Tadayuki Nishide

High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan

PURPOSE To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.

Effect of intracameral anesthesia on the corneal endothelium

Purpose: To evaluate the effects of intracameral anesthesia on the corneal endothelium. Setting: Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan. Methods: This study comprised 24 eyes of 12 white rabbits. One eye of 3 rabbits each was injected with preservative‐free lidocaine at concentrations of 0.02, 0.2, or 2% and the fellow eye injected with balanced salt solution (BSS®) as a control. The anesthetic agent was injected into the anterior chamber using a bimanual technique. Immediately after enucleation, the cornea was examined by scanning electron microscopy. Results: Scanning electron microscopy revealed no abnormal findings in the eyes injected with lidocaine 0.02 or 0.2% when compared with eyes in the control group. Scanning electron microscopy of the eyes injected with lidocaine 2% showed irregular hexagonal endothelial cells and a significant loss of microvilli. Conclusion: Intracameral anesthesia with high concentrations of lidocaine risks corneal endothelial damage but at the low concentration usually used in cataract surgery did not appear to have an adverse effect. J Cataract Refract Surg 1998; 24:1377‐1381

Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles.

PURPOSE Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.

Reduction in choroidal thickness of macular area in polypoidal choroidal vasculopathy patients after intravitreal ranibizumab therapy

BackgroundTo evaluate changes in retinal and choroidal thickness changes after three intravitreal ranibizumab (IVR) injections for polypoidal choroidal vasculopathy (PCV) using enhanced depth-imaging-optical coherence tomography (EDI-OCT).MethodsIn this retrospective, observational case series, EDI-OCT was used to measure changes in choroidal thickness at nine points in a lattice shape in the macula before and after introductory-stage IVR.ResultsChoroidal thickness was decreased at all nine points in the lattice shape, but was significantly decreased only at the fovea.ConclusionThe subfoveal choroidal thickness may be reduced by introductory-stage IVR in patients with PCV. In particular, choroidal thickness at the fovea was reduced during the early stage of treatment.

Infliximab Monotherapy Versus Infliximab and Colchicine Combination Therapy in Patients with Behçet’s Disease

Purpose: To compare infliximab monotherapy with infliximab and colchicine combination therapy in Behçet’s disease. Methods: Clinical records of 14 Behçet’s disease patients who were administered infliximab with or without colchicine were retrospectively reviewed. Patients who were given other immunosuppresants after initiation of infliximab therapy were excluded. The frequency of ocular attacks and best-corrected visual acuity were investigated. Results: Seven patients received monotherapy and 7 received combination therapy. The mean frequency of ocular attacks significantly decreased from 2.14 to 0.22 per 6 months in monotherapy group and from 2.57 to 0.18 per 6 months in combination therapy group. No significant difference was observed between both groups in the frequency of ocular attacks and in changes in best-corrected visual acuity during 0 to 24 months. Conclusions: Infliximab is as efficacious as infliximab and colchicines together in Behçet’s disease treatment. This study suggests that colchicine administration is not necessary in Behçet’s disease patients receiving infliximab.

Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behçet's disease in Japanese patients.

Behçets disease (BD) is a chronic systemic inflammatory disorder characterized by recurrent ocular symptoms, oral and genital ulcers, and skin lesions. The etiology of BD is still uncertain, but genetic and environmental factors likely both play an important role in BD development. In the present study, we investigated whether polymorphisms of Toll-like receptor 2 (TLR2), previously reported to recognize BD candidate antigens, are associated with BD. Two hundred Japanese patients with BD and 128 Japanese healthy controls were recruited. We genotyped five single-nucleotide polymorphisms (SNPs) in the TLR2 gene and assessed the allele/genotype diversity between cases and controls for all SNPs. No significant differences in the frequency of TLR2 alleles, genotypes, and haplotypes in the BD cases were detected compared with the controls. These data indicate that TLR2 polymorphisms do not play an important role in the development of BD.

Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients

Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2′-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population. Methods: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. Results: Strong linkage disequilibrium was observed among three SNPs (D’ > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls. Conclusion: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.

Association analysis of Toll-like receptor 7 gene polymorphisms and Behçet's disease in Japanese patients.

Action of Toll-like receptors (TLRs) is deeply associated with defense mechanisms of the innate and adaptive immune responses to microbial pathogens. There have been reports of genetic polymorphisms within the TLR7 gene being closely related to a variety of inflammatory and infectious diseases. Behçets disease (BD) is an autoinflammatory disease, and the pathogenesis has yet to be fully discovered. We investigated whether polymorphisms of Toll-like receptor 7 (TLR7) are associated with BD by analyzing the frequency of eight single nucleotide polymorphisms (SNPs) within 200 Japanese BD patients and 102 randomized controls. We genotyped nine SNPs in the TLR7 gene and assessed the allele/genotype diversity between cases and controls for all SNPs. In all eight SNPs, statistically significant differences were not observed between cases and controls.

Measured visual acuity of fellow eyes as a prognostic factor in macular hole surgery.

PURPOSE To investigate the effect of the vision of the fellow eye on the visual acuity of eyes after successful macular hole surgery. DESIGN Prospective consecutive series. METHODS A consecutive series of eyes with successful macular hole closure were studied and assigned to one of two groups according to the visual acuity of the fellow eye; a group with visual acuity less than 20/200 and a group with visual acuity of 20/200 or better. Preoperative and postoperative visual acuity in the two groups was measured based on the logarithm of the minimal angle of resolution (LogMAR), and postoperative visual acuity was also determined by using the multiple-letter visual acuity chart, which permitted measurement of visual acuity at an extrafoveal point. RESULTS Group 1 (<20/200) consisted of 19 eyes and group 2 (>20/200) consisted of 51 eyes. LogMAR visual acuity at 6 months postoperatively was significantly better in group 1 than in group 2 (0.21 vs 0.41, P <.01). The logMAR change 6 months after surgery was significantly greater in group 1 than in group 2 (0.49 vs 0.23, P <.01). There was no significant difference between two groups in logMAR visual acuity at 6 months postoperatively determined with the multiple-letter visual acuity chart (0.20 vs 0.29, P >.05). CONCLUSIONS Visual recovery after successful macular hole surgery is inversely correlated with vision in the fellow eye. Learning to use eccentric fixation may contribute to visual improvement after macular hole surgery.

The Effect of Intraocular Lidocaine in White Rabbit Eyes

Purpose: Recently, intraocular lidocaine anesthesia has been used in cataract surgery. We studied the toxicity of intraocular unpreserved lidocaine for corneal endothelial cell and retina using Japanese white rabbits.Methods: The rabbits were divided into two groups. One group was injected intracamerally and the other was injected intravitreally with 0.2 ml of unpreserved lidocaine of 0%, 0.02%, 0.2%, or 2% concentration. The number of corneal endothelial cells was measured 1 week after the injection. After measurements, the rabbit corneas were studied histologically. The retina was examined by electroretinogram prior to initial injection through 1 week after the injection.Results: There was no significant change in number of corneal endothelial cells after injection of 0.2% lidocaine. However, histological abnormality was seen in corneal endothelial cells after 2% lidocaine injection. There was also significant change in electroretinogram with 2% lidocaine injection. No histological abnormality was seen in the retina 1 week after the injection.Conclusion: The rabbit cornea and retina manifested no serious changes after the injection of lidocaine at less than 0.2% concentration functionally and histologically.