Shinji Ohkubo

Effects of Age, Sex, and Axial Length on the Three-Dimensional Profile of Normal Macular Layer Structures

PURPOSE To identify sex-related differences and age-related changes in individual retinal layer thicknesses in a population of healthy eyes across the lifespan, using spectral domain optical coherence tomography (SD-OCT). METHODS In seven institutes in Japan, mean thicknesses of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor inner segment (IS), and photoreceptor outer segment (OS) were measured using SD-OCT with a new automated segmentation protocol in 256 healthy subjects. RESULTS Interoperator coefficients of variability for measurements of each layer ranged from 0.012 to 0.038. The RNFL, GCL, IPL, and INL were thinnest in the foveal area, whereas the OPL+ONL and OS were thickest in this area. Mean thicknesses of the INL and the OPL+ONL were significantly greater in men (P = 0.002 and 0.001, respectively). However, mean RNFL thickness was greater in women (P = 0.006). Thicknesses of the RNFL, GCL, IPL, INL, and IS correlated negatively with age. Thickness of the OPL+ONL was not correlated with age, and thickness of the OS correlated positively with age. Inner retinal (RNFL+GCL+IPL) thickness over the whole macula correlated negatively with age (P < 0.001), but outer retinal (OPL+ONL+IS+OS) thickness did not. Thicknesses of layers did not correlate with axial length. CONCLUSIONS Macular layer thicknesses measured on SD-OCT images in healthy eyes showed significant variations by sex and age. These findings should inform macular layer thickness analyses in SD-OCT studies of retinal diseases and glaucoma.

Peripapillary Retinal Nerve Fiber Layer Thickness Determined by Spectral-Domain Optical Coherence Tomography in Ophthalmologically Normal Eyes

OBJECTIVES To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in normal eyes using spectral-domain optical coherence tomography and to study potentially related factors. METHODS In 7 institutes in Japan, RNFLT in 7 concentric peripapillary circles with diameters ranging from 2.2 to 4.0 mm were measured using spectral-domain optical coherence tomography in 251 ophthalmologically normal subjects. Multiple regression analysis for the association of RNFLT with sex, age, axial length, and disc area was performed. RESULTS Retinal nerve fiber layer thickness decreased linearly from 125 to 89 μm as the measurement diameter increased (P < .001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = -0.40 to -0.32; P < .001) and negatively correlated with disc area in the 2 innermost circles but positively correlated in the 3 outermost circles (PCC = -0.30 to -0.22 and 0.17 to 0.20; P ≤ .005). Sex and axial length did not correlate with RNFLT (P > .08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (P < .001); positively correlated with disc area (PCC = 0.13 to 0.51; P ≤ .04); and negatively correlated with RNFLT (PCC = -0.51 to -0.15; P ≤ .01). CONCLUSIONS In normal Japanese eyes, RNFLT significantly correlated with age and disc area, but not with sex or axial length. Retinal nerve fiber layer thickness decreased linearly as the measurement diameter increased. The decay slope of RNFLT was steepest in the nasal and inferior quadrants and steeper in eyes with increased RNFLT or smaller optic discs.

Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma

Purpose:  This study aimed to investigate the effects of preoperative intravitreal bevacizumab (IVB) on outcomes in trabeculectomy for neovascular glaucoma (NVG).

The 5-year incidence of bleb-related infection and its risk factors after filtering surgeries with adjunctive mitomycin C: collaborative bleb-related infection incidence and treatment study 2.

PURPOSE To report the 5-year incidence of bleb-related infection after mitomycin C-augmented glaucoma filtering surgery and to investigate the risk factors for infections. DESIGN Prospective, observational cohort study. PARTICIPANTS A total of 1098 eyes of 1098 glaucoma patients who had undergone mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation performed at 34 clinical centers. METHODS Patients were followed up at 6-month intervals for 5 years, with special attention given to bleb-related infections. The follow-up data were analyzed via Kaplan-Meier survival analysis and the Cox proportional hazards model. MAIN OUTCOME MEASURES Incidence of bleb-related infection over 5 years and risk factors for infections. RESULTS Of the 1098 eyes, a bleb-related infection developed in 21 eyes. Kaplan-Meier survival analysis revealed that the incidence of bleb-related infection was 2.2±0.5% (cumulative incidence ± standard error) at the 5-year follow-up for all cases, whereas it was 7.9±3.1% and 1.7±0.4% for cases with and without a history of bleb leakage, respectively (P = 0.000, log-rank test). When only eyes with a well-functioning bleb were counted, it was 3.9±1.0%. No differences were found between the trabeculectomy cases and the combined surgery cases (P = 0.398, log-rank test) or between cases with a fornix-based flap and those with a limbal-based flap (P = 0.651, log-rank test). The Cox model revealed that a history of bleb leakage and younger age were risk factors for infections. CONCLUSIONS The 5-year cumulative incidence of bleb-related infection was 2.2±0.5% in eyes treated with mitomycin C-augmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation in our prospective, multicenter study. Bleb leakage and younger age were the main risk factors for infections.

In Vivo Quantitative Evaluation of the Rat Retinal Nerve Fiber Layer with Optical Coherence Tomography

PURPOSE To determine whether optical coherence tomography (OCT) is useful for quantitative evaluation of the thickness of the rat retinal nerve fiber layer (RNFL) in an optic nerve crush model. METHODS An OCT system was developed with a modified commercial time-domain OCT and a superluminescent diode with a bandwidth of 150 nm. Optical components were optimized to acquire rat retinal images. The right optic nerve was crushed intraorbitally with a clip. The left eye served as the untreated control. Circumpapillary OCT scans with a circle diameter of 500 microm centered on the optic disc were performed before and 1, 2, and 4 weeks after the crush. Repeatability and reproducibility of RNFL thickness measurements were evaluated. The RNFL thicknesses at 400, 500, and 600 microm from the center of the optic disc determined by linear vertical OCT scans were compared with thicknesses in retinal sections. RESULTS The mean RNFL thicknesses in circumpapillary OCT scans were 27.9 +/- 1.8, 29.2 +/- 2.4, 19.9 +/- 2.3, and 4.5 +/- 3.6 microm before and 1, 2, and 4 weeks after the crush, respectively. RNFL thickness was unchanged 1 week after the crush, but then decreased significantly and progressively after the second week (P < 0.01). Coefficients of repeatability and reproducibility were less than 10% except for the crushed eyes at 4 weeks. RNFL thicknesses in OCT images correlated significantly with thicknesses determined histologically (r = 0.90, P < 0.001). CONCLUSIONS OCT is a useful and valuable tool for quantitative evaluation of rat RNFL thickness.

Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma?

PurposeWe investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). Patients and MethodsWe retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. ResultsNinety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P<0.0001). Twenty-one eyes (38.2%) from the enlarged group exhibited recurrent DH. In 48 eyes (87.3%) from the enlarged group, the enlargement of RNFLD was toward the fovea. When DHs located apart from RNFLD were excluded, RNFLD enlarged in the direction of DH in 21 of 25 eyes (84.0%). The cumulative probability of non progression in the visual field was significantly lower in the enlarged group (10–year survival rate: 0.52±0.11) than in the stable group (10-year survival rate: 0.89±0.08) (P=0.0019). ConclusionsThe enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field.

Focal relationship between structure and function within the central 10 degrees in glaucoma.

PURPOSE To investigate which measurements of inner macular thickness are the most useful for evaluating the focal relationship with visual sensitivity within the central 10° in glaucoma and which layers require correction for retinal ganglion cell (RGC) displacement. METHODS Sixty eyes of 60 subjects with glaucoma were included. Sensitivity of each test point of 10-2 standard automated perimetry was compared with the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), GCL+ inner plexiform layer (IPL), and RNFL+GCL+IPL (GCC), with and without RGC displacement, using Spearmans rank correlation coefficients. Visual sensitivity was evaluated by unlogged 1/Lambert (1/L) values. RESULTS Retinal nerve fiber layer thickness correlated significantly with the sensitivities of all test points except for some in the papillomacular bundle region when adjusting for RGC displacement (rs = 0.287-0.767, P < 0.05). In the central 5.8°, the GCL and (GCL+IPL) thickness correlated significantly with the sensitivities of all test points when adjusting for RGC displacement (GCL: rs = 0.363-0.729, P < 0.01; (GCL+IPL): rs = 0.359-0.715, P < 0.01). The GCC thickness correlated significantly with the sensitivities of all 68 test points when adjusting for RGC displacement (rs = 0.359-0.767, P < 0.01). RGC displacement improved the correlation between sensitivity and GCL, (GCL+IPL), and GCC in the central 4 points (GCL: rs = from 0.270-0.470 to 0.421-0.540; (GCL+IPL): rs = from 0.195-0.450 to 0.381-0.549; GCC: rs = from 0.132-0.449 to 0.359-0.562). CONCLUSIONS The GCC is the most useful parameter to evaluate structure and function within the central 10° in glaucoma. Adjusting for RGC displacement is essential to evaluate the relationship between structure of the GCL-related layer and function at the central macula.

Endophthalmitis Caused by Enterococcus mundtii

ABSTRACT Enterococcus mundtii has rarely been isolated from environmental or human sources. We report the identification of E. mundtii as a pathogen of human infectious disease by DNA sequencing of 16S rRNA and sodA genes in a case of endophthalmitis developed in a 66-year-old immunocompetent gardener.

Reproducibility of thickness measurements of macular inner retinal layers using SD-OCT with or without correction of ocular rotation.

PURPOSE To evaluate the intervisit reproducibility of spectral-domain optical coherence tomography (SD-OCT) measurement of the macular retinal nerve fiber layer thickness (mRNFLT); combined ganglion cell layer and inner plexiform layer (GCL+IPL) thickness; and ganglion cell complex (GCC) thicknesses (sum of mRNFLT and GCL+IPL thicknesses) compared with that of circumpapillary RNFLT (cpRNFLT) and the effect of ocular rotation on reproducibility. METHODS SD-OCT imaging was performed twice on different days in one eye of 58 normal subjects and 73 glaucoma patients. The reproducibility was evaluated for the entire 4.8-mm × 4.8-mm macular area and subareas (upper and lower halves, 2 × 2, 4 × 4, and 8 × 8 grids), and the 360°, upper, and lower halves mean cpRNFLT with and without correction of ocular rotation. RESULTS The coefficients of variation (CVs) of GCL+IPL and GCC thickness measurements averaged below 1.0% for the entire and upper and lower half macular areas, and below 4.2% in the macular subareas in normal and glaucoma eyes, which were significantly smaller (P < 0.001) than those of mRNFLT measurements in the same areas of the same eyes. The CVs of mRNFLT measurements were significantly smaller than those of the cpRNFLT only in the lower half mean area in normal eyes. The reproducibility was minimally affected by correction of ocular rotation or presence of glaucoma. CONCLUSIONS The reproducibility of the macular (GCL+IPL) and GCC thickness measurements was better than that of mRFNLT and cpRNFLT in normal and glaucoma eyes and minimally affected by correction of ocular rotation.

Clinical Factors Related to Recurrence of Anterior Segment Neovascularization After Treatment Including Intravitreal Bevacizumab

PURPOSE To investigate the impact of clinical factors on the recurrence of anterior segment neovascularization after intravitreal bevacizumab injection. DESIGN Retrospective, consecutive, interventional case series. METHODS Charts of 54 eyes of 54 consecutive patients who received intravitreal bevacizumab injections (1.25 mg) for the treatment of anterior segment neovascularization were reviewed. The mean follow-up period +/- standard deviation was 16 +/- 8 months (range, 4 to 31 months). For eyes with incomplete panretinal photocoagulation, additional retinal ablation was performed within 1 month after bevacizumab injection. Differences in clinical factors were compared between eyes with and without recurrence. Baseline clinical factors were age, gender, predisposing diagnosis, status and clinical stages of anterior segment neovascularization, fundus neovascularization, visual acuity, baseline intraocular pressure, previous retinal ablation, previous intraocular surgeries, lens status, history of glaucoma, hemoglobin A1c level, hypertension, and creatinine level. Factors after intravitreal bevacizumab administration were additional retinal ablation, intraocular surgeries, mean intraocular pressure until recurrence, and visual acuity. Univariate and multivariate Cox proportional hazards regression analyses were performed to evaluate the contribution of these factors to recurrence. Kaplan-Meier survival analysis with the log-rank test was performed with recurrence as the end point. RESULTS Recurrence occurred in 26 (48%) eyes a mean +/- standard deviation of 4.7 +/- 3.0 months (range, 2 to 11 months) after bevacizumab injection. Multivariate analysis identified trabeculectomy after bevacizumab injection as the primary inhibitory factor for recurrence (hazard ratio, 0.23; 95% confidence interval, 0.094 to 0.55; P = .001). Kaplan-Meier survival analysis showed that trabeculectomy after bevacizumab injection provided a significantly better survival rate (P < .001). CONCLUSIONS Recurrence of anterior segment neovascularization after intravitreal bevacizumab injection occurs despite intensive retinal ablation: trabeculectomy may suppress recurrence.