## 3 Results  
Seventeen consecutive children--7 males and 10 females--aged between 6 and 12 years (\(8.52\pm 2.00\) years) showing one or more EDs were enrolled. Totally, 38 permanent teeth affected by EDs were analyzed: 23 white/creamy opacities and 11 yellow/brown ones; among them, 8 were linear, 16 appeared as small patches and 10 as diffuse areas (Figures 1 and 2). Hypoplasia was found in 4 teeth, with a degree of severity from low-medium (pit, groove and/or lines) in 2 teeth, to severe, in the remaining 2 teeth showing diffuse hypoplastic areas with serious reduction or lack of enamel thickness (Figures 3 and 4). Figure 1: (**a**) Initial clinical presentation and T\({}_{0}\) (**b**–**e**) and T\({}_{2}\) (**f**) confocal images of a white/cream opacity without structural defects of the two-third of the vestibular surface of the upper right central incisor in an 8-year-old female. (**b**,**c**) At T\({}_{0}\), at the boundaries of the defect, marked *B* in (**a**), enamel architecture was preserved and identifiable both at the superficial layers, 10 μm beneath the surface (**b**), and at the deepest visible layers, 300 μm beneath the surface (**c**). The diffuse bright points corresponded  
to the lack of mineral compounds, replaced by scattered deposits of bright organic substance. (**d**,**e**) At T\({}_{0}\), at the center of the defect, marked as <<D>> in (**a**), bright organic matrix was not arranged in the classical interprismatic regular net, neither at the superficial layers, 10 \(\upmu\)m beneath the surface (**d**), nor at the deepest visible layers, 300 \(\upmu\)m beneath the surface (**e**). (**f**) At T\({}_{2}\), enamel prisms still lack at the center of the defect, but the site appeared fulfilled by inhomogeneous and irregular accumulation of bright material, presumably organic casein phosphopeptide (CPP). Scale bars: 100 \(\upmu\)m.  
Figure 2: Diffuse white opacities without structural defects of both upper central incisors in an 8-year-old male before and after the casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) treatment. (**a**) At T\({}_{0}\), both teeth showed linear (arrows) and patchy (dotted circle) white opacities. (**b**,**c**) T\({}_{0}\) reflectance confocal microscopy (RCM) of the linear opacities marked, respectively, as <<B>> and <<C>> in (**a**): the enamel architecture was well preserved few layers below the surface (10 \(\upmu\)m below) while sparse dark areas (hyporefractive) expressed the slight disarrangement of the organic interprismatic substance, usually highly refractive. (**d**) T\({}_{0}\) RCM of the small patched opacity marked as <<D>> in (**a**): evident deposits of organic substance (hyper-refractive) and inhomogeneous mineralization. (**e**) T\({}_{1}\) RCM of a dental surface, immediately after the CPP-ACP application: the mousse appeared dispersed in the ultrasound gel used to perform RCM imaging, revealing to be a highly refractive granular compound, reflecting the CPP composition. (**f**,**g**) RCM before (T\({}_{0}\)) (**f1**,**g1**) and immediately after (T\({}_{1}\)) (**f2**,**g2**) CPP-ACP application at the patchy area of the upper right central incisor, showing the evident differences in organic accumulation within the dark areas. (**h**) At T\({}_{2}\), the patchy opacity of the upper right central incisor seems to have clinically totally disappeared. (**i**-**m**) The related T\({}_{2}\) RCM images showed a more refractive enamel arrangement through the layers: 10 \(\upmu\)m (i), 150 \(\upmu\)m (l) and 300 \(\upmu\)m (m). Scale bars: 100 \(\upmu\)m.  
Figure 4: **(a)** T\({}_{0}\) clinical picture of a yellow/brown patchy opacity with severe hypoplasia affecting the vestibular one/half of upper right central incisor and multiple, linear and patchy white/creamy opacities of the vestibular one/half of the upper left central incisor in a 9-year-old female.