北村 裕太

Although ocular complications following COVID-19 vaccination have been reported, particularly retinal vascular occlusion and uveitis, their definitive causal relationships remain uncertain. This report presents a case of central retinal artery occlusion (CRAO) with paracentral acute middle maculopathy (PAMM) developed one day after receiving Pfizer COVID-19 vaccine, with a favorable outcome. The patient experienced sudden vision loss in her left eye, and her vision dropped to hand motion the day after vaccination. The initial examination suggested CRAO, but optical coherence tomography (OCT) revealed PAMM. We administered intravenous d-mannitol and acetazolamide and performed ocular massage. Two days later, her corrected visual acuity improved to 0.4, and further improvement to 1.2 occurred after 16 days. To the best of our knowledge, no reports have documented CRAO with PAMM following mRNA COVID-19 vaccination. The relationship between COVID-19 vaccination and retinal vascular occlusion remains unknown, highlighting the need for further research.

Although the advent of molecular-targeted drugs has improved the prognosis of various cancers, the long-term prognosis and side effects as the first-line therapy for metastatic choroidal tumors remain unclear. We describe a case in which the first-line therapy of osimertinib has shown long-term successful and minimum side effect responses for metastatic choroidal tumors in a patient with advanced-stage lung cancer. The patient was a 62-year-old man who complained of foggy vision and visual field defects in his left eye for 1 month. When he visited his local doctor, a serous retinal detachment was noted in the left eye, and he was referred to our hospital for further examination. The patient had no history of systemic disease. A fundus examination of his left eye showed a slightly elevated choroidal lesion along with the superior retinal vascular arcade. Optical coherence tomography showed a serous retinal detachment around the lesion. Fluorescein angiography showed that the site of the lesion had spotty and mottled hyperfluorescence in the early phase and ring hypofluorescence in the late phase. We suspected a metastatic choroidal tumor and performed a whole-body computed tomography scan, which indicated lung cancer and metastasis to the left iliac bone. The patient was referred to the department of respiratory medicine of our hospital, and after a thorough examination, a diagnosis of lung adenocarcinoma (stage IV-B, epidermal growth factor receptor [EGFR] gene mutation positive) was made. Treatment with osimertinib was initiated, and shrinkage of the primary tumor was observed. The elevated choroidal lesion and serous retinal detachment resolved after 2 months of treatment, and no recurrence was observed during the 20 months of treatment. The use of osimertinib as primary treatment for EGFR mutation-positive lung cancer was found to significantly reduce the size of metastatic choroidal tumors and to have a relatively long-lasting antitumor effect without serious ocular complications.

Activation of neurotrophic factor signaling is a promising therapy for neurodegeneration. However, the transient nature of ligand-dependent activation limits its effectiveness. In this study, we solved this problem by inventing a system that forces membrane localization of the intracellular domain of tropomyosin receptor kinase B (iTrkB), which results in constitutive activation without ligands. Our system overcomes the small size limitation of the genome packaging in adeno-associated virus (AAV) and allows high expression of the transgene. Using AAV-mediated gene therapy in the eyes, we demonstrate that iTrkB expression enhances neuroprotection in mouse models of glaucoma and stimulates robust axon regeneration after optic nerve injury. In addition, iTrkB expression in the retina was also effective in an optic tract transection model, in which the injury site is near the superior colliculus. Regenerating axons successfully formed pathways to their brain targets, resulting in partial recovery of visual behavior. Our system may also be applicable to other trophic factor signaling pathways and lead to a significant advance in the field of gene therapy for neurotrauma and neurodegenerative disorders, including glaucoma.

PURPOSE: Blunt ocular trauma rarely results in optic nerve avulsion. Here, we report a case of incomplete optic nerve avulsion caused by the impact of a badminton shuttlecock. OBSERVATIONS: The patient was a 16-year-old healthy male. A badminton shuttlecock hit his right eye from a short distance. On his first visit to the local eye clinic, his visual acuity in the right eye was hand motion. About 4-mm hyphema in height was observed in the right eye. Three days after the injury, visual acuity improved to 20/50, but the intraocular pressure increased to 40 mmHg; hence, intraocular pressure (IOP)-lowering medication was initiated. Five days after the injury, although hyphema had decreased gradually, he noticed a worsening of vision and was referred to our department. In his right eye, visual acuity was reduced to finger-counting, IOP was 38 mmHg. Slit-lamp examination of the right eye revealed a dilated pupil, hyphema, and angle recession. Fundus examination revealed dilation of the central retinal vein and edematous changes around the optic nerve head. Optical coherence tomography showed a very deep depression of the optic nerve head and partial rupture of the optic nerve axons. B-mode ultrasonography showed hypolucency just posterior to the optic nerve head. Goldmann perimetry revealed a central visual field defect in the right eye. Computed tomography showed no signs of optic canal fracture. These findings suggest that incomplete optic nerve avulsion had occurred. We performed IOP-lowering and anti-inflammatory therapy. After treatment, visual acuity was restored to 20/50, and the deep depression of the optic nerve head recovered to an almost normal range. CONCLUSION AND IMPORTANCE: It was assumed that the impact of the badminton shuttlecock caused irreversible changes in the optic nerve head, but the visual function partially improved with IOP-lowering and anti-inflammatory therapy. Because eye injury in badminton can cause severe damage to visual function, every badminton player needs to wear an appropriate eye shield, and rules or guidelines to prevent untoward accidents are needed in badminton.

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9-/-), DOCK10 (DOCK10-/-), or DOCK11 (DOCK11-/-) had been deleted and examined the phenotypic effects of these gene deletions in MOG35-55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10-/- mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10-/- and DOCK11-/- mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10-/- mice. No apparent phenotype was observed for DOCK9-/- mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10-/- mice. Up-regulation of C-C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10-/- astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.

To determine the effectiveness of a single or a combination of topical neurotrophic factors (NFs) in protecting retinal ganglion cells (RGCs) in the rat optic nerve crush (ONC) model, the left ONC was performed to induce the death of the RGCs in adult Sprague-Dawley rats. The NFs studied were tauroursodeoxycholic acid (TUDCA), citicoline, neurotrophin-4 (NT-4), combined TUDCA/citicoline (Doublet-1), combined TUDCA/NT-4 (Doublet-2), combined TUDCA/citicoline/NT-4 (Triplet), and PBS. After 2 weeks, the number of RGCs was determined by Brn3a immunostaining. The optic nerves were immunostained for anti-Growth Associated Protein-43(GAP-43) and -200kD neurofilament heavy antibody to study optic nerve regeneration. Two weeks after the ONC, the densities of RGCs in all treated eyes were significantly higher than that of the PBS treated eyes. In the Triplet group, the number of RGC axons after ONC was significantly higher than that in all of the single treatment groups and the number of TUNEL positive cells was significantly reduced and the number of GAP-43 immunopositive axons was significantly greater than those in the PBS group. Neovascularization was observed only in the Doublet-1 group. We conclude that the combination of the three NFs was the most effective way to protect RGCs after the ONC.

A 17-year-old male presented with acute bilateral paracentral scotomata and blurred vision. Funduscopic examination showed bilateral macular serous retinal detachment and yellow-white placoid lesions at the level of retinal pigment epithelium. OCT study showed typical VKH disease findings with marked choroidal thickening and macular serous retinal detachment partly with subretinal septa in both eyes. FA demonstrated hypofluorescence at the placoid lesions in the early phase and hyperfluorescence in the late phase. Laboratory investigation showed negative result for HLA-DR4 serotype and the patient's cerebrospinal fluid test values were within normal range. We made the diagnosis of APMPPE from these results. At 2-month follow-up without the use of corticosteroids, OCT reexamination showed complete amelioration of subretinal fluid in both eyes. Patchy pigmentary lesions also resolved clinically with partial chorioretinal scars. The results in this case suggested OCT findings in APMPPE patients could be similar to characteristic features usually found in acute VKH disease. We recommend comprehensive assessments such as FA, cerebral spinal fluid analysis, and HLA typing which help in leading proper diagnosis.

The purpose of this study is to identify the risk factors for a recurrence or persistence of diabetic macular oedema (DME) after a sub-Tenon's capsule triamcinolone acetonide (STTA) injection. The medical records of 124 patients (124 eyes) treated by STTA were reviewed. The age, sex, HbA1c level, best-corrected visual acuity, central macular thickness, insulin use, pioglitazone use, systemic hypertension, serous retinal detachment, proteinuria, panretinal photocoagulation, microaneurysm photocoagulation (MAPC), subthreshold micropulse diode laser photocoagulation (SMDLP), cataract surgery, and history of vitrectomy were examined by logistic regression analysis. Procedures of MAPC and SMDLP were significantly associated with DME treated with STTA (P = 0.0315, P = 0.04, resp.). However, a history of vitrectomy was found to have significantly fewer recurrences or persistent DME after STTA (P = 0.0464). In conclusion, patients who required combined MAPC or SMDLP with a STTA injection had significantly higher refractoriness to STTA, but postvitrectomy may prevent the recurrence or persistence of DME after STTA injection.

Fatty acyl-AMP ligases (FAALs) activate fatty acids as acyladenylates, and subsequently catalyze their transfer onto the acyl carrier proteins (ACPs) of polyketide synthases (PKSs) or nonribosomal peptide synthetases to produce lipidic metabolites. Myxococcus xanthus contains a polyketide biosynthesis gene cluster in which putative FAAL (FtpD) and ACP (FtpC) genes are located close to a type III PKS (FtpA) gene. Here we describe the characterization of these three proteins in vitro. FtpD adenylated stearic acid and produced stearoyl-FtpC. The stearoyl moiety was then transferred to FtpA. When extender substrates (malonyl-CoA and methylmalonyl-CoA) were added to the reaction, the alkylresorcinol 5-heptadecyl-4-methyl-benzene-1,3-diol was synthesized. Further in vitro analysis indicated that FtpA produces an alkylresorcylic acid as the direct product, and that this decarboxylates to alkylresorcinol nonenzymatically. This is the first report of a FAAL supplying a long-chain fatty acyl-ACP starter substrate to a type III PKS.