Eiichi Uchio

Simulation model of an eyeball based on finite element analysis on a supercomputer

BACKGROUND/AIMS A simulation model of the human eye was developed. It was applied to the determination of the physical and mechanical conditions of impacting foreign bodies causing intraocular foreign body (IOFB) injuries. METHODS Modules of the Hypermesh (Altair Engineering, Tokyo, Japan) were used for solid modelling, geometric construction, and finite element mesh creation based on information obtained from cadaver eyes. The simulations were solved by a supercomputer using the finite element analysis (FEA) program pam-crash (Nihon ESI, Tokyo, Japan). It was assumed that rupture occurs at a strain of 18.0% in the cornea and 6.8% in the sclera and at a stress of 9.4 MPa for both cornea and sclera. Blunt-shaped missiles were shot and set to impact on the surface of the cornea or sclera at velocities of 30 and 60 m/s, respectively. RESULTS According to the simulation, the sizes of missile above which corneal rupture occurred at velocities of 30 and 60 m/s were 1.95 and 0.82 mm. The missile sizes causing scleral rupture were 0.95 and 0.75 mm at velocities of 30 and 60 m/s. CONCLUSIONS These results suggest that this FEA model has potential usefulness as a simulation tool for ocular injury and it may provide useful information for developing protective measures against industrial and traffic ocular injuries.

Treatment of retinal detachment resulting from myopic macular hole with internal limiting membrane removal

PURPOSE To examine the efficacy of vitrectomy with internal limiting membrane removal for retinal detachment resulting from a macular hole in highly myopic eyes. METHODS Eleven consecutive highly myopic eyes (11 patients) with retinal detachment resulting from a macular hole were treated by vitrectomy with removal of the internal limiting membrane, which was stained with indocyanine green and sulfur hexafluoride gas injection. Postoperatively, the patients were instructed to remain prone for 2 weeks. The excised specimens were evaluated with transmission electron microscopy. RESULTS The mean postoperative follow-up was 9.2 +/- 2.3 months (range, 7 to 13 months). In 10 of the 11 eyes (91%) the retina was reattached during the initial surgery. Redetachment occurred in one eye, which was successfully treated during the second surgery. Best-corrected visual acuity improved in all eyes and ranged from 20/400 to 20/50. Pathologic examination showed that the internal limiting membrane and epiretinal tissues were present in all specimens. CONCLUSIONS The use of indocyanine green staining can facilitate removal of a macular internal limiting membrane and overlying epiretinal membrane, resulting in complete relief of the macular traction. Primary removal of the internal limiting membrane may contribute to a high initial success rate for retinal reattachment and be an important adjuvant to the treatment of retinal detachment resulting from a macular hole in highly myopic eyes.

A Large Prospective Observational Study of Novel Cyclosporine 0.1% Aqueous Ophthalmic Solution in the Treatment of Severe Allergic Conjunctivitis

PURPOSE To evaluate the effectiveness and safety of a novel cyclosporine 0.1% aqueous ophthalmic solution in a large population with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). METHODS A prospective observational postmarketing study was initiated in Japan. A total of 594 patients with VKC or AKC were started on this drug within 1 year after market launch (January 2006) and completed a 6-month follow-up. These patients were observed clinically, and subjective ocular symptoms (itching, discharge, tearing, photophobia, foreign body sensation, and pain), objective signs (hyperemia, swelling, follicle, papillae, and giant papillae for the tarsal conjunctiva; hyperemia and edema for the bulbar conjunctiva; Trantas dots and swelling for the limbus; and corneal involvement), and adverse events were recorded. RESULTS All scores for symptoms and signs significantly decreased from Month 1 through Month 6 of treatment in both VKC and AKC. Median total symptom scores at baseline, Month 1, and Month 6 were 6, 2, and 1, respectively, for VKC, and 7, 3, and 2, respectively, for AKC. Similarly, median total sign scores were 12, 7, and 5, respectively, for VKC, and 14, 10, and 7, respectively, for AKC. The percentage of patients able to complete topical cyclosporine 0.1% therapy within 6 months due to alleviation of symptoms was higher for VKC (44.4%) than for AKC (21.9%). In both VKC and AKC, approximately 30% of steroid users were able to discontinue topical steroids. Adverse drug reactions (ADRs) were found in 12.0% of patients, and the most common ADR was eye irritation (4.4%). Infectious corneal complications were observed in five AKC patients, including two cases of bacterial corneal ulcer and three cases of herpetic keratitis; all of these patients were concomitantly using topical steroids. CONCLUSIONS Topical cyclosporine 0.1% is an effective and safe treatment for VKC and AKC.

Successful switching to adalimumab in an infliximab-allergic patient with severe Behçet disease-related uveitis.

Infliximab has demonstrated remarkable effects on controlling uveitis in patients with Behçet’s disease (BD). However, there is no way except for discontinuation of infliximab treatment in patients who are intolerant to the agent due to hypersensitivity reactions. We here report successful switching from infliximab to adalimumab in a BD patient. Treatment with infliximab had maintained clinical remission in the patient having refractory ocular lesions to cyclosporine until the patient had experienced repeated infliximab-related infusion reactions. Discontinuation of the therapy led to another ocular attacks immediately. Switching to adalimumab induced clinical remission again. Our experience suggest adalimumab is a safe and effective option for patients having hypersensitivity to infliximab.

Rapid Diagnosis of Adenoviral Conjunctivitis on Conjunctival Swabs by 10-Minute Immunochromatography

PURPOSE Several methods are available for the diagnosis of acute conjunctivitis, all of which are time-consuming or require the use of a well-equipped laboratory. A new method, immunochromatography (IC), for detecting the presence of adenovirus (Ad) has been developed. Two direct rapid tests to detect Ad antigen, IC and enzyme immunoassay (EIA), were compared with regard to sensitivity, specificity, and technical complexity. METHODS The study materials consisted of 130 swabs from patients with conjunctivitis (95 samples of adenoviral conjunctivitis proven by positive virus DNA on polymerase chain reaction [PCR], 35 samples of nonadenoviral conjunctivitis proven by PCR). IC is a one-step procedure that detects the presence of adenoviral antigen by sandwich EIA on a paper disc. RESULTS In 95 adenoviral DNA-positive samples by PCR, the sensitivity and specificity of IC were 54.7% and 97.1%, respectively, whereas those of EIA were 50.5% and 100%, respectively. By IC, PCR-positive Ad type 3 was recognized in 31%; Ad4 in 100%; Ad7 in 60%; Ad8 in 67%; and Ad37 in 59%, showing similar positivity rates for different serotypes (except Ad7) to those using EIA. Visual determination of the presence of Ad took an average of 10 minutes by IC compared with 70 minutes by EIA. CONCLUSIONS These results indicate that IC is a more rapid and easier test compared with EIA, and it has high specificity. Detection of Ad antigen by this simple and rapid method will serve physicians as a useful tool for early diagnosis and prevention of adenoviral conjunctivitis.

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous disorder characterized by abnormal vascularization of the peripheral retina, which can result in retinal detachment and severe visual impairment. In a large Dutch FEVR family, we performed linkage analysis, exome sequencing, and segregation analysis of DNA variants. We identified putative disease-causing DNA variants in proline-alanine-rich ste20-related kinase (c.791dup; p.Ser265ValfsX64) and zinc finger protein 408 (ZNF408) (c.1363C>T; p.His455Tyr), the latter of which was also present in an additional Dutch FEVR family that subsequently appeared to share a common ancestor with the original family. Sequence analysis of ZNF408 in 132 additional individuals with FEVR revealed another potentially pathogenic missense variant, p.Ser126Asn, in a Japanese family. Immunolocalization studies in COS-1 cells transfected with constructs encoding the WT and mutant ZNF408 proteins, revealed that the WT and the p.Ser126Asn mutant protein show complete nuclear localization, whereas the p.His455Tyr mutant protein was localized almost exclusively in the cytoplasm. Moreover, in a cotransfection assay, the p.His455Tyr mutant protein retains the WT ZNF408 protein in the cytoplasm, suggesting that this mutation acts in a dominant-negative fashion. Finally, morpholino-induced knockdown of znf408 in zebrafish revealed defects in developing retinal and trunk vasculature, that could be rescued by coinjection of RNA encoding human WT ZNF408 but not p.His455Tyr mutant ZNF408. Together, our data strongly suggest that mutant ZNF408 results in abnormal retinal vasculogenesis in humans and is associated with FEVR.

Japanese Guideline for Allergic Rhinitis 2014.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1

BACKGROUND/AIMS It is reported by the national surveillance of ocular infectious diseases in Japan that 4.3% of cases of epidemic keratoconjunctivitis (EKC) diagnosed clinically were caused by herpes simplex virus (HSV). Clinical and virological studies of patients with HSV conjunctivitis were carried out. METHODS The study population consisted of 478 patients with acute follicular conjunctivitis. Virological analysis was carried out for adenovirus (Ad) and HSV by the cell culture method and fluorescein antibody (FA) method. Polymerase chain reaction for Chlamydia trachomatis was also carried out. RESULTS From 23 patients, HSV type 1 was isolated but Ad or C trachomatis was not isolated. 87% of cases were unilateral. Most cases showed clinical resolution within 9 days. Early corneal lesions and preauricular lymphadenopathy were less frequent in HSV conjunctivitis than in adenoviral conjunctivitis, especially that due to subgenus D. No case showed a positive result for HSV by the FA method using conjunctival swabs; however, the FA test was positive in all strains isolated by cell culture. CONCLUSIONS These results indicate that it is difficult clinically to differentiate HSV conjunctivitis from adenoviral conjunctivitis in the acute stage, since the clinical features of adenoviral conjunctivitis are similar to those of HSV conjunctivitis. A biological difference may exist between HSV strains causing keratitis and conjunctivitis.

Surgically-induced inflammation with 20-, 23-, and 25-gauge vitrectomy systems: an experimental study.

Purpose: To evaluate postoperative intraocular inflammation induced in rabbit eyes subjected to surgery using different vitrectomy systems. Methods: The 20-, 23-, and 25-gauge vitretomy were performed on a total of 12 rabbit eyes, divided into 3 respective groups, and 4 rabbit eyes were used as a normal control group. The surgery consisted of posterior vitreous detachment induction and core vitretomy. The main outcome measures were operative time, volume of balanced saline solution consumed and the intravitreal total protein concentration, determined by bicinchoninic acid protein assays, obtained by vitreous tap on postoperative days 1, 3, and 7. Results: The intravitreal protein averages in the 20-, 23-, and 25-gauge vitretomy groups were, respectively, 31 ± 4.1, 21 ± 2.3, and 7 ± 3.4 mg/mL on postoperative Day 1 (0.13 ± 0.02 mg/mL in the control eye). The intravitreal protein concentration level was significantly lower with the 25-gauge than with 20- or 23-gauge vitrectomy (P < 0.001), and there were no significant differences in intravitreal protein between the 20- and 23-gauge system on postoperative days 1 and 3. At 7 days postoperatively, there were no significant differences in the intravitreal protein levels among the three groups. Significantly less balanced saline solution was consumed in the 25-gauge vitrectomy group (P < 0.001). Conclusion: Postoperative intraocular inflammation can vary among vitrectomy systems. A smaller gauge can minimize the inflammation associated with vitrectomy.

Ten years’ surveillance of viral conjunctivitis in Sapporo, Japan

Abstract · Background: We set out to establish the epidemiology of viral conjunctivities over a 10-year period in Sapporo, northern Japan. · Methods: A total of 965 patients with clinically suspected viral conjunctivitis during the 10-year period from 1985 to 1994 in Sapporo were evaluated. · Results: Among the 965 patients, cumulative frequency of adenovirus (Ad) was 721 (75%). The dominant serotype of Ad changed with time; each serotype peaked at 3- to 5-year intervals. Adenoviral conjunctivitis occurred most often in July and August each year. Ad3 and Ad4 were predominantly identified in patients 30–39 years old. No enterovirus 70 has been detected. Herpes simplex virus (HSV) and Chlamydia trachomatis had no significant peak. HSV was isolated throughout the year, and C. trachomatis had two peaks of detection: in March and from July to September. HSV and C. trachomatis were predominantly detected in patients 20–29 years old. · Conclusion: In this study, the main etiological agent of viral conjunctivitis in Sapporo, Japan, was Ad; however, attention should be paid to non-adenoviral agents, such as HSV and C. trachomatis, as possible causes of acute conjunctivitis.