Revisiting Cryptocyanine Dye, NK-4, as an Old and New Drug: Review and Future Perspectives.

NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4's antioxidative and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases.

Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy.

Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.

Effect of NK-5962 on Gene Expression Profiling of Retina in a Rat Model of Retinitis Pigmentosa.

PURPOSE: NK-5962 is a key component of photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis (OUReP™). Previously, we found that NK-5962 solution could reduce the number of apoptotic photoreceptors in the eyes of the Royal College of Surgeons (RCS) rats by intravitreal injection under a 12 h light/dark cycle. This study aimed to explore possible molecular mechanisms underlying the anti-apoptotic effect of NK-5962 in the retina of RCS rats. METHODS: RCS rats received intravitreal injections of NK-5962 solution in the left eye at the age of 3 and 4 weeks, before the age of 5 weeks when the speed in the apoptotic degeneration of photoreceptors reaches its peak. The vehicle-treated right eyes served as controls. All rats were housed under a 12 h light/dark cycle, and the retinas were dissected out at the age of 5 weeks for RNA sequence (RNA-seq) analysis. For the functional annotation of differentially expressed genes (DEGs), the Metascape and DAVID databases were used. RESULTS: In total, 55 up-regulated DEGs, and one down-regulated gene (LYVE1) were found to be common among samples treated with NK-5962. These DEGs were analyzed using Gene Ontology (GO) term enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. We focused on the up-regulated DEGs that were enriched in extracellular matrix organization, extracellular exosome, and PI3K-Akt signaling pathways. These terms and pathways may relate to mechanisms to protect photoreceptor cells. Moreover, our analyses suggest that SERPINF1, which encodes pigment epithelium-derived factor (PEDF), is one of the key regulatory genes involved in the anti-apoptotic effect of NK-5962 in RCS rat retinas. CONCLUSIONS: Our findings suggest that photoelectric dye NK-5962 may delay apoptotic death of photoreceptor cells in RCS rats by up-regulating genes related to extracellular matrix organization, extracellular exosome, and PI3K-Akt signaling pathways. Overall, our RNA-seq and bioinformatics analyses provide insights in the transcriptome responses in the dystrophic RCS rat retinas that were induced by NK-5962 intravitreal injection and offer potential target genes for developing new therapeutic strategies for patients with retinitis pigmentosa.

Visual Evoked Potential Recovery by Subretinal Implantation of Photoelectric Dye-Coupled Thin Film Retinal Prosthesis in Monkey Eyes With Macular Degeneration.

Retinal prosthesis or artificial retina is a promising modality of treatment for outer retinal degeneration, caused by primary and secondary loss of photoreceptor cells, in hereditary retinal dystrophy and age-related macular degeneration, respectively. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. The dye-coupled films were implanted by vitreous surgery in the subretinal space of monkey eyes with macular degeneration which had been induced by cobalt chloride injection from the scleral side. A pilot 1-month observation study involved 6 monkeys and a pivotal 6-month observation study involved 8 monkeys. Of 8 monkeys in 6-month group, 3 monkeys underwent dye-coupled film removal at 5 months and were observed further for 1 month. The amplitude of visual evoked potential which had been reduced by macular degeneration did recover at 1 month after film implantation and maintained the level at 6 months. Optical coherence tomography showed no retinal detachment, and full-field electroretinograms maintained a-wave and b-wave amplitudes, indicative of no retinal toxicity. Pathological examinations after 6-month implantation showed structural integrity of the inner retinal layer in close apposition to dye-coupled films. The implanted films which were removed by vitrectomy 5 months later showed light-evoked surface electric potentials by scanning Kelvin probe measurement. The photoelectric dye-coupled film (OUReP), which serves as a light-receiver and a displacement current generator in the subretinal space of the eye, has a potential for recovering vision in diseases with photoreceptor cell loss, such as retinitis pigmentosa and age-related macular degeneration.

Positive bacterial culture in conjunctival sac before cataract surgery with night stay is related to diabetes mellitus.

BACKGROUND: The aim of this study is to elucidate background clinical factors in patients with positive bacterial culture for the conjunctival sac before cataract surgery in Japan. METHODS: Retrospective review was made on medical records of 576 consecutive patients who underwent conjunctival sac culture before cataract surgery with night stay at a hospital in 2 years from January 2013 to December 2014. In the patients with sequential bilateral surgeries, the data were chosen for bacterial culture in the eye which had earlier surgery. The age at surgery ranged from 33 to 100 years (mean, 76.7 years). Clinical factors, analyzed in relation with positive or negative bacterial culture, included the sex, the age, the presence of hypertension or diabetes mellitus, history of cancer, and history of hospital-based surgery at other specialties. RESULTS: Bacterial culture of the conjunctival sac was positive in 168 patients while negative in 408 patients. In multiple regression analysis, the positive bacterial culture was related with the older age (P = 0.01), the presence of diabetes mellitus (P = 0.004), and the history of hospital-based surgery at other specialties (P = 0.001). CONCLUSIONS: Elderly patients with diabetes mellitus or previous hospital-based surgeries at other specialties have a higher rate of positive bacterial culture in the conjunctival sac before cataract surgery. This study would provide a hint for identifying patients at risk for carrying bacterial flora in the conjunctival sac.

Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation.

Photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. The dye-coupled films or plain films were implanted subretinally in both eyes of 10 Royal College of Surgeons rats with hereditary retinal dystrophy at the age of 6 weeks. Visual evoked potentials in response to monocular flashing light stimuli were recorded from cranially-fixed electrodes, 4 weeks and 8 weeks after the implantation. After the recording, subretinal film implantation was confirmed histologically in 7 eyes with dye-coupled films and 7 eyes with plain films. The recordings from these 7 eyes in each group were used for statistical analysis. The amplitudes of visual evoked potentials in the consecutive time points from 125 to 250 ms after flash were significantly larger in the 7 eyes with dye-coupled film implantation, compared to the 7 eyes with plain film implantation at 8 weeks after the implantation (P < 0.05, repeated-measure ANOVA). The photoelectric dye-coupled polyethylene film, as retinal prosthesis, gave rise to visual evoked potential in response to flashing light.

Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation.

Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP™, retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP™. The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P < 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P < 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P < 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.

Clinicopathological correlation for the role of fluorodeoxyglucose positron emission tomography computed tomography in detection of choroidal malignant melanoma.

BACKGROUND: The purpose of this study was to redefine the role of whole-body 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography fused with computed tomography (PET/CT) in the clinical diagnosis of choroidal malignant melanoma. METHODS: The study design was a retrospective case series involving 7 consecutive patients with choroidal malignant melanoma who underwent enucleation to reach the final pathological diagnosis. FDG-PET/CT was performed together with magnetic resonance imaging and ophthalmological examinations before the surgery. The area, thickness, longest diameter, and circumference of the tumor mass were measured on pathological sections, and were correlated with maximum standardized uptake values (SUVmax) of the tumors on FDG-PET/CT. RESULTS: Abnormally high uptake of FDG was noted in the affected eyes of 5 patients, but not in the eyes of 2 patients. The 5 patients with high uptake showed nodular tumors extruding into the vitreous cavity while the 2 patients with absence of uptake showed diffusely infiltrating tumors in the wide area of the choroid with or without a small mushroom-like protrusion. One patient with diffuse infiltration showed concurrent liver metastases with high uptake on PET/CT while another patient with a nodular tumor developed liver metastases a year later. The tumors with higher SUVmax had a tendency to have a wider area and greater thickness on pathological sections (ρ = 0.775, P = 0.0557, Spearman rank correlation test). CONCLUSIONS: FDG-PET/CT showed correlation of the uptake with tumor sizes but was limited in detecting diffusely infiltrating tumors in the choroid without nodular formation.

Spontaneous regression and rare relapse after excisional biopsy in long-term observation of 31 patients with primary conjunctival lymphoma.

To elucidate long-term outcome in primary conjunctival lymphoma, a review was conducted of 31 consecutive patients: 21 men and 10 women with an age range of 28 to 85 (median, 61) years at presentation and follow-up periods ranging from 1 to 19 (median, 7) years. Conjunctival lymphoma was on the right side in 10 patients, on the left side in 12, and on both sides in 9. Upper, lower, or both fornix lesions in 28 patients were all diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), while thick nasal bulbar conjunctival lesions in 3 patients were differently diagnosed as MALT lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, respectively. Seven patients underwent local radiation (30 Gy): as initial treatment in 5 patients and treatment for relapse in 2 patients. The remaining 24 patients were observed without additional treatment after excisional biopsy: 5 of these 24 patients showed relapse 0.5 to 6 years later and underwent excisional biopsy again that revealed MALT lymphoma. Of the 5 patients with relapse, only one with second-time relapse underwent radiation. Fluorodeoxyglucose positron emission tomography was performed in 18 patients and showed no systemic lesions: high uptake was noted in the residual conjunctival lesions of 4 patients and in the relapsed conjunctival lesions of 3 patients. One patient died of rectal cancer while no patients died of lymphoma. Observation is an option in patients with primary conjunctival lymphoma after excisional biopsy. Radiation is a treatment option in the case of relapse.

Rare Combination of Abducens Nerve Palsy and Optic Neuritis on the Same Side: Case Report and Review of 8 Patients in Literature.

The concurrent development of abducens nerve palsy and optic neuritis on the same side is rare. Here we presented an 82-year-old man who developed the combination of abducens nerve palsy and optic neuritis on the left side 2 months after the sixth inoculation of COVID-19 mRNA vaccine. In past history at 45 years old, he experienced subarachnoid hemorrhage and underwent surgery for the clipping of intracranial aneurysm. The patient had no systemic symptoms, such as general fatigue, fever, arthralgia, and skin rashes. Physical and neurological examinations were also unremarkable. Since the aneurysmal metal clip used at that time was not compatible with magnetic resonance imaging, he underwent computed tomographic (CT) scan of the head and showed no space-occupying lesion in the orbit, paranasal sinuses, and brain. As an old lesion, the anterior temporal lobe on the left side had low-density area with metallic artifact on the left side of the skull base, indicative of metal clipping. In 4 weeks of observation from the initial visit, he showed complete recovery of visual acuity and became capable of abducting the left eye in full degrees. We also reviewed 8 patients with the combination of abducens nerve palsy and optic neuritis in the literature to reveal that the combination of signs did occur in mild meningitis with rare infectious diseases and in association with preceding herpes zoster in the first branch of the trigeminal nerve. The course of the present patient suggested that the combination of signs might be vaccine-associated.

Vogt-Koyanagi-Harada disease in pregnancy: Case report and review of 32 patients in the literature.

Key Clinical Message: Systemic prednisolone including steroid pulse therapy would be safe in 32 pregnant women, who developed Vogt-Koyanagi-Harada disease in the literature. Prednisolone administration would be shortened by monitoring of serous retinal detachment with optical coherence tomography. Abstract: A 30-year-old woman in 31 weeks of pregnancy with metamorphopsia and headache was diagnosed Vogt-Koyanagi-Harada disease. She underwent steroid pulse therapy and oral prednisolone 20 mg daily for 3 weeks until complete resolution of serous retinal detachment monitored by optical coherence tomography. Oral prednisolone was tapered and discontinued until uneventful delivery.

Decades of stability of conjunctival vascular malformations in two patients.

Key Clinical Message: Conjunctival hemangioma and lymphangioma are rare and their long-term follow-up description has been scarce. In our two patients, conjunctival vascular and lymphatic malformations remained stable in decades and could be observed without treatment. Abstract: A 65-year-old woman with diabetic retinopathy underwent glaucoma surgery to construct a filtering bleb adjacent to conjunctival hemangioma, and showed bleb function and stable hemangioma for a decade. A 1.5-year-old girl with right eye lid and cheek swelling by orbital to facial lymphangioma was followed for visual acuity development. Conjunctival lymphangioma was stable in 20 years.

Morphometric Analysis of the Eye by Magnetic Resonance Imaging in MGST2-Gene-Deficient Mice.

Strabismus, a neuro-ophthalmological condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione S-transferase 2 (MGST2) gene as one of the potential candidates for comitant strabismus susceptibility in a Japanese population. The MGST2 gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and it is also found in the protection against oxidative stress by decreasing the reactivity of oxidized lipids. To look for the roles of the MGST2 gene in the development, eye alignment, and overall morphology of the eye as the possible background of strabismus, MGST2 gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the MGST2 exon 2. The ocular morphology of the KO mice was analyzed through high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. The morphometric analyses showed that the height, width, and volume of the eyeballs in MGST2 KO homozygous mice were significantly greater than those of wild-type mice, indicating that the eyes of MGST2 KO homozygous mice were significantly enlarged. There were no significant differences in the axis length and axis angle. These morphological changes may potentially contribute to the development of a subgroup of strabismus.

Pericardial Effusion in Association With Periodontitis: Case Report and Review of 8 Patients in Literature.

Periodontal diseases are well-known background for infective endocarditis. Here, we show that pericardial effusion or pericarditis might have origin also in periodontal diseases. An 86-year-old man with well-controlled hypertension and diabetes mellitus developed asymptomatic increase in pericardial effusion. Two weeks previously, he took oral new quinolone antibiotics for a week because he had painful periodontitis along a dental bridge in the mandibular teeth on the right side and presented cheek swelling. The sputum was positive for Streptococcus species. He was healthy and had a small volume of pericardial effusion for the previous 5 years after drug-eluting coronary stents were inserted at the left anterior descending branch 10 years previously. The differential diagnoses listed for pericardial effusion were infection including tuberculosis, autoimmune diseases, and metastatic malignancy. Thoracic to pelvic computed tomographic scan demonstrated no mass lesions, except for pericardial effusion and a small volume of pleural effusion on the left side. Fluorodeoxyglucose positron emission tomography disclosed many spotty uptakes in the pericardial effusion. The patient denied pericardiocentesis, based on his evaluation of the risk of the procedure. He was thus discharged in several days and followed at outpatient clinic. He underwent dental treatment and pericardial effusion resolved completely in a month. He was healthy in 6 years until the last follow-up at the age of 92 years. We also reviewed 8 patients with pericarditis in association with periodontal diseases in the literature to reveal that periodontal diseases would be the background for developing infective pericarditis and also mediastinitis on some occasions.

Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis.

We have developed a photoelectric dye-coupled polyethylene film as a prototype of retinal prosthesis, which we named Okayama University-type retinal prosthesis. The purposes of this study are to conduct behavior tests to assess vision in Royal College of Surgeons (RCS) rats that underwent subretinal implantation of the dye-coupled film and to reveal retinal response to the dye-coupled film by immunohistochemistry. Polyethylene films were made of polyethylene powder at refined purity, and photoelectric dyes were coupled to the film surface at higher density compared with the prototype. Either dye-coupled film or dye-uncoupled plain film used as a control was implanted subretinally from a scleral incision in both eyes of an RCS rat at 6 weeks of the age. Behavior tests 2, 4, 6, and 8 weeks after implantation were conducted by observing head turning or body turning in the direction consistent with clockwise or counterclockwise rotation of a black-and-white-striped drum around a transparent cage housed with the rat. After the behavior tests at 8 weeks, rats' eyes were enucleated to confirm subretinal implantation of the films and processed for immunohistochemistry. In the behavior tests, the number of head turnings consistent with the direction of the drum rotation was significantly larger in RCS rats with dye-coupled- compared with plain-film implantation [P < 0.05, repeated-measure analysis of variance (ANOVA), n = 7]. The number of apoptotic neurons was significantly smaller in eyes with dye-coupled- compared with plain-film implantation (P < 0.05, Mann-Whitney U test, n = 6). In conclusion, subretinal implantation of photoelectric dye-coupled films restored vision in RCS rats and prevented the remaining retinal neurons from apoptosis.

Stereoscopic three-dimensional images of an anatomical dissection of the eyeball and orbit for educational purposes.

The purpose of this study was to develop a series of stereoscopic anatomical images of the eye and orbit for use in the curricula of medical schools and residency programs in ophthalmology and other specialties. Layer-by-layer dissection of the eyelid, eyeball, and orbit of a cadaver was performed by an ophthalmologist. A stereoscopic camera system was used to capture a series of anatomical views that were scanned in a panoramic three-dimensional manner around the center of the lid fissure. The images could be rotated 360 degrees in the frontal plane and the angle of views could be tilted up to 90 degrees along the anteroposterior axis perpendicular to the frontal plane around the 360 degrees. The skin, orbicularis oculi muscle, and upper and lower tarsus were sequentially observed. The upper and lower eyelids were removed to expose the bulbar conjunctiva and to insert three 25-gauge trocars for vitrectomy at the location of the pars plana. The cornea was cut at the limbus, and the lens with mature cataract was dislocated. The sclera was cut to observe the trocars from inside the eyeball. The sclera was further cut to visualize the superior oblique muscle with the trochlea and the inferior oblique muscle. The eyeball was dissected completely to observe the optic nerve and the ophthalmic artery. The thin bones of the medial and inferior orbital wall were cracked with a forceps to expose the ethmoid and maxillary sinus, respectively. In conclusion, the serial dissection images visualized aspects of the local anatomy specific to various procedures, including the levator muscle and tarsus for blepharoptosis surgery, 25-gauge trocars as viewed from inside the eye globe for vitrectomy, the oblique muscles for strabismus surgery, and the thin medial and inferior orbital bony walls for orbital bone fractures.

Postural stability changes during large vertical diplopia induced by prism wear in normal subjects.

To test the effect of double vision on postural stability, we measured postural stability by electric stabilometry before prism-wearing and immediately, 15, 30, and 60min after continuous prism-wearing with 6 prism diopters in total (a 3-prism-diopter prism placed with the base up in front of one eye and with the base down in front of the other eye) in 20 normal adult individuals with their eyes open or closed. Changes in stabilometric parameters in the time course of 60min were analyzed statistically by repeated-measure analysis of variance. When subjectsｾ eyes were closed, the total linear length (cm) and the unit-time length (cm/sec) of the sway path were significantly shortened during the 60-minute prism-wearing (p＜0.05). No significant change was noted in any stabilometric parameters obtained with the eyes open during the time course. In conclusion, postural stability did not change with the eyes open in the condition of large vertical diplopia, induced by prism-wearing for 60min, while the stability became better when measured with the eyes closed. A postural control mechanism other than that derived from visual input might be reinforced under abnormal visual input such as non-fusionable diplopia.

A simple method for culturing Acanthamoeba from soft contact lens at a clinical laboratory of a hospital: Case report of Acanthamoeba keratitis.

Key Clinical Message: A simple culturing method for Acanthamoeba available at a clinical laboratory is a key for making timely diagnosis and starting treatment with topical 0.02% chlorhexidine gluconate eye drops, together with 0.1% miconazole or fluconazole eye drops. Abstract: A 19-year-old woman with pain and injection in the right eye showed spotty corneal infiltration and radiating linear opacity. Suspicious of Acanthamoeba keratitis, corneal scraping, and the soft contact lens were sent to in-house clinical laboratory to culture successfully Acanthamoeba on Sabouraud dextrose agar plate painted with heat-treated dead bacilli.

Resection of Orbital Myxoma With Magnetic Resonance Imaging Evidence of Ethmoid Sinus Origin: Case Report and Review of 20 Patients in the Literature.

A 41-year-old woman showed a palpable mass at the superonasal orbital edge on the right side. Magnetic resonance imaging demonstrated a lobulated fluid-containing tubular mass which extended anteriorly to posteriorly along the medial orbital wall, nasal to the eyeball. She was followed once a year for 8 years until the age of 49 years when she decided to undergo surgical resection because of the enlarged mass. The lobulated large mass was resected and the pathology showed sparsely distributed spindle cells, positive for CD34, in alcian blue-positive mucous substances, indicative of myxoma. Postoperative magnetic resonance imaging showed residual lobulated tubular mass along the optic nerve on the medial side and superior to the eyeball. The residual orbital mass showed stable structure with more evident connection with the ethmoid sinus lesion, suggestive of the ethmoid origin, in 12 years until the age of 61 years. In the review of 20 patients with orbital myxomas in the literature, in addition to this case, roughly classified locations in the orbit were retrobulbar in 8 patients, on the lateral side of the orbit in 4, on the superior side in 6, on the medial side in 1 (this patient), and in the orbit with no specific description in 2. In pathological examinations, immunohistochemistry was not done in 8 patients, done but all negative in 2, and positive in 11 patients: nerve sheath myxoma was diagnosed in 3 patients based on positive S100 staining. Orbital myxoma is rare but considered in differential diagnosis of orbital masses.

Bilateral Optic Neuritis and Hypophysitis With Diabetes Insipidus 1 Month After COVID-19 mRNA Vaccine: Case Report and Literature Review.

Either optic neuritis (neuropathy) or hypopituitarism has been known to occur separately after COVID-19 vaccination. In this report, we describe the rare combination of hypophysitis and optic neuritis which occurred after COVID-19 vaccination. A 74-year-old woman began to have thirst, polydipsia, and polyuria, and was diagnosed as central diabetes insipidus 1 month after the fourth COVID-19 mRNA vaccine. Head magnetic resonance imaging (MRI) disclosed the thickened pituitary stalk and enlarged pituitary gland with high contrast enhancement as well as the absence of high-intensity signals in the posterior pituitary lobe on the T1-weighted image, leading to the diagnosis of lymphocytic hypophysitis. She was well with desmopressin nasal spray until further 2 months later, when she developed bilateral optic neuritis, together with gait disturbance, intention tremor of the upper extremities, urinary retention, constipation, abnormal sensation in the distal part of the lower extremities, and moderate hemiplegia on the left side. Autoantibodies, including anti-aquaporin 4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG), were all negative. She showed multifocal spinal cord lesions on MRI and oligoclonal bands in the cerebrospinal fluid obtained by spinal tap, and so underwent steroid pulse therapy with methylprednisolone in the tentative diagnosis of multiple sclerosis, resulting in visual acuity recovery and alleviation of neurological symptoms. In the literature review, the combination of optic neuritis and hypophysitis, mostly with diabetes insipidus, was reported in 15 patients as case reports before the years of COVID-19 pandemic. The COVID-19 vaccination would trigger the onset of hypophysitis and optic neuritis in this patient.