Optical coherence tomographic findings of glaucomatous eyes with papillomacular retinoschisis.

OBJECTIVES: To investigate the relationship between the shape of the optic nerve head (ONH) margin detected by optical coherence tomography (OCT) and the clinical characteristics of glaucomatous eyes with papillomacular retinoschisis (PMRS). METHODS: The medical record of patients with a PMRS in a glaucomatous eye were reviewed. The eyes were placed into two groups determined by the shape of the ONH margin in the OCT images; eyes with an externally oblique ONH margin (Group 1) and eyes with an internally oblique ONH margin (Group 2). We compared the clinical characteristics of the PMRS of these two groups. RESULTS: We studied 31 eyes of 29 patients with PMRS and glaucoma with 24 eyes in Group 1 and 7 eyes in Group 2. The optic nerve fibre layer schisis on the lamina cribrosa (LC), beta zone, and gamma zone, and found that the LC defects were detected significantly more frequently in Group 1 than in Group 2 eyes (P < 0.05). A retinal nerve fibre schisis was observed around the ONH significantly more frequently in Group 2 than in Group 1 eyes (P < 0.01). CONCLUSION: The cases of glaucoma-associated PMRS could be classified into two groups according to the obliquity of the ONH. They had differences in the findings of OCT and FA. The possibility that the mechanism of PMRS development is different in both groups is suggested.

Characteristics of subretinal particles detected after pars plana vitrectomy for rhegmatogenous retinal detachment.

BACKGROUND: To determine the incidence and characteristics of the multiple subretinal particles (SRPs) present after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). METHODS: The medical records of 224 eyes of 224 patients that underwent PPV for RRD were reviewed. The presence of SRPs in the subretinal fluid blebs and the presence of subretinal deposits were determined by optical coherence tomography (OCT) and fundus autofluorescence (FAF). The characteristics of the FAF and infrared reflectance (IR) images of a scanning laser ophthalmoscope in eyes with SRPs (SRPs group) were compared to that of eyes without SRPs (control group). RESULTS: SRPs were observed in 27 eyes (12%), and they were completely resolved in 20 eyes (74%) after 6 months. The incidence of macula-off RRD (85%) and preoperative precipitates (41%) were significantly higher in the SRPs group than that in the control group (64%, P = 0.046; 12%, P = 0.002). The axial length was significantly shorter in the SRPs group than that in the control group (25.04 ± 1.54 mm, 26.00 ± 1.78 mm, P = 0.012). The preoperative and postoperative best-corrected visual acuity were not significantly different between the two groups (P = 0.702, P = 0.337). The subretinal fluid bleb determined by OCT were hyperfluorescent in the FAF images in 24 eyes (89%), and the subretinal deposits were hypofluorescent with solid appearance by OCT other than fluid in 3 eyes (11%). The hypofluorescent subretinal deposits in the FAF images were bright in the IR images in 2 eyes. CONCLUSIONS: The SRPs consist of lipofuscin-related hyperfluorescent subretinal fluid and the subretinal deposits containing bright IR melanin particles of proliferating retinal pigment epithelial cells.

Image sharpening algorithms improve clarity of surgical field during 3D heads-up surgery.

BACKGROUND: Image-sharpening algorithms with color adjustments enable real-time processing of the surgical field with a delay of 4 msec for heads-up surgery using digital three-dimensional displays. The aim of this study was to investigate the usefulness of the algorithms with the Artevo 800® digital microscope. METHODS: Seven vitreoretinal surgeons evaluated the effects of image-sharpening processing on the clarity of the surgical field with the Artevo 800® system that is used for cataract and vitreous surgeries. The scorings were made on a 10-point scale for anterior capsulotomy, phacoemulsification, cortex aspiration, core vitrectomy, and peeling of an epiretinal membrane or an internal limiting membrane. In addition, the images during the internal limiting membrane peeling were processed with or without color adjustments. We also evaluated the skewness (asymmetry in the distribution of the pixels) and kurtosis (sharpness in the distribution of the pixel) of the images to evaluate the contrast with each intensity of image-sharpening. RESULTS: Our results showed that the mean visibility score increased significantly from 4.9 ± 0.5 at 0% (original image) to 6.6 ± 0.5 at 25% intensity of the image-sharpening algorithm (P < 0.01). The visibility scores of the internal limiting membrane increased significantly from 0% (6.8 ± 0.3, no color adjustments) to 50% after the color adjustments (7.4 ± 0.4, P = 0.012). The mean skewness decreased significantly from 0.83 ± 2.02 at 0% (original source) to 0.55 ± 1.36 at 25% intensity of the image-sharpening algorithm (P = 0.01). The mean kurtosis decreased significantly from 0.93 ± 2.14 at 0% (original image) to 0.60 ± 1.44 at 25% intensity of the image-sharpening algorithm (P = 0.02). CONCLUSIONS: We conclude that the image-sharpening algorithms can improve the clarity of the surgical field during 3D heads-up surgery by decreasing the skewness and kurtosis. TRIAL REGISTRATION: This was a prospective clinical study performed at a single academic institution, and the procedures used were approved by the Institutional Review Committee of the Kyorin University School of Medicine (reference number, 1904). The procedures also conformed to the tenets of the Declaration of Helsinki.

Effects of image-sharpening algorithm on surgical field visibility during 3D heads-up surgery for vitreoretinal diseases.

We conducted clinical and experimental studies to investigate the effects of image-sharpening algorithms and color adjustments, which enabled real-time processing of live surgical images with a delay of 0.004 s. The images were processed with image-sharpening intensities of 0%, 12.5%, 25%, and 50% during cataract surgery, vitrectomy, peeling of epiretinal membrane, and peeling of internal limiting membrane (ILM) with the Ngenuity 3D visualization system. In addition, the images obtained with a yellow filter during the ILM peeling were processed with color adjustments. Five vitreoretinal surgeons scored the clarity of the images on a 10-point scale. The images of a 1951 United States Air Force grating target placed in no fluid (control), saline, and 0.1% and 1% milk solution were evaluated. The results showed that the mean visibility score increased significantly from 5.0 ± 0.6 at 0% to 6.4 ± 0.6 at 12.5%, 7.3 ± 0.7 at 25%, and 7.5 ± 0.9 at 50% (P < 0.001). The visibility scores during ILM peeling improved significantly with color adjustments (P = 0.005). In the experimental study, the contrast of the grating targets blurred by the 0.1% and 1% milk solution increased significantly by the image-sharpening procedure. We conclude that the image-sharpening algorithms and color adjustments improved the intraoperative visibility of 3D heads-up surgery.

Effect of the COVID-19 Pandemic on Surgical Outcomes for Rhegmatogenous Retinal Detachments.

We reviewed the medical records of 438 eyes in 431 patients who had undergone surgeries for rhegmatogenous retinal detachments (RRD) or proliferative vitreoretinopathy (PVR ≥ Grade C) to determine whether the COVID-19 pandemic had affected outcomes. The patients were divided into 203 eyes in Group A that had undergone surgery from April to September 2020, during the pandemic, and 235 eyes in Group B that had undergone surgery from April to September 2019, before the pandemic. The pre- and postoperative visual acuity, macular detachment, type of retinal breaks, size of the RRD, and surgical outcomes were compared. The number of eyes in Group A was fewer by 14%. The incidence of men (p = 0.005) and PVR (p = 0.004) was significantly higher in Group A. Additionally, the patients in Group A were significantly younger than in Group B (p = 0.04). The differences in the preoperative and final visual acuity, incidence of macular detachment, posterior vitreous detachment, types of retinal breaks, and size of the RRD between the two groups were not significant. The initial reattachment rate was significantly lower at 92.6% in Group A than 98.3% in Group B (p = 0.004). The COVID-19 pandemic affected the surgical outcomes for RRD with higher incidences of men and PVR, younger aged patients and lower initial reattachment rates even though the final surgical outcomes were comparable.

Spatial organization of activity evoked by focal stimulation within the rat spinal dorsal horn as visualized by voltage-sensitive dye imaging in the slice.

In a prior study using laser scanning photostimulation, we found a pronounced cell type-specific mediolateral asymmetry in the local synaptic connectivity in the superficial laminae of the spinal dorsal horn (Kosugi M, Kato G, Lukashov S, Pendse G, Puskar Z, Kozsurek M, Strassman AM. J Physiol 591: 1935-1949, 2013). To obtain information on dorsal horn organization that might complement findings from microelectrode studies, voltage-sensitive dye imaging was used in the present study to examine patterns of activity evoked by focal electrical stimulation, in the presence and absence of synaptic blocking agents, at different positions in transverse, parasagittal, and horizontal slices of the dorsal horn of 2- to 3-wk -old male rats. A pronounced difference in responsiveness was found between medial and lateral dorsal horn, in that medial sites in the superficial dorsal horn showed much larger synaptic responses to focal stimulation than lateral sites. This difference appeared to be a result of a difference in the intrinsic elements of the dorsal horn, rather than a difference in the inputs from the white matter, because the stimulus intensities were subthreshold for evoking synaptic responses from stimulation at sites in the white matter, although it is also possible that the greater responsiveness is due, at least in part, to activation of Aß primary afferent fibers that pass through the medial dorsal horn. The results raise the possibility of differences between medial and dorsal horn that need to be taken into account in the interpretation of studies of dorsal horn organization.NEW & NOTEWORTHY We used voltage-sensitive dye imaging to obtain information on spatial aspects of dorsal horn organization that are difficult to examine with single-cell approaches because of the limitations of microelectrode sampling. The most noteworthy finding was a previously unreported, extreme difference between medial and lateral dorsal horn in responsiveness to focal stimulation that appears to result, at least in part, from a greater degree of excitability or local connectivity in medial dorsal horn.

Macular Hole Associated with Vogt-Koyanagi-Harada Disease at the Acute Uveitic Stage.

We describe a case with macular hole (MH) associated with Vogt-Koyanagi-Harada (VKH) disease. A 71-year-old Japanese woman presented with visual loss and headaches. The best-corrected visual acuity (BCVA) was 0.02 in the right eye (RE) and 0.1 in the left eye (LE). The patient was diagnosed with VKH based on circumferential choroidal detachments, multiple serous retinal detachments, and optic disc hyperemia. The multiple serous retinal detachments improved with high-dose corticosteroid therapy and gradual tapering. The BCVA was recovered to 1.2/0.7 in the RE/LE. Six weeks after the initial administration of steroid, vitreomacular traction was found by optical coherence tomography in the LE, which progressed to stage 4 MH with the BCVA of 0.2 in the LE. Twenty-three weeks after the initial treatment, vitrectomy was performed with the standard surgical procedures, including inner limiting membrane peeling around the fovea and air tamponade. The MH was closed successfully and the BCVA was 0.4 in the LE 5 weeks after the vitrectomy. This is the first report of a case with MH secondary to the acute uveitic stage of VKH. Successful closure of MH was achieved with the standard surgical intervention for an idiopathic MH. To conclude, at the early stage of VKH, there is a possibility of MH formation due to the rapid progress of vitreous traction following the inflammation, and the surgical procedure could be effective to resolve this secondary disorder.

Three-dimensional organization of local excitatory and inhibitory inputs to neurons in laminae III-IV of the spinal dorsal horn.

Laser scanning photostimulation was used to map the distribution of the synaptic input zones (sites that give local synaptic inputs) for dorsal horn laminae III-IV neurons, in parasagittal and transverse slices of the rat lumbar spinal cord, and examine how these inputs differed for neurons of different morphologies. All neurons received local excitatory and inhibitory synaptic inputs from within laminae III-IV, while a subset of neurons also received excitatory input from the superficial laminae, especially lamina IIi, as well as the II/III border region. Two anatomical properties were found to be predictive of the dorsoventral position of a neuron's input zone relative to its soma: (1) both excitatory and inhibitory input zones were more dorsal for neurons with longer dorsal dendrites, and (2) excitatory, but not inhibitory, input zones were more dorsal (relative to the soma) for more ventral neurons, with the transition between the dorsal input zones of laminae III-IV neurons and the ventral input zones of lamina II neurons occurring at the II/III border. The observed morphophysiological correlations support the idea that interlaminar connectivity is mediated via translaminar dendritic extensions and that, more generally, local connectivity within the dorsal horn is governed by rules relating the position of a neuron's soma and dendrites to the position of the local presynaptic neurons from which it receives inputs, which are specific to the axis and direction (dorsal vs. ventral), whether the input is excitatory or inhibitory, and the laminar position of the postsynaptic neuron.

Separate inhibitory and excitatory components underlying receptive field organization in superficial medullary dorsal horn neurons.

Extracellular recording has shown that dorsal horn neurons can have an inhibitory surround outside their excitatory receptive field, but cannot reveal inhibitory inputs within the excitatory field, or show the underlying excitatory and inhibitory synaptic inputs that determine net output. To study the underlying components of receptive field organization, in vivo patch-clamp recording was used to compare the size and distribution of subthreshold, suprathreshold, and inhibitory fields, in neurons in the mouse superficial medullary dorsal horn that were characterized by their responses to noxious and innocuous mechanical facial stimulation. Subthreshold excitatory fields typically extended some distance beyond the borders of the suprathreshold field, and also commonly exhibited broader stimulus selectivity, in that the majority of nociceptive-specific neurons exhibited subthreshold responses to brush. Separate voltage-clamp recording of excitatory and inhibitory inputs using different holding potentials revealed that inhibition could be evoked from both within and outside the excitatory field. In nociceptive neurons, inhibition tended to be maximal at the excitatory receptive field center, and was usually greater for pinch than brush, although the selectivity for pinch versus brush was not as great as with excitatory responses. Based on current data on dorsal horn organization, we propose that the localized peak of inhibition at the excitatory field center could be mediated by local interneurons, while the more widespread surrounding inhibition may depend on supraspinal circuitry.

Categorization of biologically significant objects, food and gender, in rhesus monkeys. I. Behavioral study.

Macaque monkeys have a highly evolved visual system comparable to that of humans. One of the important visual functions is performing discriminations among biologically significant objects such as food or heterosexual partners. In the present study, we examined whether rhesus monkeys could categorize two-dimensional images related to food or gender using a visual discrimination task. Three rhesus monkeys were trained to make distinctions of food from non-food items, and between male and female monkeys, using 60 or more different pictures of each category. After more than 9 months of training, the monkeys discriminated a variety of foods from non-food and different males from females with more than 80% accuracy, even when the stimuli were used for the first time or presented only once in a session. The proportion of correct responses and response latencies showed better performance in discrimination of food/non-food than that of gender. The results suggest that rhesus monkeys are able to perform visual discrimination of highly abstract biologically significant categories with better performance in a food-related category than a gender-related one, using two-dimensional visual information.

Slow oscillation of membrane currents mediated by glutamatergic inputs of rat somatosensory cortical neurons: in vivo patch-clamp analysis.

Using in vivo patch-clamp technique, the slow oscillation of membrane currents was characterized by its synaptic nature, correlation with electroencephalogram (EEG) and responses to different anesthetic agents, in primary somatosensory cortex (SI) neurons in urethane-anesthetized rats. In more than 90% of the SI neurons, the slow oscillation of the inward currents (0.1-2.5 Hz) with the duration of several hundreds of a millisecond was observed at the holding membrane potential of -70 mV. The reversal potential of the inward currents was approximately 0 mV and was suppressed by application of an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist. In most cases (> 90%) the inward current was synchronized with positive wave of the surface EEG recorded from ipsilateral and even contralateral cortical regions. The frequency as well as duration of the slow oscillation decreased by a volatile anesthetic agent, isoflurane (1.5-5.0%), and excitatory postsynaptic currents (EPSCs) were almost abolished at the highest concentration. Intraperitoneal injection of pentobarbital (25 mg/kg) also decreased the frequency of the slow oscillation without affecting short EPSCs. When gamma-aminobutyric acid A (GABA(A)) receptors were activated by local microinjection of muscimol (3 x 10(-3) m, 1-10 microL) into the thalamus, the frequency of the slow oscillation markedly decreased, but was not abolished completely. These findings suggest that the slow oscillation of the inward currents is generated by the summation of glutamatergic EPSCs, and affected by isoflurane and pentobarbital differently. In addition, GABAergic system in the thalamus can affect the frequency, but is not essentially implicated in the genesis of the slow oscillation.

An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta).

We have previously shown that a decrease in gamma-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 +/- 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 +/- 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600-1200 and 1800-2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 +/- 0.2 mo) than in sham/controls (25.5 +/- 0.9 mo, P<0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18-20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.

Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats.

Stimulation of the rostral ventromedial medulla (RVM) is believed to exert analgesic effects through the activation of the serotonergic system descending to the spinal dorsal horn; however, how nociceptive transmission is modulated by the descending system has not been fully clarified. To investigate the inhibitory mechanisms affected by the RVM, an in vivo patch-clamp technique was used to record IPSCs from the substantia gelatinosa (SG) of the spinal cord evoked by chemical (glutamate injection) and electrical stimulation (ES) of the RVM in adult rats. In the voltage-clamp mode, the RVM glutamate injection and RVM-ES produced an increase in both the frequency and amplitude of IPSCs in SG neurons that was not blocked by glutamate receptor antagonists. Serotonin receptor antagonists were unexpectedly without effect, but a GABAA receptor antagonist, bicuculline, or a glycine receptor antagonist, strychnine, completely suppressed the RVM stimulation-induced increase in IPSCs. The RVM-ES-evoked IPSCs showed fixed latency and no failure at 20 Hz stimuli with a conduction velocity of >3 m/s (3.1-20.7 m/s), suggesting descending monosynaptic GABAergic and/or glycinergic inputs from the RVM to the SG through myelinated fibers. In the current-clamp mode, action potentials elicited by noxious mechanical stimuli applied to the receptive field of the ipsilateral hindlimb were suppressed by the RVM-ES in more than half of the neurons tested (63%; 10 of 16). These findings suggest that the RVM-mediated antinociceptive effects on noxious inputs to the SG may be exerted preferentially by the direct GABAergic and glycinergic pathways to the SG.

In vivo and in vitro patch-clamp recording analysis of the process of sensory transmission in the spinal cord and sensory cortex.

Following the integration and modification of the sensory inputs in the spinal cord, the information is transmitted to the primary sensory cortex where the integrated information is further processed and perceived. Processing of the sensory information in the spinal cord has been intensively investigated. However, the mechanisms of how the inputs are processed in the cortex are still unclear. To know the correlation of the sensory processing in the dorsal horn and cortex, in vivo and in vitro patch-clamp recordings were made from rat dorsal horn and sensory cortex. Although dorsal horn neurons showed spontaneous and evoked EPSCs by noxious and non-noxious stimuli, most somatosensory neurons located at 100 to 1000 microm from the surface of the cortex exhibited an oscillatory activity and received synaptic inputs from non-noxious but not noxious receptors. These observations suggest that the synaptic responses in cortical neurons are processed in a more complex manner; and this may be due to the reciprocal synaptic connection between thalamus and cortex.

Application of in vivo patch-clamp technique to pharmacological analysis of synaptic transmission in the CNS.

Slice preparations as well as acutely dissociated and cultured neurons from various regions in the CNS have been widely used to analyze pharmacological properties of synaptic responses and receptors expressed at the pre- and post-synaptic sites. However, the essential properties are not obviously different from neuron to neuron. These characteristics of neurons in the CNS make it difficult to elucidate their functional significances. It is, therefore, preferable that the pharmacological analysis should be made from identified neurons by stimulation of identified inputs. The in vivo patch-clamp recording technique allows us to clarify the synaptic responses evoked by the various known natural stimuli applied to the skin or other parts and makes it possible to interpret with more certainty the behavioral changes by synaptic plasticity observed at the single cell level. Although the in vivo technique has obvious advantages in analysis of physiological responses, this method is, however, confined so far to neurons located at the near surface of the CNS for pharmacological analysis, because of the diffusion problem of the chemical to deeper neurons. Thus, combinatorial studies with dissociated or cultured neurons or with slice preparations are clearly required for further understanding of pharmacological properties of neurons in the CNS.

Aging-related changes in in vivo release of growth hormone-releasing hormone and somatostatin from the stalk-median eminence in female rhesus monkeys (Macaca mulatta).

GH release decreases with aging in primates. However, it is unclear whether the age-related decrease in GH release is due to a decrease in stimulatory GHRH or an increase in inhibitory somatostatin (SS) from the hypothalamus. In the present study, we measured the release of GHRH and SS in the stalk-median eminence of conscious aged (n = 7, 27.0 +/- 0.7 yr old) and young adult female monkeys (n = 12, 5.0 +/- 0.3 yr old) using the push-pull perfusion method. Mean GHRH levels during morning (0600-1200 h) and evening (1800-2400 h) in aged monkeys were 3- to 4-fold lower than in young monkeys. Pulse analysis indicated that pulse frequency, pulse amplitude, and baseline GHRH release in aged monkeys were much lower than in young adults. In contrast, mean SS levels in aged monkeys during mornings and evenings were 2-fold higher than in young monkeys. Pulse analyses indicated that amplitude and baseline levels of SS were significantly higher in aged monkeys than in young adults. There were no significant changes in the pulse frequency of SS release. Therefore, the aging-related decrease in GH release is due to a substantial decrease in GHRH release and an increase in SS release from the hypothalamus.