Yugo Kimura

Three-dimensional imaging of lamina cribrosa defects in glaucoma using swept-source optical coherence tomography.

PURPOSE To visualize lamina cribrosa defects using three-dimensional (3D) swept-source optical coherence tomography (SS-OCT), and to determine the factors associated with this feature. METHODS All subjects were examined using an SS-OCT prototype system, which uses a tunable laser as a light source, operated at 100,000 Hz A-scan repetition rate in the 1050-nm wavelength. A 3D raster scan protocol consisting of 256×256 A-scans was acquired over a square area of 3 mm×3 mm centered on the optic disc. En face sectioned volume and serial en face images and orthogonal (horizontal and vertical) serial B-scans were evaluated. RESULTS A total of 182 eyes of 111 patients with glaucoma and 29 healthy eyes of 26 subjects were included. Twenty full-thickness focal lamina cribrosa defects were found in 12 (6.6%) of 182 eyes with glaucoma, whereas no lamina defects were found in healthy eyes. Nine eyes (75.0%) showed 15 full-thickness lamina cribrosa defects near the margin of the lamina cribrosa, and 3 eyes showed 4 lamina defects at the margin, as if detached from the sclera. Focal lamina cribrosa defects corresponded with neuroretinal rim thinning, concurrent or previous disc hemorrhages, abnormal circumpapillary retinal nerve fiber layer thickness, and visual field defects. The presence of lamina cribrosa defects was significantly associated with longer axial length and disc hemorrhages (P=0.033 and 0.024, respectively). CONCLUSIONS 3D SS-OCT imaging allows visualization of the lamina cribrosa defects, which may be more prevalent in eyes with longer axial length and related to disc hemorrhages.

Microstructure of Peripapillary Atrophy and Subsequent Visual Field Progression in Treated Primary Open-Angle Glaucoma

PURPOSE To investigate the relationship between the microstructure of β-zone peripapillary atrophy (PPA) and the subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG), including highly myopic eyes. DESIGN Retrospective cohort study. PARTICIPANTS A total of 129 patients with POAG who had been followed up for a minimum of 2 years and had undergone at least 5 reliable standard automated perimetry tests after spectral-domain (SD) optical coherence tomography (OCT) examination. METHODS β-Zone PPA was evaluated from 3 SD OCT scans centered on the optic disc. Upper and lower scans were defined as scans at 30° above and below the horizontal scan, respectively. From 3 scans of each eye, β-zone PPA was classified as PPA(+BM) or PPA(-BM) on the basis of the presence or absence of Bruchs membrane (BM), respectively. Eyes were classified into 3 groups according to the horizontal scan images: group A (only PPA(+BM)), group B (both PPA(+BM) and PPA(-BM)), and group C (only PPA(-BM)). Factors associated with the subsequent mean deviation (MD) slope after OCT examination were analyzed, and the hemifield total deviation (TD) slope was assessed in eyes with unilateral hemifield VF defects in the corresponding direction. MAIN OUTCOME MEASURES Subsequent MD slope after OCT examination. RESULTS The VF progression in group A was faster than in group C (P = 0.004). A larger PPA(+BM) width was associated with a faster MD slope in all eyes (P < 0.001) and highly myopic eyes (P < 0.001) and with a faster TD slope in eyes with superior or inferior hemifield VF defects in the corresponding direction (P = 0.002 and P = 0.035, respectively). A larger PPA(-BM) was correlated with a slower MD slope in all eyes (P = 0.030 and P = 0.034) but not in highly myopic eyes. CONCLUSIONS There were significant differences in VF progression according to the microstructure of the β-zone PPA in eyes with POAG. The PPA(+BM) width may be an important risk factor for VF progression in POAG, including high myopia, and the PPA(-BM) width may have a protective effect for VF progression in this subtype of POAG.

Alterations in the Neural and Connective Tissue Components of Glaucomatous Cupping After Glaucoma Surgery Using Swept-Source Optical Coherence Tomography

PURPOSE To visualize changes in deep optic nerve head (ONH) structures following glaucoma surgery using (3-dimensional [3D]) swept-source optical coherence tomography (SS-OCT) and to determine the clinical and structural factors associated with postoperative lamina cribrosa (LC) and prelaminar neural tissue (PLT) changes. METHODS In this prospective observational case series, SS-OCT thin-sliced datasets of the ONH covering a 3- × 3-mm area comprised of 256 B-scans (interval between scans = ∼12 μm) were obtained before and 3 months after the surgery and evaluated in 73 eyes of 73 patients with glaucoma. Bruchs membrane opening (BMO) and anterior LC boundary were manually delineated by two methods; one in every four B-scans (64 B-scans per eye) and 15 equally spaced horizontal B-scans in BMO area, excluding both ends (interval between scans = 96-120 μm). After former delineation, the point with maximum LC depth among 64 B-scans was automatically calculated, and LC depth and PLT thickness were averaged among 5 points adding 4 points 100 μm apart from this point vertically and horizontally. Associations between the percent change in LC depth and other clinical and structural parameters were tested for statistical analysis. RESULTS Lamina cribrosa depth and axial length significantly decreased and PLT thickness significantly increased after surgery. The percent change of maximum LC depth correlated significantly with the percent change of IOP (P = 0.008), baseline LC depth (P = 0.032), and visual field mean deviation (P = 0.035; at the point with maximum LC depth), while the percent change of axial length correlated with IOP reduction (P = 0.002) but not with visual field mean deviation. CONCLUSIONS Swept-source optical coherence tomography enables 3D analysis of deep ONH structures, and the change in LC depth after glaucoma surgery have association with IOP change and the severity of glaucomatous optic neuropathy.

Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.

PURPOSE To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter). METHODS Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts. RESULTS AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG. CONCLUSIONS Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT.

Peripapillary scleral deformation and retinal nerve fiber damage in high myopia assessed with swept-source optical coherence tomography.

PURPOSE To study peripapillary morphologic changes in highly myopic eyes using swept-source optical coherence tomography at a longer wavelength. DESIGN Prospective cross-sectional study. METHODS Peripapillary regions of 196 eyes of 107 patients with high myopia (refractive error, <-8.0 diopters or axial length, >26.0 mm) were analyzed quantitatively and qualitatively with an swept-source optical coherence tomography prototype system that uses a tunable laser light source operated at a 100,000-Hz A-scan repetition rate in the 1-μm wavelength region. The visual field was evaluated by standard automated perimetry. Area of peripapillary atrophy β and presence of scleral protrusion temporal to the optic disc were assessed. RESULTS Peripapillary atrophy β area, but not disc area, was significantly larger in eyes with visual field defect (3.16 ± 2.70 mm(2); range, 0.00 to 12.85 mm(2)) than those without visual field defect (2.31 ± 2.83 mm(2); range, 0.00 to 17.70 mm(2)). Temporal scleral protrusion was detected by color stereo disc photography in 22 (19.5%) of 113 eyes with visual field defect and in 4 (4.8%) of 83 eyes without visual field defect. Scleral bending demonstrated a wide range of angles (mean, 31.0 ± 21.1 degrees; range, 2 to 80 degrees). The angle of scleral bending, but not the distances from scleral bend to disc margin or foveal center, correlated significantly with retinal nerve fiber layer thickness above the bend (r = -0.557, P = .007) and visual field defect severity (r = -0.445, P = .038). CONCLUSIONS Swept-source optical coherence tomography visualizes peripapillary deep structures in high myopia. Some cases of high myopia may be affected by direct scleral compression or stretching at the peripapillary region.

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Purpose To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia. Methods A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure β-peripapillary atrophy (PPA) lengths with and without Bruchs membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well. Results LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P<0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P<0.001), and larger vertical/horizontal tilt angles (vertical, P<0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P<0.001) and vertical tilt angle (P<0.001) were identified as significant. Conclusions The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.

Asymmetry Analysis of Macular Inner Retinal Layers for Glaucoma Diagnosis

PURPOSE To determine if asymmetry in thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer, ganglion cell complex, and total retina between upper and lower macula halves can predict glaucoma. DESIGN Retrospective case-control series. METHODS One hundred twenty-two eyes of 122 patients (30 normal eyes and 30 preperimetric, 31 early, and 31 advanced glaucoma eyes) were studied. The RNFL, ganglion cell layer, ganglion cell complex, and total retina were segmented and measured on 10 vertical B-scans over a 30 × 15 degree macular area. The equation asymmetry index =|log10 (lower hemiretinal thickness/upper hemiretinal thickness)| was used to calculate asymmetry indices for 8 pairs of upper and lower 0.5-mm segments equidistant from the fovea on each scan. Areas under the receiver operating characteristic curve (AROCs) for mean thickness and mean asymmetry index of 10 B-scans were compared. RESULTS The overlap in values for normal and glaucomatous eyes was minimal for the ganglion cell layer asymmetry index. Thickness parameters decreased with the severity of glaucoma, whereas asymmetry indices did not. AROCs for thickness measurements tended to increase with increasing glaucoma severity (preperimetric, 0.746-0.808; early, 0.842-0.940; advanced, 0.943-0.995), whereas AROCs for asymmetry indices did not have distinct ranges according to glaucoma severity (advanced, 0.819-0.996; early, 0.861-0.998; preperimetric, 0.773-0.994). The AROC for the ganglion cell layer asymmetry index remained almost perfect regardless of glaucoma severity (0.994-0.998). CONCLUSIONS Macular retinal layer thickness asymmetry indices, particularly for the ganglion cell layer, show promise as early indicators of glaucomatous retinal damage.

Macular Structure Parameters as an Automated Indicator of Paracentral Scotoma in Early Glaucoma

PURPOSE To evaluate the predictive ability of macular parameters defined in the significance map created using spectral-domain optical coherence tomography (SD-OCT) for paracentral visual field defects in early glaucoma. DESIGN Prospective comparative study. METHODS We studied 78 early-glaucomatous eyes of 78 patients, who underwent SD-OCT and standard automated perimetry 10-2. Macular layer parameters included the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) + inner plexiform layer (IPL), and RNFL + GCL + IPL. The minimal distance between the area with abnormal (P < 1%) thickness and foveal center was defined as the shortest distance. A wider area of an abnormally thinned (<1%) region, within either an inferior or a superior hemicircle with a diameter of 6 mm centered at the fovea, was defined as the macular abnormal area. A circumpapillary RNFL parameter was defined in its 36 sectors. Areas under the receiver operating characteristic curves (ROCs) were calculated to discriminate between eyes with (n = 39) and without (n = 39) paracentral visual field defects in the central 5 degrees. RESULTS Measurement reproducibility was almost perfect in the macular parameters at P < 1% (intraclass correlation, 0.907-0.942). Areas under the ROC were significantly higher (P ≤ 0.01) in the macular parameters (0.870-0.930), including the shortest distance of GCL + IPL/RNFL + GCL + IPL, and the macular abnormal area of RNFL/GCL + IPL/RNFL + GCL + IPL than in the circumpapillary RNFL parameter (0.676). When specificity was fixed at ≥90%, the shortest distance of GCL + IPL (area under the ROC = 0.874) and the macular abnormal area of RNFL (area under the ROC = 0.894) showed sensitivities greater than 50%. CONCLUSIONS Macular structural parameters defined on an SD-OCT significance map may be potentially useful predictors of the presence of paracentral scotoma.

Microcystic inner nuclear layer changes and retinal nerve fiber layer defects in eyes with glaucoma

Objective To examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors. Design Retrospective, cross-sectional, observational study. Methods Two hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area. Results Microcystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions. Conclusions Microcystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.

Cisplatin-conjugated degradable gelatin microspheres: fundamental study in vitro

The object of this study was to generate cisplatin-conjugated gelatin microspheres (GMSs) and to confirm the subsequent release of cisplatin in vitro. The GMSs (1 mg) were immersed in 50 microl of a cisplatin solution (0.06, 0.15, 0.27, 0.30 or 0.54 mg ml(-1)) at 38 degrees C to allow conjugation. The cisplatin-conjugated GMSs were then extensively washed in double-distilled water and freeze-dried. The platinum concentration in the GMSs samples was investigated as a function of the concentration of cisplatin solution used in their preparation, the number of immersions in cisplatin (1, 2, 3, 4 or 5) and the period of immersion (1, 6 or 11 h). In vitro release tests were performed at different time intervals (1, 3, 6, 12 or 24 h) to allow the rate of cisplatin release to be calculated. The platinum concentration of the GMSs increased in proportion to the concentration of cisplatin solution and the length or number of immersions in cisplatin. In vitro release tests demonstrate that the release rate (%) from GMSs after 1, 3, 6, 12 or 24 h was 4.8, 5.5, 7.6, 10.0 and 12.4, respectively. We demonstrated the ability of GMSs to bind cisplatin forming cisplatin-conjugated GMSs. Moreover, we showed that cisplatin continued to bind GMSs strongly during the in vitro release test.