Purpose-We aimed to characterize and grade the spectrum of foveal hypoplasia based on different stages of arrested development of the fovea. Grading was performed using morphological findings obtained by ultrahigh resolution spectral domain optical coherence tomography (UHR-OCT). Best corrected visual acuity (BCVA) was calculated for different grades. Design-Observational Case SeriesParticipants and Controls-Sixty-nine patients with foveal hypoplasia (albinism (n=34), PAX6 mutations (n=10), isolated cases (n=14), achromatopsia (n=11)) and 65 control subjects were examined.Methods-A 7x7mm retinal area was sampled using a 3-dimensional scanning protocol (743x75; AxB scans) with UHR-OCT (SOCT Copernicus HR, 3μm axial resolution). Gross morphological abnormalities were documented. B-scans at the fovea were segmented using a longitudinal reflectivity profile. Logarithm of Minimum Angle of Resolution (LogMAR) BCVA was obtained.Main Outcome Measures-Grading was based on presence or absence of foveal pit, widening of outer nuclear layer (ONL) and outer segment (OS) at the fovea. Quantitative measurements were performed for comparing atypical foveal hypoplasia in achromatopsia. BCVA was compared to the grade of foveal hypoplasia Results-Four grades of foveal hypoplasia were distinguished grade 1: shallow foveal pit, presence of ONL widening, presence of OS lengthening; grade 2: grade 1 but absence of foveal pit, grade 3: grade 2 but absence of OS lengthening; grade 4: grade 3 but absence of ONL widening). There was significant difference in visual acuity (VA) associated with each grade (p<0.0001). Grade 1 was associated with the best VA (median VA = 0.2), while grade 2, 3 and 4 was associated with progressively poorer VA with a median VA of 0. 44, 0.60 and 0.78 Correspondence and address for reprints: Professor Irene Gottlob (ig15@le.ac.uk) HHMI Author ManuscriptHHMI Author Manuscript HHMI Author Manuscript respectively. The atypical features seen with foveal hypoplasia associated with achromatopsia were characterized by decreased retinal (RT) and ONL thickness and deeper foveal depth (FD).Conclusions-We have developed a structural grading system for foveal hypoplasia based on the stage at which foveal development was arrested, which helps to provide a prognostic indicator for VA and is applicable in a range of disorders associated with foveal hypoplasia. Atypical foveal hypoplasia in achromatopsia shows different characteristics.Normal foveal development occurs in stages where the pit formation for the incipient fovea starts at fetal week 25 and the excavation is complete 15-45 months after birth. 1 Disruption of this developmental process leads to foveal hypoplasia which is a characteristic morphological abnormality associated with conditions such as albinism, PAX6 mutations or it may occur in isolation. [2][3][4][5] With the advent of optical coherence tomography (OCT) it is now possible to document the varying degrees of foveal hypoplasia which are likely to represent the different stages of arrested deve...

PURPOSE.To characterize the time course of normal foveal development in vivo in term infants and young children using handheld spectral-domain optical coherence tomography (HH-SDOCT). METHODS.We obtained 534 HH-SDOCT scans from 261 infants, children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each retinal layer was manually segmented in ImageJ and correlated with gestational age (GA) and visual acuity (VA). The developmental trajectories of each retinal layer at the fovea, parafovea, and perifovea were calculated using fractional polynomial modeling.RESULTS. The central macular thickness (CMT) increases logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL), inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in thickness exponentially until 18 months GA. Interestingly, the parafoveal and perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner segment, and outer segment of the photoreceptors increase in thickness logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The parafoveal and perifoveal outer retinal layers increase in thickness more gradually until 146 months GA. The thickness of the outer retinal layers and CMT were strongly correlated with VA, with r ¼ 0.54 (P < 0.0001) and r ¼ 0.52 (P < 0.0001), respectively. CONCLUSIONS.We have modeled for the first time the complex, nonlinear developmental trajectories for each retinal layer and demonstrate that development continues until adolescence. Our description of normal development will be helpful in diagnosing, monitoring, and understanding pediatric retinal disease.

In order to determine whether somatostatin coexists with GABA or glycine in neurones in rat spinal dorsal horn, a combined pre- and post-embedding immunocytochemical study was carried out. One hundred six somatostatin-immunoreactive neurones located in lamina II and the dorsal half of lamina III were tested with antiserum or monoclonal antibody to GABA and none of these cells showed GABA-like immunoreactivity. However, 8 out of 13 somatostatin-immunoreactive neurones located deeper in the dorsal horn (ventral lamina III and lamina IV) showed glycine-like immunoreactivity, and 6 of these were also GABA-immunoreactive. We have previously shown that neurotensin-immunoreactive neurones in laminae II and III are also not immunoreactive when tested with GABA antiserum (Todd et al.: Neuroscience 47:685-691, 1992), and a double-labelling fluorescence method was therefore used to compare the distribution of somatostatin and neurotensin within the superficial dorsal horn. The two types of peptide-immunoreactivity were never found in the same profile. These results suggest that somatostatin and neurotensin are present in different populations of non-GABAergic neurones in rat superficial dorsal horn, but that some somatostatin-containing neurones in the deeper part of the dorsal horn contain glycine, with or without GABA.