Interactive Threshold Research Articles

Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in mild to moderate nonproliferative diabetic retinopathy: a randomized proof-of-concept clinical trial.

Microglia have been associated with inflammatory changes underlying diabetic retinopathy. To investigate whether low-dose oral doxycycline monohydrate, a drug capable of inhibiting microglial activation, can improve or slow the deterioration of retinal function and whether it can induce regression or slow progression of diabetic retinopathy in patients with mild to moderate nonproliferative diabetic retinopathy (NPDR). Randomized, double-masked, 24-month proof-of-concept clinical trial. We randomized 33 patients (from the Penn State Hershey Eye Center) with at least 1 eye with mild to moderate NPDR (Early Treatment Diabetic Retinopathy Study level 20-43) to doxycycline monohydrate, 50 mg/d, or daily placebo for 24 months. Mean change at 24 months compared with baseline in the foveal sensitivity of matrix frequency-doubling perimetry in each treatment group. We also compared the 2 groups with respect to change from baseline to 24 months in functional variables (Humphrey photopic visual field testing using the Swedish interactive thresholding algorithm 24-2 strategy, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomical variables (diabetic retinopathy severity level, area of retinal thickening, central subfield thickness on optical coherence tomography, and macular volume on optical coherence tomography). From baseline to month 24, no significant difference was detected between groups with respect to all visual function and anatomical outcomes assessed. Although a link between low-dose oral anti-inflammatory agents and subclinical improvement in inner retinal function has been suggested in patients with severe NPDR or non-high-risk proliferative diabetic retinopathy, the same association was not found in the present study of patients with mild to moderate NPDR. The different findings in the 2 patient populations may relate to a differential effect of doxycycline on different stages of diabetic retinal dysfunction, or the sample size of the present study may be too small to detect a treatment effect of doxycycline in patients with mild to moderate NPDR. clinicaltrials.gov Identifier: NCT00917553.

Evaluation of acquired color vision deficiency in glaucoma using the Rabin cone contrast test.

To evaluate acquired color vision deficiency in glaucoma by using the Rabin cone contrast test (RCCT). Twenty-seven eyes of 27 patients with glaucoma (glaucoma group) and 27 eyes of 27 normal subjects (control group) were included in this study. Long (L), medium (M), and short (S) CCT scores (L CCTs, M CCTs, and S CCTs, respectively) were measured using the RCCT in both groups. Visual field examinations were performed with Humphrey automated perimetry using the Swedish interactive thresholding algorithm 30-2, and the mean deviation (MD) was evaluated. The macular ganglion cell/inner plexiform layer (GCIPL) thickness was measured using high-definition optical coherence tomography in the glaucoma group. The mean M CCTs and S CCTs in the glaucoma group were significantly lower (P<0.05 for both comparisons) than in the control group (M CCTs, 80.7±16.8 vs. 91.9±8.22; S CCTs, 83.9±19.5 vs. 97.4±3.77, respectively); the L CCTs did not differ significantly (P=0.065) from those of the controls (91.8±12.8 vs. 97.4±3.50, respectively). The M CCTs and S CCTs were correlated significantly with those of MD (M CCTs, r=0.47; S CCTs, r=0.44; P<0.05 for both comparisons) and GCIPL thickness (M CCTs, r=0.70; P<0.0001; S CCTs, r=0.57; P<0.01). The chromatic discrimination thresholds measured by RCCT in the glaucoma group were significantly different from those measured in the control group and were correlated with the MD and GCIPL thickness. The RCCT may be useful for evaluating acquired color vision deficiency in glaucoma and may help advance current understanding of the pathophysiology of glaucomatous damage.

Optic Disc and Retinal Nerve Fiber Layer Thickness Descriptive Analysis in Megalopapilla

To evaluate the optic disc and retinal nerve fiber layer (RNFL) thickness in megalopapilla cases by confocal scanning laser ophthalmoscopy and Stratus optical coherence tomography (OCT). To assess the importance of these measurements in diagnosing megalopapilla. This study included 59 eyes (30 patients) diagnosed as megalopapilla. All subjects underwent a complete ophthalmic examination that included intraocular pressure and central corneal thickness measurements and standard automated perimetry using the Swedish Interactive Threshold Algorithm and the 24-2 program (Humphrey Field Analyzer; Carl Zeiss Meditec Inc., Dublin, CA). Confocal scanning laser ophthalmoscopy examinations were performed with the Heidelberg retina tomograph (HRTII; Heidelberg Engineering, Germany). Thickness of the RNFL around the optic disc was measured with Stratus OCT, version 4.0.1 (Stratus OCT; Carl Zeiss Meditec). A descriptive analysis was made using SPSS (version 12.0; SPSS Inc., Chicago, IL) statistical software. The mean global optic disc area for all eyes with megalopapilla was 3.28±0.53 mm and was not statistically different among races (P≥0.159) or sex (P≥0.108). The average RNFL thickness was 102.5±12.68 μm. Pattern standard deviation was 3.8±2.4 and mean deviation was -1.22±2.65. Central corneal thickness mean value was 543±35.9 μm. Intraocular pressure (average from 3 measurements) ranged from 10.0 to 20.6 mm Hg (14.4±2.7). In megalopapilla, the optic disc is abnormally large. The RNFL thickness is normal. These findings are essential for distinguishing megalopapilla from the optic glaucomatous neuropathy.

Validating the sumi quality of life questionnaire with rasch analysis.

To validate the Sumi Visual Disability Questionnaire (Sumi VDQ) to estimate visual disability in glaucoma patients using Rasch analysis. A total of 162 glaucoma patients underwent visual field (VF) testing in both eyes (Humphrey 24-2 Swedish Interactive Threshold Algorithm [SITA] standard program). The binocular VF was then calculated using the integrated VF (IVF) method. Visual disability was scored using the Sumi VDQ, which was originally written in Japanese and contains 30 items (questions). Response scale analysis, targeting, and infit statistics associated with Rasch analysis were evaluated. Unidimensionality was analyzed using principal component analysis (PCA). In addition, the correlation between the person parameter obtained with Rasch analysis and the mean of total deviation values (mTD) in the IVF was compared with the correlation between the arithmetic sum of visual disability score and mTD of the IVF. All 30 items in the Sumi VDQ showed productive infit values (0.61-1.46). The person parameters distributed between -4.50 and 3.62, while the item difficulty targeting parameters distributed between -0.88 and 2.06. None of the PCA components had eigenvalues whose lower limit of 95% confidence interval (CI) exceeded 2 (0-1.5). There was a significant relationship between person parameter and mTD of IVF (r = -0.78, P < 0.001), which was significantly stronger (Meng-Rosenthal-Rubin method, P = 0.002) than that between arithmetic sum of visual disability score and mTD of IVF (r = -0.61, P < 0.001). The Sumi VDQ has constructive psychometric properties. In particular, the Rasch analysis-derived person parameter appears to be clinically more meaningful than the arithmetic sum of visual disability score.

Reducing variability in visual field assessment for glaucoma through filtering that combines structural and functional information.

To reduce variability and improve measurements of true change signal in visual field (VF) assessments through the use of filters that combine functional and structural test results. Humphrey VF data (Swedish Interactive Thresholding Algorithm [SITA] Standard, 24-2) and confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]) data from 1057 eyes of 637 participants were used to derive a filter. Another dataset, consisting of VF and HRT data from 112 eyes of 62 participants each with ≥5 visits, was used to test the filter. At each VF location per eye, the trend over time was modeled by a linear model (LM), and a nonlinear model (NLM), using filtered or unfiltered data, but with the last visit excluded. The SD of residuals from the trends, and prediction errors (PE) for the last visit were compared between filtered and unfiltered data. The filter was reconstructed and analyses were repeated after truncating VF data so that thresholds < 19 dB were replaced by 19 dB to reduce noise. The SD of the residuals at all 52 VF locations for all analyses was reduced by filtering (P < 0.001). The PE was reduced by filtering at 43 and 47 VF locations (P < 0.05) for LM analyses on observed and truncated data, and all 52 VF locations (P < 0.05) for both NLM analyses. Truncating data before filtering reduced variability (P < 0.01) at 41 and 40 VF locations for LM and NLM analyses. Filtering can reduce variability about trends in longitudinal sequences of VF data, and improves the accuracy of predicting the next test result.

Prediction of Glaucomatous Visual Field Progression: Pointwise analysis

Purpose: To evaluate whether pointwise regression analysis of serial measures of retinal sensitivity can predict future visual field (VF) loss.Methods: Medical records of 158 patients with glaucomatous eyes with at least 6 years follow-up and 10 reliable VF exams were retrospectively analyzed. The entire follow-up period was divided into two, roughly corresponding to the first (early period) and second (late period) half of follow-up. Retinal sensitivity data obtained from the Swedish interactive threshold algorithm standard or full-threshold VF tests were analyzed, and linear and first-order exponential regression analyses of retinal sensitivity against time were performed to obtain the slope of regression analysis in each VF test location. Paired t tests were used to compare the slopes of the early and late period in each regression analysis.Results: When assessed by linear regression analysis, inferior nasal location showed highest rate of change (–0.52 dB/year) in early period. Late period showed generally faster rate of progression compared to early period. Superior arcuate and superior and inferior nasal locations showed that early and late slopes did not show significant difference (p value, 0.19 ∼ 0.49). Central and edged locations showed significant difference between the two slopes (p value < 0.05). First-order exponential regression analysis showed similar result.Discussion: Superior arcuate and superior and inferior nasal areas in VF had a consistent rate of change of retinal sensitivity, indicating that these locations may have the higher capability for prediction of future deterioration. These results suggest that location should be considered when predicting glaucomatous VF progression.

Controlling the velocities and the number of emitted particles in the tunneling to open space dynamics

A scheme to control the many-boson tunneling process to open space is derived and demonstrated. The number of ejected particles and their velocities can be controlled by two parameters, the threshold of the potential and the interparticle interaction. Since these parameters are fully under experimental control, this is also the case for the number of ejected particles and their emission spectrum. The process of tunneling to open space can hence be used, for example, for the quantum simulation of complicated tunneling ionization processes and atom lasers. To understand the many-body tunneling process, a generalization of the model introduced in [Proc. Natl. Acad. Sci. USA, 109, 13521 (2012)] for tunneling in the absence of a threshold is put forward and proven to apply for systems with a non-zero threshold value. It is demonstrated that the model is applicable for general interparticle interaction strengths, particle numbers and threshold values. The model constructs the many-body process from single-particle emission processes. The rates and emission momenta of the single-particle processes are determined by the chemical potentials and energy differences to the threshold value of the potential for systems with different particle numbers. The chemical potentials and these energy differences depend on the interparticle interaction. Both the number of confined particles and their rate of emission thus allow for a control by the manipulation of the interparticle interaction and the threshold. Numerically exact results for two, three and one hundred bosons are shown and discussed. The devised control scheme for the many-body tunneling process performs very well for the dynamics of the momentum density, the correlations, the coherence and of the final state, i.e., the number of particles that remain confined in the potential.

Diffusion-weighted MRI: association between patient characteristics and apparent diffusion coefficients of normal breast fibroglandular tissue at 3 T.

The purpose of this study is to assess associations between patient characteristics and apparent diffusion coefficient (ADC) values of normal breast fibroglandular tissue on diffusion-weighted imaging (DWI) at 3 T. The retrospective study included 103 women with negative bilateral findings on 3-T breast MRI examinations (BI-RADS category 1). DWI was acquired during clinical breast MRI scans using b = 0 and b = 800 s/mm(2). Mean ADC of normal breast fibroglandular tissue was calculated for each breast using a semiautomated software tool in which parenchyma pixels were selected by interactive thresholding of the b = 0 s/mm(2) image to exclude fat. Intrasubject right- and left-breast ADC values were compared and averaged together to evaluate the association of mean breast ADC with age, mammographic breast density, and background parenchymal enhancement. Overall mean ± SD breast ADC was 1.62 ± 0.30 × 10(-3) mm(2)/s. Intrasubject right- and left-breast ADC measurements were highly correlated (R(2) = 0.89; p < 0.0001). Increased breast density was strongly associated with increased ADC (p ≤ 0.0001). Age and background parenchymal enhancement were not associated with ADC. Normal breast parenchymal ADC values increase with mammographic density but are independent of age and background parenchymal enhancement. Because breast malignancies have been shown to have low ADC values, DWI may be particularly valuable in women with dense breasts owing to greater contrast between lesion and normal tissue.

Effect of Doxycycline vs Placebo on Retinal Function and Diabetic Retinopathy Progression in Patients With Severe Nonproliferative or Non–High-Risk Proliferative Diabetic Retinopathy

Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR). To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR), and to determine the potential usefulness of visual function end points to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR. We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR. Patients were randomized to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months. Change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). From baseline to month 24, mean FDP foveal sensitivity decreased in the placebo group (-1.9 dB) and increased in the doxycycline group (+1.8 dB) (P = .02). A higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group was detected at 6 months (P = .04), and this significant difference persisted at 12 and 24 months. A difference between the groups was not detected with respect to the other visual function outcomes and all anatomic outcomes assessed. To our knowledge, this is the first observation suggesting a link between a low-dose oral anti-inflammatory agent and subclinical improvement in inner retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the inflammatory component of DR. Furthermore, study results suggest that FDP, which primarily measures inner retinal function, is responsive to intervention and may be a useful clinical trial end point for proof-of-concept studies in patients with DR. clinicaltrials.gov Identifier: NCT00511875.

It takes a village to raise a tide: non-linear multiple-mode coupling and mode identification in KOI-54

We explore the tidal excitation of stellar modes in binary systems using Kepler observations of the remarkable eccentric binary KOI-54 (HD 187091; KIC 8112039), which displays strong ellipsoidal variation as well as a variety of linear and non-linear pulsations. We report the amplitude and phase of over 120 harmonic and anharmonic pulsations in the system. We use pulsation phases to determine that the two largest amplitude pulsations, the 90th and 91st harmonics, most likely correspond to axisymmetric m = 0 modes in both stars, and thus cannot be responsible for resonance locks as had been recently proposed. We find evidence that the amplitude of at least one of these two pulsations is decreasing with a characteristic time-scale of ∼100 yr. We also use the pulsations’ phases to confirm the onset of the travelling wave regime for harmonic pulsations with frequencies ≲50 Ωorb, in agreement with theoretical expectations. We present evidence that many pulsations that are not harmonics of the orbital frequency correspond to modes undergoing simultaneous non-linear coupling to multiple linearly driven parent modes. Since coupling among multiple modes can lower the threshold for non-linear interactions, non-linear phenomena may be easier to observe in highly eccentric systems, where broader arrays of driving frequencies are available. This may help to explain why the observed amplitudes of the linear pulsations are much smaller than the theoretical threshold for decay via three-mode coupling.

Investigation of the accuracy of breast tissue segmentation methods for the purpose of developing breast deformation models for use in adaptive radiotherapy

Realistic modelling of breast deformation requires the breast tissue to be segmented into fibroglandular and fatty tissue and assigned suitable material properties. There are a number of breast tissue segmentation methods proposed and used in the literature. The purpose of this study was to validate and compare the accuracy of various segmentation methods and to investigate the effect of the tissue distribution on the segmentation accuracy. Computed tomography (CT) data for 24 patients, both in supine and prone positions were segmented into fibroglandular and fatty tissue. The segmentation methods explored were: physical density thresholding; interactive thresholding; fuzzy c-means clustering (FCM) with three classes (FCM3) and four classes (FCM4); and k-means clustering. Validation was done in two-stages: firstly, a new approach, supine-prone validation based on the assumption that the breast composition should appear the same in the supine and prone scans was used. Secondly, outlines from three experts were used for validation. This study found that FCM3 gave the most accurate segmentation of breast tissue from CT data and that the segmentation accuracy is adversely affected by the sparseness of the fibroglandular tissue distribution.

Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction

The task of breast density quantification is becoming increasingly relevant due to its association with breast cancer risk. In this work, a semi-automated and a fully automated tools to assess breast density from full-field digitized mammograms are presented. The first tool is based on a supervised interactive thresholding procedure for segmenting dense from fatty tissue and is used with a twofold goal: for assessing mammographic density (MD) in a more objective and accurate way than via visual-based methods and for labeling the mammograms that are later employed to train the fully automated tool. Although most automated methods rely on supervised approaches based on a global labeling of the mammogram, the proposed method relies on pixel-level labeling, allowing better tissue classification and density measurement on a continuous scale. The fully automated method presented combines a classification scheme based on local features and thresholding operations that improve the performance of the classifier. A dataset of 655 mammograms was used to test the concordance of both approaches in measuring MD. Three expert radiologists measured MD in each of the mammograms using the semi-automated tool (DM-Scan). It was then measured by the fully automated system and the correlation between both methods was computed. The relation between MD and breast cancer was then analyzed using a case–control dataset consisting of 230 mammograms. The Intraclass Correlation Coefficient (ICC) was used to compute reliability among raters and between techniques. The results obtained showed an average ICC=0.922 among raters when using the semi-automated tool, whilst the average correlation between the semi-automated and automated measures was ICC=0.838. In the case–control study, the results obtained showed Odds Ratios (OR) of 1.38 and 1.50 per 10% increase in MD when using the semi-automated and fully automated approaches respectively. It can therefore be concluded that the automated and semi-automated MD assessments present a good correlation. Both the methods also found an association between MD and breast cancer risk, which warrants the proposed tools for breast cancer risk prediction and clinical decision making. A full version of the DM-Scan is freely available.

Correlation of Retinal Nerve Fiber Layer Thickness and Visual Fields in Glaucoma: A Broken Stick Model

To determine the retinal nerve fiber layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. Retrospective cross-sectional study. Eighty-seven healthy and 108 glaucoma subjects (1 eye per subject) were recruited from an academic institution. All patients had VF examinations (Swedish Interactive Threshold Algorithm 24-2 test ofthe Humphrey Visual Field Analyzer 750i) and spectral-domain optical coherence tomography RNFL scans. Comparison of RNFL thickness values with VF threshold values showed a plateau of VF threshold values at high RNFL thickness values and then a sharp decrease at lower RNFL thickness values. A broken stick statistical analysis was used to estimate the tipping point at which RNFL thickness values are associated with VF defects. The slope for the association between structure and function was computed for data above and below the tipping point. The mean RNFL thickness value that was associated with initial VF loss was 89μm. The superior RNFL thickness value that was associated with initial corresponding inferior VF loss was 100μm. The inferior RNFL thickness value that was associated with initial corresponding superior VF loss was 73μm. The differences between all the slopes above and below the aforementioned tipping points were statistically significant (P< .001). In open-angle glaucoma, substantial RNFL thinning or structural loss appears to be necessary before functional visual field defects become detectable.

Disparity between Visual Fields and Optical Coherence Tomography in Hydroxychloroquine Retinopathy

American Academy of Ophthalmology recommendations for screening for hydroxychloroquine (HCQ) retinopathy advise objective measures, such as spectral-domain optical coherence tomography (SD-OCT) and multifocal electroretinography (mfERG) along with visual fields. However, the relative sensitivity and specificity of screening tests have not been fully resolved. We characterize a subset of patients with toxicity who show unusual disparity between fields and SD-OCT and thus have implications for screening practice. Review of charts and clinical data. Patients at Stanford and Kaiser Permanente who had used HCQ with greater than 1000 g cumulative exposure. There were more than 2000 such individuals, among whom 150 had clear evidence of toxicity. Patients were evaluated by visual fields (10-2 white Swedish Interactive Threshold Algorithm pattern deviation plots), SD-OCT, and sometimes mfERG or fundus autofluorescence. Relative findings on visual fields in comparison with SD-OCT. There were 11 patients among those with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT. None had a history of macular disease or evidence for any other cause of bull's eye maculopathy. Conversely, all cases with a clear degree of parafoveal damage on SD-OCT showed at least some focal spots of parafoveal field loss. Approximately 10% of patients with early HCQ toxicity showed prominent ring scotomas on field testing without obvious SD-OCT abnormality. This should encourage the inclusion of visual fields as a key screening tool, even when SD-OCT (a more specific and objective test) also is performed. The combination of visual fields and SD-OCT gives both sensitivity and specificity while avoiding unnecessary stoppage of the drug.

Gli3/Spop Multivalent Interactions are Concentration-Dependent

It has been recently shown that many ubiquitin ligase substrates have multiple weak degrons instead of one strong one. These substrates are largely disordered, which allows for access to each degron. The biological function of these multiple degrons is unclear. Gli3, an intrinsically disordered, zinc-finger-containing transcription factor, is an effector of Hedgehog (Hh) signaling. Gli3 degradation is mediated by the E3 cullin-RING ubiquitin ligase speckle-type POZ protein (SPOP). SPOP binding motifs within Gli3 were identified by peptide microarray analysis and Gli3 was found to potentially have >70 binding motifs. Each SPOP monomer binds a single SBC motif, implying the abundance of motifs serves a function other than stoichiometric binding. SPOP itself is capable of forming concentration-dependent, dynamic oligomeric complexes. In this study, biophysical and structural techniques were used to characterize the oligomeric properties of SPOP and how binding of a multivalent Gli3 substrate affects these properties. Preliminary results suggest that individual degrons have similar weak binding affinities, with no site preferentially bound. Results also show that there is a concentration threshold for interactions between Gli3 and SPOP to occur. Further studies will continue to investigate this concentration-dependence and assess how this mechanism of binding may regulate Gli3 function and correct Hh signal transduction.

A Comparison of False-negative Responses for Full Threshold and SITA Standard Perimetry in Glaucoma Patients and Normal Observers

To compare false-negative (FN) rates for Full Threshold (FULL) and Swedish Interactive Threshold Algorithm (SITA) Standard automated perimetry in healthy control subjects and glaucoma patients. One eye of 19 glaucoma patients and 5 normal control subjects underwent 5 visual field examinations within 6 weeks on the Humphrey Field Analyzer II using the 24-2 FULL and SITA testing procedures. The order of presentation of test procedures was counterbalanced across participants. We obtained FN response procedures that presented stimuli 9 dB greater than a previously determined threshold value at specific locations in the visual field (FULL) or up to 20 dB greater than the threshold value (SITA), and evaluated whether the patient responded to these suprathreshold stimuli. We compared the percentage of FN responses for the FULL and SITA tests before (Peridata output) and after postprocessing of data. The percentage of FNs was almost twice as high for FULL testing compared with the 2 SITA analyses. The SD of FN percentages was half as large for SITA postprocessing compared with FULL and SITA Peridata procedures. Because the distributions were not normally distributed, a Kruskal-Wallis analysis of variance was performed and revealed a statistically significant difference (H=13.094, P<0.001) for FN percentages among the 3 evaluations. FULL test procedures yield about twice as many FNs as SITA procedures. This may be related to the SITA method of testing for FN in relatively normal areas as opposed to any location (even if it has low sensitivity) with FULL. Because FN responses can be due to either high variability in damaged areas or pathologic variations, these revised FN procedures provide greater assistance in properly interpreting visual field results.

Spatial Changes of Central Field Loss in Diabetic Retinopathy After Laser

To explore the spatial distribution of central visual field loss in untreated proliferative diabetic retinopathy (PDR) and to quantify the effect of medium-pulse Optos-guided 20-millisecond Pascal laser treatment on the central field. Visual field data (Swedish Interactive Threshold Algorithm 24-2) from 99 eyes (66 patients) with treatment-naive PDR were used to train a self-organizing map (SOM) that classified the defects into nine patterns. Twenty-eight eyes of 23 patients treated with 20-millisecond Pascal retinal laser photocoagulation underwent Optos widefield fundus fluorescein angiography (WF-FFA) at baseline and 3 months after treatment. Postlaser changes in SOM patterns and global indices were analyzed. Visual field defect changes (Total Deviation [TD]) with eccentricity and extent of initial loss were analyzed. Grading of WF-FFA after laser was undertaken by two masked retina specialists. At baseline, 44.4% of PDR eyes showed early visual field loss patterns (1 to 3), with 23.2% classified into the advanced patterns (7 to 9). Mild SOM patterns had more superior hemifield field defects, whereas advanced patterns involved both superior and inferior hemifield field loss. After laser, a significant shift to early SOM patterns were observed (p = 0.02), as well as improvement of Mean Deviation and Pattern Standard Deviation (p = 0.003 and p = 0.06, respectively). Improvement of TD was commonly observed in test locations of 0 to 10, 10 to 20, and 20 to 30 degrees. Greater improvement was observed with deeper baseline TD (p < 0.001). Masked WF-FFA image grading showed 78.6% PDR regression. The SOM method is a promising technique to classify and monitor over time PDR-associated visual field defects. Medium-pulse Optos-guided 20-millisecond Pascal laser treatment improved the spatial patterns and global parameters of central field defects.

Retinal Blood Vessel Positional Shifts and Glaucoma Progression

To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. Retrospective cohort study. Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with ≥8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<-0.02 decibels [dB]/year), moderate (-0.02 to-0.65 dB/year), or fast (≥-0.65 dB/year) progression. To determine whether graders' assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P= 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P< 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs.-0.29 dB/year; 95% confidence interval [CI], 0.03-0.48); P= 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P= 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1-4.5; P= 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7-83.6; P< 0.001) and DH (OR, 4.6; 95% CI, 1.5-15.5; P< 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.

Baseline thickness of macular ganglion cell complex predicts progression of visual field loss

Previous studies reported that the thickness of the macular ganglion cell complex (mGCC) showed good diagnostic ability for detecting glaucoma. However, its impact on the progression of visual field loss in primary open angle glaucoma (POAG) is unknown. The purpose of this study was to assess whether baseline mGCC thickness is associated with the progression of visual field loss in POAG. Fifty-six patients with POAG were included in the study. All patients were followed for more than 2years after baseline optical coherence tomography (OCT) measurements. They had at least five reliable Humphrey visual field tests with 30-2 Swedish Interactive Threshold Algorithm standard tests during the follow-up period. The subjects were divided into two groups according to the slope of the mean deviation (MD): the fast progression group (MD slope < -0.4dB/y) and the slow progression group (MD slope ≥ -0.4dB/y). Factors compared between the groups were as follows: age, baseline intraocular pressure (IOP), mean IOP during the follow-up, refraction, baseline MD, pattern standard deviation (PSD), and baseline OCT measurements. There were no significant differences between the two groups in age, baseline IOP, mean IOP during the follow-up, refraction, baseline MD or PSD, average thickness of retinal nerve fiber layer (RNFL), or disc parameters. However, the baseline mGCC thickness (average and inferior hemifield) was significantly thinner in the fast progression group than in the slow progression group (74.0 ± 7.2μm vs. 80.3 ± 8.6μm; 68.0 ± 6.6μm vs. 78.2 ± 11.6μm, respectively). Moreover, global loss volume and focal loss volume, which are parameters of mGCC, showed significantly higher rates in the fast progression group than in the slow progression group. In multivariate analysis, only mGCC thickness of the inferior hemifield was associated with disease progression (P = 0.007). Baseline mGCC thickness can be predictive of progressive visual field loss in patients with POAG.

Exclusion of Influences of ARMS2 Polymorphisms on the Central Visual Field in Retinitis Pigmentosa

Purpose: To investigate the effects of polymorphisms of the age-related maculopathy susceptibility 2 (ARMS2) gene on the central visual field defects in retinitis pigmentosa (RP). Subjects and Methods: The visual field was evaluated using the 10-2 Swedish Interactive Threshold Algorithm Fast Program and mean deviation (MD) slope, and regression coefficients of average sensitivity of the central 4 points (Cent4) were compared between each genetic subgroup. Results: The MD slope (right/left) was as follows: GG, -1.37 ± 2.18/ -0.89 ± 1.15; GT, -0.56 ± 1.40/-0.77 ± 1.04; TT, -0.75 ± 0.64/ -0.38 ± 0.92 dB/year. The Cent4 was as follows: GG, -1.34 ± 2.37/-1.60 ± 3.21; GT, -1.15 ± 2.08/1.07 ± 1.80; TT, -1.20 ± 0.91/-0.65 ± 1.37 dB/year. No significant differences in the degree of progression were observed when comparing groups. Conclusions: These data suggest that polymorphisms of the ARMS2 do not modify the progression of the central field of vision in RP patients.