Kohei Takayama

A novel method to detect local ganglion cell loss in early glaucoma using spectral-domain optical coherence tomography.

PURPOSE To test the glaucoma-discriminating ability of a new method for detecting local ganglion cell loss using spectral-domain optical coherence tomography (OCT). METHODS This study included 58 glaucomatous and 48 healthy eyes from Japanese subjects. Combined thickness of the ganglion cell layer and inner plexus layer (GCIPL) was measured on a macular cube scan in Cirrus HD-OCT. Average GCIPL thickness within a macular elliptical annulus and minimum GCIPL thickness on 360 spokes extending from the inner to the outer radius of the elliptical annulus were calculated. Area under the receiver operating characteristic curve (AROC) to discriminate between healthy eyes and early (mean deviation [MD], ≥-6 dB)/advanced (MD, <-6 dB) glaucomatous were compared between parameters. RESULTS Forty-three were normal-tension glaucoma, and 15 were high-tension glaucoma. The mean minimum GCIPL thickness was 77.0 μm in healthy eyes and 60.6 μm in glaucomatous eyes (P < 0.001). For the intersession repeatability, the coefficients of variation for average GCIPL and minimum GCIPL were 0.98 and 1.85 in glaucomatous eyes, and 0.89 and 1.85 in healthy eyes, respectively. Minimum GCIPL thickness AROC (0.896) was significantly higher (P = 0.0062) than average GCIPL thickness (0.821) for early glaucoma, whereas minimum GCIPL AROC (0.991) was comparable (P = 0.103) to average GCIPL (0.964) for advanced glaucoma. The minimum GCIPL thickness AROC was comparable (P = 0.861) to average circumpapillary retinal nerve fiber layer (cpRNFL) thickness (0.890) for early glaucoma. CONCLUSIONS In Japanese patients with 74.1% of normal-tension glaucoma, the minimum GCIPL on spokes may be useful for detecting early glaucoma.

Optical Coherence Tomographic Evaluation of Foveal Hard Exudates in Patients with Diabetic Maculopathy Accompanying Macular Detachment

OBJECTIVE To study morphologic changes of serous retinal detachment (SRD) and hyperreflective dots, which have been reported to be precursors of hard exudates, detectable in SRD using optical coherence tomography (OCT) to assess whether or not the OCT findings are correlated with the subfoveal deposition of hard exudates in patients with diabetic macular edema (DME) accompanied by SRD. DESIGN Retrospective chart review. PARTICIPANTS Twenty-eight eyes of 19 patients with DME accompanied by SRD. METHODS We imaged SRD and the hyperreflective dots in SRD using spectral domain OCT (SD-OCT). The number and distribution of the hyperreflective dots in SRD were evaluated before the initial treatment at our hospital for DME accompanied by SRD. Based on a difference in the SD-OCT findings, the study eyes were divided into 2 groups: eyes with a few dots and those with many dots. We studied the clinical course of these 2 groups to assess whether or not the findings of SRD and hyperreflective dots on the SD-OCT images were correlated with deposition of hard exudates in the subfoveal space during follow-up. MAIN OUTCOME MEASURES Correlation of the SD-OCT findings of SRD and hyperreflective dots with deposition of hard exudates in the subfovea of patients with DME accompanied by SRD. RESULTS Subfoveal deposition of hard exudates was seen in 11 of the 28 eyes at the final examination. Before initial treatment at our hospital, 14 eyes had a few hyperreflective dots SRD and 14 eyes had many hyperreflective dots. Whereas no deposition of hard exudates in the subfoveal space was seen in the former eyes, it was seen in 11 of the latter 14 eyes (P < 0.0001). In addition, using SD-OCT, we found discontinuity of the outer border of detached neurosensory retina in 9 of the 28 eyes. Of these 9 eyes, 1 was in the group with few hyperreflective dots and eight were in the group with many hyperreflective dots (P = .0046). CONCLUSIONS In patients with DME accompanied by SRD, SD-OCT revealed that hyperreflective dots may be associated with the subfoveal deposition of hard exudates during follow-up.

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.

High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy.

PURPOSE To study pathologic changes in the photoreceptors in eyes with idiopathic macular telangiectasia (MacTel) type 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO). METHODS Thirteen eyes with nonproliferative MacTel type 2 and 10 normal eyes underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with an original prototype AO-SLO system. All eyes with MacTel type 2 were examined with fluorescein angiography (FA), fundus autofluorescence (FAF), confocal blue reflectance (CBR), and fundus-monitoring microperimetry (MP). RESULTS All eyes with MacTel type 2 had ring-like dark areas and/or small patchy regions on AO-SLO images; significantly lower cone density than that of normal eyes in each hemisphere at 0.5 mm from the foveal center; an area with parafoveal reflectance in CBR that was larger than the hyperfluorescence area in FA, the area of increased FAF, the dark areas on AO-SLO, and the area of decreased retinal sensitivity on MP. Dark areas on AO-SLO roughly corresponded to the leakage area in FA, but dark areas were also seen in areas without FA leakage in 11 eyes, including an eye with the earliest clinical signs of MacTel. Visual acuity and retinal sensitivity correlated with mean cone density 0.5 mm from the center of the fovea. CONCLUSIONS In eyes with MacTel type 2, AO-SLO revealed unique dark regions in the cone mosaic and decreased cone density that was associated with decreased vision, even in areas with normal vasculature, which suggests that this feature represents early neuronal changes involved in the pathogenesis of MacTel type 2.

High-resolution imaging of the retinal nerve fiber layer in normal eyes using adaptive optics scanning laser ophthalmoscopy.

Purpose To conduct high-resolution imaging of the retinal nerve fiber layer (RNFL) in normal eyes using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Methods AO-SLO images were obtained in 20 normal eyes at multiple locations in the posterior polar area and a circular path with a 3–4-mm diameter around the optic disc. For each eye, images focused on the RNFL were recorded and a montage of AO-SLO images was created. Results AO-SLO images for all eyes showed many hyperreflective bundles in the RNFL. Hyperreflective bundles above or below the fovea were seen in an arch from the temporal periphery on either side of a horizontal dividing line to the optic disc. The dark lines among the hyperreflective bundles were narrower around the optic disc compared with those in the temporal raphe. The hyperreflective bundles corresponded with the direction of the striations on SLO red-free images. The resolution and contrast of the bundles were much higher in AO-SLO images than in red-free fundus photography or SLO red-free images. The mean hyperreflective bundle width around the optic disc had a double-humped shape; the bundles at the temporal and nasal sides of the optic disc were narrower than those above and below the optic disc (P<0.001). RNFL thickness obtained by optical coherence tomography correlated with the hyperreflective bundle widths on AO-SLO (P<0.001) Conclusions AO-SLO revealed hyperreflective bundles and dark lines in the RNFL, believed to be retinal nerve fiber bundles and Müller cell septa. The widths of the nerve fiber bundles appear to be proportional to the RNFL thickness at equivalent distances from the optic disc.

Photoreceptor Damage and Foveal Sensitivity in Surgically Closed Macular Holes: An Adaptive Optics Scanning Laser Ophthalmoscopy Study

PURPOSE To assess photoreceptor structure using adaptive optics scanning laser ophthalmoscopy (AO SLO) and spectral-domain optical coherence tomography (SD OCT) and to evaluate the relationship between structural abnormalities and foveal sensitivity in eyes with surgically closed macular hole (MH). DESIGN Prospective, interventional case series. METHODS Twenty-one eyes of 19 patients with idiopathic MH underwent a full ophthalmologic examination, including SD OCT at baseline. Imaging with SD OCT, an original prototype AO SLO system, and microperimetry were performed at 6 months after surgery. RESULTS All patients underwent anatomically successful MH closure. On AO SLO, dark areas (0.004 to 0.754 mm(2)) were seen in all eyes after MH repair. Lower cone density correlated with poorer postoperative visual acuity and lower mean foveal sensitivity (both P < .001). Larger dark areas on AO SLO correlated with poorer postoperative visual acuity (P = .003) and lower mean foveal sensitivity (P = .006). Cone density was significantly lower and dark areas were significantly larger in eyes that had defects of the outer segments in the fluid cuff before surgery (P = .018 and P = .001, respectively) and moderately reflective foveal lesions after surgery (P < .001 and P < .001, respectively). Larger dark areas correlated with longer symptom duration before surgery (P < .001). CONCLUSIONS Structural damage to the photoreceptor layer correlated with greater decreases in visual function in eyes with surgically closed MH. AO SLO imaging is a useful and quantitative tool for detecting photoreceptor abnormalities and their association with visual acuity and retinal sensitivity in eyes with closed MH.

The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy

PURPOSE To investigate the source of moving particles in parafoveal capillaries detected by adaptive optics scanning laser ophthalmoscopy (AO-SLO). METHODS AO-SLO videos were acquired from the parafoveal areas of eyes of healthy subjects. The gray-scale values inside and outside the moving particles were measured and compared. Thereafter, successive frames of the captured videos were analyzed under higher magnification to detect changes in the gray values of bright spots inside the capillaries, before and during passage of the particles. Simultaneously, changes in the gray values of areas without the bright spots were measured for comparison. Then, the authors analyzed the packing arrangements of the bright spots in the particles, and measured the particle velocity using spatiotemporal images of the target capillary. RESULTS There were no significant differences in the gray values between the moving particles and the cone mosaic outside the parafoveal capillaries adjacent to the particles. The gray value of the bright spots in the dark shadow of the vessels increased when the particles passed through, while the dark areas without bright spots remained dark. There were no significant differences in the packing arrangements between the bright spots and surrounding cone mosaic. Further, the concordance rate of packing arrangements of bright spots between two consecutive moving particles in the capillary was 95.8%. The mean particle velocity was 1.34 ± 0.42 mm/s. CONCLUSIONS The particles moving in the capillaries are suggested to be reflections of photoreceptor aggregates that pass through circulating transparent objects such as leukocytes or plasma gaps.

High-Resolution Imaging of Retinal Nerve Fiber Bundles in Glaucoma Using Adaptive Optics Scanning Laser Ophthalmoscopy

PURPOSE To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). DESIGN Prospective cross-sectional study. METHODS Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. RESULTS The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). CONCLUSIONS AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function.

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.

Macular Cone Abnormalities in Retinitis Pigmentosa with Preserved Central Vision Using Adaptive Optics Scanning Laser Ophthalmoscopy

Purpose To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Methods Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. Results In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. Conclusions Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.