Jiro Numaga

Ocular and systemic factors relevant to diabetic keratoepitheliopathy.

Purpose. This study examines the contribution of ocular and systemic factors to diabetic keratoepitheliopathy. Methods. The presence and severity of keratoepitheliopathy was investigated in 114 eyes of patients with diabetes and 59 eyes of patients without diabetes. The ocular factors examined were the status of the lipid layer of the tear fluid assessed with the specular reflection video-recording system, corneal sensitivity using the Cochet–Bonnet method, tear volume by the cotton thread test, tear film stability by tear breakup time, and grade of diabetic retinopathy. The systemic factors examined included patient age, hemoglobin A1c value, and duration of diabetes mellitus. Multivariate regression analysis was performed to assess the factors related to keratoepitheliopathy. Results. The incidence of keratoepitheliopathy was 22.8% and 8.5% in patients with and without diabetes, respectively. Ocular measures, such as nonuniformity of tear lipid layer, corneal sensitivity, and tear breakup time, were significantly worse in patients with diabetes than in patients without diabetes (p < 0.05). Multivariate regression analysis showed that the status of the tear lipid layer was significantly relevant to diabetic keratoepitheliopathy (p < 0.05). Conclusion. Qualitative abnormalities in tear secretion seem relevant to the development of diabetic keratoepitheliopathy. The tear lipid layer interference pattern may yield useful information for the elucidation of the mechanism and treatment of diabetic keratoepitheliopathy.

Anterior capsular contraction after cataract surgery in eyes of diabetic patients

AIM To investigate change in the area of anterior capsular opening (ACO) after cataract surgery and its relation to the degree of postoperative anterior inflammation in patients with diabetes mellitus (DM). METHODS 31 eyes of 31 patients with DM and 30 eyes of 30 normal controls scheduled to undergo cataract surgery were examined prospectively. The area of ACO was measured with an anterior eye segment analysis system (EAS-1000) on the day following surgery and 3, 6, and 12 months after surgery. Comparative analyses were made on the area of ACO relative to the presence of DM and diabetic retinopathy (DR). The percentage reduction of area of ACO was calculated from values 1 day and 12 months after surgery, and multiple regression analysis was performed on the presence of DM, patient age, ACO area on the first postoperative day, and aqueous flare intensity 1 day and 12 months after surgery. RESULTS The area was significantly smaller in the DM group at 3 (p=0.015, Studentst test), 6 (p=0.011), and 12 (p=0.010) months postoperatively. Patients having DR showed significantly smaller ACO area than the non-DR group 3 (p=0.039), 6 (p=0.033), and 12 (p=0.028) months after surgery. Multiple regression analysis revealed that presence of DM (p=0.003) and aqueous flare intensity 12 months after surgery (p=0.039) significantly correlated with the percentage reduction of area of ACO. Age, ACO area at 1 day postoperatively, and aqueous flare intensity immediately after surgery were not relevant to ACO contraction. CONCLUSIONS Anterior capsular contraction after cataract surgery was greater in eyes of DM patients, especially in those with DR and increased permeability of the blood-aqueous barrier.

Plasma and whole-blood chemokine levels in patients with Behcet's disease

BackgroundChemokines are a family of chemoattractants of leukocytes that play a critical role for leukocyte recruitment in various inflammatory diseases. The purpose of this study is to investigate the involvement of chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the peripheral blood, with a special reference to disease activities of the patients with Behçets disease (BD).MethodsThe study population consisted of totally 55 patients with BD who had panuveitis (20 patients with active BD, 35 patients with inactive BD) as well as 19 healthy volunteers as control. Disease activity was defined according to the existence of ocular inflammation. IL-8 and MCP-1 concentration levels in the plasma and whole-blood samples were measured by enzyme-linked immunosorbent assay. Whole-blood samples were obtained by lysing cell membranes of peripheral blood cells.ResultsMost of the plasma IL-8 samples were below the detectable limit. Whole-blood IL-8 levels were readily measured. The levels in the patients with active BD were significantly higher than the other two groups. The patients with active and inactive BD showed higher plasma and whole-blood levels of MCP-1 than controls. The plasma and whole-blood MCP-1 levels of the samples collected at the same time showed a linear correlation.ConclusionA close relationship was found to exist between the cell-associated IL-8 and the disease activity, while a persistent role of MCP-1 was observed in BD. Measuring the whole-blood levels of chemokines is useful for monitoring the disease activity.

Common Variants on Chromosome 9p21 Are Associated with Normal Tension Glaucoma

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10−8, odds ratio (OR)  = 2.00 with 95% confidence interval (CI) 1.55–2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10−11, OR  = 2.13 with 95% CI 1.69–2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.

Risk factors for contraction of the anterior capsule opening after cataract surgery.

Purpose: To investigate the factors contributing to contraction of the anterior capsule opening (ACO) after cataract surgery in normal eyes. Setting: Department of Ophthalmology, University of Tokyo, School of Medicine, Tokyo, and Kaiya Eye Clinic, Hamamatsu, Japan. Methods: This study included 141 eyes of 141 patients scheduled to have cataract surgery. The area of the ACO was determined by diaphanoscopy using the EAS‐1000 anterior eye segment analysis system 1 day and 9 months postoperatively, after which the percentage reduction in the ACO area was calculated. Aqueous flare intensity was measured with a laser flare‐cell meter 1 week and 9 months after surgery. Multiple regression analysis was performed to determine which factors were correlated with the percentage reduction in the ACO area. Variables tested included patient age, axial length, the ACO area on the first postoperative day, and flare values 1 week and 9 months after surgery. Results: Patient age (r = 0.193, P = .029) and flare intensity 9 months after surgery (r = 0.255, P = .007) were significantly correlated with the percentage reduction in the ACO area (R2 = 0.133). The axial length, ACO area 1 day postoperatively, and flare value at 1 week were not correlated with ACO contraction. Conclusion: Contraction of the ACO after cataract surgery is related to instability of the blood‐aqueous barrier.

Initial trabeculectomy with mitomycin C in eyes with uveitic glaucoma with inactive uveitis

PURPOSE To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). DESIGN Retrospective non-randomized comparative interventional case series. METHODS A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP<or=15 mm Hg without anti-glaucoma medications) and qualified success (IOP<or=15 mm Hg with topical anti-glaucoma medications). The incidences of postoperative complications were also examined. RESULTS Complete success rate for postoperative IOP control at 5 years after trabeculectomy was 57.1+/-7.5% (mean+/-SE) in UG, being comparable to that in POAG (53.7+/-6.1%), and those of qualified success was 64.7+/-7.0 and 65.9+/-5.5% (P=0.60 and 0.53) respectively. Persistence of filtrating blebs was shorter in UG than in POAG (P=0.031). Postoperative inflammation in UG was associated with worse postoperative IOP control and loss of filtering bleb (P=0.027 and 0.021). Postoperative long-standing ocular hypotony was more frequent in UG (P=0.0063). CONCLUSIONS An MMC trabeculectomy for UG with inactive uveitis as an initial ocular surgery had IOP control comparable to that for POAG, suggesting that pre-existing uveitis itself is not a risk factor for failure of a filtering surgery.

Identification of Subgenus C Adenoviruses by Fiber-Based Multiplex PCR

ABSTRACT Subgenus C human adenoviruses, which include serotypes 1, 2, 5, and 6, are often associated with respiratory illness, ocular infections, gastroenteritis, and systemic infection among immunocompromised patients. To address the problems associated with the conventional typing methods, we developed a fiber-based multiplex PCR assay for simple and specific identification of adenovirus type 1, 2, 5, and 6 field isolates. To design type-specific primers, adenovirus type 1 and 6 fiber genes were sequenced. The assay correctly identified prototype strains of adenovirus serotypes 1, 2, 5, 6, as well as 21 previously typed adenovirus field isolates. Mixing two different prototype DNAs produced two amplicons of different lengths, thus clearly distinguishing the prototypes. The results correlated 100% with serological tests and 95% with the previously described PCR-restriction fragment length polymorphism method. The detection of dual infection is an added benefit of the assay. No nonspecific amplification was detected with other adenovirus serotypes or with nonadenoviral DNA. Our fiber-based multiplex PCR assay will provide a convenient tool for type-specific identification of subgenus C adenovirus isolates in various clinical situations and in epidemiological investigations and is a better alternative than the hexon-based assay.

Glycemic control and lens transparency in patients with type 1 diabetes mellitus.

PURPOSE To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.

Nepafenac 0.1% versus fluorometholone 0.1% for preventing cystoid macular edema after cataract surgery

PURPOSE: To compare a topical nonsteroidal antiinflammatory drug (nepafenac 0.1%) and a topical steroidal antiinflammatory drug (fluorometholone 0.1%) in preventing cystoid macular edema (CME) and blood–aqueous barrier (BAB) disruption after small‐incision cataract extraction with foldable intraocular lens (IOL) implantation. SETTING: Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan. DESIGN: Randomized double‐masked single‐center clinical trial. METHODS: Patients were randomized to receive nepafenac 0.1% eyedrops or fluorometholone 0.1% eyedrops for 5 weeks after phacoemulsification with foldable IOL implantation. The incidence and severity of CME were evaluated by fluorescein angiography, retinal foveal thickness on optical coherence tomography, and BAB disruption on laser flare–cell photometry. RESULTS: Thirty patients received nepafenac and 29 patients, fluorometholone. Five weeks postoperatively, the incidence of fluorescein angiographic CME was significantly lower in the nepafenac group (14.3%) than in the fluorometholone group (81.5%) (P<.0001). The fovea was thinner in the nepafenac group than in the fluorometholone group at 2 weeks (P=.0266) and 5 weeks (P=.0055). At 1, 2, and 5 weeks, anterior chamber flare was significantly less in the nepafenac group than in the fluorometholone group (P<.0001, P<.0001, and P=.0304, respectively). The visual acuity recovery from baseline was significantly greater in the nepafenac group (80.0%) than in the fluorometholone group (55.2%) (P=.0395). There were no serious side effects in either group. CONCLUSION: Nepafenac was more effective than fluorometholone in preventing angiographic CME and BAB disruption, and results indicate nepafenac leads to more rapid visual recovery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Imaging Mouse Retinal Ganglion Cells and Their Loss In Vivo by a Fundus Camera in the Normal and Ischemia-Reperfusion Model

PURPOSE To visualize retinal ganglion cells (RGCs) and their gradual loss in the living mouse. METHODS With the use of B6.Cg-Tg(Thy1-CFP)23Jrs/J mice, which express cyan fluorescent protein (CFP) in RGCs, and a commercially available mydriatic retinal camera attached with a 5 million-pixel digital camera to visualize RGCs in vivo, the authors recorded fundus photographs longitudinally in the ischemia reperfusion model group and the untreated group to evaluate longitudinal changes in the number of RGCs in experimental models. Moreover, RGCs expressing CFP were evaluated histologically by a retrograde-labeling method and retinal whole mount or sections. RESULTS The authors devised an in vivo imaging technique using a conventional retinal camera and visualized RGCs at the single-cell level. In the ischemia reperfusion model, a longitudinal reduction in the number of RGCs was demonstrated in each mouse eye. The number of RGCs and the fluorescence intensity of the nerve fiber decreased considerably during the first week. The percentages of RGCs decreased to 34.2% +/- 7.5%, 24.1% +/- 9.1%, 23.0% +/- 9.3%, and 22.2% +/- 8.4% (mean +/- SD, n = 5) of the percentages before injury at 1, 2, 3, and 4 weeks after injury, respectively (P < 0.001). In this transgenic mouse, 97% of CFP-expressing cells were RGCs and 73% of RGCs expressed CFP. CONCLUSIONS This in vivo technique allows noninvasive, repeated, and longitudinal evaluation of RGCs for investigation of retinal neurodegenerative diseases and new therapeutic modalities for them.