Suchergebnisse

Purpose: To investigate the structure–function relationship in eyes with drusen with mesopic and scotopic microperimetry. Methods: We analyzed structural and functional data from 43 eyes with drusen. Functional data were acquired with mesopic and scotopic two-color (red and cyan) microperimetry. Normative values were calculated using data from 56 healthy eyes. Structural measurements were green autofluorescence and dense macular optical coherence tomography scans. The latter were used to calculate the retinal pigment epithelium elevation (RPE-E) and the photoreceptor reflectivity ratio (PRR). The pointwise structure–function relationship was measured with linear mixed models having the log-transformed structural parameters as predictors and the sensitivity loss (SL, deviation from normal) as the response variable. Results: In the univariable analysis, the structural predictors were all significantly correlated (P < 0.05) with the SL in the mesopic and scotopic tests. In a multivariable model, mesopic microperimetry yielded the best structure–function relationship. All predictors were significant (P < 0.05), but the predictive power was weak (best R2 = 0.09). The relationship was improved when analyzing locations with abnormal RPE-E (best R2 = 0.18). Conclusions: Mesopic microperimetry shows better structure–function relationship compared to scotopic microperimetry; the relationship is weak, likely due to the early functional damage and the small number of tested locations affected by drusen. The relationship is stronger when locations with drusen are isolated for the mesopic and scotopic cyan test. Translational Relevance: These results could be useful to devise integrated structure–function methods to detect disease progression in intermediate age-related macular degeneration. ; DPC and GM received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant 116076 (Macustar). This joint undertaking receives support from the European Union's Horizon 2020 research and innovation program ...

Abstract Purpose: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. Procedures: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. Results: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). Conclusions: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD. ; Name of action: Intermediate AMD: Development of novel clinical endpoints for clinical trials in patients with a regulatory and patient access intention - MACUSTAR This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116076. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Adnan Tufail,1 Sue Lightman,1 Ahmed Kamal,2 Uwe Pleyer,3 Nuria María Gajate Paniagua,4 Corrine Dot,5,6 Xiao-Yan Li,7 Jenny Jiao,7 Jean Lou,7 Yehia Hashad7 For the CONSTANCE Study Group 1Moorfields Eye Hospital, London, UK; 2Aintree University Hospital, Liverpool, UK; 3University Eye Hospital, Uveitis Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin, and Berlin Institute of Health, Berlin, Germany; 4University Hospital of Burgos, Burgos, Spain; 5Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France; 6French Military Health Service Academy, Val de Grâce, Paris, France; 7Allergan Plc, Irvine, CA, USA Purpose: To evaluate the long-term safety of dexamethasone intravitreal implant (DEX) in patients treated for macular edema associated with retinal vein occlusion (RVO) or noninfectious posterior segment uveitis (NIPSU) in clinical practice.Patients and methods: Multicenter (102 sites in France, Germany, Spain, UK), prospective, observational, post-authorization safety study in adult patients treated with DEX. Data collected up to 2 years after enrollment included serious adverse events (SAEs) and adverse events of special interest (AESIs; adverse drug reactions that are considered important risks associated with DEX and listed in the European Union Ozurdex Risk Management Plan).Results: Overall, 803 patients (652 RVO, 151 NIPSU) received on-study DEX treatment, and 73.1% completed 24 months of follow-up; 72.6% were DEX-naïve. Median number of on-study injections per treated eye was 2 (range, 1–7); median reinjection interval was 27.1 weeks. Nonocular SAEs affected 9.5% of patients; none were considered DEX-related. Ocular SAEs (most common: cataract progression) occurred in 3.2% of treated eyes. SAEs were similar in eyes stratified by previous DEX use and number of on-study DEX injections (≤2 or >2), in both RVO and NIPSU. The most common AESIs were cataract formation and progression (20.0% and 19.2% of treated phakic eyes, n=551), increased intraocular pressure (19.0% of treated eyes), and vitreous hemorrhage (3.3% of treated eyes). Cataract progression was more frequent in baseline phakic eyes that were previously treated with DEX or received >2 on-study DEX injections.Conclusion: The long-term safety profile of DEX was acceptable. No new safety concerns were identified. Keywords: corticosteroid, dexamethasone, drug delivery device, retinal vein occlusion, safety profile, uveitis

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. ; Name of action: Intermediate AMD: Development of novel clinical endpoints for clinical trials in patients with a regulatory and patient access intention - MACUSTAR This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116076. This Joint Undertaking receives support from the European Union's Horizon 2020 research and ...