Incidence of ocular inflammation among patients with active tuberculosis or nontuberculous mycobacterial infections in a tertiary hospital in Japan.

PURPOSE: This study aimed to elucidate the incidence of ocular involvement among patients with active tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection in a hospital in Japan. METHODS: Patients with active TB or NTM infection at Yoshijima Hospital from April 2017 to July 2018 were included in this retrospective study. All patients underwent ophthalmic examinations, including fundus evaluation under pupil dilation, before initiation of antibiotic therapy. Patients with ocular inflammation were regularly followed up by ophthalmologists. RESULTS: In total, 101 patients with active TB and 27 patients with active NTM infection underwent ophthalmic examinations during the study period. Seven patients with TB (6.9%) had ocular inflammation; four had bilateral involvement. In these seven patients, ocular inflammation comprised anterior uveitis (n = 2), intermediate uveitis (n = 1), posterior uveitis (n = 4). Choroidal tubercles were observed in two patients with posterior uveitis. Female sex was associated with higher incidence of ocular inflammation among patients with TB. Conversely, no patients with NTM infection had ocular inflammation. CONCLUSION: Ocular inflammation was present in approximately 7% of patients with active TB. Although TB choroiditis is presumed to be rare in Japan, approximately 30% of the patients with ocular inflammation exhibited choroidal lesions in this study. In contrast, no ocular inflammation was observed among patients with systemic NTM infection.

Effects of kallidinogenase in patients undergoing vitrectomy for diabetic macular edema.

PURPOSE: To evaluate the effectiveness of the combination of vitrectomy with kallidinogenase for diabetic macular edema (DME). METHODS: This study was designed as a prospective, randomized, multicenter study comparing 19 eyes of 19 patients who received 150 units of kallidinogenase administered a day for 52 weeks from the day after vitrectomy (study group) with 20 eyes of 20 patients who received no kallidinogenase (control group). The main outcome measurements included logMAR visual acuity and central foveal thickness (CFT) before surgery and at 3, 6, 9, and 12 months after vitrectomy. RESULTS: During follow-up, 11 patients dropped out (six in the study group and five in the control group), leaving 28 eyes in 28 patients for analysis (13 in the study group and 15 in the control group). Visual acuity improved significantly at 12 months in both groups compared with before surgery. The degree of improvement did not differ significantly between the groups. At 12 months, the mean CFT decreased significantly in both groups, with no significant difference in the rate of change between the two groups. In the study group, the visual acuity and CFT significantly improved from 3 to 12 months and from 6 to 12 months, whereas these parameters did not continue to improve in the control group after 6 months (for visual acuity) or 3 months (for CFT). CONCLUSION: After vitrectomy for DME, visual acuity and CFT improved significantly in both groups, but only patients treated with kallidinogenase continued to have significant improvement throughout the study period.

Up-regulation of semaphorin 4A expression in human retinal pigment epithelial cells by PACAP released from cocultured neural cells.

Development and homeostasis of multicellular organisms require interactions between neighbouring cells. We recently established an in vitro model of cell-cell interaction based on a collagen vitrigel membrane. We have now examined the role of neural cells in retinal homeostasis by coculture of human retinal pigment epithelial (RPE) cells and neural cells on opposite sides of such a membrane. The neural cells (differentiated PC12 cells) induced up-regulation of semaphorin 4A (Sema4A), a member of the semaphorin family of neural guidance proteins, in RPE (ARPE19) cells. This effect of the neural cells was mimicked by the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and was abolished by the PACAP antagonist PACAP(6-38). Coculture with neural cells or stimulation with PACAP also induced the phosphorylation of extracellular-signal-regulated kinase in ARPE19 cells, and this effect of the neural cells was inhibited by PACAP(6-38). Finally, among various cytokines examined, only the amount of interleukin-6 released by cocultures of ARPE19 and neural cells differed from that released by ARPE19 cells cultured alone. Interleukin-6 was not detected in culture supernatants of neural cells, and the reduction in the amount of interleukin-6 released by the cocultures compared with that released by ARPE19 cells alone was prevented by PACAP(6-38). Our findings suggest that PACAP released from retinal neural cells (photoreceptors or optic nerve cells) may regulate Sema4A expression in RPE cells and thereby contribute to the maintenance of retinal structure and function. Development and homeostasis of multicellular organisms require interactions between neighbouring cells. With the use of a coculture system based on a collagen vitrigel membrane, we have now shown that neural cells induce up-regulation of the neural guidance protein Sema4A in RPE cells. This effect of neural cells appears to be mediated by the neuropeptide PACAP. PACAP released from retinal neural cells (photoreceptors or optic nerve cells) may thus regulate Sema4A expression in RPE cells and thereby contribute to the maintenance of retinal structure and function.

Inner retinal layer comparisons of eyes with exudative age-related macular degeneration and eyes with age-related macular degeneration and glaucoma.

BACKGROUND: The incidence of glaucoma increases with age, as does age-related macular degeneration (AMD), with the reported incidence of glaucoma among AMD subjects being 5.4 %. Optical coherence tomography (OCT) can detect glaucomatous changes in the inner retina with high sensitivity. The purpose of this study was to compare ganglion cell complex (GCC) parameters and the thickness of the peripapillary retinal nerve fiber layer (RNFL) in normal eyes to that observed in eyes with age-related macular degeneration (AMD) and eyes with both AMD and glaucoma. METHODS: The GCC components [GCC thickness, focal loss volume (FLV), and global loss volume (GLV)] and peripapillary RNFL thickness were measured using RTVue spectral-domain OCT (SD-OCT). The GCC and RNFL parameters of normal eyes, AMD eyes treated with different types of therapy, and AMD eyes with and without glaucoma were evaluated using nonparametric tests. Univariate and multivariate analyses were used to determine whether the GCC and RNFL parameters could be used to differentiate AMD eyes with glaucoma from those without glaucoma. RESULTS: Seventy-one normal eyes, 120 eyes with AMD, and 23 eyes with AMD and glaucoma were studied. The values of all GCC components were significantly different in the normal eyes from those observed in the eyes with AMD, except for the RNFL thicknesses. The GCC and RNFL parameters were not significantly different between the eyes receiving different types of therapy among the AMD groups. The RNFL thickness was significantly correlated with glaucoma diagnosis in AMD eyes. CONCLUSIONS: These findings indicate that there is damage to the inner retinal layers in eyes with AMD. The RNFL thickness can be a useful parameter for differentiating eyes with AMD from eyes with both AMD and glaucoma.

Differential expression of semaphorin 3A and its receptors during mouse retinal development.

Semaphorins not only function in axon guidance during development but also contribute to various other biological processes. We have now examined the expression of semaphorin 3A (Sema3A) and its receptor components neuropilin 1 (Npn1) and plexin A (PlxA) during development of the mouse retina. Immunohistofluorescence analysis revealed that the expression patterns of Sema3A and Npn1 were similar during embryonic and postnatal development. The expression pattern of PlxA was also similar to those of Sema3A and Npn1 during embryonic and early postnatal (before eye opening) developments. However, the pattern of PlxA expression changed markedly after eye opening, with the expression disappearing from the optic nerve and increasing in intensity in the retinal pigment epithelium. Immunoprecipitation analysis showed that Sema3A interacted with PlxA in the retinal pigment epithelial cell line ARPE19 but not in the retinal ganglion cell line RGC5, whereas the opposite pattern of association was apparent for Sema3A and Npn1. Given that atmospheric oxygen is thought to play a role in the differentiation and maintenance of various ocular cell types, our results suggest that Sema3A-PlxA signalling activated by an effect of ambient oxygen on PlxA expression may contribute to differentiation of the retinal pigment epithelium.

A polymorphism of LOC387715 gene is associated with age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is one of the leading causes of blindness among older adults in developed countries and also in Japan. Previous research suggests that AMD is etiologically a complex disease, caused by multiple genes and environmental factors. Association studies have identified that a complement factor H gene (CFH) variant is a major risk factor for AMD in Caucasians. However, we and two other groups have reported no association between CFH and AMD in the Japanese population. Recent studies have suggested that LOC387715 on chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this study, we examined the association between LOC387715 and AMD in Japanese, and our results show that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20 (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715 compared with the non-risk genotype. A polymorphism of LOC387715 gene is associated with AMD in the Japanese population.

A five-year review of patients admitted with the diagnosis of bacterial endophthalmitis.

We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intra-vitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic.

Purification and characterization of cis-aconitic acid decarboxylase from Aspergillus terreus TN484-M1.

cis-Aconitic acid decarboxylase (CAD) was assumed to be a key enzyme in the production of itaconic acid by comparing the activity of CAD from Aspergillus terreus TN484-M1 with that of CAD from the low-itaconate yielding strain Aspergillus terreus CM85J. The constitutive CAD was purified to homogeneity from A. terreus TN484-M1 by ammonium sulfate fractionation, and column chromatography on DEAE-toyopearl, Butyl-toyopearl, and Sephacryl S200HR, and then characterized. A molecular mass of 55 kDa for the native enzyme was determined by SDS-PAGE. The enzymic activity was optimal at a pH of 6.2 and temperature of 45 degrees C. The K(m) value for cis-aconitic acid was determined as 2.45 mM (pH 6.2, 37 degrees C). The enzyme was completely inactivated by Hg+, Cu2+, Zn2+, p-chloromercuribenzoate, and 5,5'-dithio-bis(2-nitrobenzoate).

Retinal detachment in the mentally retarded.

PURPOSE: To report the clinical features and surgical outcomes of retinal detachment in mentally retarded patients. METHODS: Retrospective review of records of mentally retarded patients who had retinal reattachment surgery at the authors' institutions between February 1994 and February 2000. There were 8 patients with 13 surgically treated eyes. Demographic and clinical data were abstracted from the patients' medical records. RESULTS: The retina of 12/13 (92%) eyes remained reattached after a follow-up ranging from 9 to 78 months. In 6 eyes of the 4 patients whose visual acuity (VA) could be determined, VA improved in 5 eyes of 3 patients. In the remaining 4 patients whose VA could not be determined, improved behavioral patterns suggesting a successful surgical outcome were observed in 3 patients with bilateral retinal detachment, although in one of these patients only unilateral retinal reattachment was achieved. The findings in the eyes in this study agree with the findings in reports on patients with traumatic retinal detachment. CONCLUSIONS: The retinal reattachment rate is fair in the mentally retarded compared with the rate in other segments of the population. Ophthalmological examinations should be provided regularly for mentally retarded persons to keep open the possibility for early sight-improving surgery.

Eyelid lengthening combined with penetrating keratoplasty for exposure keratopathy in Graves' ophthalmopathy--a case report.

Upper eyelid retraction is a well-known component of Graves' disease. With greater degrees of retraction, corneal exposure is usually increased. We report here on a patient with corneal perforation following exposure keratopathy due to upper eyelid retraction. The patient was treated with penetrating keratoplasty and an upper eyelid lengthening procedure using Goretex dura substitute as an interpositional graft material. The exposure keratopathy resolved postoperatively and this condition has been maintained for 45 months since the operation, with a good cosmetic outcome and symmetry of the palpebral fissures.

Spontaneous disappearance of coronary pseudoaneurysm due to coronary artery perforation following percutaneous coronary intervention.

In recent years, while therapeutic outcome after percutaneous coronary intervention is improving due to the introduction of drug-eluting stent and device development, procedure-related complications including coronary perforation may ineluctably occur though at low-frequency, even if careful manipulations are performed under IVUS guidance. Meanwhile, coronary pseudoaneurysm subsequent to coronary perforation is one of the complications at chronic phase infrequently experienced following percutaneous coronary intervention. To date, the incidence and natural history of pseudoaneurysm following coronary artery perforation remain unclear. We experienced a case with coronary pseudoaneurysm developed 2 weeks after Ellis II-type coronary artery perforation which spontaneously disappeared 4 months later. As the mechanism of disappearance, thrombotic occlusion was confirmed upon intravascular ultrasound.

A case of idiopathic ventricular fibrillation in which implanted loop recorder was useful in application decision for implantation of implantable cardioverter-defibrillator.

Establishing a symptom-rhythm correlation in patients with unexplained syncope is complicated because of its sporadic, infrequent, and unpredictable nature. Recently, an implantable loop recorder (ILR) has become available to evaluate undiagnosed recurrent arrhythmic episodes particularly in unexplained syncopes, and its usefulness has been reported in patients with recurrent syncopes that remain unexplained after conventional work-up. A 65-year-old man was referred to our hospital for loss of consciousness with nocturnal paroxysmal seizures. He had experienced several similar episodes. No family history of sudden death was evident, and apparent structural heart disease was absent. Coronary angiography with intracoronary ergonovine provocation showed vasospasm in left coronary artery without organic stenosis. Ventricular tachyarrhythmias were not induced by programmed electrical stimuli. According to the guideline, he was at once categorized as having class IIb indication for implantable cardioverter defibrillator implantation. However, his symptoms were not relieved despite administration of anti-anginal medications including nitrates and calcium antagonist. Implantation of an ILR was performed and revealed an episode of ventricular fibrillation during generalized-convulsion attack during sleep. ILR is useful in determining the presence of fatal arrhythmias during syncope, although conventional diagnostic testing, such as electrocardiogram, Holter monitoring, and external loop recording, is inconclusive.

No association of complement factor H gene polymorphism and age-related macular degeneration in the Japanese population.

PURPOSE: The aim of this study was to determine whether genetic polymorphism of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in the Japanese population. METHODS: Genomic DNA was examined in a cohort of 67 Japanese patients with AMD and 107 controls. TT/TC/CC genotypes on exon 9 were screened for sequence alternation by polymerase chain reaction analysis and through sequencing. RESULTS: The mean ages +/- SD of AMD patients and control subjects were 73 +/- 8.5 years and 72 +/- 8.7 years, respectively. There was no significant difference between CFH genotypes in the AMD group (TT, 76%; TC, 19%; CC, 5%) and the control group (TT, 80%; TC, 17%; CC, 3%). The frequencies of T and C alleles were 86% and 14%, respectively, in the AMD group and 89% and 11%, respectively, in the control group. CONCLUSION: CFH gene polymorphism is not associated with AMD in the Japanese population. Moreover, the frequency of the C allele is low among the Japanese population.

High glucose concentration induces elevated expression of anti-oxidant and proteolytic enzymes in cultured human retinal pigment epithelial cells.

We investigated the differential protein expression patterns of retinal pigment epithelial (RPE) cells exposed to increased glucose concentrations. Cultured human RPE cells (ARPE-19) were exposed for 4 days with normal blood glucose concentration (5.5 mM D-glucose), followed by exposure to either normal (5.5 mM) or high (33 mM) concentrations of D-glucose for 48h. Protein extracts of glucose-treated RPE cells were then subjected to comparative proteome analysis based on 2-D gel electrophoresis. Protein spots were visualized by silver staining. The differentially expressed proteins were excised and digested in-gel with trypsin, then analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The expression levels of cathepsin B, glutathione peroxidase and heat shock protein 27 were increased, and that of protein disulfide isomerase decreased in high glucose treated RPE compared to normal glucose. The isoelectric point of copper/zinc-containing superoxide dismutase (Cu/Zn-SOD) shifted toward acidic region in response to high glucose. Cu/Zn-SOD activity in high glucose group was significantly lower than that in normal glucose group (P<0.05, Mann-Whitney U-test). Systematic survey of protein expression has revealed that RPE cells respond to acute, pathologically high glucose levels by the elevated expression of anti-oxidant and proteolytic enzymes.

Proteome analysis of human vitreous proteins.

PURPOSE: Various protein contents such as enzymes, growth factors, and structural components are responsible for biological activities in organs. We have created a map of vitreous proteins and developed a proteome analysis of human vitreous samples to understand the underlying molecular mechanism and to provide clues to new therapeutic approaches in eyes with proliferative diabetic retinopathy (PDR). METHODS: Vitreous and serum samples were obtained from subjects with idiopathic macular hole (MH, 26 cases) and PDR (33 cases). The expressed proteins in the samples were separated by two-dimensional (2-D) polyacrylamide gel electrophoresis. Protein spots were visualized by silver staining, and their expression patterns were analyzed. Some protein spots of concern were excised from the 2-D gels, digested in situ with trypsin, and analyzed by mass spectrometry. RESULTS: More than 400 spots were detected on 2-D gels of MH cases, of which 78 spots were successfully analyzed. The spots corresponded to peptide fragments of 18 proteins, including pigment epithelium-derived factor, prostaglandin-D2 synthase, and interphotoreceptor retinoid-binding protein. These were not identified in the corresponding serum samples. These proteins were also expressed in PDR samples, with no distinct tendency to increase or decrease compared with the MH samples. More than 600 spots were detected on 2-D gels of PDR cases, of which 141 spots were successfully analyzed. The spots corresponded to peptide fragments of 38 proteins. Enolase and catalase were identified among four detected spots. Neither was found in MH vitreous or in PDR serum samples. CONCLUSION: A map of protein expression was made in human vitreous from eyes with MH and PDR. In the PDR eyes, the increased protein expression observed was due to barrier dysfunction and/or production in the eye. Proteome analysis was useful in systematic screening of various protein expression in human vitreous samples.