title: Bruch's membrane diffusivity for vascular endothelial growth factors may explain variable response to wet age-related macular degeneration treatment: clinical implications.
abstract: The hypothesis presented is that diffusivity of vascular endothelial growth factors (VEGF) across Bruch's membrane is an important parameter that distinguishes prompt and slow responders to anti-VEGF treatment in wet age-related macular degeneration (AMD). Accordingly, slow-responders have a high diffusivity and will attain peak VEGF levels on the choroidal side of Bruch's membrane rapidly, probably before or around the time of the next monthly anti-VEGF injection. If a fixed dose of anti-VEGF is used at each monthly treatment (as is the current practice), depending on the initial level of VEGF at that time of injection, VEGF with each treatment will vary. Therefore, diffusion will occur at a different concentration gradient in each treatment cycle subsequent to the injection. Hence, by Fick's Second Law of Diffusion, the slope of the concentration versus time curve for each treatment cycle will be different from the preceding cycle. This leads to a different peak concentration just prior to the next monthly injection. So, when a fixed dose of the anti-VEGF is used at each monthly treatment peak VEGF level fluctuates instead of going down continuously which prolongs the treatment. Thus, doses of anti-VEGF may have to be tapered to decrease the concentration gradient and to slow down the rate of diffusion of VEGF. Diffusivity of Bruch's membrane with regards to VEGF is a simple concept that can explain the variable response to anti-VEGF treatment in wet AMD. If validated through clinical trial the treatment protocol for wet AMD can be more precise and tailored to individual patients.
authors.affiliation: Eye Center South and Alabama College of Osteopathic Medicine, United States. Electronic address: ram.r.peddada@gmail.com.
authors.forename: Ram R
authors.initials: RR
authors.lastname: Peddada
mesh_terms: D000375:Aging; D016570:Bruch Membrane / Q000503:physiopathology*; D020256:Choroidal Neovascularization; D004058:Diffusion; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy*; D008962:Models, Theoretical; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A