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We report a case of bilateral frosted branch angiitis (FBA) following mRNA-1273 COVID-19 vaccination. A 79-year-old male was referred to our hospital with a sudden onset of blurred vision in the right eye, which occurred during his return home after receiving the third dose of a messenger RNA (mRNA) COVID-19 vaccine. Fundoscopy revealed severe retinal vasculitis with sheathing of the artery and vein in the right eye more so than in the left eye, suggestive of bilateral FBA. Optical coherence tomography showed significant macular edema and serous retinal detachment in the right eye. Polymerase chain reaction assay detected Epstein-Barr virus (EBV) in the aqueous humor, and antibody against the EBV viral capsid antigen was positive for IgM. The next day, best-corrected visual acuity (BCVA) worsened to 0.08 due to macular edema in the left eye. After 2 courses of pulse steroid therapy and intravenous infusion of acyclovir, macular edema had disappeared and sheathing of retinal vessels was improving. At 5 months after the mRNA COVID-19 vaccination, BCVA was maintained 0.15 in the right eye and 0.7 in the left eye. Severe uveitis, such as FBA, can occur after mRNA COVID-19 vaccination.

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Purpose: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare form of ocular syphilis. However, its pathophysiology is not fully understood. Laser speckle flowgraphy (LSFG) can facilitate the non-invasive evaluation of blood flow and allow investigations into the effects of treatments in various ocular diseases. We report a case of ASPPC that presented with symptoms only in the right eye but showed bilateral disease in LSFG. Observations: A 54-year-old man presented with decreased vision and visual field defects in the right eye 2 days prior to the initial visit. Fundoscopy images showed a typical yellowish placoid lesion in the macular area, and optical coherence tomography showed disruption of the outer retinal layers and nodular appearance of the retinal pigment epithelium. Fluorescence angiography showed excessive leakage of the placoid lesion characterized by hypofluorescent dots in the inner area ("leopard spotting"). The patient was diagnosed with unilateral ASPPC based on multiple imaging and serological tests. Penicillin was administered for 2 weeks, and the patient showed improvement in symptoms and restoration of the retinal structure. The mean blur rate of the right/left eye was 2.1/5.9 arbitrary units (AU) before treatment and increased to 4.5/9.3 AU 6 months after treatment. Conclusions and importance: Despite the absence of typical imaging signs and symptoms in the left eye, both eyes may have been affected with different degrees of severity. Thus, LSFG may facilitate the evaluation of treatment effects and the prediction of ocular inflammatory diseases in the early stages.

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Introduction: Allergic conjunctivitis is treated with oral anti-allergy agents or topical eye drops, but the response is often incomplete, and symptoms persist. We considered that topical treatment with an antihistamine ointment (diphenhydramine-Restamin Cream®) on the eyelids could be effective as supplemental therapy. This study investigates the efficacy and safety of Restamin Cream® for allergic conjunctivitis. Methods: In patients with allergic conjunctivitis, Restamin Cream® was applied to both eyelids twice a day for 2 weeks. There was a 2-week observation period before treatment and a 2-week washout period after treatment. Patients recorded symptoms (eye itching and watering) on a visual analogue scale for the entire 6-week period. Assessment of quality of life, evaluation of conjunctivitis, and measurement of visual acuity and intraocular pressure were conducted at the start of observation, at initiation of treatment, at completion of treatment, and at the end of washout. Results: 7 patients were enrolled; 5 completed the study and 2 discontinued due to adverse reactions. The quality of life score and objective ocular findings improved in all 5 patients. Visual analogue scale scores for itching and watering also improved significantly in 3 and 2 patients, respectively. Adverse reactions included local skin irritation in 3/7 patients, and transient blurred vision and eye pain in 1 patient each. There were no changes of visual acuity or intraocular pressure. Conclusions: Application of diphenhydramine ointment to the eyelids was effective for allergic conjunctivitis (AU)

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BACKGROUND: We investigated the presence of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), proinflammatory cytokines, and soluble cytokine receptors in the tear fluid of patients with noninfectious corneal ulcers in the peripheral cornea. METHODS: The subjects were 20 eyes of 17 patients with peripheral noninfectious corneal ulcers and 20 eyes of 20 volunteers. Tear samples were taken by the Schirmer test I method and the presence of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, and MMP-13) and TIMPs (TIMP-1, TIMP-2, and TIMP-4) were investigated using an MMP antibody array system. The concentrations of proinflammatory cytokines {IL-1ß, IL-6, and TNF-α (tumor necrosis factor-alpha)} and soluble cytokine receptors {soluble (s) IL-1R1, sIL-1R2, sIL-2Rα, sIL-4R, sIL-6R, sTNFR1, sTNFR2, s-vascular endothelial growth factor receptor (VEGFR) 1, sVEGFR2, sVEGFR3, and sgp130} were determined using the multiplex bead immunoassay system. RESULTS: The concentrations of MMP-8 and MMP-9 were significantly up-regulated in the tear fluid of the ulcer patients, whereas TIMPs concentrations did not change. The concentrations of IL-1ß, IL-6, sIL-1R2, sIL-6R, sTNFR1, and sTNFR2 were up-regulated in the ulcer patients, whereas sgp130 and sVEGFR1 concentrations significantly decreased. CONCLUSIONS: The presence of some MMPs increased significantly in the patients with peripheral noninfectious corneal ulcers, whereas the presence of TIMPs remained unchanged. Although some proinflammatory cytokines were up-regulated, their antagonists, soluble cytokine receptors, were also up-regulated. It is thus possible that the up-regulation of MMPs disrupts the balance between the MMPs and TIMPs and that this balance may play a pivotal role in the pathophysiology of corneal ulceration.

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PURPOSE: We evaluated an anti-inflammatory effect of TNF receptor 1 (TNFR1) ectodomain shedding in ocular surface. METHODS: Human corneal epithelial cell (HCEC) was first pretreated by TNF-α. Ectodomain shedding was stimulated by uridine triphosphate (UTP) or peptidoglycan (PGN), with or without shedding inhibition using TNF-α processing inhibitor (TAPI). The phosphorylation of the NF-κB inhibitory protein, IκB, was assessed by Western blotting and concentrations of soluble TNFR1 (sTNFR1) in culture medium were analyzed by ELISA. Tear fluid from patients with Sjögren syndrome and graft-versus-host disease (GVHD) was collected and analyzed by ELISA for sTNFR1 concentration. Five dry eye patients underwent topical treatment using diquafosol sodium eye drops, a purinergic P2Y2 receptor agonist, and the tear fluid of the patients was sampled before and 4 weeks after the treatment for sTNFR1 ELISA. RESULTS: Phosphorylation of IκB was diminished by adding UTP or PGN, and this down-regulation of IκB phosphorylation was reversed by adding TAPI. In HCEC medium, sTNFR1 release was increased significantly by adding UTP or PGN, and inhibited significantly by adding TAPI. In the tears of the patients with Sjögren syndrome and GVHD, sTNFR1 expression was upregulated. In the tears of the patients with short breakup time (BUT) dry eye, sTNFR1 concentrations (ng/mL) in the tears were 1.30 ± 0.58 ng/mL for the pretreatment baseline, and 1.64 ± 0.70 after treatment, statistically significantly higher than those for the pretreatment (P < 0.01). CONCLUSIONS: Ectodomain shedding of sTNFR1 blocked TNF-α-induced intracellular signaling in corneal epithelium. The upregulation of sTNFR1 in inflamed ocular surfaces suggests an anti-inflammatory role of sTNFR1 ectodomain shedding at the ocular surface.

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A surprising shortage of information surrounds the mechanisms by which bone marrow stromal cells (BMSC) restore lost neurologic functions when transplanted into the damaged central nervous system. In the present study, we sought to elucidate whether BMSCs express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into injured spinal cord. To examine this, we harvested and cultured rat femoral BMSCs. We then subjected Sprague-Dawley rats to thoracic spinal cord injury (SCI) with a pneumatic impact device. Fluorescence-labeled BMSCs (n = 7) were transplanted stereotactically or the vehicle in which these cells were cultured (n = 4) was introduced stereotactically into the rostral site of SCI at 7 days after injury. We evaluated GABA receptor function by measuring the binding potential for 125I-iomazenil (125I-IMZ) through in vitro autoradiography at 4 weeks after BMSC transplantation and simultaneously examined the fate of the transplanted BMSCs by immunocytochemistry. We found that the transplanted BMSC migrated toward the core of the injury and were densely distributed in the marginal region at 4 weeks after transplantation. BMSC transplantation significantly increased the binding potential for 125I-IMZ (p = 0.0376) and increased the number of GABA receptor-positive cells (p = 0.0077) in the marginal region of the injury site. Some of the transplanted BMSCs were positive for microtubule-associated protein-2 and the alpha1 subunit of GABA(A) receptor in the region of injury. These findings suggest that BMSCs have the potential to support the survival of neurons in the marginal region of SCI and can partly differentiate into neurons, regenerating spinal cord tissue at the site of injury.

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UNLABELLED: Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.

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The purpose of our study is to evaluate the effect of a single drop of latanoprost on the intraocular pressure and blood-aqueous barrier permeability in 8 patients with uveitis. The degree of inflammation was determined by the intensity of aqueous flare measured with a laser flare cell meter every 2 hours from 11:00 to 17:00 hours for 2 days. Intraocular pressure was measured at 11:00 and 17:00 hours with a Goldmann applanation tonometer on both days. Patients were given one drop of 0.005% latanoprost at 11:00 hours on day 2 and results were compared with day 1 when latanoprost was not administered. There was no significant difference in the intensity of aqueous flare or intraocular pressure between day 1 and day 2. A single drop of latanoprost had little effect on intraocular pressure and aqueous flare intensity in patients with uveitis.

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