Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.     

Formation of cyclic structures in the cationic ring-opening polymerization of 1,3-dioxolane

The cationic ring-opening polymerization of acetals is prone to cyclization of the polymer chains. This is also the case for the polymerization of 1,3-dioxolane. Literature states that this cyclization can be reduced by applying the Active Monomer mechanism, at least if no competition with the Active Chain End mechanism occurs. In this work, a detailed characterization of the different distributions resulting from the cationic ring-opening polymerization of 1,3-dioxolane via the Active Monomer mechanism is made by a combination of gel permeation chromatography, ¹H NMR, and for the first time by matrix assisted laser desorption/ionization time of flight mass spectrometry. The influence of monomer addition speed, catalyst to initiator ratio and solvent were studied on both kinetics and composition of the product. Furthermore, it was found that increasing the conversion and monomer to initiator ratios leads to an increased amount of cyclic structures and to broader distributions, in correspondence with the Jacobson–Stockmayer theory. Furthermore, ion trapping experiments using ³¹P NMR provide insights into the actual reaction mechanism. Finally, purification of the products after the reactions led to a reduction of the cyclic fraction.

Elucidating the mechanism of the cationic ring-opening polymerization of dioxolane using gel permeation chromatography, matrix assisted laser desorption/ionization time of flight mass spectrometry and ³¹P NMR.