superficial and deep retinal layers and the choriocapillaris were acquired. Outcome parameters included vessel density (VD) and vessel skeleton density (VSD) of the superficial and deep retinal layers, as well as flow voids of the choriocapillaris. Results: Twenty-eight eyes of 17 patients and 31 age-matched control eyes of 18 healthy subjects were included. VD and VSD of the deep retinal layer were significantly reduced in hypertensive crisis (P ≤ 0.004). Choriocapillaris signal intensity was more heterogeneous in patients, and flow voids exhibited confluence with a larger average area and a lower absolute count (P ≤ 0.045). These changes were independent of time since onset of hypertensive crisis and of the presence and extent of retinopathy. Deep retinal changes were associated with renal end-organ failure (P = 0.045). Conclusions: Hypertensive crisis is associated with a significant reduction in retinal and choroidal capillary perfusion based on OCTA findings. These alterations are independent of retinopathy and related to end-organ damage. Translational Relevance: OCTA might help distinguish hypertensive urgency from hypertensive emergency earlier than currently possible.

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.

IMPORTANCEThere is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment. OBJECTIVE To assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD). DESIGN, SETTING, AND PARTICIPANTS This international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity [BCVA], low-luminance visual acuity [LLVA], Moorfields Acuity Test [MAT], Pelli-Robson Contrast Sensitivity [CS], and International Reading Speed Test [IReST]) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited.MAIN OUTCOMES AND MEASURES Intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states.RESULTS A total of 301 participants (mean [SD] age, 71 [7] years; 187 female participants [62.1%]) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61).CONCLUSIONS AND RELEVANCE BCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.

The purpose of this study was to design and evaluate an instrument for assessing vision-related quality of life appropriate for the specific visual impairment characteristic for all stages of age-related macular degeneration (AMD), with a focus on the low luminance deficit in early/intermediate stages. Methods:A standardized questionnaire was developed in three steps with participants with early, intermediate, and late AMD: (1) based on in-depth interviews (n = 19) and two focus group discussions (n = 5 each), content was developed followed by 2. (2) The questionnaire development using cognitive debriefing interviews (n = 3) and leading to a preliminary version of the questionnaire. (3) This version was then administered to 127 participants with early, intermediate, and late AMD. Psychometric properties, such as response category functioning (floor and ceiling effects) and targeting of item difficulty to patient ability of the pilot Vision Impairment in Low Luminance (VILL) questionnaire were evaluated using Rasch analysis. Results:The preliminary VILL questionnaire consisted of 68 items with a 5-step response scale. Several items were removed based on floor/ceiling effects or misfit and a final pool of 37 items remained. The response scale was collapsed to four categories as one category was underutilized. The targeting of the instrument was good with minimal difference in person and item means (0.52 logits). Precision was also good with a person separation index of 3.55 and reliability of 0.93. There was evidence of multidimensionality (eigenvalue of the first contrast = 5.95) in the scale, which could be resolved by splitting the items into subscales including a reading, mobility, and emotional well-being subscale.Conclusions: Individuals with AMD report difficulties with vision-related activities and functioning under visually challenging conditions at all stages of the disease. These aspects were considered when developing the 37-item VILL, which demonstrates promising psychometric characteristics. Further assessments of reliability and validity are warranted. Translational Relevance:The VILL questionnaire is a new patient-reported outcome (PRO) measure developed for future use in AMD studies.

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.