Yusuke Saeki

Histological evidence of redox system breakdown caused by superoxide dismutase 1 (SOD1) aggregation is common to SOD1-mutated motor neurons in humans and animal models

Living cells produce reactive oxygen species (ROSs). To protect themselves from these ROSs, the cells have developed both an antioxidant system containing superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2, thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts superoxide radicals into hydrogen peroxide (H2O2), and H2O2 is then converted into harmless water (H2O) and oxygen (O2) by Prx2 and GPx1 that directly regulate the redox system. To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala→Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1: the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident. Based on the fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1.

Survey of Japanese ophthalmic surgeons regarding perioperative disinfection and antibiotic prophylaxis in cataract surgery

Purpose To elucidate Japanese trends for perioperative disinfection and antibiotic selection during cataract surgeries. Methods Perioperative iodine use and antibiotic prophylaxis for cataract surgery were surveyed in eight regions in Japan by mail or through interviews from February 1 to March 1, 2014. Results We surveyed 572 surgeons, of whom 386 (67%) responded. Most of the surgeons (94%) used iodine compounds before surgery for periocular skin disinfection (povidone–iodine [PI]: 79%; polyvinyl alcohol-iodine [PAI]: 15%) or conjunctival disinfection (85%; PI: 36%; PAI: 49%). Preoperative conjunctival iodine was primarily used as an eye wash (irrigation: 95%) and less often as an eye drop (5%). It was determined that 31% of surgeons waited 30 seconds or more between periocular disinfection and conjunctival disinfection. During surgery, 14% of surgeons used iodine several times, including immediately before intraocular lens insertion, and 7% used the Shimada technique (repeated iodine irrigation). Preoperative antibiotic eye drops were used by 99% of surgeons, and antibiotics were added to the irrigation bottle by 22%. The surgeons reported use of subconjunctival antibiotic injections (23%), antibiotic ointments (79%), and intracameral antibiotics (7%: 22 moxifloxacin; 6 levofloxacin). All surgeons prescribed postoperative eye drops, with 10% initiating the drops on the day of surgery. Conclusion Iodine compounds are commonly used preoperatively, but few institutions use iodine compounds intraoperatively, particularly with repeated application. The selection of antibiotic administration and disinfection technique has to be at the surgeon’s discretion. However, intracameral antibiotic and intraoperative iodine compound use are techniques that should be widely recognized.

A Japanese Survey of Perioperative Antibiotic Prophylaxis in Cataract Surgery.

PurposeThe objective of this study was to identify trends in the use of perioperative antibiotic prophylaxis in cataract surgery in Japan. DesignThis was a national survey by mail or interview. MethodsThe use of perioperative antibiotic prophylaxis in cataract surgery was evaluated by conducting a survey in 6 regions within Japan from October 1, 2011, to March 1, 2012. ResultsResponses were received from 285 (75%) of the 387 surgeons who were surveyed. The results revealed that 89% (255/285) administered ophthalmic antibiotic ointment. Forty-seven percent (133/285) used antibiotics in forms other than ophthalmic ointments within 6 hours after surgery, 7% (19/285) used eyedrops, 24% (67/285) used antibiotics via an irrigation bottle, 1% (2/285) used intracameral injections, and 24% (69/285) used subconjunctival injections. ConclusionsAlthough poor intraocular penetration of ophthalmic ointments has been reported, ophthalmic ointments are widely used. The fact that antibiotics should ideally be administered within 6 hours after surgery is not widely recognized. However, intracameral injection, which achieves much higher antibiotic concentration in the anterior chamber than other methods, is a technique that should be widely acknowledged.

Clinical and virological analysis of epidemic keratoconjunctivitis caused by adenovirus type 54 in a regional ophthalmic clinic in Kyushu, Japan

Background Human adenovirus type 54 (HAdV-54) is a novel type of adenovirus that belongs to species D and has thus far been detected only in Japan in patients with epidemic keratoconjunctivitis (EKC). There was a large nationwide outbreak of HAdV-54 EKC from 2015 to 2016 in Japan. The clinical characteristics of an outbreak of HAdV-54 conjunctivitis treated in a regional ophthalmic clinic in Fukuoka, Japan, in 2016 were analyzed. Patients and methods A consecutive series of 55 cases diagnosed clinically as EKC confirmed by HAdV-54 detection from conjunctival scrapings by polymerase chain reaction (PCR) method between 17 June 2016 and 29 August 2016 were enrolled. Viral DNA copies were counted by real-time PCR method. The clinical findings were recorded at the first visit to the clinic and evaluated. Results In the analysis of the relationship between mean clinical score groups and several factors, such as days after onset, sex, HAdV DNA number on a logarithmic scale, and age, most factors did not show a significant difference in clinical score between groups. However, mean clinical score of cases aged <23 years was significantly higher than that of cases aged ≥23 years (P<0.01). The correlation coefficient between DNA copies on a logarithmic scale and clinical score was 0.280, and a significant correlation was observed (P<0.05). Multiple subepithelial corneal infiltrates (MSI) were observed in 24 out of 31 cases (77%). Conclusion These results suggested that the clinical features in the early phase of HAdV-54 keratoconjunctivitis were milder but the rate of MSI observed in the late phase was higher than those in previous epidemics of several HAdV types. The significant difference in clinical severity between age groups might be a virological characteristic of HAdV-54.

A case of type 54 human mastadenovirus keratoconjunctivitis causing severe broad epithelial defect ten years after LASIK surgery

Epidemic keratoconjunctivitis (EKC) is a keratitis caused by the highly infectious human mastadenovirus (HAdV) (1,2). Here, we report a case of EKC caused by HAdV type 54 (1–3) and resulting in extensive corneal epithelial defect. The case occurred 10 years after laserassisted in situ keratomileusis (LASIK) surgery. A 36-year-old man presented with pain in his right eye 10 years following uncomplicated LASIK procedures for myopia in both eyes at another hospital. All family members had contracted EKC from the man’s 2-yearold son, who was diagnosed by a local ophthalmologist using a rapid diagnostic test in early August 2015. On August 11 (day 1), the man noticed pain in his right eye. He visited a local ophthalmology clinic and was prescribed 0.5% levofloxacin and 0.1% fluorometholone eye drops. The pain gradually worsened, and an ocular infection was evident in his left eye on day 6; the man presented at Fukuoka University Hospital on day 7. On examination, the man had difficulty opening the right eye due to edema of the eyelid. The right eye had a severe ocular infection, and a conjunctival pseudomembrane was observed (Fig. 1A). The right cornea had a circular epithelial defect coinciding with the LASIK flap edge (Fig. 1B, C). The left eye also had an ocular infection, but no epithelial defect or subepithelial opacification was observed. Visual acuity was 20/20 (uncorrectable) in the right and 20/25 (corrected) in the left eye. Conjunctival scrapings of the right and left eyes were positive and negative, respectively, on immunochromatography testing (Capilia Adeno Eye, Tauns Laboratories Inc., Izunokuni, Japan). HAdV-54 was detected in the conjunctival scrapings of both eyes, using the method reported previously that is based on polymerase chain reaction amplification, sequencing, and phylogenetic analysis (4). Based on the clinical course, slit lamp examination findings, and laboratory test results, we diagnosed the man’s condition as EKC. The conjunctival pseudomembrane was removed, and the patient was treated with 0.1% betamethasone and 0.3% gatifloxacin eye drops.

Clinical and allergological analysis of ocular manifestations of sick building syndrome

Purpose The disease concept of sick building syndrome (SBS) is still unclear. Ocular mucous membrane irritation is one of the major symptoms of SBS. However, the immunological aspects of the ocular complications of SBS are not yet clarified. The clinical and allergological aspects of SBS cases with ocular disorders with special reference to allergic conjunctival diseases (ACD) were analyzed, especially with respect to local immunological features. Methods Twelve cases of SBS with ocular findings and 49 cases of ACD (allergic conjunctivitis [AC], atopic keratoconjunctivitis [AKC], and vernal keratoconjunctivitis [VKC]) for comparison were evaluated. The clinical findings in SBS and ACD were scored, and tear film breakup time (BUT) was measured. Cytokine (interferon-γ [IFN-γ], interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, and IL-13) concentrations in tears were analyzed by cytometric bead arrays. Eosinophil count in peripheral blood, total IgE in serum, and multiple allergen simultaneous test (MAST) for antigen-specific IgE were also measured. Results In SBS, conjunctival lesions were observed in all cases, and corneal abnormalities were found in two-thirds of the cases. Limbal lesions were observed in 2 pediatric cases. Mean serum total IgE level in SBS was significantly higher than that in AC; however, it was significantly lower than that in AKC and VKC. Eosinophil count in peripheral blood and number of positive allergens in MAST were significantly lower in SBS than in AKC and VKC. Significant elevation of tear IL-4 was observed in SBS and ACD. However, in contrast to ACD, elevation of other cytokines in tears was not observed in SBS. Mean tear BUT in SBS was in the normal range. Conclusion From these results, SBS is thought to be partially induced by an allergic response. However, clinical dissociation of the ocular clinical findings and local immunological features in tear cytokines may suggest that SBS belongs to a different entity from ACD.

A case of Mooren's ulcer associated with a pterygium.

Moorens ulcer is a clinical entity exhibiting characteristic peripheral circuniferential corneal ulceration. The pathogenesis of Moorens ulcer is related to conjunctival invasion, and often a pseudopterygium is observedin the subsiding stage of Moorens ulcer. It is very rare, however, for Moorens ulcer to occur in the area of a true pterygium. To the best of our knowledge, there is only one report, published in 1976, 1 on this rare complication. We herein report a case of Moorens ulcer that occurred in the same area as a preexisting pterygium and the results of an immunohistochemical study on excised tissues to elucidate the pathogenesis of this complication.