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.

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Background: It is known that giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often occur together. So far, the prevalence of GCA in newly diagnosed PMR patients has not been evaluated in a prospective ultrasound study. Objective: The aim of this study was to assess the prevalence of GCA using vascular ultrasound in patients with newly diagnosed PMR. Design: A consecutive cohort of newly diagnosed PMR patients was prospectively evaluated for the presence of GCA with the use of systematic musculoskeletal and vascular ultrasound examination. Methods: Overall, 60 patients with newly diagnosed PMR were prospectively enrolled. Symptoms and laboratory findings were collected. All patients underwent ultrasound of shoulder and hip joints, and vascular ultrasound evaluating the facial, temporal, carotid, vertebral and axillary arteries. Patients were diagnosed with GCA if they had ultrasound imaging findings of GCA. Patients with PMR (PMR-group) and patients with PMR and GCA (PMR–GCA-group) were compared, and a C-reactive protein (CRP) cut-off value was evaluated. Results: GCA was diagnosed in 28 of 60 PMR patients (46%). The PMR-group consisted of 20 (62.5%) females with a mean age of 69 (±9.9) years, while the PMR–GCA-group consisted of 11 (39.3%) females with a mean age of 74 (±8.4) years. In 13 of 28 patients (46%) in the PMR–GCA-group, GCA was subclinical and only diagnosed by ultrasound. The PMR–GCA-group showed higher values of joint effusion and significantly higher CRP values. A CRP cut-off value of 26.5 mg/litre (reference range 0–5 mg/litre) yielded a sensitivity of 66% with a specificity of 73% for GCA. Conclusion: GCA was found in 46% of newly diagnosed PMR patients; 22% of the patients with PMR had asymptomatic GCA. Joint effusions were higher in the PMR–GCA-group, with significant results for the hip joint. A CRP cut-off value of ⩾26.5 mg/litre in PMR can help in the identification of subclinical GCA.

Background: Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied. Methods: We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany. Results: Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis ( n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia ( n = 2) and myositis ( n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40–420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p < 0.0001). Conclusion: Rh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).

Objectives To analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD). Methods Thirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition. Results Sensitivity of DECT for gout was 63% (95% CI 0.41–0.81) with a specificity of 92% (0.41–0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23–0.83) and 92% (0.74–0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73–0.99) and a specificity of 83% (0.52–0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59–1.00) and 92% (0.74–0.99), respectively. Conclusion DECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis. Key Points• DECT offers a lower sensitivity for acute gout flares than previously described.• DECT sensitivity for acute CPP crystal arthritis is less than the already validated ultrasound.

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Purpose To analyze the intersession repeatability of structural biomarkers in eyes with early and intermediate age-related macular degeneration (iAMD) within the cross-sectional part of the observational multicenter MACUSTAR study. Methods Certified site personnel obtained multimodal imaging data at two visits (38 ± 20 [mean ± standard deviation] days apart), including spectral-domain optical coherence tomography (SD-OCT). One junior reader performed systematic and blinded grading at the central reading center, followed by senior reader review. Structural biomarkers included maximum drusen size classification (>63 to ≤125 µm vs. >125 µm), presence of large pigment epithelium detachments (PEDs), reticular pseudodrusen (RPD), vitelliform lesions, and refractile deposits. Intrasession variability was assessed using Cohen's κ statistics. Results At the first visit, 202 study eyes of 202 participants were graded as manifesting with either early ( n = 34) or intermediate ( n = 168) AMD. Grading of imaging data between visits revealed perfect agreement for the maximum drusen size classification (κ = 0.817; 95% confidence interval, 0.70–0.94). In iAMD eyes, perfect to substantial agreement was determined for the presence of large PEDs (0.87; 0.69–1.00) and RPD (0.752; 0.63–0.87), while intersession agreement was lower for the presence of vitelliform lesions (0.649; 0.39–0.65) and refractile deposits (0.342; −0.029–0.713), respectively. Conclusions Multimodal retinal imaging analysis between sessions showed a higher repeatability for structural biomarkers with predefined cutoff values than purely qualitative defined parameters. Translational Relevance A high repeatability of retinal imaging biomarkers will be important to implement automatic grading approaches and to establish robust and meaningful structural clinical endpoints for future interventional clinical trials in patients with iAMD.

Cerebral small vessel disease (CSVD) is an important contributor to cognitive impairment and stroke. Previous research has suggested associations with alterations in single retinal layers. We have assessed changes of all individual retinal layers in CSVD using high-resolution optical coherence tomography (OCT) for the first time. Subjects with recent magnetic resonance imaging (MRI) underwent macular and peripapillary retinal imaging using OCT for this case–control study. Number and volume ratio index (WMRI) of white matter lesions (WML) were determined on MRI. Data were analyzed using multiple linear regression models. 27 CSVD patients and 9 control participants were included. Ganglion cell layer (GCL) volume was significantly reduced in patients with CSVD compared to age-matched controls (p = 0.008). In patients with CSVD, larger foveal outer plexiform layer (OPL) volume and decreased temporal peripapillary retinal nerve fiber layer (RNFL) thickness were significantly associated with a higher WMRI in linear regression when controlling for age (p ≤ 0.033). Decreased foveal GCL volume and temporal-inferior RNFL thickness at Bruch’s membrane opening (MRW), and increased temporal MRW were associated with a higher WML burden (p ≤ 0.037). Thus, we identified alterations in several OCT layers in individuals with CSVD (GCL, OPL, MRW and RNFL). Their potential diagnostic value merits further study.