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Snakes show remarkably deviated "body plan" from other squamate reptiles. In addition to limb loss, they have accomplished enormous anatomical specialization of the skull associated with the pit organs and the reduction of the tympanic membranes and auditory canals in the outer ears. Despite being the most diverse group of snakes, our knowledge of the embryonic staging for organogenesis and cranial ossification has been minimal for Colubridae. Therefore, in the present observation, we provide the first embryonic description of the Japanese rat snake Elaphe climacophora. We based our study on the Standard Event System (SES) for external anatomical characters and on a description of the cranial ossification during post-ovipositional development. We further estimated the relative ossification timing of each cranial bony element and compared it with that of selected other snakes, lizards, turtles, and crocodilians. The present study shows that the relative ossification timing of the palatine and pterygoid bones is relatively early in squamates when compared to other reptiles, implying the developmental integration as the palate-pterygoid complex in this clade and functional demands for the unique feeding adaptation to swallow large prey with the help of their large palatine and pterygoid teeth. Furthermore, unlike in species with pit organs, the prootic bone of Ela. climacophora is expanded to provide articulation with the supratemporal, thereby contributing to the hearing system by detecting substrate vibration. We also demonstrate that the relative timing of the prootic ossification is significantly accelerated in colubrids compared to snakes with pit organs. Our finding suggests that the temporal changes of the prootic ossification underpin the evolution of the perception of the ground-bourne sound signals among snakes.
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Objectives: Our purpose was to examine the effectiveness of pattern scanning laser trabeculoplasty (PSLT) as an additional treatment for patients of open-angle glaucoma (OAG) receiving maximized ocular hypotensive medications (OHM). Methods: A total of 40 eyes of 33 patients (average age 72.7 ± 10.7 years) who had not previously undergone open glaucoma surgery or laser trabeculoplasty and were treated with maximized OHM between June 2018 and March 2022 were included. A 360-degree PSLT was conducted, and postoperative intraocular pressure (IOP) and survival curves at 1, 3, 6, 9, and 12 months were evaluated. Results: According to the Kaplan-Meier survival analysis, the average survival time was 8.1 months and the survival rate at 12 months was 0.55, with death defined as postoperative IOP reduction of less than 10% or requiring additional treatment. The average survival time was 4.9 months and the survival rate at 12 months was 0.28, with death defined as postoperative IOP reduction of less than 20% or requiring additional treatment. Nine eyes showed increased IOP (three eyes) or worsened visual field (six eyes) during the course and underwent additional open glaucoma surgery. In the 31 eyes which received no additional treatment after PSLT, the mean preoperative IOP was 18.5 ± 3.9 mmHg, which reduced to 15.3 ± 4.1 mmHg (p = 1.62 × 10-6), 15.5 ± 3.4 mmHg (p = 1.51 × 10-5), 15.7 ± 4.0 mmHg (p = 1.75 × 10-5), 14.7 ± 4.38 (p = 2.89 × 10-6), and 15.0 ± 4.0 mmHg (p = 5.74 × 10-9) at 1, 3, 6, 9, and 12 months after PSLT, respectively. The IOP reduction rate one year after PSLT was 18.7%. Of the 31 eyes, 13 (42%) achieved a 20% reduction in IOP compared to the baseline. Conclusions: Adjunctive treatment with PSLT in OAG patients receiving maximized OHM may be effective over 12 months of follow-up.
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This report details a documented case of fatal King cobra (Ophiophagus hannah) envenomation in the Philippines. A 46-year-old woman from a mountainous town in Leyte was bitten on her left thigh by a snake. Despite receiving prompt medical attention, including administration of fluids and oxygen, she went into arrest and succumbed within 2.5 hours of the bite. Inadequate pre-hospital care, including endotracheal intubation and assisted ventilation, highlights a notable gap in emergency medical services. Photographic evidence, verified by a herpetologist, confirmed the involvement of a King cobra, with venom presenting with a swift and lethal systemic effect that led to the patient's demise, despite minimal local manifestations. This incident accentuates the urgent need for accessible, effective antivenom and improved snakebite management protocols in the Philippines. It also calls for heightened awareness and preparedness among pre-hospital healthcare providers and the public, alongside advocating for more research into snakebite envenomation.
Subject(s)
Elapid Venoms , Elapidae , Snake Bites , Animals , Female , Middle Aged , Humans , Philippines , Fatal Outcome , Antivenins/therapeutic useABSTRACT
PURPOSE: To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. METHODS: After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. RESULTS: EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. CONCLUSIONS: It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.
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Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited. In this study, we explored extracellular long non-coding RNAs (lncRNAs) released from primary sensory neurons as biomarker candidates for oxaliplatin-induced peripheral neuropathy. Because many human-specific lncRNA genes exist, we induced peripheral sensory neurons from human induced pluripotent stem cells. Oxaliplatin treatment changed the levels of many lncRNAs in extracellular vesicles (EVs) released from cultured primary sensory neurons. Among them, the levels of release of lncRNAs that were considered to be selectively expressed in dorsal root ganglia were correlated with those of lncRNAs in plasma EV obtained from healthy individuals. Several lncRNAs in plasma EVs early after the initiation of treatment showed greater changes in patients who did not develop chronic neuropathy that persisted for more than 1 year than in those who did. Therefore, these extracellular lncRNAs in plasma EVs may represent predictive biomarkers for the development of chronic peripheral neuropathy induced by oxaliplatin.
Subject(s)
Biomarkers , Induced Pluripotent Stem Cells , Oxaliplatin , Peripheral Nervous System Diseases , RNA, Long Noncoding , Sensory Receptor Cells , Oxaliplatin/adverse effects , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/blood , Induced Pluripotent Stem Cells/metabolism , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/metabolism , Biomarkers/blood , Biomarkers/metabolism , Peripheral Nervous System Diseases/blood , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/pathology , Male , Extracellular Vesicles/metabolism , Extracellular Vesicles/drug effects , Female , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Chronic Disease , Middle Aged , Cells, CulturedABSTRACT
Purpose: To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma. Methods: Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images. Results: GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01). Conclusion: GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.
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PURPOSE: To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. METHODS: This retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting. RESULTS: A strong correlation was seen between human and software counts. Pearson's correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; P<0.001 each). IL-6 levels correlated with both vitreous cell counts and cell counts observed on macular WOCT (human-counted group +0.339, P = 0.04; software-counted group +0.349, P = 0.03). Infectious uveitis showed higher IL-6 levels (P = 0.016) and high cell counts compared with non-infectious uveitis (P = 0.04). CONCLUSIONS: Vitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.
Subject(s)
Uveitis, Posterior , Uveitis , Humans , Middle Aged , Aged , Interleukin-6 , Retrospective Studies , Tomography, Optical Coherence/methods , Uveitis/diagnostic imaging , RetinaABSTRACT
BACKGROUND: Peripheral nerve injury to dorsal root ganglion (DRG) neurons develops intractable neuropathic pain via induction of neuroinflammation. However, neuropathic pain is rare in the early life of rodents. Here, we aimed to identify a novel therapeutic target for neuropathic pain in adults by comprehensively analyzing the difference of gene expression changes between infant and adult rats after nerve injury. METHODS: A neuropathic pain model was produced in neonatal and young adult rats by spared nerve injury. Nerve injury-induced gene expression changes in the dorsal root ganglion (DRG) were examined using RNA sequencing. Thymic stromal lymphopoietin (TSLP) and its siRNA were intrathecally injected. T cells were examined using immunofluorescence and were reduced by systemic administration of FTY720. RESULTS: Differences in changes in the transcriptome in injured DRG between infant and adult rats were most associated with immunological functions. Notably, TSLP was markedly upregulated in DRG neurons in adult rats, but not in infant rats. TSLP caused mechanical allodynia in adult rats, whereas TSLP knockdown suppressed the development of neuropathic pain. TSLP promoted the infiltration of T cells into the injured DRG and organized the expressions of multiple factors that regulate T cells. Accordingly, TSLP caused mechanical allodynia through T cells in the DRG. CONCLUSION: This study demonstrated that TSLP is causally involved in the development of neuropathic pain through T cell recruitment.
Subject(s)
Neuralgia , Thymic Stromal Lymphopoietin , Rats , Animals , Ganglia, Spinal , Hyperalgesia/etiology , T-Lymphocytes , Cytokines , NeuronsABSTRACT
Primary sensory neurons regulate inflammatory processes in innervated regions through neuro-immune communication. However, how their immune-modulating functions are regulated in concert remains largely unknown. Here, we show that Neat1 long non-coding RNA (lncRNA) organizes the proinflammatory gene expressions in the dorsal root ganglion (DRG) in chronic intractable neuropathic pain in rats. Neat1 was abundantly expressed in the DRG and was upregulated after peripheral nerve injury. Neat1 overexpression in primary sensory neurons caused mechanical and thermal hypersensitivity, whereas its knockdown alleviated neuropathic pain. Bioinformatics analysis of comprehensive transcriptome changes indicated the inflammatory response was the most relevant function of genes upregulated through Neat1. Consistent with this, upregulation of proinflammatory genes in the DRG following nerve injury was suppressed by Neat1 knockdown. Expression changes of these proinflammatory genes were regulated through Neat1-mRNA interaction-dependent and -independent mechanisms. Notably, Neat1 increased proinflammatory genes by stabilizing its interacting mRNAs in neuropathic pain. Finally, Neat1 in primary sensory neurons contributed to spinal inflammatory processes that mediated peripheral neuropathic pain. These findings demonstrate that Neat1 lncRNA is a key regulator of neuro-immune communication in neuropathic pain.
Subject(s)
Neuralgia , RNA, Long Noncoding , Trauma, Nervous System , Animals , Rats , RNA, Long Noncoding/genetics , Ganglia, Spinal , Neuralgia/genetics , RNA, Messenger , TranscriptomeABSTRACT
PURPOSE: The purpose of this study was to develop artificial intelligence algorithms that can distinguish between orbital and conjunctival mucosa-associated lymphoid tissue (MALT) lymphomas in pathological images. METHODS: Tissue blocks with residual MALT lymphoma and data from histological and flow cytometric studies and molecular genetic analyses such as gene rearrangement were procured for 129 patients treated between April 2008 and April 2020. We collected pathological hematoxylin and eosin-stained (HE) images of lymphoma from these patients and cropped 10 different image patches at a resolution of 2048 × 2048 from pathological images from each patient. A total of 990 images from 99 patients were used to create and evaluate machine-learning models. Each image patch of three different magnification rates at ×4, ×20, and ×40 underwent texture analysis to extract features, and then seven different machine-learning algorithms were applied to the results to create models. Cross-validation on a patient-by-patient basis was used to create and evaluate models, and then 300 images from the remaining 30 cases were used to evaluate the average accuracy rate. RESULTS: Ten-fold cross-validation using the support vector machine with linear kernel algorithm was identified as the best algorithm for discriminating between conjunctival mucosa-associated lymphoid tissue and orbital MALT lymphomas, with an average accuracy rate under cross-validation of 85%. There were ×20 magnification HE images that were more accurate in distinguishing orbital and conjunctival MALT lymphomas among ×4, ×20, and ×40. CONCLUSION: Artificial intelligence algorithms can successfully distinguish HE images between orbital and conjunctival MALT lymphomas.
Subject(s)
Conjunctival Neoplasms , Eye Neoplasms , Lymphoma, B-Cell, Marginal Zone , Humans , Lymphoma, B-Cell, Marginal Zone/genetics , Artificial Intelligence , Conjunctival Neoplasms/diagnosis , Conjunctival Neoplasms/pathology , Machine LearningABSTRACT
A limited number of studies have investigated the clinical characteristics of snakebite envenomation by exotic (non-native) snakes in Japan. This study reviewed the literature to determine the status and risk of bites by exotic pet snakes in Japan. We reviewed reports of snakebite due to exotic snakes in Japan published between 2000 and 2022, excluding reports of bites by snakes native to Japan, such as Gloydius blomhoffii, Rhabdophis tigrinus, and Protobothrops flavoviridis. During the study period, 11 exotic snakebites were recorded, involving 11 species. The majority of those bitten (10/11 cases) were male, all cases were hand injuries, and there were no fatalities. The snakes responsible belonged to the Colubridae (4/11 cases), Viperidae (4/11 cases), and Elapidae (3/11 cases) families. Cases of envenomation by G. brevicaudus, Bungarus candidus, and Dendroaspis angusticeps were of particular interest. Ten of the eleven patients developed local cytotoxic signs, and three developed "compartment syndrome," in which the surgeons performed decompressive incisions. Two bites from elapid snakes and one from a viperid snake resulted in respiratory failure. Antivenom was given in two cases. Complications were observed, such as acute kidney injury, rhabdomyolysis, coagulopathy, and residual dysfunction of the affected finger. Emergency rooms should be prepared to manage patients who have been bitten by exotic snakes, even though the number of reported cases is not high in Japan. Initial stabilization of patients is crucial, before a definitive diagnosis is made, as with native snakebite envenomation. Finger bites are reported in most cases, which may result in functional impairment of the fingers. In order to collect more comprehensive patient data in Japan, a reporting system for all snakebite envenomations should be considered.
Subject(s)
Blood Coagulation Disorders , Colubridae , Snake Bites , Viperidae , Animals , Male , Female , Snake Bites/complications , Japan/epidemiology , Snakes , Antivenins/therapeutic use , Elapidae , Blood Coagulation Disorders/etiologyABSTRACT
This study retrospectively determined the relationship between vitreous IL-6 levels and clinical and laboratory data collected from uveitis patients. We examined an unknown cause of posterior uveitis, collecting vitreous fluid to investigate vitreous IL-6 levels. The samples were analyzed in consideration of clinical and laboratory factors, such as the male/female ratio. The present study included 82 eyes from 77 patients with a mean age of 66.20 ± 15.41 years. The IL-6 concentrations of the vitreous specimens were 6255.0 ± 14,108.3 pg/mL in males and 277.6 ± 746.3 pg/mL in females, which was found to be a statistically significant difference (p = 0.048) (n = 82). There was also a statistically significant correlation between vitreous IL-6 concentrations, serum C-reactive protein (CRP) value and white blood cell counts (WBCs) (n = 82). In multivariate analysis, vitreous IL-6 levels were significantly correlated with gender and CRP in all cases (p = 0.048 and p < 0.01, respectively) and were also significantly correlated with CRP in non-infectious uveitis (p < 0.01). In infectious uveitis, there were no significant differences between IL-6 level and several variables. Vitreous IL-6 concentrations were higher in males than in females in all cases. In non-infectious uveitis, vitreous IL-6 levels were correlated with serum CRP. These results might suggest that intraocular IL-6 levels depend on gender differences in posterior uveitis, and intraocular IL-6 levels in non-infectious uveitis may reflect systemic inflammations, including increased serum CRP.
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PURPOSE: The present study assesses the utility of en-face widefield optical coherence tomography angiography (OCTA) imaging for evaluating the retinal vascular network during the course of treatment in acute retinal necrosis(ARN). OBSERVATIONS: OCTA images of two cases of acute retinal necrosis were analyzed. Case 1 was a 15-year-old male with visual crowding in his right eye who had best-corrected visual acuity of 16/20 and intraocular pressure of 25 mmHg in his right eye on initial evaluation. Case 2 was a 57-year-old male with visual crowding in his left eye who had best-corrected visual acuity of 20/20 in his left eye on initial examination and intraocular pressure of 19.3 mmHg. In both patients, dynamic changes could be tracked by en-face ultra-widefield OCTA imaging before and up to 1 year after surgical treatment. The images showed arteriovenous anastomosis and the nonperfused area on the surface of the retina. CONCLUSIONS AND IMPORTANCE: En-face widefield OCTA is useful for monitoring the structure of retinal vessels over time in acute retinal necrosis. Wide-angle OCTA is used to non-invasively examine retinal vascular dynamic changes in ARN. OCTA artifacts due to intraocular inflammation appeared, making interpretation difficult. These will remain as issues in the future. It seems difficult for a while to completely replace FA due to the problem of image clarity.
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PURPOSE: To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis. METHOD: We retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT. RESULTS: This study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (p<0.01). Compared to "Ophthalmoscopic findings", "W-OCT VO" offered 78.6% sensitivity and 30% specificity for all cases (p = 0.19). In addition, "W-OCT Cells" did not differ significantly from "FAG findings" for all cases (P = 0.424). CONCLUSION: W-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.
Subject(s)
Panuveitis , Uveitis, Posterior , Uveitis , Male , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Tomography, Optical Coherence/methods , Uveitis, Posterior/diagnostic imaging , Panuveitis/diagnostic imaging , Uveitis/diagnostic imaging , Inflammation , Ophthalmoscopy , Fluorescein Angiography/methods , Vitreous Body/diagnostic imagingABSTRACT
microRNAs (miRNAs) are extracellularly released by cells for intercellular communication, while intracellularly, they inhibit the expression of specific genes. An increasing number of studies suggest that extracellular miRNAs have great potential as both therapeutic targets and disease-specific biomarkers in a variety of diseases, including pain disorders. However, little is known about miRNA release from dorsal root ganglion (DRG) neurons in neuropathic pain caused by peripheral nerve injury. In this study, we investigated the changes in the extracellular release of miRNAs from DRG neurons in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve. We found increased release of six miRNAs (let-7d, miR-21, miR-142-3p, miR-146b, miR-203-3p and miR-221) from primary cultured DRG neurons prepared from rats 7 days after nerve injury. Among these, miR-221 was also increased in serum from days 7 to 28 after nerve injury. In contrast, serum miR-221 levels and its release from DRG neurons were unchanged in an inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant. These results suggest that the increased release of specific miRNAs by DRG neurons may be involved in the pathophysiology of neuropathic pain through extracellular as well as intracellular mechanisms. Furthermore, serum miR-221 may be useful as a biomarker of neuropathic pain caused by peripheral nerve injury.
Subject(s)
MicroRNAs , Neuralgia , Peripheral Nerve Injuries , Rats , Animals , Ganglia, Spinal/metabolism , Peripheral Nerve Injuries/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neuralgia/etiology , Sciatic Nerve/injuriesABSTRACT
The aim was to investigate the structural changes of the retina using en face ultra-widefield optical coherence tomography (OCT) images during the treatment of hypotony maculopathy with traumatic cyclodialysis. Case 1 was a 43-year-old male patient with visual crowding in his left eye (metallic wire injury that occurred 3 weeks previously) who was referred to our department. Although best-corrected visual acuity was 20/20 in his left eye on initial evaluation, intraocular pressure was 6 mm Hg. Case 2 was a 20-year-old male patient with visual crowding in his left eye (baseball ball injury that occurred 4 weeks previously) who was referred to our department. Although best-corrected visual acuity was 16/20 in his left eye on initial examination, intraocular pressure was 5 mm Hg. Surgical interventions were performed in both cases. En face ultra-widefield OCT images were able to be used to trace dynamic changes before the intervention and up to 1 year later. The images obtained in these two cases made it possible to confirm the progress from wrinkles on the surface of the retina to normalization of vascular structure and improvement of ellipsoid zone disruption. En face ultra-widefield OCT is useful for monitoring multilayer structures of the retina in hypotony maculopathy cases.
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BACKGROUND: Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported. METHODS: An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively. RESULTS: Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14-85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation. CONCLUSION: Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.
Subject(s)
Cataract , Uveitis, Posterior , Uveitis , Adolescent , Adult , Aged , Aged, 80 and over , Cataract/etiology , Female , Humans , Inflammation , Male , Middle Aged , Postoperative Complications/surgery , Retrospective Studies , Uveitis/complications , Uveitis/diagnosis , Uveitis/surgery , Vitrectomy/adverse effects , Vitrectomy/methods , Young AdultABSTRACT
Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P<0.01). No significant change in PD-L1 expression was observed in this study (P = 0.15). Staining patterns of FOXP3, CD8, and CXCR4 were examined separately between tumor cells and stromal cells in SCC tumors. Differences in staining of FOXP3 in Tregs and CD8 in tumor-infiltrating lymphocytes in tumor stroma in the Tis group were observed compared with the Tadv group (each P<0.01). In addition, double immunostaining of CXCR4/FOXP3 was correlated with progression-free survival (P = 0.049). Double immunostaining of CXCR4/FOXP3 correlated with American Joint Committee on Cancer T-stage, independent of age or Ki67 index (P<0.01). Our results show that FOXP3 and the CXCR4/FOXP3 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. The tumor microenvironment of conjunctival SCC should be considered in the future development of treatment options.
Subject(s)
Carcinoma, Squamous Cell , Conjunctival Neoplasms , Forkhead Transcription Factors , Receptors, CXCR4 , T-Lymphocytes, Regulatory , CD8-Positive T-Lymphocytes , Carcinoma, Squamous Cell/immunology , Conjunctival Neoplasms/immunology , Forkhead Transcription Factors/metabolism , Humans , Lymphocytes, Tumor-Infiltrating , Prognosis , Receptors, CXCR4/metabolism , Retrospective Studies , Tumor MicroenvironmentABSTRACT
Orofacial neuropathic pain can cause considerable disruptions in patients' daily lives, especially because of a lack of effective medications as its underlying causative mechanisms are not fully understood. Here, we found neuron-specific expression of the interleukin (IL)-33 receptor in the trigeminal spinal subnucleus caudalis (Vc), distinct from the spinal dorsal horn. Reduction in head withdrawal threshold in response to von Frey filament stimulation of the whisker pad skin was inversely correlated with the upregulation of IL-33 in the Vc after infraorbital nerve injury (IONI). Neutralization of IL-33 in the Vc alleviated mechanical allodynia in the whisker pad skin after IONI; conversely, intracisternal administration of IL-33 elicited mechanical allodynia in the whisker pad skin, which was relieved by GluN2B antagonism. Moreover, IL-33 triggered the potentiation of GluN2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents and phosphorylation of synaptosomal GluN2B in the Vc, whereas IONI-induced GluN2B phosphorylation was inhibited by neutralization of IL-33 in the Vc. IL-33-induced GluN2B phosphorylation was mediated by phosphorylation of Fyn kinase, and inhibition of the Fyn kinase pathway prevented the development of IL-33-induced mechanical allodynia. Our findings provide insights into a new mechanism by which IL-33 directly regulates synaptic transmission and suggest that IL-33 signaling could be a candidate target for therapeutic interventions for orofacial neuropathic pain.