Validation of a new technique using 4-0 nylon thread as a guide for tube insertion of the Ahmed glaucoma valve into the ciliary sulcus.

ABSTRACT: In this study, we validated the new technique for inserting the tube of the Ahmed glaucoma valve (AGV) into the ciliary sulcus. AGV tube insertion was performed by introducing a 4-0 nylon thread into the anterior chamber from the corneal incision on the opposite side of the AGV. The thread was placed in the lumen of a 23-G needle that was inserted into the sclera and ciliary sulcus from the AGV side. Withdrawing the 23-G needle, the thread was led out of the eye from the scleral wound, passing through the ciliary sulcus. The thread was then placed in the AGV tube lumen, and the tube was inserted through the scleral wound into the ciliary sulcus by using the thread as a guide, as per the Seldinger technique. In all seven eyes, the tube was precisely inserted into the ciliary sulcus without serious intraoperative complications such as vitreous straying of the tube.

A CASE OF EALES DISEASE OBSERVED BY WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: The purpose of this study was to report a 30-year-old woman with Eales disease, showing bilateral proliferative tissue. The retinal vessels were evaluated using widefield optical coherence tomography angiography (widefield OCTA), which has a wider angle of view compared with conventional instruments. METHODS: This is a case report. RESULTS: Widefield OCTA showed an extensive nonperfusion area and A-V shunt in both eyes and a vascular structure in the left eye that appeared to be retinal neovascularization. Ultra-widefield fluorescein angiography revealed no filling delay in the early phase, a vast nonperfusion area from the midperiphery to the ora serrata in bilateral eyes, and retinal neovascularization in the left eye. Based on the results of ultra-widefield angiography, OCTA examination, and systemic examination, a diagnosis of Eales disease was finally made after all the differential diseases had been excluded. CONCLUSION: In a patient with Eales disease, the peripheral nonperfusion area and retinal neovascularization that were consistent with the ultra-widefield angiography findings were noninvasively confirmed by widefield OCTA. Widefield OCTA is useful in the detection of peripheral changes of the fundus.

Relationship Between Patient-Friendly Audiovisual Systems and MRI Contrast Agent to Adverse Reactions.

BACKGROUND: Patient-friendly audiovisual (AV) systems in head MRI examinations can potentially reduce patient anxiety and contrast-enhanced MRI (CE-MRI) adverse reactions to gadolinium. PURPOSE: To evaluate whether a patient-friendly AV system reduces the rate of adverse reactions to gadolinium-based contrast agents. STUDY TYPE: Retrospective. POPULATION: Four thousand eight hundred thirty-two outpatients (2462 female) attending for clinical CE-MRI studies. (Gadoteridol: 1971, Meglumine gadoterate: 2733, Gadobutrol: 128.) FIELD STRENGTH/SEQUENCE: Routine CE-MRI of head and neck using a 1.5 T or 3 T scanner with or without a patient-friendly AV system. ASSESSMENT: One thousand one hundred fifty-nine patients were scanned on MRI machines equipped with patient-friendly AV systems (AV group) and 3673 on MRI machines without AV systems (control group). Adverse reaction rate and symptoms were reviewed by referring to the system database and electronic medical records and compared between the two groups. Adverse reactions were defined as physiological reactions, such as vomiting and allergic-like reactions, such as urticaria, occurring within 1 hour of contrast injection. We compare patient backgrounds, adverse reaction rate, adverse reactions symptoms and the severity between the two groups. STATISTICAL TESTS: Adverse reaction rate with and without a patient-friendly AV system were compared using Fisher's exact test. The relationship between patient-friendly AV systems and the occurrence of adverse reactions was evaluated with logistic regression. Statistical significance was set at P < 0.05. RESULTS: Of the 4832 patients enrolled, 65 (1.35%) experienced adverse reactions. The most common adverse reactions in both groups were urticaria and pruritus. Adverse reaction rate was significantly lower in the AV group than in the control group (0.7% vs. 1.6%). No significant difference was observed in the severity (P = 1.000) of adverse reactions and symptoms (allergic-like reaction: P = 0.08, physiologic reaction: P = 1.000) between the two groups. DATA CONCLUSION: The patient-friendly AV system significantly reduce adverse reaction occurrence to gadolinium-based contrast agents. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

A New Technique Using a 4-0 Nylon Thread as a Guide for Easy and Precise Tube Insertion of Ahmed Glaucoma Valve Implant Into Ciliary Sulcus.

We present a new technique for inserting the tube of the Ahmed glaucoma valve (AGV) (model FP7; Rancho Cucamonga, CA: New World Medical) implant into the ciliary sulcus, easily and precisely, using a 4-0 nylon thread as a guide. An 88-year-old woman received AGV implantation for secondary angle recession glaucoma with underlying pseudoexfoliation syndrome in her left eye. She had a history of trauma with mild intraocular lens (IOL) oscillation and poor mydriasis, with maximum pupil diameter of 3.5 mm. Ciliary sulcus tube insertion in such patients sometimes becomes difficult, however, using a 4-0 nylon thread as a guide, precise insertion was achieved easily in the following way. A 4-0 nylon thread was placed into the anterior chamber through a 1 mm incision opposite the site of the AGV implant. Subsequently, a 23G needle was inserted into the sclera 2 mm from the corneal limbus in the same quadrant as AGV implants. The tip of the 23G needle proceeded horizontally to the iris, through the sclera and ciliary body, and into the ciliary sulcus. At the center of the pupil, the 4-0 nylon thread was introduced into the lumen of the 23G needle. Subsequently, the 23G needle, together with the 4-0 nylon thread in the lumen was withdrawn out of the eye. The 4-0 nylon was then inserted into the tube lumen of the AGV implant. Finally, by using 4-0 nylon as a guide, the Ahmed tube was inserted into the ciliary sulcus precisely without much difficulty.

Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo.

Here we describe the microglia-targeting adeno-associated viral (AAV) vectors containing a 1.7-kb putative promoter region of microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (Iba1), along with repeated miRNA target sites for microRNA (miR)-9 and miR-129-2-3p. The 1.7-kb genomic sequence upstream of the start codon in exon 1 of the Iba1 (Aif1) gene, functions as microglia preferential promoter in the striatum and cerebellum. Furthermore, ectopic transgene expression in non-microglial cells is markedly suppressed upon adding two sets of 4-repeated miRNA target sites for miR-9 and miR-129-2-3p, which are expressed exclusively in non-microglial cells and sponged AAV-derived mRNAs. Our vectors transduced ramified microglia in healthy tissues and reactive microglia in lipopolysaccharide-treated mice and a mouse model of neurodegenerative disease. Moreover, live fluorescent imaging allowed the monitoring of microglial motility and intracellular Ca2+ mobilization. Thus, microglia-targeting AAV vectors are valuable for studying microglial pathophysiology and therapies, particularly in the striatum and cerebellum.

Lacrimal Duct Obstruction and Infection Associated with Non-Traumatic Corneal Perforation: A Case Series.

Purpose: To report a case series of lacrimal duct obstruction and infection associated with non-traumatic corneal perforation. Case Series: This study included 6 eyes in 6 patients with non-traumatic corneal perforation treated between April 2019 and March 2021. All 6 cases were associated with lacrimal duct obstruction and infection. Purulent discharge caused by lacrimal duct infection was observed in all 6 patients (100%). However, three of the 6 patients (50%) did not show purulent discharge at initial examination and lacrimal duct obstruction was therefore not initially recognized. Dry eye was observed in five of the 6 patients (83%) and may have caused corneal deterioration, increasing susceptibility to perforation. Further, dry eye masks symptoms of lacrimal duct obstruction and infections, such as epiphora and regurgitation of purulent discharge, making the association with lacrimal duct obstruction and infection difficult to determine. All patients were treated for both corneal perforation and lacrimal duct disease, and conditions improved, with no recurrence of either corneal perforation or lacrimal duct disease. Conclusion: In patients with a combination of lacrimal duct disease and corneal perforation, treatment of both diseases resulted in stabilization of patient condition. Dry eyes may mask symptoms of lacrimal duct diseases, such as epiphora and purulent discharge, and lacrimal duct disease may thus be underdiagnosed.

Obscured interdigitation zone at the early stage of gyrate atrophy: A case report.

PURPOSE: To report an early stage of gyrate atrophy (GA) of the retina and choroid for which spectral-domain optical coherence tomography (SD-OCT) images revealed an obscured interdigitation zone (IZ). OBSERVATION: A 13-year-old boy was referred to our department due to blurred vision in his left eye. Best corrected visual acuity was 20/20 and 20/25 in the right and left eye, respectively. Fundus examination revealed scalloped atrophic peripheral chorioretinal lesions in both eyes. Concentrations of plasma and urine ornithine were 1192 nmol/mL and 1930 µmol/g·cre, respectively. Consequently, he was diagnosed with GA. Although Goldmann perimetry found no abnormalities, electroretinogram (ERG) revealed loss of the rod responses and significant attenuation of the cone responses in both eyes. Detailed analysis of the posterior part of the fundus using multifocal electroretinogram showed poor responses, specifically in the nasal macular area of the left eye. SD-OCT showed an obscured IZ corresponding to the attenuated cone response determined by ERG. There was preservation of the retinal pigment epithelium, ellipsoid zone and external limiting membrane. CONCLUSIONS AND IMPORTANCE: Obscured IZ during early stage GA was confirmed in a teenage patient with a chief complaint of blurred vision. OCT is useful in the detection of minute morphological changes that occur earlier in GA.

Karyopherin-ß1 Regulates Radioresistance and Radiation-Increased Programmed Death-Ligand 1 Expression in Human Head and Neck Squamous Cell Carcinoma Cell Lines.

Nuclear transport receptors, such as karyopherin-ß1 (KPNB1), play important roles in the nuclear-cytoplasmic transport of macromolecules. Recent evidence indicates the involvement of nuclear transport receptors in the progression of cancer, making these receptors promising targets for the treatment of cancer. Here, we investigated the anticancer effects of KPNB1 blockage or in combination with ionizing radiation on human head and neck squamous cell carcinoma (HNSCC). HNSCC cell line SAS and Ca9-22 cells were used in this study. Importazole, an inhibitor of KPNB1, or knockdown of KPNB1 by siRNA transfection were applied for the blockage of KPNB1 functions. The roles of KPNB1 on apoptosis induction and cell surface expression levels of programmed death-ligand 1 (PD-L1) in irradiated HNSCC cells were investigated. The major findings of this study are that (i) blockage of KPNB1 specifically enhanced the radiation-induced apoptosis and radiosensitivity of HNSCC cells; (ii) importazole elevated p53-upregulated modulator of apoptosis (PUMA) expression via blocking the nuclear import of SCC-specific oncogene ΔNp63 in HNSCC cells; and (iii) blockage of KPNB1 attenuated the upregulation of cell surface PD-L1 expression on irradiated HNSCC cells. Taken together, these results suggest that co-treatment with KPNB1 blockage and ionizing radiation is a promising strategy for the treatment of HNSCC.

Effects of Neutralizing Antibody Production on AAV-PHP.B-Mediated Transduction of the Mouse Central Nervous System.

Adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV serotype 9, is highly permeable to the blood-brain barrier. A major obstacle to the systemic use of AAV-PHP.B is the generation of neutralizing antibodies (NAbs); however, temporal profiles of NAb production after exposure to AAV-PHP.B, and the influence on later AAV-PHP.B administration, remains unknown. To address these, AAV-PHP.Bs expressing either GFP or mCherry by neuron-specific or astrocyte-specific promoters were intravenously administered to mice at various intervals, and brain expression was examined. Injection of two AAV-PHP.Bs, separated temporally, showed that as little as a 1-day interval between injections resulted in a significant decrease in expression of the second transgene, with a complete loss of expression after 7 days, paralleling an increase in serum NAb titers. Brain parenchymal injection was explored to circumvent the presence of NAbs. Mice systemically pre-treated with an AAV-PHP.B were injected intra-cerebrally with an AAV-PHP.B expressing GFP. After 2 weeks, marked GFP expression in the cerebellum was evident, showing that pre-existing NAbs did not affect the AAV-PHP.B directly injected into the brain. In contrast, reversing the injection order, i.e., cerebellar injection followed by systemic injection, completely eliminated expression of the second transgene. We confirmed that intra-cerebellar injection produced NAbs in the serum, but not in the cerebrospinal fluid (CSF). Our results indicate that the preclusion of brain transduction by a second AAV-PHP.B administration begins from the first day following systemic injection and is established within 1 week. Serum NAbs can be avoided by directly injecting AAV-PHP.Bs into brain tissue.

Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.

Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein (EGFP) under the control of the constitutive CBh promoter (a hybrid of cytomegalovirus early enhancer and chicken ß-actin promoter). Age-matched control marmosets were treated with standard AAV9-capsid vectors. The animals were sacrificed 6 weeks after the viral injection. Based on the results, only limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV-PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia neurons. Indeed, the soma and axons in the projection from the spinal cord to the nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV-PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B transduction efficiency in the CNS of marmosets was comparable to that of AAV9 vectors.

Minimal Purkinje Cell-Specific PCP2/L7 Promoter Virally Available for Rodents and Non-human Primates.

Cell-type-specific promoters in combination with viral vectors and gene-editing technology permit efficient gene manipulation in specific cell populations. Cerebellar Purkinje cells play a pivotal role in cerebellar functions. Although the Purkinje cell-specific L7 promoter is widely used for the generation of transgenic mice, it remains unsuitable for viral vectors because of its large size (3 kb) and exceedingly weak promoter activity. Here, we found that the 0.8-kb region (named here as L7-6) upstream of the transcription initiation codon in the first exon was alone sufficient as a Purkinje cell-specific promoter, presenting a far stronger promoter activity over the original 3-kb L7 promoter with a sustained significant specificity to Purkinje cells. Intravenous injection of adeno-associated virus vectors that are highly permeable to the blood-brain barrier confirmed the Purkinje cell specificity of the L7-6 in the CNS. The features of the L7-6 were also preserved in the marmoset, a non-human primate. The high sequence homology of the L7-6 among mouse, marmoset, and human suggests the preservation of the promoter strength and Purkinje cell specificity features also in humans. These findings suggest that L7-6 will facilitate the cerebellar research targeting the pathophysiology and gene therapy of cerebellar disorders.

A Case of Blunt Trauma of the Eyeball Associated With an Inferior Oblique Muscle and an Inferior Rectus Muscle Rupture.

Rupture of the extraocular muscle in the absence of significant injury to the eyeball and adnexa is uncommon. The authors report a case of blunt trauma of the eyeball associated with an inferior oblique muscle and an inferior rectus muscle rupture. A 55-year-old man slipped and fell down hitting his eye on an extended windshield wiper blade. Although he had treatment in the emergency room, he complained of diplopia in the primary position 1 day postoperatively. After noticing ruptures of the inferior oblique muscle and an inferior rectus muscle during exploratory surgery, the authors carefully repaired it. Diplopia in the primary position had disappeared within 1 month after the operation and by 6 months postoperatively. The movement of the eye had almost completely recovered.

Retinal ganglion cell analysis in multiple evanescent white dot syndrome.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is an acute and usually unilateral retinopathy that occurs predominantly in young adults. This report presents the outcomes of ganglion cell analysis (GCA) in MEWDS. CASE PRESENTATION: A 41-year-old woman was diagnosed as MEWDS in right eye. At her initial visit, the deviation map of the ganglion cell analysis showed there was a decrease of the ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness in both eyes, even though her left eye was not affected. A 29-year-old woman was also diagnosed as MEWDS in right eye. Although the deviation map of ganglion cell analysis showed there was a decrease of the GCL + IPL thickness in both eyes at her initial visit, her right eye was not affected. CONCLUSION: GCA indicated there was a decrease (<1% of the distribution of normals) of the ganglion cell layer + inner plexiform layer thickness in both the affected and fellow eyes in 7 of 9 patients diagnosed as MEWDS in our hospital. Although the lesions responsible for MEWDS are thought to disrupt the photoreceptor outer segments, we observed changes in the inner retina in both the affected and fellow eye of MEWDS patients.

Animal-type malignant melanoma associated with nevus of Ota in the orbit of a Japanese woman: a case report.

We present a patient with an animal-type malignant melanoma associated with the nevus of Ota in the orbit who showed a good prognosis after a combination of orbital extirpation, chemotherapy, stereotactic radiotherapy, and gamma knife. A 42-year-old Japanese woman presented with two tumors, one pathologically diagnosed as right-sided intraconal animal-type malignant melanoma and the other intracranially, presumed to be of the same pathogenesis and both were considered to have arisen from the nevus of Ota. She underwent an extirpation of the orbit, chemotherapy (DAV therapy, which is a combination of dacarbazine, nimustine, and vincristine), stereotactic radiotherapy (54 Gy in 27 fractions), and gamma knife (marginal dose was 17 Gy, target volume was 0.2 ml). She has been alive for 33 months since the extirpation, with no sign of local recurrence, new metastasis, nor enlargement of the intracranial tumor. Not just combination therapy but also the low malignancy of animal-type melanoma may have contributed toward the good prognosis.

Vitreous changes in high myopia observed by swept-source optical coherence tomography.

PURPOSE: To observe vitreous changes in high myopia using swept-source optical coherence tomography (SS-OCT). METHODS: We performed slit-lamp biomicroscopy and SS-OCT in the highly myopic right eyes of 151 patients (mean age, 52.7 years; mean refraction, -11.4 diopters [D]) and the right eyes with no myopia of 363 healthy control volunteers (mean age, 52.8 years; mean refraction, -1.4 D). To estimate the sizes of the posterior precortical vitreous pockets (PPVPs), we measured the height between the fovea and the anterior border of the PPVPs. RESULTS: Patients with partial posterior vitreous detachments (PVDs) around the macula and complete PVDs in high myopia were significantly (P < 0.0001) younger (47.1 ± 14.1 and 61.2 ± 12.0 years, respectively) than controls (59.0 ± 9.6 and 69.7 ± 6.6 years). The PPVPs with no PVDs were significantly (P < 0.001) higher in 32 eyes with high myopia (984 ± 292 µm) than 164 controls (553 ± 166 µm). After a complete PVD with a Weiss ring developed, the vitreous cortex was on the macula in 40.5% of the eyes with high myopia, which differed significantly (P < 0.0001) from the 8.7% of the controls. Myopic foveoschisis was present in 14 (9.3%) of 151 eyes. In eyes with foveoschisis, three (21.4%) eyes had partial PVDs and 11 (78.6%) eyes had complete PVDs; there was no residual cortex in 8 (72.7%) of 11 eyes with complete PVDs. CONCLUSIONS: Highly myopic eyes may have larger PPVPs than normal eyes. Partial PVDs around the macula and complete PVDs occur at younger ages. The vitreous cortex more frequently remains on the macula after development of complete PVDs in highly myopic eyes.