THREE-DIMENSIONAL CHARACTERISTICS OF FOUR MACULAR INTRARETINAL LAYER THICKNESSES IN SYMPTOMATIC AND ASYMPTOMATIC CARRIERS OF G11778A MUTATION WITH LEBER'S HEREDITARY OPTIC NEUROPATHY.

PURPOSE: To characterize by spectral domain optical coherence tomography the three-dimensional thicknesses of four macular intraretinal layers in symptomatic and asymptomatic carriers of G11778A mutation with Leber's hereditary optic neuropathy. METHODS: Twenty-five eyes (7 symptomatic eyes and 18 asymptomatic eyes) of patients with Leber's hereditary optic neuropathy from one Chinese family and 16 normal eyes were enrolled. Macular radial scans by spectral domain optical coherence tomography and custom software produced intraretinal three-dimensional thickness maps. The macula was divided into nine regions, and each region included four intraretinal layers: nerve fiber layer, ganglion cell layer and inner plexiform layer, inner nuclear layer and outer plexiform layer, and the outer retinal layer. RESULTS: Nerve fiber layer in the symptomatic eyes was significantly thinner than in normal eyes for most of the macular regions; however in the asymptomatic eyes, it was increased in three regions. Ganglion cell layer and inner plexiform layers in all regions of symptomatic eyes were significant thinner than in asymptomatic eyes and controls. Inner nuclear layer and outer plexiform layers in six regions of symptomatic and asymptomatic eyes were significantly thicker than in controls. The outer retinal layer of asymptomatic eyes was thicker than in most control regions. CONCLUSION: Intraretinal thickness changes in asymptomatic patients could be prodromal events that indicate the imminent conversion to symptomatic patients with Leber's hereditary optic neuropathy.

Primary visual cortex of the brain is associated with optic nerve head changes in neuromyelitis optica spectrum disorders.

OBJECTIVE: To explore the association between the primary visual cortex in the brain and optic nerve head changes, ONH, (structural thickness and microvascular changes) in neuromyelitis optica spectrum disorder (NMOSD). METHODS: Nineteen patients who were aquaporin-4 (AQP-4) seropositive NMOSD patients and twenty-two healthy controls (HC) were enrolled for this cross-sectional study. Optical coherence tomographic angiography (OCT-A) was used to image and measure the capillaries density (RPC, radial peripapillary capillaries) and structural thickness (pRNFL, peripapillary retinal nerve fiber layer) around the optic nerve head. A resting-state functional magnetic resonance imaging was used to image and evaluate the gray matter volume (GMV) and functional connectivity (FC) the brain of each participant. We assessed the primary visual cortex (lingual gyrus, calcarine sulcus and thalamus) of the brain. RESULTS: Changes in RPC density showed a significant association (P < 0.05) with FC of the right lingual gyrus, bilateral calcarine gyrus and left thalamus respectively. pRNFL thickness showed significant association with FC of the right lingual gyrus (Rho = 0.374, P = 0.016), right calcarine gyrus (Rho = 0.355, P = 0.023) and left thalamus (Rho = 0.376, P = 0.015) respectively. CONCLUSIONS: Visual impairment, structural and microvascular changes around optic nerve head is associated with the functional visual networks in NMOSD. Our report suggests that structural and microvascular changes around the ONH reflect the changes in the primary visual cortex of the brain.

Foveal pit morphological changes in asymptomatic carriers of the G11778A mutation with Leber's hereditary optic neuropathy.

AIM: To investigate the foveal pit morphology changes in unaffected carriers and affected Leber's hereditary optic neuropathy (LHON) patients with the G11778A mutation from one family. METHODS: This study was a prospective cross-sectional study. Both eyes from 16 family members (age from 9 to 47y) with the G11778A mutation were analyzed and compared with 1 eye from 20 normal control subjects. Eleven family members with the G11778A mutation but without optic neuropathy were classified as unaffected carriers (n=22 eyes). Five family members (n=10 eyes) expressed the LHON phenotype and were classified as affected patients. Retinal images of all the subjects were taken by optical coherence tomography (OCT), and an automatic algorithm was used to segment the retina to eight layers. Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry. RESULTS: Thicker foveal thickness, thinner foveal pit depth, and flatter foveal slopes were observed in unaffected carriers and affected LHON patients (all P<0.001). Further, the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers (all P<0.001). Compared with the control group, affected LHON patients had a thinner retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL+IPL), and total retina (all P<0.01). The retinal nerve fiber layer (RNFL) of affected patients was 38.0% thinner than that of controls while the GCL+IPL was 40.1% thinner. CONCLUSION: The foveal pit morphology shows changes in both unaffected carriers and affects patients. RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.

Alterations in the Brain Structure and Functional Connectivity in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.

PURPOSE: To investigate the mechanisms underlying the gray matter volume (GMV) and functional connectivity (FC) changes in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) patients. METHODS: This cross-sectional study consisted of 21 patients with aquaporin-4 antibody-positive NMOSD and 22 age- and sex-matched healthy controls. All participants underwent cerebral magnetic resonance imaging and testing each individual's visual acuity was done. RESULTS: Neuromyelitis optica spectrum disorder patients showed significantly reduced GMV in the left calcarine, left thalamus and right lingual gyrus of the NMOSD patients when compared to HC (P < 0.05). NMOSD patients showed significantly decreased FC values (P < 0.05) in both the left and right calcarine, right lingual gyrus and left thalamus, respectively, when compared to HC. We also observed a positive correlation between the FC values of the left thalamus, bilateral calcarine gyrus and the visual acuity, respectively (P < 0.05). Furthermore, a negative association was seen between the duration of the disease, frequency of optic neuritis, and the FC values in the lingual gyrus, bilateral calcarine gyrus, and right lingual gyrus, respectively (P < 0.05). CONCLUSION: Reduced visual acuity and frequency of optic neuritis are associated with alterations in the GMV and FC in NMOSD. Our current study, which provides imaging evidence on the impairment involved in NMOSD, sheds light on pathophysiological responses of optic neuritis attack on the brain especially on the visual network.

Efficient non-unique probes selection algorithms for DNA microarray.

BACKGROUND: Temperature and salt concentration are very helpful experimental conditions for a probe to hybridize uniquely to its intended target. In large families of closely related target sequences, the high degree of similarity makes it impossible to find a unique probe for every target. We studied how to select a minimum set of non-unique probes to identify the presence of at most d targets in a sample where each non-unique probe can hybridize to a set of targets. RESULTS: We proposed efficient algorithms based on Integer Linear Programming to select a minimum number of non-unique probes using d-disjunct matrices. Our non-unique probes selection can also identify up to d targets in a sample with at most k experimental errors. The decoding complexity of our algorithms is as simple as O(n). The experimental results show that the decoding time is much faster than that of the methods using d-separable matrices while running time and solution size are comparable. CONCLUSIONS: Since finding unique probes is often not easy, we make use of non-unique probes. Minimizing the number of non-unique probes will result in a smaller DNA microarry design which leads to a smaller chip and considerable reduction of cost. While minimizing the probe set, the decoding ability should not be diminished. Our non-unique probes selection algorithms can identify up to d targets with error tolerance and the decoding complexity is O(n).

Ultra-high resolution profiles of macular intra-retinal layer thicknesses and associations with visual field defects in primary open angle glaucoma.

The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma.

Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients.

Purpose: To determine the ability of fractal dimension to detect early changes in the retinal microvascular network imaged by optical coherence tomography angiography (OCT-A) in type 2 diabetic patients. Methods: Sixty-seven patients with type 2 diabetic mellitus (DM) (48 with no diabetic retinopathy [DR], 19 with minimal DR) and 40 control subjects. Macular OCT-A images of the superficial and deep retinal capillary layers in a 2.5-mm diameter concentric annular zone (excluding the foveal avascular zone) were subdivided into six annular rings and four quadrants. A custom automated algorithm was developed to quantify the complexity and density of the two retinal capillary layers by fractal analysis. Results: Compared to controls, the fractal dimensional parameter (Dbox) of the two retinal capillary layers in most regions was significantly lower in diabetic patients with minimal DR (P < 0.05). The Dbox of the diabetic patients with no DR was also decreased in most regions of the deep retinal capillary layer (P < 0.05), but not in the superficial retinal capillary layer (P > 0.05). Based on the receiver operating characteristic curve analysis, the Dbox values for the deep retinal capillary layer had the highest index to discriminate diabetic patients with and without minimal DR from controls. Conclusions: Fractal dimension based on OCT-A has the potential to quantitatively characterize retinal microvascular changes in the early stage of DM. Changes in the fractal dimension in the deep retinal capillary layer could be an early indicator of microvasculature changes associated with retinopathy in type 2 diabetic patients.

Real-Time Monitoring of Suprachoroidal Space (SCS) Following SCS Injection Using Ultra-High Resolution Optical Coherence Tomography in Guinea Pig Eyes.

PURPOSE: To monitor the change of suprachoroidal space (SCS) using ultra high resolution-optical coherence tomography (UHR-OCT) following SCS injection with different drug formulations. METHODS: An amount of 10 or 20 µL of saline or indocyanine green (ICG) or triamcinolone acetonide (TA) suspension (40 or 80 mg/mL) was injected suprachoroidally into the guinea pig eye with a 30-gauge needle. Immediately after injection, the eyes were imaged by UHR-OCT from 60 minutes up to 24 hours. At each time point, the SCS area on each OCT cross-section was measured in pixels with Image J and the area change from the baselines was analyzed over time. RESULTS: A 20-µL injection produced 130% to 200% SCS expansion compared to a 10-µL injection for saline and TA suspension (P < 0.01). After SCS injection, the time that expansion persisted was formulation dependent. Thus, expansion in response to injection of TA suspension, ICG, and saline persisted for 24 hours, 180 minutes, and 60 minutes, respectively. Moreover, ICG injection produced a significantly larger area of distribution in the SCS than the TA suspension (0.626 vs. 0.275 cm(2), P < 0.0001). CONCLUSIONS: The SCS is expandable and can recover to preinjection status after injected fluid is cleared by physiological processes. The injection-induced SCS expansion is volume-dependent, and the drug/dye retained in the SCS is formulation-dependent. The current injection technique with a volume of 20 µL or less is well tolerated in guinea pig eyes.

Macular Thickness Profiles of Intraretinal Layers in Myopia Evaluated by Ultrahigh-Resolution Optical Coherence Tomography.

PURPOSE: To investigate the thickness and variation profiles of 8 intraretinal layers in myopia. DESIGN: Prospective cross-sectional study. METHODS: Young subjects with spherical equivalents ranging from +0.50 to -10.25 diopters and good corrected vision were divided into emmetropic (n = 20), low myopic (n = 50), and high myopic (n = 30) groups. Retinal images centered on the fovea along the horizontal and vertical meridians were obtained by ultrahigh-resolution optical coherence tomography (OCT). Macular images were segmented into 8 intraretinal layers by an automatic segmentation algorithm to yield thickness profiles within a 6-mm-diameter circle divided into central, pericentral, and peripheral regions. RESULTS: For intraretinal layers in the central region, the outer segment of receptors layer was thicker in the high myopic group and positively correlated with axial length. In the pericentral and peripheral regions, all layers except the ganglion cell and inner plexiform layer had thickness changes in high myopia. The total thickness of the peripheral region was less than in the emmetropic controls owing to thinner inner nuclear layer, combined Henle fiber and outer nuclear layer, and outer segment of receptors layer. Nevertheless, the thicknesses of the combined myoid and ellipsoid zone and the combined interdigitation zone and retinal pigment epithelium/Bruch complex in the peripheral region were greater than for the emmetropic controls. CONCLUSIONS: Intraretinal layer thicknesses in young high myopic eyes varied significantly from emmetropic controls, especially in the peripheral region. Ultrahigh-resolution OCT with automated segmentation can detect changes in retinal macular microstructure during the development of myopia.

Biometry of anterior segment of human eye on both horizontal and vertical meridians during accommodation imaged with extended scan depth optical coherence tomography.

PURPOSE: To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation. METHODS: Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR). RESULTS: There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation. CONCLUSION: The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation.