AIE-ESIPT Photoluminescent Probe Based on 3-(3-Hydroxypyridin-2-yl)isoquinolin-4-ol for the Detection of Intracellular Hydrogen Peroxide.

Excited-state intramolecular proton transfer (ESIPT) molecules, which feature large Stokes shifts to avoid self-absorption, play an essential role in photoluminescent bioimaging probes. Herein, we report the development of an ESIPT molecule 3-(3-hydroxypyridin-2-yl)isoquinolin-4-ol (PiQ). PiQ not only undergoes a distinct ESIPT process unlike the symmetrical 2,2'-bipyridyl-3,3'-diol but also exhibits aggregation-induced emission (AIE) characteristics. PiQ self-assembles into aggregates with an average size of 241.0±51.9 nm in aqueous solutions, leading to significantly enhanced photoluminescence. On the basis of the ESIPT and AIE characteristics of PiQ, the latter is functionalized with a hydrogen peroxide-responsive 4-pinacoratoborylbenzyl group (B) and a carboxylesterase-responsive acetyl group (A) to produce a photoluminescent probe B-PiQ-A. The potential of PiQ for applications in bioimaging and chemical sensing is underscored by its efficient detection of both endogenous and exogenous hydrogen peroxide in living cells.

Cone Integrity in Glaucoma: An Adaptive-Optics Scanning Laser Ophthalmoscopy Study.

PURPOSE: To investigate photoreceptor changes in eyes with glaucoma. DESIGN: Cross-sectional study. METHODS: The study included 35 eyes of 35 patients with primary open-angle glaucoma who had suffered parafoveal visual field loss at least 3 years previously, as well as 21 eyes of 21 normal subjects. Eyes with an axial length ≥26.0 mm were excluded. All subjects underwent a full ophthalmologic examination, including spectral-domain optical coherence tomography (SDOCT) and prototype adaptive-optics scanning laser ophthalmoscopy (AO-SLO) imaging. RESULTS: As determined using AO-SLO, eyes with glaucoma did not differ significantly from normal eyes in terms of either cone density (26 468 ± 3392 cones/m2 vs 26 147 ± 2700 cones/m2, respectively; P = .77; measured 0.5 mm from the foveal center) or cone spatial organization (ratio of hexagonal Voronoi domain: 43.7% ± 4.4% vs 44.3% ± 4.9%; P = .76; measured 0.5 mm from the foveal center). Furthermore, SDOCT showed that the 2 groups did not differ significantly in terms of the photoreceptor-related layer thickness, and that the photoreceptor ellipsoid zone band was continuous in all normal and glaucoma eyes. In glaucoma eyes with vertically asymmetric severity, the more affected side did not significantly differ from the less affected side in terms of cone density, cone spatial organization, or photoreceptor-related layer thickness. In 8 eyes (22.9%) with glaucoma, dark, partition-like areas surrounded the cones on the AO-SLO. CONCLUSIONS: Both AO-SLO and SDOCT showed cone integrity in eyes with glaucoma, even in areas with visual field and nerve fiber loss. In AO-SLO, microcystic lesions in the inner nuclear layer may influence images of the cone mosaic.

Transconjunctival sutureless intrascleral intraocular lens fixation using intrascleral tunnels guided with catheter and 30-gauge needles.

We invented a new method for fixing an intraocular lens (IOL) in the scleral tunnel without using a wide conjunctival incision. Modified bent catheter needles were used to penetrate the IOL haptics through the sclerotomy sites. The IOL haptics were inserted into 30-guage (G) scleral tunnels guided by double 30-G needles piercing the sclera. All procedures were performed through the conjunctiva without wide incision. The procedure does not require special forceps, trocars or fibrin glue, only catheter and 30-G needles. The aid of an assistant was not required to support the IOL haptic. The procedures were easily learnt based on our previous method. As with other transconjunctival sutureless surgeries, patients feel less discomfort and the conjunctiva can be conserved for future glaucoma surgery. Complications included two cases of vitreous haemorrhage (16.7%), and one case each of postoperative hypotony, and iris capture (8.3%). Astigmatism induced by intraocular aberration was the same as we reported previously. Our method for fixing the IOL into the scleral tunnel is innovative, less expensive, less invasive and quick. This modified method is a good alternative for fixing IOL haptics into the sclera.

Intrascleral fixation technique using catheter needles and 30-gauge ultrathin needles: lock-and-lead technique.

UNLABELLED: We report a new intrascleral fixation technique for a standard 3-piece posterior intraocular lens (IOL) using catheter needles and 30-gauge ultrathin needles instead of a special forceps and minimal intraocular manipulation in eyes without capsule support. Modified catheter needles are used to deliver the IOL haptic. The IOL haptic is secured extraocularly between the cannula and needle of a catheter needle and then advanced through the sclerotomy site. Scleral tunnels are created using 30-gauge ultrathin needles, which also serve as a guide to introduce the haptics. This technique can be performed even in cases in which miosis and corneal edema prevent anterior chamber observation. The guide needle facilitates haptic insertion into the long and narrow scleral tunnels. The procedure is a good alternative to current techniques. FINANCIAL DISCLOSURE: Dr. Akimoto is a consultant to Kowa Co., Ltd. No other author has a financial or proprietary interest in any material or method mentioned.

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 ß-peripapillary atrophy (PPA) lengths with and without Bruch's 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.

High-resolution imaging of photoreceptors in macular microholes.

PURPOSE: To assess photoreceptor structure in macular microholes by using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and spectral-domain optical coherence tomography (SD-OCT) and compare with visual acuity. METHODS: Fourteen eyes from 12 patients with macular microholes underwent a full ophthalmologic examination and imaging with a fundus camera, SD-OCT, and an original prototype AO-SLO system at each visit. RESULTS: All eyes had a cone outer segment tip line disruption and a normal retinal pigment epithelium line on SD-OCT images. Adaptive optics scanning laser ophthalmoscopy revealed foveal cone disruption (13 eyes, round or oval; 1 eye, T-shaped) in all eyes. Cone disruption area (mean = 14,805 ± 9120 µm(2); range, 3495-35,901 µm(2)) positively correlated with logMAR visual acuity at the first visit (P = 0.015, rs = 0.679). During the follow-up period, cone disruption area increased in two eyes, was stable in seven eyes, and decreased in five eyes. At the last visit, cone disruption area (mean = 8717 ± 7432 µm(2); range, 0-25,746 µm(2)) also positively correlated with logMAR visual acuity (P = 0.035, rs = 0.610). In one patient with bilateral microholes and no apparent vitreous traction, lesion size gradually increased. Cone disruption area decreased and visual acuity improved following oral prednisone therapy. CONCLUSIONS: Cone disruption occurs in eyes with macular microholes and a larger cone disruption area translates into a poorer visual acuity. Macular microholes, which are commonly observed as foveal cone inner and outer segment disruptions, may occur in eyes with or without vitreofoveal traction.

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. Bruch's 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.

Imaging of localized retinal nerve fiber layer defects in preperimetric glaucoma using spectral-domain optical coherence tomography.

PURPOSE: To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction. PATIENTS AND METHODS: Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise-reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT. RESULTS: All 40 RNFL defects identified by photography had angular widths <30 degrees and no disruption of RNFL reflectivity on Spectralis. Circumpapillary RNFL (cpRNFL) boundaries were accurately determined by Spectralis for 38 (95.0%) of the 40 defects, by RTVue-100 for 25 (62.5%), and by Stratus OCT for 23 (57.5%). Sensitivity for the detection of RNFL defects (cpRNFL thinning to <1% of normal for an age-matched database) was 15% for Stratus, 42.5% for RTVue, and 47.5% for Spectralis on sector maps and significantly higher for SD-OCT on temporal-superior-nasal-inferior-temporal (TSNIT) thickness graphs: RTVue-100 (57.5%; P=0.031) and Spectralis (90.0%; P=0.0001). On the basis of TSNIT thickness graphs, sensitivity for the detection of RNFL defects was significantly higher for Spectralis compared with RTVue-100 (P=0.001) and Stratus (P=0.0005). Spectralis TSNIT graphs were more sensitive (P=0.001) for glaucoma detection without significant reduction (P=0.125) in specificity compared with Spectralis sector maps. CONCLUSIONS: Our results suggest that accurate measurement of cpRNFL thickness by speckle noise-reduced SD-OCT and a comparison of the results with normative database using TSNIT graphs are required to improve the sensitivity for detecting preperimetric RNFL defects.

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.

Macular imaging in highly myopic eyes with and without glaucoma.

PURPOSE: To determine how evaluations of macular structures on spectral-domain optical coherence tomography compare with those of the optic disc and circumpapillary retinal nerve fiber layer (RNFL) in discriminating between highly myopic eyes with and without glaucoma. DESIGN: Retrospective, comparative study. METHODS: The appearances of ganglion cell layer and RNFL on Spectralis macular scans (Heidelberg Engineering) and optic disc on photographs were evaluated by 2 observers. The receiver operating characteristic regression was conducted for macular ganglion cell complex and circumpapillary RNFL measurements on RTVue-100 (Optovue). RESULTS: Ninety highly myopic eyes (-6.0 to -15.0 diopters; mean deviation [MD], -5.6 ± 5.1 dB) and 91 non-highly myopic eyes (1.0 to -5.5 diopters; MD, -4.9 ± 5.7 dB) were enrolled. In highly myopic eyes (<-6 diopters), the Cohen κ for qualitative decisions by observers was 0.363 for photographs and 0.946 for Spectralis macular scans, and observers' evaluations of Spectralis macular scans were more accurate (94.5% and 94.5%, respectively; P < .0001) than their evaluations of photographs (71.4% and 80.2%, respectively). In the receiver operating characteristic regression analyses assessing the influences of age, sex, MD, and axial length, the better MD (P = .002 to .016) and longer axial length (P = .031 to .041) were associated significantly with diagnostic performances for all or some spectral-domain optical coherence tomography parameters. The receiver operating characteristic curves of average macular ganglion cell complex and circumpapillary RNFL thicknesses were comparable at low MD. CONCLUSIONS: In high myopes, observers' assessments of the spectral-domain optical coherence tomography macular scans may agree better and be more accurate than observers' optic disc assessments. Glaucoma diagnostic performance of the macular ganglion cell complex may be less affected by axial length compared with that of circumpapillary RNFL.

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.

Objective assessment of foveal cone loss ratio in surgically closed macular holes using adaptive optics scanning laser ophthalmoscopy.

PURPOSE: To use adaptive optics scanning laser ophthalmoscopy (AO-SLO) to quantify cone loss ratio in the foveola in order to assess foveal cone status and to investigate relationships between foveal structural abnormalities and visual function in patients with macular hole (MH) after surgery. METHODS: We evaluated 10 normal eyes of 10 healthy volunteers and 19 eyes of 18 patients in whom anatomically successful MH closure had been performed. All subjects underwent a comprehensive ophthalmologic examination that included measurements of spectral-domain optical coherence tomography and AO-SLO. RESULTS: On AO-SLO regular cone mosaic was seen in all normal eyes whereas dark regions suggesting cone loss were seen in all eyes after MH repair. Visual acuity was better in eyes without dark regions at the center of the fovea than in eyes with them (P = 0.001). Cone loss ratio in the foveola correlated with postoperative visual acuity (P<0.001), mean foveal sensitivity (P = 0.029), thinner inner and outer segments at the center of the fovea (P = 0.002), larger size of the disrupted inner and outer segment junction line (P = 0.018), and cone outer segment tip line (P<0.001). Cone loss ratio in the foveola was significantly greater in eyes that had moderately reflective foveal lesions after surgery (P = 0.006). CONCLUSIONS: AO-SLO is a useful means of assessing foveal cone damage objectively and quantitatively. The location and extent of cone damage, especially if it involves the foveola, is an important factor determining visual function after MH surgery.

Measurement of macular ganglion cell layer and circumpapillary retinal nerve fiber layer to detect paracentral scotoma in early glaucoma.

BACKGROUND: Glaucoma patients with paracentral scotoma are at higher risk of losing central vision than those without glaucoma. The purpose of this study was to determine whether macular inner retinal layer (MIRL) measurements with spectral-domain optical coherence tomography (SD-OCT) outperform circumpapillary retinal nerve fiber layer (cpRNFL) measurements in discriminating between eyes with and without paracentral scotoma. METHODS: This retrospective study included 63 early glaucomatous eyes of 63 patients with (PSI group) or without (PSF group) paracentral visual field (VF) defects. MIRL thicknesses, including macular ganglion cell complex (mGCC), macular ganglion cell layer + inner plexiform layer (mGCL+), macular RNFL (mRNFL), and cpRNFL thickness were measured using a SD-OCT instrument (3D OCT-2000). The MIRL and cpRNFL were divided into 50 grid cells and 36 sectors, respectively, which were numbered from center/temporal to periphery/nasal. Discriminating ability of the methods for number of cells/sectors with abnormal thickness (<5% of normal) and average thickness in the hemisphere corresponding to the VF defects (termed hemi-thickness) was compared by area under the receiver operating characteristics curves (AROCs). RESULTS: The number of abnormal nearest sectors of cpRNFL and all MIRL parameters were significantly smaller in the PSI group than in the PSF group (P ≤ 0.001-0.047), whereas no significant differences were found for average or hemi-cpRNFL thickness. The AROCs of the number of abnormal nearest cells for mGCC and mGCL+ and average hemi-thickness for mGCC, mGCL+, and mRNFL were comparable and significantly higher than those of the number of abnormal nearest sectors/cells for cpRNFL (P = 0.0002-0.0063) and mRNFL (P = 0.0003-0.0267) parameters. CONCLUSIONS: Regional assessment of MIRL thickness as measured by SD-OCT may potentially be an effective method for predicting central involvement of VF defects in early glaucoma.

Comparison of cone pathologic changes in idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy.

PURPOSE: To compare pathologic changes in the photoreceptors of eyes with idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO). DESIGN: Prospective cross-sectional study. METHODS: Eleven eyes with idiopathic macular telangiectasia type 1, 14 eyes with 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 idiopathic macular telangiectasia were examined with fluorescein angiography (FA), confocal blue reflectance, and microperimetry. RESULTS: Compared with normal eyes (29 017 ± 5507 cones/mm(2)), those with idiopathic macular telangiectasia type 1 had significantly lower cone density on the temporal side (18 427 ± 4908 cones/mm(2), P = .010). The FA leakage area (5.90 ± 3.23 mm(2)) was larger than the dark regions (2.45 ± 2.40 mm(2)) on AO-SLO (P = .003)-which were observed only in the FA leakage area. Compared with normal eyes, those with idiopathic macular telangiectasia type 2 had significantly lower cone density in all areas (P < .05 for all). Patchy dark regions were also seen in areas without FA abnormalities in 12 eyes. Higher mean retinal sensitivity correlated with greater mean cone density 0.5 mm from the center of the fovea (type 1: P = .010; type 2: P < .001). CONCLUSIONS: Idiopathic macular telangiectasia type-specific differences in the distribution of photoreceptor abnormalities were shown in the AO-SLO images. For both idiopathic macular telangiectasia types 1 and 2, visual impairment was associated with cone damage.

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.

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.

Retinal nerve fiber layer defects in highly myopic eyes with early glaucoma.

PURPOSE: To compare the retinal nerve fiber layer (RNFL) defects in early glaucomatous eyes between highly and non-highly myopic eyes. METHODS: Sixty-one highly myopic eyes (< -6.0 diopters [D]) of 61 patients and 55 non-highly myopic eyes of 55 patients with early visual field (VF) defects were studied. The angular locations and widths of the RNFL defects were measured from red-free fundus photographs. The RNFL defect closest to the fovea was designated the "nearest RNFL defect" of each hemisphere. RESULTS: In total, 131 RNFL defects were found in highly myopic eyes and 82 in non-highly myopic eyes. Twenty-seven (44.3%) of the 61 highly myopic eyes, but only 8 (14.5%) of the 55 non-highly myopic eyes had their nearest RNFL defects between 0° and 10° (P < 0.001). Although the frequencies of paracentral scotomas were comparable between the two groups, the rate of inferotemporal paracentral scotomas was significantly higher in the high myopia group (P = 0.02). The numbers of nearest RNFL defects in the superior hemisphere or extending over both hemispheres were significantly higher in the high-myopia group. Multiple logistic regression analyses showed that high myopia and the nearest RNFL defect involving the papillomacular bundle were significantly associated with paracentral scotomas (odds ratio [OR]: 4.78, P < 0.05, and OR: 5.31, P < 0.001, respectively). High myopia was significantly associated with the nearest RNFL defect involving the papillomacular bundle (OR: 2.95, P < 0.05). CONCLUSIONS: These findings suggest that highly myopic eyes are more susceptible to papillomacular bundle damage in early glaucoma.

In vivo imaging of lamina cribrosa pores by adaptive optics scanning laser ophthalmoscopy.

PURPOSE: To visualize and assess the surface-level pores of the lamina cribrosa in patients with glaucoma by using a prototype adaptive optics scanning laser ophthalmoscopy (AOSLO) system. METHODS: The numbers of laminar pores were compared between color disc photography, scanning laser ophthalmoscopy (SLO) without AO, and AOSLO. The pore area and elongation index were examined for correlation with ocular parameters such as the mean deviation, disc area, cup/disc ratio, disc ovality index, intraocular pressure (IOP), and axial length in the AOSLO images. RESULTS: The 40 eyes (20 normal and 20 glaucomatous) of 40 subjects were enrolled. The AOSLO provided laminar pore images of better quality than other imaging methods, and the number of visible pores was significantly greater in the AOSLO images than in the other imaging methods (the color disc photographs [P < 0.001] and SLO without AO images [P < 0.001]) when compared for 26 subjects. When compared for 40 subjects using AOSLO, the pore area was significantly larger in glaucomatous subjects than in normal subjects (P = 0.031), but elongation index was not. The pore area correlated significantly with the axial length (P = 0.008) in normal subjects, with the untreated IOPs (P = 0.002) in the glaucomatous subjects, and with the axial length (P = 0.001) and cup/disc ratio (P = 0.012) in the total subjects. Via multiple regression analysis, significant correlations with pore area were found for axial length in the normal (ß = 0.684, P = 0.001) and total subjects (ß = 0.496, P < 0.001) and untreated IOP in the glaucomatous (ß = 0.506, P = 0.023) and total subjects (ß = 0.331, P = 0.014). CONCLUSIONS: AOSLO is a useful imaging technology for assessing laminar pore morphology. The laminar pore area may be affected by axial length and IOP.

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.