Abstract:Intravitreal ranibizumab is a first‐line therapy for neovascular age‐related macular degeneration (nAMD), but there is a need to optimize patient outcomes while minimizing treatment burden. Here, we developed an indirect response, nonlinear, mixed effects model of disease progression and drug effect in anti‐vascular endothelial growth factor (VEGF) treatment‐naïve patients. A total of 1,524 treatment‐naïve patients and 29,754 visual acuity observations from the ANCHOR, MARINA, PIER, and EXCITE clinical trials … Show more
“…The general model structure was first developed by Holz et al 21 based on data of the RCTs MARINA, ANCHOR, and PIER. It was then extended and applied by Mulyukov et al 22 and Agostini et al 23 . In the present study, the model is extended and applied for the first time to real-world data.…”
Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an ‘optimal treatment’ control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.
“…The general model structure was first developed by Holz et al 21 based on data of the RCTs MARINA, ANCHOR, and PIER. It was then extended and applied by Mulyukov et al 22 and Agostini et al 23 . In the present study, the model is extended and applied for the first time to real-world data.…”
Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an ‘optimal treatment’ control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.
“…We first present a continuous model for the response of the measurements to the treatment regimen. Our general approach is motivated by the work in [5], though the terms we use are different.…”
Section: Section 2: Linear Continuous Modelsmentioning
The standard of care treatment for neovascular age-related macular degeneration, delivered as ocular injection, is based on anti-vascular endothelial growth factor (anti-VEGF). The course of treatment may need to be modified quickly for certain patients based on their response. Models that track both the concentration and the response to an anti-VEGF treatment are presented. The specific focus is to assess the existence of analytical solutions for the different types of models. Both an ODE-based model and a map-based model illustrate the dependence of the solution on various biological parameters and allow the measurement of patient-specific parameters from experimental data. A PDE-based model incorporates diffusive effects. The results are consistent with observed values, and could provide a framework for practitioners to understand the effect of the therapy on the progression of the disease in both responsive and non-responsive patients.
“…Macular disintegration is an ailment that affects macular part of the retina and the main reason for vision loss in AMD [56]. 2014 the widespread presence of AMD was about 8.7%.…”
Section: Age Related Macular Degenerationmentioning
Restoring vision is the most important center of attention of our research program, On the other hand, to attain our objective and convey the preeminent eminence of stem cell therapy; we have to understand the fundamental biology of stem cells. (RPE) Retinal Pigmented epithelium layer degenerates and contributing to a succession of actions resulting in visual impairments. Regenerative medicine holds promise for the spanning almost for all body system and the eye is an ideal organ to use in research because it is the only part of nervous system that is the visible and easily accessible. This review outlines advances in therapy and the main spotlight for the improvement and advance of cell therapies that are being confronted today.
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