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.

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.

Retinal structural alterations and macular sensitivity in idiopathic macular telangiectasia type 1.

PURPOSE: To evaluate the relationship between the abnormalities of retinal structures showed on spectral-domain optical coherence tomography and the changes in the macular sensitivity measured by microperimetry in eyes with idiopathic macular telangiectasia type 1. METHODS: Eleven eyes of 11 patients with macular telangiectasia type 1 were reviewed. Morphologic changes in the retina and retinal sensitivity of eyes with macular telangiectasia type 1 were studied using spectral-domain optical coherence tomography and microperimetry. RESULTS: Spectral-domain optical coherence tomographic images revealed disruptions in the photoreceptor inner segment-outer segment (IS/OS) junction in all the eyes and intraretinal cystoid spaces in 10 eyes. In the points that had intraretinal cystoid spaces, the mean retinal sensitivity was 6.8 ± 5.5 dB where the IS/OS was disrupted and 13.4 ± 4.0 dB where the IS/OS was intact (P < 0.001). In the points that had intact IS/OS and no cystoid spaces, the mean retinal sensitivity was 15.3 ± 4.3 dB, which was better than that of points that had intact IS/OS with cystoid spaces (P < 0.001). CONCLUSION: Retinal sensitivity is influenced not only by intraretinal cystoid spaces but also by IS/OS disruptions, and the IS/OS alterations reduce the visual function more severely.

High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy.

OBJECTIVE: To compare, in eyes with an idiopathic epiretinal membrane (ERM), photoreceptor cell structural abnormalities identified on high-resolution images obtained by adaptive optics scanning laser ophthalmoscopy (AO-SLO) with the severity of metamorphopsia and anatomic findings on spectral-domain optical coherence tomography (SD-OCT). DESIGN: Observational case series. PARTICIPANTS: Twenty-five eyes of 24 patients with idiopathic ERM and 20 normal eyes of 20 volunteer subjects. METHODS: All participants underwent a full ophthalmologic examination, SD-OCT, and imaging with an original prototype AO-SLO system that incorporated liquid crystal-on-silicon technology. In eyes with ERM, M-CHARTS results were used to quantify metamorphopsia. MAIN OUTCOME MEASURES: Cone mosaic patterns on AO-SLO images and metamorphopsia severity. RESULTS: In normal eyes, AO-SLO images showed a regular photoreceptor mosaic pattern. In 24 (96%) of 25 eyes with ERM, "microfolds" (multiple thin, straight, hyporeflective lines in the photoreceptor layer) were identified on AO-SLO images; microfolds were not seen in normal eyes. Individual microfolds were approximately 5 to 20 µm wide, which is narrower than retinal folds seen in fundus photographs (>50 µm). Amsler charts revealed metamorphopsia around the fixation point in 12 of 13 eyes with microfolds in the fovea on AO-SLO but in none of 5 eyes without microfolds in the fovea (P < 0.001). Compared with eyes without foveal microfolds, eyes with foveal microfolds had more severe metamorphopsia (M-CHARTS distortion) in both horizontal and vertical lines (P < 0.001 for both) and greater average foveal thickness detected by SD-OCT (P=0.010). Voronoi analysis revealed that smaller numbers of cones in eyes with ERM had 6 neighbors, compared with normal eyes (P < 0.001). In eyes with ERM, average foveal thickness measured by SD-OCT correlated with visual acuity (P=0.001) and metamorphopsia scores, both horizontal (P=0.002) and vertical (P < 0.001), but visual acuity, metamorphopsia scores, and average foveal thickness were not related to SD-OCT findings of disruption in the photoreceptor inner and outer segment junction. CONCLUSIONS: Adaptive optics scanning laser ophthalmoscopy images in eyes with ERM showed abnormal cone mosaic patterns, described as microfolds in the foveal photoreceptor layer. The presence of microfolds was associated with metamorphopsia, suggesting that microfolds may be involved in the formation of metamorphopsia.

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.

Large blunt scleral rupture without retinal detachment.

Eyes with scleral rupture after blunt trauma are often complicated by proliferative vitreoretinopathy. A 56-year-old man sustained blunt trauma to his left eye. Visual acuity was light perception. The fundus was obscured by hyphema. Computed tomography imaging and the presence of extensive subconjunctival hemorrhage suggested scleral rupture. Prompt primary surgery to repair a 25-mm scleral rupture was performed under general anesthesia. No retinal detachment developed. Two years postoperatively, visual acuity increased to 12/20. This case shows that retinal detachment and proliferative vitreoretinopathy may not complicate extensive scleral ruptures under certain circumstances.

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.

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.

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.

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.

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.

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.

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.