Optic disc and peripapillary retinal nerve fiber layer characteristics associated with glaucomatous optic disc in young myopia.

PURPOSE: To explore optic disc and peripapillary retinal nerve fiber layer (RNFL) features associated with glaucomatous optic disc (GOD) in young myopia. METHODS: Presence of GOD, optic disc tilt, and disc torsion were determined using fundus photographs. If the measured disc tilt ratio was >1.3, the optic disc was classified as tilted. Optic disc torsion was defined as a >15° deviation in the long axis of the optic disc from the vertical meridian. The average and four quadrants RNFL thicknesses were assessed using spectral domain optical coherence tomography (SD-OCT). Logistic regression analyses were performed to identify factors associated with the presence of GOD. RESULTS: Nine hundred and sixty myopic subjects were recruited from four refractive surgery clinic databases. The mean age was 26.6 ± 5.7 years and spherical equivalent (SE) was -5.5 ± 2.5 diopters. Among 960 eyes, 26 (2.7%) received GOD group classification. Among 934 normal eyes, 290 (31.0%) had titled optic discs. Eighteen eyes (69.2%) in the GOD group had tilted optic discs. When compared to normal eyes, the GOD group had significantly higher tilt ratios (1.4 ± 0.2 vs. 1.2 ± 0.1, p < 0.001) and less SE (-7.8 ± 2.7 vs. -5.4 ± 2.5 diopters, p < 0.001). Greater tilt ratio (odds ratio (OR) = 4.9, p < 0.001), less SE (OR = 0.708, p < 0.001), and thinner average RNFL (OR = 0.910, p = 0.001) were significantly associated with GOD. Among 934 normal eyes, 366 (39.2%) displayed disc torsion, while among 26 glaucomatous eyes, eight (30.8%) displayed disc torsion. CONCLUSIONS: Optic disc tilt was found in approximately one-third of young myopic eyes and was independently associated with the presence of GOD.

Progression of primary open angle glaucoma in asymmetrically myopic eyes.

PURPOSE: To compare progression of primary open angle glaucoma (POAG) in asymmetrically myopic eyes within the same subject and evaluate whether the degree of myopia is related to glaucoma progression. METHODS: POAG patients with asymmetric myopia (axial length [AXL] ≥24 mm in both eyes, and the AXL difference between the right and left eyes to be ≥0.5 mm) were included. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. The progression rates of VF mean deviation (dB/year) and spectral domain optical coherence tomography measured RNFL thickness (µm/year) were compared between the more myopic eye (MME) and the less myopic eye (LME) within the same subject. RESULTS: A total of 55 patients (mean follow up period; 4.5 ± 1.0 years) were included. The mean AXL demonstrated a significant difference between MME and LME (26.3 ± 1.7 vs. 25.6 ± 1.7 mm; p = 0.036). The mean baseline VF MD (-3.8 ± 5.4 vs. -2.6 ± 4.7 dB; p = 0.21) and average RNFL thickness (77.5 ± 10.6 vs. 79.9 ± 12.3 µm; p = 0.36) did not differ between the MME and LME. Among the 55 patients, optic disc/RNFL photographic progression was noted in the MME in 15 patients, in the LME in 19 patients, and in both eyes in seven patients. VF progression was noted in the MME in seven patients, in the LME in seven patients, and in both eyes in four patients. The VF MD progression rates were -0.25 ± 0.34 dB/year in MME and -0.26 ± 0.34 dB/year in LME cases (p = 0.91). The mean progression rate of the average RNFL thickness also did not differ between the MME and LME (-0.59 ± 0.67 vs. -0.66 ± 0.72 µm/year, p = 0.68). CONCLUSIONS: The degree of myopia was not associated with glaucoma progression when assessing the same patient using either the VF or optic disc/RNFL criteria in asymmetrically myopic patients.

Lamina cribrosa depth according to the level of axial length in normal and glaucomatous eyes.

PURPOSE: To compare the lamina cribrosa (LC) depth of the optic nerve head in normal and glaucomatous eyes over a wide range of axial length (AXL). METHODS: A total of 402 eyes, including 210 normal and 192 glaucomatous eyes, were imaged by spectral domain optical coherence tomography. Normal and glaucomatous eyes were each divided into three subgroups according to the level of AXL; long (> 26 mm), mid-level (23-26 mm), and short (< 23 mm). Visual field mean deviation (VF MD), LC thickness, and LC depth were compared between normal and glaucomatous eyes in each of the AXL subgroups. These parameters were also compared between normal and glaucomatous eyes in the three AXL subgroups. Factors associated with LC depth in each AXL subgroup were evaluated by univariate and multivariate regression analyses. RESULTS: A comparison of the three AXL subgroups in normal eyes showed that the LC was thinnest in the long AXL subgroup (short; 189.7 ± 24.1 µm, mid-level; 179.9 ± 34.3 µm, long; 149.2 ± 36.2 µm, p < 0.001), but LC depth did not differ significantly in the three subgroups (short; 527.1 ± 144.4 µm, mid-level; 578.2 ± 163.5 µm, long; 594.4 ± 187.5 µm, p = 0.144). In glaucomatous eyes, glaucoma severity assessed by VF MD did not differ significantly among the three AXL subgroups (short; -6.99 ± 8.50 dB, mid-level; -6.40 ± 7.64 dB, long; -4.61 ± 5.22 dB, p = 0.168). However, LC depth was greater in the long than in the short AXL subgroup (679.5 ± 192.7 µm and 555.9 ± 134.1 µm, respectively, p = 0.004), although neither subgroup differed significantly in LC depth from the mid-level AXL subgroup (611.8 ± 162.3 µm, p = 0.385, p = 0.090). LC thickness was significantly different between normal and glaucomatous eyes (p < 0.001). LC depth was not different between normal and glaucomatous eyes in both short and mid-level AXL subgroups (p = 0.297, 0.222), but differed in the long AXL subgroup (p = 0.022). The presence of glaucoma was associated with greater LC depth only in the long AXL subgroup (p = 0.012). CONCLUSIONS: LC depth may vary according to the level of AXL in glaucomatous eyes with a similar level of glaucoma severity, with the greatest LC depth found in eyes with long AXL. Those findings suggest that glaucomatous optic disc cupping would manifest differently according to the level of AXL.

Association of macular structure, function, and vessel density with foveal threshold in advanced glaucoma.

Identifying new biomarkers associated with central visual function impairment is important in advanced glaucoma patients. This retrospective cross-sectional study enrolled 154 eyes from 154 subjects, consisting of 86 patients with advanced open-angle glaucoma (mean deviation of 24-2 visual field [VF] tests < - 15 dB) and 68 healthy controls. Structure, function, and vessel density (VD) parameters were obtained using optical coherence tomography (OCT), 24-2 standard automated perimetry, and OCT angiography, respectively. The relationships of macular thickness, central 5° and 10° VF mean sensitivity (MS), and macular VD parameters with foveal threshold (FT), representing central visual function, were investigated using partial correlation analyses and linear regression analyses, with age adjustment. Superficial and deep layer macular VD, central 5° and 10° VF MS, and best corrected visual acuity (BCVA) correlated significantly with FT after age adjustment (P < 0.05). In multivariate linear regression analyses, FT associated significantly with BCVA (ß = - 8.80, P < 0.001), central 5° MS (ß = 0.30, P = 0.037), and deep-layer global parafoveal VD (ß = 0.37, P = 0.037). Thus, deep-layer parafoveal VD is an independent predictor of FT and may be a potential biomarker for central visual function in advanced glaucoma.

High-throughput peptide quantification using mTRAQ reagent triplex.

BACKGROUND: Protein quantification is an essential step in many proteomics experiments. A number of labeling approaches have been proposed and adopted in mass spectrometry (MS) based relative quantification. The mTRAQ, one of the stable isotope labeling methods, is amine-specific and available in triplex format, so that the sample throughput could be doubled when compared with duplex reagents. METHODS AND RESULTS: Here we propose a novel data analysis algorithm for peptide quantification in triplex mTRAQ experiments. It improved the accuracy of quantification in two features. First, it identified and separated triplex isotopic clusters of a peptide in each full MS scan. We designed a schematic model of triplex overlapping isotopic clusters, and separated triplex isotopic clusters by solving cubic equations, which are deduced from the schematic model. Second, it automatically determined the elution areas of peptides. Some peptides have similar atomic masses and elution times, so their elution areas can have overlaps. Our algorithm successfully identified the overlaps and found accurate elution areas. We validated our algorithm using standard protein mixture experiments. CONCLUSIONS: We showed that our algorithm was able to accurately quantify peptides in triplex mTRAQ experiments. Its software implementation is compatible with Trans-Proteomic Pipeline (TPP), and thus enables high-throughput analysis of proteomics data.

Implications of the Relationship Between Refractive Error and Biometry in the Pathogenesis of Primary Angle Closure.

Purpose: The purpose of this study was to investigate the relationship between refractive error and ocular biometry and its implication in the pathogenesis of primary angle closure (PAC). Methods: We have retrospectively recruited 119 PAC eyes and 388 non-PAC eyes with an axial length (AL) of ≤25.0 mm and a spherical equivalent (SE) of ≥-6.0 diopters (D). Stepwise multiple regression was performed for keratometry value (K), AL, anterior chamber depth (ACD), and SE. Results: PAC eyes were more likely to be in women and have a higher IOP and shorter AL than non-PAC eyes. In a multiple regression analysis, SE was not associated with PAC. The associations between AL and SE or AL and ACD were not different in PAC eyes compared with non-PAC eyes. However, the cornea was flatter in PAC eyes (ß = -0.448, P < 0.001), and a flatter cornea was associated with more hyperopic refraction (ß = -0.454, P < 0.001) and shallower ACD (ß = 0.073, P < 0.001) in PAC eyes. ACD was not associated with SE in non-PAC eyes, but shallower ACD was associated with greater myopic refraction in PAC eyes (ß = 1.117, P = 0.006). Conclusions: PAC eyes seem to have flatter cornea compared with non-PAC eyes. A shallower ACD seems to be associated with greater myopic refraction in PAC eyes, but not in non-PAC eyes.

Improved quantitative analysis of mass spectrometry using quadratic equations.

Protein quantification is one of the principal computational problems in mass spectrometry (MS) based proteomics. For robust and trustworthy protein quantification, accurate peptide quantification must be preceded. In recent years, stable isotope labeling has become the most popular method for relative quantification of peptides. However, some stable isotope labeling methods may carry a critical problem, which is an overlap of isotopic clusters. If the mass difference between the light- and heavy-labeled peptides is very small, the overlap of their isotopic clusters becomes larger as the mass of original peptide increases. Here we propose a new algorithm for peptide quantification that separates overlapping isotopic clusters using quadratic equations. It can be easily applied in Trans-Proteomic Pipeline (TPP) instead of XPRESS. For the mTRAQ-labeled peptides obtained by an Orbitrap mass spectrometer, it showed more accurate ratios and better standard deviations than XPRESS. Especially, for the peptides that do not contain lysine, the ratio difference between XPRESS and our algorithm became larger as the peptide masses increased. We expect that this algorithm can also be applied to other labeling methods such as (18)O labeling and acrylamide labeling.

Progressive Optic Disc Tilt in Young Myopic Glaucomatous Eyes.

PURPOSE: To explore the progressive change and associated factors of optic disc tilt in young myopic glaucomatous eyes by analyzing long-term follow-up data. METHODS: Optic disc images were obtained from spectral-domain optical coherence tomography enhanced depth imaging from at least five different visits. At each visit, the disc tilt angle (DTA), defined as the angle between the Bruch's membrane opening plane and the optic canal plane, was estimated at the central frame that passes through the optic disc. Glaucoma progression was assessed on the basis of changes noted on serial optic disc and retinal nerve fiber layer photographs or changes in the visual field (VF). A linear mixed effect model was used to assess the influence of parameters (age, sex, baseline and follow-up intraocular pressure, retinal nerve fiber layer thickness, VF mean deviation, axial length, central corneal thickness), and presence of glaucomatous progression upon DTA change. RESULTS: A total of 26 eyes of 26 young myopic primary open-angle glaucoma patients (axial length >24.0 mm; mean age, 25.1 ± 4.0 years; mean follow-up, 3.3 ± 0.9 years) were included. DTA was 7.0 ± 3.4 degrees at baseline and 8.3 ± 3.8 degrees at last visit, which represents a significant difference (p < 0.001). Worse VF mean deviation (p < 0.001) and longer axial length (p = 0.006) were significantly associated with DTA increase. CONCLUSIONS: Young myopic glaucomatous eyes showed progressive optic disc tilting. Progressive optic disc tilting in young myopic glaucomatous eyes may be related to either continuous axial myopic shift or glaucomatous structural change.

Isotopic peak intensity ratio based algorithm for determination of isotopic clusters and monoisotopic masses of polypeptides from high-resolution mass spectrometric data.

Determining isotopic clusters and their monoisotopic masses is a first step in interpreting complex mass spectra generated by high-resolution mass spectrometers. We propose a mathematical model for isotopic distributions of polypeptides and an effective interpretation algorithm. Our model uses two types of ratios: intensity ratio of two adjacent peaks and intensity ratio product of three adjacent peaks in an isotopic distribution. These ratios can be approximated as simple functions of a polypeptide mass, the values of which fall within certain ranges, depending on the polypeptide mass. Given a spectrum as a peak list, our algorithm first finds all isotopic clusters consisting of two or more peaks. Then, it scores clusters using the ranges of ratio functions and computes the monoisotopic masses of the identified clusters. Our method was applied to high-resolution mass spectra obtained from a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer coupled to reverse-phase liquid chromatography (RPLC). For polypeptides whose amino acid sequences were identified by tandem mass spectrometry (MS/MS), we applied both THRASH-based software implementations and our method. Our method was observed to find more masses of known peptides when the numbers of the total clusters identified by both methods were fixed. Experimental results show that our method performed better for isotopic mass clusters of weak intensity where the isotopic distributions deviate significantly from their theoretical distributions. Also, it correctly identified some isotopic clusters that were not found by THRASH-based implementations, especially those for which THRASH gave 1 Da mismatches. Another advantage of our method is that it is very fast, much faster than THRASH that calculates the least-squares fit.

Sub-classification of myopic glaucomatous eyes according to optic disc and peripapillary features.

PURPOSE: To investigate the sub-classification of myopic glaucomatous eyes by optic disc and peripapillary features. METHODS: Optic disc tilt and torsion were determined from retinal nerve fiber layer photographs. Based on the location of the Bruch's membrane (BM) opening within the ß-zone of the peripapillary atrophy (PPA) area, the widths of ß-zone PPA (PPA1W), PPA+BM (PPA2W), and PPA-BM (PPA3W) were measured with enhanced depth imaging spectral-domain optical coherence tomography. Cluster analysis that employed partitioning around medoids was performed with these parameters, the presence of inward rotation of BM ending axial length (AXL), and central corneal thickness. RESULTS: A total of 115 eyes (AXL≥24 mm) were included. Two clusters produced maximum overall silhouette widths (average = 0.43). Visual field (VF) mean deviation was not different between cluster 1 (52 eyes; -4.02±3.01 dB) and cluster 2 (63 eyes; -5.21±5.62 dB; p = 0.174). In cluster 1 compared to cluster 2, optic disc tilt was significantly greater, PPA1W and PPA3W were longer, and AXL was longer (all p<0.001). The presence of an inward rotation of BM ending was more frequent in cluster 2 (p = 0.043). Forty-one eyes (78.8%) in cluster 1 had superior VF defects while 10 eyes (19.2%) had inferior defects, and only one eye (2%) had defects in both hemifields. Eyes in cluster 2 were more evenly distributed: 55.6% had superior defects, 34.9% had inferior defects, and 9.5% had defects in both hemifields (p = 0.023). CONCLUSIONS: Myopic glaucomatous eyes characterized by optic disc and peripapillary configurations can be classified as two distinct types, and the most distinct difference between the two was degree of optic disc tilt and width of PPA. The location of VF defects were also significantly different between two clusters.

A new route to the stable capture and final immobilization of radioactive cesium.

Radioactive Cs released from damaged fuel materials in the event of nuclear accidents must be controlled to prevent the spreading of hazardous Cs into the environment. This study describes a simple and novel process to safely manage Cs gas by capturing it within ceramic filters and converting it into monolithic waste forms. The results of Cs trapping tests showed that CsAlSiO4 was a reaction product of gas-solid reactions between Cs gas and our ceramic filters. Monolithic waste forms were readily prepared from the Cs-trapping filters by the addition of a glass frit followed by thermal treatment at 1000°C for 3h. Major findings revealed that the Cs-trapping filters could be added up to 50wt% to form durable monoliths. In 30-50wt% of waste fraction, CsAlSiO4 was completely converted to pollucite (CsAlSi2O6), which is a potential phase for radioactive Cs due to its excellent thermal and chemical stability. A static leaching test for 28 d confirmed the excellent chemical resistance of the pollucite structure, with a Cs leaching rate as low as 7.21×10-5gm-2/d. This simple scheme of waste processing promises a new route for radioactive Cs immobilization by synthesizing pollucite-based monoliths.

Ganglion cell and inner plexiform layer thickness determined by spectral domain optical coherence tomography in patients with brain lesions.

PURPOSE: To evaluate the thickness of the macular ganglion cell and inner plexiform layer (GCIPL) using spectral domain optical coherence tomography (SD OCT) in patients with brain lesions. METHODS: This case-control study included 58 healthy subjects and 98 patients with brain lesions confirmed by MRI. GCIPL and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were determined using the Cirrus SD OCT. Area under the receiver operating characteristic curve (AUC) values of pRNFL and GCIPL thickness were used to discriminate patients with brain lesions from normal controls. RESULTS: Average GCIPL thickness showed a good correlation with visual field mean deviation (r(2)=0.342, p<0.001). All GCIPL parameters, including average thickness (71.9±8.6 vs 85.1±4.8 µm, p<0.001), differed between the patient and control groups. The AUC of the average GCIPL thickness was significantly greater than that of average pRNFL thickness (0.941 vs 0.823, p<0.001). CONCLUSIONS: Our results suggest that various kinds of brain lesions with different locations show considerable reduction in GCIPL thickness. Thickness of the GCIPL performed better than conventional pRNFL thickness for the diagnosis of retinal ganglion cell damage induced by brains lesions. The pattern of GCIPL loss may be of particular usefulness in recognising a potential intracranial lesion in cases suspected of having normal-tension glaucoma. GCIPL thickness determined by OCT can be an early and useful marker to estimate the status of the visual pathway in various brain lesions.