PurposeThe foveal avascular zone (FAZ) is altered in numerous diseases. We assessed factors (axial length, segmentation method, age, sex) impacting FAZ measurements from optical coherence tomography (OCT) angiography images.MethodsWe recruited 116 Caucasian subjects without ocular disease, and acquired two 3 × 3 mm AngioVue scans per each right eye (232 total scans). In images of the superficial plexus, the FAZ was segmented using the AngioVue semiautomatic nonflow measurement tool and ImageJ manual segmentation. In images from the full retinal thickness, the FAZ was segmented using the AngioAnalytics automatic FAZ tool. Repeatability, reliability, and reproducibility were calculated for FAZ measurements (acircularity, area).ResultsFAZ area (mean ± SD) for manual segmentation was 0.257 ± 0.104 mm2, greater than both semiautomatic (0.231 ± 0.0939 mm2) and automatic (0.234 ± 0.0933 mm2) segmentation (P < 0.05). Not correcting for axial length introduced errors up to 31% in FAZ area. Manual area segmentation had better repeatability (0.022 mm2) than semiautomatic (0.046 mm2) or automatic (0.060 mm2). FAZ acircularity had better repeatability with automatic than manual segmentation (0.086 vs. 0.114). Reliability of all area measurements was excellent (intraclass correlation coefficient [ICC] = 0.994 manual, 0.969 semiautomatic, 0.948 automatic). Reliability of acircularity measurements was 0.879 for manual and 0.606 for automatic.ConclusionWe identified numerous factors affecting FAZ measurements. These errors confound comparisons across studies and studies examining factors that may correlate with FAZ measures.Translational RelevanceUsing FAZ measurements as biomarkers for disease progression requires assessing and controlling for different sources of error. Not correcting for ocular magnification can result in significant inaccuracy in FAZ measurements, while choice of segmentation method affects both repeatability and accuracy.

PurposeTo develop an automated reference frame selection (ARFS) algorithm to replace the subjective approach of manually selecting reference frames for processing adaptive optics scanning light ophthalmoscope (AOSLO) videos of cone photoreceptors.MethodsRelative distortion was measured within individual frames before conducting image-based motion tracking and sorting of frames into distinct spatial clusters. AOSLO images from nine healthy subjects were processed using ARFS and human-derived reference frames, then aligned to undistorted AO-flood images by nonlinear registration and the registration transformations were compared. The frequency at which humans selected reference frames that were rejected by ARFS was calculated in 35 datasets from healthy subjects, and subjects with achromatopsia, albinism, or retinitis pigmentosa. The level of distortion in this set of human-derived reference frames was assessed.ResultsThe average transformation vector magnitude required for registration of AOSLO images to AO-flood images was significantly reduced from 3.33 ± 1.61 pixels when using manual reference frame selection to 2.75 ± 1.60 pixels (mean ± SD) when using ARFS (P = 0.0016). Between 5.16% and 39.22% of human-derived frames were rejected by ARFS. Only 2.71% to 7.73% of human-derived frames were ranked in the top 5% of least distorted frames.ConclusionARFS outperforms expert observers in selecting minimally distorted reference frames in AOSLO image sequences. The low success rate in human frame choice illustrates the difficulty in subjectively assessing image distortion.Translational RelevanceManual reference frame selection represented a significant barrier to a fully automated image-processing pipeline (including montaging, cone identification, and metric extraction). The approach presented here will aid in the clinical translation of AOSLO imaging.

The mammalian visual cortex is immature at birth and undergoes postnatal structural and functional adjustments. The exact timing of the vulnerable period in rodents remains unclear. The critical period is characterized by inhibitory GABAergic maturation reportedly dependent on brain-derived neurotrophic factor (BDNF). However, most of the studies were performed on experimental/transgenic animals, questioning the relationship in normal animals. The present study aimed to conduct in-depth analyses of the synaptic and neurochemical development of visual cortical neurons in normal and monocularly-deprived rats and to determine specific changes, if any, during the critical period. We found that (i) against a gradual increase in excitation and inhibition with age, a transient period of synaptic and neurochemical imbalance existed with suppressed excitation and enhanced inhibition at postnatal days 28 to 33/34; (ii) during this window, the expression of BDNF and tropomyosin-related kinase B (TrkB) receptors decreased, along with glutamatergic GluN1 and GluA1 receptors and the metabolic marker cytochrome oxidase, whereas that of GABA Rα1 receptors continued to rise; (iii) monocular deprivation reduced both excitatory and inhibitory synaptic activity and neurochemicals mainly during this period; and (iv) in vivo TrkB agonist partially reversed the synaptic imbalance in normal and monocularly-deprived neurons during this time, whereas a TrkB antagonist accentuated the imbalance. Thus, our findings highlight a transitory period of synaptic imbalance with a negative relationship between BDNF and inhibitory GABA. This brief critical period may be necessary in transitioning from an immature to a more mature state of visual cortical functioning.

Cone photoreceptors of the 13-lined ground squirrel (13-LGS) undergo reversible structural changes during hibernation, including cone outer segment disc degeneration and inner segment mitochondria depletion. Here, we evaluated cone structure with adaptive optics scanning light ophthalmoscopy (AOSLO) before, during, and after hibernation. Also, intra-animal comparisons of cone structure were made at distinct physiological states (pre-hibernation, torpor, interbout euthermia, and post-hibernation) with AOSLO and transmission electron microscopy. Our results indicate that the 13-LGS cone mosaic is only transiently affected by structural remodeling during hibernation. Outer segment remodeling starts during torpid states during a period of fall transition in room temperature, with more severe structural changes during bouts torpor in cold temperature. Cones return to euthermic-like structure during brief periods of interbout euthermia and recover normal waveguiding properties as soon as 24 hours post-hibernation. Cone structure is visible with split-detector AOSLO thrSoughout hibernation, providing evidence that intact outer segments are not necessary to visualize cones with this technique. Despite the changes to cone structure during hibernation, cone density and packing remained unchanged throughout the seasonal hibernation

No abstract