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.

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.

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.

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.

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.

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.

Nontuberculous mycobacterial abscess of lacrimal sac and eyelid debridement: Case report.

Key Clinical Message: It is important to stain acid-fact bacilli on the smear of abscess puncture in addition to Gram stain to detect nontuberculous and tuberculous mycobacteria in the early phase since both can cause rare and challenging extrapulmonary manifestations. Abstract: A 56-year-old otherwise healthy woman developed abscess from dacryocystitis in the right lower eyelid. The smear of puncture fluid showed acid-fast bacilli and Mycobacterium abscessus was identified after a month. The early start of clarithromycin/ethambutol was switched to clarithromycin/levofloxacin. Debridement specimen after 7-month treatment showed granulomatous tissue with no bacilli.

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 Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature.

A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

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.

ANCA-associated vasculitis with scleritis, corneal melt, and perforation rescued by rituximab: Case report and literature review.

Key Clinical Message: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, specifically with myeloperoxidase (MPO)-ANCA, would have a risk for developing corneal melt and perforation abruptly in a short period. It is desirable to have a team of collaboration of rheumatologists and other specialties. Abstract: An 80-year old man who had been diagnosed 5.5 years previously as ANCA-associated vasculitis by temporal artery biopsy developed corneal melt and perforation with scleritis in both eyes. He underwent successful cataract surgery and retained ambulatory vision with the aid of intravenous rituximab. Two additional patients with similar manifestations were found in the literature.

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.

Are Prophylactic Systemic Antibiotics Required in Patients with Cataract Surgery at Local Anesthesia?

The reduced use of antimicrobial drugs has been recommended worldwide, according to the global action for antimicrobial resistance published in 2015 by the World Health Organization. In this study, we retrospectively reviewed the incidence of surgical site infection in consecutive patients with cataract surgeries at a single hospital in the 6-year process when prophylactic systemic antibiotics were reduced in a step-by-step manner. The entire study period from 2016 to 2022 was divided into five stages, based on the use of systemic antibiotics. In stage 1 with 649 cataract surgeries, an intravenous drip infusion of cefazolin 1 g was given at surgery, followed by oral cefdinir 100 mg in the evening on surgery day and three times for two postoperative days. In stage 2 with 541 cataract surgeries, oral cefdinir 100 mg was given in the late morning before surgery, in the evening, and three times (300 mg in total) for two postoperative days. In stage 3 with 103 cataract surgeries, oral levofloxacin 500 mg was given in the late morning before surgery and once in the morning for two postoperative days. In stage 4 with 545 cataract surgeries, oral levofloxacin 500 mg was given only in the late morning before surgery. In stage 5 with 311 cataract surgeries, no systemic antibiotics were given. As common procedures in all stages, moxifloxacin eye drops were given four times daily as topical antibiotics in the 3 days before surgery and about 2 weeks after surgery. At surgery, the ocular surface was frequently irrigated with saline-diluted povidone iodine at 0.5% working concentration. No postoperative infection was recorded in any stage. This study showed neither harm nor risk in reduced use and, consequently, no use of prophylactic systemic antibiotics in cataract surgery as far as local precautionary measures were secured.

Temporal association of vitreous hemorrhage and hypertension after COVID-19 mRNA vaccines.

Vitreous hemorrhage as common eye presentation and hypertension as common systemic presentation are difficult to designate whether they are coincidental or causal in terms of adverse events of COVID-19 vaccinations. Temporal association of hypertension and vitreous hemorrhage was noted in a patient repeatedly after the second and third COVID-19 vaccinations.

Diffuse large B-cell lymphoma in the course of systemic sarcoidosis: A case report and review of 30 Japanese patients with sarcoidosis-lymphoma syndrome.

We report a patient with sarcoidosis who developed diffuse large B-cell lymphoma. A 71-year-old woman with persistent cough was diagnosed pathologically with sarcoidosis by resection of the right upper lung lobe with a nodule after an unsuccessful attempt of transbronchial needle aspiration for mediastinal lymphadenopathy. She was referred for an eye examination and found to have spotty retinal degeneration on the lower fundi of both eyes, together with residual macular edema and vitreous opacity in the left eye. At 76 years, she underwent cataract surgery and vitrectomy to gain a visual acuity of 0.6 in the left eye. At 77 years, she developed a cough and fever, and showed leukopenia and thrombocytopenia. Computed tomography showed multiple small nodular lesions in both lungs, and bilateral hilar, mediastinal, and hepatic lymphadenopathy. Fluorodeoxyglucose positron emission tomography demonstrated high uptake in the liver, spleen, pancreatic head, and lymph nodes. Bone marrow biopsy was intact, but liver biopsy revealed anomalous large lymphoid cells in the sinusoids which were positive for CD20 and showed a high Ki-67 index, leading to the diagnosis of diffuse large B-cell lymphoma. Chemotherapy with 8 courses of THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with rituximab, followed by intrathecal injection of methotrexate, cytarabine, and dexamethasone, resulted in complete remission. She maintained complete remission for 10 years until 88 years old at present. The literature review found 30 patients, including this case, who developed lymphoma in the course of sarcoidosis. A novel pathological diagnosis is required in the setting of acute symptomatic changes and novel lesions on imaging in patients with sarcoidosis.

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.

Photorefraction with Spot Vision Screener versus Visual Acuity Testing as Community-Based Preschool Vision Screening at the Age of 3.5 Years in Japan.

Nationwide in Japan, a community-based vision-screening program in 3.5-year-old children is conducted in three steps: questionnaires and home visual acuity testing as the primary screening; visual acuity testing by nurses and pediatricians' inspection in community health centers as the secondary screening; and examinations by ophthalmologists as the tertiary screening. In this study, we introduced photorefraction with a Spot vision screener in addition to visual acuity testing to answer the clinical question of whether photorefraction could better detect eye diseases and potentially replace visual acuity testing. Photorefraction was performed on 813 consecutive 3.5-year-old children in a center. The children were sent to tertiary examinations, which were based on the Spot vision screener standard, in addition to the visual acuity testing standard: failure in either eye to pass 0.5 visual acuity in a center. A notice to visit ophthalmologists was issued for 95 children (11%), and documents with the diagnosis were sent back to the Heath Office for 76 children (80%). The rate of children with anisometropic or ametropic amblyopia or accommodative esotropia as treatment-requiring diseases was highest in cases of no pass at both standards (10/15 = 66%), and higher in cases of no pass only at the Spot vision screener standard (13/45 = 28%), compared with cases of no pass only at the visual acuity testing standard (6/33 = 18%, p = 0.0031). Photorefraction, in addition to visual acuity testing and inspection led to additional eye diseases detection at 3.5 years. Visual acuity testing at home would not be omitted in the introduction of photorefraction.

COVID-19 mRNA Vaccine-Associated Uveitis Leading to Diagnosis of Sarcoidosis: Case Report and Review of Literature.

A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.