Hisataka Fujimoto

Foveal Microstructure and Visual Acuity after Retinal Detachment Repair : Imaging Analysis by Fourier-Domain Optical Coherence Tomography

PURPOSE To evaluate foveal microstructural changes in eyes with anatomically successful repair of rhegmatogenous retinal detachments (RRDs). DESIGN Retrospective, consecutive, observational case series. PARTICIPANTS Fifty-three eyes of 51 consecutive patients with macula-on RRDs (15 eyes) or macula-off RRDs (38 eyes) after anatomically successful surgical repair. METHODS A microscopic fundus examination was conducted followed by Fourier-domain optical coherence tomography (FD-OCT) to assess the postoperative foveal microstructure. The correlation between the postoperative best-corrected visual acuity (BCVA) and microstructural findings at the fovea was evaluated. MAIN OUTCOME MEASURES Images of the foveal microstructure obtained by FD-OCT and the BCVA measured on the same day. RESULTS We obtained FD-OCT images a mean of 10.3+/-7.3 months (range, 1-25) postoperatively. Foveal anatomic abnormalities were detected in 33 eyes (62%); disruption of the junction between the photoreceptor inner and outer segments (IS/OS) in 23 eyes (43%), of which 9 eyes (39%) had a disrupted external limiting membrane (ELM); residual subretinal fluid in 6 eyes (11%), epiretinal membranes in 12 eyes (23%), and cystoid macular edema in 2 eyes (4%). Disruption of the photoreceptor IS/OS junction was observed only in macula-off eyes, whereas other microstructural abnormalities were observed in both macula-on and macula-off eyes. In preoperative macula-off eyes, the postoperative BCVA was significantly correlated with the integrity of the photoreceptor IS/OS and ELM signals detected by FD-OCT postoperatively (r=0.805; P<0.001). Of the 16 eyes followed by FD-OCT, the photoreceptor IS/OS junction was restored in 7 (64%) of the 11 eyes with a disrupted back-reflection line from the IS/OS junction, but without disrupted ELM signals at the initial examination. Of the 5 eyes with disrupted back-reflection lines from both IS/OS junction and ELM at the initial examination, the photoreceptor layer was not restored completely during the follow-up period in any eyes. CONCLUSIONS After anatomically successful RRD repair, FD-OCT is a valuable, noninvasive tool for evaluating foveal microstructural changes. The integrity of the photoreceptor IS/OS junction and ELM signals detected by FD-OCT may account for visual restoration in patients with preoperative macula-off RRDs. Preservation of the ELM postoperatively may predict the subsequent restoration of the photoreceptor layer.

Morphologic Changes in Acute Central Serous Chorioretinopathy Evaluated by Fourier-Domain Optical Coherence Tomography

OBJECTIVE To investigate morphologic alterations around fluorescein leakage sites using Fourier-domain optical coherence tomography (FD OCT) in acute central serous chorioretinopathy (CSC). DESIGN Observational case series. PARTICIPANTS Twenty-one eyes with acute CSC with subjective symptoms for under 3 months. METHODS Patients underwent measurement of visual acuity, fundus observations, and FD OCT examinations at every visit with the intervals of 2 to 4 weeks until subretinal fluid (SRF) resolved. Fluorescein angiography was performed at baseline to confirm dye leakage sites. Horizontal and vertical OCT scans (B-scans and consecutive raster scans) of the fovea and fluorescein leakage sites were obtained. MAIN OUTCOME MEASURES Morphologic changes in the retinal pigment epithelium (RPE), detached retina, and subretinal space around the leakage sites were evaluated repeatedly during follow-up. RESULTS The mean period between baseline and the final examination was 108 days (mean no. of examinations, 3.9). Among 23 leakage sites in 21 eyes, FD OCT showed RPE abnormalities in 22 (96%) sites (14 sites [61%] with a pigment epithelial detachment [PED] and 8 [35%] with a protruding or irregular RPE layer). Fibrinous exudates in the subretinal space and sagging/dipping of the posterior layer of the neurosensory retina above the leakage sites were seen at 12 (52%) and 10 (43%) leakage points, respectively. An RPE defect at the edge of or within the PED was observed in 5 leakage sites (22%); in 2 of these, a defect was detectable after the SRF decreased. The posterior surface of the detached retina was smooth in 17 eyes (81%) and granulated in 4 eyes (19%) (mean duration of subjective symptoms, 10 days and 42 days, respectively). The smooth posterior detached retina became granulated in the presence of residual SRF. A PED remained at the 5 leakage sites in 5 eyes (22%) despite SRF resolution. CONCLUSIONS Fourier-domain OCT examinations showed detailed morphologic changes in eyes with acute CSC including an RPE defect within the PED at a leakage site through which fluid might pass from the sub-RPE to the subretinal area. Fourier-domain OCT findings may offer new information to facilitate understanding of the mechanisms of acute CSC.

Neural Coding of Syntactic Structure in Learned Vocalizations in the Songbird

Although vocal signals including human languages are composed of a finite number of acoustic elements, complex and diverse vocal patterns can be created from combinations of these elements, linked together by syntactic rules. To enable such syntactic vocal behaviors, neural systems must extract the sequence patterns from auditory information and establish syntactic rules to generate motor commands for vocal organs. However, the neural basis of syntactic processing of learned vocal signals remains largely unknown. Here we report that the basal ganglia projecting premotor neurons (HVCX neurons) in Bengalese finches represent syntactic rules that generate variable song sequences. When vocalizing an alternative transition segment between song elements called syllables, sparse burst spikes of HVCX neurons code the identity of a specific syllable type or a specific transition direction among the alternative trajectories. When vocalizing a variable repetition sequence of the same syllable, HVCX neurons not only signal the initiation and termination of the repetition sequence but also indicate the progress and state-of-completeness of the repetition. These different types of syntactic information are frequently integrated within the activity of single HVCX neurons, suggesting that syntactic attributes of the individual neurons are not programmed as a basic cellular subtype in advance but acquired in the course of vocal learning and maturation. Furthermore, some auditory–vocal mirroring type HVCX neurons display transition selectivity in the auditory phase, much as they do in the vocal phase, suggesting that these songbirds may extract syntactic rules from auditory experience and apply them to form their own vocal behaviors.

Effect of instillation of eyedrops for dry eye on optical quality.

PURPOSE To investigate the effects of viscosity and suspensibility of eyedrops for dry eye by evaluating an eyedrop with one of the solutions or no solution (0.3% sodium hyaluronate ophthalmic solution, 3% diquafosol ophthalmic solution, and 2% rebamipide ophthalmic suspension) on ocular higher-order aberrations (HOAs) and forward light scatter. METHODS We evaluated ocular HOAs and forward light scatter before and 1, 5, and 10 minutes after instillation of three eyedrops for dry eye in 15 healthy subjects. Saline served as the control. The HOAs were measured for a 4-mm pupil using a wavefront sensor. The obtained aberration data were analyzed in the central 4-mm diameter for total HOAs up to the sixth-order Zernike polynomials. Forward light scatter was quantified with a straylight meter. RESULTS A significant increase was seen in the HOAs 1 minute after instillation of the three eyedrops for dry eye; the HOAs recovered to the baseline level thereafter. When 0.3% sodium hyaluronate was compared with 2% rebamipide and 3% diquafosol, the HOAs increased significantly (P < 0.01 for both comparisons) immediately after instillation. A significant increase in forward light scatter occurred 1 minute after instillation of rebamipide suspension and returned to the preinstillation level 5 minutes after instillation. No significant changes in forward light scatter occurred after instillation of 3% diquafosol or 0.3% sodium hyaluronate. CONCLUSIONS Quantitative serial measurement of HOAs and forward light scatter showed that the temporal reduction in optical quality may be attributed mainly to increased HOAs after instillation of highly viscous 0.3% sodium hyaluronate ophthalmic solution and to increased forward light scatter after instillation of 2% rebamipide ophthalmic suspension in healthy subjects.

A wireless neural recording system with a precision motorized microdrive for freely behaving animals

The brain is composed of many different types of neurons. Therefore, analysis of brain activity with single-cell resolution could provide fundamental insights into brain mechanisms. However, the electrical signal of an individual neuron is very small, and precise isolation of single neuronal activity from moving subjects is still challenging. To measure single-unit signals in actively behaving states, establishment of technologies that enable fine control of electrode positioning and strict spike sorting is essential. To further apply such a single-cell recording approach to small brain areas in naturally behaving animals in large spaces or during social interaction, we developed a compact wireless recording system with a motorized microdrive. Wireless control of electrode placement facilitates the exploration of single neuronal activity without affecting animal behaviors. Because the system is equipped with a newly developed data-encoding program, the recorded data are readily compressed almost to theoretical limits and securely transmitted to a host computer. Brain activity can thereby be stably monitored in real time and further analyzed using online or offline spike sorting. Our wireless recording approach using a precision motorized microdrive will become a powerful tool for studying brain mechanisms underlying natural or social behaviors.

Quantitative Evaluation of the Natural Progression of Keratoconus Using Three-Dimensional Optical Coherence Tomography.

PURPOSE We quantified the chronologic progression of keratoconus using anterior segment optical coherence tomography (AS-OCT). METHODS A total of 217 eyes from 113 patients with keratoconus, keratoconus suspect, or forme fruste keratoconus were evaluated by corneal tomography using swept-source OCT. Age-dependent changes in the radius of the posterior best-fit sphere (Rpost), minimum corneal thickness (Tmin), and distance from the thinnest point to the corneal vertex (Dmin) were examined over follow-up periods of up to 5.79 years and were analyzed using generalized estimating equation (GEE) nonlinear regression model. RESULTS Annual changes in Rpost (mean, -0.017 mm) and Tmin (-2.69 μm) were significantly higher in younger patients (P < 0.01, GEE nonlinear regression) and in patients with higher maximal K value (Kmax; P < 0.01, GEE nonlinear regression), whereas no changes were observed in Dmin. Even in patients 30 years or older, 14% of eyes revealed remarkable progression in Rpost. In eyes with acute hydrops, annual changes in Rpost (-0.22 mm) and Tmin (-33.8 μm) before acute corneal hydrops were more than 10 times faster than those in other eyes (P < 0.001, GEE nonlinear regression). CONCLUSIONS Chronologic measurements of corneal tomography in keratoconus demonstrated that the progression of steepening at posterior corneal surface was found not only in patients under 30 years but also in older patients, particularly in advanced keratoconus. The rate of progression can be measured by mapping of corneal curvature and thickness using OCT, and the risk of progression was greater in younger patients with steeper Kmax.

Late postnatal shifts of parvalbumin and nitric oxide synthase expression within the GABAergic and glutamatergic phenotypes of inferior colliculus neurons.

The inferior colliculus (IC) is partitioned into three subdivisions: the dorsal and lateral cortices (DC and LC) and the central nucleus (ICC), and serves as an integration center of auditory information. Recent studies indicate that a certain population of IC neurons may represent the non‐GABAergic phenotype, while they express well‐established cortical/hippocampal GABAergic neuron markers. In this study we used the optical disector to investigate the phenotype of IC neurons expressing parvalbumin (PV) and/or nitric oxide synthase (NOS) in C57BL/6J mice during the late postnatal period. Four major types of IC neurons were defined by the presence (+) or absence (–) of PV, NOS, and glutamic acid decarboxylase 67 (GAD67): PV+/NOS−/GAD67+, PV+/NOS+/GAD67+, PV+/NOS−/GAD67−, and PV−/NOS+/GAD67−. Fluorescent in situ hybridization for vesicular glutamate transporter 2 mRNA indicated that almost all GAD67− IC neurons represented the glutamatergic phenotype. The numerical densities (NDs) of total GAD67+ IC neurons remained unchanged in all subdivisions. The NDs of PV+/NOS−/GAD67+ neurons and PV−/NOS+/GAD67− neurons were reduced with age in the ICC, while they remained unchanged in the DC and LC. By contrast, the NDs of PV+/NOS+/GAD67+ neurons and PV+/NOS−/GAD67− neurons were increased with age in the ICC, although there were no changes in the DC and LC. The cell body size of GAD67+ IC neurons did not vary according to the expression of PV with or without NOS. The present findings indicate that the expression of PV and NOS may shift with age within the GABAergic and glutamatergic phenotypes of IC neurons during the late postnatal period. J. Comp. Neurol. 525:868–884, 2017.

Regional Differences in Tear Film Stability and Meibomian Glands in Patients With Aqueous-Deficient Dry Eye.

Objectives: To noninvasively investigate regional differences in tear film stability and meibomian glands in patients with aqueous-deficient dry eye. Methods: Forty-nine dry eyes and 31 normal eyes were analyzed. A corneal topographer with a tear film scanning function was used for noninvasive tear film break-up time (NI-TFBUT) measurements and meibomian gland observations. The NI-TFBUT values and location of the first tear film break-up point were recorded in four quadrants. Meibomian gland loss was graded for each eyelid using meiboscores. Lid margin abnormality was scored from zero to four according to the number of existing abnormalities. The NI-TFBUT values and meiboscores were compared between two groups, and regional differences in NI-TFBUT values and meiboscores were analyzed. Also, the correlation between the NI-TFBUT and ocular surface examination results were investigated. Results: The NI-TFBUT values and meiboscores were significantly lower and higher, respectively, for the dry eye group than for the normal group. In the dry eye group, the occurrence rate for first tear film break-up was the highest in the inferior nasal quadrant, and the mean meiboscore was significantly higher for the upper eyelids than for the lower eyelids. The NI-TFBUT and lid margin abnormality scores showed a weak negative correlation, and the NI-TFBUT values and meiboscores showed no correlation. Conclusions: Compared to normal eyes, aqueous-deficient dry eyes show significant regional differences in tear film stability and meibomian glands. Considering these regional differences, the overall observation of the ocular surface, including both upper and lower eyelids, will aid clinicians in understanding this condition better.

Rigid gas-permeable contact lens–assisted cataract surgery in patients with severe keratoconus

&NA; We describe rigid gas‐permeable (RGP) contact lens–assisted cataract surgery in patients with severe keratoconus. During cataract surgery in cases with severe keratoconus, the intraocular images are distorted and visual perspective is lost because of irregular corneal astigmatism. Poor visibility can lead to complications, including posterior capsule rupture and corneal endothelial cell damage. To overcome these problems, an RGP contact lens was placed on the cornea in 2 cases. The image distortion decreased markedly, and the visual perspective improved. Intraocular manipulations such as irrigation/aspiration were performed safely. Improvement in transillumination led to good visualization of the anterior and posterior capsules. No intraoperative or postoperative complications developed in either case. This technique provided excellent visualization during cataract surgery in patients with severe keratoconus. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Time-dependent localization of high- and low-sulfated keratan sulfates in the song nuclei of developing zebra finches

Keratan sulfate proteoglycans (KSPGs) and chondroitin sulfate proteoglycans (CSPGs) consist of a protein core with covalently attached glycosaminoglycan side chain. Although CSPGs are known to regulate the end of the critical period, the role of KSPGs in brain development remains unclear. Young male zebra finches memorise song templates during development. The brain regions that are responsible for song learning, known as song nuclei, are recognized as a suitable model for the study of brain development. To understand the potential role of KSPGs, here we examined the localization of KSs with different degrees of sulfation in the brain of developing male zebra finches. Exclusively in the song nuclei, an increase in expression of 5‐D‐4‐positive (5‐D‐4+) high‐sulfated KS started after hatching, and reached a plateau at the end of the sensory period, during which the young bird listens to and memorises the song of an adult tutor. By contrast, weak and ubiquitous expression of BCD‐4+ low‐sulfated KS remained unchanged until the end of the sensory period, and first increased in the song nuclei at the end of the sensorimotor period, during which the young bird produces plastic songs. Immunoblot analysis showed that phosphacan was a common core protein of 5‐D‐4+ KS and BCD‐4+ KS. Finally, we confirmed that the sulfotransferase responsible for the synthesis of high‐sulfated KS was exclusively localised in the song nuclei. Our observations suggest that time‐dependent localization of KSPGs with different sulfation patterns in the song nuclei may underlie song learning in developing male zebra finches.